U.S. patent application number 11/298641 was filed with the patent office on 2006-07-20 for chiral ligands for application in asymmetric syntheses.
Invention is credited to Dieter Arlt, Benjamin Meseguer.
Application Number | 20060161022 11/298641 |
Document ID | / |
Family ID | 33553457 |
Filed Date | 2006-07-20 |
United States Patent
Application |
20060161022 |
Kind Code |
A1 |
Meseguer; Benjamin ; et
al. |
July 20, 2006 |
Chiral ligands for application in asymmetric syntheses
Abstract
The present invention relates to biarylbisphosphines and
intermediates thereof. The scope of the invention further
encompasses catalysts preparable from the biarylbisphosphines and
their use in asymmetric syntheses.
Inventors: |
Meseguer; Benjamin;
(Tarragona, ES) ; Arlt; Dieter; (Lerngo,
DE) |
Correspondence
Address: |
LANXESS CORPORATION
111 RIDC PARK WEST DRIVE
PITTSBURGH
PA
15275-1112
US
|
Family ID: |
33553457 |
Appl. No.: |
11/298641 |
Filed: |
December 8, 2005 |
Current U.S.
Class: |
568/17 ;
502/162 |
Current CPC
Class: |
B01J 31/24 20130101;
B01J 31/1875 20130101; B01J 2531/821 20130101; C07F 9/5329
20130101; B01J 2231/641 20130101; C07F 15/0053 20130101; C07B 53/00
20130101; C07F 9/65527 20130101; C07F 9/5027 20130101 |
Class at
Publication: |
568/017 ;
502/162 |
International
Class: |
C07F 9/02 20060101
C07F009/02; B01J 31/00 20060101 B01J031/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 2, 2004 |
WO |
PCT/EP04/05930 |
Jun 13, 2003 |
DE |
103 27 109.0 |
Aug 12, 2003 |
DE |
103 37 013.7 |
Claims
1. Compounds of the formula (I) ##STR8## in which B is a bivalent
moiety of the formula
--(CHR.sup.1).sub.n--(R.sup.2C.dbd.CR.sup.3)--(CHR.sup.4).sub.m
where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently
hydrogen or alkyl, and n and m are each independently zero or an
integer from 1 to 8, where, however, the sum of n and m is from 1
to 8, and in which, moreover, G is chlorine or hydrogen and R' and
R'' are each independently aryl or alkyl or in which B is a
bivalent moiety of the formula
--(CHR.sup.1).sub.n--(CR.sup.2R.sup.3).sub.m--(CHR.sup.4).sub.o
where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently
hydrogen or alkyl, preferably C.sub.1-C.sub.6-alkyl, and n, m and o
are each independently zero or an integer from 1 to 8, where,
however, the sum of n, m and o is from 1 to 8, preferably 3 or 4,
and in which, moreover, G is chlorine and R' and R'' are each
independently aryl or alkyl
2. Compounds as claimed in claim 1, characterized in that R.sup.1,
R.sup.2, R.sup.3 and R.sup.4 are each independently hydrogen,
methyl, ethyl, n-propyl, isopropyl, n-butyl and n-pentyl.
3. Compounds as claimed in at least one of claims 1 and 2,
characterized in that R' and R'' are each independently
C.sub.3-C.sub.8-alkyl or C.sub.5-C.sub.10-aryl which may be
unsubstituted, monosubstituted or polysubstituted by radicals which
are selected from the group of chlorine, fluorine, cyano, phenyl,
C.sub.1-C.sub.6-alkoxy and C.sub.1-C.sub.6-alkyl.
4. Compounds as claimed in at least one of claims 1 to 3,
characterized in that they are the following: (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
iphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
icyclohexyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-dimethylphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-dimethyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-4-fluorophenyl)phosphine and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butylphenyl)phosphine and also the corresponding
trans compounds, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(dipheny-
l)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(dicyclohexyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-dimethylphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(di-4-fluorophenyl)phosphine and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butylphenyl)phosphine, the stereoisomeric (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]-bis(diphenyl-
phosphines], the stereoisomeric (R) and
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphines) and also any mixtures of the enantiomers.
5. A process for preparing compounds of the formula (IV) ##STR9##
in which B, G, R' and R'' are each as defined in claim 1,
characterized in that compounds of the formula (III) ##STR10## are
reacted with a compound of the formula (VIa) or (VIb) or
successively with two different compounds of the formulae (VIa) and
(VIb) X.sup.3--(CHR.sup.1).sub.n--(R.sup.2C.dbd.CHR.sup.5) (VIa)
X.sup.4--(CHR.sup.4).sub.m--(R.sup.3C.dbd.CHR.sup.6) (VIb) in which
X.sup.3 and X.sup.4 are each chlorine, bromine, iodine or a
sulfonate and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each as
defined in claim 1, and R.sup.5 and R.sup.6 are each independently
hydrogen or C.sub.1-C.sub.4-alkyl to give compounds of the formula
(VII) ##STR11## and the compounds of the formula (VII) are then
converted in the presence of an olefin metathesis catalyst to
compounds of the formula (IV).
6. The process as claimed in claim 5, characterized in that the
compounds of the formula (VII) are subsequently reduced to
compounds of the formula (I) as claimed in claim 1.
7. Compounds of the formula (VII) ##STR12## in which R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R' and R'' are each as defined in claim
1 and R.sup.5 and R.sup.6 are each independently hydrogen or
C.sub.1-C.sub.4-alkyl.
8. Compounds as claimed in claim 7, characterized in that they are
the following: (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-cyclohexy-
l)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)-biphenyl-2,2'-diyl]bis[(di-3,5-di-t-
ert-butyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-dimet-
hylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-dimet-
hyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-4-fluorop-
henyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-di-te-
rt-butylphenyl)phosphine oxide.
9. Compounds of the formula (IV) ##STR13## in which B, R' and R''
are each as defined in claim 1.
10. Compounds as claimed in claim 9, characterized in that they are
the following: (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
icyclohexyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-4-fluorophenyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-di-tert.-butylphenyl)phosphine oxide and also the
corresponding trans compounds and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-cycl-
ohexyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(di-4-fluorophenyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butylphenyl)phosphine oxide, the stereoisomeric
(R)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]-bis(diphenyl-
phosphine oxides), the stereoisomeric
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphine oxides) and also any mixtures of the enantiomers.
11. Transition metal complexes comprising compounds as claimed in
one or more of claims 1 to 4.
12. Catalysts comprising transition metal complexes as claimed in
claim 11.
13. A process for the transition metal-catalyzed preparation of
enantiomerically enriched compounds, characterized in that it is
carried out in the presence of catalysts as claimed in claim 13.
Description
[0001] The present invention relates to biarylbisphosphines and
intermediates thereof. The scope of the invention further
encompasses catalysts preparable from the biarylbisphosphines and
their use in asymmetric syntheses.
[0002] Enantiomerically enriched biarylbisphosphines, especially
those which derive from substituted binaphthyls and biphenyls,
lead, as ligands of transition metal complex catalysts, often to
good to very good enantioselectivity (see, for example, Helv. Chim.
Acta 1988, 71, 897-929; Acc. Chem. Res. 1990, 23, 345-350; Synlett
1994, 501-503; Angew. Chem. 2001, 113, 40-75).
[0003] Steric and electronic factors, which are determined by the
type and arrangement of substituents on the biaryl system and
within the phosphine groups, influence both the enantioselectivity
and the activity of the catalysts prepared from such ligands.
[0004] In individual cases, Rh and Ru catalysts of this type are
used industrially for enantioselective C.dbd.C double bond
isomerizations and for enantioselective hydrogenations. The number
of such industrial processes has to date been restricted because
the number of available ligands which can be used with success
widely for a relatively large number of substrates is small.
Instead, the extensive investigations in this field show that,
owing to the fundamental substrate specificity of the catalyst
which has often been "tailored" for a quite specific substrate,
even slight changes within the same substrate group prevent the
required enantiomeric purity from being achieved for a very similar
product.
[0005] J. Org. Chem. 2000, 65, 6223-6226, WO 01/21625 disclose
representatives of a novel group of biphenylbisphosphines bridged
in the 6,6'-position, which, by variation of the length of the
alkylene moiety within the bridging element, enable adjustment of
the catalysts which are prepared from these ligands to certain
substrates (here: .beta.-keto esters), so that optimized
enantioselectivities are achieved. As a result of the investigation
published in J. Org. Chem., an optimized enantioselectivity is
described for a catalyst having a ligand with a
--(CH.sub.2).sub.4-- moiety as a bridging unit ("C4TunaPhos").
[0006] Independently of the aforementioned publications, a single
representative of this ligand group was disclosed in EP-A 1 095
946.
[0007] However, there is still a need to provide a group of ligands
and catalysts preparable therefrom, which enable both a generally
high level of enantioselectivity and activity and permit adjustment
to a certain substrate by variation of the substituents on the
ligand system in a simple manner.
[0008] The present invention thus provides compounds of the formula
(I) ##STR1##
[0009] in which [0010] B is a bivalent moiety of the formula
--(CHR.sup.1).sub.n--(R.sup.2C.dbd.CR.sup.3)--(CHR.sup.4).sub.m
where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently
hydrogen or alkyl, preferably C.sub.1-C.sub.6-alkyl, and n and m
are each independently zero or an integer from 1 to 8, where,
however, the sum of n and m is from 1 to 8, preferably 2 or 4 and
more preferably 2, and in which, moreover, [0011] G is chlorine or
hydrogen, preferably hydrogen, and [0012] R' and R'' are each
independently aryl or alkyl or [0013] in which [0014] B is a
bivalent moiety of the formula
--(CHR.sup.1).sub.n--(CR.sup.2R.sup.3).sub.m--(CHR.sup.4).sub.o
where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently
hydrogen or alkyl, preferably C.sub.1-C.sub.6-alkyl, and n, m and o
are each independently zero or an integer from 1 to 8, where,
however, the sum of n, m and o is from 1 to 8, preferably 3 or 4,
and in which, moreover, G is chlorine and R' and R'' are each
independently aryl or alkyl.
[0015] The invention encompasses both the pure stereoisomers and
any mixtures thereof, especially racemic mixtures. Preference is
given to the stereoisomerically enriched compounds of the formula
(I) which have a stereoisomeric purity of 95% and more, more
preferably 99% or more. In the case of compounds of the formula (I)
that can occur in two enantiomeric forms, preference is accordingly
given to an ee of 90% or more, particular preference to an ee of
98% and very particular preference to an ee of 99% or more.
[0016] In the context of the invention, all radical definitions,
parameters and illustrations above and recited below, in general or
within areas of preference, may be combined in any manner with one
another, i.e. also between the particular areas and areas of
preference.
[0017] In the context of the invention, enantiomerically enriched
means enantiomerically pure compounds or mixtures of enantiomers of
one compound in which one enantiomer is present in an enantiomeric
excess, also referred to below as ee, in comparison to the other
enantiomer. This enantiomeric excess is preferably from 10 to 100%
ee, more preferably from 80 to 100% ee and most preferably from 95
to 100% ee.
[0018] The terms stereoisomer and stereoisomerically enriched are
used in analogy for compounds for which diastereomers can also
occur.
[0019] Alkyl represents, for example, unbranched, branched, cyclic
or acyclic C.sub.1-C.sub.12-alkyl radicals which may be either
unsubstituted or at least partly substituted by fluorine, chlorine,
or unsubstituted or substituted aryl, or C.sub.1-C.sub.6-alkoxy.
Alkyl more preferably represents branched, cyclic or acyclic
C.sub.1-C.sub.12-alkyl radicals which are not further
substituted.
[0020] Aryl represents, for example, carbocyclic aromatic radicals
having from 6 to 18 skeleton carbon atoms or heteroaromatic
radicals having from 5 to 18 skeleton carbon atoms, in which no,
one, two or three skeleton carbon atoms per cycle, but at least one
skeleton carbon atoms in the entire molecule, may be substituted by
heteroatoms selected from the group of nitrogen, sulfur or oxygen.
The carbocyclic aromatic radicals or heteroaromatic radicals may
also be substituted by up to five identical or different
substituents per cycle, selected from the group of free or
protected hydroxyl, iodine, bromine, chlorine, fluorine, cyano,
free or protected formyl, C.sub.1-C.sub.12-alkyl, for example
methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl,
cyclohexyl, n-hexyl, n-octyl or isooctyl, C.sub.6-C.sub.12-aryl,
for example phenyl, C.sub.1-C.sub.6-alkoxy,
tri(C.sub.1-C.sub.6-alkyl)siloxyl, for example trimethylsiloxyl,
triethylsiloxyl and tri-n-butylsiloxyl.
[0021] Examples of carbocylic aromatic radicals having from 6 to 18
skeleton carbon atoms are, for example, phenyl, naphthyl,
phenanthrenyl, anthracenyl or fluorenyl, heteroaromatic radicals
having from 5 to 18 skeleton carbon atoms, in which no, one, two or
three skeleton carbon atoms per cycle, but at least one skeleton
carbon atom in the entire molecule, may be substituted by
heteroatoms selected from the group of nitrogen, sulfur or oxygen,
are, for example, pyridinyl, oxazolyl, thiophenyl, benzofuranyl,
benzothiophenyl, dibenzofuranyl, dibenzothiophenyl, furanyl,
indolyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, triazolyl
or quinolinyl.
[0022] In the context of the invention, protected formyl is a
formyl radical which has been protected by conversion to an aminal,
acetal or a mixed aminal acetal, the aminals, acetals and mixed
aminal acetals being acyclic or cyclic.
[0023] In the context of the invention, protected hydroxyl is a
hydroxyl radical which has been protected by conversion to an
acetal, carbonate, carbamate or carboxylate. Examples thereof are
the conversion to a tetrahydropyranyl adduct, to a
benzyloxycarbonyl derivative, allyloxycarbonyl derivative or a
tert-butyloxycarbonyl derivative.
[0024] The areas of preference for compounds of the formula (I) are
defined below. [0025] R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are
preferably each independently hydrogen, methyl, ethyl, n-propyl,
isopropyl, n-butyl and n-pentyl, more preferably hydrogen, methyl,
ethyl, n-propyl and isopropyl, and most preferably each identically
hydrogen. [0026] R' and R'' are preferably each independently, more
preferably each identically, C.sub.3-C.sub.8-alkyl or
C.sub.5-C.sub.10-aryl which is unsubstituted, monosubstituted or
polysubstituted by radicals which are selected from the group of
chlorine, fluorine, cyano, phenyl, C.sub.1-C.sub.6-alkoxy and
C.sub.1-C.sub.6-alkyl, more preferably cyclopentyl, cyclohexyl,
cycloheptenyl, phenyl, o-, m-, p-tolyl, 3,5-dimethylphenyl,
3,5-di-tert-butylphenyl, 3,5-dimethyl-4-methoxyphenyl,
3,5-di-tert-butyl-4-methylphenyl, 4-trifluoromethylphenyl,
4-fluorophenyl, 2-, 3-furyl, 2-, 3-thiophenyl, 2-N-methylpyrrolyl,
N-methyl-2-indolyl and 2-thiazolyl.
[0027] Particularly preferred compounds of the formula (I)
include:
[0028] (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
iphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
icyclohexyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethylphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-4-fluorophenyl)phosphine and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butylphenyl)phosphine and also the corresponding
trans compounds, preference being given to the cis compounds
mentioned, and also
[0029] (R)-- and
(S)--[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(diphen-
yl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(dicyclo-
hexyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethylphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethyl-4-methoxyphenyl)phosphine, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-4-fl-
uorophenyl)phosphine and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butylphenyl)phosphine, the stereoisomeric (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]-bis(diphenyl-
phosphines], the stereoisomeric (R) and
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphines) and also any mixtures of the enantiomers.
[0030] Inventive compounds of the formula (I) may be prepared, for
example, in an analogous manner to processes known per se which
have already been described for the synthesis of
biphenylbisphosphines bridged in the 6,6'-position.
[0031] For example, the corresponding 6,6-dihydroxybisphosphines
can be obtained, for example, from
[5,5'-dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl]bisphosphine or
analogous compounds by ether cleavage and are subsequently
converted by treatment with compounds of the formula (II)
X.sup.1--B--X.sup.2 (II)
[0032] in which [0033] B has the definition and areas of preference
specified in the legend of formula (I) and in which [0034] X.sup.1
and X.sup.2 are each independently chlorine, bromine or iodine
[0035] under conditions known per se (see, for example, J. Org.
Chem. 2000, 65, 6224) to the inventive compounds of the formula
(I).
[0036] To prepare compounds of the formula (I), the procedure is
preferably that
[0037] in a step a),
[0038] compounds of the formula (V) ##STR2##
[0039] are converted by ether cleavage to compounds of the formula
(III) ##STR3##
[0040] in a step b)
[0041] the compounds of the formula (III) are converted by reaction
with compounds of the formula (II) in the presence of base to
compounds of the formula (IV) ##STR4##
[0042] and in a step c)
[0043] the compounds of the formula (IV) are reduced to compounds
of the formula (I) ##STR5##
[0044] where B, G, R' and R'' each have the same definitions and
areas of preference as have already been defined under the formulae
(I) and (II).
[0045] R in formula (V) is C.sub.1-C.sub.6-alkyl.
[0046] Unless enantiomerically enriched compounds of the formula
(V) are used to prepare compounds of the formula (I), the compounds
of the formula (IV) can preferably be separated into the
stereoisomers in a manner known per se, for example by reacting
with a chiral auxiliary reagent or by continuous or batchwise
chromatography in the case of enantiomers on a chiral column
material.
[0047] The ether cleavage in step a) may, for example, be effected
in a manner known per se by reaction with BBr.sub.3 and subsequent
treatment with water.
[0048] The reaction of the compounds of the formula (III) with
compounds of the formula (II) in step b) is preferably carried out
in organic solvent in the presence of bases.
[0049] Suitable solvents are in particular alcohols, for example
methanol, ethanol, propanol, ethylene glycol or ethylene glycol
monomethyl ether, and amidic solvents, for example
N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone
or mixtures of the solvents mentioned.
[0050] The bases used may, for example, be alkali metal and
alkaline earth metal compounds such as oxides, hydroxides,
carbonates or alkoxides; examples include: calcium oxide, sodium
hydroxide, potassium carbonate or sodium methoxide. It is also
possible to use tertiary amines, for example triethylamine or
tributylamine, as bases.
[0051] The molar ratio between compound of the formula (III) and
compound of the formula (II) used is preferably between 1:1 and
1:4; in general, even a slight excess of compound of the formula
(II) is sufficient for complete reaction. The base is preferably
used in at least an equivalent amount to the compound of the
formula (III). In the case of the use of bases insoluble in the
solvent, for example of potassium carbonate in DMF, it is
appropriate to use from four to ten times the molar amount and at
the same time to ensure intensive mixing of the suspension.
[0052] The reaction in step b) may also be performed in a biphasic
system, in which case the nonaqueous phase used comprises solvents
in which the product of the formula (IV) formed is at least
predominantly soluble; dichloromethane, for example, is suitable
for this purpose. It is appropriate in this variant of the reaction
to use phase transfer catalysts, for example quaternary ammonium or
phosphine salts and tetrabutylammonium salts. Preference is given
to tetrabutylammonium salts.
[0053] The reaction temperature in the reaction of compounds of the
formula (III) to prepare the compounds of the formula (IV) may lie,
for example, in the range from about 20.degree. C. to 100.degree.
C., preferably in the range from 20.degree. C. to 80.degree. C.
[0054] The reduction of the compounds of the formula (IV) to the
compounds of the formula (II) in step c) is carried out preferably
by methods known per se, for example by reaction with
trichlorosilane in inert solvents such as toluene or xylene and in
the presence of tertiary amines such as tri-n-butylamine at reflux
temperature (see, for example, EP-A 398 132, EP-A 749 973 and EP-A
926 152).
[0055] Moreover, the inventive compounds of the formula (IV) in
which the substituent in the 6,6'-position is an alkenediyl radical
may also be prepared by reacting the compounds of the formula (III)
as defined above first [0056] with a compound of the formula (VIa)
or (VIb) or successively with two different compounds of the
formulae (VIa) and (VIb)
X.sup.3--(CHR.sup.1).sub.n--(R.sup.2C.dbd.CHR.sup.5) (VIa)
X.sup.4--(CHR.sup.4).sub.m--(R.sup.3C.dbd.CHR.sup.6) (VIb) [0057]
in which X.sup.3 and X.sup.4 are each chlorine, bromine, iodine or
a sulfonate, preferably chlorine, bromine or iodine, and [0058]
R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each as defined above
including the areas of preference, and [0059] R.sup.5 and R.sup.6
are each independently hydrogen or C.sub.1-C.sub.4-alkyl
[0060] to give compounds of the formula (VII) ##STR6##
[0061] and
[0062] then converting the compounds of the formula (VII) in the
presence of an olefin metathesis catalyst to compounds of the
formula (IV).
[0063] The compounds of the formula (IV) may then be reduced in the
above-described manner to the compounds of the formula (I).
[0064] For the reaction of the compounds of the formula (III) with
compounds of the formula (VIa) and/or (VIb), the solvents,
temperatures, molar ratios and other reaction parameters described
for step b) of the former process apply in the same manner.
[0065] For the conversions of the compounds of the formula (VII) to
compounds of the formula (IV), suitable olefin metathesis catalysts
are in particular ruthenium-carbene complexes. Preferred
ruthenium-carbene complexes are, for example, those of the formulae
(Xa) and (Xb) ##STR7##
[0066] where, in formula (Xa), [0067] Ar is aryl, Hal is chlorine,
bromine or iodine, and R.sup.7 is in each case independently
C.sub.1-C.sub.12-alkyl, C.sub.5-C.sub.12-aryl or
C.sub.6-C.sub.13-arylalkyl [0068] and where, in formula (Xb),
[0069] o-aryldiyl is an ortho-divalent C.sub.5-C.sub.24-aryl
radical which may also bear up to four radicals as have already
been defined above for aryl, Hal is chlorine, bromine or iodine, B
is an optionally mono- or di-C.sub.1-C.sub.12-alkyl-,
--C.sub.5-C.sub.12-aryl- or
--C.sub.6-C.sub.13-arylalkyl-substituted 1,2-ethanediyl or
1,2-ethenediyl, and R.sup.8 is in each case independently
C.sub.7-C.sub.12-alkyl, C.sub.5-C.sub.12-aryl or
C.sub.6-C.sub.13-arylalkyl.
[0070] The latter process for preparing compounds of the formula
(IV) is encompassed by the invention, as are the compounds of the
formulae (IV) and (VII) required to prepare the compounds of the
formula (I), both in the form of their pure stereoisomers and in
any mixtures thereof, especially the racemic mixture.
[0071] The compounds of the formula (VII) include:
[0072] (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-cyclohexy-
l)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)-biphenyl-2,2'-diyl]bis[(di-3,5-di-t-
ert-butyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-dimet-
hylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-dimet-
hyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-4-fluorop-
henyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(bisallyloxy)biphenyl-2,2'-diyl]bis[(di-3,5-di-te-
rt-butylphenyl)phosphine oxide.
[0073] Compounds of the formula (IV) include:
[0074] (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
icyclohexyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert-butyl-4-methoxyphenyl)-phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-dimethyl-4-methoxyphenyl)]-phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-4-fluorophenyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(cis-1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis[(d-
i-3,5-di-tert.-butylphenyl)phosphine oxide and also the
corresponding trans compounds, preference being given to the cis
compounds, and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bi-
s[(di-cyclohexyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-di-tert-butyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
dimethylphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis
[(di-3,5-dimethyl-4-methoxyphenyl)phosphine oxide, (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-4-fl-
uorophenyl)phosphine oxide and also (R)-- and
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis[(di-3,5--
di-tert-butylphenyl)phosphine oxide, the stereoisomeric
(R)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphine oxides), the stereoisomeric
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphine oxides) and also any mixtures of the enantiomers.
[0075] The compounds of the formula (I), preferably in
stereoisomerically enriched form, are suitable in particular as
ligands for the preparation of transition metal complexes which can
be used as catalysts for processes for preparing enantiomerically
enriched compounds.
[0076] The areas of preference for compounds of the formula (I)
apply below in the same manner as described above.
[0077] The invention therefore encompasses both transition metal
complexes comprising compounds of the formula (I) and catalysts
which comprise the inventive transition metal complexes.
[0078] Preferred transition metal complexes are those which are
obtainable by reaction of compounds of the formula (I) in the
presence of transition metal compounds.
[0079] Preferred transition metal compounds are compounds of
rhodium, iridium, ruthenium, palladium and nickel, greater
preference being given to those of rhodium, iridium and
ruthenium.
[0080] Preferred transition metal compounds are, for example, those
of the formula (VIIIa) M(Y.sup.1).sub.3 (VIIIa)
[0081] in which [0082] M is ruthenium, rhodium, iridium and [0083]
Y.sup.1 is chloride, bromide, acetate, nitrate, methanesulfonate,
trifluoromethanesulfonate or acetylacetonate and [0084] or
transition metal compounds of the formula (VIIIb)
M(Y.sup.2).sub.pB.sup.1.sub.2 (VIIIb)
[0085] in which [0086] M is ruthenium, rhodium, iridium and [0087]
Y.sup.2 is chloride, bromide, acetate, methanesulfonate,
trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate,
perchlorate, hexafluoroantimonate,
tetra(bis-3,5-trifluoromethylphenyl)borate or tetraphenylborate and
[0088] P is 1 for rhodium and iridium and is 2 for ruthenium,
[0089] B.sup.1 in each case is a C.sub.2-C.sub.12-alkene, for
example ethylene or cyclooctene, or a nitrile, for example
acetonitrile, benzonitrile or benzyl nitrile, or [0090]
B.sup.1.sub.2 together is a (C.sub.4-C.sub.12)-diene, for example
norbornadiene or 1,5-cyclooctadiene [0091] or transition metal
compounds of the formula (VIIIc) [MB.sup.2Y.sup.1.sub.2].sub.2
(VIIIc)
[0092] in which [0093] M is ruthenium and [0094] B.sup.2 represents
aryl radicals, for example cymene, mesityl, phenyl or
cyclooctadiene, norbornadiene or methylallyl [0095] or transition
metal compounds of the formula (VIIId) Me.sub.3[M(Y.sup.3).sub.4]
(VIIId)
[0096] where [0097] M is iridium or rhodium and [0098] Y.sup.3 is
chloride or bromide and [0099] Me is lithium, sodium, potassium,
ammonium or organic ammonium and [0100] or transition metal
compounds of the formula (VIIIe) [M(B.sup.3).sub.2]An (VIIIe)
[0101] where [0102] M is iridium or rhodium and [0103] B.sup.3 is a
(C.sub.4-C.sub.12)-diene, for example norbornadiene or
1,5-cyclooctadiene, [0104] An is a noncoordinating or weakly
coordinating anion, for example methanesulfonate,
trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate,
perchlorate, hexafluoroantimonate,
tetra(bis-3,5-trifluoromethylphenyl)borate or
tetraphenylborate.
[0105] Further preferred transition metal compounds are
cyclopentadienyl.sub.2Ru, Rh(acac)(CO).sub.2,
Ir(pyridine).sub.2(1,5-cyclooctadiene) or polynuclear bridged
complexes, for example [Rh(1,5-cyclooctadiene)Cl].sub.2 and
[Rh(1,5-cyclooctadiene)Br].sub.2, [Rh(ethene).sub.2Cl].sub.2,
[Rh(cyclooctene).sub.2Cl].sub.2, [Ir(1,5-cyclooctadiene)Cl].sub.2
and [Ir(1,5-cyclooctadiene)Br].sub.2, [Ir(ethene).sub.2Cl].sub.2,
and [Ir(cyclooctene).sub.2Cl].sub.2
[0106] The transition metal metal compounds used are most
preferably:
[0107] [Rh(cod)Cl].sub.2, [Rh(cod).sub.2Br],
[Rh(cod).sub.2]ClO.sub.4, [Rh(cod).sub.2]BF.sub.4,
[Rh(cod).sub.2]PF.sub.6, [Rh(cod).sub.2]OTf,
[Rh(cod).sub.2]BAr.sub.4(Ar=3,5-bistrifluoromethylphenyl)[Rh(cod).sub.2]S-
bF.sub.6 RuCl.sub.2(cod), [(cymene)RuCl.sub.2].sub.2,
[(benzene)RuCl.sub.2].sub.2, [(mesityl)RuCl.sub.2].sub.2,
[(cymene)RuBr.sub.2].sub.2, [(cymene)RuI.sub.2].sub.2,
[(cymene)Ru(BF.sub.4).sub.2].sub.2,
[(cymene)Ru(PF.sub.6).sub.2].sub.2,
[(cymene)Ru(BAr.sub.4).sub.2].sub.2,
(Ar=3,5-bistrifluoromethylphenyl),
[(cymene)Ru(SbF.sub.6).sub.2].sub.2, [Ir(cod).sub.2Cl].sub.2,
[Ir(cod).sub.2]PF.sub.6, [Ir(cod).sub.2]ClO.sub.4,
[Ir(cod).sub.2]SbF.sub.6[Ir(cod).sub.2]BF.sub.4,
[Ir(cod).sub.2]OTf,
[Ir(cod).sub.2]BAr.sub.4(Ar=3,5-bistrifluoromethylphenyl)RuCl.sub.3,
RhCl.sub.3, [Rh(nbd)Cl].sub.2, [Rh(nbd).sub.2Br],
[Rh(nbd).sub.2ClO.sub.4, [Rh(nbd).sub.2]BF.sub.4,
[Rh(nbd).sub.2]PF.sub.6, [Rh(nbd).sub.2]OTf,
[Rh(nbd).sub.2]BAr.sub.4(Ar=3,5-bistrifluoromethylphenyl)[Rh(nbd).sub.2]S-
bF.sub.6RuCl.sub.2(nbd), [Ir(nbd).sub.2]PF.sub.6,
[Ir(nbd).sub.2]ClO.sub.4,
[Ir(nbd).sub.2]SbF.sub.6[Ir(nbd).sub.2]BF.sub.4,
[Ir(nbd).sub.2]OTf,
[Ir(nbd).sub.2]BAr.sub.4(Ar=3,5-bistrifluoromethylphenyl),
Ir(pyridine).sub.2(nbd), RuCl.sub.3, [Ru(DMSO).sub.4Cl.sub.2],
[Ru(CH.sub.3CN).sub.4Cl.sub.2], [Ru(PhCN).sub.4Cl.sub.2],
[Ru(cod)Cl.sub.2].sub.n, [Ru(cod)(methallyl).sub.2] and
[Ru(acetylacetonate).sub.3].
[0108] Particularly preferred transition metal complexes are those
of the formulae (VIIIa, b, c) [M(I)Hal].sub.2 (VIIIa) [M(cod)(I)]An
(VIIIb) [M(nbd)(I)]An (VIIIc)
[0109] in which [0110] M is rhodium or iridium and [0111] Hal is
chloride, bromide or iodide and [0112] (I) is a compound of the
formula (I) and [0113] An is a noncoordinating or weakly
coordinating anion, for example methanesulfonate,
trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate,
perchlorate, hexafluoroantimonate,
tetra(bis-3,5-trifluoromethylphenyl)borate or tetraphenylborate and
[0114] compounds of the formulae (IXa, b, c, d, e, f)
[Ru(AcO).sub.2(I)] (IXa) [Ru.sub.2Cl.sub.4(I).sub.2NEt.sub.3] (IXb)
[RuHal(I)(AR)].sub.2 (IXc) [Ru(I)](An).sub.2 (IXd)
[{RuHal(I)}.sub.2(.mu.-Hal).sub.3].sup.-[(R''').sub.2NH.sub.2].sup.+
(IXe) [RuHal.sub.2(I)(diamine)] (IXf)
[0115] in which [0116] Hal is chloride, bromide or iodide and
[0117] (I) is a compound of the formula (I) and [0118] An is a
noncoordinating or weakly coordinating anion, for example
methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate,
hexafluorophosphate, perchlorate, hexafluoroantimonate,
tetra(bis-3,5-trifluoromethylphenyl)borate or tetraphenylborate and
[0119] R''' is in each case independently C.sub.1-C.sub.6-alkyl and
[0120] diamine represents chiral 1,2-diamines which are preferably
selected from the group of (S,S)-- and
(R,R)-1,2-diphenylethylenediamine and (R)-- or
(S)-1,1-bis(4-methoxyphenyl)-3-methyl-1,2-butanediamine and [0121]
AR is an arene ligand which is preferably selected from the group
of benzene, p-cymene and mesitylene.
[0122] The preparation of such complex types is known in principle
and is possible, for example, analogously to Chemistry Letters,
1851, 1989; J. Organomet. Chem., 1992, 428, 213 (VIIIa,b,c); J.
Chem. Soc., Chem. Commun., 922, 1985 (IXa,b,c,d), EP-A 945 457
(IXe) and Pure Appl. Chem., Vol. 71,8,1493-1501, 1999 (IXf).
[0123] The inventive transition metal complexes and catalysts are
suitable in particular for use in a process for the transition
metal-catalyzed preparation of enantiomerically enriched compounds
and for C.dbd.C double bond isomerizations, which is likewise
encompassed by the invention.
[0124] It is possible to use either isolated transition metal
complexes, for example those of the formulae (VIIIa-c) and (IXa-e)
or transition metal complexes prepared in situ, preference being
given to the latter.
[0125] Preference is given to using the transition metal complexes
and catalysts for asymmetric hydrogenations. Preferred asymmetric
hydrogenations are, for example, hydrogenations of prochiral
C.dbd.C bonds, for example prochiral enamines, olefins, enol
ethers, C.dbd.O bonds, for example prochiral ketones, and C.dbd.N
bonds, for example prochiral imines. Particularly preferred
asymmetric hydrogenations are hydrogenations of prochiral ketones,
especially alpha- and beta-keto esters, for example methyl or ethyl
chloroacetate and also methyl or ethyl acetoacetate.
[0126] The amount of the transition metal compound used or of the
transition metal complex used may, for example, be from 0.001 to 5
mol % based on the substrate used, preferably from 0.01 to 2 mol
%.
[0127] The enantiomerically enriched compounds preparable in
accordance with the invention are suitable in particular for
preparing agrochemicals, pharmaceuticals or intermediates
thereof.
[0128] The advantage of the present invention is that, with the aid
of the inventive catalysts, enantioselectivities and activities are
achieved which have to date not been achievable with similar
catalysts.
EXAMPLES
Example 1
Preparation of
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenylphosphine
oxide)
[0129] 3.4 ml of BBr.sub.3 (=8.77 g) were added dropwise with
stirring to a solution of 8 g of
(S)-[5,5'-dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl]bis(diphenylphosphine
oxide) in 160 ml of methylene chloride dried over CaH.sub.2, which
had been cooled to -78.degree. C. in a stirred vessel with
exclusion of moisture, and the reaction mixture was kept at this
temperature for 1 hour. The temperature was then allowed to rise to
room temperature within 2 hours and the mixture was stirred at this
temperature for a further 24 hours. Under ice cooling, a total of
50 ml of water were subsequently added dropwise with good mixing
within 1 hour, then the methylene chloride was distilled off and,
after addition of a further 110 ml of water, the mixture was kept
at 80.degree. C. with stirring for 6 hours. After cooling to RT,
the resulting precipitate was filtered off with suction through a
glass filter frit, and washed with 100 ml of water and then with
200 ml of methylene chloride with intensive mixing. After the
drying of the remaining product, 6.3 g (=82% of theory) of pure
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenylphosphine
oxide) were obtained, m.p. 236-237.degree. C.
[0130] Obtained in addition to 38 mg of the intermediate used were
123 mg of (S)-cis compound of the above-specified formula m.p.
126.degree. C.-128.degree. C., [a].sub.D=+57.6.degree. (c=1.0,
CHCl.sub.3) and
[0131] 118 mg of the (S)-trans compound of the above-specified
formula m.p. 141.degree. C.-142.degree. C., [a].sub.D=48.4.degree.
(c=1.4, CHCl.sub.3).
Example 2
Preparation of cis- and
trans-(S)-[5,5'-dichloro-6,6'-(1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis(-
diphenylphosphine oxide)
[0132] A mixture of 0.50 g (0.76 mmol) of
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenylphosphine
oxide) and of 0.42 g (3.04 mmol) of potassium carbonate in 10 ml of
DMF is stirred intensively at room temperature for 30 minutes. With
further intensive stirring, 0.223 g (3.04 mmol) of allyl chloride
is added and this mixture is kept at 40.degree. C. for 26 hours.
Subsequently, the reaction mixture is worked up analogously to the
procedure described in Example 1. In addition to 0.136 g of the
dichlorodihydroxybiphenylphosphine oxide and 58 mg of a mixed
fraction of monoallyloxy- and
bisallyloxydichlorobisphenylbisphosphine oxide, 0.395 g of pure
(S)-[6,6'-bisallyloxy-5,5'-dichlorobiphenyl-2,2'-diyl]bis(dipheny-
lphosphine oxide) is obtained. m.p. 214.degree. C.-215.degree. C.
(decomposes), [a].sub.D=56.8.degree. (c=1.0, CHCl.sub.3).
[0133] 295 mg of the above-described intermediate dissolved in 40
ml of CH.sub.2Cl.sub.2 are added dropwise at room temperature and
under an argon atmosphere over one hour to a solution of 18 mg of
1st generation Grubbs catalyst in 40 ml of dry CH.sub.2Cl.sub.2.
Afterward, the mixture is kept under reflux at 40.degree. C. for 5
hours and at room temperature over 24 hours. Subsequently, the
catalyst is destroyed by stirring under air (1 hour) and the
resulting product mixture is filtered through silica gel, and the
crude product is separated chromatographically analogously to the
procedure in Example 1.
Example 3
Preparation of
(R)-(1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis(diphenylphosphine
oxide)
[0134] A mixture of 4.1 g (6.99 mmol) of
(R)-(6,6'-dihydroxybiphenyl-2,2'-diyl)bis(diphenylphosphine oxide)
and 3.85 g (27.96 mmol) of potassium carbonate in 50 ml of
dimethylformamide is stirred at room temperature intensively for 1
hour. Afterward, 0.96 g (7.69 mmol) of cis-1,1-dichlorobut-2-ene
dissolved in 5.0 ml of DMF is added dropwise to the still
intensively stirred mixture, and the mixture is stirred at RT for a
further 12 hours and at 80.degree. C. for 8 hours. After cooling,
the reaction mixture is filtered.
[0135] After acidification with 2N hydrochloric acid, 0.71 g of the
dihydroxybisphenyl-bisphosphine oxide is recovered unchanged in
pure form from the precipitate which has been filtered off.
[0136] The filtrate is carefully brought to dryness with heating to
60.degree. C. at 0.5 mbar and subsequently dissolved in 60 ml of
dry dichloromethane. After 12 hours, this solution is filtered with
addition of silica gel as a filtration aid. A further 0.13 g of the
bisphosphine oxide used is recovered from the solid product which
has been filtered off.
[0137] The filtrate is concentrated by evaporation to afford 3.41 g
of a crude product which is separated by chromatography (Merck 9385
silica gel, eluent: ethyl acetate/methanol/water, 500:50:5). 2.76 g
of pure product of the above-specified formula are obtained. m.p.
116.degree. C.-118.degree. C., [a].sub.D=-161.1.degree. (c=1.0,
CHCl.sub.3).
Example 4
[0138] Analogously to Example 3,
(S)-cis-[6,6'-(1,6-hex-3-enedioxy)biphenyl-2,2'-diyl']bis(diphenylphosphi-
ne oxide) is m.p. 234.degree. C.-235.degree. C.,
[a].sub.D=-99.degree. (c=0.5, EtOH).
Example 5
[0139] Analogously to Example 3,
(R)-trans-[6,6'-(1,4-but-2-enedioxy)biphenyl-2,2'-diyl']bis(diphenylphosp-
hine oxide) is m.p. 192.degree. C.-194.degree. C. (decomposes),
[a].sub.D=+86.8.degree. (c=0.5, CHCl.sub.3).
Example 6
Preparation of
(R)-cis-[6,6'-(1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis(diphenyl)-phosph-
ine
[0140] The phosphine oxide from Example 3 (0.686 g, 1 mmol) was
initially charged with xylene (18 ml) under argon, and the
resulting mixture was first admixed with tri(n-butyl)amine (3.5 ml,
15 mmol) and trichlorosilane (1.5 ml, 15 mmol) and then heated
under reflux for 2 hours. The mixture was allowed to cool and
stirred briefly with degassed NaOH solution (30%, 15 ml), 25 ml of
degassed water were added and the phases were separated. The
aqueous phase was extracted 3 times with methyl tert-butyl ether
(10 ml) and the combined organic phases were first washed with sat.
sodium chloride solution and then dried over MgSO.sub.4. The
organic solvent was removed under reduced pressure and the product
was obtained as a colorless powder.
[0141] Yield: 95% of theory.
Example 7
Preparation of
(S)-cis-[6,6'-(1,4-hex-3-enedioxy)biphenyl-2,2'-diyl]bis(diphenyl)-phosph-
ine
[0142] The phosphine oxide from Example 4 was reduced entirely
analogously to Example 6 and obtained in a yield of 91%.
Example 8
Preparation of
(S)-cis-[5,5'-dichloro-6,6'-(1,4-but-2-enedioxy)biphenyl-2,2'-diyl]bis(di-
phenyl)phosphine
[0143] The phosphine oxide from Example 2 was reduced entirely
analogously to Example 6 and obtained in a yield of 94%.
Enantioselective hydrogenation of methyl acetoacetate (S1)
Example 9
[0144]
(S)-cis-[6,6'-(1,4-Hex-3-enedioxy)biphenyl-2,2'-diyl]bis(diphenyl)-
phosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg, 1 mol %) and 75 mg
of S1 were initially charged in methanol (1.3 ml) and the mixture
was heated to 50.degree. C. under a hydrogen pressure of 10 bar for
23 h. After this time, an enantiomeric purity of the product of
97.3% ee was determined.
Example 10
[0145]
(R)-cis-[6,6'-(1,4-But-3-enedioxy)biphenyl-2,2'-diyl]bis(diphenyl)-
phosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg, 1 mol %) and 75 mg
of S1 were initially charged in methanol (1.3 ml) and the mixture
was heated to 50.degree. C. under a hydrogen pressure of 10 bar for
23 h. After this time, an enantiomeric purity of the product of
98.6% ee was determined.
Example 11
[0146]
(S)-cis-[5,5'-(1,4-Dichloro-6,6'-(1,4-but-3-enedioxy)biphenyl-2,2'-
-diyl]bis(diphenyl)phosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg,
1 mol %) and 75 mg of S1 were initially charged in methanol (1.3
ml) and the mixture was heated to 50.degree. C. under a hydrogen
pressure of 10 bar for 5 h. After this time, an enantiomeric purity
of the product of 98.3% ee was determined.
Example 12 (for Comparison)
[0147]
(S)-[5,5'-Dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl]bis(diphenyl)p-
hosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg, 1 mol %) and 75 mg
of S1 were initially charged in methanol (1.3 ml) and the mixture
was heated to 50.degree. C. under a hydrogen pressure of 10 bar for
23 h. After this time, an enantiomeric purity of the product of
96.4% ee was determined.
Example 13
Preparation of
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis(diphenyl-
phosphine oxide)
[0148] 1.69 g of 1,3-dibromopropane were added at 22.degree. C. to
a solution or suspension, mixed effectively using an intensive
stirrer, of 5.0 g of
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenyl-
phosphine oxide) and of 4.2 g of potassium carbonate in 75 ml of
DMF. Afterward, the reaction mixture was stirred at room
temperature for a further 72 hours and then filtered. The solvent
was removed from the filtrate by vacuum distillation. The
(S)-[5,5'-dichloro-6,6'-bis(3-bromopropoxy)biphenyl-2,2'-diyl]bis(dipheny-
lphosphine oxide) (0.34 g) formed as a by-product was removed
chromatographically (Merck 9385 silica gel, eluent: ethyl
acetate/hexane/methanol, 10:1:1). After this chromatography, the
main product still received a small amount of the substrate used as
an impurity. To remove these impurities, this product was dissolved
in 40 ml of DMF, 160 mg of potassium carbonate and 0.15 ml of
methyl bromoacetate were added, and the mixture was stirred at room
temperature overnight. After filtration and removal of the solvent
by evaporating it off under reduced pressure, the resulting product
was separated chromatographically under the same conditions as
specified above. 4.0 g of pure product of the above-specified
formula were obtained. m.p. 135.degree.-137.degree. C.
[a].sub.D=+151.3.degree. (c=1.0, CHCl.sub.3).
Example 14
Preparation of
(S)-[5,5'-dichloro-6,6'-(1,4-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphine oxide)
[0149] 0.329 g of 1,4-dibromobutane was added at 22.degree. C. to a
solution or suspension, mixed efficiently using an intensive
stirrer, of 1.0 g of
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenyl-
phosphine oxide) and of 0.84 g of potassium carbonate in 25 ml of
DMF. Afterward, the reaction mixture was stirred first at room
temperature for 12 hours and then at 80.degree. C. for a further 36
hours. Subsequently, the resulting product mixture was filtered and
the solvent was removed from the filtrate by vacuum
distillation.
[0150] The thus obtained product was separated chromatographically
(Merck 9385 silica gel, eluent: ethyl acetate/hexane/methanol,
75:1.5:1.0). 0.67 g of pure product of the above of the
above-specified formula was obtained. m.p. 138.degree.-140.degree.
C., [a].sub.D=+15.2.degree. (c=1.0, CHCl.sub.3)
Example 15
Preparation of the stereoisomers of
(S)-[5,5'-dichloro-6,6'-(1,3-butanedioxy)biphenyl-2,2'-diyl]bis(diphenylp-
hosphine oxide)
[0151] A solution or suspension of 250 mg of
(S)-[5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl]bis(diphenylphosphine
oxide) and of 210 mg of potassium carbonate and also of 90 mg of
racemic 1,3-dibromobutane in 5.0 ml of DMF was stirred intensively
at room temperature for 12 hours and then at 80.degree. C. for 10
hours. Afterward, the reaction mixture was filtered and the
resulting filtrate was concentrated to dryness under reduced
pressure. Two pure diastereomers, each of which corresponds to the
above-specified formula, were isolated in pure form from the
resulting crude product by chromatography (Merck 9385 silica gel,
eluent: ethyl acetate/hexane/methanol, 75.0:1.5:1.0).
[0152] Diastereomer 4A (64 mg): m.p. 132.degree.-135.degree. C.
[a].sub.D=+62.4.degree. (c=1.0, CHCl.sub.3).
[0153] Diastereomer 4B (42 mg): m.p. 118.degree.-119.degree. C.
[a].sub.D=+137.7.degree. (c=1.0, CHCl.sub.3).
Example 16
Preparation of
(S)-[5,5'-dichloro-6,6'-(1,4-butanedioxy)biphenyl-2,2'-diyl]-bis(diphenyl-
)phosphine
[0154] The phosphine oxide from Example 14 (0.687 g, 1 mmol) was
initially charged with xylene (18 ml) under argon, and the
resulting mixture was first admixed with tri(n-butyl)amine (3.5 ml,
15 mmol) and trichlorosilane (1.5 ml, 15 mmol) and then heated
under reflux for 2 hours. The mixture was allowed to cool and
stirred briefly with degassed NaOH solution (30%, 14 ml), 20 ml of
degassed water were added and the phases were separated. The
aqueous phase was extracted 4 times with methyl tert-butyl ether
(MTBE) and the combined organic phases were first washed with sat.
sodium chloride solution and then dried over MgSO.sub.4. The
organic solvent was removed under reduced pressure and the product
was obtained as a colorless powder.
[0155] Yield: 97% of theory
[0156] .sup.31P-NMR (161.9 MHz, CDCl.sub.3): -13.61 ppm.
Example 17
Preparation of
(S)-[5,5'-dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]-bis(dipheny-
l)phosphine
[0157] Exactly analogously to Example 16, the product was obtained
in 98% yield.
[0158] .sup.31P-NMR (161.9 MHz, CDCl.sub.3): -10.91 ppm.
Enantioselective Hydrogenations of ethyl chloroacetoacetate (S2)
and methyl acetoacetate (S3)
Example 18
[0159]
(S)-[5,5'-Dichloro-6,6'-(1,3-propanedioxy)biphenyl-2,2'-diyl]bis(d-
iphenyl)phosphine (3.2 mg, 0.02 mol %), [(p-cumene)RuCl].sub.2 (1.5
mg, 0.01 mol %) and 4 g of S2 were initially charged in ethanol (10
ml) and the mixture was heated under a hydrogen pressure of 90 bar
to 80.degree. C. for 1 h. After this time, an enantiomeric purity
of the product of 96.5% ee was determined.
Example 19 (for Comparison)
[0160]
(S)-[5,5'-Dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl]bis(diphenyl)p-
hosphine (3.2 mg, 0.02 mol %), [(p-cumene)RuCl].sub.2 (1.5 mg, 0.01
mol %) and 4 g of S2 were initially charged in ethanol (10 ml) and
the mixture was heated under a hydrogen pressure of 90 bar to
80.degree. C. for 1 h. After this time, an enantiomeric purity of
the product of 95.1% ee was determined.
Example 20
[0161]
(S)-[5,5'-Dichloro-6,6'-(1,4-butanedioxy)biphenyl-2,2'-diyl]bis(di-
phenyl)phosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg, 1 mol %)
and 75 mg of S3 were initially charged in methanol (1.3 ml) and the
mixture was heated under a hydrogen pressure of 10 bar to
50.degree. C. for 5 h. After this time, an enantiomeric purity of
the product of 97.1% ee was determined.
Example 21 (for Comparison)
[0162]
(S)-[5,5'-dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl]bis(diphenyl)p-
hosphine (4.4 mg, 2 mol %), RuCl.sub.3 (1.4 mg, 1 mol %) and 75 mg
of S3 were initially charged in methanol (1.3 ml) and the mixture
was heated under a hydrogen pressure of 10 bar to 50.degree. C. for
5 h. After this time, an enantiomeric purity of the product of
96.4% ee was determined.
* * * * *