DESCRIPTION
Title of Invention
RUTHENIUM COMPLEX AND METHOD FOR PREPARING OPTICALLY ACTIVE
ALCOHOL COMPOUND
5
Technical Field
The present invention relates to a novel ruthenium complex and a method for preparing an
optically active alcohol compound using the same as a catalyst.
10 Background Art
A transition metal complex which has an optically active diphosphine compound as a ligand is very useful as a
catalyst for an asymmetric reaction, and until now many catalysts have been developed
Among the catalysts, in combination of a base compound, anahenim-diphosphine-diamine complex is known as
a highly active catalyst for an asymmetric hydrogenation (for example, PLT 1). As a method for synthesizing the
15 complex, [RuCl2(p-cymene)lz as a precursor of the complex reacted with an optically active diphosphine and an
optically active diarnine in order in a specific solvent is known (PLT 2), as an example. In addition, as a complex
having an optically active diphosphine and a tidentate amine ligand, the compound represented by the following
formula is known VLT 3).
[Chem. 11
The ruheniurn metal complex having an optically active diphosphine compound and a diamine compound as a
ligand is highly useful because of the use for asymmetric hydrogenation of various carbonyl compounds, showing a
high activity and high enantioselectivity, and giving an optically active alcohol compound with high optical purity.
However, such catalyst shows high performance but not for every carbonyl compound, then development of a
25 catalyst with higher activity is needed
Citation List
Patent Literature
PLT 1 : Japanese Patent Application Laid-Open (JP-A) No. 1 1 - 189600
30 PLT 2: W0 20071005550 A1
WO 20111135753
PLT 3: WO 20091007443 A2
Summary of Invention
Technical Problem
5 The present invention provides a novel ruthenium metal complex having an excellent catalytic activity with an
optically active diphosphine compound and a diamine compound as a ligan4 and an asymmetric reduction catalyst
using the metal complex, and a method for asymmetric reduction of a carbony1 compound using the metal complex
Solution to Problem
10 Inventors of the present invention intensively studied to solve the problems described above, and as a result, found
a novel ruthenium complex having an oplically active diphosphine and a tridentate diamine as a ligand which was
used for an asymmetric reduction, and also developed a method for obtaining an optically active alcohol with high
selectivity and higher activity than the catalysts of conventional technologies by using the complex as a catalyst.
Specifically, the present invention provides a novel ruthenium complex, an asymmetric reduction catalyst which
15 includes the metal complex, and a method for preparing optically active alcohols according to asymmetric reduction
by using the metal complex
The present invention provides the following [I] to [2 11.
[l] Aruthenium complex rqnesented by the following Formula (1)
[Chem. 21
(in the formula, PnP qrcxnts diphosphine and X represents an anionic pup; Ra, R~ and Rc each
independently represent a hydrogen atom, an optionally substituted Cl-Cm alkyl group, an optionally substituted
C2Ca alkenyl group, an optionally substituted c3-C~ cycloalkyl pup, an optionally substituted C+220 arallojl
group, an optionally substituted aryl group, or an optionally substituted heterucyclic group, and R~ and Rc may form
25 an akylene group or an akylenedioxy group; RN, Rm, R*, and RN4 each indepmdently represent a hydrogen atom,
an optionally substituted CI-CUa, kyl group, an optionally substituted C2Cma lkenyl group, an optionally substituted
C7Ca -1 group, or an optionally substituted C3Cs cycloalkyl pup, at least one of RN1, Rm, RM, and R~~
represents a hydrogen atom, and Rhn and Ra may form an akylene group; n m t s an integer of 0 to 3; and Ar
qmmts an optionally substituted arylene group).
30 [2] The ruthenium complex according to the above [I], wherein the ruthenium complex is a ruthenium complex
rqmented by the following Formula (2)
[Chem.3]
(in the formula, P"P represents diphosphine, X represents an anionic group; Ra, R~a,n d Rc each independently
represent a hydrogen atom, an optionally substituted CICm alkyl group, an optionally substituted C2C20 alkenyl
group, an optionally substituted C3Cs cycloalkyl group, an optionally substituted C 7 Car~alk yl p u p , an optionally
5 substituted aryl group, or an optionally substituted heterocyclic p u p , and Rb and Rc may form an alkylene group or
an alkylenedioxy group; Rd, Re, Rf and Rg each independently represent a hydrogen atom, an alkyl group having 1 to
20 carbon atoms, a halogenated alkyl group having 1 to 5 carbon atoms, a halogen atom, an optionally substituted
aryl group, an optionally substituted C3-G cycloalkyl group, a tri-mtuted silyl group or an alkoxy group having 1
to 20 carbon atoms; RN', RNZR, M and RN4e ach independently represent a hydrogen atom, an optionally substituted
10 C1Cm alkyl group, an optionally substituted c2-C~a lkenyl group, an optionally substituted CKu)a ralkyl group, or
an optionally substituted C3Cg cycloalkyl group, and at least one of RN, R ~RM, and RN4q ments a hydrogen
atom; and RN' and Ra may form an alkylene group).
[3] The ruthenium complex accordmg to the above [I] or [2], wherein the ruthenium complex is a ruthenium
complex represented by the following Formula (3)
15 [Chem. 41
(in the formula, P^P repmenls diphosphine, X qmsents an anionic p u p , Ra and Rb each independently represent
a hydrogen atom, an optionally substituted Ck-Cma lkyl group, an optionally substituted C2-(& alkenyl group, an
optionally substituted c3-C~ cycloalkyl group, an optionally substituted C7Cz aralkyl group, an optionally
substituted aryl group, or an optionally substiMed heterocyclic group; RM, RW, RN3 and RN4 each independently
represent a hydrogen atom, an optionally substituted ClCm alkyl group, an optionally substituted CzCm alkenyl
group, an optionally substituted c7C20 aralkyl p u p , or an optionally substituted C3G cycloalkyl group, and at least
one of RN, RNZR, M and RN4r epments a hydrogen atom; and RN1a nd Ra may form an alkylene group).
5 [4] The ruthenium complex accordq to any one of the above [l] to [3], wherein the diphosphine i n d i d as P"
P is a diphosphine m t e d by the following Formula (4)
R~R*P-Q-PR~R~ ( 4 )
(in the formula, R', R2, R3 and R~ each independently q m t an optionally substituted aryl group, an optionally
substituted cycloalkyl group, or an optionally substituted alkyl group, and R' and R2 andlor R3 and R4 may form a
10 ring; and Q represents an optionally substituted divalent arylene group, biphenyldiyl group, biihthalenediyl group,
bipyridinediyl group, paracyclophanediyl group, or f-ediyl group).
[5] The ruthenium complex according to any one of the above [l] to [4], wherein the diphosphine i n d i d as P"
P is an optically active diphosphine.
[6] The ruthenium complex accodng to any one of the above [l] to [5], wherein the optically active diphosphine
15 indicated as P T is an diphosphine represented by the following Formula (5)
[Chem. 51
(in the formula, R", R', R3' and R4' each independently represent a phenyl group, a cyclopentyl group w a
cyclohexyl group, and any of which is optionally substituted with a substituent group selected fmm a group
20 consisting of an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. RS, R6, R7,
R', R9 and R'' each independently qment a hydrogen atom, an akyl group having 1 to 4 carbon atoms, an alkoxy
group having 1 to 4 carbon atoms, a halogen atom, a halogenated akyl group or an diakylamino group having 1 to 4
carbon atoms and two of R ~R,~ a nd R7 may form an optionally substituted akylene group; an optionally substiM
alkylenedioxy group; or an optionally substituted mmatic ring two of R8, R9 and R'O may form an optionally
25 substiMed alkylene group; an optionally substituted allcylenedioxy group; or an optionaliy substituted aromatic ring;
and R7 and RE may form an optionally substituted alkylene group; an optionally substituted alkylenedioxy group; or
an optionally substituted aromatic ring with the proviso that any of R7 and R8 is not a hydrogen atom).
[A The ruthenium complex accordmg to the above [6], wherein R', R2, R3 and R4 in the Formula (4) and R", RZ',
R3' and R4' in the Formula (5) is a 3,5-xylyl pup.
[8] An asymmetric reduction catalyst comprising the ruthenium complex accodrg to any one of the above [5] to
[7l.
[9] A method for preparing optically active alcohols, wherein a carbonyl group is subjected to asymmetric
5 hydrogenation with the asymmetric reduction d y s t according to the above [8] in the presence of a base compound
[lo] A method for preparing optically active alcohols, wherein a carbony1 p u p is subjected to asymmetric
hydrogen-tmsfer reduction with the asymmetric reduction d y s t according to the above [a] in the p m c e of a
base compound
[I 11 A method for preparing the ruthenium complex repmented by the following Formula (I),
10 [Chem. 61
wherein the ruthenium compound repmented by the following Formula (A)
[RuX (L) (P-P) I X (A)
(in the formula (A), Ru represents a ruthenium atom, X qmxmts a halogen atom, L represents an arene
15 and P^P represents bihosphine)
is reacted with the compound having the following Formula (8)
[Chem. 7]
(in the formula, Ray Rb and R' each independently represent a hydrogen atom, an optionally substituted C1CZ0al kyl
20 group, or an optionally substituted C2Cx alkenyl group, or an optionally substituted C3Cs cycloalkyl group, or an
optionally substituted C& aralkyl pup, or an optionally substituted aryl pup, or an optionally substituted
heterocyclic group or R~a nd Rc may form an alkylene p u po r an alkylenedioxy pup;R N, R ~RM~ a,nd RN4e ach
independently represent a hydrogen atom, an optionally substituted ClCx alkyl group, an optionally substituted
C~CBalk enyl group, an optionally substituted C&U, aralkyl pup, or an optionally substituted C3Cs cycloalkyl
25 group, and at least one of RN1,R NZRY* and RN4r epreSentS a hydrogen atom; or R~ and Ra may form an alkylene
group, and n is an integer of 0 to 3 and Ar repments an optionally substituted arylene group).
[12] A method for preparing the ruthenium complex represented by the following Formula (1),
wherein the ruthenium compound m t e d by the following Formula @)
[RuXz (L) I* (B)
5 (in the formula (B), Ru represents a ruthenium atom, X w t s a halogen atow L represents an arene and m
v t s a natd number of 2 or more)
is reacted with a diphosphine represented as and then with the compound having the following Formula (8)
[Chem. 91
10 (in the formula, Ra, Rb and Rc each independently represent a hydrogen atom, an optionally substituted CICm alkyl
group, or an optionally substituted C+220 alkenyl group, or an optionally substituted C3Cg cycloalkyl pup, or an
optionally substituted C7Czo araIky1 group, or an optionally substituted aryl pup, or an optionally substituted
N1 heterocyclic group or Rba nd RCm ay form an akylene group or an alkylenedioxy group; RN 1 , RN 2 ,R M and RN4e ach
independently r e p m t a hydrogen atom, an optionally substituted CICm alkyl pup, an optionally substituted
15 C2-Cm alkenyl group, an optionally substituted C7Cm aralkyl group, or an optionally substituted C3Cs cycloakyl
pup, and at least one of RN, R ~RN,3a nd RN4r epresents a hydrogen atom; or R ~a'nd Ra may be akylene pup,
and n is an integer of 0 to 3 and Ar repments an optionally substituted arylene group).
1131 The method for preparing the ruthenium complex accordjng [ll] or [12], wh& the reaction was canied
out in w c e of a solvent, and the solvent used is an alcohol solvent.
20 [14] The method for preparing the mthenium complex according to any one of the above [l 11 to [13], additionally
wherein a base is added.
[15] The method for preparing the ruthenium complex according to any one of the above [l 11 to [14], wherein the
diphosphine indicated as P"P is a diphosphine qmented by the following Formula (4)
R ~ R ~ P - Q - P R ~ R(~4 )
25 (in the formula, R', R2, R3 and R4 each independently repment an optionally substituted aryl group, an optionally
substituted cycloalkyl pup, or an optionally substituted akyl pup, and R' and R2 andlor R3 and R4 may form a
ring; and Q repments an optionally substituted divalent arylene group, biphenyldiyl group, binaphthalenediyl group,
bipyridinediyl groupy paracyclophanediyl group, or fermmediyl group).
[16] The method for the preparing according to any one of the above [ll] to [15], wherein the diphosphine
indicated as P"P is an optically active diphosphine.
5 [17] The method for preparing the ruthenium complex according to any one of the above [I 11 to [16], wherein the
optically active diphosphine i n d i d as F T is an optically active diphosphine rept-esented by the following
Formula (5)
[Chem. 101
10 (ithe formula, R", R? R3' and R4' each independently represent a phenyl group, a cycloptyl p u p or a
cyclohexyl group, and any of which is optionally substituted with a substituent group selected k m a group
consisting of an -1 group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
R5, R6, R7, R8, R9 and R'' each independently represent a hydrogen atom, an akyl group having 1 to 4 carbon
atoms, an alkoxy p u p having 1 to 4 carbon atoms, a halogen atom, a halogenated akyl group or an diakylamino
15 p u p having 1 to 4 carbon atoms and two of R5, R6 and R7 may form an optionally substituted alkylene group; an
optionally substituted alkylenedioxy group; or an optionally substituted aromatic ring, and two of R8, R9 and R" may
form an optionally substituted akylene group; an optionally substituted akylenedioxy pup; or an optionally
substituted aromatic ring; and R7 and R8 may form an optionally substituted alkylene group; an optionally substituted
alkylenedioxy group; or an optionally substituted aromatic ring, with the proviso that R7 and R' are not a hydrogen
20 atom).
[la] The method for the prepanhg the ruthenium complex m d n g to any one of the above [I 11 to [16], wherein
R', R2, R3 and R4 in the Formula (4) and R", R2', R3'and R4' in the Formula (5) is a 3,s-xylyl group.
[19] The method fix preparing the ruthenium complex having anion group instead of halogen ion as X in the
Formula (I), that the ruthenium compound having halogen ion as X in the Formula (1) reacted with other compound
25 having anion group.
[20] The method according to [19], wherein the compounding having anion group is alkali metals carboxylate or
alkali metals soIfonate. i [21] The method according to [20], wherein alkali metal carbylate is sodium acetate; alkali metal sulfonate is
sodium trifluommethanesuEonate.
Advantageous Effects of Invention
5 The present invention provides a novel ruthenium complex and a metfiod for preparing an optically active alcohol
compound using the complex as a catalyst. The novel ruthenium complex catalysts in the present invention shows
good d v i t y in asymmetric reduction of a carbonyl compound, especially conversion rate and selectivity, also
shows enantioselectivity, etc., compad to conventional optically active ruthenium complex catalysts having
diphosphine and diamine ligand, and therefore it is i n d d y highly usefid.
10 Moreover, as the ruthenium complex is expensive, it is prefetable to minimize the amount of the ruthenium
complex used for reaction In this r e d according to the invention, a complex having high catalytic activity
which requim less amount of a catalyst for reaction than conventional asymmetric reduction complex is provided
Description of Embodiments
15 Herein*, the present invention will be explained in detail.
The ruthenium complex repmented by the Formula (1) of the invention is characterized in that a divalent arylene
group repmented by -Ar- is included therein, and it is specifically characterized in that one end of the arylene group
binds to the nrthenium atom with Rucarbon bond and the other end binds to the ahon atom in the carbon chain of a
diamine compound as a ligand with a c a r t a n e n bond. It is further characterized in that any of the two nitrogen
20 atoms in the diamine compound as a ligand has sp3 hybrididon. Moreover, the arylene group may have a
substituent p u p such as an alkoxy group.
One of the characteristics of the ruthenium complex of the invention is that it is a mthenium complex having
nrthenacycle strum.
Examples of the optionally substituted arylene group which is repmated by Ar in the ruthenium complex of the
25 Formula (1) of the invention include a divalent monocyclic, polycyclic or condensed-ring type arylene group having
6 to 36 carbon atoms, preferably 6 to 18 carbon atoms, and more preferably 6 to 12 carbon atoms, or a divalent
monocyclic, polycyclic or condensed-ring type heteroarylene group having a 3- to 8-membered, and preferably 5- to
8-membered ring in which 1 to 4, prefaably 1 to 3 or 1 or 2 heteroatoms consisting of a nitrogen atom, an oxygen
atom and a sulfk atom is included Examples of a prefened arylene group include a phenylene group, a
30 naphthalenediyl pup, a pyridinediyl group, a thiophenediyl group and a furandiyl group, and a phenylene group is
@cularly preferable. Although the position to which the divalent arylene group b i d is not specifically limited,
two adjacent carbon atom positions (i.e., ortho position) are preferable.
In addition, examples of a substitutent group which is substituted on the arylene group include a linear or branched
alkyl group, a linear or bmched alkoxy group, a cycloakyl group, a halogen atom, an aryl group, a heteroaryl group,
35 and atri-substituted silyl group.
Hereinafter, the substituent group which is substituted on the arylene p u p will be explained.
Examples of the linear or branched alkyl group, may be substituted by halogen atom such as F, include a linear
or branched alkyl group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, and more preferably 1 to 4
carbon atoms. Specific examples include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a
n-butyl group, an isobutyl group, a s-butyl group, a t-butyl group and a ttitluoromethyl group.
Examples of the linear or branched alkoxy group include a linear or branched alkoxy group having 1 to 10 carbon
5 atoms, preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms. Specific examples include a
methoxy group, an ethoxy group, a n-pmpoxy group, an i s o m x y group, a n-bmxy group, a s-butoxy group, an
isobutoxy group and a t-bmxy group.
Examples of the cycloalkyl group include a sahakd or ushated monocyclic, polycyclic or condensed-ring
type cycloalkyl group having 3 to 15 carbon atoms, and preferably 5 to 7 carbon atoms, and specilk examples
10 include a cyclopentyl group and a cyclohexyl group. One or two or more alkyl groups having 1 to 4 carbon atoms
or alkoxy groups having 1 to 4 carbon atoms may be substituted on the ring of these cycloalkyl groups.
Examples of the halogen atom include a chlorine atom, a bromine atom and a fluorine atom.
Examples of the aryl group include an aryl group having 6 to 14 carbon atoms, and specific examples include a
phenyl group, a naphthyl group, an anthryl group, a phenanthryl group and a biphenyl group. The aryl p u p may
15 have one or two or more substituent groups, and examples of the substituent group include an alkyl group having 1 to
4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms as described above.
Examples of the heteroaryl group include a 5-membered or 6-membered cyclic group having an oxygen atom, a
s u b atom or a niimgen atom, and speciiic examples include a fury1 group, a thienyl group and a pyridyl group.
Examples of the tri-substituted silyl group include a silyl group which is tri-substituted with the akyl group or the
20 aryl group d e s c n i above, and speci6c examples include a trimethylsilyl group, a triethylsilyl group, a
triisopmpylsilyl group, a tert-butyldimethylsiilyl group, a diphenylmethylsilyl group and a dimethylphenylsilyl group.
Examples of the anionic group represented by X in the ruthenium complex of the Formulae (I), (2) and (3) include
a hydride ion 0a; halo gen ion such as a chloride ion (Cl-), a bromide ion @r), or an iodide ion (IJan d a complex
anion such as BH4, BF4, BPb PFh an acetoxy group (OAc) and a trinuoromethane sulfonyloxy group (OTf).
25 Among these, a halogen ion is preferable.
The groups repmted by Ra, R~R,C , Rd, Re, ~ fR,g, RN1,R W, R~ and R~ in the ruthenium complex of the
Formulae (I), (2) and (3) will be explained hereinah.
Examples of the CICw alkyl group include a linear or branched alkyl group having 1 to 20 carbon atoms,
preferably 1 to 5 carbon atoms and more prefdly 1 to 4 carbon atoms, and specific examples include a methyl
30 group, an ethyl group, a n-pmpyl group, an isopropyl group, a n-butyl group, an isobutyl group, a set-butyl group, a
t-butyl group, an-pentyl group, a n-hexyl group, a decyl group, a dodecyl group, and a hexadecyl group.
Examples of the C2C2(, alkenyl group include a liner or branched alkenyl group having 2 to 20 carbon atoms,
preferably 2 to 10 carbon atoms and more preferably 2 to 6 cahm atoms, and specific examples include an ethenyl
group, a n-propenyl group, an isopmpenyl group, a 1-butenyl group, a 1-buten-2-yl group, a pentenyl group, and a
35 hexenyl group.
Examples of the C I Ca~lko xy group include an alkyl group having 1 to 20 carbon atoms to which an oxygen
atom is bonded, and speciiic examples include a methoxy group, an ethoxy group, a n-propoxy group, an k p p o x y
group, a n-butoxy group, a s-butoxy group, an isobutoxy group and a t-bmxy group.
The examples of halogenated CLCS alkyl group, include trifluommethyl group, pentafluomethyl group,
heptanuompmpyl p u p , trichommethyl group.
Examples of the C3-c~ cycloalkyl group include a satumted or unsaturated monocyclic, plycyclic or
5 condensed-ring type cycloallcyl group having 3 to 8 carbon atoms, and preferably 5 to 7 carbon atoms. Specific
examples include a cyclopentyl group and a cyclohexyl group.
Examples of the halogen atom include a chlorine atom, a bromine atom and a fluorine atom
Examples of the heteroaryl group include a 5-membered or &membered cyclic group having an oxygen atom, a
sulfur atom or a nitrogen atom, and specific examples include a fiql group, a thienyl group and a pyridyl group.
10 Examples of the tri-substituted silyl group include a silyl group which is tri-substiMed with the alkyl group or the
aryl group described above, and specific examples include a trimethylsilyl group, a triethylsilyl group, a
triisopmpylsiiyl group, a tat-butyldimethylsilyl group, adiphenylmethylsilyl group and a dimethylphenylsilyl group.
Examples of the C7C20 aralkyl group include an aralkyl group having 7 to 20 carbon atoms, preferably 7 to 15
carbon atoms and more preferably 7 to 10 carbon atoms in which an akyl group having 1 to 20 carbon atoms is
15 bonded to a monocyclic, plycyclic or condensed-ring type aryl group having 6 to 19 carbon atoms and preferably 6
to 14 carbon atoms. Specific examples include a benzyl group, a a-methylbenzyl group, a a,adiiylbenzyl
group, a 2-phenylethyl group and a 3-phenylpropyl group.
Otherwise, the examples of the substituent to C1-C20 alkyl group, C2C20 alkenyl group, C1-C20 alkoxy group,
halogenated CICs alkyl group, C~CcSyc loalkyl group, heteroaryl group, tri-substituted silyl group, and C&
20 aralkyl group as described above include linear or branched alkyl group, linear or branched alkoxy group, cycloalkyl
group, halogen atom, aryl group, heteroaryl group, and tri-substituted silyl group.
Examples of an aryl group in the optionally substituted aryl group include a monocyclic, plycyclic or
condensed-ring type aryl group having 6 to 20 carbon atoms, preferably 6 to 14 carbon atoms, and more preferably 6
to 12 carbon atoms. Specific examples include a phenyl group, a naphthyl group, an anthryl group, a phenanthryl
25 group and a biphenyl group, and a phenyl group is prefemble. The aryl group may have one or two or more
substitmnt groups and examples of the substituent group include an akyl group hawng 1 to 4 carbon atoms such as a
methyl group, an isopmpyl group and a t-butyl group, and; an alkoxy p u p having 1 to 4 carbon atoms such as a
methow group, an ethoxy group, a n-pmpoxy group, an h w x y group, a n-bbxy group, an isobutoxy group, a
s-butoxy group and a t-butoxy group as described above.
30 The examples of an optionally substituted hetemyclic group include a 5-membered or 6-membered cyclic group
having an oxygen atom, a s u h atom or a nitrogen atom, and specific examples include a fiql group, a thienyl
group and a pyridyl p u p . And the examples of the substituent which the hetaocyclic group has one or more than
two ot include akyl group having 1 to 4 carbon atoms such as a methyl group, an isopmpyl group, and a t-butyl
group; alkoxy group having 1 to 4 carbon atoms such as a methoxy group, an ethoxy group, a n-ppoxy group, an
35 isopmpxy group, a n-butoxy group, a s-butoxy group, an isobutoxy group and a t-butoxy group.
Moreover, examples of the alkylene group formed by R~ and Rc include a linear or branched alkylene group
having 1 to 6 carbon atoms and preferably 1 to 4 carbon atoms. Specific examples include a methylene group, an
ethylene group, a trimethylene p u p , a pmpylene group and a tebamethylene group, and these alkylene groups are
optionallysubsthtedwithanalkylgrouphaving lto4carbonatomsoranalkoxygrouphavingl to4ca.dx~natoms.
Examples of the alkylenedioxy group formed by Rb and RC include a linear or branched alkylenedioxy group
having 1 to 6 carbon atoms and prefembly 1 to 4 carbon atoms. Specific examples include a methylenedioxy group,
5 an ethylenedioxy group, and atrimethylenedioxy group.
The examples of the alkylene group formed by RN1 and Ra include a linear or branched akylene group having 1 to
6 carbon atoms and preferably 1 to 4 carbon atoms. Specific examples include a methylene group, an ethylene
group, a trimethylene group, a propylene group and a tetramethylene group, and these akylene groups are optionally
substituted with an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms.
10 The diphosphine(a1so as named bisphosphine) represented by P^P in the ruthenium complex of the Formulae (I),
(2) and (3) is not spec5cally limited if it is a diphosphine which can COO- to ruthenium. Examples thereof
include those represented by the following Formula (4)
R'R~P-Q-PR~R~ ( 4 )
(in the formula, R', R2, R3 and R4 each independently represent an optionally substituted aryl group, an optionally
15 substituted c y c l o ~glro up, or an optionally substituted alkyl group, and R' and R2 andlor R3 and R4 may form a
ring. Q represents an optionally substituted divalent arylene group, biphenyldiyl group, biihthalenediyl group,
bipyridinediyl group, paracyclophanediyl group, or fknmenediyl group.).
Examples of the optionally substituted aryl group rqmented by R', R2, R3 and R~ in the above formula include an
aryl group having 6 to 14 carbon atoms, and specific examples include a phenyl p u p , a naphthyl p u p , an anthryl
20 group, a phenanthryl group and a biphenyl group.
These aryl groups may have one or two or more substituent groups and the examples of the substituent group
include an alkyl group and an alkoxy group.
Examples of the alkyl group as a substituent group for the aryl group include a linear or branched alkyl group
having 1 to 15 carbon atoms, prefembly 1 to 10 carbon atoms and more preferably 1 to 6 carbon atoms, and specific
25 examples include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, a s-butyl
group, an isobutyl group and a t-butyl group.
Examples of the alkoxy group as a substituent group for the aryl group include a linear or branched akoxy group
having 1 to 6 carbon atoms, and specific examples include a methoxy group, an ethoxy group, a n-pmpxy group, an
isopmpoxy group, a n-butoxy group, a s-butoxy group, an isobutoxy group and a t-butoxy group.
30 Moreover, examples of the optionally substituted cycloalkyl group qmented by R', R ~R,3 and R4 include a
5-membered or 6-membered cycloalkyl group, and p r e f d examples of the cycloalkyl group include a cyclopentyl
group and a cyclohexyl group. On the ring of these cycloallqd groups, one or two or more substituent groups such
as an alkyl group or an alkoxy group, which is mentioned above as a subdtuent group for the aryl group, may be
substituted.
35 Examples of the optionally substituted alkyl group include a linear or bmched akyl group having 1 to 15 carbon
atoms, preferably 1 to 10 carbon atoms and more preferably 1 to 6 carbon atoms, and specific examples include a
methyl group, an ethyl p u p , a n-pmpyl group, an isopmpyl group, a n-butyl p u p , a s-butyl group, an isobutyl
group and a t-butyl group. These alkyl groups are optionally substituted with one or two or more substituent groups
such as alkoxy group which is mentioned as a substituent group for the aryl group in the above.
Moreover, examples of the ring which may be formed by R' and R2 andlor R3 and R4 include a ring which
includes a phosphorus atom to which R', R2, R3 and R~ are bonded, includmg a 4-membered, a 5-membered or a
5 6-membaed ring Specific examples include a phosphetane ring, a phosphomne ring, a phosphane ring,
2,4dimethyl phosphetane rin& 2,4diethyl phosphetane rin& 2,5dimethyl phosphomne ring 2,5-diethyl
phosphomne ring, 2,6dimethyl phosphane ring and 2,6-diethyl phosphane ring, and these ring compounds may be
optically active.
Moreover, examples of Q include an optionally substituted divalent arylene group, biphenyldiyl group,
10 biihthalenediyl group, bipyridinediyl group, paracyclophanediyl group, and a fxmenediyl group.
Examples of the divalent arylene group include a divalent arylene group which is derived h m the aryl group
described above. Preferred examples of the arylene group include a phenylene group. Examples ofthe phenylene
group include an e or m-phenylene group, and the phenylene group is optionally substituted with an alkyl group
having 1 to 6 carbon atoms such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl
15 group, a S-butyl group, an isobutyl group and a t-butyl group; an alkoxy group having 1 to 6 carbon atoms such as a
methoxy group, an doxy group, a n-propoxy group, an isopr~poxyg roup, a n-bmxy group, a s-bmxy group, an
isobutoxy group and a t-butoxy group; a hydroxy group; an amino group, or, a substituted amino group.
The biphenyldiyl group, biihthalenediyl group and bipyridinediyl group prefdly have a 1,l '-biaryl-22'-diyl
type structure in which an axial asymmetric structure is included, and the biphenyldiyl group, biihthalenediyl
20 group and bipyridinediyl group are optionally substituted with the alky1 group and alkoxy group described above, for
example, an alkylenedioxy group such as a methy1enedioxy group, an ethylenedioxy group and a trimethylenedioxy
group, a hyhxy group, an amino group, and a substituted amino group.
Paracyclophanediyl group may be optionally substituted with the alkyl group and alkoxy group described above,
for example, an alkylenedioxy group such as a methylenedioxy group, an ethylenedioxy group and a
25 trimethylenedioxy group, a hydroxy group, an amino group, and a substituted amino group.
Moreover, the f m e d 1 y 1 group is also optionally substituted and examples of the substituent group include an
alkyl group, an alkoxy group, an aUcy1enedioxy group, a hyhxy group, an amino group, and a substituted amino
group as described above.
Examples of the substituted amino group include an amino group which is substituted with one or two alkyl
30 groupshavinglto6carbonatoms.
Specific examples of the diphosphine represented by the Formula (4) include optically active diphosphines that are
well known in the art, and preferred examples include the compound rqmented by the following Formula (5).
The optically active disphophine represented by the following formula can be mentioned.
[Chem. 111
(in the formula, R", RZ', R3' and R' each independently represent a phenyl group, a cyclopentyl group or a
cyclohexyl group, and any of which is optionally substituted with a substituent group selected h m a group
misting of an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. R5, R6, R7,
5 R8, R9 and R'O each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy
p u p havlng 1 to 4 carbon atoms, a halogen atom, a halogenated alkyl group or an dialkylamino group having 1 to 4
carbon atoms, two of RS, R6 and R~ may form an optionally substhted akylene p u p ; an optionally substituted
alkylenedioxy group; or an optionally substituted aromatic ring, and two of R', R9 and R" may form an optionally
substituted akylene p u p ; an optionally substituted alkylenedioxy group; or an optionally substituted aromatic ring.
10 Furthermore, R7 and R8 may form an opbonally substituted akylene group; an optionally substituted alkylenedioxy
group; or an optionally substituted ammatic ring with the proviso that R7 and R8 are not a hydrogen atom.)
Re- the alkyl group, alkoxy group, halogen, alkylene group, and akylenedioxy group in the above Formula
(5), those described in the above can be mentioned The aromatic ring which is formed by two p u p s may form a
6-membered aromatic ring together with adjacent atom The aromatic ring thus formed is optionally subsiituted
15 with an alkyl group or an alkoxy group.
Preferred examples of the Formula (5) include cases in which R", RZ', R' and R4' each independently represent a
phenyl group which is optionally substituted smgular or plural number with a substituent group selected h m a group
conskting of an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 h n atoms; and R6 and
R~ forms atetramethylene p u p ; a methylenedioxy group which is opbonally substituted with an alkyl group having
20 1 to 4 carbon atoms or a fluorine atom; or forms a benzene ring together with an adjacent carbon atom; and R8 and R9
forms a tetramethylene group; a methylenedioxy group which is optionally substituted with an alkyl group having 1
to 4 carbon atoms or a fluorine atom; or forms a benzene ring together with an adjacent carbon atom.
Moreover, specific examples of more preferable optically active diphosphine of the invention include the optically
active diphosphine represented by the following Formula (6) or Formula (7).
25 [Chm12]
Specific examples of RP1 and RP2 in the Formula (6) and the specific examples of RP3 and RP4 in the Formula (7)
include a phenyl group, a ptolyl group, a m-tolyl group, an etolyl group, a 3,5-xylyl group, a 3,5di-t-butylphenyl
group, a pt-butylphenyl group, a pmethoxyphenyl group, a 3,5-di-t-butyl-4-methoxyphenygl roup, a
5 pchlomphenyl group, a mchlorophenyl group' a pfluorophenyl group and a m-fluomphenyl group.
Specisc examples of the diphosphine qmented by the Formula (4), (5), (6) and (7) of the invention include
2,2'-biidiphenylphosphino>l,l '-binaphthyl(bii); 23'-bis[di(gtolyl)phosphino]-1,l'-b'lnaphthyl ((tolbii);
22'-bis[di(m-tolyl)phosphino]-1,l'-biihthyl;2 2-bis[di(3,5-xylyl)phosphino]-1,l'-biihthyl( xylbii);
22'-bis[di@-t-butylpheny1)phosphinol-1 ,l '-biihthyk 22-bii[di(gmethoxyphenyl)phosphino]- 1,1 '-biihthy1;
10 2,2~-bis[di(3,5-di-t-buty1-4-methoxyphenyl)phosphino1]' --lb,i ihthy1;
22'-bis[di(cyclopentyl)phosphino]- 1,l '-biihthyl;2 2-bis[di(cyclohexyl)phosphino]-l ,l '-biihthy1;
2,2'-bis(diphenylphosphin0>5,5',6,6',7,7',8,8'dydro-l,l'-b'lnaphthyl;
2~'-b'Is(di-ptolylphosphin0>5~5',6,6',7,7',8,8'dydro,l- 'l- biihthy1;
2,2'-bis(di-m-tolylphosphin0)-5,5',6,6',7,7',8,8'~ydro-l,l '-binaphthyl;
15 2~'-bis(di-3,5-xylylphosphino>5,5',6,6',7,7',8,8'dydro-l,l'-binaphthyl(xylyl-H8-~~);
22'-bis(di-pt-butylphenylphosphino)-5,5',6,6',7,7',8,8'4ydro-l,l '-biihthyl;
2~'-bis(di-pmethoxyphenylphosphino>5,5',6,6',7,7',$8'+ctahydro-l ,l '-binaphthyl;
2,2'-bis(di-pchlorophenyIphosphino>5,5',6,6',7,7',8,8'4ydro- 1 ,l '-binaphthyk
2,2'-bis(dicyclopentylphosphin0)-5,5',6,6',7,7',8,8'yl,l '-biihthyl;
20 2,2'-bis(dicyclohexylphosphino>5,5',6,6',7,7',8,8'atahydro-l,1 '-binaphthyl;
((4,4'-bi-l,3-benzodioxol>5,5'-diyl)bis(&phenylphosphineXsegphos);
(4,4~-bi-1,3-be~oxol>5,5'diyl)b'idi(3,5-xy1y1)phosphine) (dm-segphos);
((4,4'-bi-1,3-benzodioxol>5,5'diyl)bis(di(3,5-di-t-buty1-4-methoxyphenyl)phosp~;
((4,4'-bi-l,3-benzodioxol)-5,5'dyl)bis(di(4-methoxyphenyl)phosphine);
25 ((4,4'-bi-l,3-benzodioxol>5,5'-diyl)bis(dicyclohexylphosphine);
22'-biis(di-ptolylphosphin0>6,6'ðoxy- 1,l '-biphenyl;
2~,6,6'-~ethoxy4,4'-biidi-3,5-xylylphosphin0~'-3b,i3p yridine (xylyl-p-phos);
2,2',6,6'-tebamethoxy4,4'-biidiphenylphosphino>3,3'-bipyri~e;
22',6,6'-tebamethoxy4,4'-biidi-ptolylphosphino>3,3'-bipyridine;
2,2',6,6'-tebamethoxy4,4'-bis(di~tolylphhino>3,3 '-bipyridine;
4,12-bidi-3,5-xylylphosphin0)[2.2]-par; 4,12-biidiphenylphosphinoj[22]-paracyclophane;
4,12-biidi-ptolylphosphino j[2.2]-pamcyclophane 4,12-bis(di~to1ylphosphinoj[2.2]-paracyc10phane;
1,l '-bis(2,4diethylphosphotano)ferrocene; 1,13-biidiphenylphosphinoj7,8-dihy~dib[f,h][1,5]dio~onin;
1,13-bis(bis(3,5~ethylpheny1)phosphinoj7,8-dihy~di~[~][1,5]dioxo(nxiynly lC3-tunephos); and
6,6'-biis(bis(3,5-dim&y1phenyl)phosphino)2J,3,3'-tetrahyb5 3'-bi-l,4--oxin (xylyl-synphos).
In addition to those described above, examples of the biiphosphine compound which can be used for the invention
include N,N-dirnethyl-l-[l'~-biidiphenylphosphino)fmwenyl]ethyle;2 ,3-bis(dipheny1phosphino)butane;
1 cyclohexyl- 1 2-biidipheny1phosphino)dhane;
2,3Qisopmpylidene-2,3-dihydroxy- 1,4-biidipheny1phosphino)butane;
12-bis[(o-methoxyphenyl)phenylphosphino]ethane; 1 J-bis(2,5+ethylphosphorano-e;
NP-bis(diphenylphosphino>N,N'-bis(1-phyylylene; 12-bis(dipheny1phosphino)propane;
2,4-bis(dipheny1phosphino)pentane; cyclohexylanisylmethylphosphine; 2,3-bis(diphenylphosphin0 j5-norbomene;
3,4-bis(diphenylphosphino>l-tmqIpyrrolidine,;1 -[lY,2-bis(diphenylphosphino)fmwenyl]ethyIa lcohol;
22'-bis(diphenylphosphinoj1, 1 ' d i c y c l o p e sodium ;
22'-bis(diphenylphosphino> 1, l-binaphthy1-5,5ydisulfonatseo,d ium ;
2,2'-bis(di(3,5-xylyl)phosphino>l,l-b'lnaphthyl-5,5'~ulfonate;
I, 1 <2,2'-biidiphenylphosphinojl ,l ' - b i n a p ;
1, 1 -(2,2'-bis(di(3,5-xylyl)phosphino)-l,l '-biqhthy14,6ydiyl)~~methylene)~~e;
(6,6'-bis(~3,3,4,4,5,5,6,6,7,7,8,8,8-trideCan~0~l)si1l'y -lbjiln,ap hthyl-2,2'diyl)bls(diphenylphosphine);
(6,6'-bis(tris(3,3,4,4,5,5,6,6,7,7,8,8,8-trideCan~0~1)~ilylj'l-,bl ilnaphthyl-2~'diyl)bis(di(3,5-xylyl)phosphine);
(22'-bis(diphenylphosphinoj1, 1 '-blnaphthyl4,4'-diyl)dimhamine.hyd bromide salt
(22'-bii(di(3,5-xylyl)phosphino>l,l '-binaphthyl-4,4'diyl)dun~e-hydrogenb romide salt;
(4,4'-bis(trimethylsiily1)-1,1 '-binaphthyl-2,2'-diyl)bls(diphenylphosphine);
(4,4'-bis(trimethyIS'iyl>1,1 '-binaphthy1-2J'diyl)bis(di(3,5-xylyl)phosphine);
(4,4'-bis(triisopmpylsilylj1,l '-bihthyl-2J'diyl)biidiphenylphosphine);
(4,4'-bis(~ppylsily1j1,1'-blnaphthyl-2J~yl)~~di(3,5-xylyl)phosphine);
2J'-bis(diphenylphosphino>l,l '-binaphthy1-4,4'-diyldiphosphonic acid;
2,2'-bis(di(3,5-xylyl>phosphino) 1, l y-b'qhthy14,4ydiy1Qh~sphonaicci d;
~y12~-bis(diphenylphosphino,)1- ' l- b h t h y l y 4 ' d i y l p h o s p h o , tetraethyl ;
(4,4'-dichlom 1,l '-b'ihthyl-2Tdiyl)bis(diphenylphoqhine);
(4,4'-dichloro-1,l '-biihthy1-2,2'-diyl)bi~di(3,5-xylyl)p;
(4,4'-dibmmo-1,l '-biihthyl-2,2'-diyl)bis(diphenylphosph;
(4,4'dibmmc- 1,1 '-blnaphthy1-2,2'dyl)bis(di(3,5-qlyl)phosphine);
5 (4,4'dimethyl-l,l'-binaphthyl-2,2'diy1)b'idiphenylphosph;
(4,4'dimethyl-1,l ' - b i i h t h y l - 2 , 2 ' d i y l ) b ( 3 - l y l h o e ) ;
(27-bis(diphenylphosphino>l ,I '-biihthyl-4,4'-diyl)b;s(diphenylmethanol);
(22'-bii(di(3'5-xylyl)phosphino>l ,l y-4
(4,4'-bis(1,1,122,3,3,4,4,5,5,6,6,8,8,9,9,10,10,11,11,12,12,13,13,13-hexacoSanu0r0-7~uomhexy1)tridecan-7-y1)
10 -1,l '-biihthyl-2,2'diyl)bik(diphenylphosphi;
(4,4'-bis(1,1,122,3,3,4,4,5,5,6,6,8,8,9,9,10,10,11,11,12,12,13,13,13-hexacosafluom7~~0mhe~1)tridecan-7-y1)
-1,l '-b'lnaphthyl-2,2'diyl)bis(di(3,5-xyl;
(7,7'+ethoxy-l ,l '-biihthyl-2,2'-diyl)bis(diphenylphosph;
(7,7'dimethoxy-1,l '-biihthyl-2,2'diyl)bis(di(3,5-xyly1)phosphine);
15 4,4'-di-tert-buty14,4',5,5'-te~dro-3~'H-3,3'-bi~htho[2,1~:1',2'e]phosphapine;
1,2-bii3Hdinaphtho[2,1 c:1',2'-e]phosphapin-4(5H)-yl)~e,
3,3'-biidiphenylphosphino)-4,4'-biphenanthme;
3,3'-biidi(3,5-~ylyl)phosphino)-4,4'-biphenanthrene;
(3,3'diphenyl-1,l ' - b i i h t h y l - 2 , 2 ' - d i y l ) ~ ;
20 (3,3'diphenyl-l,l'-~~hthyl-2~'-diy~)~Is(methylene)bk(di(3,5-xylyl)phosp~ne);
23'-bis(diphenylphosphinooxy>l ,l y -bins 2~'-bIs(di(3,5-xylyl)phosphinooxy)-l, 1 '-binaphthyl;
(3,3 'dimethyl-1, 1 '-biihthyl-2,2'diyl)bjs(oxy)bis(diphenylphosphine);
(3,3'dimethyl-1,l '-biihthyl-2,2'-diyl)bis(oxy)bis(di(3,5-~lyl)phosphine);
(3,3'-diphenyl-1,l '-binaphthyl-2,2'-diyl)bi~o~)biidiphenylphosphine);
25 (3~'~phmyl-l,l'-binaphthyl-2,2'-diyl)bi~o~)bis(~(3,5-~lyl)pho~hine);
(3,3 '-bii(3,5dimethylphenyl)-1,l ' - b i i h t h y l - 2 , 2 ' d i y I ) b I s ( o x y ) b i s ( d i p h ~ ;
(3~'-biis(3,5dimethylphenyl>l,l'-~~hthyl-~'-diyl)b~oxy)bis(di(3,5-~lyl)pho~hine);
(3,3'diphenyl- 1, 1 '-binaphthyl-2,2'diyl)bis(oxy)bIsO,Is(3,5dimethy1pheny1)phosphine);
N2,N2'-bis(diphenylphosphin0) 1 ,l '-binaphthyl12,2'-diamine;
30 N2~T-bis(di(3,5-xylyl)phosphino>,ll '-biihthyl-2,2'-diarnine;
(SP>l -[(S)u1 -[@)a2~diphenylphosphino)~l]-2diphenylphosphinofme;
(R>1-{(RP>2-[2 1 -{(SP>2-[2-(diphenylphosphino)phenyl]fmy 1} ethy ldiphenylphosphine;
35 @>1 - { ( R P > 2 - [ 2 - ( d i p h e n y l p h o s p h i n o ) p h e n y l ] f ~ ;
(SF1 -{(SP>2-[2phenyl]fmyl}ethyldiqclophosphine;
@>1 -{(RP)-2-[2~diphenylphosphino)phenyl]f~ di(2-norbony1)phosphi.e;
(SF1 -{SP>2-[2<&phenylphosphino)phenyl]fmyl}&yldi(2-no~nyl)phosp~e;
0-1 -{(RP)-2-[2-(diphenylphosphino)phenyl]f~,5-xylyl)phosphine;
(S>1-{(SP>2-[2<&phenylphosphino)phmyl]f~y1}ethyl&(3,5-xylyl)phosphine;
0-1 -{(RP>-2-[2-[di(3,5-xylyl)phosphino]ph~yl]fmyl}ethyldi(3,5-xylyl)phosphine;
5 (S>1-{(SP>2-[2-[~(3,5-~lyl)phosphino]ph~}&yldi(3,5-xylyl)phosphine;
@)- 1 -{(RP>-2-[2I -{(SP>2-[2-(diphenylphosphino)phmyl]f~}ethylbis[3,5-bis1 - { ( R P ) - 2 - [ 2 - @ S i 4 - m e t h o x y - 3 ~ 5 d i m & y l p h ~ , 5 - b i s ( ~ u o r o m & y l
)phmyl]phosphine;
10 (S>1-{(SP>2-[2-[b~4-meth0xy-3,5dim&y1pheny1)phosphin0]pheny1]f~y1}&y1bis[3,5-b~trinuommethy1)
phenyllphosphine;
3,3',4,4'-tetramethyl-1,l' dipheny1-2,2',5,5'-~ydro-lH,'lH -22'-biphosphol;
l,l'd-tert-butyl-22'-biphosphme; 22'-di-tert-butyl-22',3,3'-tetrahydro-lH, 1 'H-1, 1 '-bisisophosphoindole;
1,2-bis(2,4dimethylphosphetan-I-y1)ethane; 12-bis(2,5dimethylphosphom-1-y1)ethane;
15 12-bis(2,4dimethylphosphetan-1-ylb)e nzene; 1,2-bis(2,5-dimethylphosphoran-1- yl)benzene;
3,4-bis(2,5-dimethylphosphomn-l-yl)h-2,5dion3e,;4 -bis(2,5diethylphosphoran-1-yl)f iuan-2,5dione;
3,4-bii2,5dimethylphosphoran-1 -yl)-1 -phenyl-1H -pple-2,5dione;
1 <3,5-biitrifluoromethyl)pheny1>3,4-bis(2,5&ylphosphom-l -yl)-l H-pyrrole-2,5dione;
1 <(lR,2S,4R,5S>2,5dimethyl-7-phosphabicyclo[2.2.1]heptan-7-y1>2-((2R,5S)-2,5dimethyl-7-phosphabicyclo[2.2
20 . llheptan-7-y1)benzene;
1,l '-(benzo[b]thiophene-2,3diyl)bis(2,5dimethylphosphme);
(22',4,4'-telIamethy1-3,3',4,4'-tetrahydro-2H,2'H6,6'-bibenzo@] [1,4]dioxepin-7,7'diyl)bis(diphenylphosph;
(2~',4,4'-tetramethyl-3,3',4,4'-tetrahydro-2~'H6,6'-bibenzo@][l,4]dioxepin-7,7'diyl)bis(&(3,5-xy]yl)phosphine
1;
25 ((6R>6,7-dimethy14,7-dihyMb[e,g] [1,4]dioxosin-1,12diyl)bis(diphenylphosphine);
((6R)-6,7dimethy16,7-dihy~~[e,g][l,4d]i oxosin -1,12-d1yl)biidi(3,5-xylyl)phosphine);
(4,4',5,5',6,6'-hexamethylbiphenyl-2J'~yl)b~&phenylphosphine);
(4,4',5,5',6,6'-hexamethylbiphenyl-2,2'diyl)biidi(3 J-xyly1)phosphine);
(4,4',5,5',6,6'-hexamethoxybiphmyl-2J'diyl)bis(&phmylphosphhe);
30 (4,4',5,5',6,6'-hexamethoxybiphenyl-22'diyl)bis(di(3 J-xyly1)phosphine);
(5,5'-dichloro-4,4',6,6'-tetmmethylbiphenyl-2~~-diyl)bis(diph~;
(5,5'~~hl0ro-4~4'~6,6'-~ethylbiphenyl-2~-diyl)bk(di(3,5-xylyl)phosphine);
(5,5'ðoxy4,4',6,6'-telIamethylbiphenyl-2~'diyl)b~&phmylphosphine);
(5,5'ðoxy4,4',6,6y-~ethylbiphenyl-2~'dyl)bis(~(3~5-xylyl~hosphine);
35 2~'-biidiphenylphosphin0)-6,6'dimethoxybiphenyl-3,3'diol;
2~'-biidi(3,5-xylyl)phosphino>6,6'dimethoxybipheny1-3,3'dol;
(3,3',6,6'-~ethoxybiphenyl-2,2'diyl)biidipheny1phosphine);
(3,3 ',6,6'-tet1ametho~iphenyl-2~'-diyl)bis(di(3,5-xylyl)phosphine);
(3,3'~ppyl-6,6'+ethoxybiphenyl-2J'diyl)bis(diphenylphosphine);
(3,3'&pmpyl~,6'-dimethoxybiphenyl-2J'diyl)b'Is(di(3,5-xylyl)ph0~phine);
(6,6'ðoxy-3,3'-b'Is@tolyloxy)biphmyl-2~'~yl)b'~diphenylphosphine);
5 (6,6'ðoxy-3,3'-bis@-tolyloxy)biphenyl-2~'-diyl)bis(di(3,5-~1y1)phosphine);
2,2'-b'idiphenylphosphin0>6,6'd1methoxybipheny1-3,3'diyl bis(2J+ethylpmpanoate);
2,2'-b'Is(di(3,5-xylyl>phosphino>6,6'-dimetho~biphenyl-3,3'-diylbis(22-dimethylpmpanoate);
(5,5'dich1oro6,6'+etho~iphenyl-2J7diy1)bis(dipheny1phosphine);
( 5 , 5 ' d i c h l o r o 6 , 6 ' d i m e t h o x y b i p h e n y l - 2 ~ ' d i y l ) b ~ ;
10 6,6'-b'idipheny1phosphino)biphenyl-2J'diyl diacetate;
6,6'-biis(di(3,5-xylyl)phosphino)biphenyl-2,2'diyl diacetate;
6,6'-bis(diphenylphosphino)biphenyl-2J'-diylb~2Jðylpmpmoate);
6,6'-bis(di(3,5-xylyl)phosphino)biphenyl-22'diylbis(2J~ethylpmpanoate);
6,6'-b'is(diphenylphosphino)biphenyl-2~diylbis(2-methylpmpanoate);
15 6,6'-~Is(di(3,5-xylyl~hosphino)biphenyl-2,2'diylb~2-methylppm~);
6,6'-b'idipheny1phosphino)biphenyl-2r-diyl dicyclohexane carboxylate;
6,6'-bis(di(3,S-xyly1)phosphino)biphenyl-2yl dicyclohexane carboxylate;
( 4 , 4 ' , 6 , 6 ' - ~ t r i n u o m m e t h y 1 ) b i p h ~ ;
(4,4',6,6'-te~trinuommethyl)biphenyl-2J'diyl)bis(di(3,5-xylyl)phosphine);
20 (5-methoxy4,6ðy14',6'-bis(~fluomm&yl)biphenyl-2~diyl)bis(diphenylphosphine);
( 5 - r n e t h o x y 4 , 6 & e t h y l 4 ' , 6 ' - b ' I s ( t r i n u o ~ ;
(2JJ'J'-tetramethyl4,4'-bibem[d][l,3]dioxol-5,5'-diyl)bis(diphenylphosphine);
(2,2,2',2'-tetramethyl-4,4'-bibenzo[d][l,3]dioxol-5,5'-diyl)bis(di(3,5-~lyl)ph0~phine);
6,6'-b~diphenylphosphin0>22',3,3'-tetmhydro-7,7'-bi~~
25 6,6'-bis(di(3,5-xylyl)phosphino)2J',3,3'-tetrahydro-7,7'-bibenzofUran;
(222'2'-tetrduoro-4,4'-bibem[d] [1,3]dioxol-5,5'diyl)bis(diphenylphosphine);
(2~,2'~'-tetr~uoro-4,4'-bibenzo[d][1,3]dioxol-5,5'-diyl)bis(di(3,5-xylyl)phosphine);
2+aphthyl)-8diphenyIphosphino- 1- [3,5dioxa4-phosphacycloh~2,1-a ;3,4-aY]dmaphthalene4-yl]-1J -dihydm
quinoline;
30 4,12-b'Is(di(3,5-xy1yl)phosphin0>[2.2]-paracyclophane;
7,7'-bis(di(3,5-xylyl)phosphino)22',3,3'-~ydro-l,l'-spirob'indane Pyl-SDP);
7,7'-biidiphenylphosphino>2,2',3,3'-tet~ahydro-ll, ' -spirobiindane (SDP);
bi2diphenylphosphinophenyl) ether (DPEphos);
4,5-bis(diphenylphosphinomethyl>2,2dimethy1-1,3-dioxolan( DIOP);
35 12-biidipheny1phosphino)propane (PROPHOS);
2,3-biidipheny1phosphino)butane (CHIRAPHOS);
1,2-bis[(2-methoxyphenyl)(phenyl)phosphino]ethane (DIPAMP);
3,4bis(diphenylphosphino)- 1 -benzylpyrrolidine (DEGUPHOS);
2,3-biidiphenylphosphino)bicycl0[2.2.l]hepb5ene (NORPHOS);
1-~ary-buto~&nyl-4-diphenylphosphin2diphylphphinom&yle (BPPM);
(2,2'-bii-(dibfurstn-3,3diyl)biidiphenylphosphine (BIBFUP);
5 22-biidiphenylphosphho)3,3-biihtho[b]h (BINAPFu);
2,2'-biidiphenylphosphino)3,3'-bi[benzo[blthiophene] (BITJANP);
N , N ' - d i m e t h y l - 7 , 7 ' - b i i d i ( 3 , 5 - x y l y l ) p h o ~(X yl-Solphos);
2,3-biitertiary-butylmethylphosphino) quinoxaline (QuinoxP*);
~4b'Is(diphenylphosphho)pentan(eS KEWPHOS);
10 2,4biIS(di(3,5-xylyl>phosphino>pentane (XylSKEWPHOS);
4,4'-b'Is(diphenylphosphino)2~',5,5'-~&yl-3,3'-bi~ophen(eT MBTP);
3,3 ' -biidiphenylphosphonyl>l , 1'-22'-biidole @I-Me-2-BINPO);
(2~',5,5'-~ethyl-3,3'-bithiophen~,4'yl)diphylphhh(eB)I TIANP);
(4,4',6,6'-~ethyl-3,3'-bib[b~ophene2Jy-diy1)bis(dipheny1phosphin(ete)t raMe-BITIANP);
15 1,l '-bIs(diphenylphosphino)3,3'ðyl-1 H, 1 'H-22-biindole (BISCAF');
22'-biIs(diphenylphosphino)3,3'-bibfuran (BICUMP) and
2,2'-bis(diphenylphosphino)l , 1 '-bib[d]imidazole (BIMIP).
The diphosphine which can be used for the invention as specifically exempEed in the above may be an optically
active diphosphine.
20 Nexf a method for preparing the ruthenium complex of the invention will be explained.
The ruthenium complex of the invention can be prepared by the ruthenium compound represented as Formula (A)
reacting with diamine compound Otherwise, the ruthenium complex of the invention can be prepared by the
ruthenium compound represented as Formula (B) reacting with a diphosphine compound represented by P"P, and
then with the diamine compound.
25 The ruthenium cornpound represented as Formula (B) (hereinafter, referred to as an m e complex) is the
commercial product, or can be prepared accordmg to a known method. Otherwise, the ruthenium compound
represented as Formula (AXhaeinaAer, ~ferredto as an me-phosphine complex) is the comme~iaplm duct, or can
be prepared by the ame complex represented as Formula (B) reacting with a diphosphhe compound represented by
P^P, acc~rdintgo a known method
30 The examples of the m e represented as L in Formula (A) or Formula (B) include CsCm aromatic compound
which may have a substituent mmplexible for ruthenium atom, preferably cyclic aromatic compound. The example
of the preferably arene includes benzene; o-, m-, or pxylene; o-,m-,or p-cymene; trimethyl benzene, such as
mesitylene. The preferable examples of the mthenium compound represented as Formula (B) include the ruthenium
compound coordin- with an aromatic compound such as p~CI~@enzene)]~~~, Cl2(PCymene)]a~nd,
35 @uClz(mesitylene)]2. Otherwise, the preferable example of the ruthenium compound rep& as Formula (A)
include the ~utheniumco mpound coordinating with a aromatic compound such as puC1 (benzmep'T)]CL [RuCI
@cymenep'T)]Cl and puCl(mesitylene)(F-P)]Cl.
The examples of the diamine compound include the diamine compound having tow endmost amino group that
more than one of the amino groups have an a-substituent of aryl group, the prefdly diarnine compound
w t e d by the following Formula (8)
[Chern. 131
5
(in the formula, Ra, Rb and Rc each independently r e p m t a hydrogen atom, an optionally substituted CICm alkyl
group, or an optionally substituted CzCm alkenyl group, or an optionally substituted C3Cs cycloallojl group, or an
optionally substituted C&ZO arallOjl pup, or an optionally substituted aryl pup, or an optionally substituted
heterocyclic group or R~ and Rc may be form an alkylene group or an alkylenedioxy pup; R ~ 'R,M , RM and RN4
10 each independently represent a hydrogen atom,a n optionally substituted C1C20al kyl group, an optionally substituted
C2Cm alkenyl group, an optionally substituted CT% arallcyl group, or an optionally substituted C3Cs cycloalkyl
group, and at least one of RM,R ~RN,3a nd RN4re presents a hydrogen atom; or R ~a'nd Ra may form alkylene group,
and n is an integer of 0 to 3 and& qmsmts an optionally substituted arylene group.)
Meaning of the each symbol of the substituent group included in the Formula (8) are the same as those described
15 above.
Specific examples of the diamine compound represented by the Formula (8) used in the invention include
1,2diphenyIethylenediamine; 1,2-b1~(4-methoxyphenyl)ethylenediamine; 1 -methyl-22diphenylethylenediarnine;
1-isobutyl-2,2diphenylethylenediamine1;- isopmpyl-2,2dphenylethylenediamine( DPIPEN);
1- methy1-2,2-bls(4-methoxyphenyl)ethy(DlA~ MEN);
20 1 -isobutyl-2,2-bis(4-methoxyphenyl)ethylenediamine;
1- isopropyl-2,2-bis(4-methoxyphenyl>ethy1enediamin(eD AIPEN);
1- phenyl-2~-bis(4-methoxyphenyl)ethyl~e1;, ldiphenylethylenediamine (I,1 -DPEN);
l,l-b;s(4-rnethoxypheny1>ethylenediamineP AEN); and l-isopmpyl-2,2-bis(3-methoxyphenyl)ethylenediamine
(3-DAIPEN). These diamine compounds may be an optically active diamine compound In the case of optically
25 active diamine compound, there is (R) or (S) at the ahead of its name to show the optically activity.
Specifically, the method for preparing the ruthenium complex of the invention is as follows.
The method for preparing an arenephosphine complex is described, see e.g. J. CHEM. SOC., CHEM.
COMMUN 1208 (1 989), and by reacting the arenephosphine complex present as the prepared solution or as a solid
matter obtained after crystabifion, and solvent drying, etc. with the diamine compound r e p r e d by the Formula
30 (8) in an amount of at least one equivalent, preferably 1 to 20 equivalents, more preferably 1 to 10 equivalents, and
still more preferably 1.1 to 5 equivalents relative to the arene-phosphine complex, the nahenium complex of the
invention can be obtained In addition, the preparation method of the invention is canied out in the pmence of an
alcohol, and the alcohol may be used slngly or in combination with other solvent Examples of the alcohol used
herein include a lower alkanol such as methanol ethanol n-propanol 2-propanol and n-bhnol. Prefenred
examples of alcohol include methanol and ethanol. In addition, although an additive is not necessarily requkd, by
adding 0.1 to 2 equivalents, prefixably 0.5 to 1.5 equivalents and more prefaably 0.9 to 1.1 equivalents of a base
relative to the arene-phosphine complex, the complex can be efficiently produced.
5 Thus, the invention provides a method for preparing the ruthenium complex qresented by the Formula (I) by
reacting the amephosphine complex and the diamine compound rkpmented by the Formula (8) in the p m c e of
a lower alcohol. More specific all^ the method of the invention is carried out in the presence of a base, in particular
an organic base.
As a base, an inoganic base and an organic base can be mentioned Examples of an inorganic base include
10 potassium carbonate (GCQ), lithium hydroxide (LiOH), sodium hydrogen catoonate (NaHCQ), sodium carbonate
(NaKQ), potassium hydrogen carbonate (KHCO,), potassium methoxide (KOCH3), sodium methoxide (NaOCH3),
lithium methoxide (LiOCH3), sodium ethoxide (NaOC&CH3), sodium acetate (CH3CQNa), potassium
isopropoxide (KOCH(CH3b), potassium tert-butoxide (KOC(CH3B), potassium naphthalenide (KCl&&J cesium
carbonate (CeCQ) and silver arbmate (A&03). Examples of an organic base include organic amines such as
15 triethylamine, diethylamine, diisopropylarnine, d~hpropylethylamine, N,Ndiiethylaniline, piperidine, pyridine,
4dimethylaminopyridine, 1,5-diazabicyclo[4.3.0]nona-5ene,1 ,8diazabicyclo[5.4.0]undeca-7ae,t ri-n-butylamine
and N-methylmorpholine.
As a catalyst for asymmetric reduction, the ruthenium complex of the invention has an excellent catalytic activity.
By using the ruthenium complex ofthe invention as a catalyst for asymmetric reduction, alcohols can be produced by
20 ~ e t r irecdu ction of a carbony1 group. Examples of the carbonyl p u p for the preparation method of the
invention include a carbon/oxygen double bond such as a keto group and an ester pup. Prefmble carbonyl p u p
includes a keto group. In particular, as being in excellent in terms of enantioselectivity, etc., the catalyst for
asymmetric reduction of the invention is suitable for a method for producing optically active alcohols fbm a
prochiral keto group.
25 The method for preparing alcohols of the invention can be preferably carried out with or without a solvent.
However, it is preferably carried out by in the presence of a solvent. As for the solvent used, those which can
dissolve a substrate and a catalyst are preferable, and a single solvent or a mixture solvent is used. Specific
examples include an aromatic hydrocarbon such as toluene and xylene, an aliphatic hydrocarbon such as heme and
heptane, a halogenated hydmarbon such as methylene chloride and chlombenzene, an ether such as diethyl ether,
30 tetrahydrofmn, methyl tert-butyl ether and cycloptylmethyl ether, an alcohol such as methanol ethanol
2-propanol, n-butyl alcohol, 2-butanol and ter-butyl alcohol and a polyol such as ethylene glycol, pmpylene glycol,
12-propanediol and glycerin. Among these, an ether or an alcohol is preferable. Particularly p r e f d solvents
include tetmhydroiimq methanol ethanol and 2-propanol. Use amount of the solvent can be appropriately selected
depending on reaction condition, etc. The reaction is carried out under stining, if n m ,
35 The use amount of the catalyst varies with the reduced substrate, a &on condition or type of a catalyst, etc., but
it is generaUy in the range of 0.00001 mol% to 1 mol%, and preferably 0.0001 mol% to 0.5 mol% in terms of the
molar ratio of the ruthenium metal relative to the substrate to be reduced.
Moreover, the asymmetric reduction of the invention is prefdly canied out by adding a base compound
Examples of the base compound to be used include an inoganic base and an o@c base. Examples of the
inorganic base include potassium carbonate (K2C@), potassium hydroxide SOH), lithium hydroxide (LiOH),
sodium hydrogen carbonate (NaHCQ), sodium carbonate (NazCQ), potassium hydrogen carbaate (KHCQ), and
5 sodium hydroxide (NaOH). Examples of the organic base include an alkali.alkali earth metal salt such as potassium
methoxide (KOCH3), sodium methodde (NaOCH3), lithium methodde (LiOCH3), sodium ethoxide (NaOCHzCH3),
potassium isoppoxide (KOCH(CH3)-3, potassium tat-butoxide (KOC(CH3h), and potassium naphblenide
(KC1&&) and an organic arnine such as triethylamine, diethylamine, diisoppylethylamine, N,N-dimethyllaniline,
piperidine, ~fidine, 4dimethylaminopyridine, 1,5diazabicyclo[4.3 .O]nona-Sene,
10 1,8-diazabicyclo[5.4.O]undeca-7enet,r i-n-butylamine and N-methyhnorpholine. In addition, the base to be used in
the invention can be metal hydrides such as sodium hydride and potassium hydride. In addition, the base to be used
in the invention is not limited to the bases described above, and hydrogen and others that can generate an
amine-phosphine ruthenium hydride complex can be used. These bases can be used singly or in appmpriate
combiion of two or more. Preferred examples of the base compound include an inoqpic base and an
15 alkali.alkali earth metal salt.
The use amount of the base compound is 1 to 10000 equivalents, and preferably 10 to 5000 equivalents compared
to the mole number of the ruthenium complex, or it is in the mge of 0.00001 mol% to 50 mol%, and preferably
0.0001 mol% to 30 mol% in terms of the molar ratio of the base compound relative to the substrate to be reduced
With regard to the method of the invention, the reaction temperahue for carrying out asymmetric hydrogenation as
20 asymmetric reduction is -30°C to 100°C, and preferably 0°C to 50°C. If the d o n tern- is too low, large
amount of raw materials may remain unreacted On the other hand, if it is too high, raw materials and the catalyst
may decompose, and therefore undesirable. The present invention is also characterized in that the asymmetric
hydrogenation can be carried out at low temperature, for example -30 to 30°C.
With regard to the invention, as the catalytic system has an extremely high activity, the hydrogen p u r e as
25 atmospheric pressure (0.1 MPa) which is enough for canying out the asymmetric hydrogenation. However, it is
prefdly 0.1 MPa to 10 MPa, more preferably 0.1 MPa to 6 MPa, and still more preferably 0.1 MPa to 3 MPa.
Furthermore, the reaction time is 1 minute to 72 hours, and preferably 30 minutes to 48 hours to obtain d3iciently
high conversion rate of raw materials.
With regard to the asymmetric reduction of the invention, an asymmetric hydrogen-mfer reduction is canied out
30 by reacting the ruthenium complex of the invention in the presence of a hydrogen donor. The hydrogen donor is
not specifically limited if it was generally used for hydrogen-tmnsfer reduction, including formic acid or its salt, and
an alcohol in which a hydrogen atom is present at a position of the carbon atom substituted with a hydroxy group, i.e.,
2-propanol. However, combination of 2-ppanol and a base compound is preferable. The examples the base
which can be used herein include a tertiary organic amines such as trimethylamine, triethylamine and
35 triisopmpylamine and an inorganic base such as LiOH, NaOH, KOH and K2CO3. The base is used in an excess
amount corn@ to the ruthenium complex, for example, 1 to 10,000 times in molar ratio.
Ifthe hydrogen donor is liquid, it can be g e n d y used as a solvent for the d o n . However, it is also possible
to use a non-hydrogen donor solvent such as toluene, ktmhydrofiam, acetonitrile, dimethyl forrnamide and dimethyl
sulfoxide as a co-solve@ either singly or as a mixture for dissolving raw materials.
The use amount of the ruthenium complex as a catalyst is generally selected within the range of 0.000001 mol% to
5 moly% and preferably 0.0001 mol% to 2 m01% in terms of molar ratio of the ruthenium complex compared to the
5 s u h t e to be reduced
The use amount of the hydrogen donor compared to the substrate to be reduced is generally the same molar
amount or more, and when the hydrogen donor is formic acid or its salt, it is preferably used within the range of 1.5
times molar amounts or more, and also 20 times molar amounts or less, and preferably 10 times molar amounts or
less. On the other hand, when the hydrogen donor is 2-propanol or the like, the hydrogen donor is used in a large
10 excess with respect to the subshate h m the viewpoint of reaction equilibrium, and is usually used in a 1000-fold
molar amount or less.
The reaction tan- is selected within the range of -70 to 100°C, and preferably 0 to 70°C.
The &on pressure is not specifically limi@ and it is generally 0.05 to 0.2 MPa, preferably atmospheric
P-.
15 The reaction time is 0.5 to 100 horn, and generally 1 to 50 hours.
After the reaction is completed, a purification method which is generally used, for example, exh.action, filtration,
crystakation, distillation and various chromatographies, is canied out either slngly or in appropriate combion to
obtain desired alcohols.
20 Examples
Hereinafter, the Examples are described and the invention will be described in gmkr detail. However, the
invention is not limited by the following Examples.
Measurement of 'H-NMR spectrum and 31~-NMRsp ectrum was canied oa by using MERCURY plus 300
manufktud by Varian, Inc., and the MS measurement was carried out by using JMS-TlOOGCV m a n u f i by
25 JEOL or LCMS-IT-TOF manufktwd by Shimadzu Corporation
m a p l e 1)
Prepamtion of RuCl[(S>xylb'i][(S>daipen]:
[Chem. 141
Me0
OMe
Jnder nitrogen gas, [RuCl~(pcymene)3]~.0 7 g (5.0 mmol), (S>XylBINAF' I rnmol) and methanol
mL were added to a 200 mL 4-neck flask The mkdm was heated to 50°C and stirred for 2 hours to prepare
[RuCl(pcymeneX(S)-xylbinap)]Cl. The reaction solution was c o o k down to room tern-, then
diethylamine 736 mg (10 mmol) and (SFDADPEN 3.48 g (11.1 mmol) wae added to the &on solution, and
stirred for 3 hours at 6O0C. After concmbation, the residue was dissolved in butyl acetate and the precipitated salts
5 were sepamkd by flfdon The iilrate was concenbated and the mixture added with heptane (110 mL) was
coolug down to -lO°C. The precipitated crystals were l i l t e d to obtain the title compound (1 1.62 g) with yield of
98%.
31~-NM(R~ 6 ~ 68) :
53.2 (4 J=38.6 Hz), 61.0 (4 J=38.6 Hz)
10 TOF-mass (FD): rnl~1184.3(t heoretical value: 1184.4)
ESI: m/z=1184.3967 (theoretical value: 11 84.3890)
Elemental analysis (Wto?) Ru 8.6, P 5.2, C13.1, H 5.77, C 71.48, N 2.29 [measured value]
Elemental analysis (Wto?) Ru 8.5, P 5.2, C13.0, H 6.2, C 72.0, N 2.4 [calculated value]
(Comparative example 1)
15 w o n of trans-RuClz[@)xylb'lnap][@)daipen]:
[Chem. 151
Under nitrogen gas, (RFDAIPEN 314.4 mg (1 mmol) was added to the mixture of
[RuCl@cymeneX(R>xylbii)]Cl 1.04 g (1 mmol) and toluene 10 mL and stirred at 80°C for 2 hour;. The
20 reaction solution was concentmkd to obtain the title compound (1.2 g).
3 1 ~(c6D-6):~ 8
44.1 (d, J=37.3 Hz), 46.0 (4 J=37.3 Hz)
TOF-mass (FD): m/z=1220.3 (theoretical value: 1221.9)
Elemental analysis (Wto?) Ru 8.1, P 4.6, C15.9, H 5.8 1, C 69.86, N 2.21 [measured value]
25 Elemental analysis (wt??) Ru 8.3, P 5.1, C15.8, H 6.1, C 69.8, N 2.3 [calculated value]
(Example 2)
w o n of RuCl[(FQ-xylbjnap][(R)daipen]:
[Chem. 161
OMe
Except that (S)-XylBINAP was changed to @)-XylBW and (S>DAIPEN was changed to @)-DAIPEN, the
experiment was carried out in the same manner as Example I to obtain the tide compound with yield of 98%.
(Example 3)
5 w o n of RuCI[(R)dm-segphos][(R)daipen]:
[Chem. 171
OMe
Under nilmgen gas, [RuCl2(p-cymene)l24 .24 g (6.92 mrnol), (R)-DM-SEGPHOS 10.00 g (13.83 mmol) and
methanol 200 rnL were added to a 300 mL 4-neck flask The mixture was heated to 50°C and stirred for 2 hours.
10 The reaction solution was cooling down to room temperature, triethylamine 1.40 g (13.8 rnrnol) and (R>DAIPEN
6.52 g (20.7 mol) were added to the reaction solution, and stirred for 20 hours at 45OC. The resulted reaction
solution was cooled to -10°C. The precipitated crystals were filtered to obtain the Mle compound with yield of
59%.
3 ' ~(C&-C12~): 6 ~ ~
51.0 (d, k37.3 Hz), 55.8 (d, J=37.4 Hz)
TOF-mass (FD): m/z =1172.3 (theoretical value: 1172.3)
(Comparative example 2)
Preparation of trans-RuClz[(R)-dm-segphos][(R)daipen]:
[Chem. 181
Under nitrogen gas, (R)-DAlPEN 314.4 mg (1 rnrnol) was added to the mixture of
[RuCl(pcymeneX(R>dm-sesphos)]Cl 1.03 g (1 mmol) and toluene 10 mL and stirred at 80°C for 2 hours. The
reaction solution was concentrated to obtain the title compound (1.2 g).
3 1 ~(c6D-,5): ~6 ~ ~
46.3 (d, J=37.4 Hz), 47.0 (d, J=38.6 Hz)
As shown in Comparalive examples 1 and 2, when the diamine compound is reacted in the absence of an
alcohol only the trans form having no Rucarbon bond was produced.
Example 4)
10 Prepadon of RuI[(S)xylbinap][(S)-daipen]:
[Chm 191
Ar:
OM^
Except that puCl~@cyrnene)]zw as changed to puI@cymene)12, the experiment was carried out in the same
manner as Example 1 to obtain the title compound with yield of 55%.
31~-NM(R% ): 6
53.2 (d, J=38.6 Hz), 62.6 (d, J=38.7 Hz)
5)
Preparation of RuCl[(R)dm-segphos][(S)daipen]:
[Chem. 201
Ar: 4
OM^
Except that @)-DAIPEN was changed to (S>DAlPEN, the experiment was carried out in the same manner as
Example 3'to obtain the title compound with yield of 60%.
31 P -NMR (w)8 :
5 52.6 (4 J=38.7 Hz), 57.5 (4 J=38.6 Hz)
(Example 6)
Prepamhon of RuI[@)&-segphos][@wpen]:
[Chern. 2 11
Ar: \ /
Me0
OMe
10 Except that BuCh(pcymene)]2 was changed to BuI~@-cymene)]2t,h e experiment was carried out in the same
manner as Example 3 to obtain the title compound with yield of 50%.
3 1 ~( ~ 6-) :~8
52.1 (d, J=38.7 Hz), 57.6 (4 J=38.7 Hz)
(Example 7)
15 Preparat;on of RuCl[(R)-segphos][(R)daipen]:
[Chern. 221
OMe
Undernitmgengas, Wh(p-cymenell2 153.1 mg(0.25 mmol), @)-SEGPHOS 305.3 rng (0.5 mmol), ethanol 18
rnL and toluene 15 mL were added to a 50 mL 4-neck flask The mixture was heated to 50°C and stirred for 2
hours. The reaction solution was coolug down to room tern-, a mixture of @)-DAIPEN 471 mg (1 .SO
mmol) and ethanol 4 mL was added dropwise to the reaction solution, and then stimd for 20 hours at the same
tern-. The d t e d reaction solution was cooled to -20°C. The precipitated crystals were filtmd to obtain
5 the title compound with yield of 36%.
31~-NlvlR(C 4C12):6
53.0 (4 J=38.7 Hz), 57.7 (4 J=38.7 Hz)
TOF-mass (FD): m1~1060.8(t heoretical value: 1060.2)
(Example 8)
10 Preparaton of RuCl[(S>xylbii][(S)damen]:
[Chem. 231
Ar:
OMe
Under nitrogen gas, a mixture of [R~Cl~(PCymene6)1]2~. 8 rng (1.0 mmol), (S>XylBINAP 1.47 g (2.0 mmol)
and methanol 15 mL was heated to 50°C and stirred for 2 hours to prepare ~l@cymeneX(S>xylbii)lCl. The
15 reaction solution was cooling down to room temperature, diethylamine 147 mg (2 mmol) and
(SF1, l-bis(4-metho~henyl)pmpane-1,2-dia(mhienreeh afb, ref& to as (SFDAMEN) 0.86 g (3.0 mmol) were
added to the reaction solution, and then stirred for 3 hours at 60°C. The resulted reaction solution was concentmted
and purilied by silica gel column chromatography to obtain the title compound with yield of 59% (1.35 g).
3 1 ~(C&-): ~6
20 54.4 (4 J=38.7 Hz), 61.8 (4 J=38.7 Hz)
(Example 9)
Preparat;on of RuCl[(S>xylyl-meo-biphep][ (S)daipen]:
[Chem. 241
Ar: 4
Under nitrogen gas, a mkttm of ~~Cl~(PCymen4e4).0] ~m g (0.072 mmol), (S>Xylyl-MeO-BPHEP 99.8 mg
(0.144 mrnol) and methanol 3 mL was heated to 50°C and stirred for 2 hours to prepare
[Ru~l(pcymene~(~)-xy1~l-rneo-bi~hep)]~T1h.e reaction solution was cooling down to mom t e r n p e e ,
5 triethylamine 14.5 mg (0.14 rnmol) and (S>DAIPEN 67.9 mg (0.216 mmol) were added to the reaction solution, and
then stirred for 9 hours at 60°C. The resulted reaction solution was concentrated and purified by silica gel column
chromatography to obtain the title compound with yield of 63% (104.3 mg).
3 1 ~(c9-6):~ 6
52.1 (4 J=38.7 Hz), 58.6 (4 J=39.9 Hz)
10 mF-mass (FD): m/~1144
(Example 10)
FTqmWton of RuC1[(S>xylyl-H8-b'lnap][(S~pen]:
[Chern. 251
Ar:
15 Under nitrogen gas, a mixture of [RuCl2@cymene)lz 61.2 mg (0.1 rnmol), (S)-Xylyl-H8-BINAP 149.2 mg (0.2
rnmol) and methanol 3 mL was heated to 50°C and stirred for 2 hours to prepare
~l~ymeneX(S>xylyl-H8-bii)]Cl. The reaction solution was coohng down to mom temperahe,
triethylamine 20.3 mg (0.2 mmol) and (S>DAIPEN 94.3 mg (0.3 mrnol) were added to the reaction solution, and
tben stirred for 8 hours at 60°C. The resulted reaction solution was concentrated and purified by silica gel column
20 chromatography to obtain the title compound with yield of 46% (1 10.0 mg).
3 1 ~(c9-,5):~ 8 ~ ~
52.6 (4 J=39.9 Hz), 55.0 (4 J=39.6 Hz)
Fxample 11)
Preparaton of RuCl[(+)-xylylc3-tunephos][ (S)daipen]:
Ar: 4
OMe
Under nitrogen gas, a mixture of ~uClz@cymene)l261 .2 mg (0.1 mmol), (+)-Xyl~1-C~-TUNEPHO1S4 1.4 rng
(0.2 mmol) and methanol 3 rnL was heated to 50°C and stirred for 2 hours to prepare
5 ~uC1@cymene)((+>xylyi-c3-tunephos)]C1. The reaction solution was coolug down to room tern-,
triethylamine 20.3 mg (0.2 rnrnol) and(S>DAIE'EN 95.1 mg (0.3 mmol) were added to the &on solution, and
then stirred for 8 hours at 60°C. The resulted reaction solution was conamtrakd and purified by silica gel column
chromatography to obtain the title compound with yield of 58% (134.1 mg).
3 1 ~(c6D-6):8 ~
10 53.6 (d, J=38.7 Hz), 57.5 (4 J=38.6 Hz)
(Example 12)
Preparation of RuCl[(R)-xylyl-synphos][(R)da~pen]:
[Chem. 271
Ar: 4
\ OMe
15 Under nitrogen gas, a mktm of ~uCl~@cymene6)1].~2 mg (0.1 mmol), (R>Xylyl-SYNPHOS 150.3 mg (0.2
mmol) and methanol 3 mL was heated to 50°C and stirred for 2 hours to prepare
~uCl@cymene)((R)-xylylsynphos)]Cl. The reaction solution was coolug down to room tempemm,
triethylamine 20.3 mg (0.2 mmol) and (RkDAIPEN 95.0 mg (0.3 rnrnol) were added to the reaction soldon, and
then stined for 8 hours at 60°C. The resulted reaction solution was concentrated and purified by silica gel column
20 chromatographyto obtain the title compound with yield of 52% (124.9 mg).
3'~-NMR(T oluena): 6
52.0 (d, J=40.1 Hz), 57.5 (4 J=39.9 Hz)
(Example 13)
Preparation of RuCl[(S>xylyl-pphos][(S)da~pen]:
[Chern. 281
OMe
Ar:
Under nitmgen gas, a mixture of [RuCl~(pcymene)]6~1 .2 mg (0.1 mmol), (S)-Xylyl-P-Phos 151.5 mg (0.2
mmol) and methanol 3 rnL was heated to 50°C and stirred for 2 hours to prepare
5 BuCl@cymeneX(R>xylyl-P-phos)]Cl. The reaction solution was cooling down to room tempem,
triethylamine 20.3 mg (0.2 rnrnol) and (S)-DAIPEN 95.1 mg (0.3 mmol) were added to the laction solution, and then
stirred for 6 hours at 60°C. The resulted reaction solution was ummW and purified by silica gel column
chromatography to obtain the title compound with yield of 62% (149.6 mg).
3 1 ~volu-ene~-4):~ 6 ~
10 52.1 (4 J=38.6 Hz), 58.3 (4 J=39.9 Hz)
In the following examples, the conversion rate of 3quinuclidinol was measured by gas chromatography (HP-1,
injection tempemhut 250°C, detector tempxahm 250°C, initial column t e m p e m 100°C (maintained for 5 mim)
- tempadture elevation rate 10°C/mjn - final tempemlure 250°C), and the optical purity (Ohee) was measured by
high paformance chromatography (CHIRALPAK AD-H, eluent; hexane : 2-propanol : diethylamine = 90 : 10 : 0.1)
15 following the benzoylation of a product.
(Example 14)
w o n of (S>3quinuclidinol:
To a 100 mL autoclave with a stirrer, 3quinuclidinone (2.5 g 20.0 mmol) and RuCl[(S>xylbi][(Sjdaipen]
(0.5 mg, 0.40 pmol, 1150,000 molar fold of 3quinuclidinone) obtained fbm the Example 1 above were added
20 After the autoclave was purged with nitrogen, 2-pmpanol(15 mL) and 2-propanol solution of potassium t-butoxide
(0.1 moVL, 1.0 mL, 0.1 mmol) were added. Subsequently, the autoclave was purged with hydrogen, the mixture
was stirred at 30°C for 6 hours under hydrogen pressure of 3 MF'a. As a result of analysis of the reaction solution, it
was found that the convajion rate is 99% or more and the optical purity is 91 2 Ye.
(Example 15)
25 w o n of (S>3q~1inuclidmol:
Re- Example 14, except that the reaction temperature was changed fiom 30°C to 10°C, the same pmcedure
as Example 14 was carried out As a result of analysis of the readion solution, it was found that the conversion rate
is 99% or more and the optical purity is 94.6 Ye.
(Compaxative example 3)
30 w o n of (S)-3quinuclidinol:
To a 100 mL autoclave with a stirrer, 3quinuclidinone (1.0 g 8.0 mmol) and
trans-RuC12[(S)xylbinap][(S)daipen] (0.5 m& 0.40 pmol, 1/20,000 molar fold of 3quinuclidinone) wae added
After the autoclave was purged with nitrogen, 2-propanol (6 mL) and 2-ppanol solution of potassium t-butoxide
(0.1 mol/L, 0.4 mL, 0.04 mmol) wm added. Subsequently, the autoclave was purged with hydrogen, the mixture
5 was stirred at 30°C for 6 hours under hydrogen pressure of 3 MPa. As a result of analysis of the reaction solution, it
was found that the conversion rate is 49.8% and the optical purity is 86.2 Yoee.
When Example 14 is compared to Comparative example 3, it was found that the catalytic activity of Comparative
example 3 is only 115 or less of the catalytic activity of Example 14, and the optical purity of the product obtained is
also low in Compamtive example 3.
10 (Example 16)
-on of (R)-3quinuclidinol:
To a 100 mL autoclave with a stirrer, 3quinuclidinone (2.5 g, 20.0 mmol) and RuCl[(R)dm-segphos][(R)daipen]
obtained k m Example 3 above (0.5 mg 0.40 p o l , 1/50,000 molar equivalent fold of 3quinuclidinone) were
added After purging with nitrogen, 2-propanol(15 mL) and 2-propanol solution of t-BuOK (0.1 moVL, 1.0 mL,
15 0.1 mmol) were added Subsequently, purging with hydrogen, the mixture was stirred at 30°C for 6 hours under
hydrogen pressure of 3 MPa As a result of analysis of the d o n solution, it was found that the conversion rate is
99% or more and the optical purity is 91.1 Yoee.
(Example 17)
Preparation of (R)-3quinuclidinol:
20 Reg* Example 16, except that the reaction ternpetatwe was changed fbm 30°C to 10°C, the same procedure
as Example 16 was carried out. As a result of analysis of the reaction solution, it was found that the conversion rate
is 99% or more and the optical purity is 93.7 Yoee.
(Comparative example 4)
Prepamtion of (R)-3quinuclidinol:
25 To a 100 mL autoclave with a h r , 3quinuclidinone (1.0 g 8.0 mmol) and
trans-RuCl2[@)dm-segphos][(R~pen(]0 .5 mg 0.40 pno2 1/20,000 molar fold of 3quinuclidinone) were added.
After purging with nitrogen, 2-propanol(6 mL) and 2-pmpanol solution of t-BuOK (0.1 mom, 0.4 mL, 0.04 mmol)
were added. Subsequently, the autoclave was purged with hydrogen, the mixture was stirred at 30°C for 6 hours
under hydrogen pressure of 3 MPa As a result of analysis of the reaction solution, it was found that the conversion
30 rate is 26.7% and the optical purity is 89.7 Y e .
When Example 16 is compared to Comparative example 4, it was found that the catalytic activity of Comparative
example 4 is only 115 or less of the catalytic activity of Example 16, and the optical purity of the product obtained is
also low in Comparative example 4.
For the following examples, the conversion rate of 3-(methylarnino)l-(2-thieny1)propane-1-01 was measured by
35 using high performance liquid chromatography (Iner!sil ODs-SP, eluenc 1% aqueous solution of formic acid :
water : methanol = 5 : 90 : 5 to 5 : 5 : 90), and the optical purity (Yoee) was measured by using high performance
liquid chromatography (CHIRAL CD-Ph, eluenc 0.2 M sodium perchlorate : acetonitrile = 30 : 70) following the
benzoylation of a product.
(Example 1 8)
PqamIion of (1 S>3xylb'i] [(R)da~pen]o btained
5 h m the Example 2 above (1/3000 molar fold of 3-methylamino-l-thiophene-2-yl-propenonea)n d lithium
hydroxide (50 molar folds of the ruthenium catalyst) wm added to an autoclave. Ethanol (3 mL per 1 g of
3-methylamino-l-thiophene2-yl-propenonew) as added, then the autoclave was pwed with hydrogen and then
stirred for 6 hours at 30°C under hydrogen pressure of 4.5 MPa As a result of analysis of the reaction mixture by
HPLC, it was found that the canvasion rate is loo%, selectivity is 99.3%, and the optical purity is 99 Yoee or more.
10 In addition, the convmion rate and the selectivity were calculated according to the following equations.
Conversion rate: 10O-(HPL€ area % of the sub-)
Selectivity: (HPLC area % of the main product)!(100 - (HPLC area % of the substrate))
(Comparative example 5)
Regarding Example 18, except that RuCI[(R)-xylb'map][(R)daipen] was changed to the same amount of
15 trans-RuC12[(R>~lb'lnap][@)-daipen]th,e same procedure as Example 18 was carried out. As a result of analysis
of the reaction mixture by HPLC, it was found that the optical purity is 99 Yoee or more, but the conversion rate is
83.9% and the selectivity is only 69.2%.
(Example 19)
-on of (1 S)-3-(rnethylamino)- 142-thieny1)pmpan-1-01:
20 Regarding Example 18, except that the use amount of RuCl[(R>xylbinap][(R)-daipen] was changed to 119000
molar fold of 3-methylaminc-l-thiophene-2-yl-propenoneth,e same p d u r e a s Example 18 was canied out. As a
result of analysis of the reaction result by HPLC, it was found that the conversion rate is 99.3%, the selectivity is
95.0%, and the optical purity is 99 %ee or more.
(Example 20)
25 -on of (S>1-phenylethanol:
Under nitrogen stream, acetophenone (20 mmol), RuCl[(S>xylbi][(S)-da~pen] (11100 molar fold of
acetophenone) and t-BuOK (5 molar folds of the ruthenium catalyst) were added to a Schlenk tube. 2-pmpanol(8.3
rnL per 100 mg of acetophenone) was added, then stirred for 10 minutes at 30°C. As a result of analysis of the
reaction mixture by gas chromatography (Chirasil-DEX CB), it was found that the conversion rate is 94%, and the
30 optical purity is 98.4 Ye.
(Example 2 1)
Preparation of RuCl[(R)-tolbii] [(R)daipen] :
[Chem. 291
Under nitrogen gas, a mixture of ~l(pcymeneX(l2)-tolbinap)]Cl 1.0 g (0.85 mmol), @)-DAIPEN 440 mg
(1.28 mmol), triethylamine 90 mg (0.94 mmol) and methanol 10 mL was stirred for 16 hours at 50°C. The reaction
solution was concentmkd and purified by silica gel column chromatography to obtain the title compound with yield
5 of 26% (250 mg).
3 1 ~(c6D-6): ~6 ~ ~
60.8 (d, J=39.9 Hz), 53.0 (J=39.9 Hz)
(Example 22)
Preparation of RuCl[(S>xylb'i] [daen] :
10 [Chem. 301
Ar: 4
OM^
Under nilmgen gas, a mixture of ~uCl2@cymene)l1z5 3.1 mg (0.25 rnrnol), (S)-XylBINAP 367.5 mg (0.50
mmol) and methanol 10 mL was heated to 55°C and stirred for 2 hours to prepare
PuCl@cymeneX(S)-xylbinap)]Cl. The d o n solution was coo@ down to room tempmhm, diethylamine
15 36.6 mg (0.50 mmol), 1,l-bis(4-methoxypheny1)ethylenediamine (heremafter, ref& to as DAEN) 149.8 mg (0.55
mmol) were added to the reaction solution, and then stirred for 15 hours at 55OC. The resulted reaction solution was
cooled to O°C and the precipitated crystals were filted to obtain the title compound with yield of 66% (377.6 mg).
3 1 ~(c6-D6)~: 6 ~ ~
55.0 (d, J 4 . 1 Hz), 61.3 (4 J=38.7 Hz)
20 (Example23)
Preparation of RuCl[(S>dm-segphos][daen]:
[Chem 3 11
Ar:
\ OMe
Except that (S>XylBINAP was changed to (S)-DM-SEGPHOS, the expiment was carried out in the same
manner as Example 23 to obtain the title compound with yield of 40% (225.5 mg).
3'~-NMR( W)6 :
54.2 (d, 540.1 Hz), 57.5 (d, 540.1 Hz)
@ample 24)
-on of RuCl[(S)-xylbii] [ l,1 -DPEN] :
[Chem. 321
Except that DAEN was changed to 1,ldphenylethylenediamine (herehailer, referred to as 1,l-DPEN), the
experiment was canied out in the same manner as Example 23 to obtain the title compound with yield of 77% (414.2
mg).
3 p - m (cD~): s
55.3 (4 J=38.9 Hz), 60.7 (4 5 4 . 1 Hz)
(Example 25)
Pqaration of RuCl[(S)-bii][(S)daipen]:
[Chem. 331
Under h g e n gas, a mkhm of lJtuC1@cymene)((S>binap)]C11.0 g (I .08 mmol), (S>DAIPEN 376.4 mg (1.18
mmol), diethylamine 80 mg (1.08 mrnol) and methanol 10 rnL was stirred for 20 hours at 50°C. The reaction
solulion was cooling down to O°C and the precipitated crystals were flered to obtain the title compound with yield
of 85% (982.5 rng).
31~-NM(R w66 ):
54.6 (d, 540.1 Hz), 62.0 (d, J40.1 Hz)
5 Gxample 26)
Preparation of RuCl[(S>xyib'i][(S>3-daipen]:
[Chem. 341
Under nitrogen gas, a mixture of [puCl&~-cymene)6]4~. 3 mg (0.11 mmol), (S>XylBINAP 162 rng (0.22 rnmol)
10 and methanol 6 mL was heated to 50°C and stirred for 2 hours to prepare ~uCl(pcymene)((S>xylbimp)]CI. The
d o n solution was coolmg down to room tern-, diethylamine 16 mg (0.21 -01) and
(SF1 -isopropyl-2~-bis(3-methoxyphenyl)ete (hereinafter, r e f 4 to as (S>3-DAJPEN) 72.3 mg (0.23
mmol) were added to the reaction solution, and then stirred for 20 hours at 50°C. The resulted reaction solution was
concentrated and purified by silica gel column chromatography to obtain the title compound with yield of 44% (1 10
15 mg).
3 1 ~(C6-D6):8~ ~ ~
53.4 (4 J=38.8 Hz), 59.8 (4 J=38.8 Hz)
@=pie 27)
Preparation of RuCl[(S>xylbi][(S)-dpi@n] :
20 [Chem. 351
Under nitrogen gas, a mixture of [RuC12@cymene)126 4.3 mg (0.11 rnmol), (S>XylBINAP 162 mg (0.22 mmol)
and methanol 6 mL was heated to 50°C and stirred for 2 hours to prepare ~l(pCymeneX(S>ylbinap)]Cl. The
reaction solution was coolug down to room tern-, diethylamine 16 mg (0.21 mmol) and
25 (S>1-isopmpyl-2~4phenylethylenediamin(hem inafter, ref& to as (S>DPIPEN) 58.0 mg (0.23 mmol) were
added to the reaction solution, and then stirred for 20 hours at 50°C. The d t e d reaction solution was
concentrated and purified by silica gel column chromatowhy to obtain the title compound with yield of 61 % (150
mp>.
31~-NM(R a8 ):
53.0 (d, J=38.9 Hz), 59.7 (d, J=38.9 Hz)
5 (Example28)
w o nof R u(OT~[(S>xylb'i[]( S)drupen]:
[Chem. 361
Under nitrogen gas, a mixture of RuCl[(S>xylblnap][(S>daipen] 1.00 g (0.844 mmol), which has been obtained in
10 Example 1, NaOTf (CF3SWa) 159.7 mg (0.928 mmol) and toluene 20 mL was stirred for 5 hours at room
temperature. The reaction solution was filtered and the solvent in the filtrate was removed under reduced pressure
to obtain almost quantitatively the title compound (1.10 g).
31~-NM(RW )6:
52.5 (d, J=37.5 Hz), 58.6 (d, J=37.5 Hz)
15 ' 9 ~(C6-D6)6~: ~ ~
-59.2 (s)
TOF-mass (HI): rn/z=129824 (theoretical value 1298.37)
29)
w o n of Ru(OAc)[(S>xylbii] [(S>ikipen]:
20 [Chern.37]
b ~e
Under nitrogen gas, a mixtun: of RuCI[(S>xylb'i][(S~pen] 100 mg (0.0844 mmol), which has been
obtained in Example 1, NaOAc 13.8 mg (0.169 mmol) and toluene 2 mL was stirred for 10 hours at room
tempemhm. The reaction mixture was filtered and the solvent in the fillrate was removed under reduced p r e m
25 to obtain the title compound with yield of 93% (95.2 mg).
31~-NM(RC6 &): 8
5 1 .O (4 J=37.4 Hz), 60.6 (4 J=38.7 Hz)
ESI: m/z=1209.4337 (theoretical value: 1209.4397(&4+~]3)
(Example 30)
5 Preparation of (S>1,2,3,4-tetrahydro-1-naphthol:
To a 100 mL autoclave with a stirrer, RuCl[(R>dm-segphos][(S)da~pen] obtained h m Example 5 above (3.5 mg,
0.003 mob 111,000 molar fold of 1-tetralone) were added After purging with nitrogen, 2-pmpanol (3 mL),
1-tetralone (439 mg 3 mmol) and 2-propanol solution of t-BuOK (0.1 mom, 0.3 mL, 0.03 mmol) were added
Subsequentlyy p& with hydrogen, the mixture was stirred at 25OC for 15 hours under hydrogen pressure of 1
10 MPa As a muH of analysis of the reaction solution by using gas chromatography (Chimsil-DEX CB), it was
found tha the conve~sionm k is 99% or more and the optical purity is 96 Ye.
(Comparalive example 6)
Preparation of (S>1,2,3,4-tetrahydro-1 -naphthol:
To a 100 mL autoclave with a stirrer, trans-RuC12[(R)dm-segphos][(S~pe(n3].6 mg, 0.003 mob 111,000 molar
15 fold of I-tetralone) was added. After purging with nitrogen, 2-propanol(3 mL), 1-tetralone (439 mg, 3 mmol) and
2-ppanol solution of t-BuOK (0.1 mom, 0.3 mL, 0.03 mmol) were added. Subsequentlyyp urging with hydrogen,
the mixture was stirred at 25OC for 15 hours under hydrogen pressure of 1 MPa As a result of analysis of the
reaction solution by using gas chromatography (Chimid-DEX CB), it was found that the conversion rate is 42% and
the optical purity is 90 Ye.
20 When Example 30 is compared to Comparative example 5, it was found that the calalytic activity of Comparalive
example 5 is only 10 or less of the catalytic activity of Example 30, and the optical purity of the product obtained is
also low in Comparative example 5.
(Example 3 1)
-on of (S>1 -phenyl-1,2ethanediol:
25 To a 100 mL autoclave with a stirrer, 2-hydroxyacetophenone (340 mg, 2.5 mmol) and
RuCl[(S>xylbinap][(Sjda~pen] obtained £ram the Example 1 above (1.5 mg, 0.00125 mol, 112,000 molar fold of
2-hydroxyacetophenone) were added After purging with nitrogen, methanol (1.25 mL) and
1,8diazabicyclo[5.4.O]undeca-7-ene( 1.9 mg 0.0125 mmol) were added Subsequently, purging with hydrogen,
the mixture was dmd at 30°C for 5 hours under hydrogen pressure of 1 MPa As a result of analysis of the
30 reaction solution by using gas chromatography (HP-I), the conversion rate was found to be 99% or more. The
optical purity was measured by high performance liquid chromatography (CHR4LF'AK AS-H, eluenc hexane :
2-prop01 = 92 : 8), and it was found to be 94 Ye.
(Example 32)
Preparation of (SF1 -phenyl- l,2&ediol:
35 Regarding Example 31, except that the use amount of RuCl[(S>xyTbinap][(S)-dai] was changed (3.0 mg
0.0025 mol 1/lY000m olar fold of 2-hydroxyacetophenone) and 2-propanol(2.5 mL) was used instead of methanol
the same procedure as Example 31 was carried o~ As a result of analysis of the reaction solution by using gas
chromatography (HP-l), the conversion rate was found to be 99% or more. The optical purity was measured by
high performance liquid chromatography (CHIRAL,PAK AS-H, elm$ hexane : 2-propol= 92 : 8), and it was
found to be 90 Yoee.
(Compamtive example 7)
5 Preparation of (SF1 -phenyl- 1,2&ediol:
Regmhg Example 32, except that trans-RuCl~[(S>xylbinap][(S)da~pen] was used instead of
RuCl[(S>xylbinap][(S)daipen], the same procedure as Example 32 was canied out As a result of analysis of the
reaction solution by gas chromatogmphy (HP-1), the conversion rate was 0% i n d i e that no title compound was
obtained.
10 When Example 32 is cornpad to Comparative example 7, it was found that
tran~-RuC12[(S>xylb'lnap][(S)daipen] has no catalytic activity.
(Example 33)
Preparation of (S>1<4-methoxypheny1)- 1,2-ethanediol:
To a 100 rnL autoclave with a stirrer, 2-hydroxy-I-(4-methoxypheny1)ethanone (415 mg, 2.5 mmol) and
15 RuCl[(S>xylbinap][(S)daipen] obtained fbm the Example 1 above (3.0 mg 0.0025 mol 111000 molar fold of
2-hydroxy-1<4-methoxyphenyl)%hanone) were added After p a with nitrogen, methanol (2.5 mL) and
1,8-diazabicyclo[5.4.0]~1ndeca-7-en(3e. 8 mg, 0.025 mmol) were added. Subsequently, &r purging with hydrogen,
the mixture was stirred at 30°C for 5 hours under hydrogen pressure of 1 MPa As a result of analysis of the
reaction solution by using gas chromatogmphy (HP-I), the conversion rate was found to be 99% or more. The
20 optical purity was measured by high performance liquid chromatogmphy (C-PAK AS-fi eluent; hexane :
ethanol = 95 : 5), and it was found to be 97 Yoee.
(Example 34)
-on of (SF1 -phenylethanol:
Under nitrogen gas, to a mixture of acetophenone (120 mg 1 mmol), RuCl[(S>xylbii][(S)daIpen] obtained
25 fbm the Example 1 above (6.1 mg lDOO molar fold of acetophenone) and 2-propanol 10 mL in a Schlenk tube,
2-propanol solution (0.1 moK, 0.25 mL, 0.025 mmol) of t-BuOK was added and stirred at 26'C for 1 hour. As a
result of analysis of the reaction mixture by gas chromatogqhy (Chirasi1-DEX CB), it was found that the
conversion rate is 96%, and the optical purity is 99 Yoee.
(Comparative example 8)
30 Regarding Example 34, except that trans-RuC12[(S>xy1b'i][(S)daipen] was used in the same amount instead of
RuCl[(S>xylbinap][(S)daipen], the same procedure as Example 34 was carried out. As a result of analysis of the
reaction mixture by gas chromatography (Chirasil-DEX CB), it was found that the conversion rate is 21%, and the
optical purity is 90 Yke.
When Example 34 is compared to Comparative example 8, it was found ~ the catalytic activity of Comparative
35 example 8 is only 114 or less of the d y t i c activity of Example 34, and the optical purity of the product obtained is
also low in Compamtive example 8.
CLAIMS
[Claim 11
A ruthenium complex repmmted by the following Formula (1)
[Chem. 381
R N ~ RN4 RC
p\ (p,f;q: 1 RNI ~ h ! 2 Ra
5
(in the formula, E"-P represents diphosphine and X represents an anionic p u p ; Ra, R~ and RC each independently
represent a hydrogen atom, an optionally substituted ClCm alkyl group, an optionally substituted C2Cm akenyl
group, an optionally substituted C~CcSyc loalkyl group, an optionally substituted CSma raUOjl group, an optionally
substituted aryl group, or an optionally substituted heterocyclic pup, and Rb and Rc may form an alkylene group or
10 an alkylenedioxy group; RN1, R ~R, ~ an,d RN4 each independently represent a hydrogen atom, an optionally
substituted C1C20 alkyl pup, an optionally substituted C2C20 alkenyl group, an optionally substituted c7-c20
aralkyl group, or an optionally substituted C3Cs cycloakyl group, at least one of RN 1 ,R N 2 ,R M , and RN4r epresents a
hydrogen atom, and RN1 and Ra may form an alkylene p u p ; n repmts an integer of 0 to 3; and Ar represents an
optionally substituted arylene group).
15 [Claim 21
The ruthenium complex according to Claim 1, wherein the ruthenium complex is a ruthenium complex
represented by the following Formula (2)
[Chem. 391
20 (in the formula, P^P represents diphosphine, X repments an anionic group; Ra, Rb, and Rc each independently
represent a hydrogen atom, an optionally substituted C1-C20 alkyl group, an optionally substituted C2Cm alkenyl
pup, an optionally substituted C3Cs cycloalkyl pup, an optionally substituted C S m aralkyl group, in optionally
substituted aryl group, or an optionally substituted hetaocyclic group, and R~ and R h a y form an alkylene group or
an alkylenedioxy group. Rd, Re, Rf and Rg each independently represent a hydrogen atom, an akyl group having 1 to
20 carbon atoms, a halogenated alkyl group having 1 to 5 carbon atoms, a halogen atom, an optionally substimed
aryl group, an optionally substituted C3Cg cycloalkyl group, a tri-substituted silyl group or an alkoxy p u p having 1
Nl N2 N3 to 20 carbon atoms; R , R , R and R~ each independently represent a hydrogen atom, an optionally substituted
5 C1CX alkyl group, an optionally substituted C2Cm alkenyl group, an optionally substituted C ~ Ca~ralOlcjl group, or
an optionally substituted C3Cs cycloalkyl group, and at least one of RNl, R*, R~~ and RN4 repments a hydrogen
atom; and RNl and Ra may form an allcylene pup).
[Claim 31
The ruthenium complex according to Claim I or 2, wherein the d e n i m complex is a ruthenium
10 complex w t e d by the following Formula (3)
[Chem. 401
(in the formula, F T represents diphosphine, X repments an anionic group, Ra and Rb each independently represent
a hydrogen atom, an optionally substituted C1C20 alkyl group, an optionally substituted C2Cm alkenyl group, an
15 optionally substituted C3Cg cycloalkyl group, an opbonally substituted C7Cm aralkyl gmup, an optionally
substituted aryl group, or an optionally substituted heterocyclic group; RW, RNZ, R~~ and RM each independently
repment a hydrogen atom, an optionally substituted CICa alkyl group, an optionally substituted C2-C20 alkenyl
group, an optionally substituted C7C1 m- group, or an optionally substituted C3Csc ycloalkyl group, and at least
one of RN l ,R N 2 ,R N 3 and RM repmats a hydrogen atom; and R ~an'd Ra may form an alkylene group).
20 [Claim41
The ruthenium complex acceding to any one of Claims 1 to 3, wherein the diphosphine indicated as FPis
a diphosphine represented by the following Formula (4)
R'R~P-Q-PR~R* ( 4 )
(in the formula, R', R ~R,3 and R4 each independently repment an optionally substituted aryl group, an optionally
25 substituted cycloakyl group, or an optionally substituted alkyl group, and R' and R2 andlor R3 and R4 may form a
ring; and Q r e p m t s an optionally substituted divalent arylene group, biphenyldiyl group, biihthdenediyl group,
bipyridinediyl group, paracyclophanediyl group, or f-ediyl group).
[Claim 51
The ruthenium complex according to any one of Claims 1 to 4, wherein the diphosphine indicated as P"
P is an optically active diphosphine.
[Claim q
The ruthenium complex accordmg to any one of Claims 1 to 5, wherein the optically active diphosphine
5 indicated as P^P is an optically active diphosphine represented by the following Formula (5)
[Chem. 411
(in the formula, R", R', R3' and R4' each independently represent a phenyl group, a cyclopentyl group or a
cyclohexyl group which is optionally substituted with a substituent group selected fiom a group consisting of an alkyl
10 group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. RS, R6, R7, R8, R9 and R" each
independently qxesent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4
carbon atoms, a halogen atom, a halogenaied akyl group or an dialkylamino group having 1 to 4 carbon atoms and
two of R5, R6 and R7 may form an optionally substituted alkylene group; an optionally substituted allcylenedioxy
group; or an optionally substituted aromatic ring, two of R', R' and Rl0maY form an optionally substituted alkylene
15 group; an optionally substituted alkylenedioxy group; or an optionally substituted aromatic ring; and R7 and R8 may
form an optionally substituted alkylene group; an optionally substituted alkylenedioxy group; or an optionally
substituted aromatic rig with the that any of R~ and R8 is not a hydmgen atom).
[Claim 7]
The ruthenium complex accorchg to Claim 6, wherein R', R2, R~ and R4 in the Formula (4) and R", R',
20 R ~an'd R4' in the Formula (5) is a 3,5-xylyl group.
[Claim 81
An asymmetric reduction d y s t comprising the ruthenium complex accodhg to any one of Claims 5 to
7.
[Claim 91
25 A method for preparing optically active alcohols, wherein a carbonyl group was asymmetric
hydrogenated by the asymmetric reduction d y s t acceding to Claim 8 in the presence of a base compound
[Claim lo]
A method for preparing optically active alcohols, wherein a carbonyl group is subjected to asymmetric
hydrogen--fa reduction using the asymmetric reduction d y s t accord& to Claim 8 in the pmence of a base
compound
[Claim 111
A method for preparing the ruthenium complex repmented by the following Formula (I),
5 [Chem 421
wherein the ruthenium compound represented by the following Formula (A)
[RuX (L) (PnP) IX (A)
(in the formula (A), Ru represents a ruthenium atom, X represents a halogen atom, L represents an arene and F"7
10 represents bisphosphine)
is reacted with the compound having the following Formula (8)
[Chem. 431
(in the formula, Ra, R~ and Rc each independently represent a hydrogen atom, an optionally substituted C1-Cm alkyl
15 group, or an optionally substituted C2-C2o akenyl group, or an optionally substituted C3Cs cycloakyl group, or an
optionally substituted CKm arallcjl group, or an optionally substituted aryl group, or an optionally substituted
heterocyclic group or R~ and Rc may form an akylene group or an akylenedioxy group; R~'R, ~RM, a nd RN4e ach
independently q m t a hydrogen atom, an optionally substituted CICm -1 group, an optionally substituted
C2Cm alkenyl p u p , an optionally substituted CKzO arallojl group, or an optionally substituted C3Cs cycloalkyl
20 group, and at least one of RM, Rm, RN3 and RN4 q m t s a hydrogen atom; or RM and Ra may form an alkylene
group, and n is an integer of 0 to 3 and Ar represents an optionally substitukl arylene group).
[Claim 121
A method for preparing the ruthenium complex represented by the following Formula (I),
[Chem. 441
wherein the ruthenium compound ~ t eby tdhe fol lowing Formula (B)
[RuX2 (L) I, (B)
(in the formula (B), Ru repments a ruthenium atom, X represents a halogen atom, L represents an arene and m
5 qments a natural number of 2 or more)
is reacted with a diphosphine repmted as P"P and then with the compound having the following Formula (8)
[Chem. 451
(in the formula, Ra, Rb and RC each independently represent a hydrogen atom, an optionally substituted CI-C2, alkyl
10 group, or an optionally substituted C2C20 alkenyl p u p , or an optionally substituted C3Cs cycloakyl group, or an
optionally substituted CXU) -1 group, or an optionally substituted aryl group, or an optionally substituted
heterocyclic group or Rba nd Rc may form an alkylene group or an alkylenedioxy group;R M,R ~RM, a nd RW4ea ch
independently represent a hydrogen atom, an optionally substituted C1C20 alkyl group, an optionally substituted
c2-C~alk enyl group, an optionally substituted CSZ0ar alkyl group, or an optionally substituted C ~ CcSyc loalkyl
15 group, and at least one of RN', R ~R~,~a nd RN4r epresents a hydrogen atom; or RN' and Ra may form alkylene group,
and n is an integer of 0 to 3 and Ar represents an optionally substituted arylene group).
[Claim 131
The method for preparing the ruthenium complex accordmg to any one of Claims 11 or 12, that the
d o n was carried out in the p m c e of solvent, wherein the solvent used is an alcohol solvent.
20 [Claim 141
The method for preparing the ruthenium complex according to any one of Claims 11 to 13, additionally
wherein a base is added
[Claim 151
The method for preparing the ruthenium complex accom to any one of Claims 1 1 to 14, wherein the
25 diphosphine indicated as P"P is a diphosphine represented by the following Formula (4)
R~R*P-Q-PR~R~ ( 4 )
(in the formula, R', R~R, 3 and R* each independently represent an optionally substituted aryl group, an optionally
substituted cycloalkyl group, or an optionally substiMed alkyl p u p , and R' and R2 and/or R3 and R4 may form a
ring; and Q qmmts an ophonally substituted divalent arylene group, biphenyldiyl group, biihthalenediyl group,
bipyridinediyl p u p , paracyclophanediyl group, or femcmediyl pup).
[Claim 161
5 The method for preparing the ruthenium complex aw;oding to any one of Claims 11 to 15, wherein the
diphosphine indicated as of Claims 1 1 to 15 is an optically active diphosphine.
[Claim 1 1
The method for preparing the ruthenium complex accordmg to any one of Claims 1 1 to 16, wherein the
optically active diphosphine indicated as P"P is an optically active diphosphine repmenkd by the following
10 Formula(5)
[Chern. 461
(in the formula, R", R2', R3' and R4' each independently represent a phenyl group, a cyclopentyl group; or a
cyclohexyl group which is optionally substituted with a substituent group selected hm a p u p consisting of an alkyl
15 group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. R5, R6, R7, RB, R9 and RIO each
independently represent a hydrogen atom, an akyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4
carbon atoms, a halogen atom, a halogenated alkyl group or an dialkylamino group having 1 to 4 carbon atoms and
two of RS, R~ and R7 may form an optionally substituted alkylene p u p ; an optionally substituted alkylenedioxy
group; or an optionally substituted aromatic rin& and two of R8, R9 and R'O may form an optionally substituted
20 alkylene p u p ; an optionally substituted alkylenedioxy group; or an optionally substituted aromatic ring; and R7 and
R' may form an optionally substituted alkylene group; an optionally substituted alkylenedioxy group; or an
optionally substituted aromatic ring, with the proviso that R7 and R8 are not a hydrogen atom).
[Claim 18]
The method for preparing the ruthenium complex accordmg to any one of Claims 11 to 17, wherein R',
25 R2, R3 and R~ in the Formula (4) and R", R2', and R' in the Formula (5) is a 3,5-xylyl p u p .