HYDROGENATION CATALYST, PROCESS FOR THE PREPARATION THEREOF AND HYDROGENATION PROCESS

CATALYSEUR D'HYDROGENATION, SON PROCEDE DE PREPARATION ET PROCEDE D'HYDROGENATION

English Abstract

Reaction products of an iridium (III) salt or a hydrate thereof, a diphosphine having secondary phosphine groups and a metal or
ammonium chloride, bromide or iodide are excellent hydrogenation catalysts for ketimine. Using chiral diphosphines and prochiral ketimines,
diastereoisomeric secondary amines are obtained in high optical yields.

French Abstract

Les produits de la réaction entre un sel d'iridium (III) ou un hydrate de ce sel, une diphosphine contenant des groupes phosphine secondaires et un chlorure, bromure ou iodure d'ammonium ou métallique sont d'excellents catalyseurs d'hydrogénation pour la cétimine. L'utilisation de diphosphines chirales et de cétimines prochirales permet d'obtenir des amines secondaires diastéréoisomères avec des rendements élevés en matières optiques.

Claims

-26-
CLAIMS:
1. An iridium compound obtained by the reaction of an
iridium(III) or iridium(IV) salt or a hydrate thereof and a
diphosphine having secondary phosphine groups in the
presence of a metal or ammonium chloride, bromide or iodide.
2. An iridium compound according to claim 1, wherein
the iridium(III) salt or the hydrate thereof is of formula I
[Ir3 ~ ] [X n ~] 3/n.cndot. mH2O (I)
wherein X is the n-valent anion of an acid,
n i s 1, 2 or 3 and
m is from 0 up to 8.
3. An iridium compound according to claim 2, wherein
X n~ is the anion of an organic acid from the group of
aliphatic or aromatic carboxylic acids, sulfonic acids and
phosphonic acids containing from 1 to 12 carbon atoms that
are unsubstituted or substituted by F or Cl; or the anion of
an inorganic acid from the following group: hydrohalic
acids, tetrafluoroboric acid, tetraphenylboric acid,
hexafluoro-phosphoric, -arsenic, -antimonic and -bismuthic
acid, and the oxy acids of the elements N, P, S, F, Cl, Br
and I.
4. An iridium compound according to claim 2, wherein
X n~ is a halide.
5. An iridium compound according to claim 2, wherein
the iridium(III) salt of formula I is IrCl3.cndot.mH2O, wherein m
is a number from 1 to 4.

-27-
6. An iridium compound according to any one of
claims 1 to 5, wherein the metal chloride, bromide or iodide
comprises a cation selected from Li~, Na~ and K~
7. An iridium compound according to any one of
claims 1 to 5, wherein the ammonium chloride, bromide or
iodide comprises an ammonium cation selected from NH4~, a
primary ammonium having from 1 to 20 carbon atoms, a
secondary ammonium having from 2 to 24 carbon atoms, a
tertiary ammonium having from 3 to 24 carbon atoms, and a
quaternary ammonium having from 4 to 24 carbon atoms.
8. An iridium compound according to claim 7, wherein
the quaternary ammonium cation is a quaternary ammonium
cation of the formula phenylN~ - (C1-C6alkyl) 3,
benzylN~ (C1-C6alkyl) 3 or (C1-C6alkyl) 4N~.
9. An iridium compound according to any one of
claims 1 to 5, wherein the metal or ammonium chloride,
bromide or iodide is the bromide or the iodide.
10. An iridium compound according to claim 9, wherein
the metal or ammonium chloride, bromide or iodide is LiI,
NaI or KI or (C1-C6alkyl)4NI.
11. An iridium compound according to claim 9, wherein
the metal or ammonium chloride, bromide or iodide is tetra-
butylammonium iodide.
12. An iridium compound according to claim 1, wherein
the diphosphine having secondary phosphine groups is a
diphosphine
(a) the phosphine groups of which are bonded to a
carbon chain having from 2 to 4 carbon atoms;

-28-
(b) the phosphine groups of which are either
bonded directly or via a bridge group -CR a R b- in the ortho
positions of a cyclopentadienyl ring or are each bonded to a
cyclopentadienyl ring of a ferrocenyl;
(c) one phosphine group of which is bonded to a
carbon chain having 2 or 3 carbon atoms and the other
phosphine group of which is bonded to an oxygen atom or a
nitrogen atom bonded terminally to that carbon chain, or
(d) the phosphine groups of which are bonded to
the two oxygen atoms or nitrogen atoms bonded terminally to
a C2-carbon chain;
with the result that in the cases of (a), (b), (c)
and (d) a 5-, 6- or 7-membered ring is formed together with
the Ir atom, and R a and R b are each independently of the
other hydrogen, C1-C8alkyl, C1-C4fluoroalkyl, phenyl or benzyl
or are phenyl or benzyl having from 1 to 3 C1-C4alkyl or
C1-C4alkoxy substituents.
13. An iridium compound according to claim 1, wherein
the diphosphine contains at least one chiral carbon atom.
14. An iridium compound according to claim 1, wherein
the secondary phosphine groups contain two identical or
different radicals from the following group: linear or
branched C1-C12alkyl; unsubstituted or C1-C6alkyl- or
C1-C6alkoxy-substituted C5-C12cycloalkyl, C5-C12cycloalkyl-
CH2-, phenyl or benzyl; or phenyl or benzyl substituted by
halogen, C1-C6haloalkyl, (C1-C12alkyl) 3Si, (C6H5) 3Si,
C1-C6haloalkoxy, -NH2, phenyl2N-, benzyl2N-, morpholinyl,
piperidinyl, pyrrolidinyl, (C1-C12alkyl) 2N-, -ammonium-X1~,
-SO3M1, -CO2M1, -PO3M1 or by -COO-C1-C6alkyl, wherein M1 is an
alkali metal or hydrogen and X1~ is the anion of a monobasic
acid.

-29-
15. An iridium compound according to claim 14, wherein
the phenyl or benzyl substituted by halogen is phenyl or
benzyl substituted by F, Cl or Br.
16. An iridium compound according to claim 14 or 15,
wherein the phenyl or benzyl substituted by C1-C6haloalkoxy
is phenyl or benzyl substituted by trifluoromethoxy.
17. An iridium compound according to claim 1, wherein
the diphosphine is of the formula:
<IMG>

-30-
or <IMG>
wherein
R15 and R16 are each independently of the other
hydrogen, C1-C4alkyl, phenyl, benzyl, or phenyl or benzyl
having from 1 to 3 C1-C4alkyl or C1-C4alkoxy substituents,
R14 is hydrogen, C1-C4alkyl, phenyl, benzyl, or
phenyl or benzyl having from 1 to 3 C1-C4alkyl or C1-C4alkoxy
substituents,
R17 is hydrogen, C1-C4alkyl, phenyl, benzyl,
C1-C6alkoxy-CO-, C1-C6alkyl-CO-, phenyl-CO-, naphthyl-CO- or
C1-C4alkylNH-CO-,
A is a diphosphine group -PR2, wherein R is
C1-C6alkyl, cyclohexyl, phenyl, benzyl, or phenyl or benzyl
having from 1 to 3 C1-C4alkyl, C1-C4alkoxy, -CF3 or partially
or fully fluorinated C1-C4alkoxy substituents, and
n is 0, 1 or 2.
18. An iridium compound according to claim 17, wherein
the diphosphine is~{(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dipropyl-aminophenyl)phosphine.
19. An iridium compound according to claim 17, wherein
the diphosphine is {(R)-1-[(S)-2-

-31-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisopropyl-4-
N,N-dimethyl-aminophenyl)phosphine.
20. An iridium compound according to claim 17, wherein
the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisopropyl-4-
N,N-dibenzylyl-aminophenyl)phosphine.
21. An iridium compound according to claim 17, wherein
the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dibenzylyl-aminophenyl)phosphine.
22. An iridium compound according to claim 17, wherein
the diphosphine is {(R) -1- [(S) -2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-(1'-
pyrrolo)-phenyl)phosphine.
23. An iridium compound according to claim 17, wherein
the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dipentyl-aminophenyl)phosphine.
24. An iridium compound according to claim 17, wherein
the diphosphine is {(R) -1- [(S) -2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dimethyl-aminophenyl)phosphine.
25. An iridium compound according to claim 17, wherein
the diphosphine is 1,4-bis(diphenylphosphino)butane {(R)-1-
[(S)-2-(di(4-methoxyphenyl)phosphino)ferrocenyl]}ethyl-
di(3,5-dimethyl-4-N,N-dimethylaminophenyl)phosphine.
26. An iridium compound according to claim 17, wherein
the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-
phenyl)phosphine.

-32-
27. A process for the preparation of an iridium
compound, which comprises reacting with one another at least
equimolar amounts of an iridium(III) or iridium(IV) salt or
a hydrate thereof and a diphosphine having secondary
phosphine groups in the presence of an alkali metal or
ammonium chloride, bromide or iodide.
28. A process according to claim 27, wherein the molar
ratio of the iridium(III) or iridium(IV) salt or the hydrate
thereof to diphosphine is from 1:1 to 1:1.5.
29. A process according to claim 27 or 28, wherein the
alkali metal or ammonium chloride, bromide or iodide is used
in excess, based on the iridium(III) or iridium(IV) salt or
the hydrate thereof.
30. A process according to any one of claims 27 to 29,
wherein the reaction temperature is from -20°C to 100°C.
31. A process according to any one of claims 27 to 30,
wherein the reaction is carried out in a dipolar solvent.
32. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dipropyl-aminophenyl)phosphine.
33. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisopropyl-4-
N,N-dimethyl-aminophenyl)phosphine.
34. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisopropyl-4-
N,N-dibenzylyl-aminophenyl)phosphine.

-33-
35. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dibenzylyl-aminophenyl)phosphine.
36. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-(1'-
pyrrolo)-phenyl)phosphine.
37. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dipentyl-aminophenyl)phosphine.
38. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-N,N-
dimethyl-aminophenyl)phosphine.
39. A process according to any one of claims 27 to 31,
wherein the diphosphine is 1,4-bis(diphenylphosphino)butane
{(R)-1-[(S)-2-(di(4-
methoxyphenyl)phosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-
N,N-dimethylaminophenyl)phosphine.
40. A process according to any one of claims 27 to 31,
wherein the diphosphine is {(R)-1-[(S)-2-
(diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-
phenyl)phosphine.
41. A process for the catalytic hydrogenation of an
imine with hydrogen under elevated pressure in the presence
of an iridium catalyst and with or without an inert solvent,
wherein an iridium compound according to any one of claims 1
to 26 is used as the catalyst.

-34-
42. A process according to claim 41, wherein the imine
contains at least one <IMG> group.
43. A process according to claim 41, wherein the imine
contains at least one of the groups <IMG> and
<IMG > and additionally unsaturated groups <IMG>
and <IMG>
44. A process according to claim 43, wherein free bonds
of the imine are saturated with hydrogen, organic radicals
having from 1 to 22 carbon atoms, or organic hetero radicals
having from 1 to 20 carbon atoms and at least one hetero atom
from the group O, S, N and P; or the nitrogen atom of the
group <IMG> is saturated with NH2, a primary amino group
having from 1 to 22 carbon atoms, or a secondary amino group
having from 2 to 40 carbon atoms.
45. A process according to claim 41, wherein the imine
is selected from an aldimine, a ketimine and a hydrazone.
46. A process according to claim 41, wherein the imine
is an imine of formula III
<IMG>
which is hydrogenated to form an amine of formula IV
<IMG>
wherein

-35-
R3 is linear or branched C1-C12alkyl; cycloalkyl
having from 3 to 8 ring carbon atoms; heterocycloalkyl
bonded via a carbon atom and having from 3 to 8 ring atoms
and 1 or 2 hetero atoms from the group O, S and NR6; a
C7-C16aralkyl bonded via an alkyl carbon atom; or C1-C12alkyl
substituted by cycloalkyl having 3 to 8 ring carbon atoms,
heterocycloalkyl bonded via a carbon atom and having from 3
to 8 ring atoms and 1 or 2 hetero atoms selected from O, S
and NR6, or heteroaryl having 1 or 2 hetero atoms selected
from O, S and NR6;
or
R3 is C6-C12aryl or C4-C11heteroaryl bonded via a
ring carbon atom and having 1 or 2 hetero atoms in the ring;
wherein R3 is unsubstituted or substituted by -CN, -NO2, F,
Cl, C1-C12alkyl, C1-C12alkoxy, C1-C12alkylthio, C1-C6haloalkyl,
-OH, C6-C12-aryl, C6-C12-aryloxy, C6-C12-arylthio, C7-C16-
aralkyl, C7-C16-aralkoxy, C7-C16-aralkylthio, secondary amino
having from 2 to 24 carbon atoms, -CONR4R5 or by -COOR4,
wherein each aryl portion of the aralkyl, aralkoxy and
aralkylthio radical is unsubstituted or substituted by -CN,
-NO2, F, Cl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, -OH,
-CONR4R5 or by -COOR4; and wherein
R4 and R5 are each independently hydrogen,
C1-C12alkyl, phenyl or benzyl; or
R4 and R5 together are tetra-methylene, penta-
methylene or 3-oxapentylene;
R6 is, independently of R4, defined as R4 is
defined herein; and
R1 and R2 are each independently a hydrogen atom,
C1-C12alkyl or cycloalkyl having from 3 to 8 ring carbon

-36-
atoms, wherein the C1-C12alkyl or the cycloalkyl is
unsubstituted or substituted by -OH, C1-C12alkoxy, phenoxy,
benzyloxy, secondary amino having from 2 to 24 carbon atoms,
-CONR4R5 or by -COOR4; C6-C12aryl or C7-C16aralkyl wherein the
C6-C12aryl or the C7 to C16aralkyl is unsubstituted or
substituted by -CN, -NO2, F, Cl, C1-C12alkyl, C1-C12alkoxy,
C1-C12alkylthio, C1-C6haloalkyl, -OH, C6-C12-aryl, C6-C12-
aryloxy, C6-C12-arylthio, C7-C16-aralkyl, C7-C16-aralkoxy,
C7-C16-aralkylthio, secondary amino having from 2 to 24 carbon
atoms, -CONR4R5 or by -COOR4, wherein each aryl portion of the
aralkyl, aralkoxy and aralkylthio radical is unsubstituted or
substituted by -CN, -NO2, F, Cl, C1-C4-alkyl, C1-C4-alkoxy,
C1-C4-alkylthio, -OH, -CONR4R5 or by -COOR4, and wherein R4 and
R5 are as defined herein;
R3 is as defined herein and R1 and R2 together are
alkylene having from 2 to 5 carbon atoms that is optionally
interrupted by 1 or 2 -O-, -S- or -NR6- radical, unsubstituted
or substituted by =O or R1 and R2 together are C1-C12alkyl
unsubstituted or substituted by -OH, C1-C12alkoxy, phenoxy,
benzyloxy, secondary amino having from 2 to 24 carbon atoms,
-CONR4R5 or by -COOR4 condensed with benzene, pyridine,
pyrimidine, furan, thiophene or pyrrole;
R2 is as defined herein and R1 and R3 together are
alkylene having from 2 to 5 carbon atoms that is optionally
interrupted by 1 or 2 -O-, -S- or -NR6- radical, unsubstituted
or substituted by =O or R1 and R3 together are C1-C12alkyl
unsubstituted or substituted by -OH, C1-C12alkoxy, phenoxy,
benzyloxy, secondary amino having from 2 to 24 carbon atoms,
-CONR4R5 or by -COOR4 condensed with benzene, pyridine,
pyrimidine, furan, thiophene or pyrrole;
R3 is as defined herein and R1 and R2 together form
a 5- or 6-membered heteroaryl having 1 or 2 identical or

-37-
different hetero atoms selected from O, S and NR6, wherein R6
is as defined herein;
R3 is as defined herein and R1 and R2 together are a
5- or 6-membered heteroaryl-substituted alkyl wherein the
heteroaryl thereof has 1 or 2 identical or different hetero
atoms selected from O, S and NR6 is as defined herein; or
R3 is as defined herein and R1 and R2 together form
a heterocycloalkyl or a heterocycloalkyl-substituted alkyl
each of which comprises from 4 to 6 ring atoms and 1 or 2
identical or different hetero atoms selected from the group
O, S and NR6, wherein R6 is hydrogen, C1-C12alkyl, phenyl or
benzyl.
47. A process according to claim 46, wherein R1 and R2
together form the 5- or 6-membered heteroaryl having 1 or 2
identical or different hetero atoms selected from O, S
and NR6.
48. A process according to claim 46, wherein R1 and R2
together form the 5- or 6-membered heteroaryl substituted
alkyl wherein the heteroaryl thereof has 1 or 2 hetero atoms
selected from O, S and NR6.
49. A process according to claim 46, wherein R1 and R2
together form the heterocycloalkyl or the heterocycloalkyl-
substituted alkyl.
50. A process according to claim 46, wherein in the
definitions of each of R1, R2 and R3 the C1 to C12 alkyl is
C1-C6alkyl.
51. A process according to claim 46, wherein in the
definitions of each of R1, R2 and R3 the cycloalkyl has from 3
to 6 ring carbon atoms.

-38-
52. A process according to claim 46, wherein in the
definitions of each of R1, R2 and R3 the aryl is naphthyl or
phenyl.
53. A process according to claim 46, wherein in the
definitions of each of R1, R2 and R3, aralkyl is phenylalkyl
having from 1 to 10 carbon atoms in the alkylene portion
thereof.
54. A process according to claim 46, wherein R1 and R2
together or R1 and R3 together form, with the carbon atom or
the -N=C group to which they are bonded, respectively, a 5-
or 6-membered ring.
55. A process according to claim 46, wherein in
formula I R3 is 2, 6-di-C1-C4alkylphen-1-yl, R1 is C1-C4alkyl,
and R2 is C1-C4alkyl, C1-C4alkoxymethyl or C1-C4alkoxyethyl.
56. A process according to claim 46, wherein R3 is
2,6-dimethylphen-1-yl or 2-methyl-6-ethylphen-1-yl, R1 is
ethyl or methyl, and R2 is methoxymethyl.
57. A process according to any one of claims 41 to 56,
wherein an acid is used additionally.
58. A process according to claim 57, wherein the acid
is an inorganic or organic acid.
59. A process according to claim 58, wherein the
organic acid is an aliphatic or aromatic carboxylic acid,
sulfonic acid or phosphorus(V) acid.
60. A process according to claim 58, wherein the
organic acid is acetic acid, propionic acid, trifluoroacetic
acid, chloroacetic acid or methanesulfonic acid and the
inorganic acid is H2SO4.

-39-
61. A process according to any one of claims 57 to 60,
wherein the acid is used in an amount of from 0.1 to 50% by
weight, based on the imine prior to hydrogenation.
62. A process according to any one of claims 41 to 61,
wherein the molar ratio of the imine prior to hydrogenation
to the iridium catalyst is from 500 000 to 20.
63. A process according to any one of claims 41 to 62,
wherein the reaction temperature is from -20 to 100°C.
64. A process according to any one of claims 41 to 63,
wherein the hydrogen pressure is from 5 to 150 bar.
65. A process according to claim 41, wherein the imine
is an aldimine or a ketimine formed in situ before or during
the hydrogenation.
66. A hydrogenation catalyst which is a product of
reaction of an iridium(III) or iridium(IV) salt or a hydrate
thereof with a diphosphine having secondary phosphine groups
and an alkali metal or ammonium chloride, bromide or iodide.
67. Use of an iridium catalyst according to any one of
claims 1 to 26 as a hydrogenation catalyst.

Description

O W095121176 ~ PCTlEP95100122
I-
Hydroeenation catalyst, process for the preparation thereof and hvdroQenation
process
The present invention relates to a catalyst obtainable by the reaction of
iridium salts with
diphosphines and alkali metal or ammonium halides; to a preparation process
for those
catalysts; and to a process for the hydrogenation of imines, especially in the
presence of an
acid.
US-A-4 994 615 describes a process for' the asymmetric hydrogenation of
prochiral
N-arylketimines wherein iridium catalysts having chiral diphosphine ligands
are used.
US-A-5 011995 describes a process for the asymmetric hydrogenation of
prochiral
N-alkylketimines using the same catalysts. US-A-5 112 999 discloses
polynuclear iridium
compounds and a complex salt of iridium, which contain diphosphine ligands, as
catalysts
for the hydrogenation of imines. The catalysts are prepared by reacting
iridium olefin and
iridium diolefm complexes with diphosphines.
Those homogeneous catalysis pmcesse s have proved valuable, although it is
evident,
especially in the case of relatively large batches or on an industrial scale,
that the catalysts
frequently tend to become deactivated to a greater or lesser extent depending
on the
catalyst precursor, the substrate and the diphosphine ligands that are used.
In many cases,
especially at elevated temperatures - for example at temperatures
>25°C, which are
necessary for a short reaction time - it is not possible to achieve complete
conversion. For
industrial applications of the hydrogenation process, therefore, the catalyst
productivity is
too low from the point of view of economic viability.
A further disadvantage is the fact that as starting materials for the
catalysts the iridium
olefin and iridium diolefm complexes are unstable and expensive, with the
result that it is
not possible in practice to obtain commercial quantities.
It has now been found, surprisingly, that active homogeneous iridium catalysts
can be
obtained from simple iridium salts, which are considerably more economical, by
reacting
those salts with diphosphines in the presence of metal halides, especially
alkali metal or
ammonium halides.
It has also been found, surprisingly, that the catalyst activity can be
increased if during the
hydrogenation the reaction mixture comprises an acid in addition to the
catalyst. It has
also unexpectedly been found that at the same time the deactivation of the
catalysts can be

218I3~ t~.
W095/21176 ~: PCl'IEF95100222
y.6
considerably reduced or completely eliminated.
The invention relates to iridium compounds that are obtainable by reacting
iridium(III) or
iridium(IV) salts or hydrates thereof and a diphosphine having secondary
phosphine
groups in the presence of a metal chloride, bromide or iodide or an ammonium
chloride,
bromide or iodide.
The iridium(Iln sale or hydrates thereof may be, for example, of formula I
I~~lIX"els/n ~2~ W
wherein X is the n-valent anion of an acid,
n is 1, 2 or 3, and
m is 0 or a whole number or a fraction greater than 0 and up to 8.
The iridium(I~ salts or hydrates thereof may be, for example, of formula Ia
M2~(IrX'~]2~~mH2O
wherein
X' is halogen, especially F, CI or Br,
M2~ is two Fi~, two allcali metal cations, for example Li~, Na~ or K~, or an
allcaline
earth metal cation, for example Mg2~, Ca2~, Sr2~ or Ba2~, and
m is 0 or a whole number or a fraction greater than 0 and up to 8.
In formulae I and/or Ia, n is preferably 1 and m is preferably 0 or a whole
number or a
fraction greater than 0 and up to 4.
The anion X can be derived from organic or inorganic acids. Examples of
organic acids
are aliphatic and aromatic carboxylic acids, sulfonic acids and phosphonic
acids that
contain from 1 to 12, preferably from 1 to 8 and especially from 1 to 4,
carbon atoms and
are unsubsitituted or substituted by F or Cl. Some specific examples are
formic, acetic,
propionic, butyric, mono-, di- or tri-chloro- or mono-, di- or tri-fluoro-
acetic acid, benzoic
acid, phenylacetic acid, methyl-, phenyl- or benzyl-phosphonic acid and methyl-
, phenyl-,
benzyl- p-toluyl- or trifiuoromethyl-sulfonic acid. Examples of inorganic
acids are the
hydrohalic acids, tetrafluoroboric acid, tetraphenylboric acid, hexafluoro-
phosphoric,

W095121176 (~ PCT/EP95/00222
-3
-arsenic, -antimonic and -bismuthic acid, and the oxy acids of the elements N,
P, S, F, C1,
Br and I. Specific examples are HCI, HBr" HI, BFq, HB(phenyl)q, HPF6, HSbCl6,
HAsF6,
HSbF6, HCIOq, HBrOq, HIOq, HzSO3, HzSOq, HNOz, HN03, H3P03 and H3POq.
Preferred acids from which XI'e in formula I can be derived are HCI, HBr, HI,
HZSOq,
HCIOq, HClO3, HBrOq, HIOq, HNO3, H31?03, H3POq, CF3SO3H, C6H5SO3Fi, CF3COOH
and CC13COOH. In a special form, X~'~ in formula I is a monovalent anion (n is
prefer-
ably 1), especially a halide and morn especially Cle. The iridium(III) salt of
formula I is
especially IrCl3~mH20, wherein m is a number from 1 to 4.
Virtually any of the halogen compounds c~f the metals of the main groups and
subgroups
of the Periodic Table of the Elements can be used as the metal halides,
provided that they
are soluble in the reaction mixture and do not act as oxidising agents towards
the other
reactants in the reaction mixture. The use of alkali metal halides is
preferred.
The metal and alkali metal rations in the metal and alkali metal halides are
preferably the
Li, Na, K, Rb or Cs rations, especially Lid, Na~ and K~. The ammonium ration
in the
ammonium halides may be NI-~y~, primary ammonium having preferably from 1 to
20
carbon atoms, secondary ammonium having preferably from 2 to 24 carbon atoms,
tertiary
ammonium having preferably from 3 to 2~4 carbon atoms, and quaternary ammonium
having preferably from 4 to 2A carbon atoms. Preference is given to quaternary
ammonium, especially of the formula phenyIN~(Cl-C6alkyl)3, benzylN~(Ct-
C6alkyl)3 or
(Cl-C6alkyl)qN~. Of the alkali metal halides and ammonium halides, the
bromides and
especially the iodides are preferrcd. In a preferred form, the alkali metal
halides and
ammonium halides are LiI, NaI or KI or (Cl-C6alkyl)qNI. Tetrabutylammonium
iodide is
especially preferred
The diphosphines having secondary phosphine groups are preferably those
(a) the phosphine groups of which are bonded to different carbon atoms of a
carbon chain
having from 2 to 4 carbon atoms, or
(b) the phosphine groups of which are either bonded directly or via a bridge
group
-CRaRb- in the ortho positions of a cyclopentadienyl ring or are each bonded
to a cyclo-
pentadienyl ring of a ferrocenyl, or
(c) one phosphine group of which is bonded to a carbon chain having 2 or 3
carbon atoms
and the other phosphine group of which is bonded to an oxygen aeom or a
nitrogen atom
bonded terminally to that carbon chain, or

WO 95121176 ~ ~ ~ PCTIEP95100222
-4-
,l : .
(d) the phosphine groups of which are bonded to the two oxygen atoms or
nitrogen atoms
bonded terminally to a C2-carbon chain;
with the result that in the cases of (a), (b), (c) and (d) a 5-, 6- or 7-
membered ring is
formed together with the Ir atom, and Ra and Rb are each independently of the
other
hydrogen, CI-Csalkyl, CI-C4fluoroalkyl, phenyl or benzyl or are phenyl or
benzyl having
from I to 3 Ct-C4alkyI or CI-C~alkoxy substituents. Rb is preferably hydrogen.
Ra is
preferably Ct-Cyalkyl and especially methyl.
The diphosphine contains preferably at least one chiral carbon atom and is
especially an
optically pure stereoisomer (enantiomer or diastereoisomer), or a pair of
diastereoisomers,
since the use of catalysts containing those ligands Ieads to optical induction
in asymmetric
hydrogenation reactions.
The phosphine groups contain preferably two identical or different, preferably
identical,
unsubstituted or substituted hydrocarbon radicals having from 1 to 20,
especially from 1 to
12 carbon atoms. Preference is given to diphosphines wherein the secondary
phosphine
groups contain two identical or different radicals from the following group:
linear or
branched CI-Cl2alkyl; unsubstituted or CI-C6alkyl- or CI-C6aIkoxy-substituted
Cs-Cl2cycloalkyl, CS-Cl2cycloalkyl-CH2-, phenyl or benzyl; and phenyl or
benzyl
substituted by halogen (e.g. F, Cl or Br), CI-C6haloallryl, (CI-Cl2alkyl)3Si,
(C~fis)3Si,
CI-C6haloalkoxy (e.g. trifluoromethoxy), -NH2, phenyl2N-, benzyl2N-,
morpholinyl,
piperidinyl, pyrrolidinyl, (CrCl2~Yl)2N-, -~onium-XIO, -S03M1, -C02M1, -P03M1
or by -COO-Ct-C6atkyl (e.g. -COOCH3), wherein MI is an alkali metal or
hydrogen and
Xle is the anion of a monobasic acid. MI is preferably H, Li, Na or K. Ale ,
as the anion
of a monobasic acid, is preferably Cl~, Bre or the anion of a carboxylic acid,
for example
formate, acetate, trichloroacetate or trifluoroacetate.
A secondary phosphine group may also be a radical of the formula
\ ~ P \ ~ or , wherein
m and n are each independently of the other an integer from 2 to 10, and the
sum of m+n is
from 4 to 12, especially from 5 to 8. Examples thereof are [3.3.17- and
[4.2.Ij-phobyl of

2~.8136:~. .
WO 95121176 ~ PCTIEP95I00222
-5-
the formulae
and P I.
Examples of alkyl that preferably contains from 1 to 6 carbon atoms are
methyl, ethyl,
n-propyl, isopropyl, n-, iso- and tert-butyJL and the isomers of pentyl and
hexyl. Examples
of unsubstituted or allcyl-substituted cycloalkyl are cyclopentyl, cyclohexyl,
methyl- or
ethyl-cyclohexyl and dimethylcyclohexyl. Examples of alkyl-, alkoxy- or
haloalkoxy-
substituted phenyl and benzyl are methylphenyl, dimethylphenyl,
trimethylphenyl, ethyl-
phenyl, methylbenzyl, methoxyphenyl, di~methoxyphenyl, trifluoromethylphenyl,
bis-tri-
fluoromethylphenyl, tris-trifluoromethylphenyl, trifluoromethoxyphenyl and bis-
trifluoro-
methoxyphenyl. Preferred phosphine groups are those that contain identical or
different,
preferably identical, radicals from the group Ct-Cbalkyl; cyclopentyl and
cyclohexyl that
are unsubstituted or have from 1 to 3 Ct-CQallcyl or Cl-C4alkoxy substituents,
benzyl and,
especially, phenyl that is unsubstituted or has firm 1 to 3 Cl-C4alkyl, Ct-
C4alkoxy, F, Cl,
Ct-Cafluoroalkyl or Ct-C,~fluoroalkoxy substituents.
The diphosphine is preferably of formula II, IIa, IIb, IIc or IId,
R7R$P-Rg-PRtaRll (B)~
R7RsP-O-R12 PR1aR11 (Ba),
R7R8P-NR~-Rt2-PRipRll (Bb),
R7R8P-O-R13-O-PRipRll (Bc)>
R7R$P-NR~-Rig-NR~ PRtp121t (Ild),
wherein
R7, R8, Rip and Rt 1 are each independenl;ly of the others a hydrocarbon
radical having
from 1 to 20 carbon atoms that is unsubstituted or substituted by Ct-Csalkyl,
Cl-C6alkoxy,
halogen, Ct-C6haloalkyl, (Ct-Cl2alkyl)3Si, (C6H5)3Si, Ct-Cbhaloalkoxy, -NH2,
phenyl2N-,
benzyl2N-, morpholinyl, piperidinyl, pywolidinyl, (Ct-Ct2alkyl)2N-, -ammonium-
X16

WO 95!21176 ~ ~ ~ ~ PCTIJEP95/00222 .
-6-
-S03M1, -C02M1, -P03M1 or by -COO-C1-C6alkyl, ,v~herein Ml is an alkali metal
or
hydrogen and X10 is the anion of a monobasic,~
n
R9 is linear Cy-C4alkylene that is unsubstituted or substituted by C1-C6alkyl,
CS- or
C6-cycloalkyl, phenyl, naphthyl or by benzyl; 1,2- or 1,3-cycloalkylene or -
cycIoalkenyl-
ene, -bicycloalkylene or -bicycloallcenylene having from 4 to 10 carbon atoms,
each of
which is unsubstituted or substituted by Cl-C6alkyl, phenyl or by benzyl; 1,2-
or
1,3-cycloallcylene or -cycloalkenylene,-bicycloallrylene or -bicycloalkenylene
having
from 4 to 10 carbon atoms, each of which is unsubstituted or substituted by C1-
Cbalkyl,
phenyl or by benzyl, and in the 1- and/or 2-positions or in the 3-position of
which methyl-
cne or C2-C4alkylidene is bonded; 1,4-butylene substituted in the 2,3-
positions by
R21R~C~ and unsubstituted or substituted in the 1,4-positions by Cl-C6allryl,
O-
phenyl or by benzyl, wherein R21 and Rte, are each independently of the other
hydrogen,
Cl-Cbalkyl, phenyl or benzyl; 3,4- or 2,4-pyrrolidinylene or 2-methylene-
pyrrolidin-4-yl
the nitrogen atom of which is substituted by hydrogen, Cl-Cl2alkyl, phenyl,
benzyl,
Cl-Cl2alkoxycarbonyl, Cl-Csacyl or by Cl-Cl2allcylaminocarbonyl; or 1,2-
phenylene,
2-benzylene, 1,2-xylylene, 1,8-naphthylene,2,2'-dinaphthylene or 2,2'-
diphenylene,each
of which is unsubstituted or substituted by C1-C4alkyl;
or R9 is a radical of the formula
X14- ~14-
Fe ~ Fe Vila ,
Fe ~ Fe ~ Ru

~i8~~6~
WO 95121176 ~ ' PCTIEP95100222
CHRt4- ~- CHRt4-
Fe ~ or Fe
~14-
wherein R14 is hydrogen, C1-Cgallcyl, C1-C4fluomalkyl, phenyl or phenyl having
from
1 to 3 Cl-C4alkyl or Cl-C4alkoxy substituents;
R12 is linear C2- or C3-alkylene that is unsubstituted or substituted by Cl-
C.~alkyl, CS- or
C6-cycloallcyl, phenyl, naphthyl or by benzyl; 1,2- or 1,3-cycloalkylene or -
cycloalkenyl-
ene, -bicycloalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms,
each of
which is unsubstituted or substituted by Cl-C6alkyl, phenyl or by benzyl; or
1,2- or 1,3-
cycloalkylene or -cycloalkenylene, -bicycloalkylene or -bicycloalkenylene
having from 4
to 10 carbon atoms, each of which is unsubstituted or substituted by Cl-
C6alkyl, phenyl or
by benzyl, and in the 1- and/or 2-positions or in the 3-position of which
methylene or
Cz-C4alkylidene is bonded; 3,4- or 2,4-pytrolidinylene or 3-methylene-
pyrrolidin-4-yl the
nitrogen atom of which is substituted by hydrogen, Cl-Cl2alkyl, phenyl,
benzyl,
Cl-Cl2alkoxycarbonyl, Cl-Csacyl or by Cl-Cl2atkylaminocarbonyl; or 1,2-
phenylene,
2-benzylene, 1,2-, 2,3- or 1,8-naphthylene, each of which is unsubstituted or
substituted by
Cl-C4allryl; and
R13 is linear Caallrylene that is unsubstituted or substituted by Cl-C6alkyl,
CS- or
C6-cycloalkyl, phenyl, naphthyl or by benzyl; 1,2-cycloallcylene or-
cycloallcenylene,
-bicycIoalkylene or -bicycloalkenylene having from 4 to 10 carbon atoms, each
of which
is unsubstituted or substituted by C1-C6allcyl, phenyl or by benzyl; 3,4-
pyrrolidinylene the
nitrogen atom of which is substituted by hydrogen, Cl-Cl2alkyl, phenyl,
benzyl,
Cl-Cl2alkoxycarbonyl, Cl-Csacyl or by Cl-Cl2allcylaminocarbonyl; or 1,2-
phenylene that
is unsubstituted or substituted by Cl-C4allcyl, or is a radical, less two
hydroxy groups in
the ottho positions, of a mono- or di-saccharide, and
R~ is hydrogen, Cl-C4alkyl, phenyl or ben.zyl.
R7, Rg, Rlp and Rl1 are preferably identical or different, preferably
identical, radicals from
the following group: Cl-C6alkyl; cyclopentyl and cyclohexyl that are
unsubstituted or

~1~~~~~
WO 95/21176 PCTIEP95/00222
g~_'y. ~.
have from 1 to 3 Ct-C4alkyl or CI-C4allcoxy substituents, benzyl and,
especially, phenyl
that is unsubstituted or has from 1 to 3 Ct-C4alkyl, CI-C4alkoxy, F, Cl, CI-
C4fluoroalkyl
or CI-C4fluoroalkoxy substituents.
A preferred subgroup of diphosphines is formed by those of the formulae
R\ls
R R
I5 15 iCH-A
~CIi-A ~C- //
A
/ I -A, / Ii~, ~ ,
RI6 Rls
-A
RI6
A
A-HRtSC
A C\ /Rts
~ ~ ~ , ~CHR~S-A,
/ 'O Rts N
p A-HRteC I
Rp
CHRts-A CHRts-A
CHRtsA
(C 2)a
N
I CHR~s-A
R»
A A
N
I
Rte

W095/21176 ~ ~~ ' PCTlEP95/00222
-9-
CHR14-A
and 1''e A
wherein
RIS and R16 are each independently of the other hydrogen, CI-C4alkyl, phenyl,
benzyl, or
phenyl or benzyl having from i to 3 CI-C,4allryl or CI-C4alkoxy substituents,
R14 is hydrogen, CI-C4alkyl, phenyl, bens:yl, or phenyl or benzyl having from
i to 3
CI-C4alkyl or CI-C4alkoxy substituents,
R17 is hydrogen, CI-C4atkyl, phenyl, bens:yl, CI-Cbalkoxy-CO-, CI-C6alkyl-CO-,
phenyl-CO-, naphthyl-CO- or CI-CQa1ky11~TH-CO-,
A is a diphosphine group -PRz, wherein R. is CI-C6alkyl, cyclohexyl, phenyl,
benzyl, or
phenyl or benzyl having from i to 3 CI-C4alkyl, CI-CQallcoxy, -CP3 or
partially or fully
fluorinated CI-C4alkoxy substituents, and
nis0,ior2.
Of those diphosphines, chirally substituted compounds are especially
preferred.
Some preferred examples of diphosphines are as follows (Ph is phenyl):
a H3C 'CH-PPh2
HsC~ ~-PPh //z
-PPh2
z
CH2-PPh2 ,
/CH-PPh z
H 2 Ra = methyl. g-b -- '~-PPh
cyclohexyl.
phenyl Rb = H. methyl
Ph2PHpC\/
Rc
PPhy PPh2
> , PhzPH2C
PPhz PPh2 Rc=H, methyl, phenyl
Rd = H, methyl, phenyl

WO 95121176 2 1 8 1 3 ~~~ PCT/EP95100222 .
-IO-
~s
t~
Fh2P
CH3
Ph2PHC p CHg ~-CHZ-PPh2
N
~p C\CH
PhZPHC 3 Re
CH Re =-CO2-~-~tYl. -CO-tert-butyl, FI.
-CO-phenyl. -CO-NH-Cl-C4elkyl
Ph2P PPhp
CHZ-PPh2
N (CHp)n
CH2-PPhp
Rf
n=O,lor2
Rf=Cl-CqallO'1, benryl
~la -P(Rgh
";.gHg Fe P~2
,
PPhp
Rlq = Cl-Cqa11ry1. especially methYL
RB =phenyl or cyclohexyl that is
unsuhstituted oz has from 1
to 3 methyl. -CFg or methoxy
substituents
Suitable diphosphines and diphosphinites have been described, for example, by
H.B. Kagan in Chiral Ligands for Asymmetric Catalysis, Asymmetric Synthesis,
Volume 5, pp. 13-23, Academic Press, Inc., N.Y. (1985). The preparation of
ferrocenyl
diphosphine ligands is described, for example, in EP-A-0 564 406 and by T.
Hayashi et al.
in Bull. Chem. Soc. Jpn., 53, pages 1136-1151.
Prefesed diphosphines are
j (R)-1-j(S)-2-diphenylphosphino)ferrocenyI] }ethyl-di(3,5-dimethyl-4-N,N-
dipropyl-
aminophenyl)phosphine

WO 95121176 - ~ PCT/EP95/00222
11-
{(R)-1-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-diisopropyl-4-N,N-
dimethyl-
aminophenyl)phosphine
{ (R)-1-[(S)-2-diphenylphosphino)ferrocenyl] }ethyl-di(3,5-diisopropyl-4-N,N-
dibenzylyl-
aminophenyl)phosphine
{(R)-1-[(S)-2-diphenylphosphino)ferrocenyI]}ethyl-di(3,5-dimethyl-4-N,N-
dibenzylyl-
aminophenyl)phosphine
{(R~1-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-4-(1'-
pyrrolo)-
phenyl)phosphine
{ (R)-1-[(S)-2-diphenylphosphino)ferrocenyl] }ethyl-di(3,5-dimethyl-4-N,N-
dipentyl-
aminophenyl)phosphine
{ (R)-1-[(S)-2-diphenylphosphino)ferrocenyl] }ethyl-di(3,5-dimethyl-4-N,N-
dimethyl-
aminophenyl)phosphine
1,4-bis(diphenylphosphino)butane
{(R)-1-j(S)-2-di(4-methoxyphenyl)phospltino)fertvcenyl]}ethyl-di(3,5-dimethyl-
4-N,N-
dimethylaminophenyl)phosphine and preferably
((R)-1-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethyl-
phenyl)phosphine.
The invention relates also to a process for the preparation of iridium
compounds, which
comprises reacting with one another at least equimolar amounts of an
iridium()II) or
iridium(I~ salt or a hydrate thereof and a diphosphine in the presence of an
alkali metal
or ammonium chloride, bromide or iodide.
The process includes the preferences indicated hereinbefore. The molar ratio
of the
iridium(iB) of iriditnn(IV) salt or a hydrate thereof to diphosphine may be,
for example,
from 1:1 to 1:1.5, preferably from 1:1 to 1:1.1. The alkali metal or ammonium
chloride,
bromide or iodide is preferably used in excess based on the iridium salt or
the hydrate
thereof. The excess may be, for example, up to fivefold, preferably up to
tenfold, based on
1 mol of iridium salt or the hydrate thereof.
The process can be carried out in the absence or in the presence of a solvent.
It is
advantageous to use the same solvent as that to be used subsequently in the
hydrogenation.
Suitable solvents, which can be used alone or as a mixture of solvents, are
especially
dipolar solvents. Examples of solvents are: aliphatic and aromatic
hydrocarbons, such as
pentane, hexane, cyclohexane, methylcyclohexane, benzene, toluene and xylene;
alcohols,
such as methanol, ethanol, n- or iso-propanol, n-, iso- or tert-butanol,
ethylene glycol,
diethylene glycol, propanediols, ethylene glycol monomethyl ether or monoethyl
ether,

w0 95121176 ~ ~ ~ PCTIEP95100222
-12-
ethers, such as diethyl ether, diethylene glycol dimethy5l' ether,
tetrahydrofuran and
dioxane; halogenated hydrocarbons, such as met~lene chloride, chloroform,
1,1,2,2-tetra-
chloroethane and chlorobenzene; esters and lactones, such as ethyl acetate,
butymlactone
and valemlactone; acid amides and lactams, such as dimethylformamide,
dimethylacet-
amide and N-methylpyrrolidone, and ketones, such as acetone, dibutyl ketone,
methyl iso-
butyl ketone and methoxyacetone.
The reaction temperature may be, for example, from -20°C to
100°C, preferably from 0°C
to 80°C and especially from 10°C to 70°C.
The process can be carried out, for example, as follows: the iridium salt or
the hydrate
thereof, a diphosphine and a metal, especially an allcali metal, or ammonium
chloride,
bromide or iodide, are inttvduced, where appropriate a solvent is added, and
the mixture is
stirred until the reaction is complete. The end of the reaction can be
determined, for
example, by chromatography by determining the consumption of phosphine or,
preferably,
by spectroscopy, for example by means of 1H-NMR. The reaction time may be, for
example, up to 10, generally up to 5 and advantageously up to 2, hours. A
homogeneous
reaction mixture is obtained from which a solvent used concomitantly can be
removed.
The homogeneous residue can be isolated or used further directly as a
homogeneous
catalyst for hydrogenations.
The iridium compounds obtainable or prepared according to the invention are
outstanding-
ly suitable as homogeneous hydrogenation catalysts for the hydrogenation of
imines,
especially for the asymmetric hydrogenation of prochiral and chiral imines.
Chemical
conversions are frequently complete and high optical yields of over 70 ~'o or
more can be
achieved.
The invention relates also to a process for the catalytic hydrogenation of
imines with
hydrogen under elevated presstue in the presence of iridium catalysts and with
or without
an inert solvent, which process comprises using as catalyst an iridium
compound accord-
ing to the invention or an iridium compound prepared according to the
invention.
In a preferred form, there is additionally added to the reaction mixture an
ammonium or
alkali metal chloride, bromide or iodide, especially when an excess of those
halides has
not been used in the preparation of the catalyst.

~.~~13~~~
WO 95121176 PCTIEP95100222
-13-
In a further, especially preferred form, the reaction mixture additionally
contains an acid.
Suitable imines are especially those that contain at least one ~C=N- group. If
the
groups are substituted asymmetrically and. are thus compounds having a
prochiral
ketimine group, it is possible in the proces s according to the invention for
mixtures of
optical isomers or pure optical isomers to be formed if enantioselective or
diastereo-
selective iridium catalysts are used. The irnines may contain further chiraI
carbon atoms.
The free bonds in the above formulae may be saturated with hydrogen or organic
radicals
having from 1 to 22 carbon atoms or organic hetero radicals having from 1 to
20 carbon
atoms and at least one hetero atom from ttte group O, S, N and P. The nitrogen
atom of the
group j~N- may also be saturated with NH2 or a primary amino group having
from 1 to 22 carbon atoms or a secondary amino group having from 2 to 40
carbon atoms.
The organic radicals may be substituted, far example, by F, Cl, Br, Ct-
C4haloalkyl
wherein halogen is preferably F or Cl, -CN, -N02, -C02H, -CONH2, -S03H, -POgHy
or
CI-Cl2allryl esters or amides, or by phenya esters or benzyl esters of the
groups -C02H,
-S03H and -P03H2. Aldimine and ketimine groups are especially reactive, with
the result
that using the process according to the invention it is possible selectively
to hydrogenate
~~N-groups in addition to the ~~ ~ and/or ~C=O groups. Aldimine and
ketimine groups are also to be understood to include j~N-1~ hydrazone groups.
The process according to the invention is suitable especially for the
hydrogenation of
aldimines, ketimines and hydrazones with the formation of corresponding amines
and
hydrazines, respectively. The ketimines are preferably N-substituted It is
preferable to use
chiral indium catalysts and to hydrogenate; enantiomerically pure, chiral or
prochiral
ketimines to prepare optical isomers, the aptical yields Lnantiomeric excess,
ee) being,
for example, higher than 30 %, preferably higher than 50 °!o, and
yields of more than 90 %a
being achievable. The optical yield indicates the ratio of the two
stereoisomers formed,
which ratio may be, for example, greater than 2:I and preferably greater than
4:1.
The imines are preferably imines of formula III

WO 95121176 ~ 1$13 G f pCT11EP95/00222
-14-
K ;.
,.e.. ,
R ,..~ ,
j~N-R3 '.°~s~
R2
which are hydrogenated to form amines of formula IV
R1
/CH NH Rg m,)
R2
wherein
R3 is preferably a substituent and wherein
R3 is linear or branched Cl-Cl2alkyl, cycloalkyl having from 3 to 8 ring
carbon atoms;
heterocycloalkyl bonded via a carbon atom and having from 3 to 8 ring atoms
and 1 or 2
hetero atoms from the group O, S and NR6; a C7-Cl6aralkyl bonded via an alkyl
carbon
atom or Cl-Cl2alkyl substituted by the mentioned cycloalkyl or
heterocycloalkyl or
heteroaryl;
or wherein
R3 is C6-C12ary1, or C4-Cilheteroaryl bonded via a ring carbon atom and having
1 or 2
hetero atoms in the ring; Rg being unsubstituted or substituted by -CN, -N02,
F, Cl,
Cl-Cl2~Yl. Cl-Cl2~oxy, Cl-Cl2alkylthio, Cl-C6haloalkyl, -OH, C6-C12-aryl or
-aryloxy or -arylthio, C7-C16-aralkyl or -aralkoxy or -aralkylthio, secondary
amino having
from 2 to 24 carbon atoms, -CONR4R5 or by -COOR4, and the aryl radicals and
the aryl
groups in the aralkyl, aralkoxy and aralkylthio in tum being unsubstituted or
substituted by
-CN, -N02, F, CI, Cl-C4-allryl, -alkoxy or -allrylthio, -OH, -CONR4R5 or by -
COOR4;
R4 and RS are each independently of the other hydrogen, Cl-Cl2atkyl, phenyl or
benzyl, or
RQ and RS together are tetra- or penta-methylene or 3-oxapentylene;
R6 has independently the same meaning as given for R4;
Rl and R2 are each independently of the other a hydrogen atom, Cl-Cl2alkyl or
cycloalkyl
having from 3 to 8 ring carbon atoms, each of which is unsubstituted or
substituted by
-OH, Ct-Cl2alkoxy, phenoxy, benzyloxy, secondary amino having from 2 to 24
carbon
atoms, -CONR4R5 or by -COOR4; C6-Cl2aryl or C7-Cl6aralkyl that is
unsubstituted or
substituted as R3, or -CONR4R5 or -COOR4, wherein R4 and RS are as defined
herein-
before; or

~~.81366
WO 95/21176 PCTIEP95/00222
-15-
R3 is as defined hereinbefore and RI and R.2 together are alkylene having from
2 to S
carbon atoms that is optionally interrupted by 1 or 2 -O-, -S- or -NR6-
radicals, and/or
unsubstituted or substituted by ~ or as Rll and R2 above in the meaning of
alkyl, and/or
condensed with benzene, pyridine, pyrimirHne, furan, thiophene or pyrrole; or
R2 is as defined hereinbefore and Rt and R.3 together are alkylene having from
2 to 5
carbon atoms that is optionally interrupted by 1 or 2 -O-, -S- or -NR6-
radicals, and/or
unsubstituted or substituted by ~ or as RL and R2 above in the meaning of
alkyl, and/or
condensed with benzene, pyridine, pyrimidine, furan, uhiophene or pyrrole.
Rl, R2 and R3 can be substituted in any desired positions by identical or
different radicals,
for example by from 1 to 5, preferably from 1 to 3, substituents.
The radicals Rl, R2 and R3 may contain one or more chirality centres.
Suitable substituents far RL and R2 and R3 are: CL-C12-, preferably CL-C6-,
and especially
CL-C4-alkyl, -alkoxy or -alkylthio, e.g. melhyl, ethyl, propyl, n-, iso- and
tert-butyl, the
isomers of pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodecyl, and
corresponding
alkoxy and alkylthio radicals;
Ct-C.s-, preferably Ct-C4-haloalkyl having preferably F and Cl as halogen,
e.g. trifluoro-
or trichloro-methyl, difluorochloromethyl, fluorodichloromethyl, 1,1-
difluoroeth-1-yl,
1,1-dichloroeth-1-y1, 1,1,1-trichloro- or 1,1.,1-trifluotneth-2-yl,
pentachloroethyl, penta-
fluoroethyl, 1,1,1-trifluoro-2,2-dichloroethyl, n-perkluoropropyl, iso-
perfluoropropyl,
n-perfluorobutyl, fluoro- or chloro-methyl, difluoro- or dichloro-methyl, I-
fluoro- or
1-chloro-eth-2-yl or -eth-1-yl, I-, 2- or 3-fluoro- or 1-, 2- or 3-chloro-prop-
1-yl or
-prop-2-yl or -prop-3-yl, I-fluoro- or 1-chluro-but-I-yl, -but-2-yl, -but-3-yl
or -but-4-yl,
2,3-dichloro-prop-1-yl, 1-chloro-2-fluoro-prop-3-yl, 2,3-dichlorobut-I-yl;
Cs-C12-aryl, -aryloxy or -arylthio, in which aryl is preferably naphthyl and
especially
phenyl, C~-Ct6-aralkyl, -atxllcoxy and -aralkylthio, in which the aryl radical
is preferably
naphthyl and especially phenyl and the alkylene radical is linear or branched
and contains
from 1 to 10, preferably from 1 to 6 and especially from 1 to 3, carbon atoms,
for example
benzyl, naphthylmethyl, 1- or 2-phenyl-eth-1-yl or -eth-2-yl, 1-, 2- or 3-
phenyl-prop-1-yl,
-prop-2-yl or -prop-3-yl, with benzyl being especially preferred;
the radicals containing the aryl groups mentioned above may in turn be mono-
or poly-
substituted, for example by Ct-CQ-alkyl, -alkoxy or -alkylthio, halogen, -OH, -
CONRQRS

WO 95/21176 ~ 1813 G 6 PCT/EP95100222 ,
-16-
or by -COORS, wherein R4 and RS are as defined; examples are methyl, ethyl, n-
and iso-
propyl, butyl, corresponding allcoxy and alkylthio radicals, F, Cl, Br,
dimethyl-, methyl-
ethyl- and diethyl-carbamoyl and methoxy-, ethox~y'", phenoxy- and benzyloxy-
carbonyl;
<°
b
halogen, preferably F and C1;
secondary amino having from 2 to 24, preferably from 2 to 12 and especially
from 2 to 6
carbon atoms, the secondary amino preferably containing 2 alkyl groups, for
example
dimethyl-, methylethyl-, diethyl-, methylpropyl-, methyl-n-butyl-, di-n-propyl-
,
di-n-butyl-, di-n-hexyl-amino;
-CONR4R5, wherein Ry and RS are each independently of the other Ct-C12-,
preferably
Cl-C6-, and especially Ct-Cy-allryl, or R4 and RS together are tetra- or penta-
methylene or
3-oxapentylene, the alkyl being linear or branched, e.g. dimethyl-,
methylethyl-, diethyl-,
methyl-n-propyl-, ethyl-n-propyl-, di-n-propyl-, methyl-n-butyl-, ethyl-n-
butyl-, n-propyl-
n-butyl- and di-n-butyl-carbamoyl;
-COOR4, wherein R4 is Ct-C12-, preferably CI-C6-alkyl, which may be linear or
branched,
e.g. methyl, ethyl, n- and iso-propyl, n-, iso- and tert-butyl, and the
isomers of pentyl,
hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl.
Rl, R2 and R3 may contain especially functional groups, such as keto groups, -
CN, -N02,
carbon double bonds, N-O-, aromatic halogen groups and amide groups.
Rl and R2 as heteroaryl are preferably a 5- or 6-membered ring having 1 or 2
identical or
different hetero atoms, especially O, S or N, which contains preferably 4 or 5
carbon
atoms and can be condensed with benzene. Examples of heteroaromatics from
which RI
can be derived are furan, pyrrole, thiophene, pyridine, pyrimidine, indole and
quinoline.
Rl and R2 as heteroaryl-substituted allcyl are derived preferably from a 5- or
6-membered
ring having 1 or 2 identical or different hetero atoms, especially O, S or N,
which contains
preferably 4 or 5 carbon atoms and can be condensed with benzene. Examples of
hetero-
aromatics are furan, pyrrole, thiophene, pyridine, pyrimidine, indole and
quinoline.
Rt and R2 as heterocycloalkyl or as heterocycloalkyl-substituted alkyl contain
preferably
from 4 to 6 ring atoms and I or 2 identical or different hetero atoms from the
group O, S

W O 95121176
PCT/EP95/00222
-17-
and NR6. It can be condensed with benzene. It may be derived, for example,
from pyrrol-
idine, teirahydrofuran, tetrahydrothiophene, indane, pyrazolidine,
oxazolidine, piperidine,
piperazine or morpholine.
Rt, R2 and R3 as alkyl are preferably unsulbstituted or substituted Cl-C6-,
especially
Cl-C4-alkyl, which may be linear or branched. Examples are methyl, ethyl, iso-
and
n-propyl, iso-, n- and tert-butyl, the isomem of pentyl, hexyl, heptyl, octyl,
nonyl, decyl,
undecyl and dodecyl.
Rt, R2 and R3 as unsubstituted or substituted cycloallryl contain preferably
from 3 to 6,
especially 5 or 6, ring carbon atoms. Examples are cyclopropyl, cyclobutyl,
cyclopentyl,
cyclohexyl, cycloheptyl and cyclooctyl.
Rl, R2 and R3 as aryl are preferably unsubstiutted or substituted naphthyl and
especially
phenyl. Rl, R2 and R3 as atalkyl are preferably tlnsubstituted or substituted
phenylalkyl
having from 1 to 10, preferably from I to 6 and especially from I to 4 carbon
atoms in the
alkylene, the alkylene being linear or branched. Examples are especially
benzyl, and
I-phenyleth-1-yl, 2-phenyleth-1-yl, I-phenylprop-I-yl, I-phenylprop-2-yl, I-
phenyl-
prop-3-yl, 2-phenylprop-I-yl, 2-phenylprop-2-yl and 1-phenylbut-4-yl.
In R2 and R3 as -CONR4R5 and -COOR4, lt4 and RS are preferably Cl-C6-,
especially
Cl-C4-alkyl, or R4 and RS together are tetclmethylene, pentamethylene or 3-
oxapentylene.
Examples of alkyl are mentioned hereinbel:ore.
Rl and R2 together or Rl and R3 together as alkylene are preferably
interrupted by 1-O-,
-S- or -NR6-, preferably -O-. Rl and R2 together or Rl and R3 together form,
with the
carbon atom or with the -N=C group to which they are bonded, respectively,
preferably a
5- or 6-membered ring. For the substituents the preferences mentioned
hereinbefore apply.
As condensed alkylene, Rl and R2 together or Rl and R3 together are preferably
aIkylene
condensed with benzene or pyridine. Examples of allcylene are: ethylene, I,2-
or
1,3-propylene, 1,2-, 1,3- or 1,4-butylene, I,5-pentylene and 1,6-hexylene.
Examples of
interrupted or ~-substituted alkylene are 2-oxa-1,3-propylene, 2-oxa-1,4-
butylene,
2-oxa- or 3-oxa-1,5-pentylene, 3-thia-1,5-pentylene, 2-thia-1,4-butylene, 2-
thia-
1,3-propylene, 2-methylimino-1,3-propylene, 2-ethylimino-1,4-butylene, 2- or 3-
methyl-
imino-1,5-pentylene, 1-oxo-2-oxa-1,3-propylene, 1-oxo-2-oxa-I,4-butylene, 2-
oxo-3-oxa-
1,4-butylene, 1-oxa-2-oxo-1,5-pentylene. Examples of condensed allcylene are:

WO 95121176 ~ ~ ~ PCTI~P95100222 .
-18-
CH CH .'~. ~ CH
'v \ ~ ~ i H2
, , \
O CH
N 2
Examples of condensed and interrupted and unsubstituted or -0-substituted
alkylene are:
CH2' ~ / ( O~ iH2' / ~ S~CH2 / ( O~CO
,
R4 and RS are preferably each independently of the other hydrogen, Ct-C4alkyl,
phenyl or
benzyl. R6 is preferably hydrogen or CI-C4alkyl.
A further preferred group is formed by prochiral imines in which in formula
III RI, R2 and
R3 are each different from the others and R3 is not hydrogen.
In an especially preferred group, in formula III Rg is 2,6-di-CI-C4allrylphen-
I-yl and
especially 2,6-dimethylphen-1-yl or 2-methyl-6-ethylphen-1-yl, Rt is CI-
C4allcyl and
especially ethyl or methyl, and R2 is CI-C4allcyl, Ct-C4allcoxymethyl or Ct-
C4alkoxyethyl,
and especially methoxymethyl.
Of those compounds, imines of formulae
CH3' ~CHpOCHg CH3\ j HpOCH3
C C
N N
CH3 CH3 Via) and C2H5 - - CH3 (IIIb) are especially
/ /
\ \
important, as is the imine of the formula
CH3 N-C-CH20CHs
CH3
$ CH3

WO 95121176 ~ ~, R ~ ,~ ~ ~ PCT/EP95/00222
19-
Imines of formula III are known or they can be prepared in accordance with
known
processes from aldehydes or ketones and primary amines.
The iridium catalysts can be added to the reaction mixture as isolated
compounds. It has,
however, proved advantageous to prepare the catalysts in situ with or without
a solvent
before the reaction and to use them further directly for the hydrogenation,
for example
first adding an acid to the catalyst prepared in situ.
The iridium catalysts are preferably used in amounts of from 0.0001 to 10 mol
%,
especially from 0.001 to 10 mol %, and more especially from O.OI to 5 mol %,
based on
the imine.
The molar ratio of the itmne to the iridium catalyst may be, for example, from
1000 000
to 10, preferably from 500 000 to 20, and especially from 300 000 to 100.
The process is preferably carried out at a temperature of firom -20 to
100°C, especially
from 0 to 80°C and more especially from 10 to 70°C, and
preferably under a hydrogen
pressure of from 2 x 105 to 1.5 x 10~ Pa ('from 5 to 150 bar), especially from
106 to 10~ Pa
(from 10 to 100 bar).
An advantageous form of the hydrogenation process according to the invention
comprises
the additional use of an ammonium or alkali metal chloride, bromide: or
iodide. Those
chlorides, bromides and iodides are preferably used in amounts of from 0.01 to
200 mol %, especially from 0.05 to 100 a~ol % and more especially from 0.5 to
50 mol ~Yo,
based on the iridium catalyst. The iodides are preferred. Ammonium is
preferably tetra-
alkylammonium having from 1 to 6 carbon atoms in the alkyl groups, and the
alkali metal
is preferably sodium, lithium or potassium. Tetrabutylammonium iodide is
especially
preferred
The reaction can be carried out in the absence or in the presence of aprotic
or protic
solvents. Suitable solvents, which can be used alone or as a mixture of
solvents, are
especially aprotic solvents. Examples are:
aliphatic and aromatic hydrocarbons, such as pentane, hexane, cyclohexane,
methylcyclo-
hexane, benzene, toluene and xylene; ethers, such as diethyl ether, diethylene
glycol

PCTIEP95100222
W 0 95/21176
-20-
r
s.l...
dimethyl ether, tetrahydrofutan and dioxane;,h~~ genated hydrocarbons, such as
methyl-
ene chloride, chloroform, 1,1,2,2-tetrachloroethane and chlorobenzene; esters
and
lactones, such as ethyl acetate, butyrolactone and valerolactone; acid amides
and lactates,
such as dimethylfotmatnide, dimethylacetatnide and N-methylpytTOlidone, and
ketones,
such as acetone, dibutyl ketone, methyl isobutyl ketone and methoxyacetone.
Also
suitable are alkanols, such as methanol, ethanol, propanol, butanol or
methoxyethanol.
A special form of the process according to the invention comprises the
additional use of an
acid. It may be an inorganic or, preferably, an organic acid. The acid is
preferably used in
at least the same molar amount as the iridium catalyst (equally catalytic
amounts) and can
also be used in excess. The excess tray even consist in the use of the acid as
solvent.
Preferably from 0.1 to 50 ~Yo by weight of acid is used, based on the
unsaturated organic
compound. In many cases it can be advantageous to use anhydrous acids.
Some examples of inorganic acids are H2SO4, highly concentrated sulfittzc acid
(oleum),
H3P04, otthophosphoric acid, HF, HCI, HBr, HI, HC104, HBF4, HPF6, HAsFb,
HSbCl6,
HSbFb and HB(phenyl)4. H2S04 is preferred.
Examples of organic acids are aliphatic or aromatic, optionally halogenated
(fluorinated or
chlorinated) carboxylic acids, sulfonic acids, phosphorus(V) acids (for
example
phosphoric acids, phosphorous acids) having preferably from 1 to 20,
especially from 1 to
12 and more especially from 1 to 6, carbon atoms. Examples are formic acid,
acetic acid,
propionic acid, butyric acid, benzoic acid, phenylacetic acid,
cyclohexanecarboxylic acid,
chlotro- or fluoro-acetic acid, dichloro- or difluoro-acetic acid, trichloro-
or n-ifluoro-acetic
acid, chlorobenzoic acid, tnethanesulfonic acid, ethanesulfonic acid,
benzenesulfonic acid,
chlorobenzenesulfonic acid, trifluoromethanesulfonic acid, methylphosphonic
acid and
phenylphosphonic acid. Preferred acids are acetic acid, propionic acid,
ttifluoroacetic acid,
methanesulfonic acid and chloroacedc acid
In detail, the process according to the invention can be carried out by first
preparing the
catalyst. A solution of the unsaturated organic compound is added to the
catalyst solution
(or vice versa) and, in an autoclave, hydrogen pressure is applied, thus
removing the
protective gas that is advantageously used. The reaction mixture is heated, if
desired, and
then hydrogenated. Where appropriate, when the reaction has ceased the
reaction mixture
is cooled and the autoclave is depressurised. The reaction mixture can be
expelled from
the autoclave under pressure with nitrogen and the hydrogenated organic
compound can

CA 02181366 2004-11-22
30041-74
-21-
be isolated and purified in a manner known per se, for example by
precipitation, extraction
or distillation. The catalyst can then be used again, if necessary with the
addition of fresh
catalyst to compensate for losses.
In the case of the hydrogenation of aldimines and ketimines, the aldimines and
ketimines
can also be formed in situ before or during the hydrogenation. In a prefen~ed
form, an
amine and an aldehyde or a ketone are mined together and added to the catalyst
solution
and the aldimine or ketimine formed in situ is hydrogenated. It is also
possible, however,
to use an amine, a ketone or an aldehyde together with the catalyst as the
initial batch and
to add the ketone or the aldehyde or the amine thereto, either all at once or
in metered
amounts. When using that method it can be advantageous to remove the water of
reaction
arising from the imine formation, for example by means of azeotropic
distillation or by the
addition of water-binding agents.
The amines that can be prepared according to the invention are biologically
active
compounds or are intermediates for the preparation of t such compounds,
especially in the
field of the preparation of pharmaceuticals and agrochemicals. For example,
o,o-dialkyl-
arylketamine derivatives, especially those containing alkyl and/or
alkoxyallcyl groups, are
effective as fungicides, especially as herbicides. The derivatives may be
amine salts, acid
amides, for example chloroacetic acid amides, . tertiary amines and ammonium
salts (see,
for example, EP-A-0 077 755 and EP-A-0115 470).
The invention relates also to hydrogenation catalysts that are products of the
reaction of an
iridium(111) or iridium(IVJ salt or the hydrates thereof with a diphosphine
having
secondary phosphine groups and an alkali metal or ammonium chloride, bromide
or
lOdlde.
The invention relates also to the use as a hydrogenation catalyst of a
reaction product of an
iridium(ITI) or iridium(IV) salt or the hydrates thereof, a diphosphine having
secondary
phosphine groups and an alkali metal or ammonium chloride, bromide or iodide.
The Examples that follow illustrate the invention in more detail. The chemical
conversion
is determined by gas chromatography (DB 17/30 W column (15 m), manufacturer.
JCW
Scientific Inc. USA, temperature programme: from 60°Gl min to
220°C, DT:
10° x min'1]. The optical yields (enantiotneric excess, ee) are
determined either by gas
chromatography [ChirasilMVal column, 50 m, manufacturer: Alltech, USA, T =
150°C,

CA 02181366 2004-11-22
30041-74
-22-
isothetmic], by HPLC (Chiracel OD column) or by 1H-NMR spectroscopy (using
shift
reagents).
Example A 1: Preparation of an iridium catalyst
9.1 mg (0.029 mmol) of IrCl3 hydrate, 21.4 mg (0.033 mmol) of { (R)-1-[(S)-2-
diphenyl-
phosphino)fenvcenyl] ) ethyl-di(3,5-dia~ethylphenyl)phosphine and 150 mg (0.4
mmol) of
tetrabutylammonium iodide are dissolved in 20 ml of tetrahydrofuran and then
stirred for
2 hours at 50°C. The solvent is then removed. There remains a solid
soluble residue which
is used further directly in Example B 1.
B) Auplication Examples
Example B 1: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl~N-(1-
methoxymethyl~
ethylamine
The residue from Example A1 is dissolved in 2.5 ml of acetic acid. That
catalyst solution
and 5 ml (0.024 mol) of N-(2'- methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethylkth-1-yl-,
ideneamine are transferred in sucxession to a 50 ml steel autoclave which is
under an inert
gas. In four cycles (10 bar, normal pressure), the inert gas is displaced by
hydrogen. A
pressure of 25 bar of hydrogen is then applied. After a reaction time of 10
hours at 25°C
the reaction is discontinued. The conversion is 100 96 and the optical yield
is 78.8 96 (S).

W O 95!21176 PCTIEP95100222
-23-
Example B2: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
A catalyst is prepared analogously to the manner described in Example Al,
starting from
9.1 mg (0.029 mmol) of IrCl3 hydrate, 21.4 mg (0.033 mmol) of {(R)-1-[(S)-2-
diphenyl-
phosphino)ferrocenyl] }-ethyl-di(3,5-dime:thylphenyl)phosphine and 150 mg (0.5
mmol) of
tetrabutylammonium chloride in 20 ml of THF. That catalyst is dissolved in 2.5
ml of
acetic acid. The hydrogenation is then carried out analogously to Example Bl
at 60 bar of
hydrogen and 25°C. The reaction time is 43 hours, the conversion 73 R5
and the enantio-
meric excess 37 ~ (S).
Example B3: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
The process is carried out analogously to Example B2, but with the following
modified
reaction conditions:
150 mg (1.3 mmol) of potassium bromide.. The reaction time is 91 hours, the
conversion
100 % and the enantiomeric excess 63 3'0 (S).
Example B4: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
The process is carried out analogously to Example B2, but with the following
modified
reaction conditions:
23.1 mg (0.033 mmol) of {(R)-1-j(S)-2-Biphenylphosphino)felrocenyl]}ethyl-
di(3,5-
dimethyl-4-N,N-di-propylaminophenyl)pl'aosphine, 150 g (0.4 mmol) of
tetrabutyl-
ammonium iodide, 30 bar of hydrogen. Thle inaction time is 3.5 hours, the
conversion
97 % and the enantiomeric excess 81.7 % (S).
Example B5: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
The process is carried out analogously to Example B2, but with the following
modified
reaction conditions:
14.1 mg (0.033 mmol) of (2R,4R)-bis(diphenylphosphino)pentane, 150 mg (0.4
mmol) of
tetrabutylammonium iodide, 30 bar of hyiirogen. The reaction time is 21.5
hours, the
conversion 95 % and the enantiomeric excess 46.9 96 (S).

ms~3ss
WO 95121176 PCT/EP95100222 t
_ z~,~.. >,. ,
Example B6: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
The process is carried out analogously to Example B2, but with the following
modified
reaction conditions:
15.4 mg (0.029 mmol) of IrBrg hydrate, 19.5 mg (0.033 mmol) of ((R)-I-[(S)-2-
di-
(2-methylphenyl)phosphino)ferrocenyl]}ethyl-diphenylphosphine, 0.1 ml of
trifluoroacetic
acid in 5 ml of toluene, 150 mg (0.4 mmol) of tetrabutylammonium iodide. The
reaction
time is 71 hours, the conversion 15 % and the enantiomeric excess 29.4 96 (S).
Example B7: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
The process is carried out analogously to Example B2, but with the following
modified
reaction conditions:
19.9 mg (0.033 mmol) of (R)(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene,
0.1 ml of
methanesulfonic acid in 2.5 ml of toluene and 2 ml of isopropanol, 150 mg (0.4
mmol) of
tetrabutylammonium iodide, 30 bar of hydrogen. The reaction time is 56 hours,
the
conversion 75 35 and the enantiomeric excess 31 %.
Example B8: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-
methoxymethyl)ethyl-
amine
A catalyst is prepared analogously to the manner described in Example Al,
starting from
9.1 mg (0.029 mmol) of IrCl3 hydrate, 15.6 mg (0.033 mmol) of (4S,5S)-(+)-4,5-
bis(di-
phenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane and 150 mg (0.4 mmol) of
tetra-
butylammonium iodide in 20 ml of THF. The catalyst is dissolved in 5 ml of
isopropanol.
The hydrogenation is then carried out analogously to Example B 1 at 30 bar of
hydrogen
and 25°C. The reaction time is 22 hours, the conversion 21 rYo.
Example B9: Preparation of N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(I-
methoxymethyl)ethyl-
amine
In succession, 5 ml (0.024 mmol) of N-(2'-methyl-6'-ethyl-phen-I'-yl)-N-(1-
methoxy-
methyl)ethylideneamine, 2 ml of acetic acid, 14.6 mg (0.03 mmol) of H2IrC16 ~
6 H20,
21.4 mg (0.033 mmol) of ((R)-I-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-
di(3,5-di-
methylphenyl)phosphine and 150 mg (0.5 mmol) of tetrabutylammonium chloride
are
transferred to a 50 ml steel autoclave. The autoclave is then closed and
placed under an
argon atmosphere. Finally, the gas blanket is changed and a pressure of 25 bar
of hydrogen
is applied. After a reaction time of 18 hours at room temperature, a
conversion of 92 %

WO 95121176 ~ ~ ~ ~ ~ ~' PCTIEP95/00222
and an ee of 76.6 ~Yo (S) are obtained.