U.S. patent application number 11/402244 was filed with the patent office on 2006-08-17 for chiral monophosphorus compounds.
Invention is credited to Friederike Agel, Claus Dreisbach, Birgit Drieben-Holscher, Benjamin Meseguer, Hans-Christian Militzer, Thomas Prinz, Ulrich Scholz.
Application Number | 20060183930 11/402244 |
Document ID | / |
Family ID | 7701090 |
Filed Date | 2006-08-17 |
United States Patent
Application |
20060183930 |
Kind Code |
A1 |
Dreisbach; Claus ; et
al. |
August 17, 2006 |
Chiral monophosphorus compounds
Abstract
The present invention relates to catalysts comprising chiral
monophosphorus compounds and their use, the chiral monophosphorus
compounds themselves and also their precursors.
Inventors: |
Dreisbach; Claus;
(Leichlingen, DE) ; Meseguer; Benjamin;
(Tarragona, ES) ; Prinz; Thomas; (Leverkusen,
DE) ; Scholz; Ulrich; (Muhlheim, DE) ;
Militzer; Hans-Christian; (Odenthal, DE) ; Agel;
Friederike; (Aachen, DE) ; Drieben-Holscher;
Birgit; (Aachen, DE) |
Correspondence
Address: |
LANXESS CORPORATION
111 RIDC PARK WEST DRIVE
PITTSBURGH
PA
15275-1112
US
|
Family ID: |
7701090 |
Appl. No.: |
11/402244 |
Filed: |
April 10, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10256700 |
Sep 27, 2002 |
7057061 |
|
|
11402244 |
Apr 10, 2006 |
|
|
|
Current U.S.
Class: |
556/13 ;
558/73 |
Current CPC
Class: |
C07F 9/65744 20130101;
C07C 67/303 20130101; B01J 31/185 20130101; C07B 53/00 20130101;
C07C 231/12 20130101; C07C 45/505 20130101; B01J 2231/4261
20130101; C07C 69/34 20130101; C07C 67/303 20130101; C07C 233/47
20130101; C07C 233/47 20130101; C07C 231/12 20130101; B01J 2231/645
20130101; C07C 231/18 20130101; C07B 2200/07 20130101; C07F 9/6571
20130101; C07C 231/18 20130101; C07F 9/65719 20130101; B01J
2231/643 20130101; C07F 9/657154 20130101; B01J 2531/822
20130101 |
Class at
Publication: |
556/013 ;
558/073 |
International
Class: |
C07F 9/02 20060101
C07F009/02 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 1, 2001 |
DE |
10148551.4 |
Claims
1. Compounds of the general formula (XI) ##STR17## where R.sup.1 is
an unsubstituted or substituted 1,1'-biphenyl-2,2'-diyl radical and
Akt is chlorine, bromine, iodine or dialkylamino.
2. A method of preparing chiral phosphonites, chiral
phosphoramidites or chiral phosphites comprising providing the
compounds according to claim 1.
3. A method of conducting asymmetric 1,4-additions, asymmetric
hydroformylations, asymmetric hydrocyanations, asymmetric Heck
reactions and asymmetric hydrogenations comprising providing the
compounds of claim 1.
4. Catalysts comprising transition metal complexes of chiral
monophosphorus compounds of the general formula (I), ##STR18##
where R.sup.1 is an unsubstituted or substituted
1,1'-biphenyl-2,2'-diyl radical and R.sup.2 is a radical selected
from the group consisting of substituted or unsubstituted alkyl,
substituted or unsubstituted aryl, substituted or unsubstituted
alkoxy, substituted or unsubstituted aryloxy and tertiary
amino.
5. Catalysts according to claim 4, which are produced from chiral
monophosphorus compounds of the general formula (I) and metal
compounds.
6. Process for preparing chiral compounds, comprising catalyzing
the preparation with catalysts according to claim 4.
7. Process for preparing chiral compounds, comprising catalyzing
the preparation with catalysts according to claim 5.
8. Process for the asymmetric hydrogenation of substrates,
comprising catalyzing the hydrogenation with catalysts according to
claim 4.
9. Process for the asymmetric hydrogenation of substrates,
comprising catalyzing the hydrogenation with catalysts according to
claim 5.
10. Process according to claim 8, wherein catalysts used are
catalysts produced from chiral monophosphorus compounds according
to any of claims 1 and metal compounds of the general formula
(XIIIe) [M(B.sup.3).sub.2]An (XIIIe), where M is rhodium and
B.sup.3 is a (C.sub.4-C.sub.12)-diene such as norbornadiene or
1,5-cyclooctadiene and An is a noncoordinating or weakly
coordinating anion.
11. Process according to claim 8, which is carried out in at least
one solvent selected from the group consisting of chlorinated
alkanes, C.sub.1-C.sub.6-alcohols aromatic hydrocarbons, ketones
and carboxylic esters.
12. Process as claimed in claim 8, which is carried out at
temperatures of from -20 to 200.degree. C.
13. Process according to claim 8, which is carried out under a
hydrogen pressure of from 0.1 to 200 bar.
14. Process according to claim 8, wherein the amount of the metal
compound used or of the transition metal complex used is from 0.001
to 5 mol % based on the substrate used.
15. Process according to claim 6, wherein the substrate conversion
rate is above 1 000 h.sup.-1.
16. A method of preparing chiral active compounds in
pharmaceuticals and agrochemicals or intermediates thereof
comprising providing the compounds of prepared according to the
process of claim 15.
Description
[0001] This application is a Divisional of Ser. No.10/256,700 filed
on Sep. 27, 2002.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to catalysts comprising chiral
monophosphorus compounds and their use, the chiral monophosphorus
compounds themselves and also their precursors. For the purposes of
the invention, chiral monophosphorus compounds are, in particular,
chiral monophosphites, monophosphoramidites and
monophosphonites.
[0004] 2. Brief Description of the Prior Art
[0005] It is already known that chiral monophosphites or their
transition metal complexes can be used for asymmetric syntheses
(cf. A. Alexakis, Tetrahedron Asymmetry, 1997, 8, 3193-3196; C.
Claver et al., Chem. Commun., 2000, 2383-2384; W. Chen, J. Xiao,
Tetrahedron Letters, 42, 2001, 2897-2899; M. Reetz, G. Mehler,
Angew. Chem., 2000, 112, 4047-4049). The use of chiral
monophos-phoramidites or their transition metal complexes in
asymmetric syntheses is known, for example from van den Berg et
al., J. Am. Chem. Soc., 2000, 122, 11539-11540, and H. Waldmann,
Chem. Eur. J. 2000, 6, 671-675, and the use of chiral
monophosphonites is known from C. Claver et al., Chem. Commun.,
2000, 961-962.
[0006] However, all chiral ligands known hitherto are derived from
the basic framework of 2,2'-dihydroxy-1,1'-binaphthyl or other
polycyclic dihydroxybisaryls. The dis-advantage of such ligands is
that only limited substitution opportunities are available for
varying the electronic and steric properties. Use in various
asymmetric reaction types and applicability to many substrates
does, however, make a broad range of possible substitutions
desirable.
[0007] Furthermore, there is a need to develop catalysts which,
particularly when used in asymmetric hydrogenations, give not only
a high enantioselectivity but also high conversions and mild to
moderate reaction conditions.
SUMMARY OF THE INVENTION
[0008] It has now surprisingly been found that chiral
monophosphorus compounds of the general formula (I) or catalysts
based on these are particularly suitable for asymmetric syntheses,
##STR1## where [0009] R.sup.1 is an unsubstituted or substituted
1,1'-biphenyl-2,2'-diyl radical and R.sup.2 is a radical selected
from the group consisting of substituted or unsubstituted alkyl,
substituted or unsubstituted aryl, substituted or unsubstituted
alkoxy, substituted or unsubstituted aryloxy and tertiary amino.
[0010] R.sup.2 is preferably substituted or unsubstituted alkoxy or
substituted or unsubstituted aryloxy or tertiary amino,
particularly preferably substituted or unsubstituted alkoxy or
substituted or unsubstituted aryloxy.
DETAILED DESCRIPTION OF THE INVENTION
[0011] The following is a detailed description of the invention
with particular reference to its preferred elements. Unsubstituted
or substituted alkyl is, by way of example and preferably, an
unbranched, branched, cyclic or acyclic C.sub.1-C.sub.18-alkyl
radical which is either unsubstituted or at least partially
substituted by fluorine, chlorine, bromine, oxo, hydroxy,
unsubstituted or substituted aryl, C.sub.1-C.sub.6-alkoxy such as
methoxy, ethoxy, isopropoxy or n-propoxy, n-butoxy, or tert-butoxy,
primary, secondary or tertiary amino, cyano or carboxyl groups or
derivatives thereof. Examples of derivatives of carboxyl groups are
esters, amides and salts.
[0012] Unsubstituted or substituted alkyl is particularly
preferably a branched, cyclic or acyclic C.sub.3-C.sub.12-alkyl
radical which is either unsubstituted or at least partially
substituted by fluorine, oxo, hydroxy, methoxy, ethoxy, phenyl,
2-methoxyphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, amino,
dimethylamino, diethylamino, diisopropylamino, cyano or carboxyl
groups, their salts such as sodium or potassium salts or their
esters such as methyl or ethyl esters or their amides such as
dimethylamides or diethylamides.
[0013] Unsubstituted or substituted alkyl is very particularly
preferably isopropyl, tert-butyl, cyclohexyl, 1-butyl, 2-butyl,
2-ethylhex-1-yl, benzyl, 2-methoxybenzyl, 2-pyridylmethyl,
1-phenylethyl.
[0014] Unsubstituted or substituted alkoxy is, by way of example
and preferably, an unbranched, branched, cyclic or acyclic
C.sub.1-C.sub.18-alkoxy radical which is either unsubstituted or at
least partially substituted by fluorine, chlorine, bromine, oxo,
free or protected hydroxy, C.sub.1-C.sub.6-alkoxy such as methoxy,
ethoxy, isopropoxy or n-propoxy, n-butoxy or tert-butoxy,
substituted or unsubstituted C.sub.6-C.sub.10-aryl such as phenyl
or 2-pyridyl, primary, secondary or tertiary amino, cyano or
carboxyl groups or derivatives thereof.
[0015] Unsubstituted or substituted alkoxy is particularly
preferably an unbranched, branched, cyclic or acyclic
C.sub.2-C.sub.12-alkoxy radical which is either unsubstituted or at
least partially substituted by fluorine, chlorine, free or
protected hydroxy, substituted or unsubstituted phenyl, 2-pyridyl,
C.sub.1-C.sub.6-alkoxy such as methoxy, ethoxy, isopropoxy or
n-propoxy, n-butoxy or tert-butoxy, C.sub.1-C.sub.6-dialkylamino,
C.sub.1-C.sub.6-alkylcarbonylamino, benzoylamino,
4-methylphenylsulphonylamino, imidazolyl, phthalimidyl,
C.sub.1-C.sub.6-alkyloxycarbonyl,
C.sub.1-C.sub.4-dialkylaminocarbonyl.
[0016] Unsubstituted or substituted alkoxy is very particularly
preferably an unbranched, branched, cyclic or acyclic
C.sub.2-C.sub.6-alkoxy radical which is either unsubstituted or at
least partially substituted by fluorine, chlorine, free or
protected hydroxy, mono-substituted or disubstituted or
unsubstituted phenyl, 2-pyridinyl, C.sub.1-C.sub.4-dialkylamino,
C.sub.1-C.sub.4-alkylcarbonylamino, benzoylamino,
4-methylphenyl-sulphonylamino, imidazolyl, phthalimidyl,
C.sub.1-C.sub.4-alkyloxycarbonyl,
C.sub.1-C.sub.4-dialkyl-aminocarbonyl, C.sub.1-C.sub.4-alkoxy such
as methoxy, ethoxy, isopropoxy or n-propoxy, n-butoxy or
tert-butoxy.
[0017] Unsubstituted or substituted alkoxy is even more preferably
methoxy, ethoxy, isopropoxy, cyclohexyloxy, phenoxy,
(R)-1-phenylethoxy or (S)-1-phenylethoxy.
[0018] Substituted or unsubstituted aryl is, by way of example and
preferably, a carbocyclic aromatic radical having from 6 to 18
framework carbon atoms or a heteroaromatic radical having from 5 to
18 framework carbon atoms in which no, one, two or three framework
carbon atoms per ring, but at least one framework carbon atom in
the total molecule, can be replaced by heteroatoms selected from
the group consisting of nitrogen, sulphur and oxygen. Furthermore,
the carbocyclic aromatic radicals or heteroaromatic radicals can be
substituted by up to five identical or different substituents per
ring selected from the group consisting of free or protected
hydroxy, iodine, bromine, chlorine, fluorine, cyano, free or
protected formyl, C.sub.1-C.sub.12-alkyl such as methyl, ethyl,
n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl, n-hexyl,
n-octyl or isooctyl, C.sub.6-C.sub.12-aryl such as phenyl,
tri(C.sub.1-C.sub.6-alkyl)siloxyl such as trimethylsiloxyl,
triethylsiloxyl or tri-n-butylsiloxyl and radicals of the general
formula (II), A-B-D-E (II), where, independently of one another,
[0019] A is absent or is a C.sub.1-C.sub.8-alkylene radical such as
methylene, 1,2-ethylene, 1,1-ethylene, 1,3-propylene,
1,2-propylene, 1,4-butylene or 2,3-butylene and [0020] B is absent
or is oxygen, sulphur or NR.sup.3, [0021] where [0022] R.sup.3 is
hydrogen, C.sub.1-C.sub.16-alkyl such as methyl, ethyl, n-propyl,
isopropyl, n-butyl, tert-butyl, cyclohexyl, n-hexyl, n-octyl or
isooctyl or C.sub.6-C.sub.10-aryl such as phenyl or 2-, 3- or
4-tolyl and [0023] D is a carbonyl group and [0024] E is R.sup.4,
OR.sup.4, NHR.sup.5 or N(R.sup.5R.sup.6).sub.2, [0025] where [0026]
R.sup.4 is C.sub.1-C.sub.12-alkyl, C.sub.6-C.sub.10-aryl and [0027]
R.sup.5 and R.sup.6 are each, independently of one another,
C.sub.1-C.sub.8-alkyl or C.sub.6-C.sub.10-aryl or the
N(R.sup.5R.sup.6).sub.2 moiety is a cyclic amino radical, and
radicals of the general formulae (IIIa) and (IIIb) A-E (IIIa) A-COX
(IIIb) where A and E are as defined above and X is OH, NH.sub.2 or
OM, where M can be an alkali metal ion, half an equivalent of an
alkaline earth metal ion, an ammonium ion or an organic ammonium
ion.
[0028] Examples of carbocyclic aromatic radicals having from 6 to
18 framework carbon atoms are phenyl, naphthyl, phenanthrenyl,
anthracenyl or fluorenyl, heteroaromatic radicals having from 5 to
18 framework carbon atoms in which no, one, two or three framework
carbon atoms per ring, but at least one framework carbon atom in
the total molecule, can be replaced by heteroatoms selected from
the group consisting of nitrogen, sulphur and oxygen are, for
example, pyridinyl, oxazolyl, thienyl, benzofuranyl, benzothienyl,
dibenzofuranyl, dibenzothienyl, furanyl, indolyl, pyridazinyl,
pyrazinyl, pyrimidinyl, triazolyl or quinolinyl.
[0029] For the purposes of the invention, protected formyl is a
formyl radical which has been protected by conversion into an
aminal, acetal or a mixed aminal-acetal, with the aminals, acetals
and mixed aminal-acetals being able to be acyclic or cyclic.
[0030] For the purposes of the invention, protected hydroxy is a
hydroxy radical which has been protected by conversion into an
acetal, carbonate, carbamate or carboxylate. Examples are
conversion into a tetrahydropyranyl adduct, into a
benzyloxycarbonyl, allyloxycarbonyl or tert-butyloxycarbonyl
derivative.
[0031] Substituted or unsubstituted aryloxy is, by way of example
and preferably, a radical of the formula (IV) --O--Ar (IV) where Ar
has the same widest meaning as indicated above for substituted or
unsubstituted aryl.
[0032] Unsubstituted or substituted aryloxy is particularly
preferably a radical of the general formula (IV), in which Ar is
phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridinyl, pyrazinyl,
pyridazinyl or pyrimidinyl which can be substituted by no, one, two
or three further substituents per ring selected from the group
consisting of free or protected hydroxy, bromine, chlorine,
fluorine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl,
n-pentyl, n-hexyl, phenyl, benzyl, C.sub.1-C.sub.12-perfluoroalkyl
such as trifluoromethyl, pentafluoroethyl, and substituents of the
general formulae (II) and (IIIa) and (IIIb) in which, in each case
independently of one another, [0033] A is absent or is methylene,
[0034] B is absent or is oxygen or NR.sup.3, [0035] where [0036]
R.sup.3 is hydrogen, methyl or ethyl and [0037] D is a carbonyl
group and [0038] E is R.sup.4, OR.sup.4, NHR.sup.5 or
NR.sup.5R.sup.6, [0039] where [0040] R.sup.4 is methyl, ethyl,
n-propyl, isopropyl, n-butyl, tert-butyl, benzyl, 2-hydroxyethyl,
trifluoromethyl or phenyl and [0041] R.sup.5 and R.sup.6 are each,
independently of one another, methyl, ethyl, n-propyl, isopropyl,
n-butyl, benzyl, 2-hydroxyethyl or phenyl or [0042] the
NR.sup.5R.sup.6 moiety is morpholinyl, piperidinyl or pyrolidinyl
and [0043] X is OH, NH.sub.2, or OM, where M is a sodium, potassium
or ammonium ion.
[0044] Unsubstituted or substituted aryloxy is very particularly
preferably a radical of the general formula (IV), in which Ar is
phenyl which is substituted by no, one or two further substituents
selected from the group consisting of fluorine, chlorine, cyano,
methoxy, methyl, ethyl, phenyl, trifluoromethyl, and radicals of
the general formulae (II) and (IIIa) and (IIIb) in which [0045] A
and B are absent and [0046] D is a carbonyl group and [0047] E is
R.sup.4 or OR.sup.4, [0048] where [0049] R.sup.4 is methyl, ethyl
or phenyl.
[0050] Unsubstituted or substituted aryloxy is even more preferably
phenoxy, 2,4-di-methylphenoxy, 3,5-dimethylphenoxy,
3,5-bis(trifluoromethyl)-phenoxy, 4-methylphenoxy, 3-methylphenoxy,
3-methoxyphenoxy, 4-methoxyphenoxy, 2-methoxyphenoxy,
2-methylphenoxy, 2,4-dichlorophenoxy, 2-ethoxycarbonyl-phenyl,
2-methoxycarbonyl, 2-acetylphenyl, 4-acetylphenyl or
2,6-dimethylphenoxy.
[0051] Tertiary amino is, for example, alkylarylamino, dialkylamino
or diarylamino, preferably dialkylamino or diarylamino. Cyclic
amino radicals are also encompassed by the invention.
[0052] Preferred examples of tertiary amino are di(substituted or
unsubstituted (C.sub.1-C.sub.12-alkyl)amino such as dimethylamino,
diethylamino, diisopropylamino, di-n-butylamino,
di-(R)-phenylethylamino, di-(S)-phenylethylamino, dibenzylamino and
di(substituted or unsubstituted C.sub.6-C.sub.10-aryl)amino, such
as diphenylamino, di-(p-tolyl)amino or cyclic amino radicals such
as R,R-dimethylpyrrolidino, S,S-dimethylpyrrolidino, morpholino,
piperidino, tetramethylpiperidino. [0053] R.sup.1 is, by way of
example and preferably, an unsubstituted or substituted
1,1'-biphenyl-2,2'-diyl radical of the general formula (VI),
##STR2## where the radicals R.sup.7, R.sup.8, R.sup.9and R.sup.10
are each selected independently from the group consisting of
fluorine, chlorine, bromine, unsubstituted or substituted protected
hydroxy, unsubstituted or substituted C.sub.1-C.sub.6-alkyl,
unsubstituted or substituted C.sub.1-C.sub.6-alkoxy, unsubstituted
or substituted C.sub.1-C.sub.6-alkylthio, cyano, free or protected
formyl, unsubstituted or substituted C.sub.6-C.sub.12-aryl,
tri(C.sub.1-C.sub.6-alkyl)siloxyl and radicals of the general
formula (II), A-B-D-E (II), where, independently of one another,
[0054] A is absent or is a C.sub.1-C.sub.8-alkylene radical and
[0055] B is absent or is oxygen, sulphur or NR.sup.3, [0056] where
[0057] R.sup.3 is hydrogen, C.sub.1-C.sub.16-alkyl or
C.sub.6-C.sub.10-aryl and [0058] D is a carbonyl group and [0059] E
is R.sup.4, OR.sup.4, NHR.sup.5 or NR.sup.5R.sup.6, [0060] where
[0061] R.sup.4 is C.sub.1-C.sub.12-alkyl or C.sub.6-C.sub.10-aryl
and [0062] R.sup.5 and R.sup.6 are each, independently of one
another, C.sub.1-C.sub.8alkyl or C.sub.6-C.sub.10-aryl or the
NR.sup.5R.sup.6 moiety is a cyclic amino radical, and radicals of
the general formulae (IIIa) and (IIIb) with the widest meaning
indicated above.
[0063] The two radicals R.sup.10 together can also be bridging. The
invention also encompasses cases in which the two radicals R.sup.10
are each chiral or are together chiral and bridging.
[0064] Furthermore, the two radicals can also form a nonaromatic
ring.
[0065] R.sup.1 is particularly preferably an unsubstituted or
substituted 1,1'-biphenyl-2,2'-diyl radical of the general formula
(VI) in which the radicals R.sup.7, R.sup.8, R.sup.9 and R.sup.10
are each selected independently from the group consisting of
fluorine, chlorine, bromine, free or protected hydroxy,
unsubstituted or substituted C.sub.1-C.sub.4-alkyl, unsubstituted
or substituted C.sub.1-C.sub.4-alkoxy, unsubstituted or substituted
C.sub.1-C.sub.4-alkylthio, cyano, C.sub.6-aryl,
tri(C.sub.1-C.sub.4-alkyl)siloxyl and radicals of the general
formula (II), A-B-D-E (II) where, independently of one another,
[0066] A is absent or is a C.sub.1-C.sub.4-alkylene radical and
[0067] B is absent or is oxygen or NR.sup.3, [0068] where R.sup.3
is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.6-C.sub.10aryl and
[0069] D is a carbonyl group and [0070] E is R.sup.4, OR.sup.4,
NHR.sup.5 or NR.sup.5R.sup.6, [0071] where R.sup.4 is
C.sub.1-C.sub.6-alkyl or C.sub.6-C.sub.10aryl and [0072] R.sup.5
and R.sup.6 are each, independently of one another,
C.sub.1-C.sub.4-alkyl or C.sub.6-aryl or the NR.sup.5R.sup.6 moiety
is a cyclic amino radical, [0073] and radicals of the general
formulae (IIIa) and (IIIb) with the widest meaning indicated
above.
[0074] The two radicals R.sup.10 can together also be bridging.
Bridges formed in this way are, preferably and by way of example,
bridges of the formula (VII) --O-G.sup.1-K-G.sup.2-O-- (VII) where
G.sup.1 and G.sup.2 can each, independently of one another, either
be absent or be a carbonyl group or a carbonylamino group, [0075] K
can be an unsubstituted or substituted C.sub.2-C.sub.6-alkylene
chain. [0076] R.sup.1 is very particularly preferably an
unsubstituted or substituted 1,1'-biphenyl-2,2'-diyl radical of the
general formula (VI) in which the radicals R.sup.7, R.sup.8,
R.sup.9 and R.sup.10 are each selected independently from the group
consisting of fluorine, chlorine, bromine, free or protected
hydroxy, unsubstituted or substituted C.sub.1-C.sub.4-alkyl,
unsubstituted or substituted C.sub.1-C.sub.4-alkoxy and radicals of
the general formula (II), A-B-D-E (II) in which, independently of
one another, [0077] A is absent and [0078] B is absent or is
oxygen, and [0079] D is a carbonyl group and [0080] E is R.sup.4,
OR.sup.4, NHR.sup.5 or NR.sup.5R.sup.6, [0081] where R.sup.4 is
C.sub.1-C.sub.4-alkyl or C.sub.6-C.sub.10-aryl and [0082] R.sup.5
and R.sup.6 are each, independently of one another,
C.sub.1-C.sub.4-alkyl or the NR.sup.5R.sup.6 moiety is a cyclic
amino radical, [0083] and radicals of the general formulae (IIIa)
and (IIIb) with the widest meaning indicated above or the two
radicals R.sup.10 are bridges of the general formula (VII) in which
G can either be absent or be a carbonyl group or a carbonyl amino
group and [0084] K is an unsubstituted or substituted
C.sub.2-C.sub.4-alkylene chain. [0085] R.sup.1 is even more
preferably one of the following radicals: ##STR3## ##STR4## or a
radical of the general formula (VIII) ##STR5## where
G.sup.1-K-G.sup.2 together represent (R)-1,2-propanediyl,
(S,S)-1,2-cyclohexanediyl, (R,R)-1,2-cyclohexanediyl,
1,2-ethanediyl, 1,3-propanediyl, 1,4-butanediyl or
1,4-dioxobutanediyl or one of the following radicals: ##STR6##
##STR7## ##STR8## It may be pointed out at this point that any
combinations of the abovementioned preferred meanings of R.sup.2
with the preferred meanings of R.sup.1 are encompassed by the
invention.
[0086] The invention encompasses all stereoisomeric compounds of
the chiral monophosphorus compounds of the general formula (I),
both in pure form and in the form of any mixtures of stereoisomeric
compounds, for example racemates or diastereomeric mixtures.
[0087] Preferred compounds of the general formula (I) are: [0088]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl isopropyl
phosphite, [0089]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl isopropyl
phosphite, [0090]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl(R)-1-phenylethyl
phosphite, [0091]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl(S)-1-phenylethyl
phosphite, [0092]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl(R)-1-phenylethyl
phosphite, [0093]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl(S)-1-phenylethyl
phosphite, [0094]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl cyclohexyl
phosphite, [0095]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl cyclohexyl
phosphite, [0096]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl phenyl
phosphite, [0097]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl phenyl
phosphite, [0098]
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl
2,6-dimethylphenyl phosphite, [0099]
(R)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl
2,6-dimethylphenyl phosphite, [0100]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
isopropyl phosphite, [0101]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
isopropyl phosphite, [0102]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(ra-
c)-1-phenyl-ethyl phosphite, [0103]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(ra-
c)-1-phenyl-ethyl phosphite, [0104]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(S)-
-1-phenyl-ethyl phosphite, [0105]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(S)-
-1-phenyl-ethyl phosphite, [0106]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(R)-
-1-phenyl-ethyl phosphite, [0107]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl(R)-
-1-phenyl-ethyl phosphite, [0108]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
diphenylmethyl phosphite, [0109]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
diphenylmethyl phosphite, [0110]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
methyl phosphite, [0111]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
methyl phosphite, [0112]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
2,6-dimethyl-phenyl phosphite, [0113]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
2,6-dimethyl-phenyl phosphite, [0114]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
2,6-diisopropylphenyl phosphite, [0115]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
2,6-diisopropylphenyl phosphite, [0116]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
phenyl phosphite, [0117]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1'-biphenyl-2,2'-diyl
phenyl phosphite, [0118]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1
'-biphenyl-2,2'-diyl ethyl phosphite, [0119]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1
'-biphenyl-2,2'-diyl ethyl phosphite [0120]
(S)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1
'-biphenyl-2,2'-diyl 4-tert-butyl-phenyl phosphite, [0121]
(R)-5,5',6,6'-tetramethyl-3,3'-bis(tert-butyl)-1,1
'-biphenyl-2,2'-diyl 4-tert-butyl-phenyl phosphite.
[0122] The chiral monophosphorus compounds of the invention can be
prepared in a manner known per se. For example, they can be
prepared by [0123] reacting diols of the general formula (IX),
HO--R.sup.1--OH (IX) where R.sup.1 is as defined under the general
formula (I), [0124] with activated phosphines of the general
formula (X) (Akt).sub.nP(R.sup.2).sub.3-n (X) where [0125] Akt is
chlorine, bromine, iodine, dialkylamino such as dimethylamino or
diethylamino and [0126] R.sup.2 is as defined under the general
formula (I) and [0127] n is 2 or 3, [0128] in the presence of a
base such as triethylamine or after deprotonation of the starting
diol of the general formula (IX).
[0129] Akt is preferably chlorine or dimethylamino or diethylamino,
particularly preferably chlorine.
[0130] If n=3, compounds of the general formula (XI) ##STR9## are
initially formed as intermediates and these can be reacted in a
further step with a compound of the general formula (XII)
H--R.sup.11 (XII), where R.sup.11 is a radical selected from the
group consisting of substituted or unsubstituted alkoxy,
substituted or unsubstituted aryloxy and secondary or tertiary
amino, with these radicals being defined as under R.sup.1, either
in the presence of a base such as triethylamine or after prior
deprotonation to give the chiral monophosphorus compounds of the
general formula (I).
[0131] The compounds of the general formula (XI) are likewise
encompassed by the invention.
[0132] The separation of stereoisomers can be carried out, for
example, by separating biphenyl compounds of the general formula
(VI) into the enantiomers by cocrystallization with suitable
chiral, enantiomerically enriched auxiliaries, for example chiral
enantiomerically pure amines. The preparation of enantiomerically
pure biphenols of the general formula (VI) can likewise be carried
out by firstly reacting the mixture of stereomeric isomers with a
suitable activated phosphorus compound such as PCl.sub.3 or
P(NMe.sub.2).sub.3 (cf. K. Sasse, Methoden der Organischen Chemie,
Houben-Weyl, Georg Thieme Verlag, 1964, Vol. XII/2, 4th edition,
5-130) and reacting this product further with an enantiomerically
pure alcohol, for example menthol, to produce diastereomeric
phosphites which can be separated in a customary fashion and lead
after subsequent cleavage to the enantiomerically enriched
biphenols of the general formula (VI). Furthermore, compounds of
the formula (VI) and of the formula (I) can be separated into their
enantiomers by chromatography on chiral stationary phases.
Furthermore, enantiomerically pure biphenyl compounds of the
formula (VI) can be obtained by reaction with enantiomerically pure
biselectrophiles and substituted
2,2',6,6'-tetrahydroxy-1,1'-biphenyls using a method analogous to
that of T. Harada et al. (Organic Letters, 2000, Vol.2, p.
1319).
[0133] The invention also encompasses catalysts which comprise
transition metal complexes of the novel chiral monophosphorus
compounds of the general formula (I). These are, in particular,
transition metal complexes of ruthenium, osmium, cobalt, rhodium,
iridium, nickel, palladium, platinum and copper, preferably those
of ruthenium, rhodium, iridium, nickel, palladium, platinum and
copper.
[0134] As catalysts, it is possible to use, for example, either
isolated transition metal complexes or transition metal complexes
which are generated from the chiral monophosphorus compounds of the
general formula (I) and a metal compound.
[0135] Preference is given to using transition metal complexes
generated from chiral monophosphorus compounds of the general
formula (I) and at least one metal compound as catalysts.
[0136] Suitable metal compounds are, by way of example and
preferably, those of the general formula M(Y.sup.1).sub.p (XIIIa),
where [0137] M is ruthenium, rhodium, iridium, nickel, palladium,
platinum or copper and [0138] Y.sup.1 is chloride, bromide,
acetate, nitrate, methanesulphonate, trifluoromethanesulphonate or
acetylacetonate and [0139] p is 3 in the case of ruthenium, rhodium
and iridium, 2 in the case of nickel, palladium and platinum and 1
in the case of copper, [0140] or metal compounds of the general
formula (XIIIb) M(Y.sup.2).sub.pB.sup.1.sub.2 (XIIIb) where [0141]
M is ruthenium, rhodium, iridium, nickel, palladium, platinum or
copper and [0142] Y.sup.2 is chloride, bromide, acetate,
methanesulphonate, trifluoromethanesulphonate, tetrafluoroborate,
hexafluorophosphate perchlorate, hexafluoroantimonate,
tetra(3,5-bistrifluoromethylphenyl)borate or tetraphenylborate and
[0143] p is 1 in the case of rhodium and iridium, 2 in the case of
nickel, palladium, platinum and ruthenium and 1 in the case of
copper, [0144] B.sup.1 are each a C.sub.2-C.sub.12-alkene such as
ethylene or cyclooctene, or a nitrile such as acetonitrile,
benzonitrile or benzyl nitrile, or [0145] the B.sup.1.sub.2 moiety
is a (C.sub.4-C.sub.12)-diene such as norbornadiene or
1,5-cyclooctadiene, [0146] or metal compounds of the general
formula (XIIIc) [MB.sup.2Y.sup.1.sub.2].sub.2 (XIIIc), where [0147]
M is ruthenium and [0148] B.sup.2 is an aryl radical such as
cymene, mesityl, phenyl or cyclooctadiene, norbornadiene or
methylallyl, [0149] or metal compounds of the general formula
(XIIId) Me.sub.p[M(Y.sup.3).sub.4] (XIIId), where [0150] M is
palladium, nickel, iridium or rhodium and [0151] Y.sup.3 is
chloride or bromide and [0152] Me is lithium, sodium, potassium,
ammonium or organic ammonium and [0153] is 3 in the case of rhodium
and iridium and 2 in the case of nickel, palladium and platinum,
[0154] or metal compounds of the general formula (XIIIe)
[M(B.sup.3).sub.2]An (XIIIe), where [0155] M is iridium or rhodium
and [0156] B.sup.3 is a (C.sub.4-C.sub.12)-diene such as
norbornadiene or 1,5-cyclooctadiene and [0157] An is a
noncoordinating or weakly coordinating anion such as
methanesulphonate, trifluoromethanesulphonate, tetrafluoroborate,
hexafluorophosphate perchlorate, hexafluoroantimonate,
tetra(3,5-bistrifluoromethylphenyl)borate or tetraphenylborate.
[0158] Further suitable metal compounds are, for example,
Ni(1,5-cyclooctadiene).sub.2, Pd.sub.2(dibenzylideneacetone).sub.3,
Pd[PPh.sub.3].sub.4, cyclopentadienyl.sub.2Ru, Rh(acac)(CO).sub.2,
Ir(pyridine).sub.2(1,5-cyclooctadiene), Cu(phenyl)Br, Cu(phenyl)Cl,
Cu(phenyl)I, Cu(PPh.sub.3).sub.2Br, [Cu(CH.sub.3CN).sub.4]BF.sub.4
and [Cu(CH.sub.3CN).sub.4]PF.sub.6 or multinuclear bridged
complexes such as [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.
[0159] Preference is given to using the following metal compounds:
[0160] [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]SbF.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.2SbF.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, NiCl.sub.2,
RhCl.sub.3, PdCl.sub.2, PdBr.sub.2, Pd(OAc).sub.2,
Pd.sub.2(dibenzylideneacetone).sub.3, Pd(acetylacetonate).sub.2,
CuOTf, Cul, CuCl, Cu(OTf).sub.2, CuBr, CuI, CuBr.sub.2, CuCl.sub.2,
CuI.sub.2, [0161] [Rh(nbd)Cl].sub.2, [Rh(nbd).sub.2Br],
[Rh(nbd).sub.2]ClO.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]SbF.sub.6 RuCl.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), [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],
[Ru(acetylacetonate).sub.3]
[0162] Even greater preference is given to Rh(COD).sub.2
trifluoromethanesulphonate, Rh(nbd).sub.2PF.sub.6 and
Rh(nbd).sub.2BF.sub.4.
[0163] The amount of metal compound used can be, for example, from
25 to 200 mol % based on the chiral monophosphorus compound of the
general formula (I) which is used, preferably from 30 to 100 mol %,
very particularly preferably from 40 to 60 mol % and even more
preferably from 45 to 55 mol %.
[0164] The catalysts comprising transition metal complexes
generated in situ or isolated transition metal complexes are
suitable, in particular, for use in a process for preparing chiral
compounds.
[0165] The catalysts are preferably used for asymmetric
1,4-additions, asymmetric hydroformylations, asymmetric
hydrocyanations, asymmetric Heck reactions and asymmetric
hydrogenations, particularly preferably 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 enamines and olefins.
[0166] The amount of metal compound used or of transition metal
complex used can be, for example, from 0.001 to 5 mol % based on
the substrate used, preferably from 0.001 to 0.5 mol %, very
particularly preferably from 0.001 to 0.1 mol % and even more
preferably from 0.001 to 0.008 mol %.
[0167] In a preferred embodiment, asymmetric hydrogenations can be
carried out, for example, by generating the catalyst in situ from a
metal compound and a chiral monophosphorus compound of the general
formula (I) in the presence or absence of a suitable solvent,
adding the substrate and placing the reaction mixture under
hydrogen pressure at the reaction temperature.
[0168] As metal compounds for asymmetric hydrogenations, preference
is given to using compounds of the general formula (XIIIe)
[M(B.sup.3).sub.2]An (XIIIe), where [0169] M is rhodium and [0170]
B.sup.3 is a (C.sub.4-C.sub.12)-diene such as norbornadiene or
1,5-cyclooctadiene and [0171] An is a noncoordinating or weakly
coordinating anion such as methane-sulphonate,
trifluoromethanesulphonate, tetrafluoroborate, hexafluorophosphate,
perchlorate, hexafluoroantimonate, hexachloroantimonate,
tetra(3,5-bistrifluoromethylphenyl)borate or tetraphenylborate or
[0172] binuclear complexes such as [Rh(1,5-cyclooctadiene)Cl].sub.2
and [Rh(1,5-cyclo-octadiene)Br].sub.2, [Rh(ethene).sub.2Cl].sub.2,
[Rh(cyclooctene).sub.2Cl].sub.2.
[0173] Particularly preferred metal compounds for asymmetric
hydrogenations are [Rh(1,5-cyclooctadiene).sub.2]BF.sub.4,
[Rh(1,5-cyclooctadiene).sub.2]PF.sub.6,
[Rh(norbornadiene).sub.2]PF.sub.6 and
[Rh(norbornadiene).sub.2]BF.sub.4.
[0174] In a particularly preferred embodiment, metal compound and
monophosphorus compound are dissolved in a degassed solvent in a
baked-out glass autoclave. The mixture is stirred for about 5
minutes and the substrate in a degassed solvent is subsequently
added. After setting the appropriate temperature, the hydrogenation
is carried out under H.sub.2 pressure.
[0175] Suitable solvents for the asymmetric hydrogenation are, for
example, chlorinated alkanes such as methylene chloride,
short-chain C.sub.1-C.sub.6-alcohols such as methanol, isopropanol
or ethanol, aromatic hydrocarbons such as toluene or benzene,
ketones such as acetone or carboxylic esters such as ethyl
acetate.
[0176] The asymmetric hydrogenation is carried out, for example, at
a temperature of from -20.degree. C. to 200.degree. C., preferably
from 0 to 100.degree. C. and particularly preferably from 20 to
70.degree. C.
[0177] The hydrogen pressure can be, for example, from 0.1 to 200
bar, preferably from 0.5 to 50 bar and particularly preferably from
0.5 to 5 bar.
[0178] The catalysts of the invention are particularly suitable for
processes for preparing chiral active compounds in pharmaceuticals
and agrochemicals, or intermediates for these two classes.
[0179] The advantage of the present invention is that activities of
far above 1 000 h.sup.-1 (TOF) which have hitherto not been
achieved can be achieved using ligands which are simple to prepare,
in particular in asymmetric hydrogenations.
[0180] The invention is further illustrated but is not intended to
be limited by the following examples in which all parts and
percentages are by weight unless otherwise specified.
EXAMPLES
Example 1
Synthesis of
(S)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-dioxy)chlorophosphane
[0181] ##STR10##
[0182] A solution of 1 g (3.17 mmol) of (S)--Cl-MeO-biphenol is
added dropwise to a mixture of 0.41 ml (4.12 mmol) of PCl.sub.3 and
0.97 ml (6.98 mmol) of NEt.sub.3 in 5 ml of THF while cooling in
ice. The mixture is stirred at RT for 1 hour, the precipitate which
has formed is filtered off and is washed with a little solvent.
Removal of the solvent gives the product as a yellowish oil.
[0183] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=3.57 (s, 3H,
OCH.sub.3); 3.59 (s, 3H, OCH.sub.3); 6.92 (d, .sup.3J=8.7, 1H,
H.sub.b or b'); 7.01 (dd, 1H, .sup.3J=8.7, J(H-P)=1.1, 1H, H.sub.b
or b'); 7.46 (br d, .sup.3J=8.7, 2H, H.sub.a and a'); .sup.31P-NMR
(CDCl.sub.3): .delta. [ppm]=176.4
Examples 2-6
Synthesis of (S)-phosphites
[0184] ##STR11##
[0185] 3.17 mmol of the appropriate alcohol (i-propanol,
cyclohexanol, (R)-1-phenyl-ethanol, phenol, 2,6-dimethylphenol) are
dissolved in 5 ml of THF and admixed with 0.44 ml (3.17 mmol) of
NEt.sub.3. 1.204 g (3.17 mmol) of phosphochloridite from Example 1,
dissolved in 10 ml of THF, are added dropwise at 0.degree. C. After
1 hour, the precipitate which has formed is filtered off and is
washed with a little THF. Removal of the solvent gives the
phosphites as white to slightly yellowish solids or oils.
Example 2
(S)-5,5'-Dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl isopropyl
phosphite
[0186] ##STR12##
[0187] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=1.29 (d,
.sup.3J=6.2, 3H, CH.sub.3), 1.33 (d, .sup.3J=6.2, 3H, CH.sub.3);
3.53 and 3.54 (s, 3H, OCH.sub.3); 4.53 (dsep, .sup.3J=6.2,
J(H-P)=9.0, 1H, CH); 6.83 (dd, .sup.3J=8.7, J(H-P)=0.8, 1H, H.sub.b
or b'); 6.96 (dd, .sup.3J=8.7, J(H-P)=1.2, 1H, H.sub.b or b'); 7.37
(d, .sup.3J=8.7, 1H, H.sub.a or a'); 7.40 (dd, .sup.3J=8.7, J(H-P)
=0.5, 1H, H.sub.a or a'); .sup.31P-NMR (CDCl.sub.3): .delta.
[ppm]=145.3
Example 3
(S)-5,5'-Dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl cyclohexyl
phosphite
[0188] ##STR13##
[0189] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=1.00-2.00 (kB, 10H,
CH.sub.2); 3.53 and 3.54 (s, 3H, OCH.sub.3); 4.19 (dsep, J=4.5,
J(H-P)=9.1, 1H, CH); 6.83 (dd, .sup.3J=8.7, J(H-P)=0.7, 1H, H.sub.b
or b'); 6.96 (dd, .sup.3J=8.7, J(H-P)=1.1, 1H, H.sub.b or b'); 7.36
(d, .sup.3J=8.7, 1H, H.sub.a or a'); 7.40 (d, .sup.3J=8.7, 1H,
H.sub.a or a'); .sup.31P-NMR (CDCl.sub.3): .delta. [ppm]=146.1
Example 4
(S)-5,5'-Dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl(R)-1-phenylethyl
phosphite
[0190] ##STR14##
[0191] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=1.59 (d,
.sup.3J=6.5, 3H, CH.sub.3); 3.49 and 3.53 (s, 3H, OCH.sub.3); 5.38
(dq, .sup.3J=6.5, J(H-P) =9.4, 1H, CH); 6.17 (dd, .sup.3J =8.7,
J(H-P)=0.7, 1H, H.sub.b or b'); 6.95 (dd, .sup.3J=8.7, J(H-P)=1.1,
1H, H.sub.b or b'); 7.21 (d, .sup.3J=8.7, 1H, H.sub.a or a');
7.25-7.38 (kB, 5H, H.sub.arom); 7.38 (d, .sup.3J=8.7, 1H, H.sub.a
or a'); .sup.31P-NMR (CDCl.sub.3): .delta. [ppm]=146.9
Example 5
(S)-5,5'-Dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl phenyl
phosphite
[0192] ##STR15##
[0193] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=3.59 and 3.61 (s,
3H, OCH.sub.3); 6.90 (dd, .sup.3J=8.7, J(H-P)=0.6, 1H, H.sub.b or
b'); 7.06 (dd, .sup.3J=8.7, J(H-P)=1.1, 1H, H.sub.b or b');
7.13-7.21 (kB, 3H, H-2 and H-4); 7.32-7.38 (kB, 2H, H-3); 7.40 (d,
.sup.3J=8.7, 1 H, H.sub.a or a'); 7.47 (d, .sup.3J=8.7, 1H, H.sub.a
or a'); .sup.31P-NMR (CDCl.sub.3): .delta. [ppm]=141.4
Example 6
(S)-5,5'-Dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl
2,6-dimethylphenyl phosphite
[0194] ##STR16##
[0195] .sup.1H-NMR (CDCl.sub.3): .delta. [ppm]=2.40 (s, 6H,
CH.sub.3), 3.61 (s, 6H, OCH.sub.3); 7.02 (dd, .sup.3J=8.7,
J(H-P)=1.0, 1H, H.sub.b or b'); 7.02-7.12 (kB, 3H, H.sub.arom);
7.03 (dd, .sup.3J=8.7, J(H-P)=0.8, 1H, H.sub.b or b'); 7.45 (d,
.sup.3J=8.7, 1H, H.sub.a or a'); 7.46 (d, .sup.3J=8.7, 1H, H.sub.a
or a'); .sup.31P-NMR (CDCl.sub.3): .delta. [ppm]=145.1
Hydrogenations
Examples 7-11
Hydrogenation of Dimethyl Itaconate
[0196] In a baked-out glass autoclave, 0.02 mmol of
bis(norbornadiene)rhodium(I) tetrafluoroborate
[Rh(nbd).sub.2]BF.sub.4 and 0.04 mmol of the appropriate phosphite
are dissolved in 5 ml of degassed methylene chloride. The mixture
is stirred for about 5 minutes and 8 mmol of dimethyl itaconate and
0.2000 g of diglyme in 15 ml of degassed methylene chloride are
subsequently added. After setting the appropriate temperature, the
mixture is hydrogenated for 2 hours under a hydrogen partial
pressure of 0.5 bar. Conversion and ee are determined by gas
chromatography.
[0197] The results are summarized in Table 1. TABLE-US-00001 TABLE
1 Conversion ee [%], [%] configuration Example Ligand
(configuration) RT 0.degree. C. RT 0.degree. C. 7 R = i-Propyl (S)
from 100 100 96 (S) 97 (S) Example 2 8 R = Cyclohexyl (S) from 100
100 91 (S) 94 (S) Example 3 9 R = (R)-1-Phenylethyl (S) 100 100 97
(S) 99 (S) from Example 4 10 R = Phenyl (S) from 100 87 82 (S) 91
(S) Example 5 11 R = 2,6-Dimethylphenyl 58 41 59 (S) 74 (S) (S)
from Example 6
Example 12-13
Hydrogenation of Dimethyl Itaconate
[0198] In a baked-out glass autoclave, 0.02 mmol of
bis(bicyclo[2.1.1]hepta-2,5-diene)rhodium(I)
tetrafluoroborate[Rh(nbd).sub.2]BF.sub.4 and 0.04 mmol of the
appropriate phosphite are dissolved in 50 ml of degassed methylene
chloride. The mixture is stirred for about 5 minutes and 200 mmol
of dimethyl itaconate and 5.000 g diglyme in 250 ml of degassed
methylene chloride are subsequently added. After setting the
appropriate temperature, the mixture is hydrogenated for 2.5 hours
under a hydrogen partial pressure of 0.5 bar. Conversion and ee are
determined by gas chromatography.
[0199] The results are summarized in Table 2. TABLE-US-00002 TABLE
2 Conversion ee [%], Example Ligand (configuration) [%]
configuration 12 R = i-Propyl (S) from Example 90 97 (S) 2 13 R =
(R)-1-Phenylethyl (S) from 100 99 (S) Example 4
Example 14-18
Hydrogenation of methyl 2-acetamidoacrylate
[0200] 0.0024 mmol of the appropriate phosphite are weighed out and
admixed under argon with a solution of 0.0012 mmol of
bis(norbornadiene)rhodium(I) hexafluorophosphate
[(nbd).sub.2Rh]PF.sub.6 and 0.12 mmol of methyl 2-acetamidoacrylate
in 0.8 ml of degassed CH.sub.2Cl.sub.2. The mixture is subsequently
hydrogenated for 23 hours under a hydrogen pressure of 3 bar.
[0201] The results are summarized in Table 3. TABLE-US-00003 TABLE
3 Conversion ee [%], Examples Ligand (configuration) [%]
configuration 14 R = I-Propyl (S) from 100 94 (R) Example 2 15 R =
Cyclohexyl (S) from 100 94 (R) Example 3 16 R = (R)-1-Phenylethyl
(S) from 100 83 (R) Example 4 17 R = Phenyl (S) from Example 5 100
77 (R) 18 R = 2,6-Dimethylphenyl (S) 100 18 (R) from Example 6
Example 19-20
Hydrogenation of methyl cis-3-acetamidobutenoate
[0202] 0.0024 mmol of the appropriate phosphite are weighed out and
admixed under argon with a solution of 0.0012 mmol of
bis(bicyclo[2.1.1]hepta-2,5-diene)rhodium(I)
hexafluorophosphate[Rh(nbd).sub.2]BF.sub.4 and 0.12 mmol of methyl
cis-3-acetamidobutenoate in 0.8 ml of degassed CH.sub.2Cl.sub.2.
The mixture is subsequently hydrogenated for 23 hours under a
hydrogen pressure of 3 bar.
[0203] The results are summarized in Table 4. TABLE-US-00004 TABLE
4 Examples Ligand (configuration) Conversion [%] ee [%] 19 R =
i-Propyl (S) (Ex. 2) 4 71 20 R = Cyclohexyl (S) (Ex. 3) 3 56 (other
enantiomer)
Example 21-29
Synthesis of
3,3'-bis(1,1-dimethylethyl)-5,5',6,6'-tetramethyl-1,1'-biphenyl-2,2'-diol
phosphites (BIPHEN phosphites)
[0204] In a 250 ml Schlenk flask which had been baked out and
flushed with argon three times, 70 ml of toluene and 1.9 ml (0.0137
mol) of triethylamine were cooled to -78.degree. C. (dry
ice/acetone). 0.3 ml (0.0034 mol) of phosphorus trichloride was
added while stirring vigorously. 1 g (0.0028 mol) of solid (R)- or
(S)-BIPHEN was added to this slightly turbid suspension in a
countercurrent of argon over a period of 2-3 hours by means of a
powder feed device. A white or yellow suspension was formed and
this was warmed to room temperature overnight. The mixture was
subsequently filtered through an inversion frit under protective
gas and the solvent was removed under reduced pressure. This gave a
yellow or white solid.
[0205] A solution of about 3 mmol (1 eq, 1.1 g) of this solid was
added to 41 ml of toluene, 0.43 ml (3 mmol, 1 eq) of triethylamine
and the amount of alcohol indicated in the table (Examples 21 to
29). The solution was stirred under argon overnight at room
temperature. The mixture was subsequently filtered through an
inversion frit to remove the ammonium salt and the solvent was
removed under reduced pressure. This gave a yellow or white
solid.
[0206] The yields and physical data are summarized in Table 5.
TABLE-US-00005 TABLE 5 Amount of Example: alcohol Yield Analysis 21
0.26 g (0.0028 0.911 g (68%) .sup.31P NMR: .delta. = 135.29 mol) of
phenol of yellow solid ppm 22 0.15 ml (0.0028 0.802 g (67%)
.sup.31P NMR: .delta. = 132.45 mol; 1 eq) of of white solid ppm
ethanol 23.sup.1) 0.34 g (0.0028 1.353 g (95%) .sup.31P NMR:
.delta. = 135.77 mol; 1 eq) of 2,6- of white solid ppm
dimethylphenol 0.14 g (0.0058 mol; 1,1 eq) of sodium hydride 24
0.11 ml (0.0028 1.151 g (99%) .sup.31P NMR .delta. = 130.18 mol; 1
eq) of of white solid ppm methanol 25 0.424 ml (0.0028 0.978 g
(65%) .sup.31P NMR .delta. = 136.3 mol; 1 eq) of tert- of yellow
solid ppm butylphenol 26 0.34 ml (0.0028 0.881 g (62%) .sup.31P NMR
.delta. = 141.82 mol; 1 eq) of of whitish ppm and 138.58 (dia-
phenylethyl yellow solid stereomeric pair) alcohol 27 0.52 g
(0.0028 0.771 g (48%) .sup.31P NMR .delta. = 136.35 mol; 1 eq) of
of white solid ppm diphenyl carbinol 28 0.22 ml (0.0028 0.521 g
(33%) .sup.31P NMR: .delta. 142.84 mol; 1 eq) of of white solid ppm
isopropanol 29.sup.1) Five-fold batch 7.23 g (92%) .sup.31P NMR:
.delta. 1365.74 using 8.1 ml of yellow solid ppm (0.014 mol; 1 eq)
of 2,6- diisopropylphenol .sup.1)Additional use of sodium hydride
as base to form the phenoxide
Examples 30 to 33
Asymmetric Hydrogenation Using BIPHEN Phosphites
[0207] The ligands (from Examples 21 and 24) were weighed into the
reaction vessels (batch size: 0.09 mmol). The substrates were
subsequently each prepared as a stock solution (dilution: 0.13
mol/l) in 5.1 ml of methylene chloride and degassed. 5.6 mg of
bis-(1,5-cycloctadiene)rhodium triflate Rh(COD).sub.2OTf were in
each case added and the mixture was degassed again. In a glove box,
0.72 ml of solution was placed in each of the individual vessels (2
mol % of catalyst and 2 mol % of ligand). All batches were
hydrogenated in an autoclave (23 h, 3 bar of hydrogen pressure,
RT).
[0208] The results are summarized in Tables 6 and 7. TABLE-US-00006
TABLE 6 Hydrogenation of methyl cis-3-acetamidobutenoate Ligand 21
24 Conversion [%] 100 100 ee [%] 11.3 59 Example No. 30 31
[0209] TABLE-US-00007 TABLE 7 Hydrogenation of dimethyl itaconate
Ligand 21 24 Conversion [%] 100 100 ee [%] 14 13 Example No. 32
33
[0210] Although the invention has been described in detail in the
foregoing for the purpose of illustration, it is to be understood
that such detail is solely for that purpose and that variations can
be made therein by those skilled in the art without departing from
the spirit and scope of the invention except as it may be limited
by the claims.
* * * * *