WO2009002276A1 - Procede de condensation d'aldol mis en œuvre dans la preparation d'aldehyde ou de cetone α,β-insature(e) et son utilisation dans la synthese de pyrrole substitue ou l'arylation d'enal α,β-insature - Google Patents

Procede de condensation d'aldol mis en œuvre dans la preparation d'aldehyde ou de cetone α,β-insature(e) et son utilisation dans la synthese de pyrrole substitue ou l'arylation d'enal α,β-insature Download PDF

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WO2009002276A1
WO2009002276A1 PCT/SG2008/000230 SG2008000230W WO2009002276A1 WO 2009002276 A1 WO2009002276 A1 WO 2009002276A1 SG 2008000230 W SG2008000230 W SG 2008000230W WO 2009002276 A1 WO2009002276 A1 WO 2009002276A1
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substituted
different
substituents
group
same
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PCT/SG2008/000230
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English (en)
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Yugen Zhang
Jackie Y. Ying
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Agency For Science, Technology And Research
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration

Definitions

  • the invention relates to a process for aldol condensation comprising mixing an ⁇ -unsubstituted aldehyde or ketone with another aldehyde or ketone under dry reaction conditions in the presence of an organocatalyst .
  • the invention further relates to a process for preparing a substituted pyrrole using the aldol condensation process and a process for arylation of an ⁇ , ⁇ -unsaturated enal using the aldol condensation process.
  • Organocatalysis provides an opportunity to implement various reaction concepts in multicomponent domino reactions to prepare compounds of increasing molecular complexity from available simple precursors. Organocatalysis further provides the possibility of lowering costs, time and energy, and offers an environmentally friendlier alternative to other synthetic approaches since it often eliminates the need for using protecting groups and isolating intermediates. Organocatalytic reactions have been reported as biomimetic in many biosynthesis procedures .
  • a process for aldol condensation comprising mixing an ⁇ -unsubstituted aldehyde or ketone with another aldehyde or ketone under dry reaction conditions in the presence of an organocatalyst .
  • R 5 , R 6 and R 7 are as defined anywhere below,
  • R 6 is as defined anywhere below, and a compound of formula (VIII) :
  • R 7 is as defined anywhere below.
  • R 5 and R 8 are as defined anywhere below, which process comprises mixing, in any order:
  • the invention relates to a process for aldol condensation comprising mixing an ⁇ -unsubstituted aldehyde or ketone with another aldehyde or ketone under dry reaction conditions in the presence of an organocatalyst .
  • the process may comprise, for example, and without limitation, mixing an ⁇ -unsubstituted aldehyde with another aldehyde or ketone.
  • the ⁇ -unsubstituted aldehyde may be, for example, and without limitation, mixed with another aldehyde.
  • the other aldehyde may be, for example, and without limitation, the same compound or a different compound from the ⁇ -unsubstituted aldehyde.
  • the other aldehyde which is a different compound from the ⁇ -unsubstituted aldehyde may be an ⁇ -unsubstituted aldehyde or a ⁇ -substituted aldehyde.
  • the ⁇ -unsubstituted aldehyde may be, for example, and without limitation, mixed with a ketone.
  • the ketone may be, for example, and without limitation, an ⁇ -unsubstituted ketone or a ⁇ - substituted ketone.
  • the process may comprise, for example, and without limitation, mixing an ⁇ -unsubstituted ketone with an aldehyde or another ketone.
  • the ⁇ -unsubstituted ketone may be, for example, and without limitation, mixed with an aldehyde.
  • the aldehyde may be, for example, and without limitation, an ⁇ - unsubstituted aldehyde or a ⁇ -substituted aldehyde.
  • the ⁇ -unsubstituted ketone may be mixed with another ketone which may be, for example, and without limitation, the same compound or a different compound from the ⁇ -unsubstituted ketone.
  • the other ketone which is a different compound from the . ⁇ - unsubstituted ketone may be an ⁇ -unsubstituted ketone or a ⁇ -substituted ketone.
  • the ⁇ -unsubstituted aldehyde or ketone of the invention is not particularly limited.
  • the ⁇ -unsubstituted aldehyde or ketone may be, for example, and without limitation, a compound of formula (II):
  • R 1 and R 2 may independently be, for example, and without limitation, a hydrogen atom, a C ⁇ - ⁇ alkyl group which may be substituted with one or more substituents which are the same or different, a C 2 - 6 alkenyl group which may be substituted with one or more substituents which are the same or different, a C 2 - 6 alkynyl group which may be substituted with one or more substituents which are the same or different, a C 3 - 8 cycloalkyl group which may be substituted with one or more substituents which are the same or different, a C 3 - 8 cycloalkenyl group which may be substituted with one or more substituents which are the same or different, a C 6 - 14 aryl group which may be substituted with one or more substituents which are the same or different, a C ⁇ -14 aryl-Ci- 6 alkyl group which may be substituted with one or more substituents which are the same or different, a Ce-i4
  • the Ci_ 6 alkyl group of the alkyl containing groups which may be substituted may be, for example, and without limitation, any straight or branched alkyl, for example, methyl, ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, i-pentyl, sec-pentyl, t-pentyl, n-hexyl, i-hexyl, 1, 2-dimethylpropyl, 2- ethylpropyl, l-methyl-2-ethylpropyl, l-ethyl-2-methylpropyl, 1, 1, 2-trimethylpropyl, 1, 1, 2-triethylpropyl, 1,1- dimethylbutyl, 2, 2-dimethylbutyl, 2-ethylbutyl, 1,3- dimethylbutyl, 2-methylp
  • the C 2 - 6 alkenyl group of the C 2 -6 alkenyl group which may be substituted may be, for example, and without limitation-, any straight or branched alkenyl, for example, vinyl, allyl, isopropenyl, l-propene-2-yl, 1-butene-l-yl, 1- butene-2-yl, l-butene-3-yl, 2-butene-l-yl or 2-butene-2-yl.
  • the C 2 - 6 alkenyl group may be, for example, and without limitation, interrupted by one or more heteroatoms which are independently nitrogen, sulfur or oxygen.
  • the C2-6 alkynyl group of the C2-6 alkynyl group which may be substituted may be, for example, and without limitation, any straight or branched alkynyl, for example, ethynyl, propynyl, butynyl, pentynyl or hexynyl .
  • the C 2 - 6 alkynyl group may be, for example, and without limitation, interrupted by one or more heteroatoms which are independently nitrogen, sulfur or oxygen.
  • the C 3 -8 cycloalkyl group of the C 3 - 8 cycloalkyl group which may be substituted may be, for example, and without limitation, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl or cycloheptanyl .
  • the C3-8 cycloalkenyl group of the C3.-8 cycloalkenyl group which may be substituted may be, for example, and without limitation, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl .
  • the C 6 -i 4 aryl group of the aryl containing groups which may be substituted may be, for example, and without limitation, phenyl (Ph) , pentalenyl, indenyl, naphthyl, azulenyl, heptalenyl, benzocyclooctenyl or phenanthrenyl.
  • the Ce- 14 aryl-Ci_ 6 alkyl group of the C 6 _i 4 aryl-C ⁇ -6 alkyl group which may be substituted may be, for example, and without limitation, a Ci_ 6 alkyl group as defined anywhere above having a C ⁇ - 14 aryl group as defined anywhere above as a substituent .
  • the Ce-14 aryl-C 2 -6 alkenyl group of the C 6 _i 4 aryl- C 2 - 6 alkenyl group which may be substituted may be, for example, and without limitation, a C 2 - 6 alkenyl group as defined anywhere above having a C 6 - 14 aryl group as defined anywhere above as a substituent.
  • the C 6 -I 4 aryl-C 2 -6 alkynyl group of the C 6 _i 4 aryl- C2- 6 alkynyl group which may be substituted, may be, for example, and without limitation, a C 2 - 6 alkynyl group as defined anywhere above having a C ⁇ - 14 aryl group as defined anywhere above as a substituent.
  • the 4- to 10-membered non-aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen of the 4- to 10-membered non-aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen and which group may be substituted may contain, for example, and without limitation, from 1 to 4 heteroatoms which are independently nitrogen, sulfur or oxygen.
  • the 4- to 10-membered non-aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen may be, for example, and without limitation, pyrrolidinyl, pyrrolinyl, piperidinyl, piperazinyl, imidazolinyl, pyrazolidinyl, imidazolydinyl, morpholinyl, tetrahydropyranyl, azetidinyl, oxetanyl, oxathiolanyl, phthalimide or succinimide.
  • the 5- to 14-membered aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen of the 5- to 14-membered aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen and which group may be substituted may contain, for example, and without limitation, from 1- to 4 heteroatoms which are independently nitrogen, sulfur or oxygen.
  • the 5- to 14-membered aromatic heterocyclic group containing one or more heteroatoms which are independently nitrogen, sulfur or oxygen may be, for example, and without limitation, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pirazinyl, imidazolyl, thiazolyl or oxazolyl.
  • the cyclic structure of the cyclic structure which may be substituted may be, for example, and without limitation, a C 3 - 8 cycloalkyl group or a C 3 - B cycloalkenyl group as defined anywhere above.
  • Each of the Ci- 6 alkyl, C 2 - 6 alkenyl, C2-6 alkynyl, C 3 -S cycloalkyl, C 3 - 8 cycloalkenyl, C 6 - I4 aryl, C 6 -I 4 a£yl-Ci- 6 alkyl, C 6 -I 4 aryl-C 2 -e alkenyl, C 6 -I 4 aryl-C 2 - 6 alkynyl, 4- to 10-membered non-aromatic heterocylic, 5- to 14-membered aromatic heterocyclic groups and the cyclic structure may be ⁇ substituted with one or more substituents which are the same or different.
  • each of the above-mentioned groups and structure may be substituted with, for example, and without limitation, one to three substituents.
  • the one or more substituents for each of the above-mentioned groups and structure, which are the same or different, may be, for example, and without limitation, a halogen atom, a hydroxyl group, a thiol group, a nitro group, a nitrile group, a cyano group; a Ci_ 6 alkyl, C2- 6 alkenyl or C 2 - 6 alkynyl group which may be substituted; a C 3 - 8 cycloalkyl or C 3 _ 8 cycloalkenyl group which may be substituted; a C 6 _ 14 aryl group which may be substituted; a C 6 -i4 aryl-Ci- 6 alkyl, C 6 -I 4 aryl-C 2 - 6 alkenyl or C 6 _ 14 aryl-C 2 -6 alkynyl group which may be.
  • R 1 may be, for example, and without limitation, a hydrogen atom.
  • R 2 may be, for example, and without limitation, PhCH2, CH 3 CH 2 or CH 3 CH 2 CH 2 .
  • the other aldehyde or ketone may be, for example, and without limitation, a compound of formula (III) : (m) wherein R 3 and R 4 may independently be, for example, and without limitation, a hydrogen atom, a Ci_6 alkyl group which may be substituted with one or more substituents which are the same or different, a C 2 - 6 alkenyl group which may be substituted with one or more substituents which are the same or different, a C2-6 alkynyl group which may be substituted with one or more substituents which are the same or different, a C 3 -g cycloalkyl group which may be substituted with one or more substituents which are the same or different, a C 3 -8 cycloalkenyl group which may be substituted with one or more substituents which are the same or different, a Ce-n aryl group which may be substituted with one or more substituents which are the same or different, a C6- 1 4 aryl
  • R 1 may be Ph
  • R 2 may be a hydrogen atom
  • R 3 and R 4 which are different, may be a hydrogen atom or cyclopropyl .
  • R 1 may be methyl
  • R 2 may be a hydrogen atom
  • R 3 and R 4 which are different, may be a hydrogen atom or cyclohexyl.
  • the other aldehyde or ketone may be, for example, and without limitation, a compound of formula (II) : wherein R 1 and R 2 are as defined anywhere above.
  • R 1 may be, for example, and without limitation, a hydrogen atom.
  • R 2 may be, for example, and without limitation, PhCH 2 , CH 3 CH 2 or CH 3 CH 2 CH 2 .
  • the ⁇ -unsubstituted aldehyde may be, for example, and without limitation, a compound of formula (VI) : wherein R 5 may be, for example, and without limitation, a hydrogen atom, a Ci- 6 alkyl group which may be substituted.
  • R 5 may be, for example, and without limitation, PhCH 2 , CH 3 CH 2 or CH 3 CH 2 CH 2 .
  • a product of aldol condensation may be, for example, and without limitation, an ⁇ , ⁇ -unsaturated aldehyde or ketone. In an embodiment, a product of aldol condensation may be, for example, and without limitation, an ⁇ , ⁇ -unsaturated aldehyde.
  • a product of aldol condensation may be, for example, and without limitation, a compound of
  • R 1 , R 2 , R 3 and R 4 are as defined anywhere above.
  • a product of aldol condensation may be, for example, and without limitation, a compound of formula (IV) :
  • R 1 and R 2 are as defined anywhere above.
  • a product of aldol condensation may be, for example, and without limitation, a compound of formula (XI) : wherein R is as defined anywhere above.
  • the aldol condensation may be, for example, and without limitation, conducted under dry reaction conditions.
  • dry reaction conditions would be understood to and can be determined by those of ordinary skill in the art.
  • dry reaction conditions may involve, for example, and without limitation, using a dry solvent or molecular sieves or a combination thereof.
  • the aldol condensation may be, for example, and without limitation, conducted in the presence of a solvent.
  • a solvent Suitable solvents would be understood to and can be determined by those of ordinary skill in the art.
  • the solvent may be, for example, and without limitation, a polar solvent.
  • the solvent may be, for example, and without limitation, tetrahydrofur . an (THF), methanol, N,N-dimethylformamide (DMF) , dichloromethane (CH 2 CI 2 ) , toluene or a combination thereof.
  • the solvent may be, for example, THF, methanol, DMF, dichloromethane or a combination thereof.
  • the solvent may be, for example, DMF and methanol.
  • the aldol condensation may be, for example, and without limitation, conducted in the presence of an organocatalyst .
  • organocatalyst Suitable organocatalysts would be understood to and can be determined by those of ordinary skill in the art.
  • the organocatalyst may be, for example, and without limitation, a proline, proline methylester or imidazolidinone catalyst.
  • the organocatalyst may be, for example, and without limitation, a proline catalyst.
  • the organocatalyst may be, for example, L- proline.
  • the amount of the organocatalyst used in the invention is not particularly limited and suitable amounts of the organocatalyst would be understood to and can be determined by those of ordinary skill in the art.
  • the amount of the organocatalyst may include, for example, and without limitation, from less than about 30 mol%, between about 0.1 to 20 mol%, between about 10 to 20 mol%, and including any specific value within these ranges, such as, for example, 30 mol%, 20 mol%, 10 mol% or 5 mol%.
  • ⁇ -unsubstituted aldehyde or ketone and the other aldehyde or ketone in the aldol condensation would be understood to and can be determined by those of ordinary skill in the art.
  • the ⁇ -unsubstituted aldehyde or ketone and the other aldehyde or ketone may be used in accordance with their stoichiometric ratios.
  • reaction time is not particularly limited and suitable reaction times would be understood to and can be determined by those of ordinary skill in the art.
  • the reaction time may be, for example, and without limitation, less than about 36 hours, less than about 24 hours, between about 1 to 36 hours, between about 1 to 24 hours, between about 16 to 36 hours, between about 16 to 24 hours, and including any specific time within these ranges, such as, for example, and without limitation, 36 hours, 24 hours, 18 hours or 16 hours.
  • reaction temperature is not particularly limited and suitable reaction temperatures would be understood to and can be determined by those of ordinary skill in the art.
  • the reaction temperature may be, for example, and without limitation, less than about 60 0 C, and including any specific value within this range, such as for example, and without limitation, room temperature.
  • the reaction temperature may be, for example, room temperature.
  • the process may optionally comprise separating the aldol condensation product from the reaction mixture, for example, and without limitation, by filtration, chromatographic separation, recrystallization or other suitable separation processes.
  • a domino reaction may include, for example, and without limitation, a process involving two or more bond-forming transformations which take place under the same reaction conditions without adding additional reagents and catalysts, and in which the subsequent reactions result as a consequence of the functionality formed in the previous step.
  • the process for aldol condensation may be, for example, and without limitation, used in a continuous domino reaction.
  • the process for aldol condensation may be used, for example, and without limitation, for the synthesis of a substituted pyrrole.
  • the synthesis of a substituted pyrrole may comprise, for example, and without limitation, mixing, in any order, an ⁇ -unsubstituted aldehyde or ketone, another aldehyde or ketone, an organocatalyst , an amine-containing compound and a nitroalkane.
  • the synthesis of a substituted pyrrole may comprise, for example, and without limitation, mixing, in any order, an ⁇ -unsubstituted aldehyde or ketone, another aldehyde or ketone, and an organocatalyst, and then mixing, in any order, an amine- containing compound and a nitroalkane.
  • the ⁇ -unsubstituted aldehyde or ketone may be, for example, and without limitation, a compound of formula (II) , wherein R 1 and R 2 may be as defined anywhere above, and may be mixed with, for example and without limitation, another aldehyde which may be, for example, and without limitation, a compound of formula (III) , wherein R 3 may be as defined anywhere above and R 4 may be hydrogen.
  • the ⁇ -unsubstituted aldehyde may be, for example, and without limitation, a compound of formula (VI), wherein R 5 may be as defined anywhere above, and may be mixed with, for example, and without limitation, another aldehyde which may be the same compound.
  • the amine-containing compound may be, for example, and without limitation, a compound of formula (VII) :
  • R 6 may have, for example, and without limitation, the same meaning as R 5 as defined anywhere above.
  • R 6 may be, for example, butyl, allyl or PhCH 2 .
  • the nitroalkane may be, for example, and without limitation, a compound of formula (VIII) :
  • R 7 may be, for example, and without limitation, a Ci-6 alkyl group which may be substituted with one or more substituents which are the same or different, or a Ci-6 alkoxycarbonyl group.
  • the Ci_ 6 alkoxy of the Ci_ 6 alkoxycarbonyl group may be Ci- 6 alkyl as defined anywhere above bonded to oxygen.
  • R 7 may be, for example, ethoxycarbonyl (COOEt) .
  • the substituted pyrrole may be, for example, and without limitation, a compound of formula
  • R 1 , R 2 , R 3 , R 6 and R 7 may be as defined anywhere above .
  • the substituted pyrrole may be, for example, and without limitation, a compound of formula (V) :
  • R 5 , R 6 and R 7 may be as defined anywhere above.
  • reaction conditions for aldol condensation as described anywhere above may be used, for example, and without limitation, as the reaction conditions for aldol condensation for the preparation of the substituted pyrrole.
  • mixing of the amine-containing compound and the nitroalkane may involve, for example, and without limitation, ultrasonification.
  • reaction time for the amine-containing compound and the nitroalkane is not particularly limited and suitable reaction times would be understood to and can be determined by those of ordinary skill in the art.
  • the reaction time may be, for example, and without limitation, less than about 10 hours, less than about 8 hours, between about 1 to 8 hours, between about 2 to 8 hours, and including any specific time within these ranges, such as, for example, 2 hours, 4 hours, 6 hours or 8 hours .
  • reaction temperature for mixing of the amine- containing compound and the nitroalkane is not particularly limited and suitable reaction temperatures would be understood to and can be determined by those of ordinary- skill in the art.
  • the reaction temperature may be, for example, and without limitation, room temperature.
  • Suitable amounts of the amine-containing compound and the nitroalkane which may be used in the invention are not particularly limited. Suitable amounts would . be understood to and can be determined by those of ordinary skill in the art.
  • the process for aldol condensation and for preparing the substituted pyrrole may be, for example, and without limitation, a one-pot process.
  • the process may optionally comprise separating the substituted pyrrole product from the reaction mixture, for example, and without limitation, by filtration, chromatographic separation, recrystallization or other suitable separation processes.
  • the process for aldol condensation may be used, for example, and without limitation, for arylation of an ⁇ , ⁇ -unsaturated aldehyde.
  • the process for arylation of an a, ⁇ - unsaturated aldehyde may comprise, for example, and without limitation, mixing, in any order, an ⁇ -unsubstituted aldehyde, an organocatalyst, an aryl halide, an organometallic catalyst and a base.
  • the process for arylation of an ⁇ , ⁇ -unsaturated aldehyde may comprise, for example, and without limitation, mixing an ⁇ - unsubstituted aldehyde and an organocatalyst, and further mixing, in any order, an aryl halide, an organometallic catalyst and a base.
  • the ⁇ -unsubstituted aldehyde may be, for example, and without limitation, a compound of formula (VI), wherein R 5 may be as defined anywhere above.
  • the aryl halide may be, for example, and without limitation, a compound of formula (X) :
  • X-R8 (X) wherein X, may be, for example, and without limitation, a halogen atom, and R 8 may be, for example, and without limitation, an Ce-u aryl group which may be substituted with one or more substituents which are the same or different.
  • X may be, for example, and without limitation, fluorine, chlorine, bromine or iodine.
  • X may be, for example, bromine.
  • R 8 may be, for example, Ph.
  • the product may be, for example, and without limitation, compound of formula (IX) :
  • R 5 and R 8 may be, for example, and without limitation, as defined anywhere above.
  • the organometallic catalyst may be, for example, and without limitation, a palladium catalyst.
  • the organometallic catalyst may be, for example, palladium acetate (Pd(OAc) 2 ) /tri-t-butylphosphine (P( 11 Bu) 3 ).
  • the amount of the organometallic catalyst used in the invention is not particularly limited and suitable amounts of the organometallic catalyst would be understood to and can be determined by those of ordinary skill in the art.
  • the amount of the organometallic catalyst may include, for example, and without limitation, from less than about 10 mol%, less than about 5 mol%, between about 0.1 to 10 mol%, between about 0.1 to 5 mol%, between about 1 to 5 mol% and including any specific value within these ranges, such as, for example, 5 mol%.
  • Suitable bases would be understood to and can be determined by those of ordinary skill in the art.
  • the base may be, for example, and without limitation, CS 2 CO 3 , K 2 CO 3 or Na 2 CO 3 .
  • the base may be, for example, CS 2 CO 3 .
  • reaction conditions for aldol condensation as described anywhere above may be used, for example, and without limitation, as the reaction conditions for aldol condensation for arylation of the ⁇ , ⁇ -unsaturated aldehyde.
  • reaction time for arylation of the ⁇ , ⁇ - unsaturated aldehyde is not particularly limited and suitable reaction times would be understood to and can be determined by those of ordinary skill in the art.
  • the reaction time may be, for example, and without limitation, less than about 36 hours, less than about 24 hours, between about 1 to 36 hours, between about 1 to 24 hours, between about 16 to 36 hours, between about 16 to 24 hours, and including any specific time within these ranges, such as, for example, 36 hours, 24 hours, 18 hours or 16 hours.
  • reaction temperature for arylation of the ⁇ , ⁇ - unsaturated aldehyde is not particularly limited and suitable reaction temperatures wo.uld be understood to and- can be determined by those of ordinary skill in the art.
  • the reaction temperature may be, for example, and without limitation, 80°C.
  • Suitable amounts of the aryl halide and base which may be used in the invention are not particularly limited. Suitable amounts would be understood to and can be determined by those of ordinary skill in the art.
  • the process for aldol condensation and for arylation of the a, ⁇ -unsaturated aldehyde may be, for example, and without limitation, a one- pot process.
  • the process for aldol condensation and for arylation of the ⁇ , ⁇ -unsaturated aldehyde may optionally comprise separating the product from the reaction mixture, for example, and without limitation, by filtration, chromatographic separation, recrystallization or other suitable separation processes.
  • GC-MS Gas chromatography-mass spectrometry
  • GLC Gas liquid chromatography
  • a highly efficient organocatalysis and organometallic catalysis domino reaction involving proline catalyzed aldol condensation of simple aldeydes to form ⁇ , ⁇ -unsaturated enals and followed by palladium catalyzed arylation of the ⁇ -position of a, ⁇ -unsaturated enal with aryl bromide, was developed.
  • the invention includes isomers such as geometrical isomers, optical isomers based on asymmetric carbon, stereoisomers and tautomers and is not limited by the description of the formula illustrated for the sake of convenience.

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Abstract

L'invention concerne un procédé de condensation d'aldol, consistant à mélanger un aldéhyde ou une cétone α-non substitué(e) avec un autre aldéhyde ou cétone dans des conditions de réaction sèche, en présence d'un organocatalyseur. Ce procédé de condensation d'aldol peut être mis en œuvre pour des réactions domino, notamment dans la préparation de pyrroles substitués et dans l'arylation d'énals α,β-insaturés.
PCT/SG2008/000230 2007-06-28 2008-06-27 Procede de condensation d'aldol mis en œuvre dans la preparation d'aldehyde ou de cetone α,β-insature(e) et son utilisation dans la synthese de pyrrole substitue ou l'arylation d'enal α,β-insature WO2009002276A1 (fr)

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