CA 02239970 2005-08-31
DESCRIPTION
PROCESS FOR PREPARING OPTICALLY ACTIVE COMPOUNDS
Technical Field
The present invention relates to a method for
producing optically active compounds such as optically
active alcohols and optically active amines. More
specifically, the present invention relates to a novel,
highly practical method for producing optically active
compounds useful for various utilities such as intermediates
for synthesizing pharmaceutical chemicals, liquid crystal
materials and agents for optical resolution.
Background Art
Various methods for producing optically active
compounds have been known conventionally_ As the method for
asymmetric synthesis of optically active alcohol compounds,
for example, the following methods have been known;
(1) a method by using enzymes such as baker's yeast; and
a method for asymmetric hydrogenation of carbonyl
compounds by using metal complex catalysts. For the method
(2), in particular, a great number of examples of asymmetric
catalytic reactions have been reported for example as
follows; (1) an asymmetric hydrogenation of carbonyl
compounds with functional groups, by means of optically
active ruthenium catalysts, as described in detail in
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Asymmetric Catalysis in Organic Synthesis, Ed. R. Noyori.,
pp..56-82 (1994); (2) a method through hydrogen transfer-
type reduction by means of chiral complex catalysts of
ruthenium, rhodium or iridium, as described in Chem. Rev.,
Vo1.92, pp.1051-1069 (1992); (3) a process of asymmetric
hydrogenation of tartaric acid by means of a modified nickel
catalyst with tartaric acid as described in Oil Chemistry,
pp.882-831 (1980) and Advances in Catalysis, Vo1.32, pp.215
(1983). Ed. Y. Izumi; (4) an asymmetric hydrosilylation
method, as described in Asymmetric Synthesis, Vol.5, Chap.4
(1985), Ed. J. D. Morrison and J. Organomet. Chem. Vo1.346,
pp.413-424 (1988); and (5) a borane reduction process in the
presence of chiral ligands, as described J. Chem. Soc.,
Perkin Trans.l, pp.2039-2044 (1985) and J. Am. Chem. Soc.,
Vo1.109, pp. 5551-5553 (1987).
By the conventional method by means of enzymes,
however, alcohols can be recovered at a relatively high
optical purity, but the reaction substrate therefor is
limited and the absolute configuration in the resulting
alcohols is limited to a specific one. By the asymmetric
hydrogenation method by means of transition metal complex
catalysts, optically active alcohols can be produced at a
high selectivity, but a pressure-resistant reactor is
required therefor because hydrogen gas is used as the
hydrogen source, which is disadvantageous in terms of
operational difficulty and safety. Furthermore, the method
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through such asymmetric hydrogen transfer-type reduction by
using conventional metal complex catalysts is limited in
that the method requires reaction conditions under heating
and the reaction selectivity is insufficient,
disadvantageously in a practical sense.
Accordingly, it has been desired conventionally that a
new, very general method for synthesizing optically active
alcohols by using a highly active and highly selective
catalyst with no use of hydrogen gas be achieved.
However, no highly efficient and highly selective
method for producing such secondary alcohols through
asymmetric synthetic reaction by using catalysts similar to
those described above has not as yet been established.
As to the optically active secondary alcohols, a
method for synthesizing optically active secondary alcohols
via optical resolution of racemic secondary alcohols has
been known for some reaction substrate which can hardly be
reduced, although an excellent optical purity is hardly
attained (Asymmetric Catalysis in Organic Synthesis, Ed. R.
Noyori). Because hydrogen transfer-type reduction is a
reversible reaction according to the method,
dehydrogenation-type oxidation as its adverse reaction is
used according to the method. Therefore, the method is
called as kinetic optical resolution method. According to
the method, however, no process of producing optically
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active secondary alcohols with catalysts at a high
efficiency has been reported yet.
As the method for synthetically producing optically
active amine compounds, furthermore, a process of optically
resolving once produced racemic compounds by using optically
active acids and a process through asymmetric synthetic
reaction have been known. By the optical resolution
process, however, optically active acids should be used at
an equal amount or more to amine compounds disadvantageously
and complex procedures such as crystallization, separation
and purification are required so as to recover optically
active amine compounds. As the method through asymmetric
synthesis, alternatively, the following processes have been
known; (1) an enzymatic process: (2) a process by using
metal hydride compounds: and (3) a process of asymmetric
hydrogenation by using metal complex catalysts. As to the
process for using metal hydride compounds as described above
in ( 2 ) , a great number of reports have been issued about a
process of asymmetrically reducing carbon-nitrogen multiple
bonds by using metal hydrides with chiral modifiers. As a
general process thereof, for example, it has been known a
stoichiometric reduction process of imine compounds and
oxime compounds by using metal hydrides with an optically
active ligand, as described in Comprehensive Organic
Synthesis, FsdS. B.M. Trost and I. Flemming, Vol.8, pp.25
(1991), Organic Preparation and Procedures Inc. O. Zhu, R.
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O. Hutchins, and M. K. Huchins, Vo1.26(2), pp.193-235 (1994)
and Japanese Patent Laid-open No. 2-311446. The process
includes a number of processes with excellent reaction
selectivity, but these processes are disadvantageous because
these processes require laborious purification procedures to
recover optically active substances. As the process of
asymmetric hydrogenation of carbon-nitrogen multiple bonds
by using metal complex catalysts as the method (3), it has
been known an asymmetric hydrogenation process of imine
compounds with functional groups, by means of optically
active metal complex catalysts, as described in Asymmetric
Catalysis in Organic Synthesis, pp.82-85 (1994), Ed. R.
Noyori. But the process has a drawback in terms of reaction
velocity and selectivity.
By the method by using enzymes as the method (1),
furthermore, amines at a relatively high optical purity can
be recovered, but the reaction substrates are limited and
the resulting amines have only specific absolute
configurations. Furthermore, at a process of asymmetric
hydrogenation by means of complex catalysts of transition
metals using hydrogen gas, optically active amines have not
yet been recovered at a high selectivity or pressure-
resistant reactors are essentially required because hydrogen
gas is used as the hydrogen source. Hence, such a process
is disadvantageous because of technically difficult
operation and safety problems.
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Accordingly, it has been demanded that a novel method
for synthesizing an optically active amine by using a very
common, highly active and highly selective catalyst be
realized.
Alternatively, a great number of transition metal
complexes have been used conventionally as catalysts for
organic metal reactions; particularly because rare metal
complexes are highly active and stable with the resultant
ready handleability despite of high cost, synthetic
reactions using the complexes have been developed. The
progress of such asymmetric synthetic reactions using chiral
complex catalysts is innovative, and a great number of
reports have been issued, reporting that highly efficient
organic synthetic reactions have been realized.
Among them, a great number of asymmetric reactions
using chiral complex catalysts with optically active
phosphine ligands as the catalysts therefor have already
been developed, and some of them have been applied
industrially (Asymmetric Catalysis in Organic Synthesis, Ed.
R. Noyori).
As complexes of optically active nitrogen compounds
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coordinated with transition metals such as ruthenium, rhodium
and iridium, a great number of such complexes additionally
having excellent properties as catalysts for asymmetric
synthetic action have been known. So as to enhance the
properties of these catalysts, a great number of propositions
concerning the use of optically active nitrogen compounds of
specific structures have been done CChem. Rev. , Vo1.92,
pp.1051-1069 (1992)).
For example, reports have been issued about ( 1 ) optically
active 1,2-diphenylethylenediamines and rhodium-diamine
complexes with ligands of cyclohexanediamines, as described in
Tetrahedron Asymmetry, Vol.6, pp.705-718 (1995); (2)
ruthenium-imide complex with ligands of optically active
bisaryliminocyclohexanes,asdescribed in Tetrahedron,vo1.50,
pp.4347-4354 (1994); (3) iridium-pyridine complex with ligands
of pyridines, as described in Japanese Patent Laid-open Nos.
62-281861 and 63-119465; (4) optically active 1,2-
diphenylethylenediamines or iridium-diamine complex with
ligands of cyclohexanediamines, as described in Japanese Patent
Laid-open No.62-273990; (5) ruthenium-diamine complex of
RuCl [ p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( arene ) ( chloro- ( N-p-
toluenesulfonyl-1,2-
diphenylethylenediamine)(arene)ruthenium) (arene represents
benzene which may or may not have a substituent), which is
produced by coordinating ruthenium with optically active N-
r.
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p-toluenesulfonyl-1,2-diphenylethylenediamine [referred to as "p-
TsNHCH(C6H5)CH(C6
HS)NH2 " hereinabove and below], as described in J. Am. Chem. Soc., Vol. 117,
pp.
7562-7563(1995); J. Am. Chem. soc., Vol. 118, pp. 2521-2522 (1996) and J. Am.
Chem.
Soc., Vol. 118, pp. 4916-4917 (1996).
Even if these complexes are used, however, problems currently remain to be
overcome
for practical use, including insufficient catalyst activities, sustainability
and optical
purities, depending on the subjective reactions and reaction substrates.
DISCLOSURE OF INVENTION
So as to overcome the aforementioned problems, the present invention is to
provide a
method for producing optically active compounds, comprising subjecting a
compound
represented by the following formula (I);
Ra
=W~
Rb (I)
(wherein Ra represent a linear hydrocarbon group containing 1 to 10 carbon
atoms, a
mono-, bi- or tri-cyclic hydrocarbon group containing 3 to 14 carbon atoms, an
aryl
group, a heterocyclic group containing 2 to 13 carbon atoms and 1 to 3 hetero
atoms
selected from the group consisting of nitrogen, oxygen and sulfur atoms, or a
ferrocenyl
group; Rb represents a hydrogen atom, a linear hydrocarbon group containing 1
to 10
carbon atoms, a mono-, bi- or tri-cyclic hydrocarbon group containing 3 to 14
carbon
atoms, an aryl group, a heterocyclic group containing 2 to 13 carbon atoms and
1 to 3
hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur
atoms, or
a ferrocenyl group, or Ra and Rb are bonded together to form a ring containing
5 to 10
carbon atoms; W~ represents oxygen atom, N--H, N--Rc, N--OH or N--O--Rd; and
Rc
and Rd represent the same hydrocarbon group or heterocyclic group as described
above)
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to transfer-type asymmetric reduction in the presence of a
transition metal complex and an optically active nitrogen-
containing compound or a transition metal complex with an
optically active nitrogen-containing compound as an
asymmetric ligand, along with a hydrogen-donating organic or
inorganic compound, to produce an optically active compound
represented by the following formula (II);
Ra
~CH --W2
Rb
(wherein W2 represents OH, NH2, NH-Rc, NH-OH or NH-O-Rd; and
Ra, Rb, Rc and Rd independently represent the same as those
described above).
Additionally, the present invention is to provide a
method for producing an optically active alcohol according
to the aforementioned method, comprising asymmetrically
reducing a carbonyl compound represented by the following
formula (III);
0
RI, IC _R2
(wherein Rl represents an aromatic hydrocarbon group, a
saturated or unsaturated aliphatic hydrocarbon group or
cyclic aliphatic hydrocarbon group, which may or may not
have a substituent, or a heterocyclic group which may or may
not have a substituent and contains hetero atoms such as
nitrogen, oxygen, sulfur atoms and the like as atoms
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composing the ring; R2 represents hydrogen atom, a saturated
or unsaturated aliphatic hydrocarbon group or cyclic
aliphatic hydrocarbon group which may or may not have a
substituent, or an aromatic hydrocarbon group, or the same
heterocyclic group as described above; and R1 and R2 may
satisfactorily be bonded together to form a ring preferably
containing S to 10 carbon atoms),
to produce an optically active alcohol represented by the
following formula (IV);
OH
R1- C- R2
H
(wherein R1 and R2 are the same as described above).
Furthermore, the present invention is to provide a
method for producing an optically active amine, comprising
asymmetrically reducing an imine compound represented by the
following formula (V);
NR5
a
R3~ ~ 4
R
(wherein R3 represents an aromatic hydrocarbon group, a
saturated or unsaturated aliphatic hydrocarbon group or
cyclic aliphatic hydrocarbon group, which may or may not
have a substituent, or a~heterocyclic group which may or may
not have a substituent and contains hetero atoms such as
nitrogen, oxygen, sulfur atoms and the like as atoms
composing the ring; R4 represents hydrogen atom, a saturated
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or unsaturated aliphatic hydrocarbon group or cyclic
aliphatic hydrocarbon group which may or may not have a
substituent, or an aromatic hydrocarbon group, or the same
heterocyclic group as described above; R5 represents
hydrogen atom, or a saturated or unsaturated aliphatic
hydrocarbon group or cyclic aliphatic hydrocarbon group,
which may or may not have a substituent, or an aromatic
hydrocarbon group, or the same heterocyclic group as
described above, or the hydrocarbon group or heterocyclic
group bonded together via hydroxyl group or oxygen atom; and
R3 and R4, R3 and R5 or R4 and R5, are bonded together to
form a ring containing preferably 5 to 10 carbon atoms),
to produce optically active. amines represented by the
following formula (VI);
NHRS
CH
R3/ \R4
(wherein R3, R4 and RS are the same as described above).
Still furthermore, the present invention is to provide
a method for producing optically active secondary alcohols,
comprising subjecting racemic secondary alcohols or meso-
type
1l
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diols to hydrogen transfer reaction by using a catalyst of an
optically active ruthenium-diamine complex represented by the
following general formula (VII);
Roa
O1
* ~ \ /X _
Ru
Roa .~ ~ ~ \ H
n
Ro4 Nm
(wherein * represents an asymmetric carbon atom; R°1 and R°= are
the same or different, independently representing alkyl group,
or phenyl group or cycloalkyl group which may or may not have
an alkyl group; or R°' and R°' together form an alicyclic ring
unsubstituted or substituted with an alkyl group; R°' represents
methanesuifonyl group, trifluoromethanesulfonyl group,
naphthylsulfonyl group, camphor sulfonyl group; or
henzenesulfonyl group which may or may not be substituted with
an alkyl group, an alkoxyl group or halogen atom, alkoxycarbonyl
group; or benzoyl group which may or may not be substituted with
an alkyl group; R°' represents hydrogen atom or alkyl group;
X represents an aromatic compound which may or may not be
substituted with an alkyl group; and m and n together represent
0 or 1).
1'?
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The expression "linear hydrocarbon group" as used herein refers to a
linear hydrocarbon group containing 1 to 10 carbon atoms.
The expression "cyclic hydrocarbon group" as used herein refers to a
mono-, bi- or tri-cyclic hydrocarbon group containing 3 to l~l carbon atoms.
The expression "heterocyclic group" as used herein refers to a
heterocyclic group containing 2 to 13 carbon atoms and 1 to 3 hetero atoms
selected from the group consisting of nitrogen, oxygen and sulfur atoms.
The expression "aromatic hydrocarbon group" as used herein refers to
an aryl group.
The expression "saturated or unsaturated hydrocarbon group" as used
herein refers to a saturated or unsaturated hydrocarbon group containing 1 to
10
carbon atoms.
The expression "saturated or unsaturated cyclic hydrocarbon group" as
used herein refers to a mono-, bi- or tri-cyclic hydrocarbon group containing
3
to 10 carbon atoms.
The expression "saturated or unsaturated aliphatic hydrocarbon group"
as used herein refers to a saturated or unsaturated aliphatic hydrocarbon
group
containing 1 to 10 carbon atoms.
The expression "saturated or unsaturated cyclic aliphatic hydrocarbon
group" as used herein refers to a mono-, bi- or tri-cyclic aliphatic
hydrocarbon
group containing 3 to 10 carbon atoms.
12a
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The expression "alkoxy group" as used herein refers to an alkoxy group
containing 1 to 6 carbon atoms.
The expression "alcohol compounds" compounds when refernng to
hydrogen donating organic or inorganic compounds is intended to mean
alcohol compounds containing 1 to 10 carbon atoms.
The expression "unsaturated hydrocarbon compounds" when referring to
hydrogen donating organic or inorganic compounds is intended to mean
unsaturated hydrocarbon compounds containing 5 to 10 carbon atoms.
The expression "aromatic monocyclic or polycyclic hydrocarbon group"
refers to an aromatic mono-, bi- or tri-cyclic hydrocarbon group containing 6
to
14 carbon atoms.
The expression "hetero monocyclic or polycyclic hydrocarbon group"
refers to a hetero mono-, bi- or tri-cyclic group containing 2 to 13 carbon
atoms
and 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen
and sulfur atoms.
Best Mode for Carrying the Invention
In accordance with the present invention, the characteristic methods for
producing optically active
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compounds and catalysts therefor as described above are
provided. The detail is described below.
Firstly, the method for producing an optically active
alcohol of the general formula (I) wherein W1 is oxygen atom
and of the general formula ( II ) wherein R~ is OH ( hydroxyl group )
is described. In the formulas (I) and (II), Ra and Rb
independently represent a linear or cyclic hydrocarbon or
heterocyclic group which may or may not have a substituent, and
the carbonyl compound represented by Ra, Rb and Wl (oxygen atom)
are represented by the following formula (III) as described
above, and the optically active alcohol compound produced by
the hydrogen transfer-type asymmetric reduction of the carbonyl
compound represented by the formula (III) may satisfactorily
be represented by the formula (IV).
0
R1-C- Ra CIII>
O~;T
I
R'1 C-~.R a < I v)
Herein, Rl represents a monocyclic or polycyclic aromatic
hydrocarbon group, a saturated or unsaturated aliphatic
hydrocarbon group or cyclic aliphatic hydrocarbon group, which
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may or may not have a substituent, or a heterocyclic group which
may or may not have a substituent and contains hetero atoms such
as nitrogen, oxygen, sulfur atoms and the like as atoms composing
the ring. The cyclic aliphatic hydrocarbon group and
heterocyclic group may satisfactorily be monocyclic or
polycyclic like the aromatic hydrocarbon group. The cyclic
hydrocarbon (aromatic or alicyclic) and the heterocyclic groups
are of condensed series or non-condensed series if they are
polycyclic.
For example, R1 specifically includes aromatic monocyclic
or polycyclic groups such as phenyl group, 2-methylphenyl,
2-ethylphenyl, 2-isopropylphenyl, 2-tert-butylphenyl, 2-
methoxyphenyl,2-chlorophenyl,2-vinylphenyl,3-methylphenyl,
3-ethylphenyl, 3-isopropylphenyl, 3-methoxyphenyl, 3-
chlorophenyl, 3-vinylphenyl, 4-methylphenyl, 4-ethylphenyl,
4-isopropylphenyl, 4-tert-butylphenyl, 4-vinylphenyl,
cumenyl (cumyl), mesityl, xylyl, 1-naphthyl, 2-naphthyl,
anthryl, phenanthryl, and indenyl; hetero monocyclic or
polycyclic groups such as thienyl, furyl, pyranyl, xanthenyl,
pyridyl, pyrrolyl, imidazolynyl, indolyl, carbazoyl, and
phenanthronylyl; and ferrocenyl group.
Like these examples, the compound may satisfactorily have
various substituents as the substituent, which may be
hydrocarbon groups such as alkyl, alkenyl, cycloalkyl and
cycloalkenyl; halogen atoms; oxygen-containing groups such as
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alkoxy group, carboxyl group and ester group; nitro group; amino
group and the like.
Alternatively, RZ represents hydrogen atom, a saturated or
unsaturated aliphatic hydrocarbon group or cyclic aliphatic
hydrocarbon group which may or may not have a substituent or
an aromatic hydrocarbon group, or the same heterocyclic group
containing hetero atoms, as described above. These are for
example alkyl groups such as methyl, ethyl, propyl, butyl,
pentyl, hexyl and heptyl; cycloalkyl groups such as cyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl; unsaturated
hydrocarbon such as vinyl and allyl; and the same as those for
Rl. Furthermore, R2 may satisfactorily include derivatives of
,Q -keto acid with a functional group at position ,Q. When R1
and RZ are bonded together to form a ring, RZ is for example
a saturated or unsaturated alicyclic group to form cyclic
ketones, such as cyclopentanone, cyclohexanone, cycloheptane,
cyclopentenone, cyclohexenone, and cycloheptenone; and
saturated and unsaturated alicyclic groups with a linear or
cyclic hydrocarbon substituent group containing alkyl group,
aryl group, unsaturated alkyl group and hetero atom on
individual carbons.
According to the method for producing optically active
alcohol compounds through asymmetric reduction of carbonyl
compounds, an asymmetric reduction catalyst system of a
transition metal complex and an optically active nitrogen-
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containing compound is used for the asymmetric reduction.
As the metal catalyst, then, use is made of various
transition metals because they have ligands; particularly
preferably, use is made of a transition metal complex
represented by the following general formula (a);
~LXmLn <a)
(wherein M represents transition metals of group VIII, such as
iron, cobalt, nickel, ruthenium, rhodium, iridium, osmium,
palladium and platinum; X represents hydrogen, halogen atom,
carboxyl group, hydroxy group and alkoxy group{and the like;
L represents neutral ligands such as aromatic compounds and
olefin compounds; and m and n represent an integer ranging
from 1 to 4). As the transition metals in these transition
metal catalysts, ruthenium is one of preferable examples.
When the neutral ligands are aromatic compounds, a
monocyciic aromatic compound represented by the following
general formula ( b ) can be illustrated . Herein, R°' s are all
the same or different substituent groups, including hydrogen
atom, a saturated or unsaturated hydrocarbon group, allyl group
or a functional group containing hetero atoms. For example,
R° includes alkyl groups such as methyl, ethyl, propyl,
isopropyl, butyl, t-butyl, pentyl, hexyl, and heptyl;
cycloalkyl groupssuch ascyclopropyl,cyclobutyl,cyclopentyl,
and cyclohexyl; groups of unsaturated hydrocarbons such as
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benzyl, vinyl, and allyl; functional groups containing hetero
atoms, such as hydroxyl group, alkoxy group, and alkoxycarbonyl
group. The number of the substituents R°'s is an appropriate
number of 1 to 6, and the substituents can occupy any position.
R0 RO
<b)
R.0 SRO
The transition metal catalysts of the group VIII and the
like are used to an amount variable, depending on the size, mode
and economy of the reactor, but the catalysts may satisfactorily
be used within a molar ratio range of approximately 1/100 to
1/100,000, preferably 1/500 to 1/5,000 to the reaction
substrate carbonyl compound.
In accordance with the present invention, use is made of
optically active nitrogen-containing compounds in the
asymmetric catalyst system, and it is possibly assumed that the
compounds are present as asymmetric ligands to the transition
metal complexes or serve as such. For more easily
understandable expression, such optically active nitrogen-
containing compounds may also be illustrated as "optically
active amine compounds". The optically active amine compounds
are optically active diamine compounds represented by the
following general formula (c);
1i
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1I Rm Rm
I4
fG'--- C~ R t c )
N N
~9 ~R10 RISRI6
(wherein R', Rl°, Rls and Rl' are independently hydrogen, a
saturated or unsaturated hydrocarbon group, urethane group or
sulfonyl group; R'1, Rl~, R1' and R1' are the same or different
so that the carbon bonded with these substituent groups might
occupy the asymmetric center, including hydrogen atom, an
- aromatic group, a saturated or unsaturated aliphatic
hydrocarbon group; or cyclic aliphatic hydrocarbon group,; even
in this case, the aromatic or cyclic aliphatic group may be
monocyclic or polycyclic; the polycyclic aromatic group is any
of condensed series or non-condensed series; and furthermore,
any one of R'1 and R'I and any one of R1' and RI' are bonded together
to form a ring containing 5 to 10 carbon atoms. For
example, such compounds include optically active
diamine compounds such as optically active 1,2-
diphenylethylenediamine, 1,2-cyclohexanediamine, 1,2-
cycloheptanediamine, 2,3-dimethylbutanediamine, 1-methyl-
2,2-diphenylethylenediamine, 1-isobutyl-2,2-
diphenylethylenediamine, 1-isopropyl-2,2-
diphenylethylenediamine, 1-methyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-isobutyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-isopropyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-benzyl-2,2-di(p-
methoxyphenyl)ethyienediamine,
is
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1-methyl-2,2-dinaphthyldiamine, 1-isobutyl-2,2-
dinaphthylethylenediamine, 1-isopropyl-2,2-
dinaphthylethylenediamine and the like. Additionally,
optically active diamine compounds wherein any one or two of
substituents R' through R15 are sulfonyl group, acyl group or
urethane group are illustrated. Preferably, furthermore, use
may be made of optically active diamine compounds with one
sulfonyl group. Furthermore, the optically active diamine
( compounds ) for potential use are not limited to the illustrated
optically active ethylenediamine derivatives, and use may be
made of optically active propanediamine, butanediamine, and
phenylenediamine derivatives.
As the optically active amine compounds, use is made of
optically active amino alcohol compounds represented by the
following general formula (d).
1y X20 ~21
~ ~ C~ R12
~~ < a
1~ R is '
Rz3
Herein, at least one of Ri' and Rle is hydrogen atom, and
the remaining one is hydrogen atom, a saturated or unsaturated
hydrocarbon group, urethane group or sulfonyl group; R~9, R2°,
R~1 and Rz~ are the same or different so that the carbon bonded
with these substituent groups might occupy the asymmetric
center, including hydrogen atom, a monocyclic or polycyclic
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aromatic group, a saturated or unsaturated aliphatic
hydrocarbon group; and a cyclic aliphatic hydrocarbon group;
Rj' represents hydrogen atom, a monocyclic or polycyclic
aromatic group, a saturated or unsaturated aliphatic
hydrocarbon group and cyclic aliphatic hydrocarbon group.
Furthermore, any one of R1' and RZ° and any one of R~1 and R~~ may
satisfactorily be bonded together to form a ring containing 5
to 10 carbon atoms. Additionally, any one of R1' and Rle and any
one of RZ° and- RZ1 may satisfactorily be bonded together to form
a ring containing 5 to 10 carbon atoms. More specifically, use
may satisfactorily be made of optically active, amino-alcohols~
shown in the examples described below.
As the optically active amine compounds, furthermore, use
may be made of aminophosphine compounds represented by the
following general formula (e);
R26 R26'
C
n
N p
R2a Rzs R27 Rzs
Herein, RZ' and R~5 are hydrogen atom, a saturated or
unsaturated hydrocarbon group, urethane group, sulfonyl group
and acyl group; R26 and R26~ are the same or different so. that the
carbon bonded with these substituent groups might occupy the
asymmetric center, including hydrogen atom, a monocyclic or
polycyclic aromatic group, a saturated or unsaturated
hydrocarbon group, and a cyclic hydrocarbon group; R~' and R~°
represent hydrogen atom, and a saturated or unsaturated
'?0
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hydrocarbon group, n is an integer ranging from 1 to 4 _ More
specifically, use may be made of the optically active
aminophosphines shown in the examples.
The optically active amine compounds as illustrated above
are generally used for example at an amount at approximately
0.5 to 20 equivalents, and preferably used for example within
a range of 1 to 4 equivalents, to the transition metal complex.
In the aforementioned catalyst system to be used for the
method for producing optically active alcohols through
asymmetric reduction of carbonyl compounds, advantageously, an
additional basic substance is advantageously present
currently.
Such basic substance includes for example metal salts or
quaternary ammonium compounds represented by the following
formula (f);
MIy Cf)
(wherein Ml represents an alkali metal or alkali earth metal;
and Y represents hydroxy group, alkoxy group, mercapto group
and naphthyl group) . More specifically, Ml includes KoH, KOCH"
KOCH(CH,)~, KOC(CH,),, KCIOH,, LiOH, LiOCH" LiOCH(CH,)I,
LiOC ( CH, )" NaOH, NaOCH" NaOCH ( CH, ) ~, NaC,oHs, NaOC ( CH, ) , and the
like. Furthermore, quaternary ammonium salts may be used
satisfactorily.
The amount of the base to be used is generally about 0.5
to 50 equivalents, preferably 2 to 10 equivalents to the
transition metal complex.
'? l
CA 02239970 1998-06-08
As has been described above, the basic substance is
used for smoothly progressing the asymmetric reduction.
Therefore, the base is an important component so as to give
optically active alcohol compounds with a high optical
purity.
For the method for producing optically active alcohol
compounds through hydrogen transfer-type asymmetric
reduction in accordance with the present invention, it is
inevitable to use hydrogen-donating organic or inorganic
compounds. By these are meant compounds capable of donating
hydrogen via thermal action or catalytic action, and the
types of such hydrogen-donating compounds are not
specifically limited, but preferably include alcohol
compounds such as methanol, ethanol, 1-propanol, 2-propanol,
butanol, and benzyl alcohol; formic acid and salts thereof,
for example those in combination with amines; an unsaturated
hydrocarbon and heterocyclic compounds having in part a
saturated carbon bond, such as tetralin and decalin;
hydroquinone or phosphorous acid or the like. Among them,
alcohol compounds are preferable, and 2-propanol and formic
acid are more preferable. The amount of an organic compound
to be used and function as a hydrogen source is determined
on the basis of the solubility and economy of the reaction
substrate. Generally, the substrate concentration may be
about 0.1 to 30 $ by weight for some type of substrates, but
preferably, the concentration is 0.1 to 10 $ by weight.
22
CA 02239970 1998-06-08
When using formic acid and a combination of formic acid with
amine as a hydrogen source, no solvent is necessarily used.
If any solvent is intentionally used, use is made of
aromatic compounds such as toluene and xylene; halogen
compounds such as dichloromethane, organic compounds such as
DMSO, DMF or acetonitrile.
According to the method for producing optically active
alcohol compounds in accordance with the present invention,
hydrogen pressure is essentially not required, but depending
on the reaction conditions, hydrogen pressure may
satisfactorily be loaded. Even if hydrogen pressure is
loaded, the pressure may satisfactorily be about 1 atom. to
several atm. because the catalyst system is extremely highly
active.
The reaction temperature is about -20 to 100 from the
economical standpoint. More practically, the reaction can
be carried out around room temperature of 25 to 40 . The
reaction time varies, depending on the reaction conditions
such as the concentration of a reaction substrate,
temperature and pressure, but the reaction is on completion
from several minutes to 100 hours.
For use, the metal complex is preliminarily mixed with
an optically active amine compound as an optically active
nitrogen-containing compound, but a chiral metal complex may
be synthesized preliminarily by the following method, and
the resulting complex may be used.
23
CA 02239970 1998-06-08
More specifically, the method comprises adding an
optically active amine compound, a transition metal complex
and a complex into for example alcohol, and subsequently
heating the resulting mixture in an inactive gas under
agitation. Then, the resulting solution is cooled and
treated under reduced pressure, prior to recrystallization,
to prepare an asymmetric complex catalyst.
Together with the method for producing optically active
alcohol compounds as described above, the present invention
is to provide a method for producing optically active amine
compounds represented by the general formula (II) as
described above, wherein W1 is OH, NH2, NH-Rc, NH-OH or NH-
0-Rd, comprising asymmetric reduction by using an imine
compound represented by the general formula (I) wherein Wl
is NH, N-Rc, N-OH or N-O-Rd (Rc and Rd independently
represent a linear or cyclic hydrocarbon group which may or
may not have a substituent, or a heterocyclic group).
More specifically, for example, the present invention
is to provide a method for producing an optically active
amine compound of the following formula (VI), comprising
asymmetric reduction of an imine compound of the following
formula (V).
NR5 NHRS
(V) IH (VI)
R3/ \R4 R3/ \R4
24
CA 02239970 1998-06-08
Herein, R' and R' are almost the same as those in the case
of the carbonyl compounds and the optically active alcohol
compounds of the formulas (III) and (IV), respectively.
For example, R' is an aromatic monocyclic or polycyclic
hydrocarbon group, unsubstituted or substituted, a saturated
or unsaturated aliphatic hydrocarbon group or cyclic
hydrocarbon group, unsubstituted or substituted, or a hetero
monocyclic or polycyclic group containing hetero atoms such as
nitrogen, oxygen, sulfur atoms and the like; more specifically,
R' includes aromatic monocyclic or polycyclic hydrocarbon
groups such as phenyl group, 2-methyphenyl, 2-ethylphenyl,
2-isopropylphenyl, 2-tert-butylphenyl, 2-methoxyphenyl, 2-
chlorophenyl, 2-vinylphenyl, 3-methylphenyl, 3-ethylphenyl,
3-isopropylphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-
vinylphenyl,4-methyphenyl,4-ethylphenyl,4-isopropylphenyl,
4-tert-butylphenyl, 4-vinylphenyl, cumenyl, mesityl, xylyl,
1-naphthyl, 2-naphthyl, anthryl, phenanthryl, and indenyl
groups; hetero monocyclic or polycyclic groups such as thienyl,
furyl, pyranyl, xanthenyl, pyridyl, pyrrolyl, imidazolyl,
indolyl, carbazoyl, and phenanthronylyl; and ferrocenyl group.
Like these examples, R' may contain any of various substituents,
which may satisfactorily be hydrocarbon groups such as alkyl,
alkenyl, cycloalkyl, and cycloalkenyl; halogen atom;
oxygen-containing groups such as alkoxy group, carboxyl group
2.5
CA 02239970 1998-06-08
and ester group; nitro group: cyano group and the like.
Furthermore, R4 represents hydrogen atom, a saturated
or unsaturated hydrocarbon group, aryl group, hetero atom-
containing functional groups, including for example alkyl
groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl,
and heptyl; cycloalkyl groups such as cyclopropyl,
cyclobutyl, cyclopentyl, and cyclohexyl: unsaturated
hydrocarbons such as vinyl and allyl; and the same as those
for Rl. Additionally, RS represents hydrogen atom, a
saturated and unsaturated hydrocarbon group, aryl group, a
hetero atom-containing heterocyclic group, or the
hydrocarbon group or heterocyclic group bonded together via
hydroxyl group or oxygen atom, including for example alkyl
groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl
and heptyl; cycloalkyl groups such as cyclopropyl,
cyclobutyl, cyclopentyl, and cyclohexyl; unsaturated
hydrocarbon groups such as benzyl, vinyl and allyl; hydroxyl
group; alkyl ether groups; aryl ether groups: and the like.
Furthermore, a saturated or unsaturated cyclic imine
compound formed by bonding together R3 and R4, R3 and R5 or
R4 and R5, is illustrated.
Non-cyclic imine compounds can be synthesized readily from
the corresponding ketones and amines. In this case, the syn-form
and anti-form or a mixture enriched with either one of these
syn- and anti-forms may be used satisfactorily, but a purified
product of the mixture may be used singly or a mixture thereof
26
CA 02239970 1998-06-08
with another imine compound may also be used.
Even by the method for producing optically active amine
compounds, like the method for producing optically active
alcohol compounds, use is made of an asymmetric reduction
catalyst composed of a transition metal complex and an optically
active nitrogen-containing compound. In the transition metal
complex among them, various transition metals with ligands are
used, and particularly preferably, use is made of those similar
to a transition metal complex represented by the general formula
(a);
MXmLn Ca)
(wherein M is a transition metal of group VIII, such as iron,
cobalt, nickel, ruthenium, rhodium, iridium, osmium, palladium
and platinum; X represents hydrogen, halogen atom, carboxyl
group, hydroxy group and alkoxy group and the like; L represents
neutral ligands such as aromatic compounds and olefin
compounds; m and n represent an integer) . The transition metal
in the transition metal complex is preferably rare metal, and
specifically, ruthenium is one of preferable examples.
Like the method for producing optically active alcohols,
a monocyclic aromatic compound represented by the general
formula (b) is illustrated for the aromatic compound as the
neutral ligand. Herein, R°'s are the same or different
substituent groups, representing hydrogen atom, a saturated or
2r
CA 02239970 1998-06-08
unsaturated hydrocarbon group, aryl group, and functional
groups containing hetero atoms, for example alkyl groups such
as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl,
hexyl, and heptyl; cycloalkyl groups such as cyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl; unsaturated
hydrocarbon groups such as benzyl, vinyl, and allyl; hetero
atom-containing functional groups such as hydroxyl group,
alkoxy group and alkoxycarbonyl group. The number of the
substituents R°'s is an optional number of 1 to 6, and the
substituents each can occupy any position.
~t0 RO
Ro / ' 0 Cb)
R
R'0 R
The transition metal catalysts are used at an amount
variable, depending on the size, mode and economy of the reactor,
but the catalysts may satisfactorily be used within a molar ratio
range of approximately 1/100 to 1/100, 000, preferably 1/200 to
1/5,000 to the reaction substrate imine compound.
According to the method for producing optically active
amine compounds in accordance with the present invention,
additionally, use is made of optically active nitrogen-
containing compounds in the asymmetric catalyst system, and it
is possibly assumed that the compounds may be present as
'?3
CA 02239970 1998-06-08
asymmetric ligands in the transition metal_complexes or may
serve as such. For more easily understandable expression, such
optically active nitrogen-containing compounds are illustrated
as "optically active amine compounds". As described above, the
optically active amine compounds are optically active diamine
compounds represented for example by the following general
formula (c);
ii Rm R13
Cc)
N N
,.
R9 Rio RtsRis
(wherein R', Rl°, R15, and R16 are independently hydrogen, a
saturated or unsaturated hydrocarbon group, urethane group yr
sulfonyl group; R11, Rlj, R1' and R1' are the same or different
so that the carbon bonded with these substituent groups might
occupy the asymmetric center, including hydrogen atom, aromatic
monocyclic and polycyclic groups, a saturated or unsaturated
hydrocarbon group or cyclic hydrocarbon group; even in this case,
the aromatic, or cyclic, or cyclic aliphatic group may be
monocyclic or polycyclic; the polycyclic aromatic group is any
of condensed series or non-condensed series; and furthermore,
any one of R11 and Rl~ may satisfactorily form a ring. For example,
such compounds include optically active diamine compounds such
as optically active 1,2-diphenylethylenediamine, 1,2-
cyclohexanediamine, 1,2-cycloheptanediamine, 2,3-
'?9
CA 02239970 1998-06-08
dimethylbutanediamine,l-methyl-2,2-diphenylethylenediamine,
1-isobutyl-2,2-diphenylethylenediamine, 1-isopropyl-2,2-
diphenylethylenediamine, 1-methyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-isobutyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-isopropyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-benzyl-2,2-di(p-
methoxyphenyl)ethylenediamine, 1-methyl-2,2-
dinaphthylethylenediamine, 1-isobutyl-2,2-
dinaphthylethylenediamine, 1-isopropyl-2,2-
dinaphthylethylenediamine and the like. Additionally,
optically active diamine compounds wherein any one or two of
substituents R' through R15 are sulfonyl group, acyl group or
urethane group may also be used. Preferably, furthermore, use
may be made of optically active diamine compounds with one
sulfonyl group. Furthermore, optically active diamine
(compounds) to be possibly used are not limited to the
illustrated optically active ethylenediamine derivatives, and
use may be made of optically active propanediamine,
butanediamine, and phenylenediamine derivatives.
As the optically active amine compound, use is made of an
optically active amino alcohol compound represented by the
following general formula (d);
Riy ~=o RZR2
~C~- C~ C d )
~ R17NRI8 O 23
R
:30
CA 02239970 1998-06-08
Herein, at least one of R1' and R1' is hydrogen atom, and
the remaining one is hydrogen atom, a saturated or unsaturated
hydrocarbon group, urethane group or sulfonyl group; Rl', Rzo,
RZ1 and R~z are the same or different so that the carbon bonded
with these substituent groups might occupy the asymmetric
center, including hydrogen atom, an aromatic monocyclic or
polycyclic group,asaturated or unsaturated hydrocarbon group,
or a cyclic hydrocarbon group; RZ' represents hydrogen atom,
an aromatic monocyclic or polycyclic group, a saturated or
unsaturated hydrocarbon group and a cyclic hydrocarbon group.
Furthermore, any one of R1' and Rz° and any one of R~1 and R~~ may
satisfactorily be bonded together to form a ring, or any one
of Rl' and R18 and any one of RZ° and R~1 may satisfactorily be
bonded together to form a ring. More specifically, use is made
of optically active amino alcohols shown in the examples
described below.
As the optically active amine compound, furthermore, use
is made of aminophosphine compound represented by the following
general formula (e).
CR2~ n
N ~P Ce)
R~ ~Rzs R27 ~Rzs
Herein, RZ° and .RCS are hydrogen atom, a saturated or
unsaturated hydrocarbon group, urethane group, sulfonyl group
and acyl group; (CRi26)n are the same or different so that the
:31
CA 02239970 1998-06-08
carbon bonded with these substituent groups_might occupy the
asymmetric center, including hydrogen atom, an aromatic
monocyclic or polycyclic group, a saturated or unsaturated
hydrocarbon group, and a cyclic hydrocarbon group; Rz' and R~e
represent hydrogen atom, asaturated or unsaturated hydrocarbon
group, and allyl group. More specifically, use is made of the
optically active aminophosphines shown in the examples.
The optically active amine compounds as illustrated above
are used at an amount for example of approximately 0.5 to 20
equivalents, and preferably within a range of 1 to 2 equivalents,
to the transition metal complex.
The transition metal catalyst to be used as the catalyst
as described above and the optically active amine compound are
essential components to progress the asymmetric reduction in
a smooth manner thereby attaining a higher asymmetric yield,
and amine compounds at a higher optical purity cannot be
recovered at a sufficiently high reaction activity, if either
one of the two is eliminated.
For the method for producing optically active amines
through hydrogen transfer-type asymmetric reduction in
accordance with the present invention, the presence of a
hydrogen-donating organic or inorganic compound is
indispensable. These compounds mean compounds capable of
donating hydrogen through thermal action or catalytic action,
and the types of these hydrogen-donating compounds are not
:30
CA 02239970 1998-06-08
limited, but preferably include alcohol compounds such as
methanol, ethanol, 1-propanol, 2-propanol, butanol, and
benzyl alcohol; formic acid and salts thereof, such as those
in combination with amines; unsaturated hydrocarbons and
heterocyclic compounds having saturated carbon bonds in
part, such as tetralin and decalin; hydroquinone or
phosphorous acid or the like. Among them, alcohol compounds
are preferable, and 2-propanol is more preferable. The
amount of an organic acid to be used as a hydrogen source is
determined, depending on the solubility and economy of the
reaction substrate. Generally, the substrate is used at a
concentration of approximately 0.1 to 30 $ by weight,
depending on the type of the substrate to be used, and is
preferably at a concentration of 0.1 to 10 $ by weight.
When using formic acid and a combination of formic acid with
amine as a hydrogen source, no solvent is necessarily used,
but use may satisfactorily be made of aromatic compounds
such as toluene and xylene; halogen compounds such as
dichloromethane, or organic compounds such as DMSO, DMF or
acetonitrile, if it intended to use any solvent.
Hydrogen pressure is essentially not required, but
depending on the reaction conditions, hydrogen pressure may
satisfactorily be loaded. Even if hydrogen pressure is
loaded, the pressure may satisfactorily be about 1 atm. to
50 atm.
The reaction temperature is abaut -20°C to 100°C from the
33
CA 02239970 1998-06-08
economical standpoint. More practically, the reaction can
be carried out around room temperature of 25 to 40 . The
reaction time varies, depending on the reaction conditions
such as the concentration of a reaction substrate,
temperature and pressure, but the reaction is on completion
from several minutes to 100 hours.
The metal complex to be used in accordance with the
present invention is preliminarily mixed with an optically
active amine compound, but an asymmetric metal complex may
be preliminarily synthesized by the following method, and
the resulting complex may be used.
More specifically, for example, a method is
illustrated, comprising suspending a ruthenium-arene
complex, an optically active amine compound and
triethylamine in 2-propanol, heating the resulting mixture
in argon or nitrogen gas stream under agitation, and cooling
then the resulting reaction mixture, from which the solvent
is then removed, and re-crystallizing the resulting mixture
in an alcohol solvent to prepare an asymmetric complex.
The catalyst system to be used for the hydrogen
transfer-type asymmetric reduction in accordance with the
present invention is very characteristic and has never been
known up to now.
The optically active ruthenium-diamine complex
represented by the following formula (VII) as described bove
as one metal complex composed of a transition metal and an
34
CA 02239970 2004-02-25
optically active nitrogen-containing compound ligand is useful
as a catalyst for producing optically active secondary alcohol
compounds, comprising subjecting racemic secondary alcohol or
~meso-type diols to hydrogen transfer reaction, and therefore,
the complex draws higher attention.
Roa
O1
* Nw /x (v«)
Ru
R°4 H"r
in the formula, * represents an asymmetric carbon atom; R°1
andR°~
are the same or different, independently representing alkyl
group, or phenyl group or cycloalkyl group which may or may not
have an alkyl group; or R°1 and R°~ together form an alicyclic
ring unsubstituted or substituted with an alkyl group; R°'
represents methanesulfonyl group, trifluoromethanesulfonyl
group, naphthylsulfonyl group, camphor sulfonyl group, or
benzenesulfonyl group which may or may not be substituted with
an alkyl group, an alkoxyl group or halogen atom, alkoxycarbonyl
group, or benzoyl group which may or may not be substituted with
an alkyl group; R°' represents hydrogen atom or alkyl group;
X represents an aromatic compound which may or may not be
substituted with an alkyl group; and m and n together
represent ° or 1.
For more description of the optically active ruthenium-
diamine complex of the formula (VII), the aromatic compound
CA 02239970 1998-06-08
which may or may not have an alkyl group represented by X, for
example alkyl groups with C1 to C4, means for example benzene,
toluene, xylene, mesitylene, hexamethylbenzene, ethylbenzene,
tert-butylbenzene, p-cymene, and cumene and preferably
includes benzene, mesitylene and p-cymene.
R°1 and R°~ represent a linear or branched alkyl group, if
they represent an alkyl group, for example alkyl groups with
Cl.~to C4. More specifically, the alkyl group includes methyl,
ethyl, n-propyl, isopropyl, n-, iso-, sec- and tent-butyl.
More preferably, the group includes methyl, ethyl, n-propyl or
iso-propyl.
If R°1 and R°2 are bonded together to form an alicyclic
group,
the group may satisfactorily be a C5 to C7-membered ring. The
alkyl group which may or may not be a substituent therefor, for
example alkyl substituent group with C1 to C4, includes methyl
group, ethyl group, n-propyl group, isopropyl group, and n-,
iso-, sec- and tert-butyl groups . Preferably, the alkyl group
is methyl.
R1 and RZ as phenyl group wherein R°1 and R°~ may have an
alkyl
group, for example methyl group, specifically include phenyl,
o-, m- and p-tolyl groups.
R°1 and R°Z representing cycloalkyl group contain carbon
atoms in 5 to 6-membered rings, preferably including
cyclopentyl or cyclohexyl.
In more preferable examples, R°1 and R°2 are independently
36
CA 02239970 1998-06-08
phenyl or R°1 and R°Z together mean tetramethylene ( - ( CHZ ) a-
)
R°' represents methanesulfonyl group,
trifluoromethanesulfonyl group, naphthylsulfonyl group,
camphor sulfonyl group, or benzenesulfonyl group which may or
may not be substituted with alkyl group, for example alkyl group
with C1 to C3, alkoxy group for example alkoxy group with C1
to C3, or halogen atom, or benzoyl group which may or may not
be substituted with alkyl group, for example C1 to C4
alkoxycarbonyl groups, or alkyl group, for example C1 to C4 alkyl
group.
More specifically, R°' representing benzenesulfonyl group
which may or may not be substituted with C1 to C3 alkyl group,
C1 to C3 alkoxyl group or halogen atom, includes benzenesulfonyl,
o-, m- and p-toluenesulfonyl, o-, m-, and p-
ethylbenzenesulfonyl,o-,m-,and p-methoxybenzenesulfonyl,o-,
m-, and p-ethoxybenzenesulfonyl, o-, m-, and p-
chlorobenzenesulfonyl, 2, 4, 6-trimethylbenzenesulfonyl,
2,4,6-triisopropylbenzenesulfonyl, p-fluorobenzenesulfonyl,
and pentafluorobenzenesulfonyl, and more preferably includes
benzenesulfonyl or p-toluenesulfonyl. Specifically, R°'
representing C1 to C4 alkoxycarbonyl groups includes
methoxycarbonyl, ethoxycarbonyl, isopropyloxycarbonyl, and
tert-butoxycarbonyl, preferably including methoxycarbonyl or
tert-butoxycarbonyl. R°' representing benzoyl group which may
or may not be substituted with C1 to C4 alkyl groups specifically
:37
CA 02239970 1998-06-08
includes benzoyl, o-, m-, and p-methylbenzoyl, o-, m-, and
p-ethylbenzoyl, o-, m-, and p-isopropylbenzoyl, and o-, m-,
and p-tart-butylbenzoyl, preferably including benzoyl or p-
methylbenzoyl.
In the most preferable example, R~3 is methanesulfonyl,
trifluoromethanesulfonyl, benzenesulfonyl or p-toluene-
sulfonyl.
R~4 representing hydrogen atom or alkyl group, for
example CI to C4 alkyl groups, specifically includes for
example hydrogen, methyl, ethyl, n-propyl, isopropyl, n-,
iso-, sec- and tart-butyl, and more preferably includes
hydrogen atom or methyl group.
The optically active ruthenium-diamine complex is used
for the method for producing optically active secondary
alcohols from ketones as descried above in accordance with
the present invention, and in this case, the racemic
secondary alcohols as the raw material compounds in
accordance with the present invention are illustrated by the
following formula (VIII)_ It is needless to say that the
racemic alcohols are not limited to those represented by the
formula.
OH
(VIII)
R6 R~
R6 represents an aromatic monocyclic or polycyclic
hydrocarbon group, unsubstituted or substituted or a hetero
38
CA 02239970 2004-02-25
monocyclic or polycyclic group containing hetero atoms
including nitrogen, oxygen, sulfur atoms and the like,
specifically representing aromatic monocyclic or polycyclic
groups such as phenyl group, 2-methylphenyl, 2-ethylphenyl,
2-isopropylphenyl, 2-tert-butylphenyl, 2-methoxyphenyl, 2-
chlorophenyl, 2-vinylphenyl, 3-methylphenyl, 3-ethylphenyl,
3-isopropylphenyl., 3-methoxyphenyl, 3-chlorophenyl, 3-
vinylphenyl, 4-methylphenyl, 4-ethylphenyl, 4-
isopropylphenyl, 4--tert-butylphenyl, 4-vinylphenyl, cumenyl,
mesityl, xylyl, 1-naphthyl, 2-naphthyl, anthryl, phenanthryl,
and indenyl; hetero monocyclic or polycyclic groups such as
thienyl, furyl, pyranyl, xanthenyl, pyridyl, pyrrolyl,
imidazolyl, indolyl, carbazoyl, and phenthronylyl; and
ferrocenyl group. Furthermore, R' represents hydrogen atom,
a saturated or unsaturated hydrocarbon group, or a functional
group containing hetero atoms, including for example alkyl
groups such as methyl, ethyl, propyl, isopropyl, butyl, pentyl,
hexyl, and heptyl; cycloalkyl groups such as cyclopropyl,
cyclobutyl, cyclopentyl, and cyclohexyl; and unsaturated
hydrocarbons such as benzyl, vinyl, and allyl. R6 and R' may
be bonded together to form a ring, and in this case, R' includes
for example a saturated or unsaturated alicyclic group giving
a CS-C., cyclic ketone such as cyclopentanone, cyclohexanone,
cycloheptane, cyclopentenone, cyclohexenone, and
cycloheptenone; or a saturated and unsaturated alicyclic group
:39
CA 02239970 2004-02-25
with a substituent group having an alkyl group, an aryl
group, a unsaturated alkyl group or a linear or cyclic
hydrocarbon group on each of the individual carbons_
Additionally, the meso-type diols are represented for
example by the following formula (IX)_
Rg off
CHz)n cIX)
OH
It is needless to say that the meso-diols are not limited to
them.
In this case, R8 and R9 are the same and represent a
saturated or unsaturated hydrocarbon group which may or may
not have a substituent group, or R8 and R9 may be bonded
together to form a saturated, or unsaturated alicyclic group,
having preferably S to 7 carbon atoms, which may or may not have
a substituent group, and n is 1 or 2.
More specifically, the ruthenium-diamine complex of the
present invention is for example such that m and n are
simultaneously zero in the formula (VII). Herein, is used
to represent the number of carbon atoms bonded to a metal in
unsaturated ligands, and therefore, hexahapto (six carbon
atoms bonded to metal) is represented by ~ 6: p-Ts
represents p-toluenesulfonyl group; Ms represents
methanesulfonyl group; and Tf represents trifluoromethane-
sulfonyl group.
Ru[(S, S)-p-TsNCH(C6H5)CH(C6H5)NH)(r) 6-benzene)(((S, S)-N-p-
CA 02239970 1998- 06-08
toluenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benzene ) ( ( ( R, R )
-N-p-
toluenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( ( S ,
S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine)(776-p-
cymene)ruthenium)
Ru [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( ( R, R
) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine)(776-p-
cymene)ruthenium)
Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-mes itylene ) ( ( ( S
, S ) -N-
p-toluenesulfonyl-1,2-diphenylethylenediamine)(776-
mesitylene)ruthenium)
Ru [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 7) 6-mes itylene ) ( ( ( R,
R ) -N-
p-toluenesulfonyl-1,2-diphenylethylenediamine)(776-
iliesitylene)ruthenium)
Ru [ ( S , S ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benzene ) ( ( ( S , S )
-N-
methanesulfonyl-1,2-diphenylethylenediamine)(~ 6-
benzene)ruthenium)
Ru [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benz ene ) ( ( ( R, R ) -
N-
methanesulfonyl-1,2-diphenylethylenediamine)(~ 6-
benzene)ruthenium)
Ru [ ( S , S ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~7 6-p-cymene ) ( ( ( S , S
) -N-
methanesulfonyl-1,2-diphenylethylenediamine)(~76-p-
41
CA 02239970 1998-06-08
cymene)ruthenium)
Ru [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( ( R, R ) -
N-
methanesulfonyl-1,2-diphenylethylenediamine)(~ 6-p-
cymene)ruthenium)
Ru[ (S, S)-MsNCH(C6H5)CH(C6H5)NH] ( 77 6-mesitylene) ( ( (S, S)-N-
methanesulfonyl-1,2-diphenylethylenediamine)(776-
mesitylene)ruthenium)
Ru [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-mes itylene ) ( ( ( R, R
) -N-
methanesulfonyl-1,2-diphenylethylenediamine)(r~6-
mesitylene)ruthenium)
Ru [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benz ene ) ( ( ( S , S
) -N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( R, R) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-benzene ) ( ( ( R, R) -N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-p-cymene ) ( ( ( S , S )
-N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(776-
p-cymene)ruthenium)
Ru [ ( R, R ) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( ( R, R ) -
N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(776-
p-cymene)ruthenium)
Ru [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-mes itylene ) ( ( ( S ,
S ) -N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(776-
mesitylene)ruthenium)
42
CA 02239970 1998-06-08
Ru [ ( R, R) -TfNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-mes itylene ) ( ( ( R, R) -
N-
trifluoromethanesulfonyl-1,2-diphenylethylenediamine)(~ 6-
mesitylene)ruthenium)
Ru [ ( S , S ) -C6HSS02NCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benzene ) ( ( ( S
, S ) -N-
benzenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( R, R ) -C6HSSOZNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-benzene ) ( ( ( R,
R ) -N-
benzenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
Ru [ ( S , S ) -C6HSS02NCH ( C6H5 ) CH ( C6H5 ) NH ] ( r/ 6-p-cymene ) ( ( ( S
, S ) -N-
benzenssulfonyl-1,2-diphenylethylenediamine)(~ 6-p-
cymene)ruthenium)
Ru [ ( R, R) -C6HSS02NCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( ( R,
R) -N-
benzenesulfonyl-1,2-diphenylethylenediamine)(~76-p-
cymene)ruthenium)
Ru [ ( S , S ) -C6HSSO~NCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-mes itylene ) ( (
( S , S ) -
N-benzenesulfonyl-1,2-diphenylethylenediamine)(776-
mesitylene)ruthenium)
Ru [ ( R, R ) -C6HSS02NCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-mes itylene ) ( ( (
R, R ) -
N-benzenesulfonyl-1,2-diphenylethylenediamine)(~ 6-
mesitylene)ruthenium)
Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine](~ 6-benzene)(((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(~ 6-
benzene)ruthenium)
Ru[(R, R)-N-p-Ts-1,2-cyclohexanediamine](~ 6-benzene)(((R,
4:3
CA 02239970 1998-06-08
R)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(776-
benzene)ruthenium)
Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine](776-p-cymene)(((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(776-p-
cymene)ruthenium)
Ru[(R, R)-N-p-Ts-1,2-cyclohexanediamine](~ 6-p-cymene)(((R,
R)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(776-p-
cymene)ruthenium)
Ru[(S,S)-N-p-Ts-1,2-cyclohexanediamine](776-mesitylene)(((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
Ru[(R,R)-N-p-Ts-1,2-cyclohexanediamine](776-mesitylene)(((R,
R)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
Ru[(S, S)-N-Ms-1,2-cyclohexanediamine](776-benzene)(((S,
S)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-
benzene)ruthenium)
Ru[(R, R)-N-Ms-1,2-cyclohexanediamine](776-benzene)(((R,
R)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-
benzene)ruthenium)
Ru[(S, S)-N-Ms-1,2-cyclohexanediamine](776-p-cymene)(((S,
S)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-p-
cymene)ruthenium)
Ru[(R, R)-N-Ms-1,2-cyclohexanediamine](776-p-cymene)(((R,
R)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-p-
44
CA 02239970 1998-06-08
cymene)ruthenium)
Ru[(S, S)-N-Ms-1,2-cyclohexanediamine](776-mesitylene)(((S,
S)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
Ru[(R, R)-N-Ms-1,2-cyclohexanediamine](776-mesitylene)(((R,
R)-N-methanesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
Ru[(S, S)-N-Tf-1,2-cyclohexanediamine](776-benzene)(((S,
S)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
benzene)ruthenium)
Ru[(R, R)-N-Tf-1,2-cyclohexanediamine](776-benzene)(((R,
R)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
benzene)ruthenium)
Ru[(S, S)-N-Tf-1,2-cyclohexanediamine](~ 6-p-cymene)(((S,
S)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
p-cymene)ruthenium)
Ru[(R, R)-N-Tf-1,2-cycloheXanediamine](776-p-cymene)(((R,
R)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
p-cymene)ruthenium)
Ru[(S, S)-N-Tf-1,2-cyclohexanediamine](776-mesitylene)(((S,
S)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
Ru[(R, R)-N-Tf-1,2-cyclohexanediamine](776-mesitylene)(((R,
R)-N-trifluoromethanesulfonyl-1,2-cyclohexanediamine)(776-
mesitylene)ruthenium)
CA 02239970 1998-06-08
Ru [ ( S , S ) -N-C6HSS0z-1, 2-cyclohexanediamine ] ( 77 6-benzene ) ( ( ( S ,
S)-N-benzenesulfonyl-1,2-cyclohexanediamine)(~76-
benzene)ruthenium)
Ru [ ( R, R ) -N-C6HSS0z-1, 2-cyclohexanediamine ] ( 77 6-benzene ) ( ( ( R,
R)-N-benzenesulfonyl-1,2-cyclohexanediamine)(r76-
benzene)ruthenium)
Ru [ ( S , S ) -N-C6HSSOZ-1, 2-cyclohexanediamine ] ( r7 6-p-cymene ) ( ( ( S
,
S)-N-benzenesulfonyl-1,2-cyclohexanediamine)(776-p-
cymene)ruthenium)
Ru [ ( R, R ) -N-C6HSS0z-1, 2-cyclohexanediamine ] ( ~ 6-p-cymene ) ( ( ( R,
R)-N-benzeneesulfonyl-1,2-cyclohexanediamine)(776-p-
cymene)ruthenium)
Ru [ ( S, S ) -N-C6HSS02-1, 2-cyclohexanediamine ] ( 77 6-
mesitylene)(((S, S)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(~ 6-mesitylene)ruthenium)
Ru [ ( R, R) -N-C6HSS0z-1, 2-cyclohexanediamine ] ( 77 6-
mesitylene)(((R, R)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
Those of the formula (VII) wherein m and n are
simultaneously 1 are illustrated as follows . Herein, ~7 is used
to represent the number of carbon atoms bonded to a metal in
unsaturated ligands, and therefore, hexahapto(six carbon atoms
bonded to metal) is represented by ~7 6; p-Ts represents p-
toluenesulfonyl group; Ms represents methanesulfonyl group;
46
CA 02239970 1998-06-08
and Tf represents trifluoromethanesulfonyl group.
RuH [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-benz ene ) (
hydride- ( ( S ,
S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
RuH [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( 77 6-benzene ) ( hydride-
( ( R,
R)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(776-
benzene)ruthenium)
RuH [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-p-cymene ) ( hydride-
( ( S,
S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(~ 6-p-
cymene)ruthenium)
RuH [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-p-cymene ) ( hydride-
( ( R,
R)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(~ 6-p-
cymene)ruthenium)
RuH [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-mesitylene ) (
hydride-
((S, S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(77
6-mesitylene)ruthenium)
RuH [ ( R, R ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( r~ 6-mes itylene ) (
hydride-
((R, R)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)(~
6-mesitylene)ruthenium)
RuH [ ( S , S ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ~7 6-benzene ) ( hydride-
( ( S ,
S)-N-methanesulfonyl-1,2-diphenylethylenediamine)(~76-
benzene)ruthenium)
RuH [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( 77 6-benzene ) ( hydride- (
( R,
R)-N-methanesulfonyl-1,2-diphenylethylenediamine)(776-
47
CA 02239970 1998-06-08
benzene)ruthenium)
RuH [ ( S , S ) -MsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ 6-p-cymene ) ( hydride-
( ( S ,
S)-N-methanesulfonyl-1,2-diphenylethylenediamine)(776-p-
cymene)ruthenium)
RuH [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ~ 6-p-cymene ) ( hydride- (
( R,
R)-N-methanesulfonyl-1,2-diphenylethylenediamine)(r76-p-
cymene)ruthenium)
RuH [ ( S , S ) -MsNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( ~7 6-mes itylene ) (
hydride- ( ( S ,
S)-N-methanesulfonyl-1,2-diphenylethylenediamine)(776-
mesitylene)ruthenium)
RuH [ ( R, R ) -MsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-mes itylene ) (
hydride- ( ( R,
R)-N-methanesulfonyl-1,2-diphenylethylenediamine)(r76-
mesitylene)ruthenium)
RuH [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( 7) 6-benzene ) ( hydride-
( ( S ,
S)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(~ 6-benzene)ruthenium)
RuH [ ( R, R) -TfNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 fi-benzene ) ( hydride- (
( R,
R)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(776-benzene)ruthenium)
RuH [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( 77 6-p-cymene ) ( hydride-
( ( S ,
S)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(776-p-cymene)ruthenium)
RuH [ ( R, R ) -TfNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-p-cymene ) ( hydride-
( ( R,
R)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(~ 6-p-cymene)ruthenium)
~18
CA 02239970 1998-06-08
RuH [ ( S , S ) -TfNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ 6-mes itylene ) (
hydride- ( ( S ,
S)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(776-mesitylene)ruthenium)
RuH [ ( R, R) -TfNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( 77 6-mesitylene ) ( hydride-
( ( R,
R)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(776-mesitylene)ruthenium)
RuH [ ( S , S ) -C6HSSOZNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 6-benz ene ) (
hydride-
((S, S)-N-benzenesulfonyl-1,2-diphenylethylenediamine)(~76-
benzene)ruthenium)
RuH [ ( R, R ) - C6HSSO~NCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( 77 6-benzene ) (
hydride-
((R, R)-N-benzenesulfonyl-1,2-diphenylethylenediamine.)(~ 6-
benzene)ruthenium)
RuH [ ( S , S ) - C6HSSOZNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( 77 s-p-
cymene)(hydride-((S, S)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(r76-p-cymene)ruthenium)
RuH [ ( R, R) - C6HSSOZNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( 77 s-p-
cymene)(hydride-((R, R)-N-trifluoromethanesulfonyl-1,2-
diphenylethylenediamine)(7)6-p-cymene)ruthenium)
RuH [ ( S , S ) - C6H5SOzNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ~ s-
mesitylene)(hydride-((S, S)-N-benzenesulfonyl-1,2-
diphenylethylenediamine)(776-mesitylene)ruthenium)
RuH [ ( R, R ) - C6HSSOZNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ~ s-
mesitylene)(hydride-((R, R)-N-benzenesulfonyl-1,2-
diphenylethylenediamine)(776-mesitylene)ruthenium)
RuH[(S, S)-N-p-Ts-1,2-cyclohexanediamine](7)6-
49
CA 02239970 1998-06-08
benzene)(hydride-((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(R, R)-N-p-Ts-1,2-cyclohexanediamine](776-
benzene)(hydride-((R, R)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(S, S)-N-p-Ts-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(77g-p-cymene)ruthenium)
RuH[(R, R)-N-p-Ts-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((R, R)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH[(S, S)-N-p-Ts-1,2-cyclohexanediamine](776-
mesitylene)(hydride-((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH[(R, R)-N-p-Ts-1,2-cyclohexanediamine](776-
mesitylene)(hydride-((R, R)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH[(S, S)-N-Ms-1,2-cyclohexanediamine](776-
benzene)(hydride-((S, S)-N-methanesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(R, R)-N-Ms-1,2-cyclohexanediamine](776-
benzene)(hydride-((R, R)-N-methanesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(S, S)-N-Ms-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((S, S)-N-methanesulfonyl-1,2-
CA 02239970 1998-06-08
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH[(R, R)-N-Ms-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((R, R)-N-methanesulfonyl-1,2-
cyclohexanediamine)(~ 6-p-cymene)ruthenium)
RuH((S, S)-N-Ms-1,2-cyclohexanediamine](776-
mesitylene)(hydride-((S, S)-N-methanesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH[(R, R)-N-Ms-1,2-cyclohexanediamine](776-
mesitylene)(hydride-((R, R)-N-methanesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH[(S, S)-N-Tf-1,2-cyclohexanediamine](~ 6-
benzene)(hydride-((S, S)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(R, R)-N-Tf-1,2-cyclohexanediamine](776-
benzene)(hydride-((R, R)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH[(S, S)-N-Tf-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((S, S)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH[(R, R)-N-Tf-1,2-cyclohexanediamine](776-p-
cymene)(hydride-((R, R)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH[(S, S)-N-Tf-1,2-cyclohexanediamine](776-
mesitylene)(hydride-((S, S)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
51
CA 02239970 1998-06-08
RuH[(R, R)-N-Tf-1,2-cyclohexanediamine](r76-
mesitylene)(hydride-((R, R)-N-trifluoromethanesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH [ ( S , S ) -N- C6HSSO2-1, 2-cyclohexa-nediamine ] ( 77 6-
benzene)(hydride-((S, S)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH [ ( R, R ) -N- C6HSS02-1, 2-cyclohexanediamine ] ( 77 6-
benzene)(hydride-((R, R)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-benzene)ruthenium)
RuH [ ( S, S ) -N- C6HSS02-1, 2-cyclohexanediamine ] ( 77 6-p-
cymene)(hydride-((S, S)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH [ ( R, R) -N- C6HSSOz-1, 2-cyclohexanediamine ] ( 77 6-p-
cymene)(hydride-((R, R)-N-benzeneesulfonyl-1,2-
cyclohexanediamine)(776-p-cymene)ruthenium)
RuH [ ( S, S ) -N- C6HSSOz-1, 2-cyclohexanediamine ] ( 77 e-
mesitylene)(hydride-((S, S)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
RuH [ ( R, R ) -N- C6HSSOz-1, 2-cyclohexanediamine ] ( 77 s-
mesitylene)(hydride-((R, R)-N-benzenesulfonyl-1,2-
cyclohexanediamine)(776-mesitylene)ruthenium)
Among the compounds represented by the general formula
(VII) in accordance with the present invention, the complex of
the formula (VII) wherein m and n are simultaneously 0 can be
52
CA 02239970 1998-06-08
produced as follows. More specifically,
Ru[(S, S)-, (R, R)-TsNCH(ROl)CH(R02)NH](r) 6-p-cymene)-
(((S, S) and (R, R)-N-toluenesulfonyl-1,2-disubstituted
ethylenediamine)(t) 6-p-cymene)ruthenium (wherein ROl and R02
are the same as described above and Ts is p-toluenesulfonyl
group), is readily synthesized by reacting a raw
material [RuCl2(r~ 6-p-cymene)] 2(tetrachlorobis('g 6-p-
cymene)diruthenium) prepared by the method described in a
reference J. Chem. Soc., Dalton Trans., pp.233 - 241(1974)
with (S, S)-, (R, R)-TsNHCH(ROl)CH(R02)NH2((S, S) and
(R, R)-N-p-toluenesulfonyl-1,2-disubstituted ethylenedia-
mine) in the presence of alkali metal hydroxide or alkali
metal alcolate in a solvent.
The reaction is generally carried out quantitatively,
by reacting a raw material [RuCl2(r) 6-p-cymene)]
2(tetrachlorobis(r) 6-p-cymene)diruthenium (1 mole) and (S,
S)-, (R, R)-TsNHCH(ROl)CH(R02)NH2(((S, S) and (R, R)-N-p-
toluenesulfonyl-1,2-disubstituted ethylenediamine)(2 moles)
with alkali metal hydroxide or alkali metal alcolate in the
stream of inactive gases such nitrogen, helium or argon in
an inactive solvent at a temperature of -10 to 50 °C for 30
minutes to 3 hours, and leaving the reaction product to
stand alone, prior to liquid separation procedure to remove
the aqueous phase, and subsequently removing the solvent
under reduced pressure.
53
CA 02239970 1998-06-08
The alkali metal hydroxide or alkali metal alcolate
specifically includes NaOH, NaOCH3, NaOC2H5, KOH, KOCH3,
KOC2H5, LiOH, Li0CH3, and Li0C2H5, preferably including NaOH
or KOH. The amount of the alkali metal hydroxide or alkali
metal alcolate is 5 to 10 fold the amount of ruthenium. The
inactive solvent appropriately includes for example
hydrocarbons such as benzene, toluene, xylene, cyclohexane,
and methylcyclohexane; ethers such as dimethyl ether,
diethyl ether, diisopropyl ether, methyl tert-butyl ether,
tetrahydrofuran, 1,3-dioxolanee, and 1,4-dioxane;
halogenated hydrocarbons such as chloroform, methylene
chloride and chlorobenzene.
The complex can be produced by another method.
Specifically,
Ru[(S, S)-. (R, R)-TsNCH(RHl)CH(R02)NH](r( 6-p-cymene)(((S,
S) and {R, R)-N-toluenesulfonyl-1,2-disubstituted ethylene-
diamine)(r( 6-p-cymene)ruthenium (wherein R~1 and R~~ are the
same as described above and Ts is p-toluenesulfonyl group ) ,
is readily synthesized by reacting a raw material
RuCl[(S, S)-, (R, R)- TsNCH{ROl)CH(R02)NH2]('~ 6-p-cy-
mene)(chloro-((S, S) and (R, R)-N-p-toluenesulfonyl-1,2-
disubstituted ethylenediamine)(r) 6-p-cymene)ruthenium pre-
pared through the reaction of [RuCl2(r( 6-p-cymene)
2(tetrachlorobis('~ 6-p-cymene)diruthenium, {S, S)-, (R, R)-
TsNHCH(R~l)CH{R02)NH2{(S, S) and {R, R)-N-p-toluenesul-
fonyl-1,2-disubstituted ethylenediamine) with a tertiary
54
CA 02239970 1998-06-08
amine (for example, triethylamine) for example by the method
described in J. Am. Chem. Soc., Vo1.117, pp.7562-7563
(1995), J. Am. Chem. Soc., Vo1.118, pp.2521-2522 (1996) and
J. Am. Chem. Soc., Vo1.118, pp.4916-4917 (1996), in the
presence of alkali metal hydroxide or alkali metal alcolate
in a solvent.
The reaction is generally carried out quantitatively,
by reacting a raw material RuCl[(S, S)-, (R, R)-
TsNCH(RO1)CH(R02)NH2](r~ 6-p-cymene)(chloro-((S, S) and
(R, R)-N-p-toluenesulfonyl-1,2-disubstituted ethylenedi-
amine)('~ 6-p-cymene)ruthenium) (1 mole) with alkali metal
hydroxide or alkali metal alcolate in the stream of inactive
gases such nitrogen, helium or argon in an inactive solvent
at a temperature of -10 to 50°C for 30 minutes to 3 hours,
and leaving the reaction product to stand alone, prior to
liquid separation procedure to remove the aqueous phase, and
subsequently removing the solvent under reduced pressure.
The alkali metal hydroxide or alkali metal alcolate
specifically includes NaOH, Na0CH3, NaOC2H5, KOH, KOCH3,
KOC2H5, LiOH, Li0CH3, and Li0C2H5, preferably including NaOH
or KOH. The amount of the alkali metal hydroxide or alkali
metal alcolate is 1 to 2-fold in mole the amount of
ruthenium. The inactive solvent appropriately includes for
example hydrocarbons such as benzene, toluene, xylene,
cyclohexane, and methylcyclohexane; ethers such as dimethyl
ether, diethyl ether, diisopropyl ether, methyl tert-butyl
CA 02239970 1998-06-08
ether, tetrahydrofuran, 1,3-dioxolane, and 1,4-dioxane; and
halogenated hydrocarbons such as chloroform, methylene
chloride and chlorobenzene.
In accordance with the present invention, the complex
represented by the general formula (V) wherein m and n are
simultaneously 1 can be produced as follows. More
specif ically,
RuH[(S, S)-, (R, R)-TsNCH(RO1)CH(R02)NH2)(r~ 6-p-cymene)-
(hydride-((S, S) and (R, R)-N-toluenesulfonyl-1,2-disubsti-
toted ethylenediamine)(r) 6-p-cymene)ruthenium) (wherein RO1
and R02 are the same as described above and Ts is p-
toluenesulfonyl group), is readily synthesized, by reacting
a raw material Ru[(S, S)-, (R, R)-TSNCH(RO1)CH(R02)NH] (r( 6-
p-cymene)(( (S, S) and (R, R)-N-toluenesulfonyl-1,2-
disubstituted ethylenediamine) (r~ 6-p-cymene) ruthenium)
(wherein RO1 and R02 are the same as defined above; and Ts
represents p-toluenesulfonyl group) in an alcohol solvent.
The reaction is generally carried out quantitatively,
by reacting a raw material Ru[(S, S)-, (R, R)-
TsNCH(ROl)CH(R02)NH] (r) 6-p-cymene)(( (S, S) and (R, R)-N-
toluenesulfonyl-1,2-disubstituted ethylenediamine) (r) 6-p-
cymene)ruthenium)(wherein ROl and R02 are the same as
defined above; and Ts represents p-toluenesulfonyl group) in
an inactive gas stream in an alcohol solvent at a
temperature of 0 to 100°C for 3 minutes to 1 hour for
hydrogen transfer reaction, and subsequently removing the
56
CA 02239970 1998-06-08
solvent under reduced pressure. Appropriate alcohol
solvents include for example methanol, ethanol, n-propanol,
isopropanol, n-butanol, iso-butanol, and sec-butanol.
The complex can be produced by another method.
Specifically,
RuH[(S, S)-, (R, R)-TsNCH(ROl)CH(R02)NH2](~ 6-p-cymene)-(hy-
dride-((S, S) and (R, R)-N-p-toluenesulfonyl-1,2-disub-
stituted ethylenediamine)(~ 6-p-cymene)ruthenium) (wherein
RO1 and R02 are the same as described above and Ts is p-
toluenesulfonyl group), is readily synthesized, by reacting
for example a raw material Ru[(S, S)-, (R, R)-
TsNCH(RO1)CH(R02)NH] (~ 6-p-cymene)(((S, S) and (R, R)-N-
toluenesulfonyl-1,2-disubstituted ethylenediamine) (~ 6-p-
cymene) ruthenium)(wherein RO1 and R02 are the same as
defined above; and Ts represents p-toluenesulfonyl group),
in a solvent in pressurized hydrogen.
The reaction is generally carried out quantitatively,
by hydrogenating a raw material RuH[(S, S)-, (R, R)-
TsNCH(RO1)CH(R02)NH2] (~ 6-p-cymene)(hydride-((S, S) and
(R, R)-N-toluenesulfonyl-1,2-disubstituted ethylenediamine)
(~ 6-p-cymene)ruthenium)(wherein RO1 and R02 are the same as
defined above; and Ts represents p-toluenesulfonyl group),
in an inactive solvent at a temperature of 0 to 50°C for 30
minutes to 24 hours (preferably 1 to 10 hours) in
pressurized hydrogen and subsequently removing the solvent
57
CA 02239970 1998-06-08
under reduced pressure. The hydrogen pressure is within a
range of 1 to 150 atm, preferably 20 to 100 atm.
Appropriate inactive solvents include for example
hydrocarbons such as benzene, toluene, xylene, hexane,
heptane, cyclohexane, and methylcyclohexane; and ethers such
as dimethyl ether, diethyl ether, diisopropyl ether, methyl-
tert-butyl ether, tetrahydrofuran, 1,3-dioxolane and 1,4-
dioxane.
An optically active diamine of the formula (S, S)-,
(R, R)-R03NHCH(ROl)CH(R02)NH2((S, S) and (R, R)-N-
substituted-1,2-disubstituted ethylenediamines) (wherein ROl
R02 and R03 are the same as described above) is synthesized,
by using raw materials (S, S)-, (R, R)-
NH2CH(ROl)CH(R02)NH2((S, S) and (R, R)-1,2-disubstituted
ethylenediamines in a conventional manner [Protective Groups
in Organic Synthesis, Vol.2, pp.309-405(1991)l. More
specifically, (S, S)-, (R, R)-TsNHCH(RO1)CH(R02)NH2((S, S)
and (R, R)-N-P-toluenesulfonyl-1,2-disubstituted
ethylenediamines) (wherein ROl and R02 are the same as
defined above; and Ts represents p-toluenesulfonyl group)
are readily synthesized, by reacting for example (S, S)-,
(R, R)-NH2CH(ROl)CH(R02)NH2((S, S) and (R, R)-1,2-
disubstituted ethylenediamines) as raw materials with TsCl
(p-toluenesulfonyl chloride) in the presence of an alkali
(for example, tertiary amine, alkali metal salts and the
like) in a solvent.
58
CA 02239970 1998-06-08
The reaction is generally carried out quantitatively,
by reacting together
(S, S)-, (R, R)-NH2CH(ROl)CH(R02)NH2(!S, S) and (R, R)-1,2-
disubstituted ethylenediamines) (1 mole) and TsCI (p-
toluenesulfonyl chloride) (1 mole) with an alkali (for
example, triethylamine) in an inactive solvent (for example,
toluene, tetrahydrofuran, and methylene chloride) in an
inactive gas stream such as nitrogen, helium or argon or the
like at a temperature of 0 to 50 for 30 minutes to 3 hours,
subsequently adding water to the resulting mixture to gently
leave the reaction product to stand, prior to liquid
separation procedure, to remove the aqueous phase, and
evaporating the solvent under reduced pressure.
The optically active diamine (S, S)-, (R, R)-
NH2CH(ROl)CH(R02)NH2((S, S) and !R, R)-1,2-disubstituted
ethylenediamines)( wherein ROl and R02 are the same as
defined above), is known and is sometimes commercially
available or can be produced in a conventional manner or by
canventional resolution process of racemates [Tetrahedron
Lett., Vo1.32, pp.999-1002) (1991), Tetrahedron Lett.,
Vo1.34, pp_1905-1908 (1993)1.
(S, S) and (R, R)- 1,2-diphenylethylenediamines and (S,
S) and (R, R)- 1,2-cyclohexanediamines are commercially
available.
For example, the optically active diamine of the general formula
(e) can be produced by the following method [Tetrahedron
59
CA 02239970 1998-06-08
Lett., Vo1.32, pp.999-1002 (1991)].
The optically active diamine of the general formula (e)
((S, S) and (R, R)-1,2-disubstituted ethylenediamines) can be
produced readily at a high yield, by preparing cyclophosphate
from raw materials optically active 1,2-disubstituted ethylene
diols, which is then reacted with amidine to recover imidazoline,
and ring opening the imidazoline by using an acid catalyst.
The ruthenium-diamine complex of the present invention may
be isolated and used, but while generating the complex in a
reaction solution, the resulting complex is used as a catalyst
for asymmetric synthesis and the like.
The method for producing optically active secondary
alcohols by utilizing the complex of the present invention as
a hydrogen transfer-type oxidation catalyst will now be
described below.
The racemic secondary alcohols or meso-type diols to be
used as the reaction substrates for producing optically active
secondary alcohols are represented by the aforementioned
formulas ( VII I ) and ( IXI ) . In the formula ( VIII ) , the racemic
secondary alcohols in this case specifically include
1-phenylethanol, 1-(2-methylphenyl)ethanol, 1-(2-
ethylphenyl)ethanol, l-(2-isopropylphenyl)ethanol, 1-(2-
tert-butylphenyl)ethanol, 1-(2-methoxyphenyl)ethanol, 1-(2-
ethoxyphenyl)ethanol, 1-(2-isopropoxyphenyl)ethanol, 1-(2-
tert-butoxyphenyl)ethanol, 1-(2-dimethylaminophenyl)ethanol,
CA 02239970 1998-06-08
1-(3-methylphenyl)ethanol, 1-(3-ethylphenyl)-ethanol, 1-(3-
isopropylphenyl)ethanol, 1-(3-tert-butylphenyl)ethanol, 1-
(3-methoxyphenyl)ethanol, 1-(3-ethoxyphenyl)ethanol, 1-(3-
isopropoxyphenyl)ethanol, 1-(3-tert-butoxyphenyl)ethanol, 1-
(3-dimethylaminophenyl)-ethanol, 1-(4-methylphenyl)ethanol,
1-(4-ethylphenyl)-ethanol, 1-(4-isopropylphenyl)ethanol, 1-
(4-tert-butyl-phenyl)ethanol, 1-(4-methoxyphenyl)ethanol, 1-
(4-ethoxy-phenyl)ethanol, 1-(4-isopropoxyphenyl)ethanol, 1-
(4-tert-butoxyphenyl)ethanol, 1-(4-dimethylaminophenyl)-
ethanol, 1-cumenylethanol, 1-mesitylethanol, 1-xylylethanol,
1-(1-naphthyl)ethanol, 1-(2-naphthyl)ethanol, 1-phenanthryl-
ethanol, 1-indenylethanol, 1-(3,4-dimethoxyphenyl)ethanol,
1-(3,4-diethoxyphenyl)ethanol, 1-(3,4-methylenedioxy-
phenyl)ethanol, 1-ferrocenylethanol, 1-phenylpropanol, 1-(2-
methylphenyl)propanol, 1-(2-ethylphenyl)propanol, 1-(2-
isopropylphenyl)propanol, 1-(2-tert-butylphenyl)propanol, 1-
(2-methoxyphenyl)propanol, 1-(2-ethoxyphenyl)propanol, 1-(2-
isopropoxyphenyl)propanol, 1-(2-tert-butoxyphenyl)-propanol,
1-(2-dimethylaminophenyl)propanol, 1-(3-methylphenyl)-
propanol, 1-(3-ethylphenyl)propanol, 1-(3-isopropyl-
phenyl)propanol, 1-(3-tert-butylphenyl)propanol, 1-(3-
methoxyphenyl)propanol, 1-(3-ethoxyphenyl)propanol, 1-(3-
isopropoxyphenyl)propanol, 1-(3-tert-butoxyphenyl)-propanol,
1-(3-dimethylaminophenyl)propanol, 1-(4-
methylphenyl)propanol, 1-(4-ethylphenyl)propanol, 1-(4-
isopropylphenyl)propanol, 1-(4-tert-butylphenyl)propanol, 1-
61
CA 02239970 1998-06-08
(4-methoxyphenyl)propanol, 1-(4-ethoxyphenyl)propanol, 1-(4-
isopropoxyphenyl)propanol, 1-(4-tert-butoxyphenyl)-propanol,
1-(4 -dimethylaminophenyl)propanol, 1-cumenyl-propanol, 1-
mesitylpropanol, 1-xylylpropanol, 1-(1-naphthyl) propanol,
1-(2-naphthyl)propanol, 1-phenanthryl-propanol, 1-
indenylpropanol, 1-(3,4 -dimethoxyphenyl) propanol, 1-(3,4-
diethoxyphenyl) propanol, 1-(3,4-methyl-enedioxyphenyl)
propanol, 1-ferrocenylpropanol, 1-phenyl-butanol, 1-(2-
methylphenyl)butanol, 1-(2-ethylphenyl)-butanol, 1-(2-
isopropylphenyl)butanol, 1-(2-tert-butyl-phenyl)butanol, 1-
(2-methoxyphenyl)butanol, 1-(2-ethoxy-phenyl)butanol, 1-(2-
isopropoxyphenyl)butanol, 1-(2-tert-butoxyphenyl)butanol, 1-
(2-dimethylaminophenyl)butanol, 1-(3-methylphenyl)butanol,
1-(3-ethylphenyl)butanol, 1-(3-isopropylphenyl)butanol, 1-
(3-tert-butylphenyl)butanol, 1-(3-methoxyphenyl)butanol, 1-
(3-ethoxyphenyl)butanol, 1-(3-isopropoxyphenyl)butanol, 1-
(3-tert-butoxyphenyl)butanol, 1-(3-dimethylamino-
phenyl)butanol, 1-(4-methylphenyl)-butanol, 1-(4-
ethylphenyl)butanol, 1-(4-isopropylphenyl)-butanol, 1-(4-
tert-butylphenyl)butanol, 1-(4-methoxy-phenyl)butanol, 1-(4-
ethoxyphenyl)butanol, 1-(4-isopropoxy-phenyl)butanol, 1-(4-
tert-butoxyphenyl)butanol, 1-(4-dimethylaminophenyl)butanol,
1-cumenylbutanol, 1-mesityl-butanol, 1-xylylbutanol, 1-(1-
naphthyl)butanol, 1-(2-naphthyl)butanol, ~-
phenanthrylbutanol, 1-indenylbutanol, 1-(3,4-
dimethoxyphenyl)butanol, 1-(3,4-diethoxyphenyl)-butanol, 1-
62
CA 02239970 1998-06-08
(3,4-methylenedioxyphenyl)butanol, 1-ferrocenyl-butanol, 1-
phenylisobutanol, 1-(2-methylphenyl)isobutanol, 1-(2-
ethylphenyl)isobutanol, 1-(2-isopropylphenyl)-isobutanol, 1-
(2-tent-butylphenyl)isobutanol, 1-(2-
methoxyphenyl)isobutanol, 1-(2-ethoxyphenyl)isobutanol, 1-
(2-isopropoxyphenyl)isobutanol, 1-(2-tert-butoxyphenyl)-
isobutanol, 1-(2-dimethylaminophenyl)isobutanol, 1-(3-
methylphenyl)isobutanol, 1-(3-ethylphenyl)isobutanol, 1-(3-
isopropylphenyl)isobutanol, 1-(3-tert-butylphenyl)-
isobutanol, 1-(3-methoxyphenyl)isobutanol, 1-(3-ethoxy-
phenyl)isobutanol, 1-(3-isopropoxyphenyl)isobutanol, 1-(3-
tert-butoxyphenyl)isobutanol, 1-(3-dimethylaminophenyl)-
isobutanol, 1-(4-methylphenyl)isobutanol, 1-(4-ethyl-
phenyl)isobutanol, 1-(4-isopropylphenyl)isobutanol, 1-(4-
tert-butylphenyl)isobutanol, 1-(4-methoxyphenyl)isobutanol,
1-(4-ethoxyphenyl)isobutanol, 1-(4-isopropoxyphenyl)-
isobutanol, 1-(4-tent-butoxyphenyl)isobutanol, 1-(4-
dimethylaminophenyl)isobutanol, 1-cumenylisobutanol, 1-
mesitylisobutanol, 1-xylylisobutanol, 1-(1-naphthyl)iso-
butanol, 1-(2-naphthyl)isobutanol, 1-phenanthrylisobutanol,
1-indenylisobutanol, 1-(3,4-dimethoxyphenyl)isobutanol, 1-
(3,4-diethoxyphenyl)isobutanol, 1-(3,4-methylenedioxy-
phenyl)isobutanol, 1-ferrocenylisobutanol, 1-phenyl-
pentanol, 1-(2-methylphenyl)pentanol, 1-(2-ethylphenyl)-
pentanol, 1-(2-isopropylphenyl)pentanol, 1-(2-tert-butyl-
phenyl)pentanol, 1-(2-methoxyphenyl)pentanol, 1-(2-ethoxy-
63
CA 02239970 1998-06-08
phenyl)pentanol, 1-(2-isopropoxyphenyl)pentanol, 1-(2-tert-
butoxyphenyl)pentanol, 1-(2-dimethylaminophenyl)pentanol, 1-
(3-methylphenyl)pentanol, 1-(3-ethylphenyl)pentanol, 1-(3-
isopropylphenyl)pentanol, 1-(3-tent-butylphenyl)-pentanol,
1-(3-methoxyphenyl)pentanol, 1-(3-ethoxyphenyl)-pentanol, 1-
(3-isopropoxyphenyl)pentanol, 1-(3-tert-butoxy-
phenyl)pentanol, 1-(3-dimethylaminophenyl)pentanol, 1-(4-
methylphenyl)pentanol, 1-(4-ethylphenyl)pentanol, 1-(4-
isopropylphenyl)pentanol, 1-(4-tert-butylphenyl)pentanol, 1-
(4-methoxyphenyl)pentanol, 1-(4-ethoxyphenyl)pentanol, 1-(4-
isopropoxyphenyl)pentanol, 1-(4-tert-butoxyphenyl)-pentanol,
1-(4-dimethylaminophenyl)pentanol, 1-cumenyl-pentanol, 1-
mesitylpentanol, 1-xylylpentanol, 1-(1-naphthyl)pentanol, 1-
(2-naphthyl)pentanol, 1-phenanthrylpentanol, 1-
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CA 02239970 1998-06-08
indenylpentanol, 1-(3,4-dimethoxyphenyl)pentanol, 1-(3,4-
diethoxyphenyl)pentanol, 1-(3,4-
methylenedioxyphenyl)pentanol, 1-ferrocenylpentanol, 1-
indanol, 1, 2, 3,4-tetrahydro-1-naphthol, 2-cyclopenten-1-ol,
3-methyl-2-cyclopenten-1-ol, 2-cyclohexen-1-ol, 3-methyl-2-
cyclohexen-1-ol, 2-cycloheptan-1-ol, 3-methyl-2-
cycloheptan-1-ol, 2-cyclooctan-1-ol, 3-methyl-2-cyclooctan-
1-0l, and 4-hydroxy-2-cyclopenten-1-one. Additionally, the
meso-type diol represented by the formula (IX) specifically
represents meso-2-cyclopenten-1,4-diol, meso-2-cyclohexane-
1,4-diol, meso-2-cycloheptane-1,4-diol, meso-2-cyclooctan-
1,4-diol, 5,8-dihyroxy-1,4,4a, 5, 8, 8a-hexahydro-endo-1,4-
methanonaphtharene and the like.
As the ruthenium-diamine complex to be used for the hydrogen
transfer-type oxidation of the present invention, the optically
act-ive ligand diamine of the general formula ( VI I ) , namely ( R,
R) form or ( S, S ) form, may satisfactorily be used. Depending
on the selection, an objective compound of the desired absolute
configuration can be produced. Such ruthenium-diamine complex
can be used at 1/10, 000 to 1/10 fold in mole, preferably 1/2, 000
to 1/200 fold in mole to the substrate compound.
For carrying out the reaction, the substrate compound and
the ruthenium-diamine complex are added to ketone alone or an
appropriate mixture of ketone with an inactive solvent, to
prepare a homogenous solution, for reaction at a reaction
CA 02239970 1998-06-08
temperature of 0 to 100°C , preferably 10 to 50°C for 1 to
100 hours, preferably 3 to 50 hours.
Ketones including for example acetone, methyl ethyl
ketone, diethyl ketone, diisopropyl ketone, methyl tert-
butyl ketone, cyclopentanone, and cyclohexanone are used.
More preferably, acetone is better. These ketones may
satisfactorily be used singly or in a mixture with an
inactive solvent. Ketones can be used at an amount of 0.1
to 30 fold (volume/weight), depending on the type of the
substrate, but preferably at an amount of 2 to 5 fold
(volume/weight).
Appropriate inactive solvents include for example
hydrocarbons such as benzene, toluene, xylene, hexane,
heptane, cyclohexane, and methylcyclohexane; and ethers such
as dimethyl ether, diethyl ether, diisopropyl ether, methyl
tert-butyl ether, tetrahydrofuran, 1,3-dioxolane, and 1,4-
dioxane.
In accordance with the present invention, the reaction
may be carried out in a batchwise manner or a continuous
manner.
The resulting product can be purified by known
processes such as silica gel column chromatography.
66
CA 02239970 2004-02-25
EXAMPLES
Exam~~le A
<Production of optically active alcohols>
Production examples of optically active alcohols are
shown below, and the inventive method will further be
described in detail. Tables 1, 2 and 3 collectively show
reaction substrates, transition metal complexes and
optically active amine compounds as chiral ligands, which
are to be used as typical examples.
The instrumental analy is was done by using the
following individual systems.
NMR: JEOL GSX-400/Varian Gemini-200 (1H-NMR sample: TMS,
31P-NMR standard sample: phosphoric acid)
GLC: SHIMADZU GC-17A(column: chiral CP-Cyclodextrin-b-236-
M19)
HPLC: JASCO GULLIVER (column: CHIRALCEL*OJ, OB-H, OB, OD)
* Trade-mark
67
CA 02239970 1998-06-08
Table 1
Carbonyl compounds
O I \ 0 0
w /
i ~ R \ ~ ~ \ I
R~ \ z
~ 2 3 4
a R~ .. H, Rz - CHI
b R, - H, RZ - C=NS
c R, - H, Rz .. CH(CH~)z O
d R, - H. R= - C(CH~)~ / /
Ri - CHI, Rz = CHI
f R~ - Ci, Rz - CHI . NC OCH~
g R, .. OCH~, RZ 3 CHI
h R~ -CN, Rz -CHI. 5
R, - H, Ri < (CH2)~COZCzHs
O O 0 ' O
O
R \ ( \ ~ l .l I l
S S S
O S
6 R -~ CHZ 8 9 10 ~ 1 1
7 R - (CH~Z
I \ O COiCH~
/ \ \
Cl \ N
12
63
CA 02239970 1998-06-08
ab a 2
jRuCl( ateno)2Z
arena = ~ ~ . ~ ~ .
v
13 14 15 16
Asymmetric metal complexes
/ I ~ ArSO= / I ' ' ArSOZ '''
~H /
~..
Ru~ Ru
H2 SCI CI ~
27 (S,5) 28 (R,Ry
Table 3
CHI NHCH~ ~ I NHCH~ ~ I NHz
I 'OH \ I ~OH \ I , ~OH
m (~s.zr-~ ~s (~s, zr~ 21 (1s. 2~
~a (ls,2s) 2o (ls.zs~ z2 (ls,zs7
w . w I w
I , I , /
PhzP NtiZ PhzP N(CH~~~ PhzP NHz Ph2P NliZ
24 (~ Zg (~ 26 (.S~ ,
f;
CA 02239970 1998-06-08
Examples 1 through 19'
To dry 2-propanol (5.0 m1) were added various amino
alcohol compounds (0_05 mmol) as chiral ligands of optically
active amine compounds as shown in Table 3 and the ruthenium
arene complex (0.0125 mmol) shown in Table 2, for agitation
in argon or nitrogen gas atmosphere at 80°C for 20 minutes,
and the resulting mixture was cooled to room temperature, to
which were then added frozen and degassed dry 2-propanol
(45.0 ml), various carbonyl compounds (5 mmol) deaerated and
distilled as shown in Table 1, and a solution of 0.05M KOH
in 2-propanol (2.5 ml: 0.125 mmol) in this order, for
subsequent agitation at room temperature. After completion
of the reaction, dilute hydrochloric acid was added to
adjust the resulting mixture to acidity, from which most of
2-propanol was evaporated off under reduced pressure,
followed by addition of saturated sodium chloride solution.
The resulting product was extracted into ethyl acetate,
rinsed with saturated sodium chloride solution several times
and dried over anhydrous sodium sulfate. The solvent was
distilled off from the product. The final product was
analyzed by 1H-NMR (CDC13), to calculate the conversion.
Then, the product was purified by thin-layer silica gel
chromatography, and the isolated alcohol fraction was used
to determine the optical purity and absolute configuration
by HPLC or GLC. The results are collectively shown in
Table 4. Furthermore, the conversion and optical
CA 02239970 1998-06-08
purity of the sampled reaction solution can be calculated
simultaneously by GLC.
Examples 20 to 23
Using the same method as in Example 1, aminophosphine
compound was used as an optically active amine compound for the
reaction. The results are collectively shown in Table 4.
71
CA 02239970 1998-06-08
Table 4
Carbonyl
Examples [RuC I z (arene)Ligands Tme a cony% conf
~ z ee i
g
compounds .
1 13 19 la I 64 52 S
2 I3 20 la I 91 17 S
3 14 20 la 1 97 59 S
4 14 21 Ia 1 97 56 S
15 20 la 1 97 56 S
6 15 21 la 1 62 52 S
7 16 17 la 1 95 91 S
8 16 20 la 1 94 92 S
9 16 21 la 1 59 55 - S
16 22 la 1 96 75 S
11 16 20 1b 2 95 82 S
12 I6 20 lc 15 93 5 S
13 16 20 1d 20 22 40 R
14 16 20 o-Le 6 96 83 S
I6 18 o-if 1 99 89 S
16 16 20 p-lg 4 73 79 S
17 16 20 3 2 99 93 S
18 16 18 4 3 93 75 S
19 16 16 7 4 62 94 S
I 3 23 I a 1 65 0. S
4
21 13 2=1 1 a 1 6 I 61 R
22 I3 25 1a 1 70
23 13 26 La I 73 4 S
;p
CA 02239970 1998-06-08
Exam~ales 24 to 41
By using the same method as described in Example 1 and
using optically active amine compounds, the chiral Ru
complexes shown in Table 2 were synthesized. The complex
catalysts and carbonyl compounds were added to a mixture of
formic acid and triethylamine (5:2), for reaction at room
temperature for a given period. After completion of the
reaction, the reaction mixture was diluted with water, to
extract the product in ethyl acetate. After drying the
organic phase over anhydrous sodium sulfate and evaporating
the solvent off, 1H-NMR (CDC13) was analyzed to calculate
the conversion. The optical purity and absolute
configuration were determined by HPLC or GLC. The results
are collectively shown in Table 5. The conversion and
optical purity of each sampled reaction solution can be
calculated simultaneously by GLC.
In accordance with the present invention, optically
active alcohols can be produced at a high optical purity and
a high synthetic yield.
73
CA 02239970 1998-06-08
Table 5
Carbonyl _
ExamplesRu complex compounds Time ~ conv o ee Conf
ig.
24 27(S, S) la 24 >99 98 S
25 27 (S, S) 1b 60 >9g g7 S
26 27 (S, S) m-1 f 21 >99 97 S
27 27(S, S) p-if 24 >99 95 S
28 27 (S. S) m-lg 20 >99 98 S
29 27(S, S) p-Ig 50 >99 97 S
30 27(S. S) p-lh 14 >99 90 S
31 27(S. S) 1 i 60 >99 95 S
32 27 (S, S) 2 60 93 83 S
33 27 (S, S) 3 22 >99 96 S
34 27(S. S) 5 60 >54 66 S
35 27(S. S) 6 48 >99 99 S
36 27(S. S) 7 48 >99 99 S
37 27 (S, S) 8 60 70 82 S
38 27 (S, S) 9 40 47 9? S
39 28(R, R) 10 40 95 99 R
40 28 (R. R) 11 65 95 98 R
41 28(R. R) 12 ?2 68 92 R
CA 02239970 1998-06-08
Example B
<Production of optically active amines>
Production examples of optically active amines are shown
below and the present inventive method will be described in
detail. Tables 6 and 7 show reaction substrates and asymmetric
metal catalysts to be possibly used as typical examples.
The instrumental analysis was done by using the following
individual systems.
NMR: JEOL GSX-400/Varian Gemini-200 (1H-NMR sample: TMS, '1P-NMR
standard sample: phosphoric acid)
GLC: SHIMADZU GC-17A(column: chiral CP-Cyclodextrin-b-236-
M19)
HPLC: JASCO GULLIVER (column: CHIRALCEL OJ, OB-H, OB, OD)
The absolute configurations of the resulting optically
active amine compounds were determined on the basis of optical
rotation and by HPLC and X-ray structural analysis . Blanks are
not definitely shown.
CA 02239970 1998-06-08
Table 6
Imine compounds
cH,o , I , [
i
I /
CH~O ~ ~ - ~ ~ ~ [ ( ~ N \, ~ i
N
R .CsHs R
2a: Ft - CHI ' J 4a: R ~ CHI 5
2b: R - ~,4-(CH,O)=C,H,CH, 4b: R - C,HS
2c: R - 3,~-(CH~O)=C~H~(CHi)Z
2d: R - C,Hs
Ie: R - 3,4-(CH~O)~C~lil ~N
2f: R - C,HSCHZ - ~ N
ZQ: R - 1-CN~C;H~ ' CiHf
. CHs
' 6 7
N~
' / N~. / I N~ / . N / I
[
[ I I [ ~ w
S .S
. O=
a 9 ' 1a
x / ~ N ~ [ [ I
N
~ [ /
/ w
I
l2a:X-H 13 14
12D:X-C!
12c: X ~ CH~O
Enamine compounds
i
N
i
7G
CA 02239970 1998-06-08
Table 7
Asymmetric metal complexes
( ..,. ~ I
_ ~ N' /\ ; Rn Rn
Ftu Ru
Ni ~C~ C~ i wN \
so Ar ' )
s . - ArSOi
. {R.RI-1
a: ~°-arena -p.cymene ; Ar-p.CH~C°H~
b: ~'-arena .. p.cYmene ; Ar - 2,4,6-{CH~j~CsHZ
c: r~'-arena .. benzene ; Ar - 1-naphihyl
d: r~'-arena - benzene ; Ar- 2,4,6-(CH~)~C'HZ
e: ~.'-arena . benzene ; Ar .. P.CH~C'H,
i7
CA 02239970 1998-06-08
Example 42
6,7-Dimethoxy-1-methyl-3,4-dihydroxyisoquinoline (Table
6-2a) (1.03 g, 5 mmol) and a ruthenium catalyst (Table 7)
(R, R)-la (16 mg, 0.025 mmol) were dissolved in acetonitrile
( 10 ml ) , followed by addition of a mixture of formic acid-
triethylamine (5 . 2), for agitation at 28°C for 3 hours.
To the reaction mixture was added an aqueous sodium
carbonate solution to extract the product in ethyl acetate.
After evaporation of the solvent, 1H-NMR(CDC13) of the
resulting product was measured to calculate the conversion.
Then, the product was purified by silica gel chromatography,
to determine the optical purity and absolute configuration
of the resulting optically active amine by HPLC or GLC. As
collectively shown in Table 8, (S)-6,7-dimethoxy-1-methyl-
1,2,3,4-tetrahydroisoquinoline (1.02 g, yield of 99 ~, 96 g
ee) was obtained.
Examples 43 to 69
By using the same reactor as in Example 42 but using
different reaction substrates, catalysts, reaction solvents
and ratios of reaction substrates/catalysts, the same
experimental procedures as in Example 42 were carried out.
The results are collectively shown in Table 8.
78
CA 02239970 1998-06-08
Example 70
Using the same reactor as in Example 42, the enamine
compound was used for the same experimental procedures as in
Example 42, so that the reaction progressed in a smooth manner,
to recover the corresponding optically active amine compound.
The results are collectively shown in Table 8.
Comparative Example 1
Under the same conditions as in Example 42, ruthenium-
arene catalysts with no optically active amine ligands were used
as catalysts, so that the reaction was facilitated, to recover
a racemic amine compound quantitatively.
Comparative Example 2
Under the same conditions as in Example 51, ruthenium-
arene catalysts with no optically active amine ligands were used
as catalysts, so that no reaction was never facilitated.
As has been described above in detail, in accordance with
the present invention, optically active amines can be produced
at a high yield and an excellent optical purity.
l~
CA 02239970 1998-06-08
Table 8
Amines -
Examples IminesCatalystsS/C SolventsTime yield ee.
, h % % absolute
configuration
42 2a (R. R)-la200 CH,GY 3 99 96 S
43 2a - (R. 200 CHzCIz 3 99 94 S
R)-la
44 2a (S. S)-la200 CHzCIz 3 99 93 R
45 2a (R. R)-la200 aceto ne 3 99 95 S .
46 2a (R.R)-1a 200 D M 3 99 95 S
F
47 2a (R. R)-la200 DMSO 3 99 95 S
48 2a (R.R)-la 1000 CH=Clz 98 99 90 S
49 2b (S. S)-la200 CHzCIz 8 81 87 R
50 2c (S. S)-lb200 CHzCIz 16 99 92 R
51 2d (S. S)-Lc200 CHzC(z 8 99 84 R
52 2e (S.S)-lc 100 CHZCIz 12 96 84 R
53 2f (R. R)-le200 CHZCIz 18 68 82
54 2g (R.R)-le 200 CHZCIx 14 94 98
55 3 (S.S)-la 200 CHzCIz I6 99 84
56 4a (S. S)-La200 DMF 5' 86 97 R
57 46 (S.S)-la 200 D M 5 83 96 R
F
58 5 (R.R)-le 200 CHzCIz 48 59 78
59 6 (S. S)-Ic200 CHZCIz 39 22 47 S
60 7 (S.S)-lc 200 CHzCIZ 40 100 34
6I 8 (S.S)-lc I00 CHzCIZ 6 90 89 S
62 9 (S.S)-lc 100 CHzCI= 12 64 88 S
63 10 (S. S)-1d200 CHxCIz 36 72 77 S
64 11 (R. R)-le200 CHZCIz 15 13 36
65 12a (R.R)-le 200 CHZCIz 37 43 46
66 12b (R.R)-1e 200 CHzCIx 109 35 36
67 12c (R. R)-le200 CHZCIz 65 67 25
68 13 (S. S)-Ic200 CHZCIz 16 82 6~1
69 l~l (S. S)-1e200 CHZCIZ 67 r1 I2 R
70 15 (S. S)-le200 CHZCI, I2 69 ~3
[In the table, s/c means the molar ratio of
substrate/ruthenium-optically active diamine complex.]
CA 02239970 2004-02-25
Example C
<production of optically active secondary alcohols by kinetic
resolution method. of alcohols>
Production examples of optically active secondary alcohols
are shown below, and the inventive method will further be
described in detail. However, the invention is not limited to
these examples. Collectively, Table 9 shows racemic secondary
alcohols or meso-type diols to bye used as typical examples and
Table 10 shows ruthenium-diamine complexes.
Abbreviations used in the present Example are as follows .
representing the number of carbon atoms bonded to the metal
of unsaturated ligand; and hexahapto ( 6 carbon atoms bonded to
metal) is expressed as
The instrumental analysis was done by using the following
individual systems.
NMR: JEOL GSX-400/Varian Gemini-200 ( 1H-NMR internal standard:
TMS)
GLC: SHIMADZU GC-17A(column: chiral CP-Cyclodextrin-b-236-
M19)
HPLC : JASCO GULLIVER ( column : CHIRALCEI* OJ, OB-H, OB, OD-H, OD )
* Trade-mark
81
CA 02239970 1998-06-08
Table 9
OH OH OH
RO
' ' 1
R W I RO W ( W ( R
t a : R-H 2a : R-CHI 3a : R-CHz
t b : R-CH30 2b : R-R=CHz 3b : R-(CHz)z
t c : R-(CH~)zN
OH ~ OH
0 I
Fe R
U . 5a : R-H
5b : R-CHI
HO H HO H OH OH
H ~ H . '
HO O OH O
g 7 f3 9
g~~
CA 02239970 1998-06-08
Table 10
Ts
Calls .. N~ Cells . Ts X
~Ru-X
C H N~Ru/
a s ' ~ Cells ~ H ~H
2
t 0 : X _- p..cymene 12 : X = p-cymene
1 1 : X = mesitylene 13 : X = mesitylene
Ts Ts
N~ . N~ /X
H ~Ru X ~Ru
. ~ b ~H
2
14 : X = ~cymene 16 : X = ~.cymene
i 5 : X = mesitylene 17: X = mesityfene.
S:3
CA 02239970 1998-06-08
Reference Example 1
Synthesis of RuCl[(S, S)-p-TsNCH(C6H5)CH(C6H5)NH2j(~ 6-p-
cymene)(chloro((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)(~ 6-p-cymene)ruthenium
[RuCl2(~ 6-p-cymene)j 2(tetrachlorobis(~ 6-p-
cymene)diruthenium) (1.53 g: 2.5 mmol) and (S, S)-p-
TsNCH(C6H5)CH(C6H5)NH2((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine) (1.83 g; 5.0 mmol) and
triethylamine (1.4 ml; 10 mmol) are dissolved in 2-propanol
(50 ml) in a Schlenk's reactor which is preliminarily dried
in vacuum and of which the inside is then substituted with
argon. The reaction solution was agitated at 80 for 1 hour
and is then condensed, to recover crystal, which was then
filtered and rinsed with a small amount of water, followed
by drying under reduced pressure to recover orange crystal
(2.99 g). The yield is 94 ~.
m.p.> 100°C (decomposed)
IR(KBr)[cm 1j . 3272, 3219, 3142, 3063
3030, 2963, 2874
1H-NMR (400 MHz, 2H-chloroform, S): ppm
1.32 (d. 3H) 1.34 (d. 3H) 2.19 (s. 3H) 2.28 (s. 3H)
3.07 (m. 1H) 3.26 (m. 1H) 3.54 (m. 1H) 3.54 (m. 1H) 3.66 (d.
1H), 5.68 (d. 1H) 5.70 (d. 1H) 5.72 (d. 1H) 5.86 (d. 1H)
6.61 (m. 1Hh) 6.29-7.20 (m. 14H)
84
CA 02239970 1998-06-08
Elemental analysis
( C,1H,SCIN~OzRus )
C H N C1 Ru
Theoretical values (%) 58.53 5.54 4.40 5.57 15.89
Elemental values (%) 58.37 5.44 4.36 5.75 18.83
The present catalyst was tested by X-ray crystallography.
It was indicated that the complex was of a structure satisfying
the analysis results.
Reference Example 2
Synthes is of RuCl [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH= ] ( ~7 6
mesitylene)(chloro((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-mesitylene)ruthenium
Instead of [ RuCl~ ( ~ 6-p-cymene ) ] ~ ( tetrachlorobis ( ~7
p-cymene)diruthenium),
[ RuClz ( 7) 6-mes itylene ) ] z ( tetrachlorobis ( 77 6-
mesitylene)diruthenium) was used, and by the same procedures
as in the Reference Example 1, the aforementioned catalyst was
recovered as orange crystal. The yield was 64 %.
m.p. 218.6-222.5 (decomposed)
1H-NMR (400 MHz, ZH-chloroform, ~ ) : ppm
2. 2 4 C 3 H) . 2. 3 8 < s . 9 H) . 3 . 6 9 C d d. 1 H) , 3 . ?
9 Cd. 1 H) . 3. 9 9 Cd d. 1 H) . 4.. 1 9 Cb r d. 1 H) , S. 3
0 C s . 3 H) . 6 . 6 S - 6 . 9 3 Cm. 9 H) . 7. 0 6 - 7 . 1 5 Cm.
3 H) . 7. 3 S <d. 2 H)
CA 02239970 1998-06-08
Reference Example 3
Synthesis of RuCl[(S, S)-N-p-Ts-cyclohexane-1,2-diamine](
6-p-cymene)(chloro-((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( ~ 6-p-cymene)ruthenium)
Instead of ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHz ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine), (S, S)-N-p-
Ts-cyclohexane-1,2-diamine)((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine ) was used, and by the same procedures as in
the Reference Example 1, the aforementioned catalyst was
recovered as orange crystal. The yield is 60 ~.
Reference Example 4
Synthesis of RuCl[(S, S)-N-p-Ts-cyclohexane-1,2-diamine]( 77
6-mesitylene)(chloro-((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( 776-mesitylene)ruthenium
Instead of ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHS ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine), (S, S)-N-p-
Ts-cyclohexane-1,2-diamine)((1S, 2S)-N-p-toluenesulfonyl-
1,2-cyclohexanediamine) was used, and by the same procedures
as in the Reference Example 2, the aforementioned catalyst was
recovered as orange crystal. The yield is 58 %.
Example 71-a
Synthes is of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-
cymene)((S, S)-N-p-toluenesulfonyl-1,2-diamine)( 776-p-
86
CA 02239970 1998-06-08
cymene)ruthenium)
[ RuClZ ( ~7 6-p-cymene ) ] ~ ( tetrachlorobis ( 77 6-p-
cymene)diruthenium) (306.2 mg; 0.5 mmol) and (S, S)-p-
TsNCH ( C6H5 ) CH ( C6H5 ) NHz ( ( S , S ) -N-p-toluenesulfonyl-1, 2-
diphenylethylenediamine) (366.4 mg; 1.0 mmol) and potassium
hydroxide ( 400 mg; 7 .1 mmol ) are dissolved in methylene chloride
(7 ml) in a Schlenk's reactor which is preliminarily dried in
vacuum and of which the inside is then substituted with argon.
The reaction solution was agitated at room temperature for 5
minutes, and by adding water (7 ml) to the reaction solution,
the color of the reaction solution turned from orange to deep
purple. The organic phase was separated and rinsed in water
(7 ml). The organic phase was dried over calcium hydroxide,
from which the solvent was distilled off. Then, the resulting
product was dried under reduced pressure, to recover catalyst
No.lO of deep purple crystal (522 mg) in Table 10. The yield
is 87
m.p.> 80 °C (decomposed)
IR(KBr)[cml] . 3289, 3070, 3017, 2968
2920, 2859
1H-NMR (400 MHz, ZH-toluene, ~): ppm
1. 2 0 Cd. 3 H) . 1. 2 S Cd. 3 H) . 2. 0 5 Cs. 3 H) . 2.
Cs. 3 E-E) . 2. ~ 3 Cm. 1 H) . ~. 0 S Cd. 1 E-E) . :1. S 9
Cs. 1 E-E) . 5. 1 1 Cd. 1 E-E) . ~. 2 r Cd. 1 H) . ~. 2 S CcE.
1 H) . ~. 3 9 Cd. 1 E-E) . 6. 6 .1 Co c d. 1 H) . 6. S r Cd.
H) . .. 6 i .d. '? H) . a. ? - . . a ~;rn. 1 0 H>
8r
CA 02239970 1998-06-08
Elemental analysis
( C31H34NZ02RuS )
C H N Ru
Theoretical values (%) 62.09 5.71 4.67 16.85
Elemental values (~) 62.06 5.77 4.66 16.47
The present catalyst was tested by X-ray crystallography.
It was indicated that the complex was of a structure satisfying
the analysis results.
Example 71-b
Alternative synthes is of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] (
77
6-p-cymene)((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-p-cymene)ruthenium)
RuCl [ ( 1S , 2S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ 6-p-
cymene)(chloro-(1S, 2S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( ~ 6-p-cymene)ruthenium) (318.6 mg;
0.5 mmol) and potassium hydroxide (200 mg; 3.5 mmol) are
dissolved in methylene chloride (7 ml) in a Shlenk~s reactor
which is preliminarily vacuum dried and of which the inside is
substituted with argon. The reaction solution was agitated at
room temperature for 5 minutes, and by adding water (7 ml) to
the reaction solution, the color of the reaction solution turned
from orange to deep purple. The organic phase was separated
and rinsed in water (7 ml). The organic phase was dried over
calcium hydroxide, from which the solvent was distilled off.
88
CA 02239970 1998-06-08
Then, the resulting product was dried under reduced pressure,
to recover crystal in deep purple crystal ( 522 mg ) . The yield
is 87 %.
Example 72-a
Synthes is of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-
mesitylene)(((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-mesitylene)ruthenium)
Instead of [ RuCl~ ( ~ 6-p-cymene ) ] ~ ( tetrachlorobis ( 77 6-
p-cymene)diruthenium),
[ RuCl~ ( 77 6-mes itylene ) ] ~ ( tetrachlorobis ( ~ 6-
mesitylene)diruthenium) was used, and by the same procedures
as in the Example 71-a, the catalyst in purple crystal as No.ll
in Table 10 was recovered. The yield is 80 %.
1H-NMR (400 MHz, ~H-chloroform, ~): ppm
1. 9 1 Cs. 9 H) . 1. 9 9 Cs. 3 H) , 3. 8 3 Cd. 1 H) . 4.
1 Cs. 1 H) . 4. 9.5 Cs. 3 H) . 5. 9 2 <b r d. 1 H) . 6. 3
8~-?. 7 1 (m. 1 4 H)
Example 72-b
Alternative synthes is of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH J
6-mesitylene)(((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-mesitylene)ruthenium)
Instead of RuCl [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ~ e-p-
cymene)(chloro-((S, S)-N-p-toluenesulfonyl-1,2-
89
CA 02239970 1998-06-08
diphenylethylenediamine)( ~ 6-p-cymene)ruthenium),
RuCl [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ 6-
mesitylene)(chloro-((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-mesitylene)ruthenium)
synthesized as in the Reference Example 2 was used, and by the
same procedures as in the Example 71-b, the catalyst in purple
crystal was recovered. The yield is 90
example 73-a
Synthesis of Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine]( 776-
p-cymene)(((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( X76-p-cymene)ruthenium)
Instead of ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine), (S, S)-N-p-
Ts-1,2-cyclohexanediamine((1S, 2S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine) was used, and by the same procedures as in
the Example 71-a, the catalyst in purple crystal as No.l4 in
Table l0 was recovered. The yield is 58 %.
Example 73-b
Alternative synthesis of Ru[(S, S)-N-p-Ts-1,2-
cyclohexanediamine]( ~ 6-p-cymene)(((S, S)-N-p-
toluenesulfonyl-1,2-cyclohexanediamine)( 776-p-
cymene)ruthenium)
Instead of RuCl [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH2 ] ) ( ~ 6-
CA 02239970 1998-06-08
p-cymene)(chloro-((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine) ( X76-p-cymene)ruthenium), RuCl[(S,
S)-N-p-Ts-cyclohexane-1,2-diamine synthesized in the
Reference Example 3 was used, and by the same procedures as in
the Example 71-b, the catalyst in purple crystal was recovered.
The yield is 62 %.
Example 74-a
Synthesis of Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine]( 776-
mesitylene)((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( X76-mesitylene)ruthenium)
Instead of ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH2 ( ( S, S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine), (S, S)-N-p-
Ts-cyclohexane-1,2-diamine ((S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine) was used, and by the same procedures as in
the Example 71-a, the catalyst as No .15 shown in Table 10 was
recovered as purple crystal. The yield is 60 $.
Example 74-b
Alternative synthesis of Ru[(S, S)-N-p-Ts-1,2-
cyclohexanediamine]( 776-mesitylene)((S, S)-N-p-
toluenesulfonyl-1,2-cyclohexanediamine)(
mesitylene)ruthenium)
Instead of RuCl [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ e-p-
cymene)(chloro-(S, S)-N-p-toluenesulfonyl-1,2-
91
CA 02239970 1998-06-08
diphenylethylenediamine)( ~ 6-p-cymene)ruthenium),
RuCl[(S, S)-N-p-Ts-1,2-cyclohexanediamine]
mesitylene)(chloro-(1S, 2S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( ~6-mesitylene)ruthenium,)synthesized in
the Reference Example 4 was used, and by the same procedures
as in the Example 71-b, the aforementioned catalyst was
recovered as purple crystal. The yield is 62 %.
Example 75-a
Synthes is of RuH [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHZ ] ( ~ s-p-
cymene)(hydride-(S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( ~ 6-p-cymene)ruthenium)
Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~7 6-p-cymene ) ( ( S ,
S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine)( r~ 6-p-
cymene ) ruthenium) ( 600 mg; 1. 0 mmol ) is dissolved in 2-propanol
( 10 ml ) in a Shlenk' s reactor which is preliminarily vacuum dried
and of which the inside is substituted with argon. The reaction
solution was agitated at room temperature for 15 minutes . The
solvent was recovered under reduced pressure at room
temperature, to recover a compound in brown yellow. After
rinsing the compound in cool pentane and recrystallizing the
compound in methanol, the catalyst No.l2 in Table 10 was
recovered as orange crystal. The yield is 85
m.p. > 60 °C (decomposed)
IR(KBr)[cnil] . 3335, 3317, 3228, 3153,
9?
CA 02239970 1998-06-08
3060, 3025, 2960, 2917,
2867
1H-NMR (400 MHz, ~H-chloroform, ~): ppm
- 5. 4 7 (s. H) . 1. 5 3 (d. 3 H) . 1. (d. 3 H) .
1 5 9 2.
2 9 (d. 3 H) 4 5 (s. 3 H) . 2. 7 9 (m. H) . 2. 9 3
: 2. 1
(m. I H) . 3. 0 (d. 1 H) . 4. 0 2 (m. 1 , 5. 1 5 (.d.
8 H)
1 H) , 5. 1 9 (d. 1 H) . S. 2 9 (m. I H) . 5. 4 3 (d. 1 H)
,
5. 5 8 (d. 1 H) 6. 4 9 (d. 2 H) . 6. 9 - 7. 3 (m. 1 0 H)
. .
7. 5 9 (d. 2 H)
Elemental analysis
( C;1H36N~0=RuS )
C H N Ru
Theoretical values (%) 61.88 6.02 4.66 16.80
Experimental values (%} 61.79 5.94 4.70 16.56
The X-ray crystallography shows that the complex was of
a structure satisfying the analytical results.
Example 75-b
Alternative synthesis of RuH[(S, S)-p-
TsNCH ( C6H5 ) CH ( C6H5 ) NHz ~ ( ~ 6-p-cymene ) ( hydride- ( ( S, S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine) ( 776-p-
cymene)ruthenium)
9:3
CA 02239970 1998-06-08
Toluene (7 ml) was added into the Ru[(S, S)-p-
TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-cymene ) ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine) ( ~ 6-p-
cymene)ruthenium) (306.2 mg; 0.5 mmol) synthesized in the
Example 72 in an autoclave which was preliminarily vacuum dried
and of which the inside was substituted with argon, for reaction
at room temperature and a hydrogen pressure of 80 atm. After
elimination of the solvent and rinsing in cool pentane and
subsequent recrystallization in methanol, crystal in orange
(420 mg) was recovered. The yield is 70
Example 76-a
Synthesis of RuH [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NHz ]
mesitylene)(hydride-((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine) ( 776-mesitylene)ruthenium)
Instead of Ru [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-p-
cymene)(((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine) ( r76-p-cymene)ruthenium), Ru[(S,
S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~7 6-mes itylene ) ( ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine)
mesitylene)ruthenium) synthesized in the Example 72 was used,
and by the same procedures as in the Example 75-a, the
aforementioned catalyst No.l3 in Table 10 was recovered. The
yield was 60 ~.
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Example 76-b
Alternative synthesis of RuH[(S, S)-p-
TsNCH ( C6H5 ) CH ( C6H5 ) NHz ] ( ~ 6-mes itylene ) ( hydride- ( ( S , S ) -N-
p-
toluenesulfonyl-1,2-diphenylethylenediamine) ( 776-
mesitylene)ruthenium)
Instead of Ru [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-
cymene)(((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine) ( ~ 6-p-cymene)ruthenium), Ru[(S,
S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-mes itylene ) ( ( ( S , S ) -N-p-
toluenesulfonyl-1,2-diphenylethylenediamine) ( 776-
mesitylene)ruthenium) synthesized in the Example 72 was used,
and by the same procedures as in the Example 75-b, the
aforementioned catalyst was recovered. The yield is 60 %.
Example 77-a
Synthesis of RuH[(S, S)-N-p-Ts-1,2-cyclohexanediamine]( 77
6-p-cymene)(hydride-(S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( 776-p-cymene)ruthenium)
Instead of Ru [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-
cymene)((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-p-cymene)ruthenium),
Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine] ( 7?6-p-cymene)((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)( 776-p-
cymene)ruthenium) synthesized in the Example 73 was used, and
by the same procedures as in the Example 75-a, the catalyst No.l6
CA 02239970 1998-06-08
in Table 10 was recovered. The yield is 54 ~.
Example 77-b
Alternative synthesis of RuH[(S, S)-N-p-Ts-1,2-
cyclohexanediamine]( ~ 6-p-cymene)(hydride-(S, S)-N-p-
toluenesulfonyl-1,2-cyclohexanediamine)( 776-p-
cymene)ruthenium)
Instead of Ru [ ( S, S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-
cymene)(chloro-(S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-p-cymene)ruthenium),
Ru[(S, S)-N-p-Ts-1,2-cyclohexanediamine] ( 776-p-cymene)((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)( 776-p-
cymene)ruthenium) synthesized in the Example 73 was used, and
by the same procedures as in the Example 75-b, the catalyst was
recovered. The yield is 55 %.
example 78-a
Synthesis of RuH[(S, S)-N-p-Ts-1,2-cyclohexanediamine]( 77
6-mesitylene)(hydride(S, S)-N-p-toluenesulfonyl-1,2-
cyclohexanediamine)( 776-mesitylene)ruthenium)
Instead of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 s-p-
cymene)((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( 776-p-cymene)ruthenium),
Ru[(S,S)-N-p-Ts-1,2-cyclohexanediamine] ( 776-mesitylene)((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)( 776-
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mesitylene)ruthenium) synthesized in the Example 74 was used,
and by the same procedures as in the Example 75-a, the catalyst
No.l7 in Table 10 was recovered. The yield is 52
Example 78-b
Alternative synthesis of RuH[(S, S)-N-p-Ts-1,2-
cyclohexanediamine]( 776-mesitylene)(hydride((S, S)-N-p-
toluenesulfonyl-1,2-cyclohexanediamine)(
mesitylene)ruthenium)
Instead of Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( 77 6-p-
cymene)((S, S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)( ~ 6-p-cymene)ruthenium),
Ru[(S,S)-N-p-Ts-1,2-cyclohexanediamine]( 776-mesitylene)((S,
S)-N-p-toluenesulfonyl-1,2-cyclohexanediamine)(
mesitylene)ruthenium) synthesized in the Example 74 was used,
and by the same procedures as in the Example 75-b, the
aforementioned catalyst was recovered. The yield is 48 ~.
Example 79
Synthesis of (R)-1-indanol
Ru [ ( S , S ) -p-TsNCH ( C6H5 ) CH ( C6H5 ) NH ] ( ~ 6-p-cymene ) ( ( S,
S)-N-p-toluenesulfonyl-1,2-
diphenylethylenediamine)(ruthenium- ~ 6-p-cymene mesitylene
( 6 . 0 mg; 10 ,u mmol ) synthes ized in the Example 71 and 1-indanol
( 671 mg; 5 mmol ) were weighed in a Shlenk' s reactor which was
9r
CA 02239970 2004-02-25
preliminarily vacuum dried and of which the inside was
substituted with argon, and acetone ( 2 . 5 ml ) was then added to
the resulting mixture for agitation at 28 °C for 6 hours. The
solvent was distilled off under reduced pressure, prior to
separation by silica gel chromatography {eluent; ethyl
acetate : hexane = 1 . 3 ) , to recover (R)-indanol (286 mg) in
colorless crystal. The yield is 84 %.
m.p. 71 - 72 °C
[ Cx ]~'o = -30.1 ° (c = 1.96, chloroform)
The resulting (R)-1-indanol was analyzed by HPLC (high-
performance liquid chromatography), and the objective (R)-
1-indanol was at an optical purity of 97 ~ ee.
<HPLC analytical conditions>
Column-..CHIRALCEL*OB(manufactured by Daicell Chemical Industry,
Co.)
Developing solution: isopropanol . hexane = 10 . 90
Flow rate: 0.5 ml/min
Retention time: (S)-1-indanol 18.6 minutes
(R)-1-indanol 12.9 minutes.
Examples 80 to 93
According to the method described in Example 79, the
optically active ruthenium-diamine complexes for racemic
secondary alcohols and meso-type diols as reaction substrates
as shown in Table 9 were used for reaction under reaction
* Trade-mark
98
CA 02239970 1998-06-08
conditions of reaction time, to recover the individually
corresponding optically active secondary alcohols at high
yields. The results are collectively shown in Table 11.
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Table 11
Reaction
ExamplesSubstrates s/c time %(y %ee Product
Catalysts i a
1d)
(h~~ s
80 1 a , (S. 500 36 50 92 la (R)
S) -10
81 1 a (S. S)-11500 30 51 94 la(R)
82 1 a (S. S)-10500 22 47 92 lb(R)
83 1 b (S, S)-11500 30 44 98 lc(R)
84 1 c (S. S) 500 36 47 g7 ~ (R)
-11
85 2 a (S. S) 500 24 47 97 26 (R)
-11
79 2 b (S. S)-10500 6 46 97 3a(R)
86 3 a (S. S)-10500 6 - 49 99 36(R)
87 3 b (S. S).-11500 36 51 98 4 (R)
88 4 (S. S)-10500 4. 5 43 93 5a (R)
89 5 a (S, S) 500 5 46 95 5b (R)
-10
90 5 b (S. S) 200 3 70 96 7
-11
9I 5 (S, S) 200 3 56 87 9
-IO
92 1 a (S. S)-I4500 36 48 82 la(R)
93 1 a (S. S)-15500 36 48 86 la(R)
(In the table, s/c means the molar ratio of
substrate/ruthenium-optically active diamine complex.)
I00
CA 02239970 1998-06-08
Industrial A~Aplicabilitv
In accordance with the present invention, optically
active alcohols and optically active amines are provided,
which are useful in various fields of pharmaceutical
products, synthetic intermediates thereof, food, flavor,
cosmetics, liquid crystal materials and the like.
The ruthenium-diamine complex of the present invention
is industrially useful as a chiral catalyst providing higher
selectivity and activity in that the complex can be used for
organic synthesis such as asymmetric synthetic reactions.
If the complex is used as a hydrogen transfer-type
asymmetric reduction catalyst of racemic secondary alcohols
or meso-type diols, optically active secondary alcohols
useful as production intermediates of drugs can be produced
highly efficiently.
101
