CA2346379A1 - Substituted isophosphindolines and their use - Google Patents
Substituted isophosphindolines and their use Download PDFInfo
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- CA2346379A1 CA2346379A1 CA002346379A CA2346379A CA2346379A1 CA 2346379 A1 CA2346379 A1 CA 2346379A1 CA 002346379 A CA002346379 A CA 002346379A CA 2346379 A CA2346379 A CA 2346379A CA 2346379 A1 CA2346379 A1 CA 2346379A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6568—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms
- C07F9/65683—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms the ring phosphorus atom being part of a phosphine
Abstract
The invention relates to complex compounds containing substituted isophosphinolines according to formula (VII) or (XIII). In general formula (VII), R means hydrogen, alkyl-, aryl-, haloaryl-, haloalkyl groups, R' mean s alkyl-, aryl-, haloaryl-, haloalkyl groups, R'' and R''' mean, independently of each other, hydrogen, alkyl-, aryl-, haloalkyl- or haloaryl-, alkoxy-, amino-, dialkylamino-, sulfonate groups or fluorine and two adjacent R''/R'' , R''/R''' or R'''/R'''s can also be bridged, or in general formula (XIII), R' means alkyl-, aryl-, haloaryl-, haloalkyl groups, R'' and R''' mean, independently of each other, hydrogen, alkyl-, aryl-, haloalkyl- or haloaryl -, alkoxy-, amino-, dialkylamino-, sulfonate groups or fluorine and two adjacen t R''/R'', R''/R''' or R'''/R''' can also be bridged and R'''' is an alkanediy l- , arenediyl- or hetarenediyl group, the term alkyl or haloalkyl group including the corresponding cyclo-compounds. The invention also relates to t he use of complex compounds of this type as catalysts.
Description
Substituted isophosphindolines and their use Description The invention relates to substituted isophosphindolines and their metal complexes.
Phosphorus compounds, in particular trisubstituted phosphines, have great importance as ligands in homogeneous catalysis. Variation of the substituents on the phosphorus in such phosphorus compounds enables the electronic and stearic properties of the phosphorus ligand to be influenced in a targeted way, so that selectivity and activity in homogeneously catalyzed processes can be controlled.
The variety of structures of phosphorus ligands known hitherto is very great. These ligands can, for example, be classified by class of compound, and examples of such classes of compounds are trialkylphosphines and triarylphosphines, phosphites, phosphonites, etc. This classification according to classes of compounds is particularly useful for describing the electronic properties of the ligands.
Classification of phosphorus ligands according to their symmetry properties or according to the number of coordination positions occupied by the ligands is also possible. This structuring takes account of, in particular, the stability, activity and (potential) stereoselectivity of metal complexes bearing phosphorus ligands as catalyst precursors/catalysts.
Enantiomerically enriched chiral ligands are used in asymmetric synthesis or asymmetric catalysis; an important aspect here is that the electronic and the stereochemical properties of the ligand are optimally matched to the respective catalysis problem. There is a great need for chiral ligands which differ stereochemically or/and electronically in order to find the optimum "tailored" ligands for a particular asymmetric catalysis. In the ideal case, therefore, one has available a flexibly modifiable, chiral ligand skeleton whose stearic and electronic properties can be varied within a wide range.
Examples of such a basic ligand skeleton are metallocene catalysts for stereoselective olefin polymerization or for asymmetric catalysis.
REPLACEMENT SHEET (RULE 26) Within the class of cyclic phosphines, the phospholines have achieved particular importance. Examples of bidentate, chiral phospholines are the DuPhos and BPE ligands used in asymmetric catalysis (Burk et al., Specialty Chemicals, 1998, 58). Although these can be varied stearically within a relatively broad range, they can be varied electronically to only a very limited extent, i.e. by replacement of the arenediyl backbone in the DuPhos ligands by an ethane-1,2-diyl backbone in the BPE ligands.
The class of isophosphindolines of the formula (I) is quite similar to that of the phospholines, but is known from the literature in the form of only a few representatives: thus, known compounds are, for example the parent compound isophosphindoline of the formula (la) (Robinson et al., J.
Heterocycl. Chem., 1973, 395) and alkyl or aryl derivatives of isophosphindoline of the formula (Ib, Ic) (Mann et al., J. Chem. Soc., 1954, 2832; Schmidbaur et al., J. Organomet. Chem. 250, 1983, 171; Breen et al., J. Am. Chem. Soc., 1995, 11914), also phosphonium salts of the isophosphindoline of the formula (II) (Mann et al., J. Chem. Soc., 1954, 2832; ibid. 1958, 2516; Schmidbaur et al., J. Organomet. Chem. 250, 1983, 171).
-- ~ , _ n:
t ~.' /\~'~ \ R
In formula (la), R is hydrogen, while in the formulae (Ib/c) and (II), R is an alkyl or aryl radical.
Representatives which are substituted on the aliphatic carbon skeleton of the isophosphindoline are likewise known, but the compounds known hitherto are either monosubstituted derivatives of the formula (III) (Fluck et al., Phosphorous Sulfur, 1987, 121; Ouin et al., J. Org. Chem., 1986, 3235) or derivatives of the formula (IV) which are mentioned in WO 96/16100 and WO 96/23829 but have obviously not been synthesized hitherto.
Phosphorus compounds, in particular trisubstituted phosphines, have great importance as ligands in homogeneous catalysis. Variation of the substituents on the phosphorus in such phosphorus compounds enables the electronic and stearic properties of the phosphorus ligand to be influenced in a targeted way, so that selectivity and activity in homogeneously catalyzed processes can be controlled.
The variety of structures of phosphorus ligands known hitherto is very great. These ligands can, for example, be classified by class of compound, and examples of such classes of compounds are trialkylphosphines and triarylphosphines, phosphites, phosphonites, etc. This classification according to classes of compounds is particularly useful for describing the electronic properties of the ligands.
Classification of phosphorus ligands according to their symmetry properties or according to the number of coordination positions occupied by the ligands is also possible. This structuring takes account of, in particular, the stability, activity and (potential) stereoselectivity of metal complexes bearing phosphorus ligands as catalyst precursors/catalysts.
Enantiomerically enriched chiral ligands are used in asymmetric synthesis or asymmetric catalysis; an important aspect here is that the electronic and the stereochemical properties of the ligand are optimally matched to the respective catalysis problem. There is a great need for chiral ligands which differ stereochemically or/and electronically in order to find the optimum "tailored" ligands for a particular asymmetric catalysis. In the ideal case, therefore, one has available a flexibly modifiable, chiral ligand skeleton whose stearic and electronic properties can be varied within a wide range.
Examples of such a basic ligand skeleton are metallocene catalysts for stereoselective olefin polymerization or for asymmetric catalysis.
REPLACEMENT SHEET (RULE 26) Within the class of cyclic phosphines, the phospholines have achieved particular importance. Examples of bidentate, chiral phospholines are the DuPhos and BPE ligands used in asymmetric catalysis (Burk et al., Specialty Chemicals, 1998, 58). Although these can be varied stearically within a relatively broad range, they can be varied electronically to only a very limited extent, i.e. by replacement of the arenediyl backbone in the DuPhos ligands by an ethane-1,2-diyl backbone in the BPE ligands.
The class of isophosphindolines of the formula (I) is quite similar to that of the phospholines, but is known from the literature in the form of only a few representatives: thus, known compounds are, for example the parent compound isophosphindoline of the formula (la) (Robinson et al., J.
Heterocycl. Chem., 1973, 395) and alkyl or aryl derivatives of isophosphindoline of the formula (Ib, Ic) (Mann et al., J. Chem. Soc., 1954, 2832; Schmidbaur et al., J. Organomet. Chem. 250, 1983, 171; Breen et al., J. Am. Chem. Soc., 1995, 11914), also phosphonium salts of the isophosphindoline of the formula (II) (Mann et al., J. Chem. Soc., 1954, 2832; ibid. 1958, 2516; Schmidbaur et al., J. Organomet. Chem. 250, 1983, 171).
-- ~ , _ n:
t ~.' /\~'~ \ R
In formula (la), R is hydrogen, while in the formulae (Ib/c) and (II), R is an alkyl or aryl radical.
Representatives which are substituted on the aliphatic carbon skeleton of the isophosphindoline are likewise known, but the compounds known hitherto are either monosubstituted derivatives of the formula (III) (Fluck et al., Phosphorous Sulfur, 1987, 121; Ouin et al., J. Org. Chem., 1986, 3235) or derivatives of the formula (IV) which are mentioned in WO 96/16100 and WO 96/23829 but have obviously not been synthesized hitherto.
R' R"
P-R i ~/P-R
/ /
R, R... R,."
(III) (IV) 1,3-Disubstituted isophosphindolines (V) have previously only been known in the form of their phosphine oxides (Vla, Vlb) (Holland et al., J. Chem.
Soc. Perkin Trans. 1, 1973, 927):
R~~ H R,\ .H
W
P-R ; ! P
i , ~~ ~- , R
R' ~/ 'H R' ~ H
R' = Ph. R = Me: (V1a) R' = Ph, R ~ Ph: (Vlb) (V) (V1) The 1,3-disubstituted isophosphindolines of the formula (V), which have not been described hitherto, are achiral if the two asymmetric centers on C1 and C3 have different (opposite) absolute configurations (meso form). The remaining representatives are chiral (c2 symmetry). The chiral representatives are of particular importance since they can be used as ligands in asymmetric, catalytic syntheses.
Like the substances of the formula (V), their derivatives substituted on the aromatic carbon skeleton have also not been described hitherto.
The previously known and used phospholine ligands DuPhos and BPE
have, as mentioned above, the disadvantage that their electronic properties can be varied to only a very small extent. It is therefore an object of the present invention to provide a basic ligand skeleton which can be varied in a manner analogous to the previously known phospholine ligands but also be varied electronically within a wide range.
November 16, 2000 4 EP 009907084 This object is achieved by the provision of substituted isophosphindolines of the formula (VII) or (X111), R.. R, H R~~ R, H H R, R..
R.., \ R.., \ \ . R.,.
~P_R I ~ ~P_R...._P
R... ~ R.,. ~ ~ R,..
R,. R' H R.. R' H H R' R..
(vn) (xui) where, in the formula (VII), R is hydrogen or an alkyl, aryl, haloaryl or haloalkyl group, R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and, in the formula (X111) R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and R"" is an alkanediyl, arenediyl or heteroarenediyl group.
For the present purposes, alkyl and haloalkyl groups include the corresponding cyclo compounds. Particular preference is given to chiral substituted isophosphindolines.
The substituted isophosphindoline of the invention preferably bears alkyl, aryl, haloaryl, haloalkyl, alkoxy or/and dialkylamino groups which are AMENDED SHEET
November 16, 2000 5 EP 009907084 selected independently of one another and each contain from 1 to 20, in particular from 1 to 6, carbon atoms.
The haloalkyl or/and haloaryl groups preferably have the formulae CHal3, CH2CHal3, C2Hal5, where Hal can be, in particular, F, CI or Br. Particular preference is given to haloalkyl or/and haloaryl groups of the formulae CF3, CH2CFg, C2F5.
It is also preferred that the alkanediyl, arenediyl or heteroarenediyl group R"" of the substituted isophosphindoline has from 2 to 20 carbon atoms, more preferably 2, 3, 4, 5 or 6 carbon atoms, in particular 2 or 6 carbon atoms. Ethane-1,2-diyl, benzene-1,2-diyl or furan-3,4-diyl are particularly preferred examples of alkanediyl, arenediyl or heteroarenediyl groups R"".
Furthermore, preference is given to a substituted isophosphindoline in which R is phenyl, R' is methyl or ethyl, R" and R"' is hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl. Particular preference is given to a substituted isophosphindoline in which R is phenyl, R' is methyl or ethyl, R" and R"' are hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl, in which R" and R"' are not hydrogen or in which either R" or R"' is hydrogen.
Furthermore, preference is given to substituted isophosphindolines whose asymmetric centers in the 1 and 3 positions have the same absolute configuration. The substituted isophosphindoline of the formula (VII) has two asymmetric centers having the same absolute configuration in positions 1 and 3, while in the case of those of the formula (X111), each has two or four asymmetric centers having the same absolute configuration in the positions 1, 1', 3 and 3'.
Finally, preference is given to substituted chiral isophosphindolines which are enriched in one enantiomer.
AMENDED SHEET
WO 00/21971 5a PCT/EP99/07084 r and each contain from t~
particular from 1 to 6, carbon atoms.
The haloalkyl or/and haloaryl groups preferably have the for ulae CHal3, CH2CHal3, C2Hal5, where Hal can be, in particular, F, CI r Br. Particular preference is given to haloalkyl or/and haloaryl groups o he formulae CFg, CH2CFg, C2F5.
It is also preferred that the alkanediyl, arened~ or heteroarenediyl group R"" of the substituted isophosphindoline ha~rom 2 to 20 carbon atoms, more preferably 2, 3, 4, 5 or 6 carbon atp~Fns, in particular 2 or 6 carbon atoms. Ethane-1,2-diyl, benzene-1,2-d~~ or furan-3,4-diyl are particularly preferred examples of alkanediyl, areyfediyl or heteroarenediyl groups R"".
Furthermore, preference is giv n to a substituted isophosphindoline in which R is phenyl, R' is met I or ethyl, R" and R"' is hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl. Particular preference is given to a substituted isophosphin~oline in which R is phenyl, R' is methyl or ethyl, R" and R"' are hydroge~ methyl or/and phenylene, R"" is benzene-1,2-diyl, in which R" and R"'; pare not hydrogen or in which either R" or R"' is hydrogen.
Furthermore, pr ference is given to substituted isophosphindolines whose asymmetric c nters in the 1 and 3 positions have the same absolute configuratio . The substituted isophosphindoline of the formula (VII) has two asy etric centers having the same absolute configuration in position 1 and 3, while in the case of those of the formula (X111), each has two our asymmetric centers having the same absolute configuration in the plositions 1, 1', 3 and 3'.
~nally, preference is given to substituted chiral isophosphindolines which are enriched in_onP Pnantiomer.
The substituents R' in the substances of the formulae (VII) and (X111) are essential for the steric properties of the ligands, while the other substituents R, R"> R"' and R"" essentially determine the electronic properties by means of their donor or acceptor capabilities, and thus allow, as explained above, the reactivity, selectivity and application range in respect of substrates in catalytic reactions to be influenced over a wide range.
A further substantial difference between the compounds of the formulae (VII) and (X111) on the one hand and phospholines on the other hand is the greater rigidity of the five-membered heterocyclic ring in the compounds of the formulae (VII) and (X111), which in attributable to the replacement of the ethanediyl backbone in the phospholines by the benzene-1,2-diyl substituent in the substances of the formulae (VII) and (X111).
Representatives of the class of compounds of the formula (VII), which encompasses not only compounds of the formula (V) but also corresponding compounds substituted in the fused-on aromatic ring, have been prepared. In cases where these are chiral, the compounds have also been synthesized in a form enriched in one enantiomer.
R., R. H
R." ~\~~
a.., ~~ ; P R
R"
(VII) A number of routes are available for the synthesis of the substituted isophosphindolines of the formula (VII): for example, either the corresponding phthalic dialdehyde of the formula (VIII) or the corresponding diketone of the formula (IX) can be used as starting material.
The reaction of the phthalic dialdehyde of the formula (VIII) with two equivalents of Grignard R'-M gives firstly the corresponding dialkoxide of the formula (X) which can be reacted further to give the cyclic sulfate of the formula (XII).
Starting from the diketone of the formula (IX), this is firstly reduced by means of boron compounds or analogous compounds to give the boronic acid derivative (XI) which can likewise be converted into the cyclic sulfate (XII).
A single representative of the sulfates of the formula (XII) is a previously known compound in which R' = methyl and R" - R"' - H and which is mentioned in WO 97/13763, page 7.
Depending on reaction conditions, synthetic route and reagent, the sulfate of the formula (XII) is obtained as a mixture of diastereomers (meso/rac form) or/and enantiomers; separation of the isomers gives the stereochemically pure sulfate of the formula (XII).
R" O R" OM
R.,. \ H R... \ R, R... ( / H R... I / R' R.. R.
R" O R" OM R"' / O
(vul) (x) soy R.. O R.. R.1 R..~~O
R... I\ R, R... ~ ~ O ~ R.. R.~
R... ~ ~ R~ ~R..,. \ ~ oB X {XII) .
i ;
R" O R" R' 1. BuLi / RPH
(IX) (Xl) ~ 2. BuLi R.. R. H
R,., \ \
I'i /~P-R
R.,, i R" R' / \H
(VII) In a modification of k wn processes (Burk US 5,386,061 ), reaction of the sulfate of the for a (XII) with phosphines of the formula RPH2 (R = alkyl, aryl, hetero I) gives, via the corresponding phosphides, the correspon ' g substituted isophosphindoline.
November 16, 2000 7U EP 009907084 R" O R" OM
l R... ~ \ H ~ R... ~ \ R.
R... ~ H R... ~ R' R.. R.
R... / O
R" O R" OM
(VIII) (X) I ~ soy R.. O R.. R~ R...i ~ O
R... I R... I ' R, / O R~~ R.
R... ~ ~Y R~~ R..., ~ ~ 0 6 X ~ (XII) i /
R" O R" R' ' 1. BuLi / RPHz (IX) (XI) I 2. BuLi R.. R. H
R,., ~
~/~P-R
R... ~~~
R., R' H
(VII) In a modification of known processes (Burk US 5,386,061 ), reaction of the sulfate of the formula (XII) with phosphines of the formula RPH2 (R = alkyl, aryl, heteroarenediyl) gives, via the corresponding phosphides, the corresponding substituted isophosphindoline.
It is likewise possible to convert the isomer mixture of the sulfate of the formula (XII) into the corresponding mixture of isomeric isophosphindolines AMENDED SHEET
November 16, 2000 8 EP 009~a07084 and then to carry out a separation in order to obtain stereochemica'~y pure substituted isophosphindolines. This separation can be achie~r :d, for example, by fractional crystallization and/or chromatographically.
As phosphines of the formula RPH2, it is possible to use all types of arylphosphines and alkylphosphines as starting materials (R = aryl, alkyl).
If, instead of these, diphosphines of the formula H2P=R""-PH2 are used, the products are chelating ligands of the formula (X111) which in the case of c2-symmetric sulfates of the formula (XII) lead to chiral and then likewise c2-symmetric chelating ligands.
R, H H R, R,.
R... \ \ R...
I ' R... % \ " ~ R."
R' N H R' R~~ R., (X111) The compounds of the formulae (VII) and (X111) can be used as ligands on metals in asymmetric, metal-catalyzed reactions (e.g. asymmetric hydrogenation, transfer hydrogenations, asymmetric rearrangement, asymmetric cyclopropanation or Heck reactions) and in polymerizations.
They are particularly useful far asymmetric reactions.
The ligands of the formulae (VII) and (X111) form complexes of the type (XIV), [MxPm~nSq~Yr (XIV) where, in the formula (XIV), M is a metal center, preferably a transition metal center, L are identical or different coordinating organic or inorganic ligands and P are organic ligands, according to the invention isophosphindolines of the type (VII) or (X111), S are coordinating solvent molecules and Y are equivalents of noncoordinating anions, where x and m are integers greater than or equal to 1, n, q and r are integers greater than or equal to 0.
AMENDED SHEET
November 16, 2000 9 EP 009907084 The maximum value of the sum m + n + q is determined by the number of coordination sites available on the metal centers, but not all coordination AMENDED SHEET
sites have to be occupied. Preference is given to complexes having an "~ CA 02346379 2001-04-06 WO 00/21971 9a PCT/EP99/07084 0 1~, n, ~q and r are integers~gr~a~r~~ttl'a r equal to 0.
~'he maximum value of t~,fa,~-scrrr~i~m~+ n + q is determined by the number c oordination s~available on the metal centers, but not all coordinatio ~te$ .ba'~Te t~O'°~-'O'CCUDfe~l--RfA#A~t'-~RE6....~.~.u~A. fn nnrr,n~ac.~c haVjrlll a ~c#a~h~a~l,, pseudo octahedral, tetrahedral, pseudo tetrahedral or square planar coordination sphere, which may also be distorted, around the respective transition metal center. In such complexes, the sum m + n + q is smaller than or equal to 6x.
The complexes of the present invention contain at least one metal atom or ion, preferably a transition metal atom or ion, in particular one selected from the group consisting of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel and copper.
Preference is given to complexes having less than four metal centers, particularly preferably ones having one or more two metal centers. The metal centers can be occupied by various metal atoms and ions.
Preferred ligands L in such complexes are halide, particularly CI, Br and I, diene, particularly cyclooctadiene, norbornadiene, olefin, particularly ethylene and cyclooctene, acetato, trifluoroacetato, acetylacetonato, allyl, methylallyl, alkyl, particularly methyl and ethyl, nitrite, particularly acetonitrile and benzonitrile, and also carbonyl and hydrido ligands.
Preferred coordinating solvents S are amines, particularly triethylamine, alcohols, particularly methanol, and aromatics, particularly benzene and cumene.
Preferred noncoordinating anions Y are trifluoroacetate, BF4, C104, PFg and BAr4.
In the individual complexes, different molecules, atoms or ions of the individual constituents M, P, L, S and Y may be present.
WO 00/21971 10 PCT/EP99/070$4 Among the ionic complexes, preference is given to compounds of the type [RhPm(diene)]+Y , where Pm represents either two isophosphindolines of the type (VII) or one isophosphindoline of the type (X111).
These metal-ligand complexes can be prepared in situ by reaction of a metal salt or an appropriate precursor complex with the ligands of the formulae (VII) and (X111). Alternatively, a metal-ligand complex can be obtained by reaction of a metal salt or an appropriate precursor complex with the ligands of the formula (VII) and (X111) and subsequent isolation.
Examples of metal salts are metal chlorides, bromides, iodides, cyanides, nitrates, acetates, acetylacetonates, hexafluoroacetylacetonates, perfluoroacetates or triflates, in particular of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel and/or copper.
Examples of precursor complexes are:
cyclooctadienepalladium chloride, cyclooctadienepalladium iodide, 1,5-hexadienepalladium chloride, 1,5-hexadienepalladium iodide, bis(dibenzylideneacetone)palladium, bis(benzonitrile)palladium(II) chloride, bis(benzonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) iodide, bis(allyl)palladium, bis(methallyl)palladium, allylpalladium chloride dimer, methallylpalladium chloride dimer, tetramethylethylenediaminepalladium dichloride, tetramethylethylenediaminepalladium dibromide, tetramethylethylenediaminepalladium diiodide, (tetramethylethylenediamine)dimethylpalladium, cyclooctadieneplatinum chloride, cyclooctadieneplatinum iodide, 1,5-hexadieneplatinum chloride, 1,5-hexadieneplatinum iodide, bis(cyclooctadiene)platinum, potassium ethylenetrichloroplatinate, cyclooctadienerhodium(I) chloride dimer, norbornadienerhodium(I) chloride dimer, 1,5-hexadienerhodium(I) chloride dimer, tris(triphenylphosphine)rhodium(I) chloride, hydridocarbonyltris(triphenylphosphine)rhodium(I) chloride, bis(cyclooctadiene)rhodium(I) perchlorate, bis(cyclooctadiene)rhodium(I) tetrafluoroborate, -' CA 02346379 2001-04-06 bis(cyclooctadiene)rhodium(I) triflate, bis(acetonitrile)cyclooctadienerhodium(I) perchlorate, bis(acetonitrile)cyclooctadienerhodium(I) tetrafluoroborate, bis(acetonitrile)cyclooctadienerhodium(I) triflate, cyclopentadienerhodium(III) chloride dimer, pentamethylcyclopentadienerhodium(III) chloride dimer, (cyclooctadiene)Ru(rt3-allyl)2, ((cyclooctadiene)Ru)2(acetate)4, ((cyclooctadiene)Ru)2(trifluoroacetate)4, RuCl2(arene) dimer, tris(triphenylphosphine)ruthenium(II) chloride, cyclooctadieneruthenium(II) chloride, OsCl2(arene) dimer, cyclooctadieneiridium(I) chloride dimer, bis(cyclooctene)iridium(I) chloride dimer, bis(cyclooctadiene)nickel, (cyclododecatriene)nickel, tris(norbornene)nickel, nickel tetracarbonyl, nickel(II) acetylacetonate, (arene)copper triflate, (arene)copper perchlorate, (arene)copper trifluoroacetate, cobalt carbonyl.
The complexes based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, can be catalysts themselves or can be used for preparing catalysts based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu. All these complexes are particularly useful in the asymmetric hydrogenation of C=C, C=O or C=N bonds, in which they display high activities and selectivities. In particular, it is found to be advantageous that the ligands of the formula (X111) can be very well matched in stearic and electronic terms to the respective substrate due to the fact that they can easily be modified over a wide range.
Corresponding catalysts comprise at least one of the complexes of the invention.
Examples:
1. 1,2-bis(a-hydroxyethyl)benzene:
The preparation of 1,2-bis(u.-hydroxyethyl)benzene was carried out by literature methods: Goldschmidt et al., Chem. Ber. 1961, 94, 169.
2. Cyclic sulfate:
The preparation of the cyclic sulfate was carried out by the method of Burk (J. Am. Chem. Soc. 1993, 115, 10125) starting from 1,2-bis(a-hydroxyethyl)benzene.
38 mmol of thionyl chloride in 10 ml of CC14 are added dropwise to 31 mmol (5.1 g) of 1,2-bis(a-hydroxyethyl)benzene dissolved in 40 ml of CC14 over a period of 30 minutes. After refluxing for 2.5 hours and cooling, the solution is evaporated virtually to dryness. The residue is then taken up in CC14, acetonitrile, water (25 ml/25 mU35 ml) and cooled to 0°C. 0.20 mmol of RuCIg~H20 and 61 mml of Na104 are added one after the other to the cold mixture. After a reaction time of one hour, the reaction mixture is diluted with 170 ml of water, extracted four times with 100 ml each time of diethyl ether and the combined ether extracts are washed twice with 60 ml each time of saturated NaCI
solution. The extract solution is dried overnight over Na2S04 and subsequently evaporated to a reddish brown serum. Column chromatography using silica gel 60 as stationary phase and n-hexane/ethyl acetate 10:1 as mobile phase gives 1.0 g of pure racemic 1,2-bis(a-hydroxyethyl)benzene cyclosulfate (14°~0 of theory).
As a second method, the procedure of Zhang WO 97/13763 was employed. The yield of pure bis(a-hydroxyethyl)benzene cyclosulfate was 25%, and the 'H-NMR data reported in the literature could be reproduced.
~ H-NMR (400, 13 MHz, CDC13): b 1.92 (d, 6H, CH3), 5.56 (q, 2H, CH), 7.35 (m, 2H, CHar), 7.56 (m, 2H, CHar) ppm.
3. Isophosphindoline synthesis (modification of the method of Burk et al., J. Am. Chem. Soc. 1993, 115, 10125) 1.5 mmol of phenylphosphine are dissolved in 35 ml of kethyl-dried THF
and admixed with 0.94 ml of 1.6 M n-BuLi solution in n-hexane. After stirring for two hours at room temperature, this solution is added dropwise at -78°C to a mixture of 1.5 mmol (340 mg) of the cyclic sulfate and 20 ml of THF. Four hours after the addition was complete, another 1.09 ml of 1.6 M n-BuLi solution in n-hexane is added dropwise.
The solution is slowly warmed to room temperature overnight, and °°
excess organolithium compound is hydrolyzed using 1 ml of oxygen-free methanol. Complete evaporation of the solution gives a white residue which was firstly examined by means of 3'P-NMR as a guide.
This crude product contains many by-products in addition to the desired isophosphindoline.
31 P NMR (161.99 MHz, CDC13): S+21.7 ppm.
GC/MS (70 eV): m/e = 240 (100%, M+), 225 (25%, M+-15), 212 (9%), 192 (5%), 178 (6%), 165 (3%), 147 (16%), 131 (17%), 120 (10%), 115 (14%), 109 (12%), 91 (27%), 77 (32%), 65 (2%), 51 (2%), 39 (2%).
P-R i ~/P-R
/ /
R, R... R,."
(III) (IV) 1,3-Disubstituted isophosphindolines (V) have previously only been known in the form of their phosphine oxides (Vla, Vlb) (Holland et al., J. Chem.
Soc. Perkin Trans. 1, 1973, 927):
R~~ H R,\ .H
W
P-R ; ! P
i , ~~ ~- , R
R' ~/ 'H R' ~ H
R' = Ph. R = Me: (V1a) R' = Ph, R ~ Ph: (Vlb) (V) (V1) The 1,3-disubstituted isophosphindolines of the formula (V), which have not been described hitherto, are achiral if the two asymmetric centers on C1 and C3 have different (opposite) absolute configurations (meso form). The remaining representatives are chiral (c2 symmetry). The chiral representatives are of particular importance since they can be used as ligands in asymmetric, catalytic syntheses.
Like the substances of the formula (V), their derivatives substituted on the aromatic carbon skeleton have also not been described hitherto.
The previously known and used phospholine ligands DuPhos and BPE
have, as mentioned above, the disadvantage that their electronic properties can be varied to only a very small extent. It is therefore an object of the present invention to provide a basic ligand skeleton which can be varied in a manner analogous to the previously known phospholine ligands but also be varied electronically within a wide range.
November 16, 2000 4 EP 009907084 This object is achieved by the provision of substituted isophosphindolines of the formula (VII) or (X111), R.. R, H R~~ R, H H R, R..
R.., \ R.., \ \ . R.,.
~P_R I ~ ~P_R...._P
R... ~ R.,. ~ ~ R,..
R,. R' H R.. R' H H R' R..
(vn) (xui) where, in the formula (VII), R is hydrogen or an alkyl, aryl, haloaryl or haloalkyl group, R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and, in the formula (X111) R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and R"" is an alkanediyl, arenediyl or heteroarenediyl group.
For the present purposes, alkyl and haloalkyl groups include the corresponding cyclo compounds. Particular preference is given to chiral substituted isophosphindolines.
The substituted isophosphindoline of the invention preferably bears alkyl, aryl, haloaryl, haloalkyl, alkoxy or/and dialkylamino groups which are AMENDED SHEET
November 16, 2000 5 EP 009907084 selected independently of one another and each contain from 1 to 20, in particular from 1 to 6, carbon atoms.
The haloalkyl or/and haloaryl groups preferably have the formulae CHal3, CH2CHal3, C2Hal5, where Hal can be, in particular, F, CI or Br. Particular preference is given to haloalkyl or/and haloaryl groups of the formulae CF3, CH2CFg, C2F5.
It is also preferred that the alkanediyl, arenediyl or heteroarenediyl group R"" of the substituted isophosphindoline has from 2 to 20 carbon atoms, more preferably 2, 3, 4, 5 or 6 carbon atoms, in particular 2 or 6 carbon atoms. Ethane-1,2-diyl, benzene-1,2-diyl or furan-3,4-diyl are particularly preferred examples of alkanediyl, arenediyl or heteroarenediyl groups R"".
Furthermore, preference is given to a substituted isophosphindoline in which R is phenyl, R' is methyl or ethyl, R" and R"' is hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl. Particular preference is given to a substituted isophosphindoline in which R is phenyl, R' is methyl or ethyl, R" and R"' are hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl, in which R" and R"' are not hydrogen or in which either R" or R"' is hydrogen.
Furthermore, preference is given to substituted isophosphindolines whose asymmetric centers in the 1 and 3 positions have the same absolute configuration. The substituted isophosphindoline of the formula (VII) has two asymmetric centers having the same absolute configuration in positions 1 and 3, while in the case of those of the formula (X111), each has two or four asymmetric centers having the same absolute configuration in the positions 1, 1', 3 and 3'.
Finally, preference is given to substituted chiral isophosphindolines which are enriched in one enantiomer.
AMENDED SHEET
WO 00/21971 5a PCT/EP99/07084 r and each contain from t~
particular from 1 to 6, carbon atoms.
The haloalkyl or/and haloaryl groups preferably have the for ulae CHal3, CH2CHal3, C2Hal5, where Hal can be, in particular, F, CI r Br. Particular preference is given to haloalkyl or/and haloaryl groups o he formulae CFg, CH2CFg, C2F5.
It is also preferred that the alkanediyl, arened~ or heteroarenediyl group R"" of the substituted isophosphindoline ha~rom 2 to 20 carbon atoms, more preferably 2, 3, 4, 5 or 6 carbon atp~Fns, in particular 2 or 6 carbon atoms. Ethane-1,2-diyl, benzene-1,2-d~~ or furan-3,4-diyl are particularly preferred examples of alkanediyl, areyfediyl or heteroarenediyl groups R"".
Furthermore, preference is giv n to a substituted isophosphindoline in which R is phenyl, R' is met I or ethyl, R" and R"' is hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl. Particular preference is given to a substituted isophosphin~oline in which R is phenyl, R' is methyl or ethyl, R" and R"' are hydroge~ methyl or/and phenylene, R"" is benzene-1,2-diyl, in which R" and R"'; pare not hydrogen or in which either R" or R"' is hydrogen.
Furthermore, pr ference is given to substituted isophosphindolines whose asymmetric c nters in the 1 and 3 positions have the same absolute configuratio . The substituted isophosphindoline of the formula (VII) has two asy etric centers having the same absolute configuration in position 1 and 3, while in the case of those of the formula (X111), each has two our asymmetric centers having the same absolute configuration in the plositions 1, 1', 3 and 3'.
~nally, preference is given to substituted chiral isophosphindolines which are enriched in_onP Pnantiomer.
The substituents R' in the substances of the formulae (VII) and (X111) are essential for the steric properties of the ligands, while the other substituents R, R"> R"' and R"" essentially determine the electronic properties by means of their donor or acceptor capabilities, and thus allow, as explained above, the reactivity, selectivity and application range in respect of substrates in catalytic reactions to be influenced over a wide range.
A further substantial difference between the compounds of the formulae (VII) and (X111) on the one hand and phospholines on the other hand is the greater rigidity of the five-membered heterocyclic ring in the compounds of the formulae (VII) and (X111), which in attributable to the replacement of the ethanediyl backbone in the phospholines by the benzene-1,2-diyl substituent in the substances of the formulae (VII) and (X111).
Representatives of the class of compounds of the formula (VII), which encompasses not only compounds of the formula (V) but also corresponding compounds substituted in the fused-on aromatic ring, have been prepared. In cases where these are chiral, the compounds have also been synthesized in a form enriched in one enantiomer.
R., R. H
R." ~\~~
a.., ~~ ; P R
R"
(VII) A number of routes are available for the synthesis of the substituted isophosphindolines of the formula (VII): for example, either the corresponding phthalic dialdehyde of the formula (VIII) or the corresponding diketone of the formula (IX) can be used as starting material.
The reaction of the phthalic dialdehyde of the formula (VIII) with two equivalents of Grignard R'-M gives firstly the corresponding dialkoxide of the formula (X) which can be reacted further to give the cyclic sulfate of the formula (XII).
Starting from the diketone of the formula (IX), this is firstly reduced by means of boron compounds or analogous compounds to give the boronic acid derivative (XI) which can likewise be converted into the cyclic sulfate (XII).
A single representative of the sulfates of the formula (XII) is a previously known compound in which R' = methyl and R" - R"' - H and which is mentioned in WO 97/13763, page 7.
Depending on reaction conditions, synthetic route and reagent, the sulfate of the formula (XII) is obtained as a mixture of diastereomers (meso/rac form) or/and enantiomers; separation of the isomers gives the stereochemically pure sulfate of the formula (XII).
R" O R" OM
R.,. \ H R... \ R, R... ( / H R... I / R' R.. R.
R" O R" OM R"' / O
(vul) (x) soy R.. O R.. R.1 R..~~O
R... I\ R, R... ~ ~ O ~ R.. R.~
R... ~ ~ R~ ~R..,. \ ~ oB X {XII) .
i ;
R" O R" R' 1. BuLi / RPH
(IX) (Xl) ~ 2. BuLi R.. R. H
R,., \ \
I'i /~P-R
R.,, i R" R' / \H
(VII) In a modification of k wn processes (Burk US 5,386,061 ), reaction of the sulfate of the for a (XII) with phosphines of the formula RPH2 (R = alkyl, aryl, hetero I) gives, via the corresponding phosphides, the correspon ' g substituted isophosphindoline.
November 16, 2000 7U EP 009907084 R" O R" OM
l R... ~ \ H ~ R... ~ \ R.
R... ~ H R... ~ R' R.. R.
R... / O
R" O R" OM
(VIII) (X) I ~ soy R.. O R.. R~ R...i ~ O
R... I R... I ' R, / O R~~ R.
R... ~ ~Y R~~ R..., ~ ~ 0 6 X ~ (XII) i /
R" O R" R' ' 1. BuLi / RPHz (IX) (XI) I 2. BuLi R.. R. H
R,., ~
~/~P-R
R... ~~~
R., R' H
(VII) In a modification of known processes (Burk US 5,386,061 ), reaction of the sulfate of the formula (XII) with phosphines of the formula RPH2 (R = alkyl, aryl, heteroarenediyl) gives, via the corresponding phosphides, the corresponding substituted isophosphindoline.
It is likewise possible to convert the isomer mixture of the sulfate of the formula (XII) into the corresponding mixture of isomeric isophosphindolines AMENDED SHEET
November 16, 2000 8 EP 009~a07084 and then to carry out a separation in order to obtain stereochemica'~y pure substituted isophosphindolines. This separation can be achie~r :d, for example, by fractional crystallization and/or chromatographically.
As phosphines of the formula RPH2, it is possible to use all types of arylphosphines and alkylphosphines as starting materials (R = aryl, alkyl).
If, instead of these, diphosphines of the formula H2P=R""-PH2 are used, the products are chelating ligands of the formula (X111) which in the case of c2-symmetric sulfates of the formula (XII) lead to chiral and then likewise c2-symmetric chelating ligands.
R, H H R, R,.
R... \ \ R...
I ' R... % \ " ~ R."
R' N H R' R~~ R., (X111) The compounds of the formulae (VII) and (X111) can be used as ligands on metals in asymmetric, metal-catalyzed reactions (e.g. asymmetric hydrogenation, transfer hydrogenations, asymmetric rearrangement, asymmetric cyclopropanation or Heck reactions) and in polymerizations.
They are particularly useful far asymmetric reactions.
The ligands of the formulae (VII) and (X111) form complexes of the type (XIV), [MxPm~nSq~Yr (XIV) where, in the formula (XIV), M is a metal center, preferably a transition metal center, L are identical or different coordinating organic or inorganic ligands and P are organic ligands, according to the invention isophosphindolines of the type (VII) or (X111), S are coordinating solvent molecules and Y are equivalents of noncoordinating anions, where x and m are integers greater than or equal to 1, n, q and r are integers greater than or equal to 0.
AMENDED SHEET
November 16, 2000 9 EP 009907084 The maximum value of the sum m + n + q is determined by the number of coordination sites available on the metal centers, but not all coordination AMENDED SHEET
sites have to be occupied. Preference is given to complexes having an "~ CA 02346379 2001-04-06 WO 00/21971 9a PCT/EP99/07084 0 1~, n, ~q and r are integers~gr~a~r~~ttl'a r equal to 0.
~'he maximum value of t~,fa,~-scrrr~i~m~+ n + q is determined by the number c oordination s~available on the metal centers, but not all coordinatio ~te$ .ba'~Te t~O'°~-'O'CCUDfe~l--RfA#A~t'-~RE6....~.~.u~A. fn nnrr,n~ac.~c haVjrlll a ~c#a~h~a~l,, pseudo octahedral, tetrahedral, pseudo tetrahedral or square planar coordination sphere, which may also be distorted, around the respective transition metal center. In such complexes, the sum m + n + q is smaller than or equal to 6x.
The complexes of the present invention contain at least one metal atom or ion, preferably a transition metal atom or ion, in particular one selected from the group consisting of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel and copper.
Preference is given to complexes having less than four metal centers, particularly preferably ones having one or more two metal centers. The metal centers can be occupied by various metal atoms and ions.
Preferred ligands L in such complexes are halide, particularly CI, Br and I, diene, particularly cyclooctadiene, norbornadiene, olefin, particularly ethylene and cyclooctene, acetato, trifluoroacetato, acetylacetonato, allyl, methylallyl, alkyl, particularly methyl and ethyl, nitrite, particularly acetonitrile and benzonitrile, and also carbonyl and hydrido ligands.
Preferred coordinating solvents S are amines, particularly triethylamine, alcohols, particularly methanol, and aromatics, particularly benzene and cumene.
Preferred noncoordinating anions Y are trifluoroacetate, BF4, C104, PFg and BAr4.
In the individual complexes, different molecules, atoms or ions of the individual constituents M, P, L, S and Y may be present.
WO 00/21971 10 PCT/EP99/070$4 Among the ionic complexes, preference is given to compounds of the type [RhPm(diene)]+Y , where Pm represents either two isophosphindolines of the type (VII) or one isophosphindoline of the type (X111).
These metal-ligand complexes can be prepared in situ by reaction of a metal salt or an appropriate precursor complex with the ligands of the formulae (VII) and (X111). Alternatively, a metal-ligand complex can be obtained by reaction of a metal salt or an appropriate precursor complex with the ligands of the formula (VII) and (X111) and subsequent isolation.
Examples of metal salts are metal chlorides, bromides, iodides, cyanides, nitrates, acetates, acetylacetonates, hexafluoroacetylacetonates, perfluoroacetates or triflates, in particular of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel and/or copper.
Examples of precursor complexes are:
cyclooctadienepalladium chloride, cyclooctadienepalladium iodide, 1,5-hexadienepalladium chloride, 1,5-hexadienepalladium iodide, bis(dibenzylideneacetone)palladium, bis(benzonitrile)palladium(II) chloride, bis(benzonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) iodide, bis(allyl)palladium, bis(methallyl)palladium, allylpalladium chloride dimer, methallylpalladium chloride dimer, tetramethylethylenediaminepalladium dichloride, tetramethylethylenediaminepalladium dibromide, tetramethylethylenediaminepalladium diiodide, (tetramethylethylenediamine)dimethylpalladium, cyclooctadieneplatinum chloride, cyclooctadieneplatinum iodide, 1,5-hexadieneplatinum chloride, 1,5-hexadieneplatinum iodide, bis(cyclooctadiene)platinum, potassium ethylenetrichloroplatinate, cyclooctadienerhodium(I) chloride dimer, norbornadienerhodium(I) chloride dimer, 1,5-hexadienerhodium(I) chloride dimer, tris(triphenylphosphine)rhodium(I) chloride, hydridocarbonyltris(triphenylphosphine)rhodium(I) chloride, bis(cyclooctadiene)rhodium(I) perchlorate, bis(cyclooctadiene)rhodium(I) tetrafluoroborate, -' CA 02346379 2001-04-06 bis(cyclooctadiene)rhodium(I) triflate, bis(acetonitrile)cyclooctadienerhodium(I) perchlorate, bis(acetonitrile)cyclooctadienerhodium(I) tetrafluoroborate, bis(acetonitrile)cyclooctadienerhodium(I) triflate, cyclopentadienerhodium(III) chloride dimer, pentamethylcyclopentadienerhodium(III) chloride dimer, (cyclooctadiene)Ru(rt3-allyl)2, ((cyclooctadiene)Ru)2(acetate)4, ((cyclooctadiene)Ru)2(trifluoroacetate)4, RuCl2(arene) dimer, tris(triphenylphosphine)ruthenium(II) chloride, cyclooctadieneruthenium(II) chloride, OsCl2(arene) dimer, cyclooctadieneiridium(I) chloride dimer, bis(cyclooctene)iridium(I) chloride dimer, bis(cyclooctadiene)nickel, (cyclododecatriene)nickel, tris(norbornene)nickel, nickel tetracarbonyl, nickel(II) acetylacetonate, (arene)copper triflate, (arene)copper perchlorate, (arene)copper trifluoroacetate, cobalt carbonyl.
The complexes based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, can be catalysts themselves or can be used for preparing catalysts based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu. All these complexes are particularly useful in the asymmetric hydrogenation of C=C, C=O or C=N bonds, in which they display high activities and selectivities. In particular, it is found to be advantageous that the ligands of the formula (X111) can be very well matched in stearic and electronic terms to the respective substrate due to the fact that they can easily be modified over a wide range.
Corresponding catalysts comprise at least one of the complexes of the invention.
Examples:
1. 1,2-bis(a-hydroxyethyl)benzene:
The preparation of 1,2-bis(u.-hydroxyethyl)benzene was carried out by literature methods: Goldschmidt et al., Chem. Ber. 1961, 94, 169.
2. Cyclic sulfate:
The preparation of the cyclic sulfate was carried out by the method of Burk (J. Am. Chem. Soc. 1993, 115, 10125) starting from 1,2-bis(a-hydroxyethyl)benzene.
38 mmol of thionyl chloride in 10 ml of CC14 are added dropwise to 31 mmol (5.1 g) of 1,2-bis(a-hydroxyethyl)benzene dissolved in 40 ml of CC14 over a period of 30 minutes. After refluxing for 2.5 hours and cooling, the solution is evaporated virtually to dryness. The residue is then taken up in CC14, acetonitrile, water (25 ml/25 mU35 ml) and cooled to 0°C. 0.20 mmol of RuCIg~H20 and 61 mml of Na104 are added one after the other to the cold mixture. After a reaction time of one hour, the reaction mixture is diluted with 170 ml of water, extracted four times with 100 ml each time of diethyl ether and the combined ether extracts are washed twice with 60 ml each time of saturated NaCI
solution. The extract solution is dried overnight over Na2S04 and subsequently evaporated to a reddish brown serum. Column chromatography using silica gel 60 as stationary phase and n-hexane/ethyl acetate 10:1 as mobile phase gives 1.0 g of pure racemic 1,2-bis(a-hydroxyethyl)benzene cyclosulfate (14°~0 of theory).
As a second method, the procedure of Zhang WO 97/13763 was employed. The yield of pure bis(a-hydroxyethyl)benzene cyclosulfate was 25%, and the 'H-NMR data reported in the literature could be reproduced.
~ H-NMR (400, 13 MHz, CDC13): b 1.92 (d, 6H, CH3), 5.56 (q, 2H, CH), 7.35 (m, 2H, CHar), 7.56 (m, 2H, CHar) ppm.
3. Isophosphindoline synthesis (modification of the method of Burk et al., J. Am. Chem. Soc. 1993, 115, 10125) 1.5 mmol of phenylphosphine are dissolved in 35 ml of kethyl-dried THF
and admixed with 0.94 ml of 1.6 M n-BuLi solution in n-hexane. After stirring for two hours at room temperature, this solution is added dropwise at -78°C to a mixture of 1.5 mmol (340 mg) of the cyclic sulfate and 20 ml of THF. Four hours after the addition was complete, another 1.09 ml of 1.6 M n-BuLi solution in n-hexane is added dropwise.
The solution is slowly warmed to room temperature overnight, and °°
excess organolithium compound is hydrolyzed using 1 ml of oxygen-free methanol. Complete evaporation of the solution gives a white residue which was firstly examined by means of 3'P-NMR as a guide.
This crude product contains many by-products in addition to the desired isophosphindoline.
31 P NMR (161.99 MHz, CDC13): S+21.7 ppm.
GC/MS (70 eV): m/e = 240 (100%, M+), 225 (25%, M+-15), 212 (9%), 192 (5%), 178 (6%), 165 (3%), 147 (16%), 131 (17%), 120 (10%), 115 (14%), 109 (12%), 91 (27%), 77 (32%), 65 (2%), 51 (2%), 39 (2%).
4. Purification of the isophosphindoline by oxidation/reduction The crude isophosphindoline product is oxidized for the purposes of purification and separation of the enantiomers.
The crude product is dissolved in THF and stirred overnight at 20°C
in the presence of air, the solution is shaken with 20 ml of saturated NH4C1 solution, the aqueous phase is washed three times with 20 ml each time of diethyl ether and the combined organic phases are dried over anhydrous sodium sulfate and evaporated to dryness. The crude product obtained in this way comprises, inter alia, 1,3-dimethyl-2 phenylisophosphindoline oxide. Washing with n-hexane and subsequent separate column chromatography of the filtrate and of the filter residue (silica gel, 1. n-hexane/ethyl acetate 10:4, 2. MeOH) gives various fractions of the oxide having purities of from 70 to 90%.
Analytical data:
MS (70 eV): m/e = 256 (100%, M+), 241 (5% M+-15), 228 (5%), 200 (4%), 178 (4%), 165 (2%), 147 (1%), 132 (18%), 131 (19%), 129 (5%), 117 (58%), 115 (19%), 91 (14°~0), 77 (6%), 65 (2%), 51 (4%), 39 (2%);
t H NMR (400.13 MHz, CDC13): ~ 1.18 (dd JHH: 7.1 Hz, JpH: 16.7 Hz, 3H, CH3), 1.55 (dd JHH: 7.6 Hz, JpH: 14.8 Hz, 3H, CHg), 3.28, 3.30 (2 x m, 1 H, CH), 3.54, 3.59 (2 x m, 1 H, CH), 7.18-7.41 (m, 9H, CHar) ppm.
3~ P NMR (161.99 MHz, CgDg): cS +60.4 ppm.
Reduction 0.2 mmol (52 mg) of 1,3-dimethyl-2-phenylisophosphindoline oxide are, without additional solvent, heated with 0.13 mmol of freshly distilled phenylsilane for two hours at 90°C under a protective argon atmosphere. The reaction mixture is cooled and then extracted with 3 x 2 ml of absolute, oxygen-free diethyl ether and filtered. The filtrate is evaporated and the 1,3-dimethyl-2-phenylisophosphindoline is isolated in a purity of about 80%. Phosphorus-free by-products which have not been identified up to now were not able to be separated off.
~ H NMR (400.13 MHz, CgDg: 8 1.14 (dd JHH: 7.3 Hz, JpH: 11.2 Hz, 3H, CHg), 1.49 (dd JHH: 7.7 Hz, JpH: 14.8 Hz, 3H, CH3), 3.34, 3.40 (2 x m, 1 H, CH), 3.50, 3.62 (2 x m, 1 H, CH), 6.72....7.39 {m, 9H, CHa~) ppm;
3~ P NMR (161.99 MHz, CDC13): 8 +21.5 ppm.
The crude product is dissolved in THF and stirred overnight at 20°C
in the presence of air, the solution is shaken with 20 ml of saturated NH4C1 solution, the aqueous phase is washed three times with 20 ml each time of diethyl ether and the combined organic phases are dried over anhydrous sodium sulfate and evaporated to dryness. The crude product obtained in this way comprises, inter alia, 1,3-dimethyl-2 phenylisophosphindoline oxide. Washing with n-hexane and subsequent separate column chromatography of the filtrate and of the filter residue (silica gel, 1. n-hexane/ethyl acetate 10:4, 2. MeOH) gives various fractions of the oxide having purities of from 70 to 90%.
Analytical data:
MS (70 eV): m/e = 256 (100%, M+), 241 (5% M+-15), 228 (5%), 200 (4%), 178 (4%), 165 (2%), 147 (1%), 132 (18%), 131 (19%), 129 (5%), 117 (58%), 115 (19%), 91 (14°~0), 77 (6%), 65 (2%), 51 (4%), 39 (2%);
t H NMR (400.13 MHz, CDC13): ~ 1.18 (dd JHH: 7.1 Hz, JpH: 16.7 Hz, 3H, CH3), 1.55 (dd JHH: 7.6 Hz, JpH: 14.8 Hz, 3H, CHg), 3.28, 3.30 (2 x m, 1 H, CH), 3.54, 3.59 (2 x m, 1 H, CH), 7.18-7.41 (m, 9H, CHar) ppm.
3~ P NMR (161.99 MHz, CgDg): cS +60.4 ppm.
Reduction 0.2 mmol (52 mg) of 1,3-dimethyl-2-phenylisophosphindoline oxide are, without additional solvent, heated with 0.13 mmol of freshly distilled phenylsilane for two hours at 90°C under a protective argon atmosphere. The reaction mixture is cooled and then extracted with 3 x 2 ml of absolute, oxygen-free diethyl ether and filtered. The filtrate is evaporated and the 1,3-dimethyl-2-phenylisophosphindoline is isolated in a purity of about 80%. Phosphorus-free by-products which have not been identified up to now were not able to be separated off.
~ H NMR (400.13 MHz, CgDg: 8 1.14 (dd JHH: 7.3 Hz, JpH: 11.2 Hz, 3H, CHg), 1.49 (dd JHH: 7.7 Hz, JpH: 14.8 Hz, 3H, CH3), 3.34, 3.40 (2 x m, 1 H, CH), 3.50, 3.62 (2 x m, 1 H, CH), 6.72....7.39 {m, 9H, CHa~) ppm;
3~ P NMR (161.99 MHz, CDC13): 8 +21.5 ppm.
5. Resolution of racemic 1,3-dimethyl-2-phenylisophosphindoline 2-oxide The analytical separation of an ethanolic solution of the racemate of 1,3-dimethyl-2-phenylisophosphindoline 2-oxide is carried out by HPLC
(CHIRALCEL OD-H, n-hexane/EtOH 97:3, flow rate: 0.8 ml/min). The retention times are 13.5 min and 20.0 min.
For the preparative separation of the enantiomers of the isophosphindoline oxide and for removing the by-products, a silica gel precolumn was installed and multiple injection into the above-described analytical HPLC column and combination of a total of 75 fractions of each of the two enantiomers gave 5.3 mg of the enantiomer which eluted first and 6.2 mg of the enantiomerically pure isophosphindoline oxide which eluted second. The optical rotation of the two enantiomers could not be determined precisely.
Complexes of 1,3-dimethyl-2-phenylisophosphindoline 6. cis-bis(1,3-dimethyl-2-phenylisophosphindoline)dichloropalladium 0.07 mmol (17 mg) of 1,3-dimethyl-2-phenylisophosphindoline dissolved in 0.3 ml of absolute THF is combined with 0.035 mmol of [PdCl2(PhCH)2J dissolved in 0.6 ml of absolute THF under a protective argon atmosphere, the mixture is stirred briefly, filtered through a Pasteur pipette filled with silica gel and evaporated completely. The orange residue is analyzed. This is the cis complex of the formula PdCl2(isophosphindoline)2.
Analytical data:
.. CA 02346379 2001-04-06 MS (electron impact ionization (70 eV)): m/e = 586 (2%, PdP2+), 584 (2%, PdP2- 2H+), 317 (3%), 240 (100%, M+), 225 (28%, M+-15), 212 (3%), 192 (10%), 178 (14%), 165 (7%), 147 (24%), 131 (34%), 129 (10%), 115 (46%), 109 (12%), 91 (59%), 77 (32%), 65 (2%), 51 (2%), 39 (2%) 3~ P NMR (161.99 MHz, CgD6/THF): 8 +74.04 ppm.
(CHIRALCEL OD-H, n-hexane/EtOH 97:3, flow rate: 0.8 ml/min). The retention times are 13.5 min and 20.0 min.
For the preparative separation of the enantiomers of the isophosphindoline oxide and for removing the by-products, a silica gel precolumn was installed and multiple injection into the above-described analytical HPLC column and combination of a total of 75 fractions of each of the two enantiomers gave 5.3 mg of the enantiomer which eluted first and 6.2 mg of the enantiomerically pure isophosphindoline oxide which eluted second. The optical rotation of the two enantiomers could not be determined precisely.
Complexes of 1,3-dimethyl-2-phenylisophosphindoline 6. cis-bis(1,3-dimethyl-2-phenylisophosphindoline)dichloropalladium 0.07 mmol (17 mg) of 1,3-dimethyl-2-phenylisophosphindoline dissolved in 0.3 ml of absolute THF is combined with 0.035 mmol of [PdCl2(PhCH)2J dissolved in 0.6 ml of absolute THF under a protective argon atmosphere, the mixture is stirred briefly, filtered through a Pasteur pipette filled with silica gel and evaporated completely. The orange residue is analyzed. This is the cis complex of the formula PdCl2(isophosphindoline)2.
Analytical data:
.. CA 02346379 2001-04-06 MS (electron impact ionization (70 eV)): m/e = 586 (2%, PdP2+), 584 (2%, PdP2- 2H+), 317 (3%), 240 (100%, M+), 225 (28%, M+-15), 212 (3%), 192 (10%), 178 (14%), 165 (7%), 147 (24%), 131 (34%), 129 (10%), 115 (46%), 109 (12%), 91 (59%), 77 (32%), 65 (2%), 51 (2%), 39 (2%) 3~ P NMR (161.99 MHz, CgD6/THF): 8 +74.04 ppm.
7. cis-Bis(1,3-dimethyl-2-phenylisophosphindoline)cyclooctadienerhodium tetrafluoroborate 0.05 mmol of [Rh(COD)2]BF4 is slurried in 1.5 ml of THF and, under a protective argon atmosphere, 0.1 mmol (24 mg) of 1,3-dimethyl-2-phenylisophosphindoline dissolved in 0.1 ml of CgDg is added thereto.
After being allowed to stand for about one hour at room temperature, the rhodium COD complex dissolves to form the phospholine complex.
The compound is present as a rapidly exchanging diastereomer mixture of the formulae Rh(COD)(R-Isophos)(S-Isophos) and Rh(COD)(R-Isophos)(R-Isophos) or Rh(COD)(S-Isophos)(S-Isophos).
3~ P NMR (161.99 MHz, CgDg): 8 +62.3 ppm (broad signal).
After being allowed to stand for about one hour at room temperature, the rhodium COD complex dissolves to form the phospholine complex.
The compound is present as a rapidly exchanging diastereomer mixture of the formulae Rh(COD)(R-Isophos)(S-Isophos) and Rh(COD)(R-Isophos)(R-Isophos) or Rh(COD)(S-Isophos)(S-Isophos).
3~ P NMR (161.99 MHz, CgDg): 8 +62.3 ppm (broad signal).
8. (1,3-Dimethyl-2-phenylisophosphindoline)cyclooctadienechlororhodium 0.025 mmol of [Rh(COD)C12] is slurried in 1.0 ml of THF and, under a protective argon atmosphere, 0.05 mmol (12 mg) of 1,3-dimethyl-2-phenylisophosphindoline dissolved in 0.1 ml of CgDg is added thereto.
After stirring for about 30 minutes at room temperature, the rhodium-COD-CI complex dissolves to form the isophosphindoline complex.
3~ P NMR (161.99 MHz, CgDg): 8 +61.8 ppm (d, JpRh = 154 Hz).
After stirring for about 30 minutes at room temperature, the rhodium-COD-CI complex dissolves to form the isophosphindoline complex.
3~ P NMR (161.99 MHz, CgDg): 8 +61.8 ppm (d, JpRh = 154 Hz).
Claims (15)
1. A complex of the formula (XIV) [M x P m L n S q]Y r (XIV) where M is a metal center, P are organic ligands, L are identical or different organic or inorganic ligands, S are coordinating solvent molecules and Y are noncoordinating anionic equivalents and x and m are integers greater than or equal to 1, n, q and r are integers greater than or equal to 0, in which one or more identical or different isophosphindolines of the type (VII) or (XIII) where, in the formula (VII), R is hydrogen or an alkyl, aryl, haloaryl or haloalkyl group, R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and, in the formula (XIII) R' are alkyl, aryl, haloaryl or haloalkyl groups, R" and R"' are each, independently of one another, hydrogen, alkyl, aryl, haloalkyl or haloaryl, alkoxy, amino, dialkylamino or sulfonate groups or fluorine and two adjacent radicals R"/R", R"/R"' or R"'/R"' may also be bridged, and R"" is an alkanediyl, arenediyl or heteroarenediyl group, where the term alkyl or haloalkyl group encompasses the corresponding cyclo compounds, are present as ligands P.
2. A complex as claimed in claim 1, wherein the sum m + n + q is less than or equal to 6x.
3. A complex as claimed in claim 1 or 2 in which less than four metal centers, preferably one or two metal centers, are present.
4. A complex as claimed in any of the preceding claims, wherein the metal center or centers M x comprise at least one transition metal, in particular palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or/and copper.
5. A complex as claimed in any of the preceding claims, wherein the alkyl, aryl, haloalkyl, haloalkyl, alkoxy or/and dialkylamino groups each have, independently of one another, from 1 to 20, preferably from 1 to 6, carbon atoms.
6. A complex as claimed in any of the preceding claims, wherein the haloalkyl or/and haloaryl groups are CF3, CH2CF3, C2F5.
7. A complex as claimed in any of the preceding claims, wherein the alkanediyl, arenediyl or heteroarenediyl group R"" has from 2 to 20 carbon atoms, preferably 2, 3, 4, 5 or 6 carbon atoms, in particular 2 or 6 carbon atoms.
8. A complex as claimed in any of the preceding claims, wherein the alkanediyl, arenediyl or heteroarenediyl group R"" is ethane-1,2-diyl, benzene-1,2-diyl or furan-3,4-diyl.
9. A complex as claimed in any of the preceding claims, wherein R is phenyl, R' is methyl or ethyl, R" and R"' are hydrogen, methyl or/and phenylene, R"" is benzene-1,2-diyl.
10. A complex as claimed in any of the preceding claims in which chiral ligands P are present.
11. A complex as claimed in any of the preceding claims, wherein a ligand P is an isophosphindoline of the formula (VII) which has two asymmetric centers having the same absolute configuration in positions 1 and 3.
12. A complex as claimed in any of claims 1 to 11, wherein a ligand P is an isophosphindoline of the formula (XIII) which has three or four asymmetric centers having the same absolute configuration in positions 1, 1', 3 and 3'.
13. A complex as claimed in any of the preceding claims, wherein R is phenyl, R' is methyl, R" and R"' are hydrogen and R"" is benzene-1,2-diyl.
14. A complex as claimed in any of the preceding claims which is enriched in one enantiomer.
15. The use of a complex as claimed in any of claims 1 to 15 as catalyst for asymmetric reactions or polymerizations, in particular for asymmetric hydrogenations, transfer hydrogenations, rearrangements, cyclopropanations, Heck reactions.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19846559.9 | 1998-10-09 | ||
| DE19846559A DE19846559A1 (en) | 1998-10-09 | 1998-10-09 | New substituted isophosphindolines or bis-isophosphindolines, used in metal complex form as catalysts for polymerization or asymmetric reactions such as hydrogenation or Heck reactions |
| PCT/EP1999/007084 WO2000021971A1 (en) | 1998-10-09 | 1999-09-23 | Substituted isophosphindolines and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2346379A1 true CA2346379A1 (en) | 2000-04-20 |
Family
ID=7883936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002346379A Abandoned CA2346379A1 (en) | 1998-10-09 | 1999-09-23 | Substituted isophosphindolines and their use |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1119574B1 (en) |
| JP (1) | JP2002527445A (en) |
| CN (1) | CN1323311A (en) |
| AT (1) | ATE231514T1 (en) |
| CA (1) | CA2346379A1 (en) |
| DE (2) | DE19846559A1 (en) |
| WO (1) | WO2000021971A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245408B1 (en) | 1999-05-19 | 2001-06-12 | Hexcel Corporation | Honeycomb core with controlled crush properties |
| JP4013217B2 (en) * | 2002-01-31 | 2007-11-28 | 高砂香料工業株式会社 | A novel phosphine compound, a transition metal complex having the compound as a ligand, and an asymmetric synthesis catalyst containing the complex. |
| JP4231274B2 (en) | 2002-11-12 | 2009-02-25 | 高砂香料工業株式会社 | Phosphine compound, transition metal complex having the compound as a ligand, and catalyst for asymmetric synthesis containing the complex |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX9703613A (en) * | 1994-11-17 | 1997-08-30 | Ciba Sc Holding Ag | Thermal metathesis polymerisation process and a polymerisable composition. |
| TW350851B (en) * | 1995-01-31 | 1999-01-21 | Ciba Sc Holding Ag | Polymerizable composition and process for the preparation of network polymer |
-
1998
- 1998-10-09 DE DE19846559A patent/DE19846559A1/en not_active Withdrawn
-
1999
- 1999-09-23 CA CA002346379A patent/CA2346379A1/en not_active Abandoned
- 1999-09-23 EP EP99970392A patent/EP1119574B1/en not_active Expired - Lifetime
- 1999-09-23 WO PCT/EP1999/007084 patent/WO2000021971A1/en active IP Right Grant
- 1999-09-23 CN CN99811956A patent/CN1323311A/en active Pending
- 1999-09-23 AT AT99970392T patent/ATE231514T1/en not_active IP Right Cessation
- 1999-09-23 DE DE59904110T patent/DE59904110D1/en not_active Expired - Fee Related
- 1999-09-23 JP JP2000575877A patent/JP2002527445A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1119574B1 (en) | 2003-01-22 |
| WO2000021971A1 (en) | 2000-04-20 |
| DE19846559A1 (en) | 2000-04-20 |
| DE59904110D1 (en) | 2003-02-27 |
| JP2002527445A (en) | 2002-08-27 |
| CN1323311A (en) | 2001-11-21 |
| ATE231514T1 (en) | 2003-02-15 |
| EP1119574A1 (en) | 2001-08-01 |
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