U.S. patent application number 10/454510 was filed with the patent office on 2003-12-04 for process for preparing chiral diphosphines.
This patent application is currently assigned to RHODIA CHIMIE. Invention is credited to Halle, Rob Tel, Lemaire, Marc, Schulz, Emmanuelle, Spagnol, Michel.
Application Number | 20030225297 10/454510 |
Document ID | / |
Family ID | 9542315 |
Filed Date | 2003-12-04 |
United States Patent
Application |
20030225297 |
Kind Code |
A1 |
Lemaire, Marc ; et
al. |
December 4, 2003 |
Process for preparing chiral diphosphines
Abstract
Compounds of formula VII are described: 1 wherein A represents
phenyl or naphthyl and Ar.sub.1 and Ar.sub.2 independently
represent a saturated or aromatic carbocyclic group. The compounds
may be prepared by reducing the nitrile functions of a compound of
formula I: 2
Inventors: |
Lemaire, Marc;
(Villeurbanne, FR) ; Halle, Rob Tel; (Collonges-Au
Mont -D'Or, FR) ; Schulz, Emmanuelle;
(Sainte-Foy-Les-Lyon, FR) ; Spagnol, Michel;
(Meyzieu, FR) |
Correspondence
Address: |
BURNS, DOANE, SWECKER & MATHIS, L.L.P.
P.O. Box 1404
Alexandria
VA
22313-1404
US
|
Assignee: |
RHODIA CHIMIE
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (C.N.R.S.)
|
Family ID: |
9542315 |
Appl. No.: |
10/454510 |
Filed: |
June 5, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10454510 |
Jun 5, 2003 |
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09913831 |
Dec 11, 2001 |
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6610875 |
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09913831 |
Dec 11, 2001 |
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PCT/FR00/00083 |
Jan 14, 2000 |
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Current U.S.
Class: |
558/343 |
Current CPC
Class: |
C07C 39/38 20130101;
C07C 309/65 20130101; C07F 9/5027 20130101; C07C 37/62 20130101;
C07C 37/62 20130101; C07C 303/28 20130101; C07C 309/65 20130101;
C07C 303/30 20130101; C07B 53/00 20130101; C07F 9/5072 20130101;
C07C 303/28 20130101; C07F 9/5068 20130101; C07C 303/30
20130101 |
Class at
Publication: |
558/343 |
International
Class: |
C07F 009/02 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 19, 1999 |
FR |
99 02 119 |
Claims
1. A process for preparing a compound of formula I: 32in which: A
represents phenyl or naphthyl; and Ar.sub.1 and Ar.sub.2
independently represent a saturated aromatic or carbocyclic group;
this process comprising the steps consisting in: i) brominating a
diol of formula II: 33in which A is as defined above, using a
suitable brominating agent so as to obtain a dibromo compound of
formula III: 34in which A is as defined above; ii) esterifying the
compound of formula III obtained in the preceding step by the
action of a sulfonic acid or an activated form thereof, so as to
obtain the corresponding disulfonate; iii) substituting the two
bromine atoms with cyano groups by reacting the disulfonate
obtained in the preceding step with a suitable nucleophilic agent
so as to obtain the corresponding nitrile; iv) coupling a phosphine
of formula VI: XPAr.sub.1Ar.sub.2 VI in which X represents a
hydrogen atom or a halogen atom and Ar.sub.1 and Ar.sub.2 are as
defined above, with the nitrile obtained in the preceding step, in
the presence of a catalyst based on a transition metal, so as to
obtain the expected compound of formula I.
2. The process as claimed in claim 1, characterized in that: A
represents naphthyl or phenyl, optionally substituted with one or
more radicals chosen from (C.sub.1-C.sub.6)alkyl and
(C.sub.1-C.sub.6)alkoxy; and Ar.sub.1 and Ar.sub.2 independently
represent a phenyl group optionally substituted with one or more
(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy; or a
(C.sub.4-C.sub.8)cycloalkyl group optionally substituted with one
or more (C.sub.1-C.sub.6)alkyl groups.
3. The process as claimed in either of claims 1 and 2,
characterized in that Ar.sub.1 and Ar.sub.2 are independently
chosen from phenyl optionally substituted with methyl or
tert-butyl; and (C.sub.5-C.sub.6)-cycloalkly optionally substituted
with methyl or tert-butyl.
4. The process as claimed in either of claims 1 and 2,
characterized in that Ar.sub.1 and Ar.sub.2 are identical and
preferably represent optionally substituted phenyl.
5. The process as claimed in any one of the preceding claims,
characterized in that A represents naphthyl.
6. The process as claimed in any one of the preceding claims, for
the preparation of an optically active compound of formula I from
an optically active diol of formula II.
7. The process as claimed in any one of the preceding claims,
characterized in that the bromination is performed, in step (i) by
the action of bromine, at a temperature of between -78.degree. C.
and -30.degree. C.
8. The process as claimed in any one of the preceding claims,
characterized in that, in step (ii), the esterification is carried
out by the action of trifluoromethanesulfonic anhydride in the
presence of a base, the base preferably being chosen from pyridine
and 4-dimethylaminopyridine.
9. The process as claimed in any one of the preceding claims,
characterized in that the nucleophilic agent used in step (iii) is
CuCN.
10. The process as claimed in any one of the preceding claims,
characterized in that, in step (iv), HPAr.sub.1Ar.sub.2 is reacted
with the nitrile in the presence of
[bis(diphenylphosphino)ethane]nickel-dichl- oride and
triethylenediamine at a temperature of from 50 to 200.degree. C.
and preferably from 80 to 130.degree. C.
11. The process as claimed in any one of claims 1 to 9,
characterized in that, in step (iv), a compound of formula
XPAr.sub.1Ar.sub.2 (in which X is a halogen atom), is reacted with
the nitrile in the presence of
[bis(diphenylphosphino)ethane]nickeldichloride and zinc, at a
temperature of between 50 and 200.degree. C. and preferably between
80 and 180.degree. C.
12. The process as claimed in either of claims 10 and 11,
characterized in that the molar ratio of compound VI to the nitrile
is between 2 and 4.
13. The process as claimed in any one of claims 10 to 12,
characterized in that the reaction of the compound of formula VI
with the nitrile is carried out in N,N-dimethylformamide as
solvent.
14. A process for preparing a compound of formula VII: 35in which
A, Ar.sub.1and Ar.sub.2 are as defined in claim 1 or in claim 2,
characterized in that it comprises the reduction of the nitrile
functions of the corresponding compound of formula I as defined in
claim 1 or in claim 2, respectively, by the action of a suitable
reducing agent.
15. The process as claimed in claim 14, characterized in that the
reducing agent is lithium aluminum hydride, the reduction being
carried out in a mixture of toluene and tetrahydrofuran as
solvent.
16. The process as claimed in any one of claims 1 to 13, also
comprising the step consisting in treating the compound of formula
I in a basic medium or in an acidic medium so as to obtain the
corresponding carboxylic acid of formula: 36in which A, Ar.sub.1
and Ar.sub.2 are as defined in claim 1 or claim 2.
17. A compound of formula VII: 37in which A, Ar.sub.1 and Ar.sub.2
are as defined in any one of claims 1 to 5.
18. Use of a compound of formula I obtained by carrying out the
process as claimed in any one of claims 1 to 13, as a ligand for
preparing a metal complex which is useful in asymmetric
catalysis.
19. The use of a compound of formula VII as claimed in claim 17, as
a ligand for preparing a metal complex which is useful in
asymmetric catalysis.
20. The use as claimed in claim 19, characterized in that said
complex is intended to catalyze the asymmetric hydrogenation of
ketones.
21. The use as claimed in any one of claims 18 to 20, characterized
in that the metal complex is a ruthenium, rhodium or iridium
complex.
22. A compound of formula IV: 38in which A is as defined in any one
of claims 1 to 5 and P represents a hydrocarbon-based aliphatic
group; an aromatic carbocyclic group; or an aliphatic group
substituted with an aromatic carbocyclic group.
Description
[0001] The invention relates to a process for preparing chiral
diphosphines that are useful as bidentate ligands in the synthesis
of catalysts based on transition metals intended for asymmetric
catalysis.
[0002] Asymmetric catalysis has developed considerably in recent
years. It has the advantage of leading directly to the preparation
of optically pure isomers by asymmetric induction without it being
necessary to resolve racemic mixtures.
[0003] 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) is an
example of a diphosphorus ligand commonly used to prepare metal
complexes for the asymmetric catalysis of hydrogenation,
carbonylation and hydrosilylation reactions, C--C bond forming
reactions (such as allylic substitutions or Grignard
cross-couplings) or even asymmetric isomerization reactions of
allylamines.
[0004] The development of novel chiral ligands is desirable so as
to improve the enantioselectivity of the reactions and, more
generally, the general conditions for carrying out these
reactions.
[0005] The present invention more specifically provides a process
for preparing diphosphorus bidentate chiral ligands of
2,2'-bis(diarylphosphino)-1,1'-binaphthyl and
2,2'-bis(diarylphosphino)-1- ,1'-biphenyl type that are
functionalized on the binaphthyl or biphenyl groups, respectively.
These ligands, coordinated to transition metals such as ruthenium
or rhodium, form complexes that are useful in the asymmetric
catalysis of various reactions and more particularly of asymmetric
hydrogenation reactions.
[0006] The ligands prepared according to the process of the
invention are in particular the dicyano derivatives of formula I:
3
[0007] in which:
[0008] A represents phenyl or naphthyl; and
[0009] Ar.sub.1 and Ar.sub.2 independently represent a saturated
aromatic or carbocyclic radical.
[0010] In the context of the invention, the phenyl and naphthyl
radicals are optionally substituted.
[0011] According to the invention, the term "carbocyclic radical"
means an optionally substituted, preferably C.sub.3-C.sub.50
monocyclic or polycyclic radical. Preferably it is a
C.sub.3-C.sub.8 radical, which is preferably mono-, bi- or
tricyclic.
[0012] The carbocyclic radical may comprise a saturated portion
and/or an aromatic portion.
[0013] When the carbocyclic radical comprises more than one cyclic
nucleus (in the case of polycyclic carbocycles), the cyclic nuclei
may be fused in pairs or attached in pairs via .sigma. bonds.
[0014] Examples of saturated carbocyclic radicals are cycloalkyl
groups.
[0015] Preferably, the cycloalkyl groups are saturated cyclic
hydrocarbon-based radicals that are preferably C.sub.3-C.sub.18 and
better still C.sub.3-C.sub.10, and in particular cyclopentyl,
cyclohexyl, cycloheptyl, cyclooctyl, adamantyl or norbornyl
radicals.
[0016] Examples of aromatic carbocyclic radicals are
(C.sub.6-C.sub.18)aryl groups and in particular phenyl, naphthyl,
anthryl and phenanthryl.
[0017] The substituents on the phenyl, naphthyl and carbocyclic
radicals are such that they do not interfere with the reactions
involved in the process of the invention. These substituents are
inert under the conditions involved in bromination (step i),
esterification (step ii), nucleophilic substitution (step iii) and
coupling reactions.
[0018] Preferably, the substituents are alkyl or alkoxy groups.
[0019] The term "alkyl" means a saturated, linear or branched
hydrocarbon-based radical containing in particular up to 25 carbon
atoms and, for example, from 1 to 12 carbon atoms and better still
from 1 to 6 carbon atoms.
[0020] Examples of alkyl groups are methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl,
2-methylbutyl, 1-ethylpropyl, hexyl, iso-hexyl, neohexyl,
1-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl,
1,3-dimethylbutyl, 2-ethylbutyl, 1-methyl-1-ethylpropyl, heptyl,
1-methylhexyl, 1-propylbutyl, 4,4-dimethylpentyl, octyl,
1-methyl-heptyl, 2-ethylhexyl, 5,5-dimethylhexyl, nonyl, decyl,
1-methylnonyl, 3,7-dimethyloctyl and 7,7-dimethyloctyl
radicals.
[0021] In a particularly advantageous manner, the dicyano
derivatives of formula I are such that:
[0022] represents naphthyl or phenyl, optionally substituted with
one or more radicals chosen from (C.sub.1-C.sub.6)alkyl and
(C.sub.1-C.sub.6) alkoxy; and
[0023] Ar.sub.1 and Ar.sub.2 independently represent a phenyl group
optionally substituted with one or more (C.sub.1-C.sub.6)alkyl or
(C.sub.1-C.sub.6)alkoxy; or a (C.sub.4-C.sub.8)cyclcoalkyl group
optionally substituted with one or more (C.sub.1-C.sub.6)alkyl
groups.
[0024] Examples of preferred alkyl groups are, in particular,
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,
isopentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl, hexyl,
isohexyl, neohexyl, 1-methylpentyl, 3-methylpentyl,
1,1-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl and
1-methyl-1-ethylpropyl.
[0025] Advantageously, the alkyl radical contains from 1 to 4
carbon atoms.
[0026] The term "alkoxy" denotes an --O-alkyl radical in which
alkyl is as defined above.
[0027] Advantageously, the cycloalkyl groups are chosen from
cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and
cyclooctyl.
[0028] It should be understood that, according to the invention,
each of the naphthyl and phenyl groups representing A may be
substituted.
[0029] Among the ligands of formula I that are preferred are those
for which Ar.sub.1 and Ar.sub.2 are, independently, phenyl
optionally substituted with methyl or tert-butyl; or
(C.sub.5-C.sub.6)cycloalkyl optionally substituted with methyl or
tert-butyl.
[0030] The compounds that are most particularly preferred are those
of formula I in which Ar.sub.1 and Ar.sub.2 are identical. A
clearly preferred meaning of Ar.sub.1 and Ar.sub.2 is optionally
substituted phenyl.
[0031] Moreover, it is preferred for A to represent naphthyl
optionally substituted with one to five and preferably one to two
groups chosen from (C.sub.1-C.sub.6)alkyl and
(C.sub.1-C.sub.6)alkoxy. Better still, A represents unsubstituted
naphthyl.
[0032] When A represents optionally substituted phenyl, it is
preferred for this phenyl to be substituted in the meta position
relative to the group PAr.sub.1Ar.sub.2 with (C.sub.1-C.sub.6)alkyl
or (C.sub.1-C.sub.6)alkoxy and better still with methyl or methoxy,
the other positions of the phenyl, radical being unsubstituted.
[0033] One group of compounds that is more particularly preferred
consists of the compounds of formula I with a C.sub.2 axis of
symmetry, with the exclusion of any element of symmetry.
[0034] The notion of the C.sub.2 axis of symmetry is described in
"Elements of Stereochemistry", Wiley, New York, 1969 and in
"Advanced Organic Chemistry", Jerry March, Stereochemistry, Chapter
4.
[0035] Among this last group of preferred compounds especially
distinguished are the compounds of formulae Ia and Ib below: 4
[0036] in which Ar.sub.1 and Ar.sub.2 are as defined above and S
represents a substituent which is compatible with the reactions
involved, and in particular alkyl or alkoxy, which is preferably
C.sub.1-C.sub.6, 5
[0037] in which Ar.sub.1 and Ar.sub.2 are as defined above.
[0038] The process of the invention more specifically comprises the
steps consisting in:
[0039] i) brominating a diol of formula II: 6
[0040] in which A is as defined above, using a suitable brominating
agent so as to obtain a dibromo compound of formula III: 7
[0041] in which A is as defined above;
[0042] ii) esterifying the compound of formula III obtained in the
preceding step by the action of a sulfonic acid or an activated
form thereof, so as to obtain the corresponding disulfonate;
[0043] iii) substituting the two bromine atoms with cyano groups by
reacting the disulfonate obtained in the preceding step with a
suitable nucleophilic agent so as to obtain the corresponding
nitrile;
[0044] iv) coupling a phosphine of formula VI:
XPAr.sub.1Ar.sub.2 VI
[0045] in which X represents a hydrogen atom or a halogen atom and
Ar.sub.1 and Ar.sub.2 are as defined above, with the nitrile
obtained in the preceding step, in the presence of a catalyst based
on a transition metal, so as to obtain the expected compound of
formula I.
[0046] In step (i), the phenyl or naphthyl nucleus, respectively,
of the diol of formula II is brominated by the action of a suitable
brominating agent.
[0047] When A is an unsubstituted phenyl nucleus or a nucleus
bearing a substituent in the meta position relative to the OH
group, such as (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy,
the corresponding diol of formula IIa: 8
[0048] in which S.sub.1and S.sub.2 are as defined for S above or
independently represent a hydrogen atom or an alkyl or alkoxy
group, which is preferably C.sub.1-C.sub.6, gives the corresponding
bromo compound of formula IIIa: 9
[0049] in which S.sub.1 and S.sub.2 are as defined above.
[0050] When A is a naphthyl nucleus, the bromination of the
corresponding diol of formula IIb: 10
[0051] gives compound IIIb below: 11
[0052] More generally, the hydroxyl groups present on the phenyl
and naphthyl nuclei orient the electrophilic reaction such that the
position of the bromine atoms on these nuclei is well defined.
[0053] The bromination reaction of phenyl or naphthyl nuclei is an
electrophilic reaction which is readily performed by the action of
Br.sub.2 on the corresponding diol.
[0054] This reaction may be carried out in the presence of a
catalyst such as a Lewis acid and in particular iron chloride.
However, since the hydroxyl groups present on the phenyl and
naphthyl nuclei activate these nuclei, the bromination is readily
performed in the absence of any catalyst.
[0055] The diols of formula II are so reactive that it is desirable
to carry out the bromination at low temperature, for example
between -78.degree. and -30.degree. C. and preferably between -78
and -50.degree. C.
[0056] According to one preferred embodiment of the invention, the
bromination takes place in an inert aprotic solvent such as a
haloaromatic hydrocarbon (for example chlorobenzene or
dichlorobenzene); a nitroaromatic hydrocarbon such as a
nitrobenzene; an optionally halogenated aliphatic hydrocarbon such
as hexane, heptane, methylene chloride, carbon tetrachloride or
dichloroethane; or an alicyclic hydrocarbon.
[0057] In general, aromatic hydrocarbons with electron-poor
aromatic nuclei, i.e. nuclei bearing one or more
electron-withdrawing substituents, may be used.
[0058] Preferred solvents which may be mentioned are haloaliphatic
hydrocarbons and in particular methylene chloride.
[0059] As a variant, it is possible to perform the process in
glacial acetic acid as solvent. Under these conditions, a solution
of bromine in acetic acid is generally added dropwise to a solution
of the diol II in acetic acid.
[0060] Whether the process is performed in the presence or absence
of acetic acid, an excess of the brominating agent relative to the
diol II is used.
[0061] Preferably, the molar ratio of the brominating agent to the
diol II ranges between 2 and 5 and better still between 2 and
3.
[0062] When the process is performed in solution, the concentration
of the reagents may vary within a very wide range between 0.01 and
10 mol/l, for example between 0.05 and 1 mol/l.
[0063] In step (ii), the hydroxyl functions of the diol III are
esterified by the action of a sulfonic acid or an activated form
thereof, so as to obtain the corresponding disulfonate.
[0064] According to the invention, the nature of the sulfonic acid
used is not a deciding factor per se.
[0065] Advantageously, the sulfonic acid has the formula:
P--SO.sub.2--OH
[0066] in which P represents a hydrocarbon-based aliphatic group;
an aromatic carbocyclic group; or an aliphatic group substituted
with an aromatic carbocyclic group.
[0067] The expression "hydrocarbon-based aliphatic group" means in
particular an alkyl group as defined above, which is optionally
substituted. The nature of the substituent is such that it does not
react under the conditions of the esterification reaction. A
preferred example of a substituent for an alkyl group is a halogen
atom such as fluorine, chlorine, bromine or iodine.
[0068] The expression "aromatic carbocyclic group" means mono- or
polycyclic aromatic groups and in particular the mono-, bi- or
tricyclic groups defined above, and for example phenyl, naphthyl,
anthryl or phenanthryl.
[0069] The aromatic carbocyclic group is optionally substituted.
The nature of the substituent is not critical provided that it does
not react under the esterification conditions. Advantageously, the
substituent is optionally halogenated alkyl, alkyl being as defined
above and halogen representing chlorine, fluorine, bromine or
iodine, and preferably chlorine. As an example, "optionally
halogenated alkyl" denotes perfluoroalkyl such as trifluoromethyl
or pentafluoroethyl.
[0070] According to one preferred embodiment of the invention, the
sulfonic acid has the formula:
P--SO.sub.2--OH
[0071] in which P represents (C.sub.6-C.sub.10)aryl optionally
substituted with one or more optionally halogenated
(C.sub.1-C.sub.6)alkyl; optionally halogenated (C.sub.6-C.sub.10)
alkyl; or (C.sub.6-C.sub.10)aryl (C.sub.1-C.sub.6)alkyl in which
the aryl group is optionally substituted with one or more
optionally halogenated (C.sub.1-C.sub.6) alkyl and the alkyl group
is optionally halogenated.
[0072] Suitable examples of such sulfonic acids are
paratoluenesulfonic acid, methanesulfonic acid and
trifluoromethanesulfonic acid, the latter being particularly
preferred.
[0073] According to one preferred embodiment of the invention, an
activated derivative of the sulfonic acid is used. The term
"activated derivative" denotes a sulfonic acid in which the acid
function --SO.sub.3H is activated, for example by formation of an
anhydride bond or an --SO.sub.3Cl group.
[0074] One sulfonic acid derivative which is particularly
advantageous is the symmetrical anhydride of
trifluoromethanesulfonic acid, of formula
(CF.sub.3--SO.sub.2).sub.2O.
[0075] When the sulfonic acid has the formula P--SO.sub.3H above or
is an activated form of this acid, the disulfonate obtained after
step ii) corresponds to formula IV: 12
[0076] in which A and P are as defined above.
[0077] The conditions of the esterification reaction will be
readily developed by those skilled in the art. These conditions
depend in particular on the nature of the esterifying agent. When
the esterifying agent is a sulfonic acid, a higher reaction
temperature, of between 20 and 100.degree. C., may prove to be
necessary. Conversely, starting with an activated form of this
acid, such as an anhydride or a sulfonyl chloride, a lower
temperature may be suitable. Generally, a temperature of between
-30.degree. C. and 50.degree. C. and preferably between -15.degree.
C. and 20.degree. C. may suffice in this case.
[0078] The esterification is preferably carried out in a solvent.
Suitable solvents are, in particular, optionally halogenated
aliphatic, aromatic or cyclic hydrocarbons, such as those defined
above. Mention may be made of carbon tetrachloride and
dichloromethane. Dichloromethane is particularly preferred. Ethers
may also be used as solvent. Mention will be made, for example, of
C.sub.1-C.sub.6 dialkyl ethers (diethyl ether and diisopropyl
ether), cyclic ethers (tetrahydrofuran and dioxane),
dimethoxyethane and diethylene glycol dimethyl ether.
[0079] When the esterifying agent is an activated form of a
sulfonic acid, it is desirable to introduce a base into the
reaction medium. Examples of bases are N-methylmorpholine,
triethylamine, tributylamine, diisopropylethylamine,
dicyclohexylamine, N-methylpiperidine, pyridine,
2,6-dimethylpyridine, 4-(1-pyrrolidinyl) pyridine, picoline,
4-(N,N-dimethylamino)-pyridine, 2,6-di-t-butyl-4-methylpyridine,
quinoline, N,N-dimethylaniline and N,N-diethylaniline.
[0080] Preferred bases which will be essentially selected are
pyridine and 4-dimethylaminopyridine.
[0081] The reaction may also be performed in a two-phase mixture of
water and of an organic solvent such as a haloaliphatic hydrocarbon
(for example carbon tetrachloride) . In this case, it is preferable
to use an esterifying agent in anhydride form and to perform the
process in the presence of a water-soluble base such as KOH, NaOH
or K.sub.2CO.sub.3, preferably KOH.
[0082] The reaction of the sulfonic acid or the activated
derivative thereof with the bromo diol III is stoichiometric.
Nevertheless, it is preferable to perform the process in the
presence of an excess of the acid or the activated form thereof.
Thus, a ratio of the acid, optionally in activated form, to the
diol III of between 2 and 5 and better still between 2 and 3 is
recommended.
[0083] When the reaction is performed in solution, the
concentration of the reagents, which is not a critical parameter
according to the invention, may range between 0.1 and 10 mol/l and
advantageously between 1 and 5 mol/l.
[0084] Those skilled in the art may be inspired by the operating
conditions illustrated in J. Org. Chem., vol. 58, No. 7, 1993,
1945-1948 and Tetrahedron Letters, vol. 31, No. 7, 985-988, 1990
for carrying out the esterification.
[0085] The following step (iii) is a nucleophilic substitution. The
two bromine atoms borne by the nuclei A are displaced with cyano
groups by the action of a suitable nucleophilic agent.
[0086] So as to perform this substitution, those skilled in the art
may use any of the methods known in the art.
[0087] According to one preferred embodiment of the invention, the
nucleophilic agent used is copper cyanide.
[0088] The molar ratio of the copper cyanide to the disulfonate is
preferably greater than 2 and may advantageously range between 2
and 4 and preferably between 2 and 3.
[0089] The reaction is preferably carried out in a solvent.
Examples of solvents which may be mentioned are amides such as
formamide, dimethylformamide, dimethylacetamide,
2-N-methylpyrrolidinone and hexamethylphosphorylamide.
Dimethylformamide is clearly preferred. Pyridine is also a suitable
solvent. The reaction temperature is advantageously maintained
between 50 and 200.degree. C., for example between 70 and
190.degree. C. and better still between 80 and 180.degree. C.
[0090] A temperature which is more particularly suitable is between
100 and 190.degree. C.
[0091] The concentration of the reagents in the reaction medium
generally ranges between 0.1 and 10 mol/l, for example between 2
and 7 mol/l.
[0092] The isolation of the nitrile involves decomposing the
intermediate complex formed and trapping the excess cyanide.
[0093] The hydrolysis of the intermediate complex may be performed
either by the action of hydrated iron chloride or by the action of
aqueous ethylenediamine.
[0094] In the first case, the reaction medium is poured into an
aqueous 50-80% (g/ml) iron chloride solution containing
concentrated hydrochloric acid. The resulting solution is heated at
40-80.degree. C. until the complex has completely decomposed. The
medium is then separated out by settling and extracted
conventionally.
[0095] In the second case, the reaction medium is poured into an
aqueous ethylenediamine solution (ethylenediamine/water: 1/5-1/1
(v/v), for example 1/3 ) and the mixture is then stirred
vigorously. The medium is then separated by settling of the phases
and extracted in a manner which is known per se.
[0096] Those skilled in the art may be inspired by the work of L.
Friedman et al. published in J.O.C. 1961, 26, 1522, for isolating
the nitrile.
[0097] Starting with the disulfonate of formula IV mentioned above,
the product obtained at the end of this step is the nitrile of
formula V: 13
[0098] in which A and P are as defined above and the position of
the cyano group on the nucleus A is the same as that of the bromine
in compound IV.
[0099] In the following step (iv), a cross-coupling of a phosphine
of formula VI:
XPAr.sub.1Ar.sub.2 VI
[0100] in which X is a halogen or hydrogen atom and Ar.sub.1 and
Ar.sub.2 are as defined above, is carried out with the nitrile
obtained in the above step, in the presence of a catalyst based on
a transition metal.
[0101] This coupling leads directly to the expected compound of
formula I.
[0102] Examples of suitable catalysts are catalysts based on
nickel, palladium, rhodium, ruthenium or platinum or on a mixture
of these metals.
[0103] The preferred catalysts are nickel-based catalysts such as
those chosen from NiCl.sub.2; NiBr.sub.2; NiCl.sub.2(dppp);
NiCl.sub.2(dppb); NiCl.sub.2(dppf); NiCl.sub.2(dppe);
NiCl.sub.2(PPh.sub.3).sub.2; Ni(CO).sub.2(PPh.sub.3).sub.2;
Ni(PPh.sub.3).sub.4 and Ni[P(PhO).sub.3].sub.4 in which dppe means
(diphenylphosphino)ethane, dppp means (diphenylphosphino) propane,
dppb means (diphenylphosphino) butane and dppf means
(diphenylphosphino)ferrocenyl.
[0104] Among these catalysts, NiCl.sub.2(dppe) is preferred.
[0105] The reaction is generally carried out at a temperature of
from 50 to 200.degree. C. and preferably from 80 to 130.degree.
C.
[0106] The molar ratio of compound VI to the nitrile is at least 2.
It generally ranges between 2 and 4, for example between 2 and
3.
[0107] The amount of catalyst is preferably such that the molar
ratio of the nitrile to the catalyst ranges between 5 and 100 and
in particular between 5 and 80.
[0108] The reaction is preferably performed in a polar aprotic
solvent and in particular an amide such as those mentioned above.
In this case also, N,N-dimethylformamide is preferred.
Nevertheless, other types of polar solvent may be used, such as
(C.sub.1-C.sub.6)alkanols (ethanol) aromatic hydrocarbons (toluene,
xylene and benzene), ethers (dioxane) and acetonitrile.
[0109] The precise reaction conditions depend on the nature of the
compound of formula VI involved in the reaction.
[0110] When compound VI is HPAr.sub.1Ar.sub.2, the reaction is
advantageously performed in the presence of a base.
[0111] Bases that are particularly suitable are pyridine,
4-dimethylaminopyridine, 2,6-di-tert-butylpyridine,
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),
1,5-diazabicyclo[4.3.0]non-5-en- e (DBN) and
1,4-diazabicyclo-[2.2.2]octane (DABCO or triethylenediamine). DABCO
will advantageously be used as base. In this case, it is preferred
for the molar ratio of the nitrile to the catalyst to be between 5
and 20, for example between 7 and 15.
[0112] When the compound of formula VI is halPAr.sub.1Ar.sub.2 in
which hal is a halogen atom, preferably Cl or Br (better still Cl),
it is necessary to add zinc to the reaction medium.
[0113] The amount of zinc is preferably such that the molar ratio
of the zinc to the halPAr.sub.1AR.sub.2 ranges between 1 and 2 and
preferably between 1.2 and 1.7.
[0114] In this case, it is desirable to cool the reaction mixture
containing the solvent, the nitrile and compound VI to a
temperature of between -10.degree. C. and 20.degree. C. throughout
the addition of the zinc to the reaction medium. Then, the reaction
takes place by heating to a suitable temperature of between
50.degree. C. and 200.degree. C.
[0115] When the compound of formula VI is halPAr.sub.1Ar.sub.2, it
is preferred for the molar ratio of the nitrile to the catalyst to
be between 40 and 80, for example between 50 and 70.
[0116] For further details regarding the implementation of these
coupling reactions, those skilled in the art will refer to D. Cai
et al. J.O.C. 1994, 59, 7180 and D. J. Ager et al. Chem. Comm.
1997, 2359.
[0117] When A represents phenyl which is optionally substituted,
preferably with (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy,
the compound obtained after step (iv) has the formula Ic: 14
[0118] in which Ar.sub.1, Ar.sub.2, S.sub.1 and S.sub.2 are as
defined above for formula IIa.
[0119] When A represents naphthyl, the compound obtained after step
(iv) has the formula Ib: 15
[0120] in which Ar.sub.1 and Ar.sub.2 are as defined above.
[0121] The compounds of formula I are ligands capable of
coordinating to transition metals such as ruthenium and rhodium.
When combined with these metals, the ligands form complexes that
are useful in the asymmetric catalysis of enantioselective
hydrogenation reactions starting with varied substrates such as
.beta.-keto esters, .alpha.-keto esters and dehydroamino acids.
[0122] The present invention moreover provides a process for
converting the compounds of formula I (which contain two cyano
functions) into corresponding diaminomethyl compounds.
[0123] As a variant, it is possible to convert the two cyano
functions of the compounds of formula I into carboxylic acid,
imine, hydroxymethyl or amide functions.
[0124] The products resulting from these conversions are also
ligands which may be used in asymmetric catalysis.
[0125] Thus, according to another of its aspects, the invention
relates to a process comprising, in addition to steps (i) to (iv)
defined above, the step consisting in reducing the nitrile function
of the compound of formula I by the action of a reducing agent so
as to obtain a compound of formula VII: 16
[0126] in which A, Ar.sub.1 and Ar.sub.2 are as defined above.
[0127] A suitable reducing agent is lithium aluminum hydride
(LiAlH.sub.4).
[0128] The invention is not intended to be limited to the use of
this particular reducing agent.
[0129] The reaction is preferably carried out in a solvent or a
mixture of solvents.
[0130] When the reducing agent is LiAlH.sub.4, the solvent
advantageously comprises one or more aromatic hydrocarbons (such as
benzene, toluene or xylene) mixed with one or more ethers.
[0131] Ethers which may be mentioned are C.sub.1-C.sub.6 alkyl
ethers (diethyl ether and diisopropyl ether), cyclic ethers
(dioxane and tetrahydrofuran), dimethoxyethane and diethylene
glycol dimethyl ether.
[0132] Cyclic ethers such as tetrahydrofuran are preferred.
[0133] When the reducing agent is LiAlH.sub.4, a mixture of toluene
and tetrahydrofuran in proportions ranging between (v/v)
70-50/30-50:toluene/tetrahydrofuran (for example 60/40:toluene/THF)
will be chosen more preferably.
[0134] The reduction may be carried out at a temperature of between
20.degree. C. and 100.degree. C. and preferably between 40.degree.
C. and 80.degree. C.
[0135] A large excess of the reducing agent is usually used. Thus,
the molar ratio of the reducing agent to the compound of formula I
generally ranges between 1 and 30, for example between 2 and 20 and
in particular between 5 and 18.
[0136] The concentration of the reagents in the medium is variable;
it may be maintained between 0.005 and 1 mol/l.
[0137] The compounds of formula VII obtained according to the
process of the invention are novel and form another subject of the
invention. Among these compounds, preference is given to those for
which A represents naphthyl, which correspond to the following
formula: 17
[0138] in which Ar.sub.1 and Ar.sub.2 are as defined in claim
1.
[0139] A preferred group of these diamines consists of the
compounds of formula VIIa in which Ar.sub.1 and Ar.sub.2 are
independently chosen from phenyl optionally substituted with methyl
or tert-butyl; and (C.sub.5-C.sub.6)cycloalkyl optionally
substituted with methyl or tert-butyl.
[0140] Better still, preference is given to the compounds in which
Ar.sub.1 and Ar.sub.2 are identical and represent optionally
substituted phenyl.
[0141] As a variant, the invention provides a process comprising,
in addition to steps (i) to (iv) defined above, the step consisting
in treating the compound of formula I in a acidic medium or in
basic medium, so as to obtain the corresponding carboxylic acid of
formula VIII: 18
[0142] in which A, Ar.sub.1 and Ar.sub.2 are as defined above.
[0143] The conversion of a nitrile function into a carboxylic acid
function is described in organic chemistry textbooks. Thus, those
skilled in the art can readily determine the appropriate reaction
conditions.
[0144] One simple way of performing the process consists in using
aqueous sodium hydroxide as hydrolysis agent.
[0145] The process of the invention may be carried out starting
with an optically active compound II with conservation of the
chirality from the start to the end of the synthesis.
[0146] With the aim of conserving the chirality, the esterification
of the compound of formula III will be carried out under anhydrous
conditions in the presence of suitable bases chosen from
N-methylmorpholine, triethylamine, tributylamine,
diisopropylethamine, dicyclohexylamine, N-methylpiperidine,
pyridine, 2,6-dimethylpyridine, 4-(1-pyrrolidinyl)pyridine,
picoline, 4-(N,N-dimethylamino)pyridine,
2,6-di-t-butyl-4-methylpyridine, quinoline, N,N-dimethylaniline and
N,N-diethylaniline.
[0147] Thus, starting with a (S)-2,2'-dihydroxy-1,1'-binaphthyl,
(S)-6,6'-dibromo-2,2'-dihydroxy1,1'-binaphthyl and
(S)-6,6'-dicyano-2,2'-bis(diarylphosphino)-1,1'-binaphthyl are
successively obtained.
[0148] The same process applied to
(R)-2,2'-dihydroxy-1,1'-binaphthyl gives
(R)-6,6'-dicyano-2,2-bis(diarylphosphino)-1,1'-binaphthyl.
[0149] The optically active isomers of the compounds of formula II
are conventionally isolated from the corresponding racemic
mixtures. An optically active resolving agent is usually used to do
this.
[0150] In the case of 1,1'-bis(2-naphthol), the enantiomers may be
resolved by forming an inclusion complex with
(R,R)-1,2-cyclohexanediamin- e, (R,R) or
(S,S)-2,3-(+)-dimethoxy-N,N,N',N'-tetramethylsuccinamide or
alternatively (R,R) or
(S,S)-2,3-(+)-N,N,N',N'-tetramethyl-2,2'-dimethyl--
1,3-dioxolane-trans-dicarboxamide. These methods have been
described in the literature. Another way of performing the process
consists in forming an inclusion complex of 1'-bis(2-naphthol) with
N-benzylcinchoninium chloride. Using acetonitrile as solvent, only
the complex with one of the enantiomers precipitates, thus allowing
the two enantiomers to be separated. Reference will be made in this
respect to the studies by D. Cai published in Tetrahedron Letters,
vol. 36, No. 44, 7991-7994, 1995.
[0151] As a variant, it is possible, in order to prepare an
optically active compound of formula I, to carry out step a)
starting with a racemic diol of formula II, to resolve the bromo
derivative obtained of formula III and then to continue the
synthesis starting with the appropriate optically active bromo
compound III.
[0152] The difunctional ligands obtained according to the processes
of the invention may be used in the preparation of metal complexes
intended for the asymmetric catalysis of hydrogenation reactions,
hydrosilylation reactions, hydroboration reactions of unsaturated
compounds, epoxidation reactions of allylic alcohols, vicinal
hydroxylation reactions, hydrovinylation reactions,
hydroformylation reactions, cyclopropanation reactions,
isomerization reactions of olefins, polymerization reactions of
propylene, addition reactions of organometallic compounds to
aldehydes, allylic alkylation reactions, reactions of aldol type,
Diels-Alder reactions and, in general, reactions for the formation
of C--C bonds (such as allylic substitutions or Grignard
cross-couplings).
[0153] According to one preferred embodiment of the invention, the
complexes are used for the hydrogenation of C.dbd.O, C.dbd.C and
C.dbd.N bonds.
[0154] The complexes which may be used in reactions of this type
are rhodium, ruthenium, palladium, platinum, iridium, cobalt,
nickel or rhenium complexes, preferably rhodium, ruthenium,
iridium, palladium and platinum complexes. Even more
advantageously, rhodium, ruthenium or iridium complexes are
used.
[0155] Specific examples of said complexes of the present invention
are given below, with no limiting nature.
[0156] In the following formulae, P represents a ligand according
to the invention.
[0157] A preferred group of the rhodium and iridium complexes is
defined by the formula:
[MeLig.sub.2P]Y.sub.I IX
[0158] in which:
[0159] P represents a ligand according to the invention;
[0160] Y.sub.I represents a coordinating anionic ligand;
[0161] Me represents iridium or rhodium; and
[0162] Lig represents a neutral ligand.
[0163] Among these compounds, those in which:
[0164] Lig represents an olefin containing from 2 to 12 carbon
atoms;
[0165] Y.sub.I represents a PF.sub.6.sup.-, PCl.sub.6.sup.-,
BF.sub.4.sup.-, BCl.sub.4.sup.-, SbF.sub.6.sup.-, SbCl.sub.6.sup.-,
BPh.sub.4.sup.-, ClO.sub.4.sup.-, CN.sup.-, CF.sub.3SO.sub.3.sup.-
or halogen, preferably Cl.sup.- or Br.sup.-, anion, a
1,3-diketonate, alkylcarboxylate or haloalkylcarboxylate anion with
a lower alkyl (preferably C.sub.1-C.sub.6) radical, a
phenylcarboxylate or phenoxide anion in which the benzene ring may
be substituted with lower alkyl (preferably C.sub.1-C.sub.6)
radicals and/or halogen atoms,
[0166] are particularly preferred.
[0167] In formula IX, Lig.sub.2 may represent two Lig ligands as
defined above or a bidentate ligand such as a linear or cyclic,
polyunsaturated bidentate ligand comprising at least two
unsaturations.
[0168] It is preferred according to the invention for Lig.sub.2 to
represent 1,5-cyclooctadiene, norbornadiene or for Lig to represent
ethylene.
[0169] The expression "lower alkyl radicals" generally means a
linear or branched alkyl radical containing from 1 to 4 carbon
atoms.
[0170] Other iridium complexes are those of formula:
[IrLigP]Y.sub.I X
[0171] in which Lig, P and Y.sub.I are as defined for formula
IX.
[0172] A preferred group of ruthenium complexes consists of the
compounds of formula:
[RuY.sub.I.sup.1Y.sub.I.sup.2P] XI
[0173] in which:
[0174] P represents a ligand according to the invention;
[0175] Y.sub.I.sup.1 and Y.sub.I.sup.2, which may be identical or
different, represent a PF.sub.6.sup.-, PCl.sub.6.sup.-,
BF.sub.4.sup.-, BCl.sub.4.sup.-, SbF.sub.6.sup.-, SbCl.sub.6.sup.-,
BPh.sub.4.sup.-, ClO.sub.4.sup.- or CF.sub.3SO.sub.3.sup.- anion, a
halogen atom, more particularly chlorine or bromine, or a
carboxylate anion, preferably acetate or trifluoroacetate.
[0176] Other ruthenium complexes are those corresponding to formula
XII below:
[RuY.sub.I.sup.3arPY.sub.I.sup.4] XII
[0177] in which:
[0178] P represents a ligand according to the invention;
[0179] ar represents benzene, p-methylisopropylbenzene or
hexamethylbenzene;
[0180] Y.sub.I.sup.3 represents a halogen atom, preferably chlorine
or bromine;
[0181] Y.sub.I.sup.4 represents an anion, preferably a
PF.sub.6.sup.-, PCl.sub.6.sup.-, BF.sub.4.sup.-, BCl.sub.4.sup.-,
SbF.sub.6.sup.-, SbCl.sub.6.sup.-, BPh.sub.4.sup.-, ClO.sub.4.sup.-
or CF.sub.3SO.sub.3.sup.- anion.
[0182] It is also possible to use in the process of the invention
palladium-based and platinum-based complexes.
[0183] As more specific examples of said complexes, mention may be
made, inter alia, of Pd(hal).sub.2P and Pt(hal).sub.2P in which P
represents a ligand according to the invention and hal represents
halogen such as, for example, chlorine.
[0184] The complexes comprising a ligand according to the invention
and the transition metal may be prepared according to the known
processes described in the literature.
[0185] The complexes are generally prepared from a precatalyst
whose nature varies according to the transition metal selected.
[0186] In the case of rhodium complexes, the precatalyst is, for
example, one of the following compounds:
[Rh.sup.I(CO).sub.2Cl].sub.2; [Rh.sup.I(COD).sub.2Cl].sub.2 in
which COD denotes cyclooctadiene; or Rh.sup.I(acac)(CO).sub.2 in
which acac denotes acetylacetonate.
[0187] In the case of ruthenium complexes, precatalysts that are
particularly suitable are
bis(2-methylallyl)-cycloocta-1,5-dieneruthenium and
[RuCl.sub.2(benzene)].sub.2. Mention may also be made of Ru(COD)
(.eta..sup.3-(CH.sub.2).sub.2CHCH.sub.3).sub.2 .
[0188] By way of example, starting with
bis(2-methylallyl)-cycloocta-1,5-d- ieneruthenium, a solution or
suspension is prepared containing the metallic precatalyst, a
ligand and a fully degassed solvent such as acetone (the ligand
concentration in the solution or suspension ranging between 0.001
and 1 mol/l), to which is added a methanolic hydrogen bromide
solution. The ratio of the ruthenium to the bromine advantageously
ranges between 1:1 and 1:4 and preferably between 1:2 and 1:3. The
molar ratio of the ligand to the transition metal is itself about
1. It may be between 0.8 and 1.2.
[0189] When the precatalyst is [RuCl.sub.2(benzene)].sub.2, the
complex is prepared by mixing the precatalyst, the ligand and an
organic solvent and optionally maintaining a temperature of between
15.degree. C. and 150.degree. C. for 1 minute to 24 hours,
preferably 30.degree. C. to 120.degree. C. for 10 minutes to 5
hours.
[0190] Solvents which may be mentioned are aromatic hydrocarbons
(such as benzene, toluene and xylene), amides (such as formamide,
dimethylformamide, dimethyl-acetamide, 2-N-methylpyrrolidinone or
hexamethyl-phosphorylamide) and alcohols (such as ethanol,
methanol, n-propanol and isopropanol), and mixtures thereof.
[0191] Preferably, when the solvent is an amide, in particular
dimethylformamide, the mixture of the ligand, the precatalyst and
the solvent is heated to between 80.degree. C. and 120.degree.
C.
[0192] As a variant, when the solvent is a mixture of an aromatic
hydrocarbon (such as benzene) with an alcohol (such as ethanol),
the reaction medium is heated to a temperature of between
30.degree. C. and 70.degree. C.
[0193] The catalyst is then recovered according to the conventional
techniques (filtration or crystallization) and used in asymmetric
reactions. Nevertheless, the reaction which needs to be catalyzed
with the complex thus prepared may be carried out without
intermediate isolation of the catalyst complex.
[0194] In the text hereinbelow, the case of hydrogenation is
described in detail.
[0195] The unsaturated substrate, dissolved in a solvent comprising
the catalyst, is placed under a pressure of hydrogen.
[0196] The hydrogenation is carried out, for example, at a pressure
ranging between 1.5 bar and 100 bar, and at a temperature of
between 20.degree. C. and 100.degree. C.
[0197] The exact implementation conditions depend on the nature of
the substrate which needs to be hydrogenated. Nevertheless, in the
general case, a pressure of from 20 bar to 80 bar and preferably
from 40 bar to 60 bar, and a temperature of from 30.degree. C. to
70.degree. C., are particularly suitable.
[0198] The reaction medium may consist of the reaction medium in
which the catalyst was obtained. The hydrogenation reaction then
takes place in situ.
[0199] As a variant, the catalyst is isolated from the reaction
medium in which it was obtained. In this case, the reaction medium
for the hydrogenation reaction consists of one or more solvents,
chosen in particular from C.sub.1-C.sub.5 aliphatic alcohols such
as methanol or propanol and an amide as defined above, for example
dimethylformamide, optionally mixed with benzene.
[0200] When the hydrogenation reaction takes place in situ, it is
desirable to add to the reaction medium one or more solvents chosen
from those mentioned above, and more particularly one or more
aliphatic alcohols.
[0201] According to one preferred embodiment, fully degassed
methanol and the substrate are added to the reaction medium
containing the complex. The amount of methanol, or more generally
of solvent, which may be added is such that the concentration of
the substrate in the hydrogenation reaction medium is between
1.times.10.sup.-3 and 10 mol/l and preferably between 0.01 and 1
mol/l.
[0202] The molar ratio of the substrate to the catalyst generally
ranges from 1/100 to 1/100 000 and preferably from 1/20 to 1/2 000.
This ratio is, for example, 1/1 000.
[0203] The rhodium complexes prepared from the ligands of the
invention are more especially suitable for the asymmetric catalysis
of isomerization reactions of olefins.
[0204] The ruthenium complexes prepared from the ligands of the
invention are more especially suitable for the asymmetric catalysis
of hydrogenation reaction of carbonyl bonds, of C.dbd.C bonds and
of C.dbd.N bonds.
[0205] As regards the hydrogenation of double bonds, the suitable
substrates are of the type such as .alpha.,.beta.-unsaturated
carboxylic acid and/or .alpha.,.beta.-unsaturated carboxylic acid
derivatives. These substrates are described in EP 95943260.0.
[0206] The .alpha.,.beta.unsaturated carboxylic acid and/or the
derivative thereof corresponds more particularly to formula A:
19
[0207] in which:
[0208] R.sub.1, R.sub.2, R.sub.3 and R.sub.4 represent a hydrogen
atom or any hydrocarbon-based group, provided that:
[0209] if R.sub.1 is different than R.sub.2 and other than a
hydrogen atom, then R.sub.3 can be any hydrocarbon-based group or
functional group denoted by R,
[0210] if R.sub.1 or R.sub.2 represents a hydrogen atom and if
R.sub.1 is other than R.sub.2, then R.sub.3 is other than a
hydrogen atom and other than --COOR.sub.4,
[0211] if R.sub.1 is identical to R.sub.2 and represents any
hydrocarbon-based group or functional group denoted by R, then
R.sub.3 is other than --CH--(R).sub.2, and other than
--COOR.sub.4,
[0212] one of the groups R.sub.1, R.sub.2 and R.sub.3 possibly
representing a functional group.
[0213] A specific example which may be mentioned, inter alia, is
2-methyl-2-butenoic acid.
[0214] A first group of preferred substrates is formed by
substituted acrylic acids that are precursors of amino acids and/or
derivatives.
[0215] The expression "substituted acrylic acids" means the set of
compounds whose formula is derived from that of acrylic acid by
substituting not more than two of the hydrogen atoms borne by the
ethylenic carbon atoms with a hydrocarbon-based group or with a
functional group.
[0216] They may be symbolized by the following chemical formula:
20
[0217] in which:
[0218] R.sub.9 and R'.sub.9, which may be identical or different,
represent a hydrogen atom, a linear or branched alkyl group
containing from 1 to 12 carbon atoms, a phenyl group or an acyl
group containing from 2 to 12 carbon atoms, and preferably an
acetyl or benzoyl group,
[0219] R.sub.8 represents a hydrogen atom, an alkyl group
containing from 1 to 12 carbon atoms, a cycloalkyl radical
containing from 3 to 8 carbon atoms, an arylalkyl radical
containing from 6 to 12 carbon atoms, an aryl radical containing
from 6 to 12 carbon atoms or a heterocyclic radical containing from
4 to 7 carbon atoms,
[0220] R.sub.10 represents a hydrogen atom or a linear or branched
alkyl group containing from 1 to 4 carbon atoms.
[0221] Mention may be made more particularly of:
[0222] methyl .alpha.-acetamidocinnamate,
[0223] methyl acetamidoacrylate,
[0224] benzamidocinnamic acid,
[0225] .alpha.-acetamidocinnamic acid.
[0226] A second preferred group of substrates consists of itaconic
acid and derivatives thereof of formula: 21
[0227] in which:
[0228] R.sub.11 and R.sub.12, which may be identical or different,
represent a hydrogen atom, a linear or branched alkyl group
containing from 1 to 12 carbon atoms, a cycloalkyl radical
containing from 3 to 8 carbon atoms, an arylalkyl radical
containing from 6 to 12 carbon atoms, an aryl radical containing 6
to 12 carbon atoms a heterocyclic radical containing from 4 to 7
carbon atoms,
[0229] R.sub.10 and R'.sub.10, which may be identical or different,
represent a hydrogen atom or a linear or branched alkyl group
containing from 1 to 4 carbon atoms.
[0230] As more specific examples, mention may be made in particular
of itaconic acid and dimethyl itaconate.
[0231] A third preferred group of substrates is defined by formula
A3: 22
[0232] in which:
[0233] R".sub.10 represents a hydrogen atom or a linear or branched
alkyl group containing from 1 to 4 carbon atoms,
[0234] R.sub.13 represents a phenyl or naphthyl group optionally
bearing one or more substituents.
[0235] Specific examples which may be mentioned are the substrates
leading by hydrogenation to 2-(3-benzoyl-phenyl)propionic acid
(Ketoprofen.RTM.), 2-(4-isobutyl-phenyl)propionic acid
(Ibuprofen.RTM.) and 2-(5-methoxy-naphthyl)propionic acid
(Naproxen.RTM.)
[0236] As regards the hydrogenation of carbonyl bonds, the
appropriate substrates of ketone type correspond more preferably to
formula B: 23
[0237] in which:
[0238] R.sub.5 is different than R.sub.6,
[0239] R.sub.5 and R.sub.6 represent a hydrocarbon-based radical
containing from 1 to 30 carbon atoms optionally comprising one or
more functional groups,
[0240] R.sub.5 and R.sub.6 can form a ring optionally comprising
another hetero atom,
[0241] Z is or comprises an oxygen or nitrogen hetero atom or a
functional group comprising at least one of these hetero atoms.
[0242] These compounds are specifically described in FR 96/08060
and EP 97930607.3.
[0243] A first preferred group of such keto substrates has the
formula B1: 24
[0244] in which:
[0245] R.sub.5 is different than R.sub.6, the radicals R.sub.5 and
R.sub.6 represent a hydrocarbon-based radical containing from 1 to
30 carbon atoms optionally comprising another ketone and/or acid,
ester, thioacid or thioester function;
[0246] R.sub.5 and R.sub.6 can form a substituted or unsubstituted
carbocyclic or heterocyclic ring containing 5 or 6 atoms.
[0247] Among these compounds, the ones that are most particularly
preferred are the ketones chosen from:
[0248] methyl phenyl ketone,
[0249] isopropyl phenyl ketone,
[0250] cyclopropyl phenyl ketone,
[0251] allyl phenyl ketone,
[0252] p-methylphenyl methyl ketone,
[0253] benzyl phenyl ketone,
[0254] phenyl triphenylmethyl ketone,
[0255] o-bromoacetophenone,
[0256] .alpha.-bromoacetone,
[0257] .alpha.-dibromoacetone,
[0258] .alpha.-chloroacetone,
[0259] .alpha.-dichloroacetone,
[0260] .alpha.-trichloroacetone,
[0261] 1-chloro-3,3-dichloroacetone
[0262] 1-chloro-2-oxobutane,
[0263] 1-fluoro-2-oxobutane,
[0264] 1-chloro-3-methyl-2-butanone,
[0265] .alpha.-chloroacetophenone,
[0266] 1-chloro-3-phenylacetone,
[0267] .alpha.-methylaminoacetone,
[0268] .alpha.-dimethylaminoacetone,
[0269] 1-butylamino-2-oxopropane,
[0270] 1-dibutylamino-2-oxopropane,
[0271] 1-methylamino-2-oxobutane,
[0272] 1-dimethylamino-2-oxobutane,
[0273] 1-dimethylamino-3-methyl-2-oxobutane,
[0274] 1-dimethylamino-2-oxopentane,
[0275] .alpha.-dimethylaminoacetophenone,
[0276] .alpha.-hydroxyacetone,
[0277] 1-hydroxy-3-methyl-2-butanone,
[0278] 1-hydroxy-2-oxobutane,
[0279] 1-hydroxy-2-oxopentane,
[0280] 1-hydroxy-2-oxohexane,
[0281] 1-hydroxy-2-oxo-3-methylbutane,
[0282] .alpha.-hydroxyacetophenone,
[0283] 1-hydroxy-3-phenylacetone,
[0284] .alpha.-methoxyacetone,
[0285] .alpha.-methoxyacetophenone,
[0286] .alpha.-ethoxyacetone,
[0287] .alpha.-butoxyacetophenone,
[0288] .alpha.-chloro-p-methoxyacetophenone,
[0289] .alpha.-naphthenone,
[0290] 1-ethoxy-2-oxobutane,
[0291] 1-butoxy-2-oxobutane,
[0292] .alpha.-dimethoxyphosphorylacetone,
[0293] 3-oxotetrahydrothiophene.
[0294] Substrates of aldehyde/ketone type containing a second
carbonyl group in an .alpha., .beta., .gamma. or .delta. position
relative to the first carbonyl group are also particularly suitable
in the context of the invention. Examples of such diketo compounds
are:
[0295] .alpha.-formylacetone,
[0296] diacetyl,
[0297] 3,4-dioxohexane,
[0298] 4,5-dioxooctane,
[0299] 1-phenyl-1,2-dioxopropane,
[0300] 1-phenyl-2,3-dioxobutane,
[0301] diphenylglyoxal,
[0302] p-methoxydiphenylglyoxal,
[0303] 1,2-cyclopentanedione,
[0304] 1,2-cyclohexanedione,
[0305] acetylacetone,
[0306] 3,5-heptanedione,
[0307] 4,6-nonanedione,
[0308] 5,7-undecadione,
[0309] 2,4-hexanedione,
[0310] 2,4-heptanedione,
[0311] 2,4-octanedione,
[0312] 2,4-nonanedione,
[0313] 3,5-nonanedione,
[0314] 3,5-decanedione,
[0315] 2,4-dodecanedione,
[0316] 1-phenyl-1,3-butanedione,
[0317] 1-phenyl-1,3-pentanedione,
[0318] 1-phenyl-1,3-hexanedione,
[0319] 1-phenyl-1,3-heptanedione,
[0320] 3-methyl-2,4-pentanedione,
[0321] 1,3-diphenyl-1,3-propanedione,
[0322] 1,5-diphenyl-2,4-pentanedione,
[0323] 1,3-bis(trifluoromethyl)-1,3-propanedione,
[0324] 3-chloro-2,4-pentanedione,
[0325] 1,5-dichloro-2,4-pentanedione,
[0326] 1,5-dihydroxy-2,4-pentanedione,
[0327] 1,5-dibenzyloxy-2,4-pentanedione,
[0328] 1,5-diamino-2,4-pentanedione,
[0329] 1,5-bis(methylamino)-2,4-pentanedione,
[0330] 1,5-bis(dimethylamino)-2,4-pentanedione,
[0331] methyl 3,5-dioxohexanoate,
[0332] 3-carbomethoxy-2,4-pentanedione,
[0333] 3-carboethoxy-2,4-pentanedione,
[0334] 1,3-cyclopentanedione,
[0335] 1,3-cyclohexanedione,
[0336] 1,3-cycloheptanedione,
[0337] 5-carboethoxy-1,3-cyclopentanedione,
[0338] 2-acetyl-1-cyclopentanone,
[0339] 2-acetyl-1-cyclohexanone.
[0340] As other substrates that are particularly suitable, mention
may be made of keto acids or derivatives thereof and keto thioacids
or derivatives thereof with a functional group (acid, ester,
thioacid or thioester) in an .alpha., .beta., .gamma. or .delta.
position relative to the carbonyl group. Examples of these are:
[0341] 2-acetylbenzoic acid,
[0342] pyruvic acid,
[0343] 2-oxobutanoic acid,
[0344] 3-methyl-2-oxobutanoic acid,
[0345] phenylglyoxylic acid,
[0346] phenylpyruvic acid,
[0347] p-methoxyphenylpyruvic acid,
[0348] 3,4-dimethoxyphenylpyruvic acid,
[0349] methyl acetoacetate,
[0350] ethyl acetoacetate,
[0351] n-propyl acetoacetate,
[0352] isopropyl acetoacetate,
[0353] n-butyl acetoacetate,
[0354] t-butyl acetoacetate,
[0355] n-pentyl acetoacetate,
[0356] n-hexyl acetoacetate,
[0357] n-heptyl acetoacetate,
[0358] n-octyl acetoacetate,
[0359] methyl 3-oxopentanoate,
[0360] methyl 3-oxohexanoate,
[0361] methyl 3-oxohexanoate,
[0362] ethyl 3-oxooctanoate,
[0363] ethyl 3-oxononanoate,
[0364] ethyl 3-oxodecanoate,
[0365] ethyl 3-oxoundecanoate,
[0366] ethyl 3-oxo-3-phenylpropanoate,
[0367] ethyl 4-phenyl-3-oxobutanoate,
[0368] methyl 5-phenyl-3-oxopentanoate,
[0369] ethyl 3-oxo-3-p-methoxyphenylpropanoate,
[0370] methyl 4-chloroacetoacetate,
[0371] ethyl 4-chloroacetoacetate,
[0372] methyl 4-fluoroacetoacetate,
[0373] ethyl 3-trifluoromethyl-3-oxopropanoate,
[0374] ethyl 4-hydroxy-3-oxobutanoate,
[0375] methyl 4-methoxyacetoacetate,
[0376] methyl 4-tert-butoxyacetoacetate,
[0377] methyl 4-benzyloxy-3-oxobutanoate,
[0378] ethyl 4-benzyloxy-3-oxobutanoate,
[0379] methyl 4-amino-3-oxobutanoate,
[0380] ethyl 3-methylamino-3-oxobutanoate,
[0381] methyl 4-dimethylamino-3-oxobutanoate,
[0382] ethyl 4-dimethylamino-3-oxobutanoate,
[0383] methyl 2-methylacetoacetate,
[0384] ethyl 2-methylacetoacetate,
[0385] ethyl 2-chloroacetoacetate,
[0386] diethyl 2-acetylsuccinate,
[0387] diethyl 2-acetylglutarate,
[0388] dimethyl acetylmalonate,
[0389] thiomethyl acetoacetate,
[0390] thioethyl acetoacetate,
[0391] thiophenyl acetoacetate,
[0392] methyl pyruvate,
[0393] ethyl 3-methyl-2-oxobutanoate,
[0394] ethyl phenylglyoxolate,
[0395] methyl phenylpyruvate,
[0396] ethyl phenylpyruvate,
[0397] 3-oxobutanoic dimethylamide,
[0398] 3-oxobutanoic benzylamide,
[0399] 2-carboethoxycyclopentanone,
[0400] 2-carboethoxycyclohexanone,
[0401] ketopentalacetone,
[0402] 4-oxopentanoic acid,
[0403] 4-oxohexanoic acid,
[0404] 4-oxoheptanoic acid,
[0405] 4-oxodecanoic acid,
[0406] 4-oxododecanoic acid,
[0407] 4-phenyl-4-oxybutyric acid,
[0408] 4-p-methoxyphenyl-4-oxobutyric acid,
[0409] 4-(3,4-dimethoxyphenyl)-4-oxobutyric acid,
[0410] 4-(3,4,5-trimethoxyphenyl)-4-oxobutyric acid,
[0411] 4-p-chlorophenyl-4-oxybutyric acid,
[0412] 4-phenyl-4-oxobutyric acid.
[0413] It should be noted that when a .gamma.-keto acid or
derivative needs to be asymmetrically hydrogenated, the product
obtained is generally a .gamma.-butyrolactone derivative and, in
the case of a .delta.-keto acid, it is a valerolactone
derivative.
[0414] Other examples of ketones which may be mentioned, inter
alia, are the following monocyclic or polycyclic, saturated or
unsaturated cyclic keto compounds: 2526
[0415] in which R represents a phenyl which is unsubstituted or
substituted with alkyl or alkoxy radicals or a halogen atom; or R
represents an alkyl or cycloalkyl group which is unsubstituted or
substituted with alkyl or alkoxy radicals or a halogen atom, a
hydroxyl, ether or amine group; or R represents a halogen atom or a
hydroxyl, alkoxy or amine group.
[0416] Ketones of steroid type may also be used (for example
3-cholestanone or 5-cholesten-3-one). 27
[0417] Other keto substrates which may be mentioned are the
compounds of formula B2: 28
[0418] in which:
[0419] R.sub.5, which is other than R.sub.6, have the meaning given
above,
[0420] R.sub.7 represents:
[0421] a hydrogen atom,
[0422] a hydroxyl group,
[0423] a group OR.sub.17,
[0424] a hydrocarbon radical R.sub.17,
[0425] a group of formula 29
[0426] a group of formula 30
[0427] with R.sub.14, R.sub.15, R.sub.16 and R.sub.17 which
represent a hydrogen atom or a hydrocarbon-based group containing
from 1 to 30 carbon atoms.
[0428] Examples of compounds of formula B2 are:
[0429] N-alkylketoimines, such as:
[0430] N-isobutyl-2-iminopropane
[0431] N-isobutyl-1-methoxy-2-iminopropane
[0432] N-arylalkylketoimines, such as:
[0433] N-benzyl-1-imino-1-(phenyl)ethane
[0434] N-benzyl-1-imino-1-(4-methoxyphenyl)ethane
[0435] N-benzyl-1-imino-1-(2-methoxyphenyl)ethane
[0436] N-arylketoimines, such as:
[0437] N-phenyl-2-iminopentane
[0438] N-(2,6-dimethylphenyl)-2-iminopentane
[0439] N-(2,4,6-trimethylphenyl)-2-iminopentane
[0440] N-phenyl-1-imino-1-phenylethane
[0441] N-phenyl-1-methoxy-2-iminopropane
[0442] N-(2,6-dimethylphenyl)-1-methoxy-2-iminopropane
[0443] N-(2-methyl-6-ethylphenyl)-1-methoxy-2-iminopropane
[0444] compounds of hydrazone type, optionally N-acylated or
N-benzoylated:
[0445] 1-cyclohexyl-1-(2-benzoylhydrazono)ethane,
[0446] 1-phenyl-1-(2-benzoylhydrazono)ethane,
[0447] 1-p-methoxyphenyl-1-(2-benzoylhydrazono)ethane,
[0448] 1-p-ethoxyphenyl-1-(2-benzoylhydrazono)ethane,
[0449] 1-p-nitrophenyl-1-(2-benzoylhydrazono)ethane,
[0450] 1-p-bromophenyl-1-(2-benzoylhydrazono)ethane,
[0451] 1-p-carboethoxyphenyl-1-(2-benzoylhydrazono)ethane,
[0452] 1,2-diphenyl-1-(2-benzoylhydrazono)ethane,
[0453] 3-methyl-2-(2-p-dimethylaminobenzoylhydrazono)butane,
[0454] 1-phenyl-1-(2-p-methoxybenzoylhydrazono)ethane,
[0455] 1-phenyl-1-(2-p-dimethylaminobenzoylhydrazono)ethane,
[0456] ethyl 2-(2-benzoylhydrazono)propionate,
[0457] methyl 2-(2-benzoylhydrazono)butyrate,
[0458] methyl 2-(2-benzoylhydrazono)valerate,
[0459] methyl 2-phenyl-2-(2-benzoylhydrazono)acetate.
[0460] Other starting substrates are semicarbazones and cyclic keto
imines containing an endocyclic or exocyclic bond, such as: 31
[0461] According to one particularly preferred embodiment of the
invention, the substrate is a .beta.-keto ester (such as methyl
acetoacetate or methyl 3-oxovalerate), an .alpha.-keto ester (such
as methyl benzoylformate or methyl pyruvate), a ketone (such as
acetophenone), an olefin, an unsaturated amino acid or a derivative
thereof (in particular an ester thereof).
[0462] The complexes obtained from the ligands of formula I and the
derivatives thereof give, in particular, good enantioselectivity in
hydrogenation reactions.
[0463] More particularly, the ruthenium complexes prepared from the
ligands obtained according to the process of the invention are
suitable for the asymmetric catalysis of hydrogenation reactions of
the C.dbd.O bonds of .beta.-keto esters.
[0464] The ruthenium complexes and ligands of formula VII are
particularly suitable for the asymmetric catalysis of hydrogenation
reactions of the C.dbd.O bonds of ketones.
[0465] Thus, according to another of its aspects, the invention
relates to the use of a compound of formula I or of formula VII or
of formula VIII for the preparation of a metal complex intended for
asymmetric catalysis, and more especially a ruthenium, iridium or
rhodium complex.
[0466] The use of a ligand of formula VII for the preparation of a
metal complex and more specifically a ruthenium complex, intended
for the asymmetric catalysis of hydrogenation reactions of ketones,
forms a preferred subject of the invention.
[0467] The examples which follow illustrate the invention more
specifically.
PREPARATION 1
Preparation of (S)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphthyl
[0468] 7.7 g (26.9 mmol) of (S)-2,2'-dihydroxy-1,1'-binaphthyl are
dissolved in 145 ml of dichloromethane. The solution is cooled to
-75.degree. C. and 3.66 ml of Br.sub.2 (71.7 mmol) are then added
dropwise over 30 minutes with constant stirring. The solution is
stirred for a further 2 and a half hours and then cooled to room
temperature. After addition of 180 ml of sodium bisulfite (10% by
mass), the organic phase is washed with saturated NaCl solution and
dried over Na.sub.2SO.sub.4. After evaporating off the solvent, the
solid obtained is recrystallized from a toluene/cyclohexane mixture
at 80.degree. C. to give 9.8 g (22 mmol, 82% yield) of expected
product.
[0469] The optical rotation as measured on a Perkin-Elmer-241
polarimeter (I=10 cm, 25.degree. C., concentration c in g/dm.sup.3)
is 124.3 at c=1.015 and 578 nm.
[0470] For the preparation of the dibromo derivative of the title,
reference may be made to G. Dotsevi et al., J. Am. Chem. Soc.,
1979, 101, 3035.
PREPARATION 2
Preparation of
(S)-6,6'-dibromo-2,2'-bis(trifloromethanesulfonyloxy)-1,1'--
binaphthyl
[0471] 9.52 g (21.4 mmol) of
(S)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphth- yl are dissolved in
a mixture of 40 ml of CH.sub.2Cl.sub.2 and 5.4 ml of pyridine.
After cooling the mixture to 0.degree. C., 8.7 ml (14.5 g, 51.5
mmol) of triflic anhydride ((CF.sub.3--SO.sub.2).sub.2O) are added
slowly. After stirring for 6 h, the solvent is evaporated off and
the reaction mass is dissolved in 100 ml of ethyl acetate. After
washing with aqueous 5% HCl solution, saturated NaHCO.sub.3
solution and saturated NaCl solution, the organic phase is dried
over Na.sub.2SO.sub.4 and the solvent is then evaporated off under
reduced pressure. The yellow oil is purified by chromatography on
silica (CH.sub.2Cl.sub.2) to give 12.5 g (17.7 mmol, 83% yield) of
expected product.
[0472] [.alpha.].sub.D=151.3.degree. (c=1.005, THF), the optical
rotation being measured under the same conditions as in Preparation
1, but at the wavelength corresponding to the D line of sodium.
[0473] For the preparation of the title compound, reference also be
made to the studies by M. Vondenhof Tetrahedron Letters, 1990, 31,
985.
PREPARATION 3
Preparation of
(S)-6,6'-dibromo-2,2-bis(trifluoromethanesulfonyloxy)-1,1'--
binaphthyl
[0474] As a variant, the title compound may be prepared from
(R)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphthyl according to the
procedure described below.
[0475] 10.0 g (22.52 mmol) of
(R)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binapht- hyl are dissolved in
a solution of 6.3 g (0.11 mol) of KOH in 300 ml of degased water.
The mixture is cooled to 0.degree. C. and a solution of 11.4 ml
(19.1 g, 68 mmol) of triflic anhydride in 200 ml of CCl.sub.4 is
then added over 45 minutes such that the temperature does not
exceed 10.degree. C. After stirring for 30 min, 300 ml of
CH.sub.2Cl.sub.2 are added. The organic phase is washed with water
and then dried over MgSO.sub.4. 15.89 g of crude product are then
purified by chromatography on silica (1/1
CH.sub.2Cl.sub.2/cyclohexane) to give 12.94 g (18.27 mmol, 81%
yield) of pure product.
[0476] [.alpha.].sub.D=153.2.degree. (c=0.945, THF), the optical
rotation being measured under the same conditions as in Preparation
1, but at the wavelength corresponding to the D line of sodium.
[0477] .sup.1H NMR (CDCl.sub.3, 200 MHz): .delta. (ppm): 7.07
(d(J.sub.H-H=7.07), CH, 2H); 7.48 (dd(J.sup.1.sub.H-H=9.05;
J.sup.2.sub.H-H=1.94), CH, 2H); 7.62 (d(J.sub.H-H=9.11), CH, 2H); p
8.06 (d(J.sub.H-H=9.13), CH, 2H); 8.18 (d (J.sub.H-H=1.90), CH,
2H).
[0478] C NMR (CDCl.sub.3, 200 MHz); .delta. (ppm)=118.1
(Cq(J.sub.C-F=320)); 120.2 (Cq); 120.7 (CH); 122.0 (Cq); 123.4
(Cq); 128.2 (CH); 130.5 (CH); 131.4 (CH); 131.6 (Cq); 131.7 (CH);
133.4 (Cq).
PREPARATION 4
Preparation of
(S)-6,6'-dicyano-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-
-binaphthyl
[0479] 12.5 g (17.7 mmol) of the compound prepared in Preparation 2
and 3.5 g (38.8 mmol) of CuCN are stirred at 180.degree. C. in 20
ml of N-methylpyrrolidone for 4 h. After cooling to room
temperature, the black suspension is poured into a solution of 15
ml of diaminoethane in 35 ml of water. The solution is extracted
several times with 30 ml of CH.sub.2Cl.sub.2 and the organic phase
is washed with aqueous 10% KCN solution and saturated NaCl
solution. After drying over Na.sub.2SO.sub.4, the solvent is
evaporated off under reduced pressure. The black oil thus obtained
is purified by chromatography on silica (9/1
CH.sub.2Cl.sub.2/cyclohexane) to give 6.5 g (10.8 mmol, 61% yield)
of pure product.
[0480] [.alpha.].sub.D=-171.7.degree. (c=1.15, THF), the optical
rotation being measured under the same conditions as in Preparation
1, but at the wavelength corresponding to the D line of sodium.
[0481] .sup.1H NMR (CDCl.sub.3, 200 MHz); .delta. (ppm)=7.30
(d(J.sub.H-H=9.81), CH, 2H); 7.59 (dd(J.sup.1.sub.H-H=8.82,
J.sup.2.sub.H-H=1.65), CH, 2H); 7.78 (d(J.sub.H-H=9.11), CH, 2H);
8.29 (d(J.sub.H-H8.09), CH, 2H); 8.46 (d(J.sub.H-H=1.29), CH,
2H).
[0482] .sup.13C NMR (CDCl.sub.3, 200 MHz): .delta. (ppm)=111.7
(CN); 118.0 (Cq); 118.1 (Cq(J.sub.C-F=320)); 121.16 (CH); 123.3
(Cq); 127.7 (CH); 128.9 (CH); 131.4 (Cq); 133.2 (CH); 134.4 (Cq);
134.5 (CH); 147.4 (Cq).
[0483] For the preparation of the title compound, those skilled in
the art may refer to the studies by Friedman et al., J. Org. Chem.
1961, 26, 2522 and M. S. Neuman et al., J. Org. Chem., 1961, 26,
2525.
EXAMPLE 1
Preparation of (S)-6,6'-dicyano-2,2'-bis(diphenyl
phosphino)-1,1'-binaphth- yl (I: A=phenyl;
Ar.sub.1=Ar.sub.2=phenyl)
[0484] A solution of NiCl.sub.2dppe (371 mg, 0.7 mmol) and of
diphenylphosphine (3 ml, 17 mmol) in 14 ml of DMF (anhydrous and
degased) is heated for 30 minutes at 100.degree. C. in a 100 ml
three-necked round-bottomed flask on which is mounted an argon
inlet.
(S)-6,6'-Dicyano-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl
(4.4 g, 7.4 mmol) and DABCO (3.375 g, 30 mmol) dissolved in 20 ml
of DMF are added dropwise. The reaction medium is left at
100.degree. C. After 1.3 and 7 hours, 0.75 ml of diphenylphosphine
is added. The solution is stirred for 2 days. It is then cooled to
0.degree. C. and then filtered under argon and washed with methanol
(2.times.10 ml). Finally, the solid is dried under vacuum to give
the expected product in a yield of 50%.
[0485] Elemental analysis for C.sub.46H.sub.30N.sub.2P.sub.2
calculated: C=80.88; H=4.43; N=4.10; P=9.07; found: C=81.61;
H=4.45; N=4.11; P=8.99.
[0486] .sup.1H NMR (CDCl.sub.3, 200 MHz) .delta. (ppm): 6.59 (d,
2H, CH); 6.87 (dd, 2H, CH); 6.92-6.99 (m, 4H, CH); 7.09 (t, 4H,
CH); 7.17-7.31 (m, 12H, CH); 7.57 (d, 2H, CH); 7.95 (d, 2H, CH);
8.20 (s, 2H, CH).
[0487] .sup.13NMR (CDCl.sub.3, 50 MHz) .delta. (ppm): 109.8 (CH);
119.0 (Cq); 126.3 (CH); 127.7 (CH); 128.4 (CH); 128.5 (CH); 128.5
(CH); 128.6 (CH); 128.8 (CH); 129.3 (CH); 132.0 (CH); 132.1 (Cq);
132.9 (CH(triplet J.sub.C-P=11.7); 133.9 (Cq); 134.1 (Cq); 134.9
(CH(triplet J.sub.C-P=9.9)); 136.8 (Cq); 140.6 (Cq).
[0488] .sup.31P NMR (CDCl.sub.381 MHz) .delta. (ppm): -12.75.
EXAMPLE 2
Preparation of
(S)-6,6'-bis(aminomethyl)-2,2'-bis(di-phenylphosphino)-1,1'-
-binaphthyl (VII: Ar.sub.1=Ar.sub.2=C.sub.6H.sub.5)
[0489] 557 mg (14.7 mmol) of LiAlH.sub.4 are dissolved in a mixture
of THF (30 ml)/toluene (60 ml) in a 250 ml round-bottomed flask
placed under an argon atmosphere.
(S)-6,6'-Dicyano-2,2'-bis(diphenylphosphino)-1,1'-binap- hthyl (650
mg, 0.97 mmol) is added to this solution, which is stirred and
refluxed for 4 hours. It is then cooled to 0.degree. C. 600 .mu.l
of water and 600 .mu.l of 15% NaOH are added. 2 g of Celite are
then added and the mixture is filtered through a Millipore filter
under argon. 60 ml of dichloromethane are added and the mixture is
stirred and filtered again. This operation is carried out three
times. The organic phase obtained is washed with saturated aqueous
NaCl solution and then dried over Na.sub.2SO.sub.4. The solvent is
evaporated to give a yellow solid (657 mg, quantitative yield)
characterized by NMR (proton, carbon and phosphorus) corresponding
to the expected structure.
[0490] Elemental analysis for C.sub.46H.sub.38N.sub.2P2 calculated:
C=80.59; H=6.00; N=3.55; P=7.84; found: C=81.14; H=5.51; N=3.13;
P=7.90.
[0491] .sup.1H NMR (CDCl.sub.3, 200 MHz) .delta. (ppm): 1.68 (s,
4H, NH.sub.2); 3.81 (s, 4H, CH.sub.2); 6.72 (s, 4H, CH); 6.9-7.3
(m, 20H, CH); 7.33 (d, 2H, CH); 7.64 (s, 2H, CH); 7.76 (d, 2H,
CH).
[0492] .sup.31P NMR (CDCl.sub.3, 81 MHz) .delta. (ppm): -15.08.
EXAMPLE 3
Preparation of a Ruthenium Catalyst
[0493] The catalyst is prepared in situ. All the solvents used were
rigorously degased and are anhydrous. The reaction medium is
maintained under an argon atmosphere. The ligand and the metallic
precatalyst, bis(2-methyl-allyl) cycloocta-1,5-dieneruthenium, in a
ligand/metal molar ratio of 1:1, are directly weighed out in a 5 ml
conical-based glass reactor taken from the oven and equipped with a
stirrer. The reactor is sealed with a septum and the air is flushed
out with an argon inlet. Acetone (1 ml) is then added to give a
white suspension. This suspension is stirred for 30 minutes and a
0.29 M methanolic HBr solution is then added (Ru/Br ratio of
1/2.3). A change in the color of the solution, which turns brown,
is then observed. This solution is stirred for a further 1 hour and
the solvent is then evaporated off. The catalyst is thus obtained
with the appearance of a brown solid.
[0494] Two complexes are prepared according to this procedure.
[0495] The first, Dicyano-BINAP, starting with
(S)-6,6'-dicyano-2,2'-bis(d- iphenylphosphino)-1,1'-binaphthyl
(obtained in Example 1).
[0496] The second, Diam-BINAP, starting with
(S)-6,6'-diaminomethyl-2,2'-b-
is(diphenylphosphino)-1,1'-binaphthyl (obtained in Example 2).
EXAMPLE 4
[0497] This example illustrates the hydrogenation of a .beta.-keto
ester in the presence of the ruthenium complexes prepared in
Example 3.
[0498] The hydrogenation protocol is described below:
[0499] Methanol which has been predried over magnesium is added
(2.5 ml) under argon to the conical reactor in which the catalyst
has just been prepared. The substrate is then added (in a given
catalyst/substrate ratio). The operation consisting in placing
under vacuum and filling the reactor with argon is repeated three
times. The septum is then replaced with a pierced stopper and the
reactor is then placed in an autoclave. The autoclave is purged
three times with argon and then three times with hydrogen, after
which 40 bar of hydrogen pressure is applied. The autoclave is
placed on a hot plate (50.degree. C.) and stirring is maintained
overnight. The conical reactor is finally recovered, the stopper is
replaced with a septum and argon is reinjected into this reactor.
The reactor is placed in a centrifuge and the solution is then
extracted using a syringe. It is placed in a 50 ml round-bottomed
flask and diluted with 20 ml of methanol, thus ready to be injected
onto a chromatography column for gas chromatography to analyze the
degree of conversion and the enatioselectivity of the reaction.
[0500] More specifically, the determination of the enantiomeric
excesses is carried out by chiral gas chromatography on a column of
Macherey-Nagel type (Lipodex A 25 m.times.0.25 mm).
[0501] The test substrate is a .beta.-keto ester, namely methyl
acetoacetate. It gives, after hydrogenation, methyl
3-hydroxybutanoate. The compound obtained is the S enantiomer, the
catalysts being prepared from the compounds of Examples 1 and
2.
[0502] The results obtained for each of the complexes described in
Example 3 above are given in Table 1 below:
1TABLE 1 Degree of Enantiomeric Substrate Complex conversion (%)
excess (%) Methyl Dicyano-BINAP 25 100 acetoacetate Methyl
Diam-BINAP 100 100 acetoacetate
[0503] By way of comparison, the hydrogenation of methyl
acetoacetate is carried out in the presence of a ruthenium complex
prepared from (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl. The
reaction conditions for the hydrogenation and for the preparation
of the metal catalyst are as described above. The results obtained
are collated in Table 2, it being understood that the hydrogenation
product is, in this case, methyl (R)-3-hydroxybutanoate.
2TABLE 2 (comparative) Degree of Enantiomeric Substrate Complex
conversion (%) excess (%) Methyl BINAP 100 99 acetoacetate
[0504] As may be seen, the complexes prepared from the compounds of
Examples 1 and 2 above give excellent enantiomeric excesses.. The
catalysts of the invention thus allow a highly enantioselective
hydrogenation reaction to be carried out.
EXAMPLE 5
[0505] This example illustrates the hydrogenation of an aromatic
ketone in the presence of the ruthenium complexes prepared in
Example 3.
[0506] The hydrogenation protocol followed is as described in
Example 4, except that the substrate used is acetophenone. It leads
to phenylethanol.
[0507] The determination of the enantiomeric excesses is performed
under the same conditions as in Example 4.
[0508] The results obtained are given in Table 3 below.
3 TABLE 3 Degree of Enantiomeric Complex conversion (%) excess (%)
Dicyano-BINAP 22 2 Diam-BINAP 72 18
[0509] By way of comparison, this same substrate was hydrogenated
in the presence of the ruthenium complex with
2,2'-bis(diphenylphosphino)-1,1'-b- inaphthyl prepared in Example
4.
[0510] The hydrogenation reaction conditions are as described
above.
[0511] The results obtained are a degree of conversion of less than
1% (traces) and an enantiomeric excess of 0%.
[0512] This example shows very clearly the superiority of the
catalysts of the invention.
* * * * *