U.S. patent application number 10/738749 was filed with the patent office on 2004-07-08 for diphosphines.
Invention is credited to Brown, John Michael, Carmichael, Duncan, Doucet, Henry.
Application Number | 20040133042 10/738749 |
Document ID | / |
Family ID | 10841529 |
Filed Date | 2004-07-08 |
United States Patent
Application |
20040133042 |
Kind Code |
A1 |
Brown, John Michael ; et
al. |
July 8, 2004 |
Diphosphines
Abstract
A non-symmetrical diphosphine of the formula
R.sup.1R.sup.2P--(Z)--PR.sup.3R.sup.4 said diphosphine not having
C.sub.2 symmetry, wherein Z represents a chain of 2 to 4 carbon
atoms which may be substituted, which chain may be saturated or
unsaturated, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each
independently are aliphatic, aromatic or heteroaromatic groups
attached to the phosphorus by carbon, nitrogen, oxygen or sulphur
such that each of the moieties R.sup.1R.sup.2P and PR.sup.3R.sup.4
contains a chiral centre.
Inventors: |
Brown, John Michael;
(Oxford, GB) ; Carmichael, Duncan; (Oxford,
GB) ; Doucet, Henry; (Oxford, GB) |
Correspondence
Address: |
QUARLES & BRADY LLP
411 E. WISCONSIN AVENUE
SUITE 2040
MILWAUKEE
WI
53202-4497
US
|
Family ID: |
10841529 |
Appl. No.: |
10/738749 |
Filed: |
December 17, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10738749 |
Dec 17, 2003 |
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09830268 |
Oct 9, 2001 |
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6706926 |
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09830268 |
Oct 9, 2001 |
|
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PCT/GB99/03599 |
Oct 29, 1999 |
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Current U.S.
Class: |
568/12 |
Current CPC
Class: |
B01J 31/2409 20130101;
B01J 2531/822 20130101; B01J 2531/827 20130101; B01J 2531/828
20130101; C07B 53/00 20130101; B01J 2531/824 20130101; B01J 31/2433
20130101; C07F 9/65683 20130101; B01J 31/24 20130101; C07F 9/5027
20130101; B01J 2231/645 20130101; B01J 31/1845 20130101; B01J
2531/821 20130101 |
Class at
Publication: |
568/012 |
International
Class: |
C07F 009/02 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 29, 1998 |
GB |
9823716.7 |
Claims
1. A non-symmetrical diphosphine of the
formulaR.sup.1R.sup.2P--(Z)--PR.su- p.3R.sup.4said diphosphine not
having C.sub.2 symmetry, wherein Z represents a chain of 2 to 4
carbon atoms which may be substituted, which chain may be saturated
or unsaturated, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each
independently are aliphatic, aromatic or heteroaromatic groups
attached to the phosphorus by carbon, nitrogen, oxygen or sulphur
such that each of the moieties R.sup.1R.sup.2P and PR.sup.3R.sup.4
contains a chiral centre.
2. A diphosphine according to claim 1, wherein Z represents a chain
of 2 carbon atoms.
3. A diphosphine according to claim 1, wherein R.sup.1 and R.sup.2
are linked, and/or R.sup.3 and R.sup.4 are linked, to form a
substituted or unsubstituted 3, 4, 5, 6 or 7 membered phosphorus
heterocycle.
4. A diphosphine according to claim 3, wherein R.sup.1 and R.sup.2
are linked to form a ring of the formula: 10wherein R.sup.5 and
R.sup.6, which may be the same or different, are hydrogen, hydroxy
or C.sub.1 to C.sub.4 alkoxy and R.sup.9 and R.sup.10, which may be
the same or different, are hydrogen or C.sub.1 to C.sub.4 alkyl,
and all of R.sup.5, R.sup.6, R.sup.9 and R.sup.10 cannot be
hydrogen at the same time.
5. A diphosphine according to claim 1, wherein at least one of
R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is substituted or
unsubstituted phenyl.
6. A diphosphine according to claim 5, wherein the phenyl group is
substituted by one or more hydroxy groups.
7. A diphosphine according to claim 5, wherein the phenyl group is
substituted by one or more or C.sub.1 to C.sub.4 alkoxy groups.
8. A diphosphine according to claim 1 wherein at least one of the
phosphorus atoms is ligated to a borane.
9. A catalyst comprising a diphosphine as claimed in claim 1 and a
metal.
10. A catalyst according to claim 9, wherein the metal is rhodium,
iridium, ruthenium, palladium or platinum.
11. A catalyst according to claim 9, wherein the catalyst is
neutral or cationic.
12. A cationic catalyst according to claim 11, wherein the
counterion is halide, tetrafluoroborate, hexafluorophosphate,
hexafluoroantimonate, sulfonate of the formula R.sup.7SO.sub.3,
wherein R.sup.7 is an aliphatic or aromatic group, or boronate of
the formula (R.sup.8).sub.4B, wherein the groups R.sup.8, which may
be the same or different, are aromatic groups.
13. A process for preparing a diphosphine as defined in claim 1,
which process comprises reacting a nucleophilic
phosphorus-containing reactant with an unsaturated phosphorus
containing reactant or a cyclopropyl phosphorus containing
reactant.
14. A process according to claim 13, wherein the nucleophilic
phosphorus-containing reactant is an enantiomerically pure
phosphine.
15. A process according to claim 14, wherein the phosphine is
ligated to a borane.
16. A process according to claim 15, wherein the enantiomerically
pure phosphine is ortho-anisylphenylphosphine ligated to
borane.
17. A process according to claim 13, wherein the unsaturated
phosphorus containing reactant is an oxidised phosphorus-bonded
alkene.
18. A process according to claim 17, wherein the alkene is ethene
or 1,3-butadiene.
19. A process according to claim 13, wherein a diphosphine
intermediate comprising a primary phosphine and a tertiary
phosphine is produced.
20. A process according to claim 19, wherein the primary phosphine
is converted into a phosphorus heterocycle.
21. A process according to claim 20, wherein the phosphorus
heterocycle is formed by reaction of the primary phosphine with an
enantiomerically pure diol activated by conversion of the hydroxyl
groups into leaving groups.
22. A process according to claim 21, wherein the diol is activated
by conversion into a halogen derivative, sulphate, sulfonate or
phosphate.
23. A process according to claim 21, wherein the diol is
mannitol.
24. A process for the asymmetric catalytic conversion of a
compound, wherein the catalyst is one claimed in claim 9.
25. A process according to claim 24, wherein the compound is
asymmetrically hydrogenated.
26. A process according to claim 24, wherein the compound is an
unsaturated ester.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of application
Ser. No. 09/830,268 filed Oct. 9, 2001 which is a 371 of
PCT/GB99/03599 filed Oct. 29, 1999.
[0002] The present invention relates to diphosphines, a process for
their preparation, metal catalysts derived from them and the use of
such catalysts.
[0003] There has been much interest in the asymmetric hydrogenation
of alkenes in recent years using, in particular, rhodium catalysts
derived from P-chiral diphosphines. There is a need to improve such
processes so as to enhance the enantio-selectivity.
[0004] It is commonly believed that C.sub.2 symmetric diphosphines
along with diols and diamines are endowed with superior properties
as ligands in catalysis and this is, of course, augmented by their
ease of synthesis. According to the present invention, we have
surprisingly found that excellent results can be obtained by a
novel class of unsymmetrical diphosphines.
[0005] Accordingly the present invention provides a non-symmetrical
diphosphine of the formula
R.sup.1R.sup.2P--(Z)--PR.sup.3R.sup.4
[0006] wherein Z represents a chain of 2 to 4 carbon atoms which
may be substituted, which chain may be saturated or unsaturated,
eg. ethylenically unsaturated, R.sup.1, R.sup.2, R.sup.3 and
R.sup.4, which may be the same or different, are aliphatic,
aromatic or heteroaromatic groups attached to the phosphorus by
carbon, nitrogen, oxygen or sulphur such that each phosphorus atom
and its substituents independently form a single enantiomer. It
will be appreciated that, in general, there is a single
stereochemical configuration around each phosphorus atom. Thus one
or both phosphorus atoms may form a chiral centre. Suitable
substituents of Z are hydrogen or aliphatic, aromatic or
heteroaromatic groups.
[0007] Preferably the diphosphines are 1,2-ethanes ie. the carbon
chain is --(CH.sub.2).sub.2--. Other typical Z groups include those
having the chain structure --C--C.dbd.C--C and --C--C.dbd.C--.
[0008] Generally, the substituents R.sup.1, R.sup.2, R.sup.3 and
R.sup.4 will be connected to the phosphorus atoms by carbon atoms.
In a preferred embodiment, R.sup.1 and R.sup.2 and/or R.sup.3 and
R.sup.4 are linked together to form the substituted or
unsubstituted 3, 4, 5, 6 or 7 membered phosphorus heterocycle and
preferably a phospholane ie. a five membered ring. This ring
desirably has the formula 1
[0009] wherein R.sup.5 and R.sup.6, which may be the same or
different, are hydrogen, hydroxy or C.sub.1 to C.sub.4 alkoxy and
R.sup.9 and R.sup.10, which may be the same or different, are
hydrogen or C.sub.1 to C.sub.4 alkyl.
[0010] It is also preferred that R.sup.1, R.sup.2, R.sup.3 and/or
R.sup.4 are substituted or unsubstituted phenyl, the substituents
preferably being hydroxy or C.sub.1, to C.sub.4 alkoxy groups.
[0011] The alkyl and alkoxy groups are typically methyl and
methoxy, respectively.
[0012] It will be appreciated that although the diphosphines are
non-symmetrical R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may all be
the same provided that the stereo orientation of R.sup.1 and
R.sup.2 on the one hand, is different from that of R.sup.3 and
R.sup.4. The values of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 must
be such that each phosphorus atom and its substituents
independently form a single enantiomer.
[0013] Preferred diphosphines of the present invention have the
formula 2
[0014] wherein R.sup.5 and R.sup.6, which may be the same or
different, are hydrogen, hydroxy or C.sub.1 to C.sub.4 alkoxy.
[0015] In accordance with another aspect of the present invention
these diphosphines can be obtained in optically pure form rather
than as a mixture of isomers.
[0016] It is usually convenient if at least one of the phosphorus
atoms is ligated to a borane. This enhances the storage stability
of the phosphine. It will be appreciated that it is a simple matter
to de-boronate when it is desired to generate the ligand. Catalysts
can be obtained from the diphosphine with a, generally low valent,
metal such as rhodium, iridium, ruthenium, palladium or platinum.
The ligand can be reacted in known manner to generate the catalyst.
For example a rhodium catalyst can be obtained by reaction of the
ligand with (COD).sub.2RhBF.sub.4. By "COD", as used herein, is
meant cyclooctadiene. The preparation of the catalysts from the
ligand can be obtained in known manner as one of skill in the art
will appreciate.
[0017] The catalysts of the present invention are generally neutral
or cationic complexes. Typical counterions which can be present if
they are cationic include halide, for example fluoride or chloride,
tetrafluoroborate, hexafluorophosphonate, hexafluoroantimonate, or
sulphonate of formula R.sup.7SO.sub.3 where R.sup.7 is an aliphatic
or aromatic group, or boronate of the formula (R.sup.8).sub.4B
wherein the R.sup.8 groups which may be the same or different are
aromatic groups. The aromatic groups are typically phenyl groups
which are optionally substituted. When R.sup.7 is aliphatic it is
typically an alkyl group, for example of 1 to 4 carbon atoms such
as methyl.
[0018] The non-symmetrical diphosphines of the present invention
are generally prepared by a Michael-type addition reaction of a
nucleophilic phosphorus-containing reactant with an unsaturated,
preferably an ethylenically unsaturated, phosphorus-containing
reactant or a cyclopropyl phosphorus-containing reactant.
[0019] The nucleophilic phosphorus-containing reactant may be any
compound of the formula
R.sup.11R.sup.12PH
[0020] wherein R.sup.11 and R.sup.12, which may be the same or
different, are aliphatic, aromatic or heteroaromatic groups
attached to the phosphorus by carbon, nitrogen, oxygen or sulfur.
The nucleophilic phosphorus-containing reactant may also be an
organometallic derivative of the formula
R.sup.11R.sup.12PM
[0021] which may be ionic or covalent, and in which R.sup.11 and
R.sup.12 are as defined above and M is a suitable metal.
[0022] Preferably the nucleophilic phosphorus-containing reactant
is an enantiomerically pure phosphine and most preferably it is an
enantiomerically pure phosphine borane such as
ortho-anisylphenylphosphin- e borane.
[0023] A phosphorus atom with electron-withdrawing substituents,
attached to a double bond results in the alkene being responsive to
nucleophiles. The unsaturated phosphorus-containing reactants
suitable for use in the present invention may be oxidised
phosphorus-bonded alkenes, for example diethyl vinylphosphonate,
which may later be reduced to provide a primary phosphine. The
alkene is preferably ethene or 1,3-butadiene.
[0024] The diphosphines of the present invention are typically
prepared via a diphosphine intermediate comprising a primary
phosphine and tertiary phosphine.
[0025] The primary phosphine may be elaborated by reaction with a
doubly electrophilic carbon moiety which can provide a source of
chirality giving an enantiomerically pure product. It may be
converted into a phosphorus heterocycle by reaction with a diol
activated by conversion of the hydroxyl groups into leaving groups.
The diol may be activated by, for example, conversion into a
halogen derivative, sulphate, sulfonate or phosphate. Diols
suitable for use in the present invention include C.sub.2 to
C.sub.6 diols. The diols may be unsaturated or saturated and they
may optionally be substituted by oxygen, nitrogen, sulfur,
aliphatic, aromatic or heteroaromatic groups.
[0026] It will be appreciated that other substituents may be
attached to the primary phosphine in an analogous manner.
[0027] In the process of the present invention it is advantageous
to convert one or both of the phosphorus atoms into, for example,
oxide or sulfide derivatives, preferably borane derivatives, which
may later be converted back into the desired phosphine or
diphosphine.
DESCRIPTION OF THE DRAWING
[0028] FIG. 1 shows an example of preparation of diphosphines
according to the present invention.
DETAILED DESCRIPTION
[0029] An example of preparation of diphosphines according to the
present invention is shown in Scheme 1 of FIG. 1. In Scheme 1 the
diphosphines produced combine the phosphorus moieties of DIPAMP (R,
R-1,2,-bis[(2-methoxyphenyl)phenylphosphino]ethane) 1 and BPE
(1,2-bis[2,5-dialkyl phospholano]ethane) 2 are combined. 3
[0030] The synthesis shown in Scheme 1 of FIG. 1 is based on the
conjugate addition of the racemic phosphineborane 3 to diethyl
vinylphosphonate. Alane reduction of the product 4 gives the
primary phosphineborane 5. Following deboronation, stepwise double
nucleophilic displacement on the cyclic sulfate 6 via BuLi
deprotonation gives the diphosphines 7 and 8 as a diastereomeric
mixture. These compounds may be separated by MPLC (EtOAc/pentane).
The analogous compounds 10-OH and 11-OH may be prepared from the
mannitol derivative 9 as with a corresponding methyl ethers 10-OMe
and 11-OMe.
[0031] The catalysts of the present invention may be used in the
asymmetric catalytic conversion of a variety of compounds wherein a
new C--B, C--Si, C--O, C--H, C--N or C--C bond is formed through
the influence of the catalyst with control of the configuration at
carbon. Such reactions include, for example, catalytic
hydroboration, hydrosilylation, transfer hydrogenation, amination,
cross-coupling, Heck olefination reactions, cyclopropanation,
aziridination, allylic alkylation and cycloadditions. Preferably
the catalysts are used in asymmetric hydrogenation. Preferred
substrates for asymmetric hydrogenation include unsaturated esters
such as esters of dehydroamino acids or methylenesuccinic acids. It
has been found that using the catalysts of the present invention, a
high enantiomer excess can be obtained from unsaturated esters
under mild conditions. It is believed that a single site in the
ligand directs reaction by H-bonding to the reactant and improves
the enantio-selectivity.
[0032] The Examples which follow further illustrate the present
invention.
EXAMPLES
[0033] The Synthesis of Enantiomerically Pure
1-(2-methoxyphenylphenylphos-
phino)-2-(2,5-dimethyl-3,4-dimethoxyphospholanyl) ethane.
[0034] The cyclic sulfate precursor was prepared from the known
mannitol-derived diol. (M Sanire, Y le Merrer, H El Hafa, J-C
Depezay, F Rocchiccioli, J. Labelled Cpd. Radiopharm., 1991, 29.
305.) Each compound may be obtained on ca 5 g scales as a
crystalline solid. The cyclic sulphate 9 is preferably subjected to
short-column chromatography, to remove traces of an impurity
suspected to be the monofunctionalised sulphate (itself isolated
and characterised by nmr). Nonetheless, it can be purified by
crystallisation from ether-pentane. No acid-induced cleavage of the
isopropylidene protecting group appears to take place.
[0035] Racemic o-anisylphenylphosphine and its corresponding borane
complex were prepared without difficulty by the method of Imamoto.
(T Imamoto, T Oshiki, T Onozawa, T Katsumoto and K Sato, J. Am
Chem. Soc., 112, 5244, 1990.) No scale-up problems were encountered
and the reaction was adapted to give 40 g of product without
difficulty. Both PhArPH and PhArPH(BH.sub.3) (Ar=phenyl, o-anisyl)
smoothly underwent KOtBu-catalysed Michael addition to diethyl
vinylphosphonate. Racemic 2-anisyl-phenylphosphinoethyl
diethylphosphinoethyl phosphonate 4 and 2-diarylphosphinoethyl
diethylphosphonate were obtained as their borane complexes on a 10
g scale in five minutes at room temperature. Alane reduction of
this product gave the primary phosphine 5.
[0036] The cyclisation to diphosphines 10-OH and 11-OH was carried
out by a two-stage sequence with butyl lithium in THF. Direct
hydrolysis of the crude phosphine (TMSCl--MeOH) gave the
diastereomeric diols which, running much more slowly on silica in
pure ether than the impurities, were easily separated by column
chromatography. The faster-running diastereomer (11-OH rf=0.25) can
easily be obtained in enantiomeric excesses better than 99%.
[0037] Hydrogenation of Esters of Dehydroamino Acids or
Methylenesuccinic Acid
[0038] 2 ml of degassed dichloromethane was added to (0.105 mmol)
of diphosphine borane under argon. 1.05 mmol of HBF.sub.4 was added
then the solution was stirred at 20-25.degree. C. during 14 hours.
Then 41 mg (0.1 mmol) of [Rh(COD)2]BF.sub.4 was added. After being
stirred for 10 minutes, the solvent was removed in vacuo and the
yellow-orange residue was triturated three times with 5 ml of
diethyl ether. The ether was removed via cannula filtration or
syringe and the orange residue dried in vacuo. These complexes were
stored in Schlenk tubes under argon. For the catalytic
hydrogenation reactions the complexes were prepared just before
use. 1 ml of a solution of Rhodium complex (2 mmol.vertline.l) in
methanol was transferred under argon via cannula or syringe to a
Schlenk tube under argon or hydrogen containing 0.2 mmol of olefin.
The solution was placed under hydrogen and stirred at 20-50.degree.
C. during 2-5 hours. After evaporation of the solvent, the product
was purified by chromatography on silica
(methanol/dichloromethane). Enantiomeric excesses determined by NMR
using Eu(hfc).sub.3 as chiral shift reagent or by gas
chromatography using a column Chrompack WCOT Fused Silica,
CP-Chirasil-DEX CB, 25 meters, inlet pressure 8 psi.
[0039] The hydrogenation of dehydroamino acids of different
structures is shown in Table 1. From this it will be seen that the
configuration of the phosphine and of the phospholane can be
"matched" or "mismatched" according to their relative
configurations. For the matched cases 11-OH and 11-OMe, enantiomer
excesses of up to 92% can be obtained. It will also be seen that
the extent to which the two centres influence the course of
catalysis may differ greatly depending on the substrate.
1 TABLE 1 substrate ligand e.e. 4 10-OMe 11-OMe 10-OH 11-OH 7 8 19
S 85 S 43 S 92 S 60 R 38 S 5 10-OMe 11-OMe 10-OH 11-OH 7 8 58 S 67
S 82 S 88 S 5 R 36 R 6 11OMe 10-OH 11-OH 77 S 72 S 90 S*
Conditions: substrate : catalyst: 100 :1, (COD).sub.2Rh BF.sub.4 as
precursor, 1.3 bar, MeOH, 1-3 h. *OSO.sub.2CF.sub.3.sup.- instead
of BF.sub.4.sup.-
[0040] The results of hydrogenation of itaconate esters and
half-esters are shown in Table 2. The mismatched diastereomers of
ligand 10 gave poor e.e.s and are not included. For the
1-substituted monoester 15, the hydroxy-ligand 11-OH gives a
superior e.e. to its methyl ether. The reverse is true for the
4-substituted monoester 16, where the methyl ether 11-OMe provides
the product of higher enantioselectivity.
2 TABLE 2 substrate ligand e.e. 7 11-OMe 8-OH 85 R 95 R 8 11-OMe
11-OH 93 R* 87 R 9 8-OMe 8-OH 85 R 80 R* Conditions: substrate :
catalyst: 100 :1, (COD).sub.2Rh BF.sub.4 as precursor, 1.3 bar,
MeOH, 1-3 h. *94% e.e. with OSO.sub.2CF.sub.3.sup.- instead of
BF.sub.4.sup.-
[0041] These preliminary results indicate that, contrary to
expectation, the enantioselectivity may be sensitive to a remote
substituent in the phospholane ring. Inspection of molecular models
suggests that the MeO- or HO-groups are axial in the 5-membered
ring of the phospholane, and in the vicinity of substituents on the
coordinated alkene. Hence cooperative association between ligand
and substrate may exist through hydrogen-bonding.
* * * * *