WO2009019005A2 - Novel herbicides - Google Patents

Novel herbicides Download PDF

Info

Publication number
WO2009019005A2
WO2009019005A2 PCT/EP2008/006467 EP2008006467W WO2009019005A2 WO 2009019005 A2 WO2009019005 A2 WO 2009019005A2 EP 2008006467 W EP2008006467 W EP 2008006467W WO 2009019005 A2 WO2009019005 A2 WO 2009019005A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
alkyl
hydrogen
optionally substituted
Prior art date
Application number
PCT/EP2008/006467
Other languages
French (fr)
Other versions
WO2009019005A3 (en
WO2009019005A8 (en
Inventor
Melloney Tyte
Christopher John Mathews
Gavin John Hall
William Guy Whittingham
Jeffrey Steven Wailes
James Nicholas Scutt
Stephane André Marie JEANMART
Russell Viner
Original Assignee
Syngenta Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AP2010005137A priority Critical patent/AP2010005137A0/en
Priority to US12/672,165 priority patent/US8754242B2/en
Priority to ES08801523.5T priority patent/ES2497501T3/en
Priority to EA201000272A priority patent/EA201000272A1/en
Priority to BRPI0815651-4A priority patent/BRPI0815651B1/en
Priority to NZ583033A priority patent/NZ583033A/en
Priority to EP08801523.5A priority patent/EP2185564B1/en
Application filed by Syngenta Limited filed Critical Syngenta Limited
Priority to CN200880102362.4A priority patent/CN101855225B/en
Priority to CA2694133A priority patent/CA2694133C/en
Priority to PL08801523T priority patent/PL2185564T3/en
Priority to MX2010001364A priority patent/MX2010001364A/en
Priority to UAA201002439A priority patent/UA100700C2/en
Priority to JP2010519374A priority patent/JP5462163B2/en
Priority to AU2008285937A priority patent/AU2008285937B2/en
Publication of WO2009019005A2 publication Critical patent/WO2009019005A2/en
Publication of WO2009019005A3 publication Critical patent/WO2009019005A3/en
Priority to ZA2010/00490A priority patent/ZA201000490B/en
Publication of WO2009019005A8 publication Critical patent/WO2009019005A8/en
Priority to TNP2010000061A priority patent/TN2010000061A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems

Definitions

  • the present invention relates to novel, herbicidally active cyclopentanedione compounds, and derivatives thereof, to processes for their preparation, to compositions comprising those compounds, and to their use in controlling weeds, especially in crops of useful plants, or in inhibiting undesired plant growth.
  • Cyclopentanedione compounds having herbicidal action are described, for example, in WO 01/74770 and WO 96/03366.
  • Novel cyclopentanedione compounds, and derivatives thereof, having herbicidal and growth- inhibiting properties have now been found.
  • the present invention accordingly relates to compounds of formula I
  • G is hydrogen or an alkali metal, alkaline earth metal, sulfonium, ammonium or a latentiating group
  • R 1 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen,
  • R 2 , R 3 and R 4 are independently of each other hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen, C 1 -C 2 BIkOXy Or C 1 -C 2 haloalkoxy,
  • R 5 and R 12 are independently of each other hydrogen, CrC 3 alkyl, d-Cshaloalkyl, CrC 3 alkyoxy, d-Csalkylthio, halogen or C r C 6 alkoxycarbonyl, or
  • R 5 and R 12 join together to form a 3-7 membered carbocyclic ring, optionally containing an oxygen or sulfur atom
  • R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently of each other hydrogen or a substituent, or R 7 and R 8 , or R 9 and R 10 , together with the carbon atoms to which they are attached form a keto, an optionally substituted alkenyl or optionally substituted imino unit, or any two of R 7 , R 8 , R 9 and R 10 together form a 3-8 membered carbocyclic ring optionally containing a heteroatom selected from O, S or N and optionally substituted, or R 7 and R 10 together form a bond.
  • each alkyl moiety either alone or as part of a larger group is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, ⁇ -hexyl, isopropyl, n-butyl, sec-butyl, isobutyl, te/f-butyl or neopentyl.
  • the alkyl groups are suitably C 1 -C 6 alkyl groups, but are preferably C 1 -C 4 alkyl or C 1 -C 3 alkyl groups, and, more preferably, d ⁇ alkyl groups.
  • the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, C 3-7 cycloalkyl (itself optionally substituted with C 1-6 alkyl or halogen), C 5-7 cycloalkenyl (itself optionally substituted with C 1-6 alkyl or halogen), hydroxy, C 1-I o alkoxy, C 1-10 alkoxy(C 1-10 )alkoxy, tri(C 1-4 )alkylsilyl(C 1-6 )alkoxy, C 1-6 alkoxycarbonyl(C 1-10 )alkoxy, C 1-10 haloalkoxy, aryl(C 1-4 )-alkoxy (where the aryl group is optionally substituted), C 3-7 cycloalkyloxy (where
  • Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configu ration. Examples are vinyl, allyl and propargyl. Alkenyl and alkynyl moieties can contain one or more double and/or triple bonds in any combination. It is understood, that allenyl and alkylinylalkenyl are included in these terms. It is to be understood that the alkenyl units formed by R 7 together with R 8 are directly attached to the bridged cyclohexane ring by a double bond.
  • the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF 3 , CF 2 CI, CF 2 H, CCI 2 H, FCH 2 , CICH 2 , BrCH 2 , CH 3 CHF, (CHs) 2 CF, CF 3 CH 2 or CHF 2 CH 2 .
  • aryl refers to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
  • heteroaryl preferably refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings.
  • single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulphur.
  • Examples of such groups include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1 ,2,4-oxadiazolyl, 1 ,3,4-oxadiazolyl, 1 ,2,5-oxadiazolyl, 1 ,2,3-thiadiazolyl, 1 ,2,4-thiadiazolyl, 1 ,3,4-thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1 ,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl,
  • heteroaromatic radicals include pyridyl, pyrimidinyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, 2,1 ,3-benzoxadiazolyl and thiazolyl.
  • Another group of preferred heteroaryls comprises furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl or quinoxalinyl.
  • heterocyclyl preferably refers to a non-aromatic preferably monocyclic or bicyclic ring systems containing up to 7 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N.
  • heteroatoms selected from O, S and N.
  • examples of such rings include 1 ,3-dioxolane, oxetane, tetrahydrofuran, morpholine, thiomorpholin and piperazine.
  • the optional substituents on heterocyclyl include d. 6 alkyl and C 1-6 haloalkyl as well as those optional substituents given above for an alkyl moiety.
  • Cycloalkyl includes preferably cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Cycloalkylalkyl is preferentially cyclopropylmethyl. Cycloalkenyl includes preferably cyclopentenyl and cyclohexenyl. When present, the optional substituents on cycloalkyl or cycloalkenyl include C 1-3 alkyl as well as those optional substituents given above for an alkyl moiety.
  • Carbocyclic rings such as those formed by R 7 to gether with R 8 include aryl, cycloalkyl or carbocyclic groups, and cycloalkenyl groups.
  • the optional substituents on aryl, heteroaryl and carbocycles are preferably selected independently, from halogen, nitro, cyano, rhodano, isothiocyanato, Ci -6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy-(C 1-6 )alkyl, C 2-6 alkenyl, C 2-6 haloalkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl (itself optionally substituted with C 1-6 alkyl or halogen), C 5-7 cycloalkenyl (itself optionally substituted with C 1-6 alkyl or halogen), hydroxy, C 1-I0 alkoxy, C 1- - I0 alkoxy(C 1-10 )alkoxy, tri(C 1-4 )alkylsilyl(C 1-6 )alkoxy, C 1-6 alkoxycarbonyKCv ⁇ alkoxy, C 1-10 haloalkoxy, aryl(
  • aryl or heteroaryl include arylcarbonylamino (where the aryl group is substituted by C 1-6 alkyl or halogen), (C 1-6 )alkoxycarbonylamino (C 1-6 )alkoxycarbonyl- ⁇ /-(C 1-6 )alkylamino, aryloxycarbonylamino (where the aryl group is substituted by C 1-6 alkyl or halogen), aryloxycarbonyl- ⁇ /-(C 1-6 )alkylamino, (where the aryl group is substituted by C 1-6 alkyl or halogen), arylsulphonylamino (where the aryl group is substituted by C 1-6 alkyl or halogen), arylsulphonyl- ⁇ /-(C 1-6 )alkylamino (where the aryl group is substituted by C 1-6 alkyl or halogen), aryl-N-(C 1-6 )alkylamino
  • substituents are independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, nitro and cyano.
  • dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (C 1-6 )alkyl groups.
  • heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, pipehdine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (C 1-6 ) alkyl groups.
  • substituteduent in the definitions of R 6 to R 11 comprises preferably all substitutents given above for "aryl", “heteroaryl” and “heterocyclyl”.
  • the invention relates also to the salts which the compounds of formula I are able to form with amines, alkali metal and alkaline earth metal bases or quaternary ammonium bases.
  • alkali metal and alkaline earth metal hydroxides as salt formers, special mention should be made of the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially the hydroxides of sodium and potassium.
  • the compounds of formula I according to the invention also include hydrates which may be formed during the salt formation.
  • amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary C r C 18 alkylamines, Ci-C 4 hydroxyalkylamines and C 2 -C 4 - alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four butylamine isomers, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylamine
  • Preferred quaternary ammonium bases suitable for salt formation correspond, for example, to the formula [N(R 3 R b R 0 R d )]OH wherein R 3 , R b , R 0 and R d are each independently of the others CrC 4 alkyl.
  • Further suitable tetraalkylammonium bases with other anions can be obtained, for example, by anion exchange reactions.
  • the latentiating groups G are selected to allow its removal by one or a combination of biochemical, chemical or physical processes to afford compounds of formula I where G is H before, during or following application to the treated area or plants. Examples of these processes include enzymatic cleavage, chemical hydrolysis and photoloysis.
  • Compounds bearing such groups G may offer certain advantages, such as improved penetration of the cuticula of the plants treated, increased tolerance of crops, improved compatibility or stability in formulated mixtures containing other herbicides, herbicide safeners, plant growth regulators, fungicides or insecticides, or reduced leaching in soils.
  • R 6 and R 11 are independently of each other hydrogen, halogen, formyl, cyano or nitro or
  • R 6 and R 11 are independently of each other C r C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C r C 6 alkoxy,
  • R 13 is Ci-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
  • R 14 is hydrogen, C r C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
  • R 15 is hydrogen, C r C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C r C 6 alkoxy, C r C 6 haloalkoxy, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
  • R 16 is hydrogen, C r C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, CrC 6 alkoxy, C r C 6 haloalkoxy, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, C r C 6 alkylsulfonyl, phenylsulfonyl, heteroarylsulfonyl, amino, d-
  • R 15 and R 16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
  • R 17 and R 19 are independently of each other hydrogen, Ci-C 3 alkyl or C 3 -C 6 cycloalkyl,
  • R 18 , R 20 and R 21 are independently of each other hydrogen, C r C 6 alkyl, C 3 -C 6 alkenyl, C 3 -
  • R 22 is CrC 6 alkylcarbonyl, Ci-C 6 alkoxycarbonyl, d-C ⁇ alkylthiocarbonyl, C 1 -
  • C 6 alkylaminocarbonyl did-Csalkylaminocarbonyl, C r C 6 alkylsulfonyl, phenylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, phenylthiocarbonyl, phenylsulfonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylthiocarbonyl or heteroarylsulfonyl, where all these substituents are optionally substituted,
  • R 23 is Ci-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C r C 6 alkylcarbonyl, C 1 -
  • R 22 and R 23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and
  • R 24 is C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, d-C 6 alkylcarbonyl, C r C 6 alkoxycarbonyl, C 1 -
  • R 13 , R 14 , R 15 and R 16 are C r C 6 alkyl
  • R 17 and R 19 are hydrogen or C 1 -C 3 alkyl
  • R 18 is C 1 -C 3 alkyl
  • R 20 and R 21 are independently of each other hydrogen or d-C 3 alkyl.
  • R 6 and R 11 are independently of each other hydrogen, methyl or methyl substituted by d-C 3 alkoxy.
  • R 7 , R 8 , R 9 and R 10 are independently of each other hydrogen, halogen, hydroxyl, formyl, amino, cyano or nitro, or
  • R 7 , R 8 , R 9 and R 10 are independently of each other CrC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -
  • CealkylthioCrCealkyl d-Cealkylsulfinyld-Cealkyl, d-Cealkylsulfonyld-Cealkyl, C 3 -C 7 cycloalkyl,
  • R 7 , R 8 , R 9 and R 10 are independently of each other a group COR 13 , CO 2 R 14 or CONR 15 R 16 ,
  • R 13 is d-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted
  • R 14 is hydrogen, CrC 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
  • R 15 is hydrogen, d-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, d-C 6 alkoxy, C r C 6 haloalkoxy, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
  • R 16 is hydrogen, d-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, d-C 6 alkoxy, C r C 6 haloalkoxy, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, CrC 6 alkylsulfonyl, amino, d-C 6 alkylamino, diC r C 6 alkylamino, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
  • R 15 and R 16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
  • R 17 and R 19 are independently of each other hydrogen, C r C 3 alkyl or C 3 -C 6 cycloalkyl,
  • R 18 , R 20 and R 21 are independently of each other hydrogen, d-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -
  • R 22 and R 23 are independently of each other d-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, d-C 6 alkylcarbonyl, d-C 6 alkoxycarbonyl, d-C 6 alkylthiocarbonyl, C 1 -
  • R 22 and R 23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and
  • R 24 is d-C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 7 cycloalkyl, d-C 6 alkylcarbonyl, C 1 -
  • R 7 , R 8 , R 9 and R 10 are hydrogen.
  • R 7 , R 8 , R 9 and R 10 is methyl or ethyl.
  • R 7 , R 8 , R 9 and R 10 is an optinally substituted aryl or heteroaryl and more preferably optionally substituted phenyl, naphthyl, furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl,
  • R 7 , R 8 , R 9 and R 10 is pyridyl or pyridyl substituted by trifluoromethyl or halogen. It is also preferred that R 7 and R 10 form a bond.
  • R 7 , R 8 , R 9 and R 10 are independently of each other hydrogen, cyano, Ci-C 6 alkyl, C 2 -
  • R 17 is hydrogen or CrC 3 alkyl
  • R 18 is C 1 -C 3 alkyl.
  • R 25 and R 26 are independently of each other hydrogen, halogen, cyano or nitro, or
  • R 25 and R 26 are independently of each other d-C 6 alkyl, CrC 6 alkoxy, C r C 6 alkylamino, CUC 1 -
  • R 25 and R 26 may be joined together to form a 5-8 membered ring optionally containing a heteroatom selected from O, S or N and optionally substituted by C r C 2 alkyl or d-C 2 alkoxy,
  • R 27 is nitro or cyano, or
  • R 27 is d-C 6 alkylamino, did-C 6 alkylamino, d-C 6 alkoxy, C 3 -C 6 alkenyloxy, C 3 -C 6 alkynyloxy, phenoxy, phenylamino, ⁇ /-phenyl- ⁇ /-C r C 6 alkylamino, /V-phenyld-Cealkyl-ZV-CrC ⁇ alkylamino heteroaryloxy, heteroarylamino, ⁇ /-heteroaryl- ⁇ /-CrC 6 alkylamino or /V-heteroaryld-Cealkyl-ZV-d-d-
  • R 7 , R 8 , R 9 and R 10 are independently of each other hydrogen, methyl, ethyl or optionally substituted phenyl.
  • one of R 7 , R 8 , R 9 and R 10 is optionally substituted heteroaryl, preferably optionally substituted furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl or quinoxalinyl, and more preferably pyridyl substituted once or twice by trifluoromethyl or halogen.
  • R 1 , R 2 and R 4 are methyl and R 3 is hydrogen.
  • R 1 , R 2 and R 4 are methyl and R 3 is hydrogen
  • R 7 , R 8 , R 9 and R 10 are independently of each other hydrogen, cyano, C r C 6 alkyl, C 2 -C 6 alkenyl, CrC 6 alkoxy, Ci-C 6 alkoxyC r C 6 alkyl, 3-7 membered heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl, preferably optionally substituted heteroaryl, and in particular pyridyl substituted once or twice by trifluoromethyl or halogen.
  • R 5 and R 12 are independently of each other hydrogen or CrC 3 alkyl, where hydrogen is more preferred.
  • R 1 is methyl, ethyl, vinyl, ethynyl, cyclopropyl, difluoromethoxy, trifluoromethoxy or CrC 2 alkoxy and
  • R 2 , R 3 and R 4 are independently of each other hydrogen, methyl, ethyl, vinyl or ethynyl.
  • R 1 is ethyl and R 2 , R 3 and R 4 are independently of each other hydrogen, methyl or ethyl.
  • R 1 , R 2 and R 4 are methyl and R 3 is hydrogen.
  • the latentiating group G is preferably selected from the groups CrC 8 alkyl, C 2 -C 8 haloalkyl, phenylCrC 8 alkyl (wherein the phenyl may optionally be substituted by Ci-C 3 alkyl, CrCshaloalkyl, CrC 3 alkoxy, CrC 3 haloalkoxy, CrCsalkylthio, CrCsalkylsulfinyl, C 1 -C 3 alkylsulfonyl, halogen, cyano or by nitro), heteroaryld-C ⁇ alkyl (wherein the heteroaryl may optionally be substituted by d-Csalkyl, C r C 3 haloalkyl, C r C 3 alkoxy, C r C 3 haloalkoxy, C r C 3 alkylthio, C r C 3 alkylsulfinyl, C 1 - C 3 alkylsulfonyl, hal
  • R a is H, d-Ci ⁇ alkyl, C 2 -C 18 alkenyl, C 2 -C 18 alkynyl, C r C 10 haloalkyl, Ci-Ciocyanoalkyl, C 1 - C 10 nitroalkyl, d-doaminoalkyl, d-Csalkylaminod-Csalkyl, C 2 -C 8 dialkylaminoCrC 5 alkyl, C 3 - C 7 cycloalkylCrC 5 alkyl, d-Csalkoxyd-Csalkyl, CrCsalkenyloxyd-Csalkyl, C 3 -C 5 alkynylC r Csoxyalkyl, d-Csalkylthiod-Csalkyl, d-Csalkylsulfinyld-Csalkyl, d-Csalkylsulfonyld-Cs
  • R b is C r C 18 alkyl, C 3 -C 18 alkenyl, C 3 -C 18 alkynyl, C 2 -C 10 haloalkyl, d-C 10 cyanoalkyl
  • R e is d-C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, d-C 10 haloalkyl, d-C 10 cyanoalkyl, C 1 - C 10 nitroalkyl, d-C 10 aminoalkyl, CrCsalkylaminoCrCsalkyl, CrC ⁇ dialkylaminoCrCsalkyl, C 3 - C 7 cycloalkyld-C 5 alkyl, CrCsalkoxyCrCsalkyl, CrCsalkenyloxyd-Csalkyl, C 3 -C 5 alkynyloxyC r C 5 alkyl, CrCsalkylthioCrCsalkyl, C ⁇ CsalkylsulfinylCrCsalkyl, CrCsalkylsulfonylCrCsalkyl, C 2 - C ⁇ alkylidenea
  • R h is C r C 10 alkyl, C 3 -C 10 alkenyl, C 3 -C 10 alkynyl, C r C 10 haloalkyl, d-docyanoalkyl, C 1 - C 10 nitroalkyl, C 2 -C 10 aminoalkyl, d-CsalkylaminoCrCsalkyl, CrC ⁇ dialkylaminoCrCsalkyl, C 3 - C 7 cycloalkyld-C 5 alkyl, CrCsalkoxyCrCsalkyl, CrCsalkenyloxyd-Csalkyl, C 3 -C 5 alkynyloxyd- C 5 alkyl, d-Csalkylthiod-Csalkyl, d-CsalkylsulfinylCrCsalkyl, d-CsalkylsulfonylCrCsalkyl, C 2 - C ⁇
  • the latentiating group G is a group -C(X a )-R a or -C(X b )-X c -R b . and the meanings of X a , R a , X b , X c and R b are as defined above.
  • G is hydrogen, an alkali metal or alkaline earth metal, where hydrogen is _ especially preferred.
  • compounds of formula I may exist in different isomeric forms.
  • G is hydrogen, for example, compounds of formula I may exist in different tautomeric forms.
  • isomeric compounds of formula I may be formed.
  • a compound of formula (A) wherein R 5 and R 12 are different may give rise to a compound of formula (1a) or to a compound of formula (1 b), or to a mixture of compounds of formula (1a) and formula (1 b).
  • the O-acylation of cyclic 1 ,3-diones may be effected by procedures similar to those described, for example, by R. Haines, US4175135, and by T. Wheeler, US4422870, US4659372 and US4436666.
  • diones of formula (A) may be treated with the acylating agent in the presence of at least one equivalent of a suitable base, optionally in the presence of a suitable solvent.
  • the base may be inorganic, such as an alkali metal carbonate or hydroxide, or a metal hydride, or an organic base such as a tertiary amine or metal alkoxide.
  • suitable inorganic bases include sodium carbonate, sodium or potassium hydroxide, sodium hydride
  • suitable organic bases include trialkylamines, such as trimethylamine and triethylamine, pyridines or other amine bases such as 1 ,4-diazobicyclo[2.2.2]octane and 1 ,8- diazabicyclo[5.4.0]undec-7-ene.
  • Preferred bases include triethylamine and pyridine.
  • Suitable solvents for this reaction are selected to be compatible with the reagents and include ethers such as tetrahydrofuran and 1 ,2-dimethoxyethane and halogenated solvents such as dichloromethane and chloroform.
  • acylating agent is a carboxylic acid
  • acylation is preferably effected in the presence of a coupling agent such as 2-chloro-1- methylpyridinium iodide, ⁇ /, ⁇ /-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide and ⁇ /, ⁇ /-carbodiimidazole, and optionally a base such as triethylamine or pyridine in a suitable solvent such as tetrahydrofuran, dichloromethane or acetonitrile.
  • a coupling agent such as 2-chloro-1- methylpyridinium iodide, ⁇ /, ⁇ /-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide and ⁇ /, ⁇ /-carbodiimidazole
  • a base
  • Phosphorylation of cyclic 1 ,3-diones may be effected using a phosphoryl halide or thiophosphoryl halide and a base by procedures analogous to those described by L. Hodakowski, US4409153.
  • Sulfonylation of a compound of formula (A) may be achieved using an alkyl or aryl sulfonyl halide, preferably in the presence of at least one equivalent of base, for example by the procedure of C. Kowalski and K. Fields, J. Org. Chem., (1981), 46, 197.
  • a compound of formula (A) may be prepared by the cyclisation of a compound of formula (B), wherein R is hydrogen or an alkyl group, preferably in the presence of an acid or base, and optionally in the presence of a suitable solvent, by analogous methods to those described by T. Wheeler, US4209532.
  • the compounds of formula (B) have been particularly designed as intermediates in the synthesis of the compounds of the formula I.
  • a compound of formula (B) wherein R is hydrogen may be cyclised under acidic conditions, preferably in the presence of a strong acid such as sulfuric acid, polyphosphoric acid or Eaton's reagent, optionally in the presence of a suitable solvent such as acetic acid, toluene or dichloromethane.
  • formula (B) formula (A)
  • a compound of formula (B) wherein R is alkyl (preferably methyl or ethyl), may be cyclised under acidic or basic conditions, preferably in the presence of at least one equivalent of a strong base such as potassium tert-butoxide, lithium diisopropylamide or sodium hydride and in a solvent such as tetrahydrofuran, toluene, dimethylsulfoxide or ⁇ /, ⁇ /-dimethylformamide.
  • a strong base such as potassium tert-butoxide, lithium diisopropylamide or sodium hydride
  • a solvent such as tetrahydrofuran, toluene, dimethylsulfoxide or ⁇ /, ⁇ /-dimethylformamide.
  • a compound of formula (B), wherein R is H may be prepared by saponification of a compound of formula (C) wherein R' is alkyl (preferably methyl or ethyl), under standard conditions, followed by acidification of the reaction mixture to effect decarboxylation, by similar processes to those described, for example, by T. Wheeler, US4209532.
  • a compound of formula (B), wherein R is H may be esterified to a compound of formula (B), wherein R is alkyl, under standard conditions, for example by heating with an alkyl alcohol, ROH, in the presence of an acid catalyst.
  • a compound of formula (C), wherein R is alkyl may be prepared by treating a compound of formula (D) with a suitable carboxylic acid chloride of formula (E) under basic conditions.
  • Suitable bases include potassium te/f-butoxide, sodium bis(trimethylsilyl)amide and lithium diisopropylamide and the reaction is preferably conducted in a suitable solvent (such as tetrahydrofuran or toluene) at a temperature of between -80 0 C and 30 0 C.
  • a compound of formula (C) 1 wherein R is H 1 may be prepared by treating a compound of formula (D) with a suitable base (such as potassium tert-butoxide, sodium bis(trimethylsilyl)amide and lithium diisopropylamide) in a suitable solvent (such as tetrahydrofuran or toluene) at a suitable temperature (between -80 0 C and 30 0 C) and reacting the resulting anion with a suitable anhydride of formula (F):
  • a suitable base such as potassium tert-butoxide, sodium bis(trimethylsilyl)amide and lithium diisopropylamide
  • a suitable solvent such as tetrahydrofuran or toluene
  • Compounds of formula (D) are known compounds, or may be prepared from known compounds by known methods.
  • a compound of formula (E) may be prepared from a compound of formula (F) by treatment with an alkyl alcohol, R-OH, in the presence of a base, such as dimethylaminopyridine or an alkaline metal alkoxide (see, for example, S. Buser and A. Vasella, HeIv. Chim. Acta, (2005), 88, 3151 , M. Hart et al., Bioorg. Med. Chem. Letters, (2004), 14, 1969), followed by treatment of the resulting acid with a chlorinating reagent such as oxalyl chloride or thionyl chloride under known conditions (see, for example, C. Santelli-Rouvier.
  • a base such as dimethylaminopyridine or an alkaline metal alkoxide
  • a compound of formula (F) wherein R 7 and R 10 are hydrogen may be prepared by the reduction of a compound of formula (G) under known conditions (see, for example, Y. Baba, N. Hirukawa and M. Sodeoka, Bioorg. Med. Chem. (2005), 13 (17), 5164, M. Hart ef a/., Bioorg. Med. Chem. Letters, (2004), 14 (18), 1969, Y. Baba, N. Hirukawa, N. Tanohira and M. Sodeoka, J. Am. Chem. Soc, (2003), 125, 9740).
  • a compound of formula (G) may be prepared by reacting a compound of formula (H) with an anhydride of formula (J), optionally in the presence of a Lewis acid catalyst , and according to procedures described, for example, by O. Diels and K. Alder, Liebigs Ann. Chem., (1931), 490, 257, K. Potts and E. Walsh, J. Org. Chem., (1984), 49 (21), 4099, J. Jurczak, T. Kozluk, S. Filipek and S. Eugster, HeIv. Chim. Acta, (1982), 65, 1021 , W. Dauben, C. Kessel and K. Takemura, J. Am. Chem.
  • Compounds of formula (G) are alkenes, and as such undergo further reactions typical of alkenes to give additional compounds of formula (F) according to known procedures. Examples of such reactions include, but are not restricted to, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration of alkenes. In turn, the products from these reactions may be transformed into additional compounds of formula (F) by methods described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons.
  • a compound of formula (G) may also be prepared by reacting a compound of formula (H) with a compound of formula (K), wherein R" is hydrogen or an alkyl group, to give a compound of formula (L) and cyclising a compound of formula (L) under known conditions (see, for example, P. Sprague ef a/., J. Med. Cher ⁇ ., (1985), 28, 1580, A. Guzaev and M. Manoharan, J. Am. Chem. Soc, (2003), 125, 2380, and A. Marchand and R. Allen, J. Org. Chem., (1975), 40 (17), 2551.
  • a compound of formula (L) may also be reduced to a compound of formula (M), and a compound of formula (M) cyclised to a compound of formula (F) wherein R 7 and R 10 are hydrogen, under conditions similar to those described previously.
  • Compounds of formula (K) are known compounds, or may be prepared from known compounds by known methods.
  • Additional compounds of formula (A) may be prepared by reacting an iodonium ylide of formula (N), wherein Ar is an optionally substituted phenyl group, and an aryl boronic acid of formula (O), in the presence of a suitable palladium catalyst, a base and in a suitable solvent.
  • Suitable palladium catalysts are generally palladium(ll) or palladium(O) complexes, for example palladium(ll) dihalides, palladium(ll) acetate, palladium(ll) sulfate, bis(triphenylphosphine)- palladium(ll) dichloride, bis(tricyclopentylphosphine)palladium(ll) dichloride, bis(tricyclohexyl- phosphine)palladium(ll) dichloride, bis(dibenzylideneacetone)palladium(0) or tetrakis- (triphenylphosphine)palladium(O).
  • palladium(ll) dihalides palladium(ll) acetate, palladium(ll) sulfate, bis(triphenylphosphine)- palladium(ll) dichloride, bis(tricyclopentylphosphine)palladium(ll) dichloride, bis(tricyclo
  • the palladium catalyst can also be prepared "in situ" from palladium(ll) or palladium(O) compounds by complexing with the desired ligands, by, for example, combining the palladium(ll) salt to be complexed, for example palladium(ll) dichloride (PdCI 2 ) or palladium(ll) acetate (Pd(OAc) 2 ), together with the desired ligand, for example triphenyl- phosphine (PPh 3 ), tricyclopentylphosphine, tricyclohexylphosphine, 2-dicyclohexylphosphino- 2',6'-dimethoxybiphenyl or 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl and the selected solvent, with a compound of formula (N), the arylboronic acid of formula (O), and a base.
  • PdCI 2 palladium(ll) dichloride
  • bidendate ligands for example 1 ,1'-bis(diphenylphosphino)ferrocene or 1 ,2-bis(diphenylphosphino)ethane.
  • the palladium catalysts are used in an amount of from 0.001 to 50 mol %, preferably in an amount of from 0.1 to 15 mol %, based on the compound of formula (N).
  • the reaction may also be carried out in the presence of other additives, such as tetralkylammonium salts, for example, tetrabutylammonium bromide.
  • the palladium catalyst is palladium acetate, the base is lithium hydroxide and the solvent is aqueous 1 ,2-dimethoxyethane.
  • a compound of formula (N) may be prepared from a compound of formula (P) by treatment with a hypervalent iodine reagent such as a (diacetoxy)iodobenzene or an iodosylbenzene and a base such as aqueous sodium carbonate, lithium hydroxide or sodium hydroxide in a solvent such as water or an aqueous alcohol such as aqueous ethanol according to the procedures of K. Schank and C. Lick, Synthesis, (1983), 392, R. M. Moriarty et al., J. Am. Chem. Soc, (1985), 107, 1375, or of Z. Yang et al., Org. Lett., (2002), 4 (19), 3333.
  • a compound of formula (P) wherein R 7 and R 10 are hydrogen may be prepared by reduction of a compound of formula (Q) under known conditions.
  • Compounds of formula (R) are alkenes, and as such undergo further reactions typical of alkenes to give additional compounds of formula (P) according to known procedures. Examples of such reactions include, but are not restricted to, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration of alkenes. In turn, the products of these reactions may be transformed into additional compounds of formula (P) by methods described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons. Compounds of formula (R) wherein R 8 or R 9 are C r C 6 alkoxy are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures. In turn, the ketone may be further transformed, for example by ketalisation, oximation, reduction and the like under known conditions to give additional compounds of formula (P).
  • a compound of formula (R) may be prepared by reacting a compound of formula (S) with a cyclopentenedione of formula (T), optionally in the presence of a Lewis acid catalyst, according to procedures described, for example by B. Zwanenburg et a/., Tetrahedron (1989), 45 (22), 7109 and by M. Oda er a/., Chem. Lett., (1977), 307.
  • a compound of formula (A) may be prepared from a compound of formula I, wherein G is C r4 alkyl, by hydrolysis, preferably in the presence of an acid catalyst such as hydrochloric acid and optionally in the presence of a suitable solvent such as tetrahydrofuran, acetone or 4-methylpentan-2-one.
  • an acid catalyst such as hydrochloric acid
  • a suitable solvent such as tetrahydrofuran, acetone or 4-methylpentan-2-one.
  • a compound of formula I wherein G is C r4 alkyl may be prepared from a compound of formula (U), wherein G is Ci -4 alkyl, and Hal is a halogen (preferably bromine or iodine), by coupling with an aryl boronic acid of formula (O), in the presence of a suitable palladium catalyst and a base and preferably in the presence of a suitable ligand, and in a suitable solvent.
  • the palladium catalyst is palladium acetate
  • the base is potassium phosphate
  • the ligand is 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl
  • the solvent is toluene.
  • a compound of formula (U) may be prepared by halogenation of a compound of formula (P), followed by reaction of the resulting halide of formula (V) with a C 1-4 alkyl halide or tri-C 1-4 - alkylorthoformate under known conditions (for example by the procedures of R. Shepherd and A. White, J. Chem. Soc. Perkin Trans. 1 (1987), 2153, and Y.-L. Lin et al., Bioorg. Med. Chem. (2002), 10, 685).
  • a compound of formula (U) may be prepared by reaction of a compound of formula (P) with a C 1-4 alkyl halide or a tri-C ⁇ -alkylorthoformate, and halogenation of the resulting enone of formula (W) under known conditions.
  • a compound of formula (O) may be prepared from an aryl halide of formula (X), wherein Hal is bromine or iodine, by known methods (see, for example, W. Thompson and J. Gaudino, J. Org. Chem, (1984), 49, 5237 and R. Hawkins ef a/., J. Am. Chem. Soc, (1960), 82, 3053).
  • an aryl halide of formula (X) may be treated with an alkyl lithium or alkyl magnesium halide in a suitable solvent, preferably diethyl ether or tetrahydrofuran, at a temperature of between -80 0 C and 30 0 C, and the aryl magnesium or aryl lithium reagent obtained may then be reacted with a trialkyl borate (preferably trimethylborate) to give an aryl dialkylboronate which may be hydrolysed to provide a boronic acid of formula (O) under acidic conditions.
  • a suitable solvent preferably diethyl ether or tetrahydrofuran
  • a compound of formula (X) may be reacted with a cyclic boronate ester derived from a 1 ,2- or a 1 ,3-alkanediol such as pinacol, 2,2-dimethyl-1 ,3-propanediol and 2-methyl-2,4- pentanediol) under known conditions (see, for example, N. Miyaura et al., J. Org. Chem., (1995),
  • boronate ester may be hydrolysed under acidic conditions to give a boronic acid of formula (O).
  • An aryl halide of formula (X) may be prepared from an aniline of formula (Y) by known methods, for example the Sandmeyer reaction, via the corresponding diazonium salts.
  • Anilines of formula (Y) are known compounds, or may be made from known compounds, by known methods.
  • Additional compounds of formula (A) may be prepared by reacting a compound of formula (P), or a compound of formula (R) with an organolead reagent of formula (Z) under conditions described, for example, by J. Pinhey, Pure and Appl. Chem., (1996), 68 (4), 819 and by M. Moloney et al., Tetrahedron Lett., (2002), 43, 3407.
  • formula (P) formula (A)
  • the organolead reagent of formula (Z) may be prepared from a boronic acid of formula (O), a stannane of formula (AA), wherein R is C 1 -C 4 alkyl or by direct plumbation of a compound of formula (AB) with lead tetraacetate according to known procedures.
  • formula (AB) Further compounds of formula (A) may be prepared by reacting a compound of formula (P) or a compound of formula (R) with suitable triarylbismuth compound under conditions described, for example, by A. Yu. Fedorov ef a/., Russ. Chem. Bull. Int. Ed., (2005), 54 (11), 2602, and by P. Koech and M. Kirk, J. Am. Chem. Soc, (2004), 126 (17), 5350 and references therein.
  • a compound of formula I may be prepared from a compound of formula (AC) by suitable derivatisation under standard conditions.
  • compounds of formula (AC) are alkenes, and as such undergo further reactions typical of alkenes to give compounds of formula I according to known procedures. Examples of such reactions include, but are not restricted to, reduction, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration.
  • Compounds of formula (AC) wherein R 8 or R 9 is bromine or iodine are vinyl halides, and undergo known reactions of vinyl halides such as Suzuki-Miyaura, Sonogashira, Stille and related reactions.
  • Certain other compounds of formula (AC), wherein R 8 or R 9 is d-C ⁇ alkoxy, are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures.
  • the ketone produced may be further transformed, for example by ketalisation, oximation, reduction and the like under known conditions to give additional compounds of formula I.
  • compounds of formula (AC) wherein R 8 or R 9 is C r C 6 amino or di-C r C 6 amino are enamines, and these also may be hydrolysed to the corresponding ketone using standard procedures.
  • a compound of formula (AC), wherein G is Ci-C 4 alkyl may be prepared from a compound of formula (AD), wherein G is C 1 -C 4 alkyl and X is halogen or other suitable leaving group (such as an alkyl or arylsulfonate, or an arylselenoxide), by reaction with a compound of formula (H), optionally in a suitable solvent, and optionally in the presence of a suitable base.
  • AD compound of formula (H)
  • Suitable solvents include toluene, dichloromethane and chloroform and suitable bases include organic bases such as triethylamine, Hunig's base and 1 ,8-diazabicyclo[5.4.0]undec-7-ene.
  • suitable bases include organic bases such as triethylamine, Hunig's base and 1 ,8-diazabicyclo[5.4.0]undec-7-ene.
  • the solvent is toluene and the base is 1 ,8-diazabicyclo[5.4.0]undec-7-ene.
  • a compound of formula (AD) may be prepared from a compound of formula (AE), under known conditions.
  • a compound of formula (AD) wherein X is chlorine may be prepared by reacting a compound of formula (AE) with copper(ll) chloride and lithium chloride according to the procedure of E. Kosower ef a/., J. Org. Chem., (1963), 28, 630.
  • Compounds of formula (AE) are known compounds or may be made from known compounds by known methods (see, for example, Y. Song, B. Kim and J-N Heo, Tetrahedron Lett., (2005), 46, 5977).
  • a compound of formula (AE) wherein G is C r C 4 alkyl may be prepared from a compound of formula (AE), wherein G is hydrogen, for example by reaction with a C 1-4 alkyl halide or a tri-Ci -4 -alkylorthoformate.
  • Compounds of formula (AE), wherein G is hydrogen are known, or may be prepared from known compounds by known methods (see, for example, T. Wheeler, US4338122, US4283348, J. T.
  • a compound of formula (AE), wherein G is C 1-4 alkyl may be prepared by reacting a compound of formula (AF), wherein G is C 1-4 alkyl and Z is a halogen, preferably bromine or iodine, with a boronic acid of formula (O) in the presence of a suitable metal catalyst, a suitable base, and optionally a suitable ligand, in a suitable solvent.
  • a compound of formula (AF) wherein G is C 1-4 alkyl and Z is a halogen, preferably bromine or iodine
  • Suitable solvents include toluene and ⁇ -butanol
  • suitable bases include inorganic bases such as potassium phosphate
  • a suitable metal catalyst is a palladium catalyst, for example in the form of palladium(ll) acetate
  • suitable ligands include substituted phosphines, for example 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl.
  • a compound of formula (AF) wherein G is C 1-4 alkyl and Z is a bromine atom may be prepared by reacting a compound of formula (AG), wherein G is C 1-4 alkyl, with a suitable brominating agent, such as ⁇ /-bromosuccinimide, in a suitable solvent, such as 1 ,2-dichloroethane, as described by R. Shepherd and A. White, J. Chem. Soc. Perkin Trans. 1 (1987), 10, 2153.
  • a compound of formula (A) may be prepared from a compound of formula (AH) by suitable derivatisation under standard conditions.
  • compounds of formula (AH) are alkenes, and as such undergo further reactions typical of alkenes to give compounds of formula (A) according to known procedures. Examples of such reactions include, but are not restricted to, reduction, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration.
  • Compounds of formula (AH) wherein R 8 or R 9 is bromine or iodine are vinyl halides, and undergo known reactions of vinyl halides such as Suzuki-Miyaura, Sonogashira, Stille and related reactions.
  • a compound of formula (AH) may be prepared from a compound of formula (Al) by reaction with a compound of formula (H), optionally in a suitable solvent, and optionally in the presence of a suitable catalyst.
  • the compounds of formula (Al) have been particularly designed as intermediates in the synthesis of the compounds of the formula I.
  • the catalyst is a Lewis acid catalyst such as aluminium chloride, bismuth (III) chloride, bismuth (III) trifluoromethanesulfonate, boron trifluoride, cerium (III) chloride, copper (I) trifluoromethanesulfonate, diethylaluminium chloride, hafnium (IV) chloride, iron (III) chloride, lithium perchlorate, lithium trifluoromethanesulfonate, magnesium bromide, magnesium iodide, scandium (III) trifluoromethanesulfonate, tin (IV) chloride, titanium (IV) chloride, titanium (IV) isopropoxide, trimethyl aluminium, ⁇ /-trimethylsilyl-bis(trifluoromethanesulfonyl)imide, trimethylsilyl trifluoromethane-sulfonate, ytterbium (III) trifluoromethanesulfonate, zinc iod
  • Suitable solvents include those which are known to be effective solvents for conducting Diels-Alder reactions, among them, for example, chloroform, dichloromethane, diethyl ether, ethanol, methanol, perfluorinated alkanes, such as perfluorohexane, toluene, water.and ionic liquids such as 1-butyl-3- methylimidazolium tetrafluoroborate and 1-butyl-3-methylimidazolium hexafluorophosphate.
  • Dichloromethane is particularly preferred as a solvent.
  • a compound of formula (Al) may be prepared by oxidising a compound of formula (AJ) in a suitable solvent such as toluene, acetone, chloroform, dichloromethane or 1 ,4-dioxane.
  • a suitable solvent such as toluene, acetone, chloroform, dichloromethane or 1 ,4-dioxane.
  • oxidants include inorganic oxidants such as chromium trioxide, pyridinium dichromate, manganese dioxide and aluminium alkoxides such as aluminium isopropoxide, as well as organic oxidants such as 2,3-dichloro-5,6-dicyano-p- benzoquinone and hypervalent iodine oxidants such as 1 ,1 ,1 ,-tris(acetyloxy)-1 ,1-dihydro-1 ,2- benziodoxol-3-(1 H)-one (Dess-Martin period
  • the compounds of the formula Al have been particularly designed as intermediates for the synthesis of the compounds of the formula I.
  • Particularly useful compounds of the formula Al are those, wherein R 5 and R 12 are hydrogen.
  • R 1 , R 2 and R 4 are independently of each other methyl or ethyl.
  • R 1 , R 2 and R 4 are independently of each other methyl or ethyl, and R 3 , R 5 and R 12 are hydrogen.
  • a compound of formula (AJ) may be prepared from a compound of formula (AK) by treatment with a suitable acid catalyst in the presence of water and optionally in the presence of a suitable solvent, according to known procedures.
  • a compound of formula (AK) may be converted to a compound of formula (AJ) in the presence of an aqueous solution of an acid such as phosphoric acid or polyphosphoric acid as described, for example by K. Saito and H. Yamachika, US4371711.
  • a compound of formula (AJ) may be prepared from a compound of formula (AK) by rearrangement in the presence of a Lewis acid catalyst such as zinc chloride according to the procedure of G. Piancatelli et al., Tetrahedron, (1978), 34, 2775.
  • a compound of formula (AK) may be prepared by the reduction of a compound of formula (AL) by known conditions (see, for example R Silvestri et al., J. Med. Chem., 2005, 48, 4378-4388). reduction
  • A Compounds of formula (AL) are known, or may be made by known methods from known compounds (see, for example, L. Liebeskind et al., Org. Lett., (2003), 5 (17), 3033-3035, H. Firouzabadi, N. lranpoor and F. Nowrouzi, Tetrahedron, (2004), 60,10843, R. Silvestri et al., J. Med. Chem., (2005), 48, 4378 and references therein).
  • a compound of formula (AK) may be prepared by the addition of a suitable organometallic reagent such as an arylmagnesium halide of formula (AM) wherein Hal is a halide such as chloride, bromide or iodide, or an aryllithium reagent of formula (AN) or a diarylzinc reagent of formula (AO) to a furan-2-carboxaldehyde of formula (AP) according to known procedures (see, for example G. Panda et al., Tetrahedron Lett., (2005), 46, 3097).
  • a suitable organometallic reagent such as an arylmagnesium halide of formula (AM) wherein Hal is a halide such as chloride, bromide or iodide, or an aryllithium reagent of formula (AN) or a diarylzinc reagent of formula (AO)
  • Additional compounds of formula (AK) may be prepared from compounds of formula (AR) by reaction with a strong base, for a example an alkyl lithium reagent such as n-butyllithium, optionally in the presence of an additive such as tetramethylethylenediamine, and in a suitable solvent such as diethyl ether or tetrahydrofuran, followed by reaction with a benzaldehyde of formula (AS) as described, for example by I. Gupta and M. Ravikanth, J. Org. Chem., (2004), 69, 6796, A. M. Echavarren et a/., J. Am. Chem. Soc, (2003),125 (19), 5757, and by T. K. Chandrashekar ef a/., J. Org. Chem., (2002), 67, 6309-6319.
  • a strong base for a example an alkyl lithium reagent such as n-butyllithium,
  • organometallic reagents of formula (AM), formula (AN) and formula (AO) are known compounds or may be made by known methods from known compounds.
  • Compounds of formula (AP), formula (AR) and formula (AS) are known compounds, or may be prepared from known compounds by known methods.
  • the compounds of formula I according to the invention can be used as herbicides in unmodified form. as obtained in the synthesis, but they are generally formulated into herbicidal compositions in a variety of ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, for example in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil- in-water emulsions, oil flowables, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known, for example, from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999.
  • Such formulations can either be used directly or are diluted prior to use.
  • Diluted formulations can be prepared, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
  • the formulations can be prepared, for example, by mixing the active ingredient with formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions.
  • the active ingredients can also be formulated with other adjuvants, for example finely divided solids, mineral oils, vegetable oils, modified vegetable oils, organic solvents, water, surface-active substances or combinations thereof.
  • the active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into their surroundings in controlled amounts (e.g. slow release). Microcapsules usually have a diameter of , from 0.1 to 500 microns.
  • the active ingredients contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight.
  • the active ingredients can be present in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution.
  • the encapsulating membranes comprise, for example, natural and synthetic gums, cellulose, styrene-butadiene copolymers, polyacrylonitrile, polyacrylate, polyester, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art in this connection.
  • the formulation adjuvants suitable for the preparation of the compositions according to the invention are known perse.
  • liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylenes carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1 ,4-dioxane,
  • Water is generally the carrier of choice for the dilution of the concentrates.
  • Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montomorillonite, cottonseed husks, wheatmeal, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar materials, as described, for example, in CFR 180.1001. (c) & (d).
  • a large number of surface-active substances can advantageously be used both in solid and in liquid formulations, especially in those formulations which can be diluted with a carrier prior to use.
  • Surface-active substances may be anionic, cationic, non-ionic or polymeric and they may be used as emulsifiying, wetting or suspending agents or for other purposes.
  • Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol- alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride, polyethylene glycol esters of fatty acids,
  • Further adjuvants which can usually be used in pesticidal formulations include crystallisation inhibitors, viscosity-modifying substances, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing aids, anti-foams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion-inhibitors, fragrances, wetting agents, absorption improvers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, anti-freezes, microbiocides, and also liquid and solid fertilisers.
  • the formulations may also comprise additional active substances, for example further herbicides, herbicide safeners, plant growth regulators, fungicides or insecticides.
  • compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives.
  • the amount of oil additive used in the composition according to the invention is generally from 0.01 to 10 %, based on the spray mixture.
  • the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared.
  • Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rh ⁇ ne-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow.
  • a preferred additive contains, for example, as active components essentially 80 % by weight alkyl esters of fish oils and 15 % by weight methylated rapeseed oil, and also 5 % by weight of customary emulsifiers and pH modifiers.
  • Especially preferred oil additives comprise alkyl esters of C 8 -C 22 fatty acids, especially the methyl derivatives of C 12 -Ci 8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being important.
  • Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) and methyl oleate (CAS-112-62-9).
  • a preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH).
  • Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000.
  • the application and action of the oil additives can be further improved by combining them with surface-active substances, such as non-ionic, anionic or cationic surfactants.
  • surface-active substances such as non-ionic, anionic or cationic surfactants.
  • suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485.
  • Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C 12 -C 22 fatty alcohols having a degree of ethoxylation of from 5 to 40.
  • Examples of commercially available surfactants are the Genapol types (Clariant AG).
  • silicone surfactants especially polyalkyl-oxide-modified heptamethyltrisiloxanes, which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants.
  • concentration of surface-active substances in relation to the total additive is generally from 1 to 30 % by weight.
  • oil additives that consist of mixtures of oils or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Syngenta AG, CH) and Actipron® (BP Oil UK Limited, GB).
  • the said surface-active substances may also be used in the formulations alone, that is to say without oil additives.
  • oil additive/surfactant mixture can contribute to a further enhancement of action.
  • Suitable solvents are, for example, Solvesso® (ESSO) and Aromatic Solvent® (Exxon Corporation). The concentration of such solvents can be from 10 to 80 % by weight of the total weight.
  • Such oil additives which may be in admixture with solvents, are described, for example, in US-A-4 834 908.
  • a commercially available oil additive disclosed therein is known by the name MERGE® (BASF Corporation).
  • Further oil additives that are preferred according to the invention are SCORE® (Syngenta Crop Protection Canada) and Adigor® (Syngenta Crop Protection Canada).
  • alkylpyrrolidones e.g. Agrimax®
  • formulations of alkylpyrrolidones such as, for example, Agrimax®
  • synthetic latices such as, for example, polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®)
  • propionic acid for example Eurogkem Pen-e-trate®
  • the herbicidal formulations generally contain from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of a compound of formula I and from 1 to 99.9 % by weight of a formulation adjuvant, which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rate of application of the compounds of formula I may vary within wide limits and depends upon the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed or grass to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • the compounds of formula I according to the invention are generally applied at a rate of 1- 2000 g/ha, preferably 1- 1000 g / ha and most preferably at 1- 500 g / ha.
  • Emulsifiable concentrates active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 %
  • Dusts active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
  • Suspension concentrates active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 %
  • Wettable powders active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 %
  • Granules active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
  • Emulsifiable concentrates a) b) c) d) active ingredient 5 % 10% 25% 50% calcium dodecylbenzene- sulfonate 6 % 8% ' 6% 8 % castor oil polyglycol ether 4% - - 4% 4 %
  • Emulsions of any desired concentration can be prepared from such concentrates by dilution with water.
  • Wettable powders a) b) c) d) active ingredient 5% 25% 50% 80% sodium lignosulfonate 4% - 3% - sodium lauryl sulfate 2% 3% - 4% sodium diisobutylnaphthalene- sulfonate - 6% 5% 6% octylphenol polyglycol ether - 1 % 2% -
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, yielding wettable powders which can be diluted with water to give suspensions of any desired concentration.
  • the active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier and the solvent is subsequently evaporated off in vacuo.
  • the finely ground active ingredient is applied uniformly, in a mixer, to the carrier moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
  • Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
  • Suspension concentrates a) b) C) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether - 1 % 2 % -
  • the finely ground active ingredient is intimately mixed with the adjuvants, yielding a suspension concentrate from which suspensions of any desired concentration can be prepared by dilution with water.
  • the invention relates also to a method for the selective control of grasses and weeds in crops of useful plants, and for non-selective weed control, which comprises treating the useful plants or the area under cultivation or the locus thereof with a compound of formula I.
  • Crops of useful plants in which the compositions according to the invention can be used include especially cereals, in particular wheat and barley, rice, corn, rape, sugarbeet, sugarcane, soybean, cotton, sunflower, peanut and plantation crops.
  • crops is to be understood as also including crops that have been rendered tolerant to herbicides or classes of herbicides (for example ALS, GS, EPSPS, PPO and HPPD inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides or classes of herbicides for example ALS, GS, EPSPS, PPO and HPPD inhibitors
  • An example of a crop that has been rendered tolerant e.g. to imidazolinones, such as imazamox, by conventional methods of breeding is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.
  • the weeds to be controlled may be both monocotyledonous and dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica. Control of monocotyledonous weeds, in particular Agrostis, Avena, Setaria, Lolium, Echinochloa, Bromus, Alopecurus and Sorghum is very extensive.
  • Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).
  • Bt maize are the Bt-176 maize hybrids of NK® (Syngenta Seeds).
  • the Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins and transgenic plants able to synthesise such toxins are described in EP-A-451 878, EP- A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529.
  • transgenic plants that contain one or more genes which code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
  • Plant crops and their seed material can be resistant to herbicides and at the same time also to insect feeding ("stacked" transgenic events). Seed can, for example, have the ability to express an insecticidally active Cry3 protein and at the same time be glyphosate-tolerant.
  • the term "crops" is to be understood as also including crops obtained as a result of conventional methods of breeding or genetic engineering which contain so-called output traits (e.g. improved flavour, storage stability, nutritional content).
  • Areas under cultivation are to be understood as including land where the crop plants are already growing as well as land intended for the cultivation of those crop plants.
  • the compounds of formula I according to the invention can also be used in combination with further herbicides.
  • the compound of the formula I is one of those compounds listed in Tables 1 to 146 below.
  • the following mixtures of the compound of formula I are especially important: compound of formula I + acetochlor, compound of formula I + acifluorfen, compound of formula I + acifluorfen-sodium, compound of formula I + aclonifen, compound of formula I + acrolein, compound of formula I + alachlor, compound of formula I + alloxydim, compound of formula I + allyl alcohol, compound of formula I + ametryn, compound of formula I + amicarbazone, compound of formula I + amidosulfuron, compound of formula I + aminopyralid, compound of formula I + amitrole, compound of formula I + ammonium sulfamate, compound of formula I + anilofos, compound of formula I + asulam, compound of formula I + atraton, compound of formula I
  • the mixing partners for the compound of formula I may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 12th Edition (BCPC) 2000.
  • the compounds of formula I according to the invention can also be used in combination with safeners.
  • the compound of the formula I is one of those compounds listed in Tables 1 to 146 below.
  • the following mixtures with safeners especially, come into consideration: compound of formula I + cloquintocet-mexyl, compound of formula I + cloquintocet acid and salts thereof, compound of formula I + fenchlorazole-ethyl, compound of formula I + fenchlorazole acid and salts thereof, compound of formula I + mefenpyr-diethyl, compound of formula I + mefenpyr diacid, compound of formula I + isoxadifen-ethyl, compound of formula I + isoxadifen acid, compound of formula I + furilazole, compound of formula I + furilazole R isomer, compound of formula (I) + N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benz
  • Benoxacor, cloquintocet-mexyl, cyprosulfamide, mefenpyr-diethyl and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide are especially preferred, where cloquintocet- mexyl is particularly valuable.
  • Step 1 Preparation of (1RS,2SR,6RS, 7Sf?)-10-oxatricyclo[5.2.1.0 ,2 ⁇ .6 ],dec-8-ene-3,5-dione
  • Step 2 Preparation of (1RS,2SR,6RS, 7Sf?)-10-oxatricyclo[5.2.1.0 2 ' 6 ]decane-3,5-dione.
  • Step 3 Preparation of ⁇ 1RS,2SR,6RS, 7S/ : ?)-4-(2,6-diethyl-4-methylphenyl)-10-oxatricyclo- [5.2.1.0 2 ⁇ 3 ]decane-3,5-dione.
  • the iodonium ylide (3 g, 8.15 mmol), prepared above, is added to a solution of 2,6-diethyl-4- methylphenylboronic acid (1.57 g, 8.15 mmol), tetrabutylammonium bromide (2.63 g, 8.15 mmol), lithium hydroxide monohydrate (1.03 g, 24.5 mmol) and palladium (II) acetate (92 mg, 0.41 mmol) in 1 ,2-dimethoxyethane (80 ml) and water (20 ml) and the reaction mixture is heated at 5O 0 C for 5 hours under an atmosphere of nitrogen.
  • the reaction mixture is cooled to room temperature and partitioned between dilute aqueous hydrochloric acid and ethyl acetate.
  • the organic phase is then extracted into 0.5 M aqueous potassium carbonate solution and the organic phase discarded.
  • the aqueous phase is acidified with concentrated hydrochloric acid and extracted with ethyl acetate.
  • the organic extract is dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure.
  • Step 1 Preparation of 2-bromo-3-methoxycyclopent-2-enone.
  • Step 2 Preparation of 2-(2,6-diethyl-4-rnethylphenyl)-3-methoxycyclopent-2-enone.
  • the reaction mixture is heated at 90°C for 6.5 hours and then allowed to cool to room temperature overnight.
  • the reaction is diluted with water (400 ml) and extracted with ethyl acetate (3 x 150 ml). The combined organic extracts are washed with brine (50 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated to dryness under reduced pressure to give a brown oil.
  • the crude product is purified by column chromatography on silica gel to give 2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone.
  • Step 3 Preparation of 5-chloro-2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone.
  • Step 4 Preparation of (7RS,2/?S,6SR, 7SR)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10-oxa- tricyclo[5.2.1.0 26 ]deca-4,8-dien-3-one.
  • the pH of the aqueous phase is adjusted to approx. 2 by addition of 5 M aqueous hydrochloric acid and then extracted with ethyl acetate (3 x 10 ml). The combined organic extracts are washed with brine (10 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated to dryness under reduced pressure to give a yellow oil.
  • the crude product is purified by column chromatography on silica gel to give (7f?S,2f?S,6SS, 7SR)-4-(2,6-diethyl-4-methylphenyl)-10- oxatricyclo-[5.2.1.0 2
  • Step 1 Preparation of (1RS,2SR,6RS, 7SR)-5-methoxy-10-oxatricyclo[5.2.1.0 26 ]dec-4-en-3-one.
  • Step 2 Preparation of (7RS,2SR,6RS, ZSRH-bromo-S-methoxy-IO-oxatricyclotS ⁇ .I .O ⁇ ldec ⁇ - en-3-one.
  • Step 3 Preparation of (1RS, 2SR, 6RS, 7SR)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10- oxatricyclo[5.2.1.0 26 ]dec-4-en-3-one.
  • Step 1 Preparation of (2,4,6-trimethylphenyl)furan-2-ylmethanol.
  • Step 2 Preparation of 5-(2,4,6-trimethylphenyl)-4-hydroxycyclopent-2-enone.
  • aqueous phase is extracted into ethyl acetate and the organic solutions are combined, washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure.
  • the residue is purified by column chromatography on silica gel to give 5-(2,4,6-trimethylphenyl)-4-hydroxycyclopent-2-enone.
  • Step 3 Preparation of 2-(2,4,6-trimethylphenyl)cyclopent-4-ene-1 ,3-dione.
  • Step 4 Preparation of ( 1RS, 2SR, 6RS, 7Sf?)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.0 2l6 ]dec-8-en-3,5-dione.
  • reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give ( ⁇ f?S,2Sf?,6f?S, 7f?S)-4-(2,4,6-trimethylphenyl)-8-trimethylsilylethynyl-10-oxatricyclo- [5.2.1.0 2l6 ]decane-3,5-dione.
  • reaction mixture is then cooled to -70 0 C and a solution of 2- furaldehyde (16 ml, 18.6 g, 190 mmol) in tetrahydrofuran (50 ml) is added dropwise over 40 minutes. On completion of the addition, the reaction is allowed to warm to room temperature and stirred at room temperature for 3 hours. Saturated aqueous ammonium chloride solution ( ⁇ 500 ml) is added and the mixture is extracted into ethyl acetate. The organic solutions are combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is further purified by column chromatography on silica gel to give (5- bromo-2-ethylphenyl)-furan-2-ylmethanol.
  • Step 2 Preparation of 5-(5-bromo-2-ethylphenyl)-4-hydroxycyclopent-2-enone.
  • aqueous phase is extracted into ethyl acetate and the organic solutions are combined, washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure.
  • the residue is purified by column chromatography on silica gel to give 5-(5-bromo-2-ethylphenyl)-4-hydroxycyclopent-2-enone.
  • Step 3 Preparation of 2-(5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione.
  • Step 4 Preparation of ( 1RS, 2SR, 6RS, 7Sf?)-4-(5-bromo-2-ethylphenyl)-1 ,7-dimethyl-10- oxatricyclo[5.2.1.0 26 ]dec-8-en-3,5-dione.
  • 2,5-Dimethylfuran (2.3 ml, 21.6 mmol) and magnesium iodide (0.40 g, 1.4 mmol) are added to a solution of 2-(5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione (2.0 g , 7.2 mmol) in dichloromethane (10 ml) and the mixture is stirred at room temperature for 3 days.
  • reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give (1RS,2SR, 6f?S, 7Sf?)-4-(5-bromo-2-ethylphenyl)-1 , 7- dimethyl-10-oxatricyclo[5.2.1.0 2 6 ]dec-8-en-3,5-dione.
  • Furan (4.0 ml, 55.0 mmol) and magnesium iodide (1.00 g, 3.6 mmol) are added to a solution of 2- (5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione (5.0 g, 17.9 mmol) in dichloromethane (20 ml) and the mixture is stirred at room temperature for 3 days.
  • a further quantity of furan (1.3 ml, 17.8 mmol) is added and stirring continued for 18 hours, and then a further quantity of furan (1.3 ml, 17.8 mmol) is added and the mixture is stirred for 48 hours, and then allowed to stand at room temperature for 5 days.
  • the catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure to give ( ⁇ /?S,2Sf?,6f?S, 7Sf?)-4-(5-bromo-2-ethylphenyl)-10-oxatricyclo-[5.2.1.0 2
  • the catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure to give ( ⁇ f?S,2Sf?,6f?S, 7SR8Sf?)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.0 2i6 ]decane-3,5-dione.
  • Step 1 Preparation of (7RS,2SR6Sf?,7Sf?)-5-benzyloxy-7-hydroxymethyl-4-(2,4,6- trimethylphenylJ-IO-oxatricycloIS ⁇ .I .O ⁇ deca ⁇ . ⁇ -dien-S-one and (IRS ⁇ SR ⁇ RSJSRy ⁇ - benzyloxy-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.0 2 ' 6 ]deca-4,8-dien-3- one
  • Benzyl bromide (0.72 ml, 6.1 mmol) is added to a mixture of potassium carbonate (840 mg, 6.1 mmol) and ( ⁇ f?S,2Sf?,6f?S,7Sf?)-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.0 26 ]dec-8-ene-3,5-dione (1.80 g, 5.8 mmol) in acetone (80 ml), and the reaction mixture is heated at reflux for 4 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted with ethyl acetate.
  • Step 2 Preparation of tert-butyl carbamic acid [(7RS,2f?S,6/?S,7SR)-3-benzyloxy-5-oxo-4-(2,4,6- thmethylphenyO-I O-oxatricyclofS ⁇ .I .O ⁇ ldeca ⁇ . ⁇ -dien-i-ylJmethyl ester and tert-butyl carbamic acid [(tf?S,2SR6f?S,7Sf?)-5-benzyloxy-3-oxo-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.0 2l6 ]deca-4,8-dien-1-yl]methyl ester.
  • Step 3 Preparation of terf-butyl carbamic acid [(7RS,2Sf?,6f?S, 7SR)-3,5-dioxo-4-(2,4,6- trimethylphenylJ-IO-oxatricyclot ⁇ .i .O ⁇ dec- ⁇ -en-i-yllmethyl ester.
  • tert-butyl carbamic acid [(1RS,2SR, 6RS, 7Sf?)-3,5-dioxo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.0 26 ]dec-8-en-1- yl]methyl.
  • Step 1 Preparation of 4-bromo-2-ethylphenyllead triacetate.
  • reaction mixture is cooled to 0 0 C, and -potassium- carbonate (2.66 g,- 19.3 mmol) is added portionwise.-The mixture is stirred for 5 minutes, then filtered through a small plug of diatomaceous earth, washing with chloroform. The filtrate concentrated under reduced pressure to give 4-bromo-2-ethylphenyllead triacetate.
  • Step 2 Preparation of (7RS,2Sf?,6f?S,7SR)-4-(4-bromo-2-ethylphenyl)-10-oxatricyclo- [5.2.1.0 26 ]decane-3,5-dione.
  • the mixture is cooled to room temperature, 2 M aqueous hydrochloric acid (40 ml) is added, and the mixture is stirred vigorously for 15 minutes, then filtered through a small plug of diatomaceous earth, washing with 40ml dichloromethane.
  • the organic phase is separated, and the aqueous phase is extracted with dichloromethane (2 x 20 ml).
  • the organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure.
  • Solvent A H 2 O containing 0.1 % HCOOH
  • Solvent B CH 3 CN containing 0.1% HCOOH
  • the characteristic values obtained for each compound were the retention time (rt, recorded in minutes) and the molecular ion (typically the cation MH + ), as listed in Table T1.
  • Table 1 covers compounds of formula (A)
  • Table 2 covers compounds of formula (A), wherein R 1 is ethyl, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 3 covers compounds of formula (A) 1 wherein R 1 and R 4 are ethyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1 .
  • Table 4 covers compounds of formula (A), wherein R 1 , R 2 and R 4 are ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 5 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 6 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 7 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 8 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 9 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 10 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is ethynyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 11 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 4 is vinyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 12 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 13 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 14 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 15 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 16 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 17 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is ethynyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 18 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 4 is vinyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 19 covers compounds of formula (A), wherein R 1 is ethynyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 20 covers compounds of formula (A), wherein R 1 is ethynyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 21 covers compounds of formula (A), wherein R 1 is ethynyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 22 covers compounds of formula (A), wherein R 1 is ethynyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 23 covers compounds of formula (A), wherein R 1 is ethynyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 24 covers compounds of formula (A), wherein R 1 and R 4 are ethynyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 25 covers compounds of formula (A), wherein R 1 is vinyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 26 covers compounds of formula (A), wherein R 1 is vinyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 27 covers compounds of formula (A), wherein R 1 is vinyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 28 covers compounds of formula (A), wherein R 1 is vinyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 29 covers compounds of formula (A), wherein R 1 is vinyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 30 covers compounds of formula (A) 1 wherein R 1 and R 4 are vinyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 31 covers compounds of formula (A), wherein R 1 is methyl, R 2 , R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 32 covers compounds of formula (A), wherein R 1 is methyl, R 2 is methoxy, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 33 covers compounds of formula (A), wherein R 1 is methyl, R 2 is trifluoromethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 34 covers compounds of formula (A), wherein R 1 is methyl, R 2 is ethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 35 covers compounds of formula (A), wherein R 1 is methyl, R 2 is ethynyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 36 covers compounds of formula (A), wherein R 1 is methyl, R 2 is vinyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 37 covers compounds of formula (A), wherein R 1 is methyl, R 2 is chlorine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 38 covers compounds of formula (A), wherein R 1 is methyl, R 2 is bromine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 39 covers compounds of formula (A), wherein R 1 is methyl, R 2 is iodine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 40 covers compounds of formula (A) 1 wherein R 1 is ethyl, R 2 , R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 41 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methoxy, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 42 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is trifluoromethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 43 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 44 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is ethynyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 45 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is vinyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 46 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is chlorine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 47 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is bromine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 48 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is iodine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 49 covers compounds of formula (A), wherein R 1 and R 4 are methyl, R 2 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1 .
  • Table 50 covers compounds of formula (A), wherein R 1 and R 4 are methyl, R 2 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1 .
  • Table 51 covers compounds of formula (A), wherein R 1 and R 4 are methyl, R 2 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 52 covers compounds of formula (A), wherein R 1 is methyl, R 2 is chlorine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 53 covers compounds of formula (A), wherein R 1 is methyl, R 2 is bromine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 54 covers compounds of formula (A), wherein R 1 is methyl, R 2 is iodine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 55 covers compounds of formula (A), wherein R 1 and R 4 are ethyl, R 2 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 56 covers compounds of formula (A), wherein R 1 and R 4 are ethyl, R 2 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 57 covers compounds of formula (A), wherein R 1 and R 4 are ethyl, R 2 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 58 covers compounds of formula (A), wherein R 1 is methyl, R 2 is chlorine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 59 covers compounds of formula (A), wherein R 1 is methyl, R 2 is bromine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 60 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is chlorine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 61 covers compounds of formula (A), wherein R 1 is ethyl, R 2 is bromine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 62 covers compounds of formula (A), wherein R 1 and R 4 are methyl, R 2 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 63 covers compounds of formula (A), wherein R 1 is methyl, R 2 is methoxy, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 64 covers compounds of formula (A), wherein R 1 and R 4 are ethyl, R 2 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 65 covers compounds of formula (A), wherein R 1 , R 2 , R 3 and R 4 are methyl, R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 66 covers compounds of formula (A), wherein R 1 is difluoromethoxy, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 67 covers compounds of formula (A), wherein R 1 is difluoromethoxy, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 68 covers compounds of formula (A), wherein R 1 is trifluoromethoxy, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 67 covers compounds of formula (A), wherein R 1 is trifluoromethoxy, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 70 covers compounds of formula (A), wherein R 1 is cyclopropyl, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 71 covers compounds of formula (A), wherein R 1 is cyclopropyl, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 72 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 3 , R 5 and R 12 are hydrogen, R 4 is cyclopropyl and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 73 covers compounds of formula (A), wherein R 1 and R 2 are ethyl, R 3 , R 5 and R 12 are hydrogen, R 4 is cyclopropyl and R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined in Table 1.
  • Table 74 covers compounds of formula (AH)
  • R 1 , R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 74
  • Table 75 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 76 covers compounds of formula (AH), wherein R 1 and R 4 are ethyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 77 covers compounds of formula (AH), wherein R 1 , R 2 and R 4 are ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 78 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 3 , R 4 , R 5 and R 12 n and R 3 6 , o R8 B , D R9 11 are hydroge , and R are as defined in Table 74.
  • Table 79 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 80 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 81 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 82 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 83 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is ethynyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 84 covers compounds of formula (AH), wherein R 1 and R 2 are methyl, R 4 is vinyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 85 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 86 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 87 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 88 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 89 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 90 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is ethynyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 91 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methyl, R 4 is vinyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 92 covers compounds of formula (AH), wherein R 1 is ethynyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 93 covers compounds of formula (AH), wherein R 1 is ethynyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 94 covers compounds of formula (AH), wherein R 1 is ethynyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 95 covers compounds of formula (AH), wherein R 1 is ethynyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 96 covers compounds of formula (AH), wherein R 1 is ethynyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 97 covers compounds of formula (AH), wherein R 1 and R 4 are ethynyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 98 covers compounds of formula (AH), wherein R 1 is vinyl, R 2 is methyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 99 covers compounds of formula (AH), wherein R 1 is vinyl, R 2 is methyl, R 4 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 100 covers compounds of formula (AH), wherein R 1 is vinyl, R 2 is methyl, R 4 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 101 covers compounds of formula (AH), wherein R 1 is vinyl, R 2 is methyl, R 4 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 102 covers compounds of formula (AH), wherein R 1 is vinyl, R 2 is methyl, R 4 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 103 covers compounds of formula (AH), wherein R 1 and R 4 are vinyl, R 2 is methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 104 covers compounds of formula (AH), wherein R 1 is methyl, R 2 , R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 105 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is methoxy, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 106 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is trifluoromethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 107 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is ethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 108 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is ethynyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 109 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is vinyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined inTable 74.
  • Table 110 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is chlorine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 111 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is bromine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 112 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is iodine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 1 13 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 , R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 1 14 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is methoxy, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 115 covers compounds of formula (AH) 1 wherein R 1 and R 2 are ethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 116 covers compounds of formula (AH) 1 wherein R 1 is ethyl, R 2 is trifluoromethyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 117 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is ethynyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 118 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is vinyl, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 1 19 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is chlorine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 120 covers compounds of formula (AH) 1 wherein R 1 is ethyl, R 2 is bromine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 121 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is iodine, R 3 , R 4 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 122 covers compounds of formula (AH), wherein R 1 and R 4 are methyl, R 2 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 123 covers compounds of formula (AH), wherein R 1 and R 4 are methyl, R 2 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 124 covers compounds of formula (AH), wherein R 1 and R 4 are methyl, R 2 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 125 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is chlorine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 126 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is bromine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 127 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is iodine, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 128 covers compounds of formula (AH), wherein R 1 and R 4 are ethyl, R 2 is chlorine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 129 covers compounds of formula (AH), wherein R 1 and R 4 are methyl, R 2 is bromine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 130 covers compounds of formula (AH), wherein R 1 and R 4 are ethyl, R 2 is iodine, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 131 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is chlorine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 132 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is bromine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 133 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is chlorine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 134 covers compounds of formula (AH), wherein R 1 is ethyl, R 2 is bromine, R 3 is hydrogen, R 4 is methoxy, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 135 covers compounds of formula (AH), wherein R 1 and R 4 are methyl, R 2 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 136 covers compounds of formula (AH), wherein R 1 is methyl, R 2 is methoxy, R 3 is hydrogen, R 4 is ethyl, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 137 covers compounds of formula (AH), wherein R 1 and R 4 are ethyl, R 2 is methoxy, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 138 covers compounds of formula (AH) wherein R 1 , R 2 , R 3 and R 4 are methyl, R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 139 covers compounds of formula (A), wherein R 1 is difluoromethoxy, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 140 covers compounds of formula (A), wherein R 1 is difluoromethoxy, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 141 covers compounds of formula (A), wherein R 1 is trifluoromethoxy, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 142 covers compounds of formula (A), wherein R 1 is trifluoromethoxy, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 143 covers compounds of formula (A), wherein R 1 is cyclopropyl, R 2 and R 4 are methyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 144 covers compounds of formula (A), wherein R 1 is cyclopropyl, R 2 is methyl, R 4 is ethyl, R 3 , R 5 and R 12 are hydrogen and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 145 covers compounds of formula (A), wherein R 1 and R 2 are methyl, R 3 , R 5 and R 12 are hydrogen, R 4 is cyclopropyl and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • Table 146 covers compounds of formula (A), wherein R 1 and R 2 are ethyl, R 3 , R 5 and R 12 are hydrogen, R 4 is cyclopropyl and R 6 , R 8 , R 9 , and R 11 are as defined in Table 74.
  • a solution of pivaloyl chloride (0.055 g, 0.57 mmol) in dichloromethane (2 ml) is added dropwise to a solution of ( ⁇ S ⁇ SReRS ⁇ SRH ⁇ .e-trimethylphenyO-IO-oxatricyclofS.a.i .O ⁇ decane- 3,5-dione (0.12 g, 0.42 mmol) in dichloromethane (2 ml) at room temperature and the reaction mixture is stirred for 2 minutes.
  • a solution of triethylamine (0.08 ml) in dichloromethane (1 ml) is added and the reaction mixture is stirred at room temperature for 3 hours.
  • reaction mixture is diluted with dichloromethane (20 ml) and washed with saturated aqueous sodium bicarbonate solution.
  • the organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure to give (1RS,2SR,6RS,7SR)-5-oxo-4-(2,4 ⁇ - trimethylphenylJ-IO-oxatricyclofS ⁇ .I .O ⁇ ldec-S-en-S-yl 2,2-dimethylpropionate as a colourless oil.
  • Alopecurus myosuroides Alopecurus myosuroides (ALOMY), Avena fatua (AVEFA), Lolium perenne (LOLPE), Setaria faberi (SETFA), Digitaria sanguinalis (DIGSA), Echinochloa crus-galli (ECHCG)
  • Test compounds were applied post-emergence at 6Og ai/ha, alone and in combination with cloquintocet-mexyl at 6Og ai/ha; the adjuvant Adigor (0.5%) was included for every treatment.
  • the application volume was 200l/ha.
  • Target plants were 2-3 leaf seedlings of winter wheat 'Hereward' and winter barley 'Antoniya' grown in a greenhouse under ambient conditions. Assessments were made at 14-21 days after application.
  • the test compound T1 was applied at 100 and 20Og ai/ha, alone and in combination with a range of safeners as 1 :1 mixtures (for example at 100g + 100g; 20Og + 20Og) to the test plants - wheat and maize - at the 2-3 leaf stage.
  • a 4-way safener mixture (cloquintocet-mexyl, benoxacor, fluxofenim and compound A*) was also applied with the test compound so that each safener was used a 1 :1 ratio (for example at 100+100+100+100+100g ai/ha). Assessments were made at 14- 21 days after application.
  • Compound A is N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.

Abstract

Compounds of formula (I) wherein the substituents are as defined in claim 1, are suitable for use as herbicides.

Description

Novel herbicides
The present invention relates to novel, herbicidally active cyclopentanedione compounds, and derivatives thereof, to processes for their preparation, to compositions comprising those compounds, and to their use in controlling weeds, especially in crops of useful plants, or in inhibiting undesired plant growth.
Cyclopentanedione compounds having herbicidal action are described, for example, in WO 01/74770 and WO 96/03366.
Novel cyclopentanedione compounds, and derivatives thereof, having herbicidal and growth- inhibiting properties have now been found.
The present invention accordingly relates to compounds of formula I
Figure imgf000002_0001
wherein
G is hydrogen or an alkali metal, alkaline earth metal, sulfonium, ammonium or a latentiating group,
R1 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen,
CrC2alkoxy or CrC2haloalkoxy,
R2, R3 and R4 are independently of each other hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen, C1-C2BIkOXy Or C1-C2 haloalkoxy,
R5 and R12 are independently of each other hydrogen, CrC3alkyl, d-Cshaloalkyl, CrC3alkyoxy, d-Csalkylthio, halogen or CrC6alkoxycarbonyl, or
R5 and R12 join together to form a 3-7 membered carbocyclic ring, optionally containing an oxygen or sulfur atom, and R6, R7, R8, R9, R10 and R11 are independently of each other hydrogen or a substituent, or R7 and R8, or R9 and R10, together with the carbon atoms to which they are attached form a keto, an optionally substituted alkenyl or optionally substituted imino unit, or any two of R7, R8, R9 and R10 together form a 3-8 membered carbocyclic ring optionally containing a heteroatom selected from O, S or N and optionally substituted, or R7 and R10 together form a bond.
In the substituent definitions of the compounds of the formula I, each alkyl moiety either alone or as part of a larger group (such as alkoxy, alkylthio, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, π-hexyl, isopropyl, n-butyl, sec-butyl, isobutyl, te/f-butyl or neopentyl. The alkyl groups are suitably C1-C6 alkyl groups, but are preferably C1-C4 alkyl or C1-C3 alkyl groups, and, more preferably, d^alkyl groups.
When present, the optional substituents on an alkyl moiety (alone or as part of a larger group such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) include one or more of halogen, nitro, cyano, C3-7 cycloalkyl (itself optionally substituted with C1-6 alkyl or halogen), C5-7 cycloalkenyl (itself optionally substituted with C1-6 alkyl or halogen), hydroxy, C1-Io alkoxy, C1-10 alkoxy(C1-10)alkoxy, tri(C1-4)alkylsilyl(C1-6)alkoxy, C1-6 alkoxycarbonyl(C1-10)alkoxy, C1-10 haloalkoxy, aryl(C1-4)-alkoxy (where the aryl group is optionally substituted), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), C3- 10 alkenyloxy, C3-10 alkynyloxy, mercapto, C1-10 alkylthio, C1-10 haloalkylthio, aryl(C1-4)alkylthio (where the aryl group is optionally substituted), C3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), tri(C1-4)alkylsilyl(C1-6)alkylthio, arylthio (where the aryl group is optionally substituted), C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, arylsulfonyl (where the aryl group may be optionally substituted), ^i(C1- 4)alkylsilyl, aryldi(C1-4)alkylsilyl, (C1-4)alkyldiarylsilyl, triarylsilyl, aryl(C1-4)alkylthio(C1-4)alkyl, aryloxy(C1-4)alkyl, formyl, C1-10 alkylcarbonyl, HO2C, C1-10 alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6 alkyl)aminocarbonyl, /V-(C1-3 alkyl)-Λ/-(C-ι-3 alkoxy)aminocarbonyl, C1-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(C1-6)alkylaminocarbonyloxy, C1-6alkyliminooxy, C3-6alkenyloxyimino, aryloxyimino, aryl (itself optionally substituted), heteroaryl (itself optionally substituted), heterocyclyl (itself optionally substituted with C1-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy, (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with C1-6 alkyl or halogen), amino, C1-6 alkylamino, di(C1-6)alkylamino, C1-6 alkylcarbonylamino, Λ/-(C1-6)alkylcarbonyl-Λ/-(C1-6)alkylamino, C2-6 alkenylcarbonyl, C2-6 alkynylcarbonyl, C3-6 alkenyloxycarbonyl, C3-6 alkynyloxycarbonyl, aryloxycarbonyl (where the aryl group is optionally substituted) and arylcarbonyl (where the aryl group is optionally substituted).
Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configu ration. Examples are vinyl, allyl and propargyl. Alkenyl and alkynyl moieties can contain one or more double and/or triple bonds in any combination. It is understood, that allenyl and alkylinylalkenyl are included in these terms. It is to be understood that the alkenyl units formed by R7 together with R8 are directly attached to the bridged cyclohexane ring by a double bond.
When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.
Halogen is fluorine, chlorine, bromine or iodine.
Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF3, CF2CI, CF2H, CCI2H, FCH2, CICH2, BrCH2, CH3CHF, (CHs)2CF, CF3CH2 or CHF2CH2.
In the context of the present specification the term "aryl" refers to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
The term "heteroaryl" preferably refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulphur. Examples of such groups include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1 ,2,4-oxadiazolyl, 1 ,3,4-oxadiazolyl, 1 ,2,5-oxadiazolyl, 1 ,2,3-thiadiazolyl, 1 ,2,4-thiadiazolyl, 1 ,3,4-thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1 ,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, 2,1 ,3-benzoxadiazole, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl and indolizinyl.
Preferred examples of heteroaromatic radicals include pyridyl, pyrimidinyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, 2,1 ,3-benzoxadiazolyl and thiazolyl. Another group of preferred heteroaryls comprises furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl or quinoxalinyl.
The term "heterocyclyl" preferably refers to a non-aromatic preferably monocyclic or bicyclic ring systems containing up to 7 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1 ,3-dioxolane, oxetane, tetrahydrofuran, morpholine, thiomorpholin and piperazine. When present, the optional substituents on heterocyclyl include d.6 alkyl and C1-6 haloalkyl as well as those optional substituents given above for an alkyl moiety.
Cycloalkyl includes preferably cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Cycloalkylalkyl is preferentially cyclopropylmethyl. Cycloalkenyl includes preferably cyclopentenyl and cyclohexenyl. When present, the optional substituents on cycloalkyl or cycloalkenyl include C1-3 alkyl as well as those optional substituents given above for an alkyl moiety.
Carbocyclic rings such as those formed by R7 to gether with R8 include aryl, cycloalkyl or carbocyclic groups, and cycloalkenyl groups.
When present, the optional substituents on aryl, heteroaryl and carbocycles are preferably selected independently, from halogen, nitro, cyano, rhodano, isothiocyanato, Ci-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy-(C1-6)alkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-7 cycloalkyl (itself optionally substituted with C1-6 alkyl or halogen), C5-7 cycloalkenyl (itself optionally substituted with C1-6 alkyl or halogen), hydroxy, C1-I0 alkoxy, C1--I0 alkoxy(C1-10)alkoxy, tri(C1-4)alkylsilyl(C1-6)alkoxy, C1-6 alkoxycarbonyKCv^alkoxy, C1-10 haloalkoxy, aryl(C1-4)alkoxy (where the aryl group is optionally substituted with halogen or C1-6 alkyl), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), C3-10 alkenyloxy, C3-10 alkynyloxy, mercapto, C1-10 alkylthio, C1-10 haloalkylthio, aryl(C1-4)alkylthio, C3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), trKC^-alkylsilyKCvβJalkylthio, arylthio, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, arylsulfonyl, tri(C1-4)alkylsilyl, aryldi(C1-4)-alkylsilyl, (C1-4)alkyldiarylsilyl, triarylsilyl, C1-I0 alkylcarbonyl, HO2C, C1-10 alkoxycarbonyl, aminocarbonyl, Ci-6 alkylaminocarbonyl, di(C1-6 alkyl)-aminocarbonyl, /V-(C1-3 alkyl)-Λ/-(C1-3 alkoxy)aminocarbonyl, C1- 6 alkylcarbonyloxy, arylcarbonyloxy, d^C^alkylamino-carbonyloxy, aryl (itself optionally substituted with C1-6 alkyl or halogen), heteroaryl (itself optionally substituted with C1-6 alkyl or halogen), heterocyclyl (itself optionally substituted with C1-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted with C1-6 alkyl or halogen), heteroaryloxy (where the heteroaryl group is optionally substituted with Ci-6 alkyl or halogen), heterocyclyloxy (where the heterocyclyl group is optionally substituted with C1-6 alkyl or halogen), amino, C1-6 alkylamino, di^. 6)alkylamino, C1-6 alkylcarbonylamino, Λ/-(Ci-6)alkylcarbonyl-Λ/-(Ci-6)alkylamino, arylcarbonyl, (where the aryl group is itself optionally substituted with halogen or C1-6 alkyl) or two adjacent positions on an aryl or heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen or C1-6 alkyl. Further substituents for aryl or heteroaryl include arylcarbonylamino (where the aryl group is substituted by C1-6 alkyl or halogen), (C1-6)alkoxycarbonylamino (C1-6)alkoxycarbonyl-Λ/-(C1-6)alkylamino, aryloxycarbonylamino (where the aryl group is substituted by C1-6 alkyl or halogen), aryloxycarbonyl-Λ/-(C1-6)alkylamino, (where the aryl group is substituted by C1-6 alkyl or halogen), arylsulphonylamino (where the aryl group is substituted by C1-6 alkyl or halogen), arylsulphonyl-Λ/-(C1-6)alkylamino (where the aryl group is substituted by C1-6 alkyl or halogen), aryl-N-(C1-6)alkylamino (where the aryl group is substituted by C1-6 alkyl or halogen), arylamino (where the aryl group is substituted by C1-6 alkyl or halogen), heteroaryl amino (where the heteroaryl group is substituted by C1-6 alkyl or halogen), heterocyclylamino (where the heterocyclyl group is substituted by C1-6 alkyl or halogen), aminocarbonylamino, C1-6 alkylaminocarbonylamino, di(C1-6)alkylaminocarbonylamino, arylaminocarbonylamino where the aryl group is substituted by C1-6 alkyl or halogen), aryl-Λ/-(C1-6)alkylamino-carbonylamino where the aryl group is substituted by C1-6 alkyl or halogen), d-e alkylaminocarbonyl-AHC^alkylamino, di(C1-6)alkylaminocarbonyl-Λ/-(C1-6)alkylamino, arylaminocarbonyl-Λ/-(C1-6)alkylamino where the aryl group is substituted by C1-6 alkyl or halogen) and aryl-Λ/-(C1-6)alkylaminocarbonyl-Λ/-(C1- 6)alkylamino where the aryl group is substituted by C1-6 alkyl or halogen).
For substituted heterocyclyl groups it is preferred that one or more substituents are independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, nitro and cyano. It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (C1-6)alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, pipehdine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (C1-6) alkyl groups. It should be understood that the term "substituent" in the definitions of R6 to R11 comprises preferably all substitutents given above for "aryl", "heteroaryl" and "heterocyclyl".
The invention relates also to the salts which the compounds of formula I are able to form with amines, alkali metal and alkaline earth metal bases or quaternary ammonium bases. Among the alkali metal and alkaline earth metal hydroxides as salt formers, special mention should be made of the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially the hydroxides of sodium and potassium. The compounds of formula I according to the invention also include hydrates which may be formed during the salt formation.
Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary CrC18alkylamines, Ci-C4hydroxyalkylamines and C2-C4- alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four butylamine isomers, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n- propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N1N- diethanolamine, Λ/-ethylpropanolamine, Λ/-butylethanolamine, allylamine, n-but-2-enylamine, n- pent-2-enylamine, 2,3-dimethylbut-2-enylamine, dibut-2-enylamine, n-hex-2-enylamine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n- butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; but especially triethylamine, isopropylamine and diisopropylamine.
Preferred quaternary ammonium bases suitable for salt formation correspond, for example, to the formula [N(R3 Rb R0 Rd)]OH wherein R3, Rb, R0 and Rd are each independently of the others CrC4alkyl. Further suitable tetraalkylammonium bases with other anions can be obtained, for example, by anion exchange reactions. The latentiating groups G are selected to allow its removal by one or a combination of biochemical, chemical or physical processes to afford compounds of formula I where G is H before, during or following application to the treated area or plants. Examples of these processes include enzymatic cleavage, chemical hydrolysis and photoloysis. Compounds bearing such groups G may offer certain advantages, such as improved penetration of the cuticula of the plants treated, increased tolerance of crops, improved compatibility or stability in formulated mixtures containing other herbicides, herbicide safeners, plant growth regulators, fungicides or insecticides, or reduced leaching in soils.
Preferably, in the compounds of the formula I, R6 and R11 are independently of each other hydrogen, halogen, formyl, cyano or nitro or
R6 and R11 are independently of each other CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, CrC6alkoxy,
C3-C7 cycloalkyl, C3-C7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R6 and R11 are independently of each other a group COR13, CO2R14Or CONR15R16, CR17=NOR18,
CR19=NNR20R21, NHR22, NR22R23 or OR24 wherein
R13 is Ci-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R14 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R15 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R16 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, CrC6alkylsulfonyl, phenylsulfonyl, heteroarylsulfonyl, amino, d-
C6alkylamino, diCrC6alkylamino, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R15 and R16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
R17 and R19 are independently of each other hydrogen, Ci-C3alkyl or C3-C6cycloalkyl,
R18, R20 and R21 are independently of each other hydrogen, CrC6alkyl, C3-C6alkenyl, C3-
C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylthiocarbonyl, aminocarbonyl, CrCβalkylaminocarbonyl, diCi-Cβalkylaminocarbonyl, phenyl or heteroaryl, where all these substituents are optionally substituted, R22 is CrC6alkylcarbonyl, Ci-C6alkoxycarbonyl, d-Cβalkylthiocarbonyl, C1-
C6alkylaminocarbonyl, did-Csalkylaminocarbonyl, CrC6alkylsulfonyl, phenylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, phenylthiocarbonyl, phenylsulfonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylthiocarbonyl or heteroarylsulfonyl, where all these substituents are optionally substituted,
R23 is Ci-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, C1-
C6alkoxycarbonyl, CrC6alkylthiocarbonyl, d-Cβalkylaminocarbonyl, did-Cealkylaminocarbonyl,
CrC6alkylsulfonyl, phenyl or heteroaryl, where all these substituents are optionally substituted, or
R22 and R23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and
R24 is C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, d-C6alkylcarbonyl, CrC6alkoxycarbonyl, C1-
C6alkylthiocarbonyl, aminocarbonyl, d-Cβalkylaminocarbonyl, did-Cealkylaminocarbonyl, W(C1-
C6alkyl)silyl, phenyl or heteroaryl, where all these substituents are optionally substituted.
More preferably, R6 and R11 are independently of each other hydrogen, halogen, cyano, optionally substituted d-Cβalkyl or a group COR13, CO2R14 or CONR15R16, CR17=NOR18 or
CR19=NNR20R21, wherein
R13, R14, R15 and R16 are CrC6alkyl,
R17 and R19 are hydrogen or C1-C3 alkyl,
R18 is C1-C3 alkyl, and
R20 and R21 are independently of each other hydrogen or d-C3alkyl.
In particular, R6 and R11 are independently of each other hydrogen, methyl or methyl substituted by d-C3alkoxy.
Preferably, R7, R8, R9 and R10 are independently of each other hydrogen, halogen, hydroxyl, formyl, amino, cyano or nitro, or
R7, R8, R9 and R10 are independently of each other CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-
C6alkoxy, d-Cealkoxyd-Cealkyl, CrC6alkylthio, CrC6alkylsulfinyl, CrC6alkylsulfonyl, C1-
CealkylthioCrCealkyl, d-Cealkylsulfinyld-Cealkyl, d-Cealkylsulfonyld-Cealkyl, C3-C7 cycloalkyl,
C4-C7cycloalkenyl, tri(CrC6alkyl)silyl, aryl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R7, R8, R9 and R10 are independently of each other a group COR13, CO2R14 or CONR15R16,
CR17=NOR18, CR19=NNR20R21, NR22R23 or OR24, wherein
R13 is d-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, R14 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R15 is hydrogen, d-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, d-C6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R16 is hydrogen, d-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, d-C6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, CrC6alkylsulfonyl, amino, d-C6alkylamino, diCrC6alkylamino, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R15 and R16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
R17 and R19 are independently of each other hydrogen, CrC3alkyl or C3-C6cycloalkyl,
R18, R20 and R21 are independently of each other hydrogen, d-C6alkyl, C3-C6alkenyl, C3-
C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylthiocarbonyl, C1-
C6alkylaminocarbonyl, did-Cβalkylaminocarbonyl, phenyl or heteroaryl, where all these substituents are optionally substituted,
R22 and R23 are independently of each other d-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, d-C6alkylcarbonyl, d-C6alkoxycarbonyl, d-C6alkylthiocarbonyl, C1-
C6alkylaminocarbonyl, did-Cβalkylaminocarbonyl, d-C6alkylsulfonyl, phenyl or heteroaryl or
R22 and R23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and
R24 is d-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, d-C6alkylcarbonyl, C1-
C6alkoxycarbonyl, d-Cβalkylthiocarbonyl, d-Cβalkylaminocarbonyl, did-Cβalkylaminocarbonyl,
CrC6alkylsulfonyl, tri(CrC6alkyl)silyl, phenyl or heteroaryl, where all these substituents are optionally substituted.
More preferably, R7, R8, R9 and R10 are hydrogen.
It is also preferred that one of R7, R8, R9 and R10 is methyl or ethyl.
It is also preferred that one of R7, R8, R9 and R10 is an optinally substituted aryl or heteroaryl and more preferably optionally substituted phenyl, naphthyl, furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl,
1 ,2,4-thazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl or quinoxalinyl.
In particular, one of R7, R8, R9 and R10 is pyridyl or pyridyl substituted by trifluoromethyl or halogen. It is also preferred that R7 and R10 form a bond.
Preferably, R7, R8, R9 and R10 are independently of each other hydrogen, cyano, Ci-C6alkyl, C2-
C6alkenyl, CrC6alkoxy, d-Cealkoxyd-Cealkyl, d-Cealkylthiod-Cealkyl, Ci-C6alkylsulfinylCr
C6alkyl, d-Cβalkylsulfonyld-Cealkyl, 3-7 membered heterocyclyl, optionally substituted phenyl or optionally substituted heteroaryl, or CR17=NOR18, wherein
R17 is hydrogen or CrC3 alkyl and
R18 is C1-C3 alkyl.
In another group of preferred compounds of the formula I, R7 and R8, or R9 and R10, together form a unit =0, or form a unit =CR25R26, or form a unit =NR27, or any two of R7, R8, R9 and R10 form a 3-8 membered ring, optionally containing a heteroatom selected from O, S or N and optionally substituted by Ci-C3alkyl, CrC3alkoxy, CrC3alkylthio, d-C3alkylsulfinyl, C1-
C3alkylsulfonyl, Ci-C3haloalkyl, halogen, phenyl, phenyl substituted by Ci-C4alkyl, C1-
C4haloalkyl, CrC4alkoxy, CrC4haloalkoxy, CrC4alkylthio, CrC4alkylsulfinyl, d-C4alkylsulfonyl,
CrC4alkylcarbonyl, d-C4alkoxycarbonyl, aminocarbonyl, d-Cβalkylaminocarbonyl, diCr
C6alkylaminocarbonyl, halogen, cyano or by nitro, heteroaryl or heteroaryl substituted by C1-
C4alkyl, CrC4haloalkyl, Ci-C4alkoxy, CrC4haloalkoxy, d-dalkylthio, CrC4alkylsulfinyl, C1-
C4alkylsulfonyl, CrC4alkylcarbonyl, halogen, cyano or by nitro, wherein
R25and R26 are independently of each other hydrogen, halogen, cyano or nitro, or
R25 and R26 are independently of each other d-C6alkyl, CrC6alkoxy, CrC6alkylamino, CUC1-
C6alkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylaminocarbonyl, (JiC1-
C6alkylaminocarbonyl, /V-phenyl'/V-d-Cealkylaminocarbonyl, /V-phenyld-Cealkyl-N-d-
C6alkylaminocarbonyl, /V-heteroaryl-A/'d-Cealkylaminocarbonyl, /V-heteroaryld-Cealkyl-ZV-d-
C6alkylaminocarbonyl, phenyl, heteroaryl, C3-C8cycloalkyl or 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R25and R26 may be joined together to form a 5-8 membered ring optionally containing a heteroatom selected from O, S or N and optionally substituted by CrC2alkyl or d-C2alkoxy,
R27 is nitro or cyano, or
R27 is d-C6alkylamino, did-C6alkylamino, d-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, phenoxy, phenylamino, Λ/-phenyl-Λ/-CrC6alkylamino, /V-phenyld-Cealkyl-ZV-CrCβalkylamino heteroaryloxy, heteroarylamino, Λ/-heteroaryl-Λ/-CrC6alkylamino or /V-heteroaryld-Cealkyl-ZV-d-
C6alkylamino, where all these substituents are optionally substituted, where, more preferably, R7 and R8, or R9 and R10, together form a unit =0 or =NR27, wherein R27 is C1-3alkoxy or C2-C3 alkenyloxy. More preferably, R7, R8, R9 and R10 are independently of each other hydrogen, cyano, C1-C6SlKyI,
C2-C6alkenyl, d-C6alkoxy, CrCβalkoxyCVCealkyl, 3-7 membered heterocyclyl, optionally substituted phenyl or optionally substituted heteroaryl.
In particular, R7, R8, R9 and R10 are independently of each other hydrogen, methyl, ethyl or optionally substituted phenyl.
In particular, one of R7, R8, R9 and R10 is optionally substituted heteroaryl, preferably optionally substituted furyl, thienyl, pyrazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl or quinoxalinyl, and more preferably pyridyl substituted once or twice by trifluoromethyl or halogen.
In another group of preferred compounds of the formula I, R1, R2 and R4 are methyl and R3 is hydrogen.
In another group of preferred compounds of the formula I, R1, R2 and R4 are methyl and R3 is hydrogen, and
R7, R8, R9 and R10 are independently of each other hydrogen, cyano, CrC6alkyl, C2-C6alkenyl, CrC6alkoxy, Ci-C6alkoxyCrC6alkyl, 3-7 membered heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl, preferably optionally substituted heteroaryl, and in particular pyridyl substituted once or twice by trifluoromethyl or halogen.
In another group of preferred compounds of the formula I, R5 and R12 are independently of each other hydrogen or CrC3alkyl, where hydrogen is more preferred.
In another group of preferred compounds of the formula I, R1 is methyl, ethyl, vinyl, ethynyl, cyclopropyl, difluoromethoxy, trifluoromethoxy or CrC2 alkoxy and
R2, R3 and R4 are independently of each other hydrogen, methyl, ethyl, vinyl or ethynyl.
Preferably in this group, R1 is ethyl and R2, R3 and R4 are independently of each other hydrogen, methyl or ethyl.
Preferably in this group, R1, R2 and R4 are methyl and R3 is hydrogen.
The latentiating group G is preferably selected from the groups CrC8alkyl, C2-C8 haloalkyl, phenylCrC8alkyl (wherein the phenyl may optionally be substituted by Ci-C3alkyl, CrCshaloalkyl, CrC3alkoxy, CrC3haloalkoxy, CrCsalkylthio, CrCsalkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), heteroaryld-Cβalkyl (wherein the heteroaryl may optionally be substituted by d-Csalkyl, CrC3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, CrC3alkylthio, CrC3alkylsulfinyl, C1- C3 alkylsulfonyl, halogen, cyano or by nitro), C3-C8 alkenyl, C3-C8 haloalkenyl, C3-C8 alkynyl, C(Xa)-Ra, C(Xb)-Xc-Rb, C(Xd)-N(Rc)-Rd, -SO2-Re, -P(Xe)(Rf)-R9 or CH2-Xf-Rh wherein Xa, Xb, Xc, Xd, Xe and Xf are independently of each other oxygen or sulfur;
Ra is H, d-Ciβalkyl, C2-C18alkenyl, C2-C18alkynyl, CrC10haloalkyl, Ci-Ciocyanoalkyl, C1- C10nitroalkyl, d-doaminoalkyl, d-Csalkylaminod-Csalkyl, C2-C8dialkylaminoCrC5alkyl, C3- C7cycloalkylCrC5alkyl, d-Csalkoxyd-Csalkyl, CrCsalkenyloxyd-Csalkyl, C3-C5alkynylCr Csoxyalkyl, d-Csalkylthiod-Csalkyl, d-Csalkylsulfinyld-Csalkyl, d-Csalkylsulfonyld-Csalkyl, C2-C8alkylideneaminoxyCi-C5alkyl, d-Csalkylcarbonyld-Csalkyl, d-Csalkoxycarbonyld- C5alkyl, aminocarbonyld-Csalkyl, d-Csalkylaminocarbonyld-Csalkyl, C2- C8dialkylaminocarbonyld-C5alkyl, d-Csalkylcarbonylaminod-Csalkyl, /V-d-Csalkylcarbonyl-A/- CrCsalkylaminoCi-Csalkyl, CrCβtrialkylsilyld-Csalkyl, phenyld-C5alkyl (wherein the phenyl may optionally be substituted by Ci-C3alkyl, d-C3haloalkyl, d-C3alkoxy, d-C3haloalkoxy, Cr C3alkylthio, d-C3alkylsulfinyl, Ci-C3alkylsulfonyl, halogen, cyano, or by nitro), heteroaryld- C5alkyl, (wherein the heteroaryl may optionally be substituted by CrC3alkyl, CrC3haloalkyl, C1- C3alkoxy, CrC3haloalkoxy, d-C3alkylthio, C!-C3alkylsulfinyl, d-C3alkylsulfonyl, halogen, cyano, or by nitro), C2-C5haloalkenyl, C3-C8cycloalkyl, phenyl or phenyl substituted by d-C3alkyl, C1- C3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, heteroaryl or heteroaryl substituted by C1-C3 alkyl, CrC3haloalkyl, CrC3alkoxy, d-C3haloalkoxy, halogen, cyano or nitro, Rb is CrC18alkyl, C3-C18alkenyl, C3-C18alkynyl, C2-C10haloalkyl, d-C10cyanoalkyl, C1- C10nitroalkyl, C2-C10aminoalkyl, d-Csalkylaminod-Csalkyl, d-Cβdialkylaminod-Csalkyl, C3- C7cycloalkylCrC5alkyl, CrCsalkoxyCrCsalkyl, QrCsalkenyloxyd-Csalkyl, C3-C5alkynyloxyd- C5alkyl, d-CsalkylthioCrCsalkyl, CrCsalkylsulfinyld-Csalkyl, d-Csalkylsulfonyld-Csalkyl, C2- CβalkylideneaminoxyCrCsalkyl, CrCsalkylcarbonyld-Csalkyl, C^CsalkoxycarbonylCrCsalkyl, aminocarbonyld-Csalkyl, d-Csalkylaminocarbonyld-Csalkyl, C2-C8dialkylaminocarbonylCr C5alkyl, d-Csalkylcarbonylaminod-Csalkyl, W-d-Csalkylcarbonyl-ZV-d-Csalkylaminod-Csalkyl, CrCβthalkylsilylCrCsalkyl, phenyld-C5alkyl (wherein the phenyl may optionally be substituted by d-C3alkyl, CrC3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, d-C3alkylthio, CrC3alkylsulfinyl, CrC3alkylsulfonyl, halogen, cyano, or by nitro), heteroarylCrC5alkyl, (wherein the heteroaryl may optionally be substituted by d-C3alkyl, CrC3haloalkyl, CrC3alkoxy, d-C3haloalkoxy, C1- C3alkylthio, CrC3alkylsulfinyl, d-C3alkylsulfonyl, halogen, cyano, or by nitro), C3-C5haloalkenyl, C3-C8cycloalkyl, phenyl or phenyl substituted by d-C3alkyl, CrC3haloalkyl, C1-C3BIkOXy, C1- C3haloalkoxy, halogen, cyano or nitro, heteroaryl or heteroaryl substituted by C1-C3 alkyl, C1- C3haloalkyl, CrC3alkoxy, d-C3haloalkoxy, halogen, cyano or nitro, Rc and Rd are each independently of each other hydrogen, CrC10alkyl, C3-C10alkenyl, C3- C10alkynyl, C2-C10haloalkyl, d-C10cyanoalkyl, CrC^nitroalkyl, CrC10aminoalkyl, C1- CsalkylaminoCrCsalkyl, C2-C8dialkylaminoCrC5alkyl, Cs-CyCycloalkylCrCsalkyl, d-CsalkoxyCr C5alkyl, C3-C5alkenyloxyCrC5alkyl, d-Csalkynyloxyd-Csalkyl, CrCsalkylthiod-Csalkyl, C1- C5alkylsulfinylCi-C5alkyl, d-Csalkylsulfonyld-Csalkyl, C2-C8alkylideneaminoxyC1-C5alkyl, C1- CsalkylcarbonylCrCsalkyl, d-Csalkoxycarbonyld-Csalkyl, aminocarbonyld-Csalkyl, C1- Csalkylaminocarbonyld-Csalkyl, C2-C8dialkylaminocarbonylCrC5alkyl, C1- Csalkylcarbonylaminod-Csalkyl, Λ/-C1-C5alkylcarbonyl-Λ/-C2-C5alkylaminoalkyll C3- CβtrialkylsilylCT-Csalkyl, phenylCrC5alkyl (wherein the phenyl may optionally be substituted by Ci-C3alkyl, CrC3haloalkyl, d-C3alkoxy, d-C3haloalkoxy, CrC3alkylthio, d-C3alkylsulfinyl, C1- C3alkylsulfonyl, halogen, cyano, or by nitro), heteroaryld-Csalkyl, (wherein the heteroaryl may optionally be substituted by d-C3alkyl, CrC3haloalkyl, CrC3alkoxy, d-C3haloalkoxy, C1- C3alkylthio, d-C3alkylsulfinyl, d-C3alkylsulfonyl, halogen, cyano, or by nitro), C2-C5haloalkenyl, C3-C8cycloalkyl, phenyl or phenyl substituted by CrC3alkyl, d-C3haloalkyl, d-C3alkoxy, C1- C3haloalkoxy, halogen, cyano or nitro, heteroaryl or heteroaryl substituted by C1-C3 alkyl, C1- C3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, heteroarylamino or heteroarylamino substituted by C1-C3 alkyl, d-C3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, diheteroarylamino or diheteroarylamino substituted by C1-C3 alkyl, C1- C3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, phenylamino or phenylamino substituted by CrC3alkyl, d-C3haloalkyl, CrC3alkoxy, d-C3haloalkoxy, halogen, cyano or by nitro, diphenylamino or diphenylamino substituted by CrC3alkyl, d-Cshaloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or by nitro or C3-C7cycloalkylamino, di-C3-C7cycloalkylamino or C3-C7cycloalkoxy or Rc and Rd may join together to form a 3-7 membered ring, optionally containing one heteroatom selected from O or S,
Re is d-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, d-C10haloalkyl, d-C10cyanoalkyl, C1- C10nitroalkyl, d-C10aminoalkyl, CrCsalkylaminoCrCsalkyl, CrCβdialkylaminoCrCsalkyl, C3- C7cycloalkyld-C5alkyl, CrCsalkoxyCrCsalkyl, CrCsalkenyloxyd-Csalkyl, C3-C5alkynyloxyCr C5alkyl, CrCsalkylthioCrCsalkyl, C^CsalkylsulfinylCrCsalkyl, CrCsalkylsulfonylCrCsalkyl, C2- Cβalkylideneaminoxyd-Csalkyl, CrCsalkylcarbonylCrCsalkyl, CrCsalkoxycarbonylCTCsalkyl, aminocarbonylCrCsalkyl, d-CsalkylaminocarbonylCrCsalkyl, C2-C8dialkylaminocarbonylCr C5alkyl, d-CsalkylcarbonylaminoCrCsalkyl, /V-d-Csalkylcarbonyl-ZV-CrCsalkylaminoCrCsalkyl, Cs-CβtrialkylsilylCrCsalkyl, phenyld-C5alkyl (wherein the phenyl may optionally be substituted by d-C3alkyl, d-C3haloalkyl, CrC3alkoxy, C^Cshaloalkoxy, CrC3alkylthio, Ci-C3alkylsulfinyl, d-C3alkylsulfonyl, halogen, cyano, or by nitro), heteroaryld-C5alkyl (wherein the heteroaryl may optionally be substituted by d-C3alkyl, d-C3haloalkyl, CrC3alkoxy, CrCshaloalkoxy, C1- C3alkylthio, CrC3alkylsulfinyl, CrC3alkylsulfonyl, halogen, cyano, or by nitro), C2-C5haloalkenyl, CrCecycloalkyl, phenyl or phenyl substituted by CrC3alkyl, d-C3haloalkyl, CrC3alkoxy, C1- C3haloalkoxy, halogen, cyano or nitro, heteroaryl or heteroaryl substituted by C1-C3 alkyl, C1- C3haloalkyl, d-C3alkoxy, d-C3haloalkoxy, halogen, cyano or by nitro, heteroarylamino or heteroarylamino substituted by C1-C3 alkyl, d-C3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or by nitro, diheteroarylamino or diheteroarylamino substituted by C1-C3 alkyl, C1- C3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, phenylamino or phenylamino substituted by CrC3alkyl, d-C3haloalkyl, CrC3alkoxy, C1-C3(IaIOaIkOXy, halogen, cyano or nitro, diphenylamino, or diphenylamino substituted by d-C3alkyl, CrC3haloalkyl, CrC3alkoxy, C1- C3haloalkoxy, halogen, cyano or nitro, or C3-C7cycloalkylamino, diCs-dcycloalkylamino or C3- C7cycloalkoxy, C1-C1OaIkOXy, Ci-C10haloalkoxy, CrC5alkylamino or C2-C8dialkylamino Rf and R9 are are each independently of each other CrC10alkyl, C2-C10alkenyl, C2-C10alkynyl, C1- C10alkoxy, d-C10haloalkyl, CrC10cyanoalkyl, d-C10nitroalkyl, d-doaminoalkyl, C1- Csalkylaminod-Csalkyl, CirCsdialkylaminod-Csalkyl, C3-C7cycloalkylCrC5alkyl, d-Csalkoxyd- C5alkyl, Cs-Csalkenyloxyd-Csalkyl, C3-C5alkynyloxyCrC5alkyl, d-Csalkylthiod-Csalkyl, C1- C5alkylsulfinylCrC5alkyl, d-Csalkylsulfonyld-Csalkyl, CrCsalkylideneaminoxyd-Csalkyl, C1- CsalkylcarbonylCrCsalkyl, d-Csalkoxycarbonyld-Csalkyl, aminocarbonyld-Csalkyl, C1- CsalkylaminocarbonylCrCsalkyl, C2-C8dialkylaminocarbonylCrC5alkyl, C1- CsalkylcarbonylaminoCrCsalkyl, Λ/-C1-C5alkylcarbonyl-Λ/-C2-C5alkylaminoalkyl, C3- C6trialkylsilylCi-C5alkyl, phenylCrC5alkyl (wherein the phenyl may optionally be substituted by CrC3alkyl, CrC3haloalkyl, d-C3alkoxy, CrC3haloalkoxy, d-C3alkylthio, CrC3alkylsulfinyl, C1- C3alkylsulfonyl, halogen, cyano, or by nitro), heteroarylCrC5alkyl (wherein the heteroaryl may optionally be substituted by CrC3alkyl, d-C3haloalkyl, C1-C3BIkOXy, CrC3haloalkoxy, C1- C3alkylthio, Ci-C3alkylsulfinyl, CrC3alkylsulfonyl, halogen, cyano, or by nitro), C2-C5haloalkenyl, C3-C8cycloalkyl, phenyl or phenyl substituted by CrC3alkyl, C^Cshaloalkyl, CrC3alkoxy, C1- C3haloalkoxy, halogen, cyano or nitro, heteroaryl or heteroaryl substituted by C1-C3 alkyl, C1- C3haloalkyl, d-Csalkoxy, CrC3haloalkoxy, halogen, cyano or by nitro, heteroarylamino or heteroarylamino substituted by C1-C3 alkyl, CrC3haloalkyl, C^Csalkoxy, CrC3haloalkoxy, halogen, cyano or by nitro, diheteroarylamino or diheteroarylamino substituted by CrC3 alkyl, C1- C3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, phenylamino or phenylamino substituted by CrC3alkyl, CrC3haloalkyl, CrCsalkoxy, CrC3haloalkoxy, halogen, cyano or nitro, diphenylamino, or diphenylamino substituted by CrC3alkyl, C^Cshaloalkyl, CrC3alkoxy, C1- C3haloalkoxy, halogen, cyano or nitro, or C3-C7cycloalkylamino, diC3-C7cycloalkylamino or C3- C7cycloalkoxy, CrC10haloalkoxy, CrC5alkylamino or C2-C8dialkylamino, benzyloxy or phenoxy, wherein the benzyl and phenyl groups may in turn be substituted by CrC3alkyl, CrC3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, halogen, cyano or nitro, and
Rh is CrC10alkyl, C3-C10alkenyl, C3-C10alkynyl, CrC10haloalkyl, d-docyanoalkyl, C1- C10nitroalkyl, C2-C10aminoalkyl, d-CsalkylaminoCrCsalkyl, CrCβdialkylaminoCrCsalkyl, C3- C7cycloalkyld-C5alkyl, CrCsalkoxyCrCsalkyl, CrCsalkenyloxyd-Csalkyl, C3-C5alkynyloxyd- C5alkyl, d-Csalkylthiod-Csalkyl, d-CsalkylsulfinylCrCsalkyl, d-CsalkylsulfonylCrCsalkyl, C2- Cβalkylideneaminoxyd-Csalkyl, d-Csalkylcarbonyld-Csalkyl, d-CsalkoxycarbonylCrCsalkyl, aminocarbonylC^-Csalkyl, Ci-CsalkylaminocarbonylCrCsalkyl, Ca-CβdialkylaminocarbonylCr C5alkyl, Ci-C5alkylcarbonylaminoCi-C5alkyl, /V-CrCsalkylcarbonyl-N-CrCsalkylaminoCrCsalkyl, Cs-CβtrialkylsilylCrCsalkyl, phenylCrC5alkyl (wherein wherein the phenyl may optionally be substituted by Ci-C3alkyl, CrC3haloalkyl, CrC3alkoxy, CrCshaloalkoxy, CrC3alkylthio, C1- C3alkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), heteroaryld-Csalkyl (wherein the heteroaryl may optionally be substituted by Ci-C3alkyl, CrC3haloalkyl, CrC3alkoxy, C1- C3haloalkoxy, C^Csalkylthio, CrC3alkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), phenoxyCrC5alkyl (wherein wherein the phenyl may optionally be substituted by CrC3alkyl, C1- C3haloalkyl, CrC3alkoxy, C1-C3IIaIOaIkOXy, C^Csalkylthio, d-Csalkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), heteroaryloxyCrC5alkyl (wherein the heteroaryl may optionally be substituted by CrC3alkyl, CrC3haloalkyl, CrC3alkoxy, Ci-C3haloalkoxy, CrC3alkylthio, C1- C3alkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), C3-C5haloalkenyl, C3-C8cycloalkyl, phenyl or phenyl substituted by Ci-C3alkyl, CrC3haloalkyl, C!-C3alkoxy, CrC3haloalkoxy, halogen or by nitro, or heteroaryl, or heteroaryl substituted by CτC3alkyl, CrC3haloalkyl, C1- C3alkoxy, CrC3haloalkoxy, halogen, cyano or by nitro.
In particular, the latentiating group G is a group -C(Xa)-Ra or -C(Xb)-Xc-Rb. and the meanings of Xa, Ra, Xb, Xc and Rb are as defined above.
It is preferred that G is hydrogen, an alkali metal or alkaline earth metal, where hydrogen is _ especially preferred.
It should be understood that in those compounds of formula I where G is a metal, ammonium (such as NH4+; N(alkyl)4+) or sulfonium (such as S(alkyl)3+) cation, the corresponding negative charge is largely delocalised across the 0-C=C-C=O unit.
Depending on the nature of the substituents, compounds of formula I may exist in different isomeric forms. When G is hydrogen, for example, compounds of formula I may exist in different tautomeric forms.
Figure imgf000016_0001
This invention covers all such isomers and tautomers and mixtures thereof in all proportions. Also, when substituents contain double bonds, cis- and frans-isomers can exist. These isomers, too, are within the scope of the claimed compounds of the formula I.
A compound of formula I wherein G is C1-C8 alkyl, C2-C8 haloalkyl, phenylCi-C8alkyl (wherein the phenyl may optionally be substituted by CrC3alkyl, CrC3haloalkyl, CrC3alkoxy, C1- C3haloalkoxy, Ci-C3alkylthio, CrC3alkylsufinyl, Ci-C3 alkylsulfonyl, halogen, cyano or by nitro), heteroarylCrC8alkyl (wherein the heteroaryl may optionally be substituted by CrC3alkyl, C1- C3haloalkyl, CrC3alkoxy, CrC3haloalkoxy, CrC3alkylthio, CrC3alkylsulfinyl, C1-C3 alkylsulfonyl, halogen, cyano or by nitro), C3-C8 alkenyl, C3-C8 haloalkenyl, C3-C8 alkynyl, C(Xa)-Ra, C(Xb)-Xc- Rb, C(Xd)-N(Rc)-Rd, -SO2-Re, -P(Xe)(Rf)-R9 or CH2-Xf-Rh where Xa, Xb, Xc, Xd, Xe, Xf, Ra, Rb, Rc, Rd, Re, Rf, R9 and Rh are as defined above may be prepared by treating a compound of formula (A), which is a compound of formula I wherein G is H, with a reagent G-Z, wherein G-Z is alkylating agent such as an alkyl halide (the definition of alkyl halides includes simple C1-C8 alkyl halides such as methyl iodide and ethyl iodide, substituted alkyl halides such as phenylC^ C6alkyl, chloromethyl alkyl ethers, Cl — CH2-Xf-Rh, wherein Xf is oxygen, and chloromethyl alkyl sulfides CI— CH2-Xf-Rh, wherein Xf is sulfur), a C1-C8 alkyl sulfonate, or a di-CrC8-alkyl sulfate, or with a C3-C8 alkenyl halide, or with a C3-C8 alkynyl halide, or with an acylating agent such as a carboxylic acid, HO-C(Xa)Ra, wherein Xa is oxygen, an acid chloride, CI-C(Xa)Ra, wherein Xa is oxygen, or acid anhydride, [RaC(Xa)]2O, wherein Xa is oxygen, or an isocyanate, R0N=C=O1 or a carbamoyl chloride, CI-C(Xd)-N(R°)-Rd (wherein Xd is oxygen and with the proviso that neither Rc or Rd is hydrogen), or a thiocarbamoyl chloride, CI-C(Xd)-N(Rc)-Rd (wherein Xd is sulfur and with the proviso that neither Rc or Rd is hydrogen) or a chloroformate, CI-C(Xb)-Xc-Rb, (wherein Xb and Xc are oxygen), or a chlorothioformate CI-C(Xb)-Xc-Rb (wherein Xb is oxygen and Xc is sulfur), or a chlorodithioformate CI-C(Xb)-Xc-Rb, (wherein Xb and Xc are sulfur),or an isothiocyanate, R0N=C=S, or by sequential treatment with carbon disulfide and an alkylating agent, or with a phosphorylating agent such as a phosphoryl chloride, CI-P(Xe)(Rf)-R9 or with a sulfonylating agent such as a sulfonyl chloride CI-SO2 — Re, preferably in the presence of at least one equivalent of base.
Figure imgf000018_0001
formula (A) (I)
Depending on the nature of the substituents R1 to R12, and of the group G, isomeric compounds of formula I may be formed. For example, a compound of formula (A) wherein R5 and R12 are different may give rise to a compound of formula (1a) or to a compound of formula (1 b), or to a mixture of compounds of formula (1a) and formula (1 b).
Figure imgf000018_0002
formula (Ia) formula (Ib)
The O-alkylation of cyclic 1 ,3-diones is known; suitable methods are described, for example, by T. Wheeler US4436666. Alternative procedures have been reported by M. Pizzorno and S. Albonico, Chem. Ind. (London), (1972), 425; H. Born et al., J. Chem. Soc, (1953), 1779; M. Constantino et al., Synth. Commun., (1992), 22 (19), 2859; Y. Tian et al., Synth. Commun., (1997), 27 (9), 1577, S. Chandra Roy et al., Chem. Letters, (2006), 35 (1), 16, and P. Zubaidha et ai, Tetrahedron Lett., (2004), 45, 7187.
The O-acylation of cyclic 1 ,3-diones may be effected by procedures similar to those described, for example, by R. Haines, US4175135, and by T. Wheeler, US4422870, US4659372 and US4436666. Typically diones of formula (A) may be treated with the acylating agent in the presence of at least one equivalent of a suitable base, optionally in the presence of a suitable solvent. The base may be inorganic, such as an alkali metal carbonate or hydroxide, or a metal hydride, or an organic base such as a tertiary amine or metal alkoxide. Examples of suitable inorganic bases include sodium carbonate, sodium or potassium hydroxide, sodium hydride, and suitable organic bases include trialkylamines, such as trimethylamine and triethylamine, pyridines or other amine bases such as 1 ,4-diazobicyclo[2.2.2]octane and 1 ,8- diazabicyclo[5.4.0]undec-7-ene. Preferred bases include triethylamine and pyridine. Suitable solvents for this reaction are selected to be compatible with the reagents and include ethers such as tetrahydrofuran and 1 ,2-dimethoxyethane and halogenated solvents such as dichloromethane and chloroform. Certain bases, such as pyridine and triethylamine, may be employed successfully as both base and solvent. For cases where the acylating agent is a carboxylic acid, acylation is preferably effected in the presence of a coupling agent such as 2-chloro-1- methylpyridinium iodide, Λ/,Λ/-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide and Λ/,Λ/-carbodiimidazole, and optionally a base such as triethylamine or pyridine in a suitable solvent such as tetrahydrofuran, dichloromethane or acetonitrile. Suitable procedures are described, for example, by W. Zhang and G. Pugh, Tetrahedron Lett., (1999), 40 (43), 7595-7598 and T. lsobe and T. Ishikawa, J. Org. Chem., (1999), 64 (19), 6984.
Phosphorylation of cyclic 1 ,3-diones may be effected using a phosphoryl halide or thiophosphoryl halide and a base by procedures analogous to those described by L. Hodakowski, US4409153.
Sulfonylation of a compound of formula (A) may be achieved using an alkyl or aryl sulfonyl halide, preferably in the presence of at least one equivalent of base, for example by the procedure of C. Kowalski and K. Fields, J. Org. Chem., (1981), 46, 197.
A compound of formula (A) may be prepared by the cyclisation of a compound of formula (B), wherein R is hydrogen or an alkyl group, preferably in the presence of an acid or base, and optionally in the presence of a suitable solvent, by analogous methods to those described by T. Wheeler, US4209532. The compounds of formula (B) have been particularly designed as intermediates in the synthesis of the compounds of the formula I. A compound of formula (B) wherein R is hydrogen may be cyclised under acidic conditions, preferably in the presence of a strong acid such as sulfuric acid, polyphosphoric acid or Eaton's reagent, optionally in the presence of a suitable solvent such as acetic acid, toluene or dichloromethane.
Figure imgf000020_0001
formula (B) formula (A)
A compound of formula (B) wherein R is alkyl (preferably methyl or ethyl), may be cyclised under acidic or basic conditions, preferably in the presence of at least one equivalent of a strong base such as potassium tert-butoxide, lithium diisopropylamide or sodium hydride and in a solvent such as tetrahydrofuran, toluene, dimethylsulfoxide or Λ/,Λ/-dimethylformamide.
A compound of formula (B), wherein R is H, may be prepared by saponification of a compound of formula (C) wherein R' is alkyl (preferably methyl or ethyl), under standard conditions, followed by acidification of the reaction mixture to effect decarboxylation, by similar processes to those described, for example, by T. Wheeler, US4209532.
1. saponification
2. decarboxylation
Figure imgf000020_0003
Figure imgf000020_0002
formula (C) formula (B)
A compound of formula (B), wherein R is H, may be esterified to a compound of formula (B), wherein R is alkyl, under standard conditions, for example by heating with an alkyl alcohol, ROH, in the presence of an acid catalyst.
A compound of formula (C), wherein R is alkyl, may be prepared by treating a compound of formula (D) with a suitable carboxylic acid chloride of formula (E) under basic conditions. Suitable bases include potassium te/f-butoxide, sodium bis(trimethylsilyl)amide and lithium diisopropylamide and the reaction is preferably conducted in a suitable solvent (such as tetrahydrofuran or toluene) at a temperature of between -80 0C and 30 0C. Alternatively, a compound of formula (C)1 wherein R is H1 may be prepared by treating a compound of formula (D) with a suitable base (such as potassium tert-butoxide, sodium bis(trimethylsilyl)amide and lithium diisopropylamide) in a suitable solvent (such as tetrahydrofuran or toluene) at a suitable temperature (between -80 0C and 30 0C) and reacting the resulting anion with a suitable anhydride of formula (F):
base,
Figure imgf000021_0001
Figure imgf000021_0002
Figure imgf000021_0003
formula (C) formula (F)
Compounds of formula (D) are known compounds, or may be prepared from known compounds by known methods.
A compound of formula (E) may be prepared from a compound of formula (F) by treatment with an alkyl alcohol, R-OH, in the presence of a base, such as dimethylaminopyridine or an alkaline metal alkoxide (see, for example, S. Buser and A. Vasella, HeIv. Chim. Acta, (2005), 88, 3151 , M. Hart et al., Bioorg. Med. Chem. Letters, (2004), 14, 1969), followed by treatment of the resulting acid with a chlorinating reagent such as oxalyl chloride or thionyl chloride under known conditions (see, for example, C. Santelli-Rouvier. Tetrahedron Lett., (1984), 25 (39), 4371 ; D. Walba and M. Wand, Tetrahedron Lett., (1982), 23 (48), 4995; J. Cason, Org. Synth. Coll. Vol. Ill (169), 1955).
Figure imgf000022_0001
formula (F) formula (E)
A compound of formula (F) wherein R7and R10 are hydrogen may be prepared by the reduction of a compound of formula (G) under known conditions (see, for example, Y. Baba, N. Hirukawa and M. Sodeoka, Bioorg. Med. Chem. (2005), 13 (17), 5164, M. Hart ef a/., Bioorg. Med. Chem. Letters, (2004), 14 (18), 1969, Y. Baba, N. Hirukawa, N. Tanohira and M. Sodeoka, J. Am. Chem. Soc, (2003), 125, 9740).
reduction
Figure imgf000022_0002
Figure imgf000022_0003
formula (F) wherein R7 and R10 = H
A compound of formula (G) may be prepared by reacting a compound of formula (H) with an anhydride of formula (J), optionally in the presence of a Lewis acid catalyst , and according to procedures described, for example, by O. Diels and K. Alder, Liebigs Ann. Chem., (1931), 490, 257, K. Potts and E. Walsh, J. Org. Chem., (1984), 49 (21), 4099, J. Jurczak, T. Kozluk, S. Filipek and S. Eugster, HeIv. Chim. Acta, (1982), 65, 1021 , W. Dauben, C. Kessel and K. Takemura, J. Am. Chem. Soc, (1980), 102, 6893, A. Pelter and B. Singaram, Tetrahedron Lett., (1982), 23, 245, M. Lee and C. Herndon, J. Org. Chem., (1978), 43, 518, B. Fisher and J. Hodge, J. Org. Chem. (1964), 29, 776, G. D'Alelio, C. Williams and C. Wilson, J. Org. Chem., (1960), 25, 1028, Z. Song, M. Ho and H. Wong, J. Org. Chem, (1994), 59 (14), 3917-3926, W. Tochtermann, S. Bruhn and C. Wolff, Tetrahedron Lett., (1994), 35(8), 1165, W. Dauben, J. Lam and Z. Guo, J. Org. Chem., (1996), 61 (14), 4816, M. Sodeoka, Y. Baba, S. Kobayashi and N. Hirukawa, Bioorg. Med. Chem. Lett., (1997), 7 (14), 1833, M. Avalos, R. Babiano, J. Bravo, P. Cintas, J. Jimenez and J. Palacios, Tetrahedron Lett., (1998), 39(50), 9301 , J. Auge, R. Gil, S. Kalsey and N. Lubin-Germain, Synlett, (2000), 6, 877, 1. Hemeon, C. Deamicis, H. Jenkins, P. Scammells and R. Singer, Synlett, (2002), 11 , 1815, M. Essers, B. Wibbeling and G. Haufe, Tetrahedron Lett., (2001), 42 (32), 5429, P. Vogel et al., Tetrahedron Asymmetry, (1996), 7 (11), 3153, Y. Baba, N. Hirukawa, N. Tanohira and M. Sodeoka, J. Am. Chem. Soc, (2003), 125, 9740, L. Ghosez et al., Tetrahedron Lett., (1988), 29 (36), 4573, H. Kotsuki, S. Kitagawa and H. Nishizawa, J. Org. Chem., (1978), 43 (7), 1471 , Y. Li et al., J. Org. Chem., (1997), 62 (23), 7926, M. Drew et al., J. Chem. Soc. Perkin Trans. 1 , (1985), 1277, R. McDonald and C. Reineke, J. Org. Chem, (1967), 32, 1878, R. Fleming and B. Murray, J. Org. Chem., (1979), 44 (13), 2280, M. Goldstein and G. Thayer Jr. J. Am. Chem. Soc, (1965), 87 (9), 1925 and G. Keglevich et al., J. Organomet. Chem., (1999), 579, 182, and references therein.
Figure imgf000023_0001
formula (H)
Compounds of formula (H) and formula (J) are known compounds, or may be made from known compounds by known methods.
Compounds of formula (G) are alkenes, and as such undergo further reactions typical of alkenes to give additional compounds of formula (F) according to known procedures. Examples of such reactions include, but are not restricted to, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration of alkenes. In turn, the products from these reactions may be transformed into additional compounds of formula (F) by methods described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons. Compounds of formula (G) wherein R8 or R9 are CrC6alkoxy are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures to give additional compounds of formula (F). Certain compounds of formula (F), for example where R7 is a halogen, may be converted into compounds of formula (G) by known methods.
A compound of formula (G) may also be prepared by reacting a compound of formula (H) with a compound of formula (K), wherein R" is hydrogen or an alkyl group, to give a compound of formula (L) and cyclising a compound of formula (L) under known conditions (see, for example, P. Sprague ef a/., J. Med. Cherπ., (1985), 28, 1580, A. Guzaev and M. Manoharan, J. Am. Chem. Soc, (2003), 125, 2380, and A. Marchand and R. Allen, J. Org. Chem., (1975), 40 (17), 2551.
Figure imgf000024_0001
formula (K) cyclisation
Figure imgf000024_0002
Figure imgf000024_0003
cyclisation
Figure imgf000024_0005
Figure imgf000024_0004
formula (F) formula (M) wherein R7 and R10 = H
A compound of formula (L) may also be reduced to a compound of formula (M), and a compound of formula (M) cyclised to a compound of formula (F) wherein R7 and R10 are hydrogen, under conditions similar to those described previously.
Compounds of formula (K) are known compounds, or may be prepared from known compounds by known methods.
Additional compounds of formula (A) may be prepared by reacting an iodonium ylide of formula (N), wherein Ar is an optionally substituted phenyl group, and an aryl boronic acid of formula (O), in the presence of a suitable palladium catalyst, a base and in a suitable solvent. catalyst , base additive, solvent
Figure imgf000025_0002
Figure imgf000025_0001
formula (N) formula (O) formula (A)
Suitable palladium catalysts are generally palladium(ll) or palladium(O) complexes, for example palladium(ll) dihalides, palladium(ll) acetate, palladium(ll) sulfate, bis(triphenylphosphine)- palladium(ll) dichloride, bis(tricyclopentylphosphine)palladium(ll) dichloride, bis(tricyclohexyl- phosphine)palladium(ll) dichloride, bis(dibenzylideneacetone)palladium(0) or tetrakis- (triphenylphosphine)palladium(O). The palladium catalyst can also be prepared "in situ" from palladium(ll) or palladium(O) compounds by complexing with the desired ligands, by, for example, combining the palladium(ll) salt to be complexed, for example palladium(ll) dichloride (PdCI2) or palladium(ll) acetate (Pd(OAc)2), together with the desired ligand, for example triphenyl- phosphine (PPh3), tricyclopentylphosphine, tricyclohexylphosphine, 2-dicyclohexylphosphino- 2',6'-dimethoxybiphenyl or 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl and the selected solvent, with a compound of formula (N), the arylboronic acid of formula (O), and a base. Also suitable are bidendate ligands, for example 1 ,1'-bis(diphenylphosphino)ferrocene or 1 ,2-bis(diphenylphosphino)ethane. By heating the reaction medium, the palladium(ll) complex or palladium(O) complex desired for the C-C coupling reaction is thus formed "in situ", and then initiates the C-C coupling reaction.
The palladium catalysts are used in an amount of from 0.001 to 50 mol %, preferably in an amount of from 0.1 to 15 mol %, based on the compound of formula (N). The reaction may also be carried out in the presence of other additives, such as tetralkylammonium salts, for example, tetrabutylammonium bromide. Preferably the palladium catalyst is palladium acetate, the base is lithium hydroxide and the solvent is aqueous 1 ,2-dimethoxyethane.
A compound of formula (N) may be prepared from a compound of formula (P) by treatment with a hypervalent iodine reagent such as a (diacetoxy)iodobenzene or an iodosylbenzene and a base such as aqueous sodium carbonate, lithium hydroxide or sodium hydroxide in a solvent such as water or an aqueous alcohol such as aqueous ethanol according to the procedures of K. Schank and C. Lick, Synthesis, (1983), 392, R. M. Moriarty et al., J. Am. Chem. Soc, (1985), 107, 1375, or of Z. Yang et al., Org. Lett., (2002), 4 (19), 3333.
Figure imgf000026_0001
formula (P) formula (N)
A compound of formula (P) wherein R7 and R10 are hydrogen may be prepared by reduction of a compound of formula (Q) under known conditions.
reduction
Figure imgf000026_0002
Figure imgf000026_0003
formula (P) formula (R) wherein R7 and R10= H
Compounds of formula (R) are alkenes, and as such undergo further reactions typical of alkenes to give additional compounds of formula (P) according to known procedures. Examples of such reactions include, but are not restricted to, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration of alkenes. In turn, the products of these reactions may be transformed into additional compounds of formula (P) by methods described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons. Compounds of formula (R) wherein R8 or R9 are CrC6alkoxy are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures. In turn, the ketone may be further transformed, for example by ketalisation, oximation, reduction and the like under known conditions to give additional compounds of formula (P).
A compound of formula (R) may be prepared by reacting a compound of formula (S) with a cyclopentenedione of formula (T), optionally in the presence of a Lewis acid catalyst, according to procedures described, for example by B. Zwanenburg et a/., Tetrahedron (1989), 45 (22), 7109 and by M. Oda er a/., Chem. Lett., (1977), 307.
Figure imgf000027_0001
formula (H) , , ._, v formula (R)
Compounds of formula (H) and formula (T) are known compounds or may be made from known compounds by known methods.
In a further approach, a compound of formula (A) may be prepared from a compound of formula I, wherein G is Cr4 alkyl, by hydrolysis, preferably in the presence of an acid catalyst such as hydrochloric acid and optionally in the presence of a suitable solvent such as tetrahydrofuran, acetone or 4-methylpentan-2-one.
Figure imgf000027_0002
formula I formula (A) wherein G is C1-4 alkyl
A compound of formula I wherein G is Cr4 alkyl, may be prepared from a compound of formula (U), wherein G is Ci-4 alkyl, and Hal is a halogen (preferably bromine or iodine), by coupling with an aryl boronic acid of formula (O), in the presence of a suitable palladium catalyst and a base and preferably in the presence of a suitable ligand, and in a suitable solvent. Preferably the palladium catalyst is palladium acetate, the base is potassium phosphate, the ligand is 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl and the solvent is toluene.
Figure imgf000028_0001
formula I
Figure imgf000028_0002
wherein G is C1-4 alkyl
A compound of formula (U) may be prepared by halogenation of a compound of formula (P), followed by reaction of the resulting halide of formula (V) with a C1-4 alkyl halide or tri-C1-4- alkylorthoformate under known conditions (for example by the procedures of R. Shepherd and A. White, J. Chem. Soc. Perkin Trans. 1 (1987), 2153, and Y.-L. Lin et al., Bioorg. Med. Chem. (2002), 10, 685). Alternatively, a compound of formula (U) may be prepared by reaction of a compound of formula (P) with a C1-4 alkyl halide or a tri-C^-alkylorthoformate, and halogenation of the resulting enone of formula (W) under known conditions.
halogenation
Figure imgf000028_0003
Figure imgf000028_0004
formula (P) formula (U)
halogenation alkylation
Figure imgf000028_0005
Figure imgf000028_0006
formula (W)
A compound of formula (O) may be prepared from an aryl halide of formula (X), wherein Hal is bromine or iodine, by known methods (see, for example, W. Thompson and J. Gaudino, J. Org. Chem, (1984), 49, 5237 and R. Hawkins ef a/., J. Am. Chem. Soc, (1960), 82, 3053). For example, an aryl halide of formula (X) may be treated with an alkyl lithium or alkyl magnesium halide in a suitable solvent, preferably diethyl ether or tetrahydrofuran, at a temperature of between -80 0C and 30 0C, and the aryl magnesium or aryl lithium reagent obtained may then be reacted with a trialkyl borate (preferably trimethylborate) to give an aryl dialkylboronate which may be hydrolysed to provide a boronic acid of formula (O) under acidic conditions.
Figure imgf000029_0001
Figure imgf000029_0002
formula (O)
Alternatively a compound of formula (X) may be reacted with a cyclic boronate ester derived from a 1 ,2- or a 1 ,3-alkanediol such as pinacol, 2,2-dimethyl-1 ,3-propanediol and 2-methyl-2,4- pentanediol) under known conditions (see, for example, N. Miyaura et al., J. Org. Chem., (1995),
60, 7508, and W. Zhu and D. Ma, Org. Lett., (2006), 8 (2), 261), and the resulting boronate ester may be hydrolysed under acidic conditions to give a boronic acid of formula (O).
An aryl halide of formula (X) may be prepared from an aniline of formula (Y) by known methods, for example the Sandmeyer reaction, via the corresponding diazonium salts.
Anilines of formula (Y) are known compounds, or may be made from known compounds, by known methods.
Sandmeyer reaction
Figure imgf000029_0004
Figure imgf000029_0003
formula (Y) formula (X)
Additional compounds of formula (A) may be prepared by reacting a compound of formula (P), or a compound of formula (R) with an organolead reagent of formula (Z) under conditions described, for example, by J. Pinhey, Pure and Appl. Chem., (1996), 68 (4), 819 and by M. Moloney et al., Tetrahedron Lett., (2002), 43, 3407.
Figure imgf000030_0001
formula (P) formula (A)
Figure imgf000030_0002
formula (R) formula (A) wherein R7 and R10 form a bond
The organolead reagent of formula (Z) may be prepared from a boronic acid of formula (O), a stannane of formula (AA), wherein R is C1-C4 alkyl or by direct plumbation of a compound of formula (AB) with lead tetraacetate according to known procedures.
Pb(OAc)4, base solvent
Figure imgf000030_0004
Figure imgf000030_0003
formula (O) formula (AA)
Pb(OAc)4
Figure imgf000030_0005
formula (AB) Further compounds of formula (A) may be prepared by reacting a compound of formula (P) or a compound of formula (R) with suitable triarylbismuth compound under conditions described, for example, by A. Yu. Fedorov ef a/., Russ. Chem. Bull. Int. Ed., (2005), 54 (11), 2602, and by P. Koech and M. Krische, J. Am. Chem. Soc, (2004), 126 (17), 5350 and references therein.
In a further approach, a compound of formula I may be prepared from a compound of formula (AC) by suitable derivatisation under standard conditions.
derivatisation
Figure imgf000031_0002
Figure imgf000031_0001
formula (AC) (I)
For example, compounds of formula (AC) are alkenes, and as such undergo further reactions typical of alkenes to give compounds of formula I according to known procedures. Examples of such reactions include, but are not restricted to, reduction, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration. Compounds of formula (AC) wherein R8 or R9 is bromine or iodine are vinyl halides, and undergo known reactions of vinyl halides such as Suzuki-Miyaura, Sonogashira, Stille and related reactions. Certain other compounds of formula (AC), wherein R8 or R9 is d-Cβalkoxy, are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures. In turn, the ketone produced may be further transformed, for example by ketalisation, oximation, reduction and the like under known conditions to give additional compounds of formula I. Similarly, compounds of formula (AC) wherein R8 or R9 is CrC6amino or di-CrC6amino are enamines, and these also may be hydrolysed to the corresponding ketone using standard procedures.
A compound of formula (AC), wherein G is Ci-C4 alkyl, may be prepared from a compound of formula (AD), wherein G is C1-C4 alkyl and X is halogen or other suitable leaving group (such as an alkyl or arylsulfonate, or an arylselenoxide), by reaction with a compound of formula (H), optionally in a suitable solvent, and optionally in the presence of a suitable base.
Figure imgf000032_0001
formula (H)
base, solvent
Figure imgf000032_0002
Figure imgf000032_0003
formula (AD) formula (AC)
Suitable solvents include toluene, dichloromethane and chloroform and suitable bases include organic bases such as triethylamine, Hunig's base and 1 ,8-diazabicyclo[5.4.0]undec-7-ene. Preferably the solvent is toluene and the base is 1 ,8-diazabicyclo[5.4.0]undec-7-ene.
A compound of formula (AD) may be prepared from a compound of formula (AE), under known conditions.
Figure imgf000032_0004
formula (AE) formula (AD)
For example, a compound of formula (AD) wherein X is chlorine may be prepared by reacting a compound of formula (AE) with copper(ll) chloride and lithium chloride according to the procedure of E. Kosower ef a/., J. Org. Chem., (1963), 28, 630.
Compounds of formula (AE) are known compounds or may be made from known compounds by known methods (see, for example, Y. Song, B. Kim and J-N Heo, Tetrahedron Lett., (2005), 46, 5977). Alternatively, a compound of formula (AE) wherein G is CrC4alkyl may be prepared from a compound of formula (AE), wherein G is hydrogen, for example by reaction with a C1-4 alkyl halide or a tri-Ci-4-alkylorthoformate. Compounds of formula (AE), wherein G is hydrogen, are known, or may be prepared from known compounds by known methods (see, for example, T. Wheeler, US4338122, US4283348, J. T. Kuethe et al., J. Org. Chem., (2002), 67, 5993, S. Buchwald et al., J. Am. Chem. Soc, (2003), 125, 11818). Alternatively, a compound of formula (AE), wherein G is C1-4alkyl, may be prepared by reacting a compound of formula (AF), wherein G is C1-4alkyl and Z is a halogen, preferably bromine or iodine, with a boronic acid of formula (O) in the presence of a suitable metal catalyst, a suitable base, and optionally a suitable ligand, in a suitable solvent.
Figure imgf000033_0001
formula (AF) formula (O) formula (AE)
Suitable solvents include toluene and π-butanol, suitable bases include inorganic bases such as potassium phosphate, a suitable metal catalyst is a palladium catalyst, for example in the form of palladium(ll) acetate, and suitable ligands include substituted phosphines, for example 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl.
Compounds of formula (AF) are known compounds, or may be prepared by methods known in the literature. For example a compound of formula (AF) wherein G is C1-4alkyl and Z is a bromine atom may be prepared by reacting a compound of formula (AG), wherein G is C1-4alkyl, with a suitable brominating agent, such as Λ/-bromosuccinimide, in a suitable solvent, such as 1 ,2-dichloroethane, as described by R. Shepherd and A. White, J. Chem. Soc. Perkin Trans. 1 (1987), 10, 2153.
Halogenation
Figure imgf000033_0002
Figure imgf000033_0003
formula (AF)
In a similar manner, a compound of formula (A) may be prepared from a compound of formula (AH) by suitable derivatisation under standard conditions. derivatisation
Figure imgf000034_0002
Figure imgf000034_0001
formula (AH) formula (A)
For example, compounds of formula (AH) are alkenes, and as such undergo further reactions typical of alkenes to give compounds of formula (A) according to known procedures. Examples of such reactions include, but are not restricted to, reduction, halogenation, epoxidation, cyclopropanation, dihydroxylation, hydroarylation, hydrovinylation and hydration. Compounds of formula (AH) wherein R8 or R9 is bromine or iodine are vinyl halides, and undergo known reactions of vinyl halides such as Suzuki-Miyaura, Sonogashira, Stille and related reactions. Certain other compounds of formula (AH), wherein R8 or R9 is d-C6alkoxy, are enol ethers, and these may be hydrolysed to the corresponding ketone using standard procedures. In turn, the ketone produced may be further transformed, for example by ketalisation, oximation, reduction and the like under known conditions to give additional compounds of formula (A). Similarly, compounds of formula (AH) wherein R8 or R9 is CrC6amino or di-Ci-Cβamino are enamines, and these also may be hydrolysed to the corresponding ketone using standard procedures.
A compound of formula (AH) may be prepared from a compound of formula (Al) by reaction with a compound of formula (H), optionally in a suitable solvent, and optionally in the presence of a suitable catalyst. The compounds of formula (Al) have been particularly designed as intermediates in the synthesis of the compounds of the formula I.
Figure imgf000034_0003
formula (H)
Figure imgf000034_0005
Figure imgf000034_0004
formula (Al) formula (AH) Compounds of the formula (Al) having the specific formulae
Figure imgf000035_0001
and are known under the CAS registry numbers 299968-82-4 and 528833-96-7, respectively.
Preferably the catalyst is a Lewis acid catalyst such as aluminium chloride, bismuth (III) chloride, bismuth (III) trifluoromethanesulfonate, boron trifluoride, cerium (III) chloride, copper (I) trifluoromethanesulfonate, diethylaluminium chloride, hafnium (IV) chloride, iron (III) chloride, lithium perchlorate, lithium trifluoromethanesulfonate, magnesium bromide, magnesium iodide, scandium (III) trifluoromethanesulfonate, tin (IV) chloride, titanium (IV) chloride, titanium (IV) isopropoxide, trimethyl aluminium, Λ/-trimethylsilyl-bis(trifluoromethanesulfonyl)imide, trimethylsilyl trifluoromethane-sulfonate, ytterbium (III) trifluoromethanesulfonate, zinc iodide and zirconium (IV) chloride. Magnesium iodide is particularly preferred. Suitable solvents include those which are known to be effective solvents for conducting Diels-Alder reactions, among them, for example, chloroform, dichloromethane, diethyl ether, ethanol, methanol, perfluorinated alkanes, such as perfluorohexane, toluene, water.and ionic liquids such as 1-butyl-3- methylimidazolium tetrafluoroborate and 1-butyl-3-methylimidazolium hexafluorophosphate. Dichloromethane is particularly preferred as a solvent.
A compound of formula (Al), may be prepared by oxidising a compound of formula (AJ) in a suitable solvent such as toluene, acetone, chloroform, dichloromethane or 1 ,4-dioxane. A wide range of oxidants are suitable for effecting this transformation, including inorganic oxidants such as chromium trioxide, pyridinium dichromate, manganese dioxide and aluminium alkoxides such as aluminium isopropoxide, as well as organic oxidants such as 2,3-dichloro-5,6-dicyano-p- benzoquinone and hypervalent iodine oxidants such as 1 ,1 ,1 ,-tris(acetyloxy)-1 ,1-dihydro-1 ,2- benziodoxol-3-(1 H)-one (Dess-Martin periodinane), Suitable procedures are described, for example, by K. Saito and H. Yamachika, US4371711. and by G. Piancatelli et al., Tetrahedron (1978), 34, 2775. The use of chromium trioxide in a mixture of sulfuric acid and acetone (Jones reagent) is preferred. oxidation
Figure imgf000036_0001
Figure imgf000036_0002
formula (AJ) formula (Al)
The compounds of the formula Al have been particularly designed as intermediates for the synthesis of the compounds of the formula I.
Particularly useful compounds of the formula Al are those, wherein R5 and R12 are hydrogen. In another group of useful compounds of the formula I, R1, R2 and R4 are independently of each other methyl or ethyl.
In another group of useful compounds of the formula I, R1, R2 and R4 are independently of each other methyl or ethyl, and R3, R5 and R12 are hydrogen.
A compound of formula (AJ) may be prepared from a compound of formula (AK) by treatment with a suitable acid catalyst in the presence of water and optionally in the presence of a suitable solvent, according to known procedures.
aqueous acid or ZnCI2, water
Figure imgf000036_0004
Figure imgf000036_0003
formula (AK) formula (AJ)
For example, a compound of formula (AK) may be converted to a compound of formula (AJ) in the presence of an aqueous solution of an acid such as phosphoric acid or polyphosphoric acid as described, for example by K. Saito and H. Yamachika, US4371711. Alternatively a compound of formula (AJ) may be prepared from a compound of formula (AK) by rearrangement in the presence of a Lewis acid catalyst such as zinc chloride according to the procedure of G. Piancatelli et al., Tetrahedron, (1978), 34, 2775.
A compound of formula (AK) may be prepared by the reduction of a compound of formula (AL) by known conditions (see, for example R Silvestri et al., J. Med. Chem., 2005, 48, 4378-4388). reduction
Figure imgf000037_0002
Figure imgf000037_0001
formula (AL) formula (AK)
Compounds of formula (AL) are known, or may be made by known methods from known compounds (see, for example, L. Liebeskind et al., Org. Lett., (2003), 5 (17), 3033-3035, H. Firouzabadi, N. lranpoor and F. Nowrouzi, Tetrahedron, (2004), 60,10843, R. Silvestri et al., J. Med. Chem., (2005), 48, 4378 and references therein).
Alternatively a compound of formula (AK) may be prepared by the addition of a suitable organometallic reagent such as an arylmagnesium halide of formula (AM) wherein Hal is a halide such as chloride, bromide or iodide, or an aryllithium reagent of formula (AN) or a diarylzinc reagent of formula (AO) to a furan-2-carboxaldehyde of formula (AP) according to known procedures (see, for example G. Panda et al., Tetrahedron Lett., (2005), 46, 3097).
Figure imgf000037_0003
formula (AM) formula (AN)
Figure imgf000037_0004
Figure imgf000037_0005
formula (AP) formula (AK)
Figure imgf000037_0006
formula (AO)
Additional compounds of formula (AK) may be prepared from compounds of formula (AR) by reaction with a strong base, for a example an alkyl lithium reagent such as n-butyllithium, optionally in the presence of an additive such as tetramethylethylenediamine, and in a suitable solvent such as diethyl ether or tetrahydrofuran, followed by reaction with a benzaldehyde of formula (AS) as described, for example by I. Gupta and M. Ravikanth, J. Org. Chem., (2004), 69, 6796, A. M. Echavarren et a/., J. Am. Chem. Soc, (2003),125 (19), 5757, and by T. K. Chandrashekar ef a/., J. Org. Chem., (2002), 67, 6309-6319.
1. alkyl lithium
Figure imgf000038_0002
formula (AR) 2.
Figure imgf000038_0001
Figure imgf000038_0003
formula (AS)
The organometallic reagents of formula (AM), formula (AN) and formula (AO) are known compounds or may be made by known methods from known compounds. Compounds of formula (AP), formula (AR) and formula (AS) are known compounds, or may be prepared from known compounds by known methods.
The compounds of formula I according to the invention can be used as herbicides in unmodified form. as obtained in the synthesis, but they are generally formulated into herbicidal compositions in a variety of ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, for example in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil- in-water emulsions, oil flowables, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known, for example, from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. Such formulations can either be used directly or are diluted prior to use. Diluted formulations can be prepared, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
The formulations can be prepared, for example, by mixing the active ingredient with formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, for example finely divided solids, mineral oils, vegetable oils, modified vegetable oils, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into their surroundings in controlled amounts (e.g. slow release). Microcapsules usually have a diameter of , from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight. The active ingredients can be present in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes comprise, for example, natural and synthetic gums, cellulose, styrene-butadiene copolymers, polyacrylonitrile, polyacrylate, polyester, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art in this connection. Alternatively it is possible for very fine microcapsules to be formed wherein the active ingredient is present in the form of finely divided particles in a solid matrix of a base substance, but in that case the microcapsule is not encapsulated.
The formulation adjuvants suitable for the preparation of the compositions according to the invention are known perse. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylenes carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1 ,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1 ,1 ,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n- octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG 400), propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and higher molecular weight alcohols, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl- 2-pyrrolidone and the like. Water is generally the carrier of choice for the dilution of the concentrates. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montomorillonite, cottonseed husks, wheatmeal, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar materials, as described, for example, in CFR 180.1001. (c) & (d).
A large number of surface-active substances can advantageously be used both in solid and in liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they may be used as emulsifiying, wetting or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol- alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts.of mono-.and di-alkyl phosphate esters; and also further- substances described e.g. in "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, New Jersey, 1981.
Further adjuvants which can usually be used in pesticidal formulations include crystallisation inhibitors, viscosity-modifying substances, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing aids, anti-foams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion-inhibitors, fragrances, wetting agents, absorption improvers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, anti-freezes, microbiocides, and also liquid and solid fertilisers.
The formulations may also comprise additional active substances, for example further herbicides, herbicide safeners, plant growth regulators, fungicides or insecticides.
The compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive used in the composition according to the invention is generally from 0.01 to 10 %, based on the spray mixture. For example, the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rhόne-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. A preferred additive contains, for example, as active components essentially 80 % by weight alkyl esters of fish oils and 15 % by weight methylated rapeseed oil, and also 5 % by weight of customary emulsifiers and pH modifiers. Especially preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-Ci8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being important. Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) and methyl oleate (CAS-112-62-9). A preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH). Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000.
The application and action of the oil additives can be further improved by combining them with surface-active substances, such as non-ionic, anionic or cationic surfactants. Examples of suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485. Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C12-C22 fatty alcohols having a degree of ethoxylation of from 5 to 40. Examples of commercially available surfactants are the Genapol types (Clariant AG). Also preferred are silicone surfactants, especially polyalkyl-oxide-modified heptamethyltrisiloxanes, which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants. The concentration of surface-active substances in relation to the total additive is generally from 1 to 30 % by weight. Examples of oil additives that consist of mixtures of oils or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Syngenta AG, CH) and Actipron® (BP Oil UK Limited, GB).
The said surface-active substances may also be used in the formulations alone, that is to say without oil additives.
Furthermore, the addition of an organic solvent to the oil additive/surfactant mixture can contribute to a further enhancement of action. Suitable solvents are, for example, Solvesso® (ESSO) and Aromatic Solvent® (Exxon Corporation).The concentration of such solvents can be from 10 to 80 % by weight of the total weight. Such oil additives, which may be in admixture with solvents, are described, for example, in US-A-4 834 908. A commercially available oil additive disclosed therein is known by the name MERGE® (BASF Corporation). Further oil additives that are preferred according to the invention are SCORE® (Syngenta Crop Protection Canada) and Adigor® (Syngenta Crop Protection Canada).
In addition to the oil additives listed above, in order to enhance the activity of the compositions according to the invention it is also possible for formulations of alkylpyrrolidones, (e.g. Agrimax®) to be added to the spray mixture. Formulations of synthetic latices, such as, for example, polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®) can also be used. Solutions that contain propionic acid, for example Eurogkem Pen-e-trate®, can also be mixed into the spray mixture as activity-enhancing agents.
The herbicidal formulations generally contain from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of a compound of formula I and from 1 to 99.9 % by weight of a formulation adjuvant, which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rate of application of the compounds of formula I may vary within wide limits and depends upon the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed or grass to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula I according to the invention are generally applied at a rate of 1- 2000 g/ha, preferably 1- 1000 g / ha and most preferably at 1- 500 g / ha.
Preferred formulations have especially the following compositions: (% = percent by weight):
Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 %
Dusts: active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
Suspension concentrates: active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 %
Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 %
Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
The following Examples further illustrate, but do not limit, the invention.
F1. Emulsifiable concentrates a) b) c) d) active ingredient 5 % 10% 25% 50% calcium dodecylbenzene- sulfonate 6 % 8% ' 6% 8 % castor oil polyglycol ether 4% - - 4% 4 %
(36 mol of ethylene oxide) octylphenol polyglycol ether - 4 % - 2 %
(7-8 mol of ethylene oxide)
NMP - - 10% 20% arom. hydrocarbon 85% 78% 55% 16% mixture C9-C12
Emulsions of any desired concentration can be prepared from such concentrates by dilution with water.
F2. Solutions a) b) c) d) active ingredient 5% 10% 50% 90%
1 -methoxy-3-(3-methoxy- propoxy)-propane - 20% 20% - polyethylene glycol MW 400 20% 10% - -
NMP - - 30% 10% arom. hydrocarbon 75% 60% - - mixture Cg-Ci2 The solutions are suitable for application in the form of microdrops.
F3. Wettable powders a) b) c) d) active ingredient 5% 25% 50% 80% sodium lignosulfonate 4% - 3% - sodium lauryl sulfate 2% 3% - 4% sodium diisobutylnaphthalene- sulfonate - 6% 5% 6% octylphenol polyglycol ether - 1 % 2% -
(7-8 mol of ethylene oxide) highly disperse silicic acid 1 % 3% 5% 10% kaolin 88% 62% 35% _
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, yielding wettable powders which can be diluted with water to give suspensions of any desired concentration.
F4. Coated granules a) b) c) active ingredient 0.1 % 5% 15 % highly disperse silicic acid 0.9 % 2% 2 % inorg. carrier 99.0 % 93% 83 %
(diameter 0.1 - 1 mm) e.g. CaCO3 or SiO2
The active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier and the solvent is subsequently evaporated off in vacuo.
F5. Coated granules a) b) c) active ingredient 0.1 % 5% 15 % polyethylene glycol MW 200 1.0 % 2% 3 % highly disperse silicic acid 0.9 % 1 % 2 % inorg. carrier 98. 0% 92% 80 %
(diameter 0.1 - 1 mm) e.g. CaCO3 or SiO2
The finely ground active ingredient is applied uniformly, in a mixer, to the carrier moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
F6. Extruder granules a) b) c) d) active ingredient 0.1 % 3% 5% 15% sodium lignosulfonate 1.5 % 2 % 3 % 4 % carboxymethylcellulose 1.4 % 2 % 2 % 2 % kaolin 97.0% 93% 90% 79% The active ingredient is mixed and ground with the adjuvants and the mixture is moistened with water. The resulting mixture is extruded and then dried in a stream of air.
F7. Dusts a) b) c) active ingredient 0.1 % 1 % 5 % talcum 39.9 % 49 % 35 % kaolin 60.0 % 50 % 60 %
Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
F8. Suspension concentrates a) b) C) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether - 1 % 2 % -
(15 mol of ethylene oxide) sodium lignosulfonate 3 % 3 % 4 % 5 % carboxymethylcellulose 1 % 1 % 1 % 1 %
37 % aqueous formaldehyde 0.2 % 0.2 % 0.2 % 0.2 % solution silicone oil emulsion 0.8 % 0.8 % 0.8 % 0.8 % water 87 % 79 % 62 % 38 %
The finely ground active ingredient is intimately mixed with the adjuvants, yielding a suspension concentrate from which suspensions of any desired concentration can be prepared by dilution with water.
The invention relates also to a method for the selective control of grasses and weeds in crops of useful plants, and for non-selective weed control, which comprises treating the useful plants or the area under cultivation or the locus thereof with a compound of formula I.
Crops of useful plants in which the compositions according to the invention can be used include especially cereals, in particular wheat and barley, rice, corn, rape, sugarbeet, sugarcane, soybean, cotton, sunflower, peanut and plantation crops.
The term "crops" is to be understood as also including crops that have been rendered tolerant to herbicides or classes of herbicides (for example ALS, GS, EPSPS, PPO and HPPD inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant e.g. to imidazolinones, such as imazamox, by conventional methods of breeding is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®. The weeds to be controlled may be both monocotyledonous and dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica. Control of monocotyledonous weeds, in particular Agrostis, Avena, Setaria, Lolium, Echinochloa, Bromus, Alopecurus and Sorghum is very extensive.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt-176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins and transgenic plants able to synthesise such toxins are described in EP-A-451 878, EP- A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants that contain one or more genes which code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops and their seed material can be resistant to herbicides and at the same time also to insect feeding ("stacked" transgenic events). Seed can, for example, have the ability to express an insecticidally active Cry3 protein and at the same time be glyphosate-tolerant. The term "crops" is to be understood as also including crops obtained as a result of conventional methods of breeding or genetic engineering which contain so-called output traits (e.g. improved flavour, storage stability, nutritional content).
Areas under cultivation are to be understood as including land where the crop plants are already growing as well as land intended for the cultivation of those crop plants.
The compounds of formula I according to the invention can also be used in combination with further herbicides. Preferably, in these mixtures, the compound of the formula I is one of those compounds listed in Tables 1 to 146 below. The following mixtures of the compound of formula I are especially important: compound of formula I + acetochlor, compound of formula I + acifluorfen, compound of formula I + acifluorfen-sodium, compound of formula I + aclonifen, compound of formula I + acrolein, compound of formula I + alachlor, compound of formula I + alloxydim, compound of formula I + allyl alcohol, compound of formula I + ametryn, compound of formula I + amicarbazone, compound of formula I + amidosulfuron, compound of formula I + aminopyralid, compound of formula I + amitrole, compound of formula I + ammonium sulfamate, compound of formula I + anilofos, compound of formula I + asulam, compound of formula I + atraton, compound of formula I + atrazine, compound of formula I + azimsulfuron, compound of formula I + BCPC, compound of formula I + beflubutamid, compound of formula I + benazolin, compound of formula I + benfluralin, compound of formula I + benfuresate, compound of formula I + bensulfuron, compound of formula I + bensulfuron-methyl, compound of formula I + bensulide, compound of formula I + bentazone, compound of formula I + benzfendizone, compound of formula I + benzobicyclon, compound of formula I + benzofenap, compound of formula I + bifenox, compound of formula I + bilanafos, compound of formula I + bispyribac, compound of formula I + bispyribac-sodium, compound of formula I + borax, compound of formula I + bromacil, compound of formula I + bromobutide, compound of formula I + bromoxynil, compound of formula I + butachlor, compound of formula I + butafenacil, compound of formula I + butamifos, compound of formula I + butralin, compound of formula I + butroxydim, compound of formula I + butylate, compound of formula I + cacodylic acid, compound of formula I + calcium chlorate, compound of formula I + cafenstrole, compound of formula I + carbetamide, compound of formula I + carfentrazone, compound of formula I + carfentrazone-ethyl, compound of formula I + CDEA, compound of formula ! + CEPC, compound-of-formula I + chlorflurenol, compound of formula I + - chlorflurenol-methyl, compound of formula I + chloridazon, compound of formula I + chlorimuron, compound of formula I + chlorimuron-ethyl, compound of formula I + chloroacetic acid, compound of formula I + chlorotoluron, compound of formula I + chlorpropham, compound of formula I + chlorsulfuron, compound of formula I + chlorthal, compound of formula I + chlorthal- dimethyl, compound of formula I + cinidon-ethyl, compound of formula I + cinmethylin, compound of formula I + cinosulfuron, compound of formula I + cisanilide, compound of formula I + clethodim, compound of formula I + clodinafop, compound of formula I + clodinafop-propargyl, compound of formula I + clomazone, compound of formula I + clomeprop, compound of formula I + clopyralid, compound of formula I + cloransulam, compound of formula I + cloransulam-methyl, compound of formula I + CMA, compound of formula I + 4-CPB, compound of formula I + CPMF, compound of formula I + 4-CPP, compound of formula I + CPPC, compound of formula I + cresol, compound of formula I + cumyluron, compound of formula I + cyanamide, compound of formula I + cyanazine, compound of formula I + cycloate, compound of formula I + cyclosulfamuron, compound of formula I + cycloxydim, compound of formula I + cyhalofop, compound of formula I + cyhalofop-butyl, compound of formula I + 2,4-D, compound of formula I + 3,4-DA, compound of formula I + daimuron, compound of formula I + dalapon, compound of formula I + dazomet, compound of formula I + 2,4-DB, compound of formula I + 3,4-DB, compound of formula I + 2,4-DEB, compound of formula I + desmedipham, compound of formula I + dicamba, compound of formula I + dichlobenil, compound of formula I + ortho- dichlorobenzene, compound of formula I + para-dichlorobenzene, compound of formula I + dichlorprop, compound of formula I + dichlorprop-P, compound of formula I + diclofop, compound of formula I + diclofop-methyl, compound of formula I + diclosulam, compound of formula I + difenzoquat, compound of formula I + difenzoquat metilsulfate, compound of formula I + diflufenican, compound of formula I + diflufenzopyr, compound of formula I + dimefuron, compound of formula I + dimepiperate, compound of formula I + dimethachlor, compound of formula I + dimethametryn, compound of formula I + dimethenamid, compound of formula I + dimethenamid-P, compound of formula I + dimethipin, compound of formula I + dimethylarsinic acid, compound of formula I + dinitramine, compound of formula I + dinoterb, compound of formula I + diphenamid, compound of formula I + diquat, compound of formula I + diquat dibromide, compound of formula I + dithiopyr, compound of formula I + diuron, compound of formula I + DNOC, compound of formula I + 3,4-DP, compound of formula I + DSMA, compound of formula I + EBEP, compound of formula I + endothal, compound of formula I + EPTC, compound of formula I + esprocarb, compound of formula I + ethalfluralin, compound of formula I + ethametsulfuron, compound of formula I + ethametsulfuron-methyl, compound of formula I + ethofumesate, compound of formula I + ethoxyfen, compound of formula I + ethoxysulfuron, compound of formula I + etobenzanid, compound of formula I + fenoxaprop-P, compound of formula I + fenoxaprop-P-ethyl, compound of formula I + fentrazamide, compound of formula I + ferrous sulfate, compound of formula I + flamprop-M, compound of formula I + flazasulfuron, compound of formula I + florasulam, compound of formula I + fluazifop, compound of formula I + fluazifop-butyl, compound of formula I + fluazifop-P, compound of formula I + fluazifop-P-butyl, compound of formula I + flucarbazone, compound of formula I + flucarbazone-sodium, compound of formula I + flucetosulfuron, compound of formula I + fluchloralin, compound of formula I + flufenacet, compound of formula I + flufenpyr, compound of formula I + flufenpyr- ethyl, compound of formula I + flumetsulam, compound of formula I + flumiclorac, compound of formula I + flumiclorac-pentyl, compound of formula I + flumioxazin, compound of formula I + fluometuron, compound of formula I + fluoroglycofen, compound of formula I + fluoroglycofen- ethyl, compound of formula I + flupropanate, compound of formula I + flupyrsulfuron, compound of formula I + flupyrsulfuron-methyl-sodium, compound of formula I + flurenol, compound of formula I + fluridone, compound of formula I + flurochloridone, compound of formula I + fluroxypyr, compound of formula I + flurtamone, compound of formula I + fluthiacet, compound of formula I + fluthiacet-methyl, compound of formula I + fomesafen, compound of formula I + foramsulfuron, compound of formula I + fosamine, compound of formula I + glufosinate, compound of formula I + glufosinate-ammonium, compound of formula I + glyphosate, compound of formula I + halosulfuron, compound of formula I + halosulfuron-methyl, compound of formula I + haloxyfop, compound of formula I + haloxyfop-P, compound of formula I + HC-252, compound of formula I + hexazinone, compound of formula I + imazamethabenz, compound of formula I + imazamethabenz-methyl, compound of formula I + imazamox, compound of formula I + imazapic, compound of formula I + imazapyr, compound of formula I + imazaquin, compound of formula I + imazethapyr, compound of formula I + imazosulfuron, compound of formula I + indanofan, compound of formula I + iodomethane, compound of formula I + iodosulfuron, compound of formula I + iodosulfuron-methyl-sodium, compound of formula I + ioxynil, compound of formula I + isoproturon, compound of formula I + isouron, compound of formula I + isoxaben, compound of formula I + isoxachlortole, compound of formula I + isoxaflutole, compound of formula I + karbutilate, compound of formula I + lactofen, compound of formula I + lenacil, compound of formula I + linuron, compound of formula I + MAA, compound of formula I + MAMA, compound of formula I + MCPA, compound of formula I + MCPA-thioethyl, compound of formula I + MCPB, compound of formula I + mecoprop, compound of formula I + mecoprop-P, compound of formula I + mefenacet, compound of formula I + mefluidide, compound of formula I + mesosulfuron, compound of formula I + mesosulfuron-methyl, compound of formula I + mesotrione, compound of formula I + metam, compound of formula I + metamifop, compound of formula I + metamitron, compound of formula I + metazachlor, compound of formula I + methabenzthiazuron, compound of formula I + methylarsonic acidτ compound of formula I + methyldymron, compound of formula I + methyl isothiocyanate, compound of formula I + metobenzuron, compound of formula I + metolachlor, compound of formula I + S-metolachlor, compound of formula I + metosulam, compound of formula I + metoxuron, compound of formula I + metribuzin, compound of formula I + metsulfuron, compound of formula I + metsulfuron-methyl, compound of formula I + MK-616, compound of formula I + molinate, compound of formula I + monolinuron, compound of formula I + MSMA, compound of formula I + naproanilide, compound of formula I + napropamide, compound of formula I + naptalam, compound of formula I + neburon, compound of formula I + nicosulfuron, compound of formula I + nonanoic acid, compound of formula I + norflurazon, compound of formula I + oleic acid (fatty acids), compound of formula I + orbencarb, compound of formula I + orthosulfamuron, compound of formula I + oryzalin, compound of formula I + oxadiargyl, compound of formula I + oxadiazon, compound of formula I + oxasulfuron, compound of formula I + oxaziclomefone, compound of formula I + oxyfluorfen, compound of formula I + paraquat, compound of formula I + paraquat dichloride, compound of formula I + pebulate, compound of formula I + pendimethalin, compound of formula I + penoxsulam, compound of formula I + pentachlorophenol, compound of formula I + pentanochlor, compound of formula I + pentoxazone, compound of formula I + pethoxamid, compound of formula I + petrolium oils, compound of formula I + phenmedipham, compound of formula I + phenmedipham-ethyl, compound of formula I + picloram, compound of formula I + picolinafen, compound of formula I + pinoxaden, compound of formula I + piperophos, compound of formula I + potassium arsenite, compound of formula I + potassium azide, compound of formula I + pretilachlor, compound of formula I + primisulfuron, compound of formula I + primisulfuron-methyl, compound of formula I + prodiamine, compound of formula I + profluazol, compound of formula I + profoxydim, compound of formula I + prometon, compound of formula I + prometryn, compound of formula I + propachlor, compound of formula I + propanil, compound of formula I + propaquizafop, compound of formula I + propazine, compound of formula I + propham, compound of formula I + propisochlor, compound of formula I + propoxycarbazone, compound of formula I + propoxycarbazone-sodium, compound of formula I + propyzamide, compound of formula I + prosulfocarb, compound of formula I + prosulfuron, compound of formula I + pyraclonil, compound of formula I + pyraflufen, compound of formula I + pyraflufen-ethyl, compound of formula I + pyrazolynate, compound of formula I + pyrazosulfuron, compound of formula I + pyrazosulfuron-ethyl, compound of formula I + pyrazoxyfen, compound of formula I + pyhbenzoxim, compound of formula I + pyributicarb, compound of formula I + pyridafol, compound of formula I + pyridate, compound of formula I + pyriftalid, compound of formula I + pyriminobac, compound of formula I + pyriminobac-methyl, compound of formula I + pyrimisulfan, compound of formula I + pyrithiobac, compound of formula I + pyrithiobac-sodium, compound of formula I + quinclorac, compound of formula I + quinmerac, compound of formula I + quinoclamine, compound of formula I + quizalofop, compound of formula I + quizalofop-P, compound of formula I + rimsulfuron, compound of formula I + sethoxydim, compound of formula I + siduron, compound of formula I + simazine, compound of formula I + simetryn, compound of formula I + SMA, compound of formula I + sodium arsenite, compound of formula I + sodium azide, compound of formula I + sodium chlorate, compound of formula I + sulcotrione, compound of formula I + sulfentrazone, compound of formula I + sulfometuron, compound of formula I + sulfometuron-methyl, compound of formula I + sulfosate, compound of formula I + sulfosulfuron, compound of formula I + sulfuric acid, compound of formula I + tar oils, compound of formula I + 2,3,6-TBA, compound of formula I + TCA, compound of formula I + TCA-sodium, compound of formula I + tebuthiuron, compound of formula I + tepraloxydim, compound of formula I + terbacil, compound of formula I + terbumeton, compound of formula I + terbuthylazine, compound of formula I + terbutryn, compound of formula I + thenylchlor, compound of formula I + thiazopyr, compound of formula I + thifensulfuron, compound of formula I + thifensulfuron-methyl, compound of formula I + thiobencarb, compound of formula I + tiocarbazil, compound of formula I + topramezone, compound of formula I + tralkoxydim, compound of formula I + tri-allate, compound of formula I + triasulfuron, compound of formula I + triaziflam, compound of formula I + tribenuron, compound of formula I + tribenuron-methyl, compound of formula I + tricamba, compound of formula I + triclopyr, compound of formula I + trietazine, compound of formula I + trifloxysulfuron, compound of formula I + trifloxysulfuron-sodium, compound of formula I + trifluralin, compound of formula I + triflusulfuron, compound of formula I + triflusulfuron-methyl, compound of formula I + trihydroxytriazine, compound of formula I + tritosulfuron, compound of formula I + [3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1 ,2,3,4- tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid ethyl ester (CAS RN 353292-31-6), compound of formula I + 4-[(4,5-dihydro-3-methoxy-4-methyl-5-oxo)-1 H-1 ,2,4-triazol-1- ylcarbonylsulfamoylJ-δ-methylthiophene-S-carboxylic acid (BAY636), compound of formula I + BAY747 (CAS RN 335104-84-2), compound of formula I + topramezone (CAS RN 210631-68-8), compound of formula I + 4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3- pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one (CAS RN 352010-68-5), and compound of formula I + 4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]carbonyl]- bicyclo[3.2.1]oct-3-en-2-one.
The mixing partners for the compound of formula I may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 12th Edition (BCPC) 2000.
The compounds of formula I according to the invention can also be used in combination with safeners. Preferably, in these mixtures, the compound of the formula I is one of those compounds listed in Tables 1 to 146 below. The following mixtures with safeners, especially, come into consideration: compound of formula I + cloquintocet-mexyl, compound of formula I + cloquintocet acid and salts thereof, compound of formula I + fenchlorazole-ethyl, compound of formula I + fenchlorazole acid and salts thereof, compound of formula I + mefenpyr-diethyl, compound of formula I + mefenpyr diacid, compound of formula I + isoxadifen-ethyl, compound of formula I + isoxadifen acid, compound of formula I + furilazole, compound of formula I + furilazole R isomer, compound of formula (I) + N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide, compound of formula I + benoxacor, compound of formula I + dichlormid, compound of formula I + AD-67, compound of formula I + oxabetrinil, compound of formula I + cyometrinil, compound of formula I + cyometrinil Z-isomer, compound of formula I + fenclorim, compound of formula I + cyprosulfamide, compound of formula I + naphthalic anhydride, compound of formula I + flurazole, compound of formula I + CL 304,415, compound of formula I + dicyclonon, compound of formula I + fluxofenim, compound of formula I + DKA-24, compound of formula I + R-29148 and compound of formula I + PPG-1292. A safening effect can also be observed for the mixtures compound of the formula I + dymron, compound of the formula I + MCPA, compound of the formula I + mecoprop and compound of the formula I + mecoprop-P.
The above-mentioned safeners and herbicides are described, for example, in the Pesticide Manual, Twelfth Edition, British Crop Protection Council, 2000. R-29148 is described, for example by P. B. Goldsbrough et al., Plant Physiology, (2002), Vol. 130 pp. 1497-1505 and references therein, PPG-1292 is known from WO09211761 and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide is known from EP365484.
Benoxacor, cloquintocet-mexyl, cyprosulfamide, mefenpyr-diethyl and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide are especially preferred, where cloquintocet- mexyl is particularly valuable.
It is preferred to apply the other herbicide together with one of the safeners mentioned above. The following Examples illustrate the invention further but do not limit the invention.
Preparation Examples:
Those skilled in the art will appreciate that certain compounds described below are β-ketoenols, and as such may exist as a single tautomer or as a mixture of keto-enol and diketone tautomers, as described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons. The compounds shown below, and in Table T1 are drawn as an arbitrary single enol tautomer, but it should be inferred that this description covers both the diketone form and any possible enols which could arise through tautomerism. Where more than one tautomer is observed in proton NMR, the data shown are for the mixture of tautomers. Furthermore, some of the compounds shown below are drawn as single enantiomers for the purposes of simplicity, but unless specified as single enantiomers, these structures should be construed as representing a mixture of enantiomers. Additionally, some of the compounds can exist as diastereoisomers, and it should be inferred that these can be present as a mixture of diastereoisomers or as any possible single diastereoisomer. Within the detailed experimental section the diketone tautomer is chosen for naming purposes, even if the predominant tautomer is the enol form.
Example 1
Preparation of (1RS.2SR, 6f?S, 7Sf?)-4-(2.6-diethyl-4-methylphenyl)-10-oxatricvclo-
[5.2.1.02|6ldecane-3.5-dione.
Figure imgf000053_0001
Step 1 : Preparation of (1RS,2SR,6RS, 7Sf?)-10-oxatricyclo[5.2.1.0 ,2 ■.6 ],dec-8-ene-3,5-dione
Figure imgf000053_0002
Furan (13.9 ml, 0.19 mol) is added to cyclopentene-1 ,4-dione (18.4 g, 0.19 mol) and the reaction mixture is stirred at room temperature for 5 days. The mixture is diluted with methanol and (1RS,2SR,6RS, 7SR)-10-oxatricyclo[5.2.1.026]dec-8-ene-3,5-dione is collected by filtration, and used without further purification in the next step.
Step 2: Preparation of (1RS,2SR,6RS, 7Sf?)-10-oxatricyclo[5.2.1.02'6]decane-3,5-dione.
Figure imgf000053_0003
(fRS^SR.βRS^SRHO-oxatricycloβ^.i .O^Jdec-δ-ene-S.δ-dione (2.1 g, 12.8 mmol), prepared in Step 1 , is dissolved in warm methanol (180 ml) and the mixture is allowed to cool to room temperature. The mixture is then hydrogenated in the presence of 5% palladium on carbon (approx. 50 mg) at 3.5 bar for 4 hours. The catalyst is removed by filtration through diatomaceous earth and the filtrate is concentrated under reduced pressure to afford (7RS,2SR,6f?S,7Sf?)-10- oxatricyclo[5.2.1.02|6]decane-3,5-dione.
Step 3: Preparation of {1RS,2SR,6RS, 7S/:?)-4-(2,6-diethyl-4-methylphenyl)-10-oxatricyclo- [5.2.1.02 <3]decane-3,5-dione.
Figure imgf000054_0001
Iodobenzene diacetate (10.3 g, 32.0 mol) and sodium carbonate (3.38 g, 32.0 mmol) are suspended in water (100 ml) and the resultant yellow suspension is stirred at room temperature for 30 minutes. Meanwhile, (I RS^SR.eRSJSRJ-IO-oxatricycloIδ^.i .O^decane-S.δ-dione (5.3 g, 32.0 mol) is added to a solution of sodium carbonate (3.38 g, 32.0 mol) in water (50 ml) and ethanol (50 ml) and the mixture is stirred at room temperature to produce an orange solution. The two mixtures are combined and stirred for 3 hours at room temperature, then the mixture is poured into water and extracted with dichloromethane. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure to give an iodonium ylide, used without further purification in the next step.
The iodonium ylide (3 g, 8.15 mmol), prepared above, is added to a solution of 2,6-diethyl-4- methylphenylboronic acid (1.57 g, 8.15 mmol), tetrabutylammonium bromide (2.63 g, 8.15 mmol), lithium hydroxide monohydrate (1.03 g, 24.5 mmol) and palladium (II) acetate (92 mg, 0.41 mmol) in 1 ,2-dimethoxyethane (80 ml) and water (20 ml) and the reaction mixture is heated at 5O0C for 5 hours under an atmosphere of nitrogen. The reaction mixture is cooled to room temperature and partitioned between dilute aqueous hydrochloric acid and ethyl acetate. The organic phase is then extracted into 0.5 M aqueous potassium carbonate solution and the organic phase discarded. The aqueous phase is acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic extract is dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to afford (^f?S,2Sf?,6f?S, 7SR)-4-(2,6-diethyl-4-methylphenyl)-10- oxatricyclo[5.2.1.02'6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.88 - 6.87 (2H , m), 4.55 - 4.54 (2H, m), 2.62 (2H, s), 2.36 - 2.27 (7H, m), 1.69 - 1.67 (2H, m), 1.40 - 1.39 (2H, m), 1.03 (6H, q).
Example 2
Preparation of (1RS.2RS.6SR, 7Sf?)-4-(2.6-diethyl-4-methylphenyl)-5-methoxy-10-oxa- tricvclo[5.2.1.02'6ldeca-4.8-dien-3-one.
Figure imgf000055_0001
Step 1 : Preparation of 2-bromo-3-methoxycyclopent-2-enone.
Figure imgf000055_0002
/V-Bromosuccinimide (24.92 g, 0.140 mol) is added, portionwise, over 1 hour to a stirred solution of 3-methoxycyclopent-2-enone (14.95 g, 0.133 mol) in 1 ,2-dichloroethane (300 ml) at 00C in an amber flask. The reaction mixture is stirred at O0C for a further 90 minutes and then any remaining solid is removed by filtration. The filtrate is evaporated to dryness under reduced pressure, the resultant solid is dissolved in warm toluene (600 ml) and washed quickly with ice- cold water (2 x 100 ml). The organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure until approximately 150 ml remains. The residue is cooled with an ice bath and left for 30 minutes. The resultant solid is removed by filtration, washed with hexane (50 ml) and air-dried to give 2-bromo-3-methoxycyclopent-2- enone.
Step 2: Preparation of 2-(2,6-diethyl-4-rnethylphenyl)-3-methoxycyclopent-2-enone.
Figure imgf000055_0003
To a stirred suspension of 2-bromo-3-methoxycyclopent-2-enone (17.5 g, 91.6 mmol), 2,6- diethyl-4-methylphenyl boronic acid (26.4 g, 137 mmol) and freshly powdered potassium phosphate (38.9 g, 183 mmol) in anhydrous, degassed toluene (450 ml) under a nitrogen atmosphere are added palladium (II) acetate (0.411 g, 1.83 mmol) and 2-dicyclohexylphosphino- 2',6'-dimethoxybiphenyl (1.51 g, 3.67 mmol). The reaction mixture is heated at 90°C for 6.5 hours and then allowed to cool to room temperature overnight. The reaction is diluted with water (400 ml) and extracted with ethyl acetate (3 x 150 ml). The combined organic extracts are washed with brine (50 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated to dryness under reduced pressure to give a brown oil. The crude product is purified by column chromatography on silica gel to give 2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone.
Step 3: Preparation of 5-chloro-2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone.
Figure imgf000056_0001
To a stirred solution of 2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone (0.715 g, 2.77 mmol) in 1 ,4-dioxane (45 ml), and under an atmosphere of nitrogen, are added copper (II) chloride (0.743 g, 5.53 mmol) and lithium chloride (0.176 g, 4.15 mmol). The reaction is heated at reflux for 7 hours and allowed to cool to room temperature overnight. The remaining solid is removed by filtration and washed with ethyl acetate (50 ml). The filtrate is washed with water (2 x 25 ml) and the aqueous washings re-extracted with ethyl acetate (15 ml). The combined organic phases are washed with brine (15 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure to give a brown oil. The crude product is purified by column chromatography on silica gel to give 5-chloro-2-(2,6-diethyl-4-methylphenyl)-3-methoxy- cyclopent-2-enone.
Step 4: Preparation of (7RS,2/?S,6SR, 7SR)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10-oxa- tricyclo[5.2.1.026]deca-4,8-dien-3-one.
Figure imgf000056_0002
To a stirred solution of 5-chloro-2-(2,6-diethyl-4-methylphenyl)-3-methoxycyclopent-2-enone (0.530 g, 1.81 mmol) in furan (40 ml) at room temperature is added by syringe pump over two hours a solution of 1 ,8-diazabicyclo[5.4.0]undec-7-ene (0.540 ml, 3.62 mmol) in furan (10 ml). The reaction is stirred at room temperature for a further 30 minutes and then evaporated to dryness under reduced pressure. The residue is diluted with water (50 ml), 2 M aqueous hydrochloric acid (25 ml) is added and the mixture is extracted with ethyl acetate (3 x 50 ml). The combined organic extracts are washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated to dryness under reduced pressure. The residue is purified by column chromatography on silica gel to give (1RS, 2RS, 6SR, 7SR)-4-(2,6-diethyl-4- methylphenyl)-5-methoxy-10-oxa-tricyclo[5.2.1.02|6]deca-4,8-dien-3-one.
1H NMR (400MHz, CDCI3) δH 6.90 (2H, s), 6.45 (1 H, dd), 6.35 (1 H, dd), 5.30 (1 H, d), 5.25 (1 H, d), 3.65 (3H, s), 3.65 (1 H, dd), 3.45 (1 H, dd), 2.35 (4H, m), 2.30 (3H, s), 1.10 (6H, m).
Note: A quantity of (1RS,2SR, 6RS, 7SR)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10- oxatricyclo[5.2.1.02|6]deca-4,8-dien-3-one is also formed during the course of this reaction.
Example 3
Preparation of (7/?S,2f?S,6SS, 7SR)-4-(2,6-diethyl-4-methylphenv0-5-methoxy-10-oxa- tricvclor5.2.1.026ldec-4-en-3-one.
Figure imgf000057_0001
To a solution of (7f?S,2ftS,6SR,7S/?)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10-oxa- tricyclo[5.2.1.02|6]deca-4,8-dien-3-one (0.052 g, 0.16 mmol) in methanol (10 ml) is added 5% palladium on carbon (10 mg). The reaction is stirred under an atmosphere of hydrogen for 90 minutes. The reaction is filtered through diatomaceous earth and the filter pad is washed with ethyl acetate (10 ml). The solvent is removed under reduced pressure to yield (ΪRS,2/?S,6- SR^SRH^.e-diethyM-methylphenyO-S-methoxy-IO-oxa-tricyclofδ^.i .O^dec^-en-S-one.
1H NMR (400MHz, CDCI3) δH 6.90 (2H, m), 4.85 (2H, m), 3.70 (3H, s), 3.60 (1 H, m), 3.35 (1 H, dd), 2.50 (2H, m), 2.35 (2H, m), 2.30 (3H, s), 1.90-1.75 (4H, m), 1.20 (3H1 1), 1.10 (3H, t). Example 4
Preparation of (1RS.2RS.6SS.7Sf?)-4-(2.6-diethyl-4-methylphenvn-10-oxatricvclo-
[5.2.1.026ldecane-3.5-dione.
Figure imgf000058_0001
To a solution of (7/?S,2RS,6SR 7Stf)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10-oxa- tricyclo[5.2.1.02 6]dec-4-en-3-one (0.049 g, 0.15 mmol) in THF (1 ml) in a 5 ml microwave vial is added 2 M aqueous hydrochloric acid (4 ml). The reaction mixture is at 140 0C under microwave irradiation for 50 minutes. The reaction mixture is cooled to room temperature, diluted with 2 M aqueous potassium carbonate solution (20 ml) and washed with diethyl ether (2 x 5 ml). The pH of the aqueous phase is adjusted to approx. 2 by addition of 5 M aqueous hydrochloric acid and then extracted with ethyl acetate (3 x 10 ml). The combined organic extracts are washed with brine (10 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated to dryness under reduced pressure to give a yellow oil. The crude product is purified by column chromatography on silica gel to give (7f?S,2f?S,6SS, 7SR)-4-(2,6-diethyl-4-methylphenyl)-10- oxatricyclo-[5.2.1.02|6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.95 (2H, s), 4.75 (2H, br), 3.40 (2H, br), 2.45 (2H, q), 2.35 (2H, q), 2.30 (3H, s), 1.80 (4H, m), 1.15 (3H, t), 1.05 (3H, t).
Example 5
Preparation of (1RS.2SR.6RS.7Sf?)-4-(2.6-diethyl-4-methylphenyl)-5-methoxy-10- oxatricyclor5.2.1.02 6ldec-4-en-3-one.
Figure imgf000058_0002
Step 1 : Preparation of (1RS,2SR,6RS, 7SR)-5-methoxy-10-oxatricyclo[5.2.1.026]dec-4-en-3-one.
Figure imgf000059_0001
Iodine (0.10 g, 0.38 mmol) is added to a solution of (7RS, 2SR, 6RSJSRyI 0-oxa- tricyclo[5.2.1.02l6]decane-3,5-dione (2.1 g, 12.65 mmol) in methanol (50 ml) and the reaction mixture is stirred for 2 hours at room temperature. The solvent is then removed under reduced pressure, dichloromethane is added and the organic layer is washed with saturated aqueous sodium thiosulfate solution, water and brine. The organic layer is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure to give (7RS,2SR,6RS, 7SR)-5-methoxy-10-oxatricyclo[5.2.1.02|6]dec-4-en-3-one and used without further purification in the next step.
Step 2: Preparation of (7RS,2SR,6RS, ZSRH-bromo-S-methoxy-IO-oxatricyclotS^.I .O^ldec^- en-3-one.
Figure imgf000059_0002
A solution of bromine (0.14 ml, 2.8 mmol) in dichloromethane (5 ml) is added dropwise to a solution of the enol ether (0.48 g, 2.6 mmol) prepared in step 1 in dichloromethane (40 ml) at 0° C and the reaction mixture is stirred for 1 hour. Triethylamine (0.64 ml, 4.6 mmol) is then added and the reaction mixture is allowed to warm to room temperature and then stirred for 3 hours. The reaction mixture is washed with 2M aqueous hydrochloric acid and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give (7RS,2SR,6RS, 7SR)-4-bromo- 5-methoxy-10-oxatricyclo[5.2.1.O26]dec-4-en-3-one.
Step 3: Preparation of (1RS, 2SR, 6RS, 7SR)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10- oxatricyclo[5.2.1.026]dec-4-en-3-one.
Figure imgf000060_0001
A mixture of (1RS, 2SR, 6RS, 7Sf?)-4-bromo-5-methoxy-10-oxatricyclo[5.2.1.026]dec-4-en-3-one (0.315 g, 1.2 mmol), 2,6-diethyl-4-methylphenylboronic acid (0.35 g, 1.8 mmol), 2-dicyclo- hexylphosphino-2',6'-dimethoxybiphenyl (20 mg, 0.048 mmol), palladium (II) acetate (5.5 mg, 0.024 mmol) and potassium phosphate (0.51 g, 2.4 mmol) are heated in degassed toluene at 95 0C for 24 hours. The reaction mixture is partitioned between dichloromethane and water, and the organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give (yRS,2Sf?,6RS, 7Sf?)-4-(2,6-diethyl-4-methylphenyl)-5-methoxy-10-oxatricyclo[5.2.1.02|6]dec-4- en-3-one.
1H NMR (400MHz, CDCI3) δH 6.90 (1 H, s), 6.80 (1 H, s), 4.73 (1 H, d), 4.66 (1 H, d), 3.58 (3H, s), 2.91 (1 H, d), 2.66 (1 H, d), 2.50 - 2.36 (4H, m), 2.30 (3H, s), 1.88 -1.81 (2H, m), 1.62 - 1.56 (2H, ■m), 1.12 - 1.09 (6H1 m).
Example 6
Preparation of (^S^SReRS^S^M^^.e-trimethylphenvn-IO-oxatricvclorδ^.i .O^idec-δ-en-
3.5-dione.
Figure imgf000060_0002
Step 1 : Preparation of (2,4,6-trimethylphenyl)furan-2-ylmethanol.
Figure imgf000061_0001
A solution of 2,4,6-trimethyl-1-bromobenzene (30.9 g,155 mmol) in tetrahydrofuran (100 ml) is added slowly to magnesium turnings (3.77 g, 155 mmol), until the magnesium is just covered. A small quantity of iodine is added and the mixture is allowed to stand at room temperature for 25 minutes and then heated and stirred until the brown colour is lost. The remainder of the aryl bromide solution is added dropwise over a 20 minute period, with occasional heating to maintain the formation of the Grignard reagent solution. The reaction is stirred at room temperature for 1 hour. A solution of furfural (12.8 ml, 155 mmol) in tetrahydrofuran (70 ml) is added dropwise, and once the addition is complete, the reaction is stirred at room temperature for 2 hours. The reaction is quenched by cautious addition of excess saturated ammonium chloride solution, then extracted into ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel affords (2,4,6-trimethylphenyl)furan-2-ylmethanol.
Step 2: Preparation of 5-(2,4,6-trimethylphenyl)-4-hydroxycyclopent-2-enone.
Figure imgf000061_0002
A solution of (2,4,6-trimethylphenyl)furan-2-ylmethanol (27.8 g, 129 mmol) in acetone (730 ml) and water (100 ml) is heated to 55 0C and polyphosphoric acid (2 g) is added. The mixture is stirred at 55 0C for 7 hours, then cooled to room temperature overnight. The reaction mixture is concentrated under reduced pressure to remove most of the acetone then ethyl acetate (500 ml) is added, and the reaction mixture is partitioned. The aqueous phase is extracted into ethyl acetate and the organic solutions are combined, washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 5-(2,4,6-trimethylphenyl)-4-hydroxycyclopent-2-enone.
Step 3: Preparation of 2-(2,4,6-trimethylphenyl)cyclopent-4-ene-1 ,3-dione.
Figure imgf000062_0001
Jones' reagent (138 ml of 1.67 M solution, 230 mmol) is added dropwise over 40 minutes to a cooled (ice-bath) solution of 5-(2,4,6-trimethylphenyl)-4-hydroxycyclopent-2-enone (49.66 g, 230 mmol) in acetone (600 ml). The mixture is stirred for 1 hour, lsopropanol (100 ml) is added and the mixture is stirred at room temperature for 2 hours. The mixture is diluted with ethyl acetate and washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure to give 2-(2,4,6-trimethylphenyl)cyclopent-4-ene-1 ,3-dione.
Step 4: Preparation of ( 1RS, 2SR, 6RS, 7Sf?)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.02l6]dec-8-en-3,5-dione.
Figure imgf000062_0002
Furan (214 ml, 3.15 mol) and magnesium iodide (7.0 g, 0.025 mol) are added to 2-(2,4,6- trimethylphenyl)cyclopent-4-ene-1 ,3-dione (27.0 g, 0.126 mol) and the mixture is stirred at room temperature for 4 days. The reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give (7f?S,2Sf?,6RS,7Sf?)-4-(2,4,6- trimethylphenylJ-IO-oxatricyclofδ^.i .O^^dec-δ-en-S.S-dione.
1H NMR (400MHz, CDCI3) δH 6.86 (2H, s), 6.47 (2H, S)1 5.01 (2H, s), 2.74 (2H, s), 2.23 (3H, s), 2.08 (3H, s), 2.06 (3H, s).
Example 7
Preparation of (1RS.2SR.6/?S.7Sffl-4-(2.4.6-trimethylphenyl)-10-oxatricvclof5.2.1.02'6ldecane-
3,5-dione.
Figure imgf000063_0001
A solution oH1RS,2SR,6RS JSR)-A-(2A,6Λήmeihy\pheny\)^0-oxa\ήc\/c\o[5.2Λ .02β]dec-8-en- 3,5-dione (205 mg, 0.66 mmol) in methanol (250 ml) is hydrogenated at 2 bar over 5% palladium on carbon (approximately 20 mgs) for 1 hour at room temperature. The catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure. Trituration with diethyl ether gives (^RS,2Sf?,6/:?S,7SR)-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02|6]decane-3,5-dione.
1H NMR (400MHz, d4-MeOH) δH 6.88 (2H, s), 4.61 (2H, s), 2.87 (2H, s), 2.27 (3H, s), 2.06 (6H, s), 1.84 - 1.82 (2H, m), 1.71 - 1.66 (2H, m).
Example 8
Preparation of (1RS.2SR.6RS, 7f?S)-4-(2.4,6-trimethylphenyl)-8-trimethylsilylethvnyl-10- oxatricvclof5.2.1.02'6ldecane-3,5-dione.
Figure imgf000063_0002
3-(Trimethylsilylethynyl)furan (10.0 g, 61 mmol) and magnesium iodide (1.11 g, 4 mmol) are added to 2-(2,4,6-trimethylphenyl)cyclopent-4-ene-1 ,3-dione (4.34 g , 20 mmol) and the mixture is stirred at room temperature for 3 days. The reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give (ϊf?S,2Sf?,6f?S, 7f?S)-4-(2,4,6-trimethylphenyl)-8-trimethylsilylethynyl-10-oxatricyclo- [5.2.1.02l6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.65 (2H, s), 6.26 (1 H, s), 4.75 (1 H, s), 4.67 (1 H, s), 2.62 (1 H, d), 2.52 (1 H, d), 2.03 (3H, S)1 1.84 (3H, s), 1.80 (3H, s), 0.00 (9H, s).
Example 9 Preparation of (^f?S.2SR6f?S,7f?S)-8-ethvnyl-4-(2,4.6-trimethylphenyl)-10-oxatricvclo- [5.2.1.02'61decane-3.5-dione.
Figure imgf000064_0001
Potassium carbonate (2.58 g, 19 mmol) is added to a stirred solution of (f/?S,2Sf?,6f?S,7f?S)-4- (2,4,6-trimethylphenyl)-8-trimethylsilylethynyl-10-oxatricyclo-[5.2.1.02|6]decane-3,5-dione (6.43 g, 17 mmol) in methanol (100 ml). The reaction mixture is stirred at room temperature for 2 hours and 30 minutes, then dilute aqueous hydrochloric acid is added and the mixture is extracted with ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure to give (1RS,2SR,6RS, 7RS)-8- ethynyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]decane-3,5-dione.
1H NMR (400MHz, d4-MeOH) δH 6.85 (2H, s), 6.72 (1 H, d), 5.03 (1 H, d), 3.96 (1 H, s), 2.92 - 2.88 (2H, m), 2.24 (3H, s), 2.06 (3H, s), 2.01 (3H, s).
Example 10
Preparation of (1RS.2SR.6RS, 7SR, 8f?S)-8-ethyl-4-(2,4,6-trimethylphenyl)-10-oxatricvclo-
[5.2.1.02'6ldecane-3.5-dione and (1RS.2SR.6RS.7SR.8SR)-8-ethyl-4-(2,4.6-trimethylphenyl)-10- oxatricvclo-r5.2.1.02|61decane-3,5-dione
Figure imgf000064_0002
A solution of (1RS,2SR,6RS, 7RS)-8-ethynyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.026]decane-3,5-dione (1.0 g , 3.3 mmol) in methanol (100 ml) and dichloromethane (100 ml) is hydrogenated at 3.5 bar over 5% palladium on carbon (approximately 50 mg) until the reaction is judged to be complete by mass spectrometry. The catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure. Purification by column chromatography on silica gel gives an approximately 1 :1 mixture of (1RS.2SR, 6f?S, 7SR, 8RS)-8-ethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]decane-3,5- dione and (ϊRS^SR.βRS.ZSR.δSRJ-δ-ethyl-^a^.e-trimethylphenyO-IO-oxatricyclo- [5.2.1.02'6]decane-3,5-dione.
(1RS,2SR,6RS, ZS^δRS^δ-ethyl^^^.e-trimethylphenyO-IO-oxatricyclo-fS^.I .O^^decane-S.S- dione: 1H NMR (400MHz, CDCI3) δH 6.82 (2H, s), 4.44 (1 H, d), 4.24 (1 H, s), 2.45 - 2.40 (2H, m), 2.22 (3H, s), 2.02 (6H, s), 1.58 - 1.52 (2H, m), 1.38 - 1.33 (1 H, m), 1.25 - 1.16 (2H1 m), 0.85 - 0.82 (3H, m).
(1RS,2SR, 6f?S,7SR,δSR)-8-ethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]decane-3,5- dione: 1H NMR (400MHz, CDCI3) δH 6.85 (2H, s), 4.51 (1 H, d), 4.43 (1 H, d), 3.07 (1 H, d), 2.82 - 2.81 (1 H, m), 2.24 (3H, s), 2.10 - 2.05 (2H, m), 2.04 (6H, s), 1.87 - 1.79 (1 H, m), 1.53 - 1.46 (2H, m), 1.00 (3H, t).
Example 11
Preparation of (1RS,2SR.6RS.7Sffl-4-(5-bromo-2-ethylphenvn-1.7-dimethyl-i 0- oxatricyclor5.2.1.026ldec-8-en-3,5-dione.
Figure imgf000065_0001
Step 1 : Preparation of (5-bromo-2-ethylphenyl)furan-2-ylmethanol
Figure imgf000065_0002
4-Bromo-2-iodoethyl benzene (50.0 g, 0.161 mol) is dissolved in anhydrous tetrahydrofuran (250 ml) and cooled to -70 0C under an atmosphere of nitrogen, lsopropylmagnesium chloride (2 M solution in THF, 100 ml, 0.200 mmol) is added dropwise with vigorous stirring over 40 minutes, maintaining the internal temp below -60 0C by external cooling. When the addition is complete, the reaction is stirred at -70 0C for 20 minutes then allowed to warm to room temperature over 1 hour and 20 minutes. The reaction mixture is then cooled to -70 0C and a solution of 2- furaldehyde (16 ml, 18.6 g, 190 mmol) in tetrahydrofuran (50 ml) is added dropwise over 40 minutes. On completion of the addition, the reaction is allowed to warm to room temperature and stirred at room temperature for 3 hours. Saturated aqueous ammonium chloride solution (~500 ml) is added and the mixture is extracted into ethyl acetate. The organic solutions are combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is further purified by column chromatography on silica gel to give (5- bromo-2-ethylphenyl)-furan-2-ylmethanol.
Step 2: Preparation of 5-(5-bromo-2-ethylphenyl)-4-hydroxycyclopent-2-enone.
Figure imgf000066_0001
A solution of (5-bromo-2-ethylphenyl)furan-2-ylmethanol (40.73 g, 0.145 mol) in acetone (1150 ml) and water (170 ml) is heated to 55 °C and 30 drops of polyphosphoric acid are added. The mixture is stirred at 55 0C for 44 hours, then cooled to room temperature. The reaction mixture is concentrated under reduced pressure to. remove. most of the acetone then ethyLacetate (500 ml), is added, and the reaction mixture is partitioned. The aqueous phase is extracted into ethyl acetate and the organic solutions are combined, washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 5-(5-bromo-2-ethylphenyl)-4-hydroxycyclopent-2-enone.
Step 3: Preparation of 2-(5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione.
Figure imgf000066_0002
Jones' reagent (75 ml of 1.67 M solution, 125 mmol) is added dropwise over 30 minutes to a cooled (ice-bath) solution of 5-(5-bromo-4-ethylphenyl)-4-hydroxycyclopent-2-enone (33 g, 117 mmol) in acetone (400 ml). The mixture is stirred for 20 minutes, then the cooling bath is removed and the mixture is stirred for 1 hour at room temperature, lsopropanol (150 ml) is added to the yellow slurry and the mixture is stirred at room temperature for 2 hours. The mixture is diluted with ethyl acetate and washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure to give 2-(5-bromo-2- ethylphenyl)cyclopent-4-ene-1 ,3-dione.
Step 4: Preparation of ( 1RS, 2SR, 6RS, 7Sf?)-4-(5-bromo-2-ethylphenyl)-1 ,7-dimethyl-10- oxatricyclo[5.2.1.026]dec-8-en-3,5-dione.
Figure imgf000067_0001
2,5-Dimethylfuran (2.3 ml, 21.6 mmol) and magnesium iodide (0.40 g, 1.4 mmol) are added to a solution of 2-(5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione (2.0 g , 7.2 mmol) in dichloromethane (10 ml) and the mixture is stirred at room temperature for 3 days. The reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give (1RS,2SR, 6f?S, 7Sf?)-4-(5-bromo-2-ethylphenyl)-1 , 7- dimethyl-10-oxatricyclo[5.2.1.02 6]dec-8-en-3,5-dione.
1H NMR (400MHz, d4-MeOH) δH 7.39 (1 H, dd), 7.18 (1 H, d), 7.16 (1 H, d), 6.35 (2H, s), 2.79 (2H, s), 2.46 (2H, q), 1.61 (6H, s), 1.07 (3H, t).
Example 12
Preparation of (1RS.2SR.6RS.7Sffl-4-(5-bromo-2-ethylphenyl)-1.7-dimethyl-IO- oxatricvclor5.2.1.02|6ldecane-3,5-dione.
Figure imgf000067_0002
A solution of (1RS, 2SR,6RS, 7Sf?)-4-(5-bromo-2-ethylphenyl)-1 ,7-dimethyl-10- oxatricyclo[5.2.1.026]dec-8-en-3,5-dione (1.63 g , 4.3 mmol) in methanol (200 ml) is hydrogenated at 3.5 bar over 5% palladium on carbon for 1 hour and 30 minutes at room temperature. The catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure. Trituration with diethyl ether gives (1 RS, 2SR, 6RS, 7SR)-A- (5-bromo-2-ethylphenyl)-1 ,7-dimethyl-10-oxatricyclo[5.2.1.02'6]decane-3,5-dione.
1H NMR (400MHz, d4-MeOH) δH 7.36 (1 H, dd), 7.17 (1 H, d), 7.15 (1 H, d), 2.81 (2H, s), 2.48 - 2.43 (2H, m), 1.84 - 1.79 (2H, m), 1.69 - 1.65 (2H1 m), 1.51 (6H, s), 1.08 (3H, t).
Example 13
Preparation of (^S^SReffSySffl^-fS-bromo^-ethylphenvD-IO-oxatricvclorδ^.i .O^ldec-δ- en-3,5-dione.
Figure imgf000068_0001
Furan (4.0 ml, 55.0 mmol) and magnesium iodide (1.00 g, 3.6 mmol) are added to a solution of 2- (5-bromo-2-ethylphenyl)cyclopent-4-ene-1 ,3-dione (5.0 g, 17.9 mmol) in dichloromethane (20 ml) and the mixture is stirred at room temperature for 3 days. A further quantity of furan (1.3 ml, 17.8 mmol) is added and stirring continued for 18 hours, and then a further quantity of furan (1.3 ml, 17.8 mmol) is added and the mixture is stirred for 48 hours, and then allowed to stand at room temperature for 5 days. The reaction mixture is dissolved in methanol and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give (1RS,2SR,6RS, 7SR)-4-(5-bτomo-2-eiby\pheny\)^0-oxaiήcyc\o[5.2Λ .02β](iec-8-en-3,5-άione.
1H NMR (400MHz, d4-MeOH) δH 7.37 (1 H, dd), 7.17 (1 H, d), 7.14 (1 H, d), 6.54 (2H, s), 4.96 (2H, s), 2.79 (2H, s), 2.44 (2H, q), 1.06 (3H, t)
Example 14
Preparation of (1RS.2SR.6RS.7Sf?)-4-(5-bromo-2-ethylphenyl)-10-oxatricvclor5.2.1.02'61decane-
3,5-dione.
Figure imgf000068_0002
A solution of (ϊf?S,2SR6RS,7Sf?)-4-(5-bromo-2-ethylphenyl)-10-oxatricyclo[5.2.1.02'6]- dec-8-en-3,5-dione (3.00 g , 8.6 mmol) in methanol (250 ml) is hydrogenated at 3.5 bar over 5% palladium on carbon for 2 hours at room temperature. The catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure to give (^/?S,2Sf?,6f?S, 7Sf?)-4-(5-bromo-2-ethylphenyl)-10-oxatricyclo-[5.2.1.02|6]decane-3,5-dione.
1H NMR (400MHz, d4-MeOH) δH 7.34 (1 H, dd), 7.15 (2H, d), 4.59 (2H, s), 2.78 (2H, s), 2.43 (2H, q), 1.81 - 1.78 (2H, m), 1.66 - 1.61 (2H, m), 1.06 (3H, t).
Example 15
Preparation of (1RS,2RS,6SR,, 7Sf?)-8-bromo-4-(2,4,6-trimethylphenyl)-10-oxatricvclo-
[5.2.1.02'6ldec-8-en-3.5-dione.
Figure imgf000069_0001
3-Bromofuran (5.2 g, 56 mmol) and magnesium iodide (1.5 g, 5.6 mmol) are added to 2-(2,4,6- trimethylphenyl)cyclopent-4-ene-1 ,3-dione (4.0 g, 18.7 mmol) and the mixture is stirred at room temperature for 2 days; small quantities of dichloromethane are added when required to aid stirring. The reaction mixture is allowed to stand at room temperature for 17 hours, then concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give (7f?S,2f?S,6Sf?,,7Sf?)-8-bromo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.026]dec-8-en-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.87 (2H1 s), 6.40 (1 H, d), 4.95 (1 H, s), 4.82 (1 H, s), 2.90 (1 H, d), 2.81 (1 H, d), 2.25 (3H, s), 2.07 (3H, s), 2.03 (3H, s).
Example 16
Preparation of (7f?S.2SR6f?S.7f?S)-8-(4-fluorophenyl)-4-(2.4.6-trimethylphenyl)-10- oxatricvclor5.2.1.02'6ldec-8-en-3,5-dione.
Figure imgf000070_0001
A mixture of (^f?S,2f?S,6Sf?,,7SR)-8-bromo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.026]dec-8-en-3,5-dione (300 mg, 0.82 mmol), 4-fluorophenylboronic acid (171 mg, 1.22 mmol), sodium 2'-dicyclohexylphosphino-2,6-dimethoxy-1 ,1'-biphenyl-3-sulfonate hydrate (17 mg, 0.03 mmol), potassium phosphate (522 mg, 2.5 mmol) and palladium acetate (4 mg, 0.02 mmol) in water (8 ml) are heated for 15O0C for 25 minutes under microwave irradiation. The mixture is cooled to room temperature and dilute aqueous hydrochloric acid is added. The mixture is filtered and the filtrate is extracted with ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. Purification by column chromatography on silica gel gives (1RS,2SR,6RS, 7f?S)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.026]dec-8- en-3,5-dione.
1H NMR (400MHz, CDCI3) δH 7.35 - 7.32 (2H, m), 6.86 (1 H, s), 6.85 (1 H, s), 6.82 - 6.77 (2H, m), 6.37 (1 H, d), 5.31 .(1 H, s), 5.03 (1 H, d), 2.82 - 2.78 (2H, m), 2.25 (3H, s), 2.07 (3H, s), 2.05 (3H, s).
Example 17
Preparation of (1RS.2SR.6RS.7Sff.8Sffl-8-(4-f1uorophenyl)-4-(2,4.6-trimethylphenyl)-10- oxatricyclof5.2.1.02|6ldecane-3,5-dione.
Figure imgf000070_0002
A suspension of (1RS,2SR,6RS, 7RS)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02'6]dec-8-en-3,5-dione (99 mg, 0.26 mmol) in methanol (20 ml) is hydrogenated at 3 bar over 5% palladium on carbon for 5 hours at room temperature. The catalyst is removed by filtration through diatomaceous earth and the solvent is evaporated under reduced pressure to give (ϊf?S,2Sf?,6f?S, 7SR8Sf?)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02i6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 7.39 (2H, dd), 7.11 (2H, t), 6.86 (1 H, s), 6.85 (1 H, s), 4.73 (1 H, d), 4.68 (1 H, d), 3.63 - 3.58 (1 H, m), 2.94 (1 H, d), 2.75 (1 H, d), 2.38 - 2.30 (1 H, m), 2.25 (3H, s), 2.08 (3H, s), 2.03 (3H, s), 1.92 (1 H, dd).
Example 18
Preparation of (1RS.2SR.6RS.7SR.8RS)-8-(3-fluorophenyl)-4-(2.4.6-trimethylphenyl)-10- oxatricvclof5.2.1.02'6ldecane-3,5-dione.
Figure imgf000071_0001
Bis(triphenylphosphine)palladium diacetate (20 mg, 0.024 mmol), 1-fluoro-3-iodo-benzene (104 mg, 0.47 mmol) and piperidine (0.16 ml, 1.6 mmol) are added to a solution of (1RS,2SR,6RS, 7Sf?)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02'6]dec-8-en-3,5-dione (0.20 g, 0.71 mmol) in dry Λ/,Λ/-dimethylformamide (2 ml). Formic acid (0.06 ml, 1.6 mmol) is added and the reaction mixture is heated at 50 0C for 2 hours. The reaction mixture is cooled to room temperature, water (1 ml) and dichloromethane (1 ml) are added, and the mixture is stirred for 1 hour. The two phases are separated, the organic phase collected and the solvent is evaporated. The residue is purified by preparative reverse-phase HPLC to give (yf?S,2SR,6RS,7SR,8RS)-8- (3-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02|6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 7.75 - 7.66 (1 H, m), 7.25 - 7.21 (1 H, m), 7.06 - 7.02 (2H, m), 6.88 (1 H, s), 6.87 (1 H, s), 4.83 (1 H, br. s), 4.59 (1 H, s), 3.00 - 2.98 (1 H, m), 2.83 - 2.70 (2H, br. s), 2.25 (3H, s), 2.20 - 2.16 (1 H, m), 2.09 (3H, s), 2.08 (3H, s), 1.92 - 1.89 (1 H, m).
Example 19
Preparation of (1RS.2SR.6RS.7SR8f?S)-8-r2.6-bis(trifluoromethyl)pyridin-4-yll-4-(2.4.6- trimethylphenvD-IO-oxatricyclorδ^.i .O^ldecane-S.δ-dione
Figure imgf000072_0001
A mixture of (^S,2SR6RS,7Sf?)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]dec-8-en- 3,5-dione (400 mg, 1.4 mmol), 2,6-bis(trifluoromethyl)-4-chloropyridine (531 mg, 1.4 mmol), palladium acetate (16 mg, 0.07 mmol), 2'-dicyclohexylphosphino-2,6-dimethoxy-1 ,1'-biphenyl (67 mg, 0.14 mmol), potassium formate (353 mg, 4.2 mmol), tetrabutylammonium chloride (389 mg, 1.4 mmol) and copper iodide (53 mg, 0.28 mmol) in dry Λ/,Λ/-dimethylformamide (6 ml) are heated at 150 0C for 30 minutes under microwave irradiation. Purification by preparative reverse- phase HPLC gives (7f?S,2Sf?,6RS;7SR8f?S)-8-[2,6-bis(trifluoromethyl)pyridin-4-yl]-4-(2,4,6- trimethylphenyl)-10-oxatricyclo[5.2.1.02|6]decane-3,5-dione.
1H NMR (400MHz d4-Me0H) δH 7.81 (1 H, s), 7.26 (1 H, s), 6.92 (1 H, s), 6.90 (1 H, s), 4.91 (1 H, d), 4.64 (1 H, s), 3.19 - 3.17 (1 H, m), 2.99 - 2.95 (2H, m), 2.32 - 2.27 (1 H, m), 2.26 (3H, s), 2.09 (3H, s), 2.07 (3H, s), 1.93 - 1.90 (1 H, m).
Example 20
Preparation of (1RS,2SR,6RS, 7Sf?,8f?S)-4-(2,4,6-trimethylphenyl)-8-vinyl-10- oxatricvclor5.2.1.02|61decane-3,5-dione.
Figure imgf000072_0002
A mixture of (1RS,2SR,6RS, 7Sf?)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.026]dec-8-en- 3,5-dione (510 mg, 1.8 mmol), vinyl iodide (280 mg, 1.8 mmol), palladium acetate (20 mg, 0.09 mmol), sodium formate (454 mg, 5.4 mmol) and tetrabuylammonium chloride (500 mg, 1.8 mmol) in dry Λ/,Λ/-dimethylformamide (15 ml) are heated at 150 0C for 20 minutes under microwave irradiation. The mixture is cooled to room temperature and partitioned between water and ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give (1RS, 2SR, 6RS, 7SR8RS)-4-(2,4,6-trimethylphenyl)-8-vinyl- 10-oxatricyclo[5.2.1.02'6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.90 - 6.89 (2H1 m ), 5.80 - 5.71 (1 H, m), 5.05 - 4.97 (2H, m), 4.68 (1 H, d), 4.44 (1 H, s), 2.81 - 2.76 (2H, m), 2.51 - 2.46 (1 H, m), 2.26 (3H, s), 2.07 (3H, s), 2.06 (3H, s), 1.89 - 1.84 (1 H, m), 1.67 - 1.62 (1 H, m).
Example 21
Preparation of methyl rαf?S.2SR6f?S.7Sf?.gf?S)-3.5-dioxo-4-(2.4.6-trimethylphenyl)-10- oxatricvclor5.2.1.026ldec-8-yl1acrylate.
Figure imgf000073_0001
Benzylidene[1 ,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(tricyclohexyl- phosphine)ruthenium (14 mg, 0.016 mmol) is added to a suspension of (1RS,2SR,6RS, 7Sf?,δf?S)-4-(2,4,6-trimethylphenyl)-8-vinyl-10-oxatricyclo[5.2.1.02'6]decane-3,5- dione (100 mg, 0.32 mmol) and methyl acrylate (0.03 ml, 0.35 mmol) in dichloromethane (1 ml) and the mixture is stirred at reflux for 2 hours. The reaction mixture is cooled to room temperature, the solvent evaporated under reduced pressure and the residue is purified by column chromatography on silica gel to give methyl [( 1 RS, 2SR, 6RS,7SR,8RS)-3, 5-d ioxo-4- (2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]dec-8-yl]acrylate. Proton NMR indicates the product comprises a mixture of E- and Z-isomers.
£-lsomer: 1H NMR (400MHz, CDCI3) δH 6.80 (2H, s), 6.74 (1 H, dd), 5.91 (1 H, d), 4.58 (1 H, d), 4.30 (1 H, s), 3.33 (3H, s), 2.85 - 2.77 (3H, m), 2.21 (3H, s), 1.97 (3H1 S)1 194 (3H1 S)1 1.94 - 1.91 (1 H, m), 1.59- 1.54 (1 H, m).
Example 22
Preparation of (1RS.2SR.6SR.7Sffl-1-hvdroxymethyl-4-(2.4.6-trimethylphenyl)-10- oxatricvclor5.2.1.02'6ldec-8-ene-3,5-dione.
Figure imgf000074_0001
Furfuryl alcohol (4 ml, 46.7 mmol) is added to 2-(2,4,6-trimethylphenyl)cyclopent-4-ene-1 ,3-dione (2.0 g, 9.3 mmol) and MgI2 (520 mg, 1.86 mmol) and the reaction is stirred for 17 hours. The reaction mixture is adsorbed onto silica gel and purified by column chromatography on silica gel to give (ΪRS,2SR)6f?S)7S/?)-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.026]dec-8-ene-3,5-dione.
1H NMR (400MHz, CDCI3) δH 6.87 (2H, s), 6.49 (1 H, d), 6.44 (1 H, d), 4.96 (1 H, d), 3.98 (1 H, d), 3.85 (1 H, d), 2.82-2.78 (2H, m), 2.24 (3H, s), 2.08 (3H, s), 2.05 (3H, s).
Example 23
Preparation of terf-butyl carbamic acid r(7f?S,2SR6f?S,7Sf?)-3,5-dioxo-4-(2.4,6-trimethylphenyl)-
10-oxatricvclor5.2.1.02'6ldec-8-en-1-yllmethyl ester.
Figure imgf000074_0002
Step 1 : Preparation of (7RS,2SR6Sf?,7Sf?)-5-benzyloxy-7-hydroxymethyl-4-(2,4,6- trimethylphenylJ-IO-oxatricycloIS^.I .O^deca^.δ-dien-S-one and (IRS^SR^RSJSRyδ- benzyloxy-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02'6]deca-4,8-dien-3- one
Figure imgf000075_0001
Benzyl bromide (0.72 ml, 6.1 mmol) is added to a mixture of potassium carbonate (840 mg, 6.1 mmol) and (^f?S,2Sf?,6f?S,7Sf?)-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo- [5.2.1.026]dec-8-ene-3,5-dione (1.80 g, 5.8 mmol) in acetone (80 ml), and the reaction mixture is heated at reflux for 4 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give a mixture of (1RS, 2SR, 6SR, 7SR)-5- benzyloxy^-hydroxymethyl^^^.δ-trimethylphenyO-IO-oxatricyclo^^.i .O^^deca^.δ-dien-S- one and (1RS.2SR, 6RS, 7SR)-5-benzyloxy-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02|6]deca-4,8-dien-3-one.
Step 2: Preparation of tert-butyl carbamic acid [(7RS,2f?S,6/?S,7SR)-3-benzyloxy-5-oxo-4-(2,4,6- thmethylphenyO-I O-oxatricyclofS^.I .O^ldeca^.δ-dien-i-ylJmethyl ester and tert-butyl carbamic acid [(tf?S,2SR6f?S,7Sf?)-5-benzyloxy-3-oxo-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02l6]deca-4,8-dien-1-yl]methyl ester.
Figure imgf000075_0002
Sodium hydride (60 mg, 1.97 mmol) is added to a cooled (0 0C) mixture of (1RS,2SR,6SR,7SR)-
5-benzyloxy-7-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.0 2,■6 ],deca-4,8-dien-3- one and (ϊf?S,2SR,6f?S, 7Sf?)-5-benzyloxy-1-hydroxymethyl-4-(2,4,6-trimethylphenyl)-10- oxatricyclo[5.2.1.02|6]deca-4,8-dien-3-one (265 mg, 0.66 mmol)in tetrahydrofuran (10 ml). The mixture is stirred for a few minutes and then tert-butyl isocyanate (0.15 ml, 1.32 mmol) is added.
The reaction is allowed warm to room temperature and stirred for 17 hours. The mixture is partitioned between water and ethyl acetate, and the organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated. The residue is purified by column chromatography on silica gel to give a mixture of te/t-butyl carbamic acid
[(ϊf?S,2RS,6f?S, 7SR)-3-benzyloxy-5-oxo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-
[5.2.1.026]deca-4,8-dien-1-yl]methyl ester and te/t-butyl carbamic acid [(1RS,2SR,6RS,7SR)-5- benzyloxy-3-oxo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02'6]deca-4,8-dien-1-yl]methyl ester.
Step 3: Preparation of terf-butyl carbamic acid [(7RS,2Sf?,6f?S, 7SR)-3,5-dioxo-4-(2,4,6- trimethylphenylJ-IO-oxatricyclotδ^.i .O^^dec-δ-en-i-yllmethyl ester.
Figure imgf000076_0001
A suspension of a mixture of [(7f?S,2f?S,6RS,7Sf?)-3-benzyloxy-5-oxo-4-(2,4,6-trimethylphenyl)- 10-oxatricyclo-[5.2.1.02|6]deca-4,8-dien-1-yl]methyl ester and terf-butyl carbamic acid [(7RS,2SR, βftSySRJ-S-benzyloxy-S-oxo^-^Ae-trimethylphenyO-IO-oxatricycIo- [5.2.1.02'6]deca-4,8-dien-1-yl]methyl ester (147 mg, 0.29 mmol) in methanol (20 ml) is hydrogenated at 3 bar over 5% palladium on carbon for 5 hours. The catalyst is removed by filtration and the filtrate is concentrated under reduced pressure to give tert-butyl carbamic acid [(1RS,2SR, 6RS, 7Sf?)-3,5-dioxo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.026]dec-8-en-1- yl]methyl.
1H NMR (400MHz, CDCI3) δH 6.83 (2H, s), 5.02 (1 H, s), 4.72 (1 H, d), 4.65 (1 H, d), 4.12 (1 H, d), 2.83 (1 H, d), 2.70 (1 H, d), 2.23 (3H, s), 2.07 (3H, s), 2.06 (3H, s), 1.86 - 1.80 (2H, m), 1.57 - 1.45 (2H, m), 1.29 (9H, s).
Example 24 Preparation of (ff?S,2SR6f?S, ZSRM^-bromo^-ethylphenvD-IO-oxatricvclo-fδ.2.1.02|61decane- 3,5-dione.
Figure imgf000077_0001
Step 1 : Preparation of 4-bromo-2-ethylphenyllead triacetate.
Figure imgf000077_0002
Dry chloroform (30 ml) is added to a mixture of lead tetraacetate (8.52 g, 19.3 mmol) and mercuric diacetate (0.28 g, 0.875 mmol) under an atmosphere of nitrogen, and the reaction mixture is stirred and heated to 40 0C. 4-Bromo-2-ethylphenylboronic acid (4.0 g, 17.5 mmol) is added in one portion and the mixture is stirred at 40 0C for 4 hours. The reaction mixture is cooled to 0 0C, and -potassium- carbonate (2.66 g,- 19.3 mmol) is added portionwise.-The mixture is stirred for 5 minutes, then filtered through a small plug of diatomaceous earth, washing with chloroform. The filtrate concentrated under reduced pressure to give 4-bromo-2-ethylphenyllead triacetate.
Step 2: Preparation of (7RS,2Sf?,6f?S,7SR)-4-(4-bromo-2-ethylphenyl)-10-oxatricyclo- [5.2.1.026]decane-3,5-dione.
Figure imgf000077_0003
4-Dimethylaminopyridine (3.67 g, 30.0 mmol) and toluene (10 ml) are added to a solution of (1RS,2SR,6RS, 7SR)^0-oxa\τ\c^c\o[5.2Λ .026]decane-3,5-d\one (1.0 g, 6.0 mmol) in chloroform (40 ml) and the reaction mixture is heated to 80 0C. 4-Bromo-2-ethylphenyllead triacetate (5.13 g, 9.04 mmol) is added portionwise over 20 minutes, and once the addition is complete the reaction mixture is stirred at 80 0C for a further 4 hours. The mixture is cooled to room temperature, 2 M aqueous hydrochloric acid (40 ml) is added, and the mixture is stirred vigorously for 15 minutes, then filtered through a small plug of diatomaceous earth, washing with 40ml dichloromethane. The organic phase is separated, and the aqueous phase is extracted with dichloromethane (2 x 20 ml). The organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give (1RS,2SR,6RS,7SR)-4-(4-bromo-2-etby\pheny\)-'\0- oxatricyclo-[5.2.1.02l6]decane-3,5-dione.
1H NMR (400MHz, CDCI3) δH 7.39 (1 H, dd), 7.27-7.33 (1 H, m), 6.97 (1 H, dd), 4.68 (2H, m), 2.74 (2H, br. s), 2.48 (2H, q), 1.78-1.87 (2H, m), 1.56 (2H, m), 1.11 (3H, t).
Additional compounds in Table T1 below were prepared by similar methods using appropriate starting materials. It should be noted that certain compounds of the invention exist as a mixture of isomers noted above, under the conditions used to obtain the 1H NMR data. Where this has occurred, the characterising data are reported for all isomers present at ambient temperature in the specified solvent. Unless otherwise stated, proton NMR spectra were recorded at ambient temperature. Compounds characterised by HPLC-MS were analysed using one of two methods described below. _.. _ __ _ _ _ _ __.
Method A
Compounds characterised by HPLC-MS were analysed using an Waters 2777 injector with a 1525 micro pump HPLC equipped with a Waters Atlantis dC18 IS column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron), Waters 2996 photodiode array, Waters 2420 ELSD and Micromass ZQ2000. The analysis was conducted using a three minute run time, according to the following gradient table:
Figure imgf000078_0001
Solvent A: H2O with 0.05% TFA Solvent B: CH3CN with 0.05% TFA Method B
Compounds characterised by HPLC-MS were analysed using a Waters 2795 HPLC equipped with a Waters Atlantis dC18 column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron, temperature 40 0C), Waters photodiode array and Micromass ZQ2000. The analysis was conducted using a three minute run time, according to the following gradient table:
Figure imgf000079_0001
Solvent A: H2O containing 0.1 % HCOOH Solvent B: CH3CN containing 0.1% HCOOH
The characteristic values obtained for each compound were the retention time (rt, recorded in minutes) and the molecular ion (typically the cation MH+), as listed in Table T1.
Table T1
Figure imgf000079_0002
Figure imgf000080_0001
br), 2.45 m),
4.73 - 2.08
s), 5.14 s), 3.00 2.38 -
(1 H, m), 2.90 (br (6H, m).
3.73 1.86 -
s), 4.79 s), (3H,
4.93 2.96 1.39 -
4.78 s), m), 1.70 (2H,
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
1.34 mins
= 1.35 mins
mins
= 1.50 mins
1.25 mins
(1 H, d), " m), - 1.87 (1 H, m).
s), 4.38 (1 H, d),
- 3.34 d), 2.47 2.02
(1 H, d), (3H, m), 1.48
Figure imgf000085_0001
Figure imgf000086_0001
m), 4.74 (1 H, dd), H, m), H, m).
1.10 mins
1.33 mins
1.77 mins
1.36 mins
(2H, m), s), -
1.36 mins
1.37 mins
4.37 (1 H, m), 2.03 (3H,
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
d), 3.07 2.10 - m),
6.82 dd), m), m).
4.97 mins
4.98 mins
mins
4.23 mins
4.48 mins
= 5.23 mins
Figure imgf000094_0001
4.22 mins
= 5.51 mins = 4.98 mins = 7.34 mins
6.54 mins
mins
mins
1.18 mins
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
Figure imgf000105_0001
Figure imgf000106_0001
Figure imgf000107_0001
Figure imgf000108_0001
Figure imgf000109_0001
Figure imgf000110_0001
Figure imgf000111_0002
The compounds of the following Tables 1 to 146 can be obtained in an analogous manner
Table 1 covers compounds of formula (A)
Figure imgf000111_0001
(I) wherein R1, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R1 are as defined in Table 1
Table 1
Figure imgf000111_0003
Figure imgf000113_0001
Figure imgf000114_0001
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
Figure imgf000132_0001
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0001
Figure imgf000136_0001
R6 R7 R8 R9 R10 R11
1 1054 H H OH OH H CH3
1 1055 CH3 H OH OH H CH3
1 1056 H H -O-C(CH3)2-O- H H
1 1057 H H -0-C(CH3); -O- H CH3
1 1058 CH3 H -0-C(CH3J2-O- H CH3
1 1059 H R' and R' form unit =0 H H H
1 1060 H R; and R' form unit =0 H H CH3
1 1061 CH3 R' and R' form unit =0 H H H
1 1062 CH3 R' and Re form unit =0 H H CH3
1 1063 H R' and R' form unit =NOCH3 H H H
1 1064 H R' and Rc form unit =NOCH3 H H CH3
1 1065 CH3 R' and R" form unit =NOCH3 H H H
1 1066 CH3 R' and Re form unit =NOCH3 H H CH3
1 1067 H R' and Rc form unit =NOCH2CH3 H H H
1 1068 H R' and R" form unit =NOCH2CH3 H H CH3
1 1069 CH3 R' and R0 form unit =NOCH2CH3 H H H
1 1070 CH3 R' and R0 form unit =NOCH2CH3 H H CH3
1 1071 H H H -0-(CH2J2-O- H
1 1072 H H H -O-(CH2).-O- CH3
1 1073 CH3 H H -O-(CH2)2-O- H
1 1074 CH3 H H -0-(CHz)2-O- CH3
1 1075 H H H -0-(CHz)3-O- H
1 1076 H H H -O-(CH2)3-O- CH3
1 1077 CH3 H H -0-(CHz)3-O- H
1 1078 CH3 H H -0-(CHz)3-O- CH3
Table 2 covers compounds of formula (A), wherein R1 is ethyl, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 3 covers compounds of formula (A)1 wherein R1and R4 are ethyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1 .
Table 4 covers compounds of formula (A), wherein R1, R2 and R4 are ethyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 5 covers compounds of formula (A), wherein R1 and R2 are methyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 6 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 7 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 8 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 9 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 10 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is ethynyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 11 covers compounds of formula (A), wherein R1 and R2 are methyl, R4 is vinyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 12 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 13 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 14 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 15 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 16 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 17 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is ethynyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 18 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R4 is vinyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 19 covers compounds of formula (A), wherein R1 is ethynyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 20 covers compounds of formula (A), wherein R1 is ethynyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 21 covers compounds of formula (A), wherein R1 is ethynyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 22 covers compounds of formula (A), wherein R1 is ethynyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 23 covers compounds of formula (A), wherein R1 is ethynyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 24 covers compounds of formula (A), wherein R1 and R4 are ethynyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 25 covers compounds of formula (A), wherein R1 is vinyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 26 covers compounds of formula (A), wherein R1 is vinyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 27 covers compounds of formula (A), wherein R1 is vinyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 28 covers compounds of formula (A), wherein R1 is vinyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 29 covers compounds of formula (A), wherein R1 is vinyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 30 covers compounds of formula (A)1 wherein R1 and R4 are vinyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 31 covers compounds of formula (A), wherein R1 is methyl, R2, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 32 covers compounds of formula (A), wherein R1 is methyl, R2 is methoxy, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 33 covers compounds of formula (A), wherein R1 is methyl, R2 is trifluoromethyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 34 covers compounds of formula (A), wherein R1 is methyl, R2 is ethyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 35 covers compounds of formula (A), wherein R1 is methyl, R2 is ethynyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 36 covers compounds of formula (A), wherein R1 is methyl, R2 is vinyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 37 covers compounds of formula (A), wherein R1 is methyl, R2 is chlorine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 38 covers compounds of formula (A), wherein R1 is methyl, R2 is bromine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 39 covers compounds of formula (A), wherein R1 is methyl, R2 is iodine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 40 covers compounds of formula (A)1 wherein R1 is ethyl, R2, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 41 covers compounds of formula (A), wherein R1 is ethyl, R2 is methoxy, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 42 covers compounds of formula (A), wherein R1 is ethyl, R2 is trifluoromethyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 43 covers compounds of formula (A), wherein R1 is ethyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 44 covers compounds of formula (A), wherein R1 is ethyl, R2 is ethynyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 45 covers compounds of formula (A), wherein R1 is ethyl, R2 is vinyl, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 46 covers compounds of formula (A), wherein R1 is ethyl, R2 is chlorine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 47 covers compounds of formula (A), wherein R1 is ethyl, R2 is bromine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 48 covers compounds of formula (A), wherein R1 is ethyl, R2 is iodine, R3, R4, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 49 covers compounds of formula (A), wherein R1 and R4 are methyl, R2 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1 .
Table 50 covers compounds of formula (A), wherein R1 and R4 are methyl, R2 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1 .
Table 51 covers compounds of formula (A), wherein R1 and R4 are methyl, R2 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 52 covers compounds of formula (A), wherein R1 is methyl, R2 is chlorine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 53 covers compounds of formula (A), wherein R1 is methyl, R2 is bromine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 54 covers compounds of formula (A), wherein R1 is methyl, R2 is iodine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 55 covers compounds of formula (A), wherein R1 and R4 are ethyl, R2 is chlorine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 56 covers compounds of formula (A), wherein R1 and R4 are ethyl, R2 is bromine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 57 covers compounds of formula (A), wherein R1 and R4 are ethyl, R2 is iodine, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 58 covers compounds of formula (A), wherein R1 is methyl, R2 is chlorine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 59 covers compounds of formula (A), wherein R1 is methyl, R2 is bromine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 60 covers compounds of formula (A), wherein R1 is ethyl, R2 is chlorine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 61 covers compounds of formula (A), wherein R1 is ethyl, R2 is bromine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 62 covers compounds of formula (A), wherein R1 and R4 are methyl, R2 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 63 covers compounds of formula (A), wherein R1 is methyl, R2 is methoxy, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 64 covers compounds of formula (A), wherein R1 and R4 are ethyl, R2 is methoxy, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1. Table 65 covers compounds of formula (A), wherein R1, R2, R3 and R4 are methyl, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 66 covers compounds of formula (A), wherein R1 is difluoromethoxy, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 67 covers compounds of formula (A), wherein R1 is difluoromethoxy, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 68 covers compounds of formula (A), wherein R1 is trifluoromethoxy, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 67 covers compounds of formula (A), wherein R1 is trifluoromethoxy, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 70 covers compounds of formula (A), wherein R1 is cyclopropyl, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 71 covers compounds of formula (A), wherein R1 is cyclopropyl, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 72 covers compounds of formula (A), wherein R1 and R2 are methyl, R3, R5 and R12 are hydrogen, R4 is cyclopropyl and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 73 covers compounds of formula (A), wherein R1 and R2 are ethyl, R3, R5 and R12 are hydrogen, R4 is cyclopropyl and R6, R7, R8, R9, R10, and R11 are as defined in Table 1.
Table 74 covers compounds of formula (AH)
Figure imgf000143_0001
wherein R1, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 74
Figure imgf000144_0001
Figure imgf000145_0001
Figure imgf000146_0001
Figure imgf000147_0001
Figure imgf000148_0001
Figure imgf000149_0001
Figure imgf000150_0001
Figure imgf000151_0001
Figure imgf000152_0001
Figure imgf000153_0001
Figure imgf000154_0001
Figure imgf000155_0001
Figure imgf000156_0001
Figure imgf000157_0001
Figure imgf000158_0001
Figure imgf000159_0001
Figure imgf000160_0001
Figure imgf000161_0001
Figure imgf000162_0001
Figure imgf000163_0001
Figure imgf000164_0001
Figure imgf000165_0001
Figure imgf000166_0001
Figure imgf000167_0001
Figure imgf000168_0001
Table 75 covers compounds of formula (AH), wherein R1 is ethyl, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 76 covers compounds of formula (AH), wherein R1and R4 are ethyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 77 covers compounds of formula (AH), wherein R1, R2 and R4 are ethyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 78 covers compounds of formula (AH), wherein R1 and R2 are methyl, R3, R4, R5 and R12 n and R 36 , o R8B, D R9 11 are hydroge , and R are as defined in Table 74. Table 79 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 80 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 81 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 82 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 83 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is ethynyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 84 covers compounds of formula (AH), wherein R1 and R2 are methyl, R4 is vinyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 85 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 86 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 87 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 88 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 89 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 90 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is ethynyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 91 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methyl, R4 is vinyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 92 covers compounds of formula (AH), wherein R1 is ethynyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 93 covers compounds of formula (AH), wherein R1 is ethynyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 94 covers compounds of formula (AH), wherein R1 is ethynyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 95 covers compounds of formula (AH), wherein R1 is ethynyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 96 covers compounds of formula (AH), wherein R1 is ethynyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 97 covers compounds of formula (AH), wherein R1 and R4 are ethynyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 98 covers compounds of formula (AH), wherein R1 is vinyl, R2 is methyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 99 covers compounds of formula (AH), wherein R1 is vinyl, R2 is methyl, R4 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 100 covers compounds of formula (AH), wherein R1 is vinyl, R2 is methyl, R4 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 101 covers compounds of formula (AH), wherein R1 is vinyl, R2 is methyl, R4 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 102 covers compounds of formula (AH), wherein R1 is vinyl, R2 is methyl, R4 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 103 covers compounds of formula (AH), wherein R1 and R4 are vinyl, R2 is methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 104 covers compounds of formula (AH), wherein R1 is methyl, R2, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 105 covers compounds of formula (AH), wherein R1 is methyl, R2 is methoxy, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 106 covers compounds of formula (AH), wherein R1 is methyl, R2 is trifluoromethyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 107 covers compounds of formula (AH), wherein R1 is methyl, R2 is ethyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 108 covers compounds of formula (AH), wherein R1 is methyl, R2 is ethynyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 109 covers compounds of formula (AH), wherein R1 is methyl, R2 is vinyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined inTable 74.
Table 110 covers compounds of formula (AH), wherein R1 is methyl, R2 is chlorine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 111 covers compounds of formula (AH), wherein R1 is methyl, R2 is bromine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 112 covers compounds of formula (AH), wherein R1 is methyl, R2 is iodine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 1 13 covers compounds of formula (AH), wherein R1 is ethyl, R2, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 1 14 covers compounds of formula (AH), wherein R1 is ethyl, R2 is methoxy, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 115 covers compounds of formula (AH)1 wherein R1 and R2 are ethyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 116 covers compounds of formula (AH)1 wherein R1 is ethyl, R2 is trifluoromethyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 117 covers compounds of formula (AH), wherein R1 is ethyl, R2 is ethynyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 118 covers compounds of formula (AH), wherein R1 is ethyl, R2 is vinyl, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 1 19 covers compounds of formula (AH), wherein R1 is ethyl, R2 is chlorine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 120 covers compounds of formula (AH)1 wherein R1 is ethyl, R2 is bromine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 121 covers compounds of formula (AH), wherein R1 is ethyl, R2 is iodine, R3, R4, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 122 covers compounds of formula (AH), wherein R1 and R4 are methyl, R2 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 123 covers compounds of formula (AH), wherein R1 and R4 are methyl, R2 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 124 covers compounds of formula (AH), wherein R1 and R4 are methyl, R2 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 125 covers compounds of formula (AH), wherein R1 is methyl, R2 is chlorine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 126 covers compounds of formula (AH), wherein R1 is methyl, R2 is bromine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 127 covers compounds of formula (AH), wherein R1 is methyl, R2 is iodine, R3 is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 128 covers compounds of formula (AH), wherein R1 and R4 are ethyl, R2 is chlorine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 129 covers compounds of formula (AH), wherein R1 and R4 are methyl, R2 is bromine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 130 covers compounds of formula (AH), wherein R1 and R4 are ethyl, R2 is iodine, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 131 covers compounds of formula (AH), wherein R1 is methyl, R2 is chlorine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 132 covers compounds of formula (AH), wherein R1 is methyl, R2 is bromine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 133 covers compounds of formula (AH), wherein R1 is ethyl, R2 is chlorine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 134 covers compounds of formula (AH), wherein R1 is ethyl, R2 is bromine, R3 is hydrogen, R4 is methoxy, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 135 covers compounds of formula (AH), wherein R1 and R4 are methyl, R2 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 136 covers compounds of formula (AH), wherein R1 is methyl, R2 is methoxy, R3is hydrogen, R4 is ethyl, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 137 covers compounds of formula (AH), wherein R1 and R4 are ethyl, R2 is methoxy, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74. Table 138 covers compounds of formula (AH) wherein R1, R2, R3 and R4 are methyl, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 139 covers compounds of formula (A), wherein R1 is difluoromethoxy, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 140 covers compounds of formula (A), wherein R1 is difluoromethoxy, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 141 covers compounds of formula (A), wherein R1 is trifluoromethoxy, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 142 covers compounds of formula (A), wherein R1 is trifluoromethoxy, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 143 covers compounds of formula (A), wherein R1 is cyclopropyl, R2 and R4 are methyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 144 covers compounds of formula (A), wherein R1 is cyclopropyl, R2 is methyl, R4 is ethyl, R3, R5 and R12 are hydrogen and R6, R8, R9, and R11 are as defined in Table 74.
Table 145 covers compounds of formula (A), wherein R1 and R2 are methyl, R3, R5 and R12 are hydrogen, R4 is cyclopropyl and R6, R8, R9, and R11 are as defined in Table 74.
Table 146 covers compounds of formula (A), wherein R1 and R2 are ethyl, R3, R5 and R12 are hydrogen, R4 is cyclopropyl and R6, R8, R9, and R11 are as defined in Table 74.
Example 25
Preparation of (1RS,2SR,6RS, 7Sf?)-5-oxo-4-(2A6-trimethylphenyl)-10-oxatricvclor5.2.1.02'6]dec- 3-en-3-yl 2.2-dimethylpropionate.
Figure imgf000175_0001
A solution of pivaloyl chloride (0.055 g, 0.57 mmol) in dichloromethane (2 ml) is added dropwise to a solution of (^S^SReRS^SRH^^.e-trimethylphenyO-IO-oxatricyclofS.a.i .O^^decane- 3,5-dione (0.12 g, 0.42 mmol) in dichloromethane (2 ml) at room temperature and the reaction mixture is stirred for 2 minutes. A solution of triethylamine (0.08 ml) in dichloromethane (1 ml) is added and the reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with dichloromethane (20 ml) and washed with saturated aqueous sodium bicarbonate solution. The organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure to give (1RS,2SR,6RS,7SR)-5-oxo-4-(2,4β- trimethylphenylJ-IO-oxatricyclofS^.I .O^ldec-S-en-S-yl 2,2-dimethylpropionate as a colourless oil.
1H NMR (400MHz, CDCI3) δH 6.84 (1 H, s), 6.82 (1 H, s), 4.75 (1 H, d), 4.55 (1 H, d), 3.45 (1 H, d), 2.78 (1 H, d), 2.24 (3H, s), 2.09 (3H, s), 2.02 (3H, s), 1.89-1.83 (2H, m), 1.63 - 1.59 (2H, m), 1.11 (9H, s).
Example 26
Preparation of carbonic acid (7f?S,2SR6f?S,7Sf?)-5-oxo-4-(2,6-diethyl-4-methylphenyl)-10- oxatricvclor5.2.1.02|6l-dec-3-en-3-yl ester ethyl ester.
Figure imgf000175_0002
A solution of ethyl chloroformate (0.071 g, 0.65 mmol) in dichloromethane (0.5 ml) is added dropwise to a solution of (7RS,2SR,6ftS,7SR)-4-(2,6-diethyl-4-methylphenyl)-10- oxatricyclo[5.2.1.02|6]decane-3,5-dione (0.172 g, 0.55 mmol) in dichloromethane (2 ml) at 0 0C and the reaction mixture is stirred. A solution of triethylamine (0.066 g, 0.65 mmol) in dichloromethane (1 ml) is added and the reaction mixture is stirred at room temperature for 17 hours, warming slowly to room temperature. The reaction mixture is diluted with dichloromethane (3 ml) and washed with saturated aqueous sodium bicarbonate solution. The organic phase is separated, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give carbonic acid (1RS,2SR,6RS, 7SR)-5-oxo-4-(2,6-diethyl-4-methylphenyl)-10-oxatricyclo- [5.2.1.02|6]-dec-3-en-3-yl ester ethyl ester as a colourless solid.
1H NMR (400MHz, CDCI3) δH 1.06 (6H,m), 1.28 (3H, t), 1.63 (2H, m), 1.87 (2H, m), 2.3 (3H, s), 2.35 (4H, m), 2.8 (1 H, d), 3.63 (1 H, d), 4.22 (2H, q), 4.64 (1 H1 d), 4.77 (1 H, d), 6.91 (2H, d).
Additional compounds in Table P1 below were prepared by similar methods using appropriate starting materials.
Table P1
Figure imgf000176_0001
Figure imgf000177_0001
Figure imgf000178_0001
Figure imgf000179_0001
Figure imgf000180_0001
B (1 H, d), 2.81 (1 H, (3H, s), 1.49 (3H, m).
B (1 H, d), H, d), - 1.50 (4H, m).
B m), 3.89 (3H, s), (3H, s), m),
Figure imgf000181_0001
B (1H, d), (1H, (3H, s), t), 1.04
d), 4.55 s), m), 1.63
4.66 d), 1.81 (2H, m). 2.81 = 2.80 (3H, s), 1.05 -
4.61 (1H, t), - 1.71
Figure imgf000182_0001
B d), 4.55 (1 H, app s), 2.04 (2H, m),
B (3H, m), s), 3.50 (0.5H, s), 1.84 - 1.24 (1 H,
dd), (3H, 1.80 -
H, d), 4.73 s), m),
6.89 (1 H, s), 2.89 s),
Figure imgf000183_0001
Figure imgf000184_0001
Figure imgf000185_0001
Biological Examples
Test Example 1
Monocotyledonous and dicotyledonous test plants were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 10 days cultivation (post-emergence) under controlled conditions in a glasshouse, the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in 0.6 ml acetone and 45 ml formulation solution containing 10.6% Emulsogen EL (Registry number 61791-12-6), 42.2% N-methyl pyrrolidone, 42.2% dipropylene glycol monomethyl ether (Registry number 34590-94-8) and 0.2 % X-77 (Registry number 11097-66-8). The test plants were then grown in a greenhouse under optimum conditions until, 15 days later for post-emergence and 20 days for pre-emergence, the test was evaluated (100 = total damage to plant; 0 = no damage to plant). Test plants:
Alopecurus myosuroides (ALOMY), Avena fatua (AVEFA), Lolium perenne (LOLPE), Setaria faberi (SETFA), Digitaria sanguinalis (DIGSA), Echinochloa crus-galli (ECHCG)
Pre-Emergence Activity
Figure imgf000186_0001
Figure imgf000187_0001
Figure imgf000188_0001
Figure imgf000189_0001
Figure imgf000190_0001
Post-Emergence Activity
Figure imgf000190_0002
Figure imgf000191_0001
Figure imgf000192_0001
Figure imgf000193_0001
Figure imgf000194_0001
Test Example 2
Test compounds were applied post-emergence at 6Og ai/ha, alone and in combination with cloquintocet-mexyl at 6Og ai/ha; the adjuvant Adigor (0.5%) was included for every treatment. The application volume was 200l/ha. Target plants were 2-3 leaf seedlings of winter wheat 'Hereward' and winter barley 'Antoniya' grown in a greenhouse under ambient conditions. Assessments were made at 14-21 days after application.
Figure imgf000194_0002
Figure imgf000195_0001
Test Example 3
The test compound T1 was applied at 100 and 20Og ai/ha, alone and in combination with a range of safeners as 1 :1 mixtures (for example at 100g + 100g; 20Og + 20Og) to the test plants - wheat and maize - at the 2-3 leaf stage. A 4-way safener mixture (cloquintocet-mexyl, benoxacor, fluxofenim and compound A*) was also applied with the test compound so that each safener was used a 1 :1 ratio (for example at 100+100+100+100+100g ai/ha). Assessments were made at 14- 21 days after application.
Figure imgf000195_0002
* Compound A is N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.

Claims

What is claimed is:
1. A compound of formula I
Figure imgf000196_0001
wherein
G is hydrogen or an alkali metal, alkaline earth metal, sulfonium, ammonium or a latentiating group,
R1 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen,
CrC2alkoxy or CrC2haloalkoxy,
R2, R3 and R4 are independently of each other hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, halomethyl, haloethyl, vinyl, ethynyl, halogen, d-C2alkoxy or C1-C2 haloalkoxy,
R5 and R12 are independently of each other hydrogen, CrC3alkyl, CrC3haloalkyl, CrC3alkyoxy,
CrC3alkylthio, halogen or CrC6alkoxycarbonyl, or
R5 and R12 join together to form a 3-7 membered carbocyclic ring, optionally containing an oxygen or sulfur atom, and
R6, R7, R8, R9, R10 and R11 are independently of each other hydrogen or a substituent, or R7 and
R8, or R9 and R10, together with the carbon atoms to which they are attached form a keto, an optionally substituted alkenyl or optionally substituted imino unit, or any two of R7, R8, R9 and R10 together form a 3-8 membered carbocyclic ring optionally containing a heteroatom selected from
O, S or N and optionally substituted, or R7 and R10 together form a bond.
2. A compound according to claim 1 , wherein
R6 and R11 are independently of each other hydrogen, halogen, formyl, cyano or nitro or
R6 and R11 are independently of each other CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, CrC6alkoxy,
C3-C7 cycloalkyl, C3-C7 cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or R6 and R11 are independently of each other a group COR13, CO2R14Or CONR15R16, CR17=NOR18,
CR19=NNR20R21, NHR22, NR22R23 or OR24 wherein
R13 is Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R14 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R15 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R16 is hydrogen, d-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, CrC6alkylsulfonyl, phenylsulfonyl, heteroarylsulfonyl, amino, C1-
C6alkylamino, diCrCβalkylamino, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R15 and R16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
R17 and R19 are independently of each other hydrogen, CrC3alkyl or C3-C6cycloalkyl,
R18, R20 and R21 are independently of each other hydrogen, CrC6alkyl, C3-C6alkenyl, C3-
C6alkynyl, C3-C7 cycloalkyl, CrCβalkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylthiocarbonyl, aminocarbonyl, CrC6alkylaminocarbonyl, diCrCβalkylaminocarbonyl, phenyl or heteroaryl, where all these substituents are optionally substituted,
R22 is CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrCβalkylthiocarbonyl, C1-
C6alkylaminocarbonyl, diCi-Cβalkylaminocarbonyl, Ci-C6alkylsulfonyl, phenylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, phenylthiocarbonyl, phenylsulfonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylthiocarbonyl or heteroarylsulfonyl, where all these substituents are optionally substituted,
R23 is CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, C1-
C6alkoxycarbonyl, CTCβalkylthiocarbonyl, d-Cβalkylaminocarbonyl, diCrCealkylaminocarbonyl,
Ci-Cβalkylsulfonyl, phenyl or heteroaryl, where all these substituents are optionally substituted, or
R22 and R23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and
R24 is C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, d-Cealkylcarbonyl, CrC6alkoxycarbonyl, C1-
C6alkylthiocarbonyl, aminocarbonyl, CrCβalkylaminocarbonyl, diCrCβalkylaminocarbonyl, tri(Cr
C6alkyl)silyl, phenyl or heteroaryl, where all these substituents are optionally substituted.
3. A compound according to claim 1 , wherein
R7, R8, R9 and R10 are independently of each other hydrogen, halogen, hydroxyl, formyl, amino, cyano or nitro, or
R7, R8, R9 and R10 are independently of each other CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-
C6alkoxy, d-CealkoxyCrCealkyl, d-Cealkylthio, CrC6alkylsulfinyl, CrC6alkylsulfonyl, C1-
C6alkylthioCrC6alkyl, d-CealkylsulfinylCrCealkyl, CrCealkylsulfonylCrCealkyl, C3-C7 cycloalkyl,
C4-C7cycloalkenyl, tri(CrC6alkyl)silyl, aryl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R7, R8, R9 and R10 are independently of each other a group COR13, CO2R14 or CONR15R16,
CR17=NOR18, CR19=NNR20R21, NR22R23 or OR24, wherein
R13 is CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R14 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or is 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R15 is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, CrC6haloalkoxy, C3-C7 cycloalkyl, C5-C7cycloalkenyl, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted,
R is hydrogen, CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, CrC6alkoxy, C^Cehaloalkoxy, C3-C 7 cycloalkyl, C5-C7cycloalkenyl, CrC6alkylsulfonyl, amino, CrC6alkylamino, diCrCβalkylamino, phenyl, heteroaryl or a 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R15 and R16 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom,
R17 and R19 are independently of each other hydrogen, CrC3alkyl or C3-C6cycloalkyl,
R18, R20 and R21 are independently of each other hydrogen, CrC6alkyl, C3-C6alkenyl, C3-
C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylthiocarbonyl, C1-
C6alkylaminocarbonyl, diCrCβalkylaminocarbonyl, phenyl or heteroaryl, where all these substituents are optionally substituted,
R22 and R23 are independently of each other d-Cβalkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, CrCβalkylcarbonyl, CrCβalkoxycarbonyl, Ci-Cβalkylthiocarbonyl, C1-
C6alkylaminocarbonyl, diCrCδalkylaminocarbonyl, CrC6alkylsulfonyl, phenyl or heteroaryl or
R22 and R23 may be joined to form an optionally substituted 3-7 membered ring, optionally containing an oxygen, sulfur or nitrogen atom, where all these substituents are optionally substituted, and R24 is CrC6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C7 cycloalkyl, CrC6alkylcarbonyl, C1- C6alkoxycarbonyl, CrC6alkylthiocarbonyl, CrCβalkylaminocarbonyl, diCrCealkylaminocarbonyl, Ci-C6alkylsulfonyl, tri(CrC6alkyl)silyl, phenyl or heteroaryl, where all these substituents are optionally substituted.
4. A compound according to claim 1 , wherein
R7 and R8, or R9 and R10, together form a unit =0, or form a unit =CR25R26, or form a unit =NR27, or any two of R7, R8, R9 and R10 form a 3-8 membered ring, optionally containing a heteroatom selected from O, S or N and optionally substituted by CrC3alkyl, Ci-C3alkoxy, CrC3alkylthio, C1- C3alkylsulfinyl, CrC3alkylsulfonyl, CrC3haloalkyl, halogen, phenyl, phenyl substituted by C1- C4alkyl, CrC^aloalkyl, C1-C4BIkOXy, CrC4haloalkoxy, C1-C4alkylthio, CrC4alkylsulfinyl, C1- C4alkylsulfonyl, CrC^lkylcarbonyl, CrC4alkoxycarbonyl, aminocarbonyl, C1- C6alkylaminocarbonyl, diCrCβalkylaminocarbonyl, halogen, cyano or by nitro, heteroaryl or heteroaryl substituted by CrC4alkyl, d-C^aloalkyl, CrC4alkoxy, CrC4haloalkoxy, C1- C4alkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, CrC^lkylcarbonyl, halogen, cyano or by nitro, wherein
R25and R26 are independently of each other hydrogen, halogen, cyano or nitro, or R25 and R26 are independently of each other CrC6alkyl, CrC6alkoxy, CrC6alkylamino, diCr C6alkylamino, CrCealkylcarbonyl, CrCβalkoxycarbonyl, CrCβalkylaminocarbonyl, diC^ C6alkylaminocarbonyl, /V-phenyl-AZ-CrCβalkylaminocarbonyl, /V-phenylCrCealkyl-ZV-Cr C6alkylaminocarbonyl, /V-heteroaryl-ZV-CrCealkylaminocarbonyl, /V-heteroarylCrCealkyl-W-Cr C6alkylaminocarbonyl, phenyl, heteroaryl, C3-C8cycloalkyl or 3-7 membered heterocyclyl, where all these substituents are optionally substituted, or
R25and R26 may be joined together to form a 5-8 membered ring optionally containing a heteroatom selected from O, S or N and optionally substituted by CrC2alkyl or C1-C2BIkOXy, R27 is nitro or cyano, or
R27 is CrCβalkylamino, diCrCβalkylamino, CrC6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, phenoxy, phenylamino, Λ/-phenyl-Λ/-CrC6alkylamino, /V-phenylCrCβalkyl-yV-CrCβalkylamino heteroaryloxy, heteroarylamino, Λ/-heteroaryl-Λ/-CrC6alkylamino or /V-heteroarylCrCealkyl-ZV-Cr C6alkylamino, where all these substituents are optionally substituted.
5. A compound according to claim 1 , wherein R1, R2 and R4 are methyl and R3 is hydrogen.
6. A compound according to claim 1 , wherein R1, R2 and R4 are methyl and R3 is hydrogen, and R7, R8, R9 and R10 are independently of each other hydrogen, cyano, Ci-C6alkyl, C2-C6alkenyl, Ci-C6alkoxy, d-CβalkoxyCrCealkyl, 3-7 membered heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl.
7. A compound according to claim 1 , wherein R5 and R12 are independently of each other hydrogen or Ci-C3alkyl.
8. A compound according to claim 1 , wherein R1 is methyl, ethyl, vinyl, ethynyl, cyclopropyl, difluoromethoxy, trifluoromethoxy or C1-C2 alkoxy and
R2, R3 and R4 are independently of each other hydrogen, methyl, ethyl, vinyl or ethynyl.
9. A process for the preparation of a compound of formula (AH)
Figure imgf000200_0001
wherein R1, R2, R3, R4, R5, R6, R8, R9, R11 and R12 are as defined in claim 1 , which comprises reacting a compound of formula (H)
Figure imgf000200_0002
with a compound of formula (Al)
Figure imgf000200_0003
in the presence or absence of a catalyst and in the presence or absence of a solvent.
10. A compound of formula (Al)
Figure imgf000201_0001
wherein R1, R2, R3, R4, R5 and R12 are as defined in claim 1 , where the compounds of the formulae
Figure imgf000201_0002
are excluded.
11. A herbicidal composition, which, in addition to comprising formulation adjuvants, comprises a herbicidally effective amount of a compound of formula I.
12. A herbicidal composition according to claim 11 , which, in addition to comprising formulation adjuvants, comprises a herbicidally effective amount of a compound of formula I and a further herbicide.
13. A herbicidal composition according to claim 11 , which, in addition to comprising formulation adjuvants, comprises a herbicidally effective amount of a compound of formula I, a further herbicide and a safener.
14. A method of controlling grasses and weeds in crops of useful plants, which comprises applying a herbicidally effective amount of a compound of formula I, or of a composition comprising such a compound, to the plants or to the locus thereof.
PCT/EP2008/006467 2007-08-08 2008-08-06 Novel herbicides WO2009019005A2 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
JP2010519374A JP5462163B2 (en) 2007-08-08 2008-08-06 New herbicide
ES08801523.5T ES2497501T3 (en) 2007-08-08 2008-08-06 Herbicidally active cyclopentanedionic compounds and their derivatives
EA201000272A EA201000272A1 (en) 2007-08-08 2008-08-06 Tricyclic bridging derivatives of cyclopentadienone as herbicides
BRPI0815651-4A BRPI0815651B1 (en) 2007-08-08 2008-08-06 CYCLOPENTAN-DERIVATIVE COMPOUNDS HERBICIDALLY ACTIVE, ITS PREPARATION PROCESS, HERBICID COMPOSITION AND METHOD FOR CONTROLING WEED GRASS AND HERBS IN USEFUL PLANT CROPS
NZ583033A NZ583033A (en) 2007-08-08 2008-08-06 Tricyclic bridged cyclopentanedione derivatives as herbicides
EP08801523.5A EP2185564B1 (en) 2007-08-08 2008-08-06 Herbicidally active cyclopentanedione compounds and derivatives thereof
PL08801523T PL2185564T3 (en) 2007-08-08 2008-08-06 Herbicidally active cyclopentanedione compounds and derivatives thereof
CN200880102362.4A CN101855225B (en) 2007-08-08 2008-08-06 Tricyclic bridged cyclopentanedione derivatives as herbicides
CA2694133A CA2694133C (en) 2007-08-08 2008-08-06 Herbicidal cyclopentanedione compounds
AP2010005137A AP2010005137A0 (en) 2007-08-08 2008-08-06 Tricyclic bridged cyclopentanedione derivatives asherbicides
MX2010001364A MX2010001364A (en) 2007-08-08 2008-08-06 Novel herbicides.
UAA201002439A UA100700C2 (en) 2007-08-08 2008-08-06 Tricyclic bridged cyclopentanedione derivatives, processes for the preparation of intermediate, herbicidal composition and method for controlling weeds in crops of useful plants
US12/672,165 US8754242B2 (en) 2007-08-08 2008-08-06 Herbicides
AU2008285937A AU2008285937B2 (en) 2007-08-08 2008-08-06 Tricyclic bridged cyclopentanedione derivatives as herbicides
ZA2010/00490A ZA201000490B (en) 2007-08-08 2010-01-21 Tricyclic bridged cyclopentanedione derivatives as herbicides
TNP2010000061A TN2010000061A1 (en) 2007-08-08 2010-02-05 Tricyclic bridged cyclopentanedione derivatives as herbicides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0715454.5 2007-08-08
GBGB0715454.5A GB0715454D0 (en) 2007-08-08 2007-08-08 Novel herbicides

Publications (3)

Publication Number Publication Date
WO2009019005A2 true WO2009019005A2 (en) 2009-02-12
WO2009019005A3 WO2009019005A3 (en) 2009-12-10
WO2009019005A8 WO2009019005A8 (en) 2010-01-28

Family

ID=38543241

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/006467 WO2009019005A2 (en) 2007-08-08 2008-08-06 Novel herbicides

Country Status (26)

Country Link
US (1) US8754242B2 (en)
EP (1) EP2185564B1 (en)
JP (1) JP5462163B2 (en)
KR (1) KR20100044825A (en)
CN (1) CN101855225B (en)
AP (1) AP2010005137A0 (en)
AR (1) AR067878A1 (en)
AU (1) AU2008285937B2 (en)
BR (1) BRPI0815651B1 (en)
CA (1) CA2694133C (en)
CL (1) CL2008002338A1 (en)
CO (1) CO6251352A2 (en)
EA (1) EA201000272A1 (en)
EC (1) ECSP109942A (en)
ES (1) ES2497501T3 (en)
GB (1) GB0715454D0 (en)
MA (1) MA31596B1 (en)
MX (1) MX2010001364A (en)
NZ (1) NZ583033A (en)
PL (1) PL2185564T3 (en)
SV (1) SV2010003475A (en)
TN (1) TN2010000061A1 (en)
TW (1) TW200920258A (en)
UA (1) UA100700C2 (en)
WO (1) WO2009019005A2 (en)
ZA (1) ZA201000490B (en)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010102758A2 (en) 2009-03-11 2010-09-16 Bayer Cropscience Ag Halogenalkylmethylenoxy-phenyl-substituted ketoenols
WO2011007146A1 (en) 2009-07-16 2011-01-20 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione derivatives
WO2011098433A1 (en) 2010-02-15 2011-08-18 Bayer Schering Pharma Aktiengesellschaft Cyclic keto-enols for therapy
WO2012059436A2 (en) 2010-11-02 2012-05-10 Bayer Cropscience Ag Phenyl-substituted bicyclooctane-1,3-dione-derivatives
US8367873B2 (en) 2008-10-10 2013-02-05 Bayer Cropscience Ag Phenyl-substituted bicyclooctane-1,3-dione derivatives
WO2013079708A1 (en) * 2011-11-30 2013-06-06 Syngenta Limited 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds, and derivatives thereof
WO2013110612A1 (en) 2012-01-26 2013-08-01 Bayer Intellectual Property Gmbh Phenyl-substituted ketoenols for controlling fish parasites
WO2014195327A1 (en) 2013-06-05 2014-12-11 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof
US9782382B2 (en) 2009-07-08 2017-10-10 Dermira (Canada), Inc. TOFA analogs useful in treating dermatological disorders or conditions
US9808003B2 (en) 2013-04-19 2017-11-07 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof
EP4053097A1 (en) 2014-12-18 2022-09-07 Corteva Agriscience LLC Ketone compound as herbicide
EP4155311A1 (en) * 2021-09-24 2023-03-29 Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno Surfactants from bio-based feedstock

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0715576D0 (en) 2007-08-09 2007-09-19 Syngenta Ltd Novel herbicides
GB0717082D0 (en) * 2007-09-03 2007-10-10 Syngenta Ltd Novel herbicides
GB0822834D0 (en) 2008-12-15 2009-01-21 Syngenta Ltd Novel herbicides
GB0901086D0 (en) 2009-01-22 2009-03-11 Syngenta Ltd Novel herbicides
GB0901834D0 (en) 2009-02-04 2009-03-11 Syngenta Ltd Novel herbicides
GB201621626D0 (en) * 2016-12-19 2017-02-01 Syngenta Participations Ag Improvements in or relating to organic compounds
CN108218921A (en) * 2017-11-13 2018-06-29 汝城县三鑫电化有限公司 A kind of preparation method of organo-bismuth complex

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996003366A1 (en) 1994-07-21 1996-02-08 Bayer Aktiengesellschaft 2-(2,4,6-trimethyl phenyl)cyclopentane-1,3-dione derivatives
WO1999048869A1 (en) 1998-03-26 1999-09-30 Bayer Aktiengesellschaft Aryl phenyl substituted cyclic ketoenols
WO2001074770A1 (en) 2000-04-03 2001-10-11 Bayer Cropscience Ag C2 phenyl-substituted cyclic keto-enols used as pesticides and herbicides
WO2004058712A2 (en) 2002-12-30 2004-07-15 Syngenta Participations Ag Herbicidally active nicotinoyl derivates
US20050164883A1 (en) 1999-09-07 2005-07-28 Thomas Maetzke Novel herbicides
WO2005123667A1 (en) 2004-06-22 2005-12-29 Syngenta Participations Ag Substituted bicyclooctenes and their use as herbicides

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4209532A (en) 1977-03-28 1980-06-24 Union Carbide Corporation Biocidal 2-aryl-1,3-cyclohexane dione compounds and alkali metal and ammonium salts thereof
US4659372A (en) 1977-03-28 1987-04-21 Union Carbide Corporation Biocidal 2-aryl-1,3-cyclohexanedione enol ester compounds
US4256659A (en) 1977-03-28 1981-03-17 Union Carbide Corporation Method of preparing 2-aryl-1,3-cyclohexanedione compounds
PT67818A (en) 1977-03-28 1978-04-01 Union Carbide Corp Process for the synthesis of biocidal 2-aryl-1,3-cycloalkanedionas and their enol esters
US4175135A (en) 1978-07-18 1979-11-20 Union Carbide Corporation Method of controlling acarina ectoparasites on warmblooded animals by orally administering to the animal an ectoparasitically effective amount of a 2-aryl-1,3-cyclohexanedione compound, and alkali metal salts, ammonium salts and enol esters thereof
US4283348A (en) 1978-09-22 1981-08-11 Union Carbide Corporation Method of preparing 2-aryl-3-cyclopentanedione compounds
US4526723A (en) 1978-09-27 1985-07-02 Union Carbide Corporation Biocidal enol esters of non-ortho substituted 2-aryl-1-3-cycloalkanedione compounds
US4371711A (en) 1979-05-30 1983-02-01 Sumitomo Chemical Company, Limited Process for producing 4-hydroxycyclopentenones
US4338122A (en) 1979-09-26 1982-07-06 Union Carbide Corporation Biocidal 2-aryl-1,3-cyclopentanedione compounds and alkali metal and ammonium salts thereof
US4409153A (en) 1980-03-28 1983-10-11 Union Carbide Corporation O-(2-Aryl-3-oxo-1-cyclohexenyl) phosphates
US4551547A (en) 1980-11-10 1985-11-05 Union Carbide Corporation Biocidal 2-aryl-1, 3-cyclopentanedione enol ester compounds
US4489012A (en) 1982-02-23 1984-12-18 Union Carbide Corporation Enol-phosphorous esters of 2-aryl-1,3-cycloalkanediones compounds
BR9508247B1 (en) 1994-07-07 2011-02-22 2-arylcyclopentane-1,3-dione derivatives, process for their preparation; pest control and herbicide compositions; uses of said derivatives; and method for the control of animal pests and unwanted vegetation.
WO1996025395A1 (en) 1995-02-13 1996-08-22 Bayer Aktiengesellschaft 2-phenyl-substituted heterocyclic 1,3-ketonols as herbicides and pesticides
US6316486B1 (en) 1995-05-09 2001-11-13 Bayer Aktiengesellschaft Alkyl dihalogenated phenyl-substituted ketoenols useful as pesticides and herbicides
US6515184B1 (en) 1995-10-13 2003-02-04 Bayer Aktiengesellschaft Cyclopentane-1,3-dione derivatives, herbicidal and pesticidal compositions containing them, methods of using them to combat pests and weeds and process for the preparation thereof
DE19538218A1 (en) 1995-10-13 1997-04-17 Bayer Ag Cyclopentane-1,3-dione derivatives
DE19708607A1 (en) 1997-03-03 1998-09-10 Bayer Ag 2-arylcyclopentane-1,3-diones
DE19808261A1 (en) 1998-02-27 1999-10-28 Bayer Ag Arylphenyl substituted cyclic ketoenols
DE69908568T2 (en) 1998-03-13 2004-05-06 Syngenta Participations Ag HERBICIDE ACTIVE 3-HYDROXY-4-ARYL-5-OXOPYRAZOLINE DERIVATIVES
JP2002524554A (en) 1998-09-15 2002-08-06 シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト Pyridine ketones useful as herbicides
AU2623399A (en) 1999-02-11 2000-08-29 Novartis Ag 3-hydroxy-4-aryl-5-pyrazoline derivatives as herbicides
DE19935963A1 (en) 1999-07-30 2001-02-01 Bayer Ag Biphenyl substituted cyclic ketoenols
PL356456A1 (en) 1999-09-07 2004-06-28 Syngenta Participations Ag Novel herbicides
DE10139465A1 (en) 2001-08-10 2003-02-20 Bayer Cropscience Ag Herbicidal composition, especially for selective weed control in crops such as cereals, containing cyclic keto enol derivative herbicide and safener, e.g. cloquintocet-mexyl or mefenpyr-diethyl
DE10249055A1 (en) 2002-10-22 2004-05-06 Bayer Cropscience Ag 2-Phenyl-2-substituted-1,3-diketones
DE10311300A1 (en) 2003-03-14 2004-09-23 Bayer Cropscience Ag New 2-alkoxy-4-halo-6-alkylphenyl-substituted (hetero)cyclic ketoenols, useful as total or selective herbicides and pesticides, e.g. insecticides, acaricides and nematocides for plant protection
DE10326386A1 (en) 2003-06-12 2004-12-30 Bayer Cropscience Ag N-heterocyclyl-phenyl-substituted cyclic ketoenols
DE10354629A1 (en) 2003-11-22 2005-06-30 Bayer Cropscience Ag 2-ethyl-4,6-dimethyl-phenyl substituted spirocyclic tetramic acid derivatives
DE102004014620A1 (en) 2004-03-25 2005-10-06 Bayer Cropscience Ag 2,4,6-phenyl-substituted cyclic ketoenols
DE102004041529A1 (en) 2004-08-27 2006-03-02 Bayer Cropscience Gmbh Herbicide combinations with special ketoenols
DE102004044827A1 (en) 2004-09-16 2006-03-23 Bayer Cropscience Ag Iodine-phenyl-substituted cyclic ketoenols
DE102005059471A1 (en) 2005-12-13 2007-07-12 Bayer Cropscience Ag Herbicidal compositions with improved action
DE102006000971A1 (en) 2006-01-07 2007-07-12 Bayer Cropscience Ag 2,4,6-trialkylphenyl-substituted cyclopentane-1,3-diones
DE102006007882A1 (en) 2006-02-21 2007-08-30 Bayer Cropscience Ag New cyclic keto enol derivatives useful for controlling animal pests and/or unwanted plant growth
DE102006018828A1 (en) 2006-04-22 2007-10-25 Bayer Cropscience Ag Alkoxyalkyl-substituted cyclic ketoenols
DE102006025874A1 (en) 2006-06-02 2007-12-06 Bayer Cropscience Ag Alkoxyalkyl-substituted cyclic ketoenols
SA07280691B1 (en) 2006-12-14 2010-11-02 سينجنتا بارتسبيشنز ايه جي Novel 4-Biphenyl-Pyran-3,5-Diones and Their Use as Herbicides
GB0704652D0 (en) 2007-03-09 2007-04-18 Syngenta Participations Ag Novel herbicides
GB0704653D0 (en) 2007-03-09 2007-04-18 Syngenta Participations Ag Novel herbicides
GB0710223D0 (en) 2007-05-29 2007-07-11 Syngenta Ltd Novel Herbicides
GB0715576D0 (en) 2007-08-09 2007-09-19 Syngenta Ltd Novel herbicides
GB0717082D0 (en) 2007-09-03 2007-10-10 Syngenta Ltd Novel herbicides
GB0812310D0 (en) 2008-07-03 2008-08-13 Syngenta Ltd Novel herbicides
GB0822834D0 (en) 2008-12-15 2009-01-21 Syngenta Ltd Novel herbicides
GB0900864D0 (en) 2009-01-19 2009-03-04 Syngenta Ltd Novel Herbicides
GB0901086D0 (en) 2009-01-22 2009-03-11 Syngenta Ltd Novel herbicides
GB0901834D0 (en) 2009-02-04 2009-03-11 Syngenta Ltd Novel herbicides
EP2429979A1 (en) 2009-05-16 2012-03-21 Syngenta Limited Novel herbicides

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996003366A1 (en) 1994-07-21 1996-02-08 Bayer Aktiengesellschaft 2-(2,4,6-trimethyl phenyl)cyclopentane-1,3-dione derivatives
WO1999048869A1 (en) 1998-03-26 1999-09-30 Bayer Aktiengesellschaft Aryl phenyl substituted cyclic ketoenols
US20050164883A1 (en) 1999-09-07 2005-07-28 Thomas Maetzke Novel herbicides
WO2001074770A1 (en) 2000-04-03 2001-10-11 Bayer Cropscience Ag C2 phenyl-substituted cyclic keto-enols used as pesticides and herbicides
WO2004058712A2 (en) 2002-12-30 2004-07-15 Syngenta Participations Ag Herbicidally active nicotinoyl derivates
WO2005123667A1 (en) 2004-06-22 2005-12-29 Syngenta Participations Ag Substituted bicyclooctenes and their use as herbicides

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8367873B2 (en) 2008-10-10 2013-02-05 Bayer Cropscience Ag Phenyl-substituted bicyclooctane-1,3-dione derivatives
US9045390B2 (en) 2009-03-11 2015-06-02 Bayer Cropscience Ag Haloalkylmethyleneoxyphenyl-substituted ketoenols
EP3153503A1 (en) 2009-03-11 2017-04-12 Bayer Intellectual Property GmbH Intermediates for halogenoalkylmethylenoxy-phenyl-substituted ketoenols
US8518985B2 (en) 2009-03-11 2013-08-27 Bayer Cropscience Ag Haloalkylmethyleneoxyphenyl-substituted ketoenols
WO2010102758A2 (en) 2009-03-11 2010-09-16 Bayer Cropscience Ag Halogenalkylmethylenoxy-phenyl-substituted ketoenols
US9782382B2 (en) 2009-07-08 2017-10-10 Dermira (Canada), Inc. TOFA analogs useful in treating dermatological disorders or conditions
WO2011007146A1 (en) 2009-07-16 2011-01-20 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione derivatives
WO2011098433A1 (en) 2010-02-15 2011-08-18 Bayer Schering Pharma Aktiengesellschaft Cyclic keto-enols for therapy
WO2012059436A2 (en) 2010-11-02 2012-05-10 Bayer Cropscience Ag Phenyl-substituted bicyclooctane-1,3-dione-derivatives
EP2719680A1 (en) 2010-11-02 2014-04-16 Bayer Intellectual Property GmbH Phenyl-substituted bicycle octane 1.3 dion derivatives
US9101133B2 (en) 2010-11-02 2015-08-11 Bayer Intellectual Property Gmbh Phenyl-substituted bicyclooctane-1,3-dione-derivatives
JP2015500222A (en) * 2011-11-30 2015-01-05 シンジェンタ リミテッド 2- (Substituted phenyl) -cyclopentane-1,3-dione compounds and derivatives thereof
US9107415B2 (en) 2011-11-30 2015-08-18 Syngenta Particpations Ag 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds, and derivatives thereof
EA027413B1 (en) * 2011-11-30 2017-07-31 Зингента Лимитед 2-(substituted-phenyl)cyclopentane-1,3-dione compounds, and derivatives thereof
WO2013079708A1 (en) * 2011-11-30 2013-06-06 Syngenta Limited 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds, and derivatives thereof
WO2013110612A1 (en) 2012-01-26 2013-08-01 Bayer Intellectual Property Gmbh Phenyl-substituted ketoenols for controlling fish parasites
US9808003B2 (en) 2013-04-19 2017-11-07 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof
WO2014195327A1 (en) 2013-06-05 2014-12-11 Syngenta Limited Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof
EP4053097A1 (en) 2014-12-18 2022-09-07 Corteva Agriscience LLC Ketone compound as herbicide
EP4155311A1 (en) * 2021-09-24 2023-03-29 Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno Surfactants from bio-based feedstock

Also Published As

Publication number Publication date
CN101855225A (en) 2010-10-06
ECSP109942A (en) 2010-03-31
GB0715454D0 (en) 2007-09-19
CA2694133A1 (en) 2009-02-12
CO6251352A2 (en) 2011-02-21
AR067878A1 (en) 2009-10-28
BRPI0815651B1 (en) 2018-03-06
TW200920258A (en) 2009-05-16
UA100700C2 (en) 2013-01-25
KR20100044825A (en) 2010-04-30
MX2010001364A (en) 2010-03-01
BRPI0815651A2 (en) 2015-02-18
WO2009019005A3 (en) 2009-12-10
TN2010000061A1 (en) 2011-09-26
EA201000272A1 (en) 2010-08-30
SV2010003475A (en) 2011-03-23
ES2497501T3 (en) 2014-09-23
AU2008285937A1 (en) 2009-02-12
MA31596B1 (en) 2010-08-02
JP2010535724A (en) 2010-11-25
US8754242B2 (en) 2014-06-17
AP2010005137A0 (en) 2010-02-28
CN101855225B (en) 2014-01-08
AU2008285937B2 (en) 2013-09-26
EP2185564A2 (en) 2010-05-19
ZA201000490B (en) 2011-07-27
US20120094832A1 (en) 2012-04-19
NZ583033A (en) 2012-04-27
WO2009019005A8 (en) 2010-01-28
PL2185564T3 (en) 2014-11-28
EP2185564B1 (en) 2014-06-18
JP5462163B2 (en) 2014-04-02
CA2694133C (en) 2016-03-22
CL2008002338A1 (en) 2009-01-02

Similar Documents

Publication Publication Date Title
EP2173755B1 (en) Novel herbicides
EP2185564A2 (en) Tricyclic bridged cyclopentanedione derivatives as herbicides
CA2679343C (en) 2-aryl-5-heterocyclyl-cyclohexane-1,3-dione compounds and their use as herbicides
CA2729724C (en) 5-heterocyclylalkyl-3-hydroxy-2-phenylcyclopent-2-enones as herbicides
US8680339B2 (en) Herbicides
CA2750446C (en) Cyclopentadione derived herbicides
EP2387569A1 (en) Novel herbicides
EP2393796A1 (en) Novel herbicides
EP2387310A1 (en) Cyclopentadione derived herbicides
EP2429979A1 (en) Novel herbicides
EP2454224A1 (en) Novel herbicides

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880102362.4

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08801523

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 2008285937

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 280/DELNP/2010

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2008801523

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12010500131

Country of ref document: PH

WWE Wipo information: entry into national phase

Ref document number: 2694133

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 583033

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: MX/A/2010/001364

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2008285937

Country of ref document: AU

Date of ref document: 20080806

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2010519374

Country of ref document: JP

ENP Entry into the national phase

Ref document number: 20107002680

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 10012629

Country of ref document: CO

Ref document number: D2010024

Country of ref document: CU

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: PI 2010000176

Country of ref document: MY

WWE Wipo information: entry into national phase

Ref document number: 201000272

Country of ref document: EA

WWE Wipo information: entry into national phase

Ref document number: DZP2010000122

Country of ref document: DZ

WWE Wipo information: entry into national phase

Ref document number: 12672165

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0815651

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20100205