DESCRIPTION
ALUMINUM COMPLEX AND USE THEREOF
TECHNICAL FIELD
The present invention utilizes a novel chiral aluminum
complex as a catalyst in cyclization of a compound having, in
a molecule, a formyl group and a double bond which allow
carbonyl-ene cyclization, the compound existing as a mixture
of optical isomers thereof, and thereby increases the ratio of
a particular optical isomer in a cyclized compound or an
unreacted compound.
In particular, the present invention enables optical
resolution of citronellal having a low enantiomeric excess
ratio by allowing preferential cyclization of only one of two
stereoisomers, resulting in an increased enantiomeric excess
ratio, or enables production of enantioenriched isopulegol from
the citronellal via selective cyclization.
BACKGROUND ART
Menthol, especially 1-menthol, has been an extremely
important refreshing flavor and been extensively used. As a
synthesis process of menthol, optical resolution of dl-menthol
and asymmetric synthesis are known (nonpatent literature 1).
In the asymmetric synthesis of 1-menthol, 1-menthol is produced
by hydrogenation of the precursor 1-isopulegol. For synthesis
of 1-isopulegol, the selective cyclization of d-citronellal is
an important step.
As the selective cyclization of d-citronellal, techniques
which use zinc bromide or other reagents have long been known.
In recent years, there are reports on highly selective
cyclization using an aluminum complex as a catalyst. For
example, highly selective cyclization which uses, as a catalyst,
an aluminum complex having a 2 ,6-diphenylphenol-derived ligand
was invented (patent literature 1). Since then, cyclization
which uses an aluminum complex having a ligand derived from
compounds having a phenolic hydroxyl group (patent literatures
2, 3 and 4), and cyclization which uses an aluminum complex
having a silyl ether moiety (patent literature 5) have been
reported. However, there is no report on selective cyclization
of only one of the two stereoisomers in racemic citronellal
using an optically active aluminum complex. Many aluminum
complexes having a biaryldiol skeleton, which is an axially
asymmetric ligand, have been reported, but among them, only a
monovalent cationic hydride complex (patent literature 6)
consists of aluminum and biaryldiol at the ratio of 2:3
(aluminum:biaryldiol).
[Citation List]
[Patent literature]
Patent Literature 1: JP-A 2002-212121
Patent Literature 2: WO 2006/069659
Patent Literature 3: WO 2006/092433
Patent Literature 4: DE 102005023953
Patent Literature 5: WO 2007/039342
Patent Literature 6: US 6090950
[Nonpatent literature]
Non Patent Literature 1:
Synthetic Flavor, Motoichi Indou, The Chemical Daily Co. , Ltd. ,
SUMMARY OF INVENTION
TECHNICAL PROBLEM
An object of the present invention is to provide a process
for obtaining an objective optically active alcohol or olefin
aldehyde with a higher optical purity, the process comprising
using a novel chiral aluminum complex as a catalyst in
intramolecular carbonyl-ene cyclization to increase the ratio
of a particular optical isomer in a cyclized compound or an
unreacted compound. In particular, the present invention
relates to a process for obtaining 1-isopulegol and
1-citronellal or d-isopulegol and d-citronellal by optical
resolution of citronellal via highly selective cyclization.
SOLUTION TO PROBLEM
The present inventors conducted extensive research to
achieve the above-mentioned object. As a result, they found
that use of, as a catalyst, an aluminum complex having an
optically active biaryldiol as a ligand allows preferential
cyclization of citronellal that fits the conformation of the
chiral ligand, resulting in improvement in the
dl-enantioselectivity, and that among four isomers, i.e.,
isopulegol, isoisopulegol, neoisopulegol and neoisoisopulegol,
isopulegol can be produced in a highly selective manner and
obtained at a high yield. Based on these findings, the present
inventors completed the present invention. Also, the chiral
ligand described above can be reused as a ligand of the aluminum
catalyst by recovery from the reaction system after completion
of the cyclization.
Namely, the present invention includes the contents of the
following [1] to [10].
[1] An aluminum complex obtainable by a reaction of 1 Eq of an
aluminum compound represented by the following general formula
(1):
Al(Lg)3 (1)
(in the formula (1), Lg represents an alkyl group, an alkoxy
group or a halogen atom) and 1.5 Eq or more of a biaryldiol
compound represented by the following general formula (2):

(in the formula (2), R1, R2, R3, R1', R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxyl group, a halogen atom,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group.
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4' , R4' and R3' , R3' and R2' , or R2' and R1'
may bind to each other to form a ring), or
by a reaction of 1 Eq of the aluminum compound represented by
the above general formula (1) , 1.1 to 1.3 Eq of the biaryldiol
compound represented by the above general formula (2) and 0.4
Eq or more of a biaryldiol compound represented by the following
general formula (3):

(in the formula (3), R5, R6, R7, R8, R5'. R6', R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8',
R8' and R7' , R7' and R6' , or R6' and R5' may bind to each other to
form a ring).
[ 2 ] The aluminum complex according to the above [1], wherein
the biaryldiol compound represented by the general formula (2)
is an optically active compound having a chiral axis.
[ 3 ] The aluminum complex according to the above [ 2 ] , wherein both
of the biaryldiol compound represented by the general formula
(2) and the biaryldiol compound represented by the general
formula (3) are optically active compounds having a chiral axis.
[4] The aluminum complex according to any of the above [1] to
[3] , which is represented by the following general formula (1' ):
[Al2(L1)n(L2)3-n]m (1')
(in the formula (1'), n represents an integer of 2 or 3; m
represents a natural number; L1 represents a ligand represented
by the following formula (2'); and L2 represents a ligand
represented by the following formula (3'):

(in the formula (2'), R1, R2, R3, R1', R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxyl group, a halogen atom.
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4', R4' and R3', R3' and R2', or R2' and R1'
may bind to each other to form a ring, and
in the formula (3'), R5, R6, R7, R8, R5', R6', R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8',
R8' and R7' , R7' and R6' , or R6' and R5' may bind to each other to
form a ring)).
[5] A process for preparing an optically active compound,
comprising performing, in the presence of an aluminum complex,
cyclization of a compound having, in a molecule, a formyl group
and a double bond which allow carbonyl-ene cyclization, the
compound existing as a mixture of optical isomers thereof, to
increase the ratio of a particular optical isomer in a cyclized
compound or an unreacted compound, the aluminum complex being
obtainable by a reaction of 1 Eq of an aluminum compound
represented by the following general formula (1):
Al(Lg)3 (1)
(in the formula (1), Lg represents an alkyl group, an alkoxy
group or a halogen atom) and 1.0 Eq or more of an optically active
biaryldiol compound having a chiral axis represented by the
following general formula (2):

(in the formula (2), R1, R2, R3, R1', R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxyl group, a halogen atom,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4', R4' and R3', R3' and R2', or R2' and R1'
may bind to each other to form a ring), or
by a reaction of 1 Eq of the aluminum compound represented by
the above general formula (1), 1.0 to 1.3 Eq of the optically
active biaryldiol compound having a chiral axis represented by
the above general formula (2) and 0.4 Eq or more of a biaryldiol
compound represented by the following general formula (3):

(in the formula (3), R5, R6, R7, R8, R5', R6', R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8',
R8' and R7' , R7' and R6' , or R6' and R5' may bind to each other to
form a ring).
[6] The process according to the above [5] , wherein the compound
having, in a molecule, a formyl group and a double bond which
allow carbonyl-ene cyclization is represented by the following
general formula (4):

(in the formula (4), n2 represents an integer of 1 or 2; R9,
R10 and R12 independently represent a hydrogen atom or an
optionally substituted alkyl group; R11 represents an
optionally substituted alkyl group or a hydroxyl group which
may be protected by a protecting group; R13, R14 and R
independently represent a hydrogen atom or an optionally
substituted alkyl group; and the wavy line represents
configuration E or Z).
[7] The process according to the above [5] , wherein the cyclized
compound is represented by the following general formula (5):

(in the formula (5), n2 represents an integer of 1 or 2; R9,
R10 and R12 independently represent a hydrogen atom or an
optionally substituted alkyl group; R11 represents an
optionally substituted alkyl group or a hydroxyl group which
may be protected by a protecting group; R13, R14 and R15
independently represent a hydrogen atom or an optionally
substituted alkyl group; and the wavy line represents
configuration E or Z).
[8] The process according to the above [5] , wherein the compound
having, in a molecule, a formyl group and a double bond which
allow carbonyl-ene cyclization is racemic citronellal or
optically active citronellal, and the cyclized compound is
optically active isopulegol.
[9] The process according to the above [8], wherein the
optically active isopulegol is 1-isopulegol.
[10] The process according to the above [8], wherein the
optically active citronellal is 1-citronellal.
ADVANTAGEOUS EFFECTS OF INVENTION
According to the present invention, cyclization of a
compound having, in a molecule, a formyl group and a double bond
which allow carbonyl-ene cyclization, the compound existing as
a mixture of optical isomers thereof, increases the ratio of
a particular optical isomer not only in a cyclized compound,
but also in an unreacted compound, and thereby an objective
optically active alcohol or olefin aldehyde can be obtained with
a higher optical purity.
BRIEF DESCRIPTION OF DRAWINGS
Fig. 1 shows the 1H-NMR chart of the solid product obtained
in Example 1.
Fig. 2 shows the enlarged view of the lower field in the
1H-NMR chart of Fig. 1.
DESCRIPTION OF EMBODIMENTS
Hereinafter, the aluminum complex of the present invention
will be described in more detail.
Regarding the aluminum compound (1) represented by the
general formula (1) used for preparation of the aluminum complex
of the present invention, Lg represents an alkyl group, an
alkoxy group or a halogen atom.
The alkyl group represented by Lg refers to a straight or
branched alkyl group having 1 to 8, preferably 1 to 4 carbon
atoms, and preferable examples thereof include straight or
branched alkyl groups having 1 to 4 carbon atoms , such as methyl,
ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl and
tert-butyl.
The alkoxy group represented by Lg refers to a straight or
branched alkoxy group having 1 to 8, preferably 1 to 4 carbon
atoms, and preferable examples thereof include straight or
branched alkoxy groups having 1 to 4 carbon atoms, such as
methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy,
isobutoxy and tert-butoxy.
Examples of the halogen atom represented by Lg include a
fluorine atom, a chlorine atom, a bromine atom and an iodine
atom.
Regarding the biaryldiol compounds represented by the
general formulae (2) and (3), and ligands derived from the
biaryldiol compounds, which are represented by the general
formulae (2') and (3'), R1, R2, R3, R1', R2', R3', R5, R6, R7, R8,
R5', R6' , R7' and R8' independently represent a hydrogen atom,
a halogen atom, a hydroxyl group, a saturated or unsaturated
carbon chain, an optionally substituted aryl group, an
optionally substituted heterocyclic group, an alkoxy group, an
aryloxy group, an aralkyloxy group, a carboxyl group which may
be protected by a protecting group, an amino group, a
substituted amino group, a nitro group, an acyl group, a
substituted silyl group or a polymer chain. R4 and R4'
independently represent a hydroxyl group, a halogen atom, a
saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group.
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group. R1 and R2, R2 and R3,
R3 and R4, R4 and R4', R4' and R3', R3' and R2' , or R2' and R1' may
bind to each other to form a ring. R5 and R6, R6 and R7, R7 and
R8, R8 and R8', R8' and R7', R7' and R6', or R6' and R5' may bind
to each other to form a ring.
Regarding the biaryldiol compounds represented by the
general formulae (2) and (3), groups represented by R1, R2, R3,
R4, R1' , R2', R3', R4', R5, R6, R7, R8, R5', R6', R7' or R8' will be
described.
Examples of the saturated or unsaturated carbon chain
include straight or branched alkyl groups having 1 to 6 carbon
atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl,
sec-butyl, iso-butyl, tert-butyl, pentyl and hexyl; cyclic
alkyl groups, such as cyclopentyl, cyclohexyl,
methylcyclohexyl and cycloheptyl; and alkenyl or alkynyl groups,
such as ethynyl, vinyl, styryl and allyl.
Examples of the halogen atom include a fluorine atom, a
chlorine atom, a bromine atom and an iodine atom.
Examples of the optionally substituted aryl group include
phenyl and naphthyl. Examples of the substituent in the aryl
group include straight or branched alkyl groups having 1 to 4
carbon atoms, and straight or branched alkoxy groups having 1
to 4 carbon atoms.
Examples of the optionally substituted heterocyclic group
include aliphatic heterocyclic groups, such as piperidino,
piperazinyl, morpholino, tetrahydrofuryl, tetrahydropyranyl
and tetrahydrothienyl; and aromatic heterocyclic groups, such
as furyl, thienyl, pyridyl, pyrimidyl, pyrazyl, pyridazyl,
pyrazolyl, imidazolyl, oxazolyl, thiazolyl, benzofuryl,
benzothienyl, quinolyl, isoquinolyl, quinoxalyl, phthalazyl,
quinazolyl, naphthyridyl, cinnolyl, benzimidazolyl,
benzoxazolyl and benzothiazolyl.
Examples of the alkoxy group include methoxy, ethoxy,
propoxy, isopropoxy, n-butoxy, tert-butoxy, pentyloxy,
hexyloxy, heptyloxy and octyloxy.
Examples of the aryloxy group include phenoxy and naphthoxy.
Examples of the aralkyloxy group include benzyloxy and
1-phenethyl.
Examples of the carboxyl group which may be protected by
a protecting group include a carboxyl group; and alkoxycarbonyl
groups having 2 to 5 carbon atoms, such as methoxycarbonyl.
Examples of the substituted amino group include mono- or
di-alkylamino groups, such as N-methylamino,
N,N-dimethylamino, N,N-diethylamino, N,N-diisopropylamino
and N-cyclohexylamino; mono- or di-arylamino groups, such as
N-phenylamino, N,N-diphenylamino, N,N-ditolylamino,
N-naphthylamino and N-naphthyl-N-phenylamino; mono- or
di-aralkylamino groups, such as N-benzylamino and
N,N-dibenzylamino; and acylamino groups, such as acetylamino,
benzoylamino and tert-butoxycarbonylamino.
Examples of the acyl group include aliphatic or aromatic
acyl groups, such as acetyl, propionyl, butyryl, valeryl,
pivaloyl, benzoyl, o-, m- or p-toluoyl, p-nitrobenzoyl and
trifluoroacetyl.
Examples of the substituted silyl group include
trimethylsilyl, triphenylsilyl, tri(p-tolyl)silyl and
dimethylphenyl silyl.
Examples of the polymer chain include a 6,6-nylon chain,
a vinyl polymer chain and a styrene polymer chain.
When n is 3 in the formula (1'), the aluminum complex of
the present invention can be easily synthesized by a reaction
of, in an inert organic solvent, the aluminum compound of the
general formula (1) with the biaryldiol compound of the general
formula (2), the molar ratio of which is 1.5- to 5-fold, and
preferably 1.5- to 2-fold, relative to the aluminum compound.
The reaction temperature ranges, for example, -30 to 60°C,
preferably -10 to 40°C, and more preferably 0 to 30°C. The
reaction duration is, for example, 0.25 to 30 hours, and
preferably 0.5 to 2 hours. Examples of the inert organic
solvent include hydrocarbons (hexane, heptane, benzene,
toluene, xylene, etc.), ethers (diethyl ether, diisopropyl
ether, tetrahydrofuran, etc.) and halogenated hydrocarbons
(dichloromethane, dichloroethane, chlorobenzene,
bromotoluene, etc.). The aluminum compound (1), and the
biaryldiol compound represented by the general formula (2) may
be used in the form of a solution diluted with the inert organic
solvent, and one of the solutions may be added all at once or
dropwise slowly to the other.
When n is 2, the aluminum complex of the present invention
can be easily synthesized as follows. First, the aluminum
compound of the formula (1) is allowed to react with the
biaryldiol compound of the formula (2) , the molar ratio of which
is 1.1- to 1.3-fold relative to the aluminum compound, in the
same inert organic solvent as exemplified in the case where n
is 3. The reaction temperature ranges, for example, -30 to 60°C,
preferably -10 to 40°C, and more preferably 0 to 30°C. The
reaction duration is, for example, 0.25 to 30 hours, and
preferably 0.5 to 2 hours. Next, 0.4 Eq or more of the
biaryldiol compound of the formula (3) is added to the reaction
mixture of the aluminum compound of the formula (1) and the diol
compound of the formula (2), which is obtained in the above
reaction, and then a further reaction is allowed to proceed.
The reaction temperature ranges, for example, -30 to 60°C,
preferably -10 to 40°C, and more preferably 0 to 30°C. The
reaction duration is, for example, 0.25 to 30 hours, and
preferably 0.5 to 2 hours. The biaryldiol compound of the
formula (3) may be diluted with the solvent or not diluted before
added to the reaction mixture. Also, the biaryldiol compound
of the formula (3) may be added thereto all at once or dropwise
slowly. The biaryldiol compound of the formula (3) can be added
to the reaction mixture of the aluminum compound of the formula
(1) and the biaryldiol compound of the formula (2), and vice
versa. It is preferable to ensure that the biaryldiol compound
of the formula (2) and the biaryldiol compound of the formula
(3) separately react with the aluminum compound (1). It is
preferable to avoid simultaneous addition of both biaryldiol
compounds.
Preferable examples of the biaryldiol compound represented
by the formula (2) or (3) of the present invention include, but
are not limited to, the following compounds.
Next, the compounds represented by the general formulae (4)
and (5) used for selective cyclization of the present invention
will be described.
Regarding the compounds represented by the general formulae
(4) and (5) , the optionally substituted alkyl group represented
by R9, R10, R11, R12, R13, R14 or R15 refers to a straight or branched
alkyl group having 1 to 8, preferably 1 to 4 carbon atoms, and
preferable examples thereof include alkyl groups having 1 to
4 carbon atoms, such as methyl, ethyl, propyl, isopropyl,
n-butyl, sec-butyl, isobutyl and tert-butyl.
Examples of the substituent in the alkyl group include
alkoxy groups having 1 to 6 carbon atoms, such as methoxy and
ethoxy; and aryl groups, such as phenyl, naphthyl and tolyl.
Regarding the hydroxyl group which may be protected by a
protecting group, which is represented by R11, examples of the
protecting group include acyl groups, such as acetyl, benzoyl
and methoxycarbonyl; aralkyl groups, such as benzyl; and
substituted silyl groups, such as trimethylsilyl and
t-butyldimethylsily1.
Subsequently, the preparation process of the present
invention, i.e. , the selective cyclization which increases the
ratio of a particular optical isomer, will be described below
by citing, as an example, production of isopulegol via
cyclization of citronellal using an aluminum complex having
1,1'-bi-2-naphthol (BINOL) as a biaryldiol compound.
However, the example below is intended for illustrative
purpose only, and the present invention is not limited to the
substrate and product shown below.
Namely, citronellal having a low to middle optical purity
is subjected to enantioselective cyclization using the
aluminum-optically active binaphthol complex of the present
invention as a catalyst, and thereby isopulegol and citronellal
can be obtained with a higher optical purity than that of the
substrate citronellal.
The amount of the aluminum complex used for the cyclization
of the present invention is not particularly limited, but it
is usually 0.05 to 10 mol%, preferably 0.5 to 5 mol%, and more
preferably 0.7 to 2 mol% relative to that of citronellal in terms
of moles of aluminum.
The preparation method of the aluminum complex used for the
cyclization of the present invention is as follows, for example.
(a) (i) mixing 1 Eq of the aluminum compound of the formula (1)
with 1.0 Eq or more of the optically active biaryldiol compound
having a chiral axis represented by the formula (2) in a reaction
system, to prepare a complex, or
(ii) allowing 1 Eq of the aluminum compound of the formula (1)
to react with 1.0 to 1.3 Eq of the optically active biaryldiol
compound having a chiral axis represented by the formula (2) ,
and mixing therewith 0.4 to 1.0 Eq of the optically active
biaryldiol compound having a chiral axis or racemic biaryldiol
compound represented by the formula (3) , to prepare a complex,
and
then adding thereto citronellal (the in situ method).
(b) mixing citronellal and a complex isolated after the
above-mentioned preparation at the time of cyclization.
Usually, each method of (a) and (b) produces the same results.
The temperature of the cyclization is not particularly
limited, but it is usually -30 to 50°C, preferably -10 to 30°C,
and more preferably 0 to 20°C. The reaction is allowed to
proceed with the temperature kept within the above-mentioned
ranges for usually 0.25 to 30 hours, and preferably 0.5 to 20
hours, and thereby gives isopulegol easily.
The cyclization of the present invention may be performed
without any solvent or in the presence of an inert solvent. Any
solvent can be used without particular limitation as long as
it does not significantly disturb the cyclization, and examples
thereof include aliphatic hydrocarbons, such as hexane, heptane
and octane; alicyclic hydrocarbons, such as cyclohexane and
methylcyclohexane; aromatic hydrocarbons, such as benzene,
toluene and xylene; halogenated hydrocarbons, such as
dichloromethane, dichloroethane, chlorobenzene and
bromotoluene; and ethers, such as diethyl ether, diisopropyl
ether, dimethoxyethane, tetrahydrofuran, dioxane and
dioxolane. Inter alia, aliphatic or aromatic hydrocarbons,
such as toluene and heptane, are more preferred.
The amount of the solvent ranges usually 0- to 20-fold, and
preferably 0.5- to 7-fold relative to that of citronellal. The
cyclization is preferably performed in an inert gas (such as
nitrogen or argon gas) atmosphere for smooth progress of
cyclization.
After completion of the cyclization, ordinary
post-treatment, such as distillation, crystallization and
various kinds of chromatography, may be performed alone or in
combination thereof, for purification of the resulting product.
For example, in the case of purification of isopulegol, highly
purified isopulegol can be obtained simply by distillation,
without need of low temperature separation. After
distillation, the residue may be subjected to ordinary
treatment with an acid or an alkali for removal of impurities
etc. including aluminum, and subsequent crystallization. Thus,
ligands can be recovered.
EXAMPLES
Hereinafter, the present invention will be illustrated in
detail by Comparative Examples and Examples, but the present
invention is not limited thereto.
Measurement of the product was performed by gas
chromatography (GC). The conditions used for the measurement
are as follows.
Analytical instrument: G5000 (Hitachi)
Column:
Conversion rate measurement BC-WAX (0.25 mm x 30 m) (GL
Sciences)
Optical purity measurement ß-DEX 225 (0.25 mm x 30 m)
(SPELCO), ß-DEX 325 (0.25 mm x 30 m) (SPELCO)
Detector: FID
The optical purity of each citronellal used in Examples is as
follows.
d-citronellal: 97.8%e.e.
1-citronellal: 96.6%e.e.
Racemic citronellal: 0.74%e.e.
(Example 1) Aluminum complex preparation and l-isopulegol
synthesis
In a 200-ml reaction flask, 1.31 g (4.59 mmol) of
(R)-l,l' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 46 ml of methylene chloride
and 3 ml (3 mmol) of a hexane solution of triethylaluminum (1.0
mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour. After this, the solvent
was distilled off and 1.40 g of a colorless to light orange solid
was obtained. The solid was reprecipitated with methylene
chloride/hexane, and the resulting product was analyzed by
1H-NMR. The analysis results are as follows.
1H-NMR(DMSO-d6): 6.86-7.26 (m, 24H), 7.68-7.93 (m, 12H)
The NMR chart is shown in Fig. 1, and the enlarged view of
the lower field thereof is shown in Fig. 2.
270 mg of the solid obtained above was added to 1.54 g (10
mmol) of d-citronellal cooled to a temperature of 0 to 5°C, and
the mixture was stirred at a temperature of 0 to 5°C for 1 hour.
After completion of the reaction, 2 ml of water and 2 ml of
toluene were added thereto, and the organic layer was analyzed
by GC. According to the analysis results, the substrate
conversion rate was 81.1%, the 1-isopulegol selectivity was
94.0%, and the ratio of 1-isopulegol to the other isomers was
96.1:3.9.
(Example 2) 1-isopulegol synthesis
In a 50-ml Schlenk flask, 229 mg (0.8 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 4.6 ml of toluene and 0.5
ml (0.5 mmol) of a toluene solution of triethylaluminum (1.0
mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of d-citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 1 hour. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC. According to the analysis results, the
substrate conversion rate was 98.5%, the 1-isopulegol
selectivity was 93.8%, and the ratio of 1-isopulegol to the
other isomers was 98.3:1.7.
(Example 3) 1-isopulegol synthesis
The same experiment as described in Example 2 was performed
except that 229 mg of (S)-2,2' -dihydroxy-1,1' -binaphthyl was
used instead of (R)-1,1'-bi-2-naphthol in Example 2.
According to the analysis results, the substrate conversion
rate was 37.4%, the 1-isopulegol selectivity was 100%, and the
ratio of 1-isopulegol to the other isomers was 73.6:26.4.
(Example 4) 1-isopulegol synthesis
In a 50-ml Schlenk flask, 22.9 mg (0.08 mmol) of
(R)-1,1'-bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 4.6 ml of toluene and 0.05
ml (0.05 mmol) of a toluene solution of triethylaluminum (1.0
mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of d-citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 20 hours. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC. According to the analysis results, the
substrate conversion rate was 94.9%, the 1-isopulegol
selectivity was 92.5%, and the ratio of 1-isopulegol to the
other isomers was 97.0:3.0.
(Example 5) 1-isopulegol synthesis
In a 50-ml Schlenk flask, 229 mg (0.8 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas . Then, 4 . 6 ml of methylene chloride
and 0.5 ml (0.5 mmol) of a toluene solution of triethylaluminum
(1.0 mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. The catalyst solution was concentrated in vacuo for
solidification, and then a white to light yellow solid was
obtained. In a nitrogen atmosphere, the solid was quickly added
to a mixed solution of 1.54 g (10 mmol) of d-citronellal and
4.6 ml of toluene, which was previously cooled to a temperature
of 0 to 5°C, and the mixture was stirred at a temperature of
0 to 5°C for 1 hour. After completion of the reaction, 2 ml
of water was added thereto, and the organic layer was analyzed
by GC. According to the analysis results, the substrate
conversion rate was 94.4%, the 1-isopulegol selectivity was
93.0%, and the ratio of 1-isopulegol to the other isomers was
96.9:3.1.
(Example 6) d-isopulegol synthesis
In a 50-ml Schlenk flask, 229 mg (0.8 mmol) of
(S)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 4.6 ml of toluene and 0.5
ml (0.5 mmol) of a toluene solution of triethylaluminum (1.0
mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of 1-citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 1 hour. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC. According to the analysis results, the
substrate conversion rate was 94.8%, the d-isopulegol
selectivity was 9 5.7%, and the ratio of d-isopulegol to the
other isomers was 97.2:2.8.
(Example 7) d-isopulegol synthesis
The same experiment as described in Example 6 was performed
except that 229 mg of (R)-2,2'-dihydroxy-1,1'-binaphthyl was
used instead of (S)-1,1'-bi-2-naphthol in Example 6.
According to the analysis results, the substrate conversion
rate was 51.2%, the d-isopulegol selectivity was 84 .9% , and the
ratio of d-isopulegol to the other isomers was 62.9:37.1.
(Example 8) Synthesis of 1-isopulegol from racemic citronellal
In a 50-ml Schlenk flask, 258 mg (0.9 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas . Then, 5 . 8 ml of methylene chloride,
5.8 ml of toluene and 0.5 ml (0.5 mmol) of a toluene solution
of triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 3.86 g (25 mmol) of racemic
citronellal was added dropwise thereto, and the mixture was
stirred at a temperature of 0 to 5°C for 1 hour. After completion
of the reaction, 2 ml of water was added thereto, and the organic
layer was analyzed by GC. According to the analysis results,
the substrate conversion rate was 48.9%, the isopulegol
selectivity was 95.6%, the enantioselectivity for
1-citronellal was 53.6%e.e., and the enantioselectivity for
1-n-isopulegol was 67.7%e.e.
(Example 9) 1-isopulegol synthesis
In a 300-ml reaction flask, 2.29 g (8.0 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 116 ml of toluene and 5 ml
(5.0 mmol) of a toluene solution of triethylaluminum (1.0 mol/L)
were successively added thereto and the mixture was stirred at
room temperature for 1 hour, to give a catalyst solution. After
the catalyst solution was cooled to a temperature of 0 to 5°C,
38.6 g (250 mmol) of d-citronellal was slowly added dropwise
thereto, and the mixture was stirred at a temperature of 0 to
5°C for 9 hours. After completion of the reaction, the reaction
mixture was concentrated in vacuo, and continuously toluene was
distilled off at a temperature of 110 to 115°C at a pressure
of 2.93 to 3.33 kPa (22 to 25 mmHg), to give 31.0 g of the
objective 1-isopulegol at the yield of 80.3%. The GC analysis
results show that the purity was 99.0% and that the ratio of
1-isopulegol to the other isomers was 98.7:1.3.
The residue obtained after distillation was diluted with
toluene, washed with an aqueous sulfuric acid solution,
concentrated and subjected to crystallization with a
toluene/heptane solution, and then 1.65 g of
(R)-1,1'-bi-2-naphthol was recovered. Using the recovered
BINOL, the same reaction as described in Example 1 was performed.
According to the analysis results, the substrate conversion
rate was 95.1%, the 1-isopulegol selectivity was 99.2%, and the
ratio of 1-isopulegol to the other isomers was 97.5:2.5.
(Example 10) Synthesis of 1-isopulegol from citronellal having
an excess of d-isomer
In a 50-ml Schlenk flask, 258 mg (0.9 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 5 .8 ml of methylene chloride,
5.8 ml of toluene and 0.5 ml (0.5 mmol) of a toluene solution
of triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 3.86 g (25 mmol) of 60%ee
citronellal (having an excess of d-isomer) was added dropwise
thereto, and the mixture was stirred at a temperature of 0 to
5°C for 3 hours. After completion of the reaction, 2 ml of water
was added thereto, and the organic layer was analyzed by GC.
According to the analysis results, the substrate conversion
rate was 71.1%, the isopulegol selectivity was 99.6%, the
enantioselectivity for 1-citronellal was 8.90%e.e., and the
enantioselectivity for 1-n-isopulegol was 91.0%e.e.
(Example 11) Synthesis of 1-isopulegol from citronellal having
an excess of d-isomer
In a 50-ml Schlenk flask, 258 mg (0.9 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas . Then, 5 . 8 ml of methylene chloride,
5.8 ml of toluene and 0.5 ml (0.5 mmol) of a toluene solution
of triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 3.86 g (25 mmol) of 20%ee
citronellal (having an excess of d-isomer) was added dropwise
thereto, and the mixture was stirred at a temperature of 0 to
5°C for 2 hours. After completion of the reaction, 2 ml of water
was added thereto, and the organic layer was analyzed by GC.
According to the analysis results, the substrate conversion
rate was 61.7%, the isopulegol selectivity was 99.5%, the
enantioselectivity for 1-citronellal was 60.8%e.e., and the
enantioselectivity for 1-n-isopulegol was 76.4%e.e.
(Example 12) Improvement of optical purity of citronellal
having an excess of d-isomer
In a 50-ml Schlenk flask, 258 mg (0.9 mmol) of
(S)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 5 . 8 ml of methylene chloride,
5.8 ml of toluene and 0.5 ml (0.5 mmol) of a toluene solution
of triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 3.86 g (25 mmol) of 60%ee
citronellal (having an excess of d-isomer) was added dropwise
thereto, and the mixture was stirred at a temperature of 0 to
5°C for 3 hours. After completion of the reaction, 2 ml of water
was added thereto, and the organic layer was analyzed by GC.
According to the analysis results, the substrate conversion
rate was 29.4%, the isopulegol selectivity was 98.9%, the
enantioselectivity for d-citronellal was 84.3%e.e., and the
enantioselectivity for d-n-isopulegol was 23.7%e.e.
(Examples 13 to 20) Synthesis of 1-isopulegol using aluminum
catalyst
The results of synthesis using various biaryldiols are shown
below. The reaction conditions are as follows. In a 50-ml
Schlenk flask, a given Eq of the biaryldiol compound of the
general formula (2) (L1H2) was placed and the air in the flask
was replaced with nitrogen gas. Then, 4 . 6 ml of a given solvent
and triethylaluminum (0.5 mmol) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. Alternatively, a given Eq of the
biaryldiol compound of the general formula (3) (L2H2) was
further added to the reaction mixture and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 1 hour. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC.
In the table, conv. represents the conversion rate of
citronellal, sel. represents the selectivity for isopulegol,
and n-sel. represents the selectivity for n-isopulegol.
(R)-BINOL, (R)-H8-BINOL, BIPOL and (R)-DiBr-H8-BINOL
represent the following compounds.
(In the scheme, Et represents an ethyl group, L1H2 represents
a biaryldiol compound represented by the general formula (2) ,
L2H2 represents a biaryldiol compound represented by the general
formula (3), and * represents a chiral carbon.)
The substrate used in Example 14 was 1-citronellal, and the
substrate used in the other Examples in the table was
d-citronellal.
(Example 21) Synthesis of 1-isopulegol f rom racemic citronellal
In a 50-ml Schlenk flask, 129 mg (0.45 mmol) of
(R)-1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 2 ml of methylene chloride,
2 ml of toluene and 0.18 ml (0.25 mmol) of a hexane solution
of trimethylaluminum (1.4 mol/L) were successively added
thereto and the mixture was stirred at room temperature for 7
hours , to give a catalyst solution. After the catalyst solution
was cooled to a temperature of 0 to 5°C, 1.93 g (12.5 mmol) of
racemic citronellal was added dropwise thereto, and the mixture
was stirred at a temperature of 0 to 5°C for 1 hour. After
completion of the reaction, 2 ml of water was added thereto,
and the organic layer was analyzed by GC. According to the
analysis results, the substrate conversion rate was 46.5%, the
isopulegol selectivity was 87.6%, the enantioselectivity for
1-citronellal was 43.8%e.e., and the enantioselectivity for
1-n-isopulegol was 76.0%e.e.
(Example 22) Synthesis of 1-isopulegol from racemic citronellal
In a 50-ml Schlenk flask, 178 mg (0.4 mmol) of
(R)-3,3' -dibromo-1,1' -bi-2-naphthol was placed and the air in
the flask was replaced with nitrogen gas. Then, 9 ml of
methylene chloride and 0.4 ml (0.4 mmol) of a toluene solution
of triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 3.09 g (20 mmol) of racemic
citronellal was added dropwise thereto, and the mixture was
stirred at a temperature of 0 to 5°C for 5 hours. After
completion of the reaction, 2 ml of water was added thereto,
and the organic layer was analyzed by GC. According to the
analysis results, the substrate conversion rate was 50.5%, the
isopulegol selectivity was 61.6%, the enantioselectivity for
1-citronellal was 15.6%e.e., and the enantioselectivity for
1-n-isopulegol was 26.3%e.e.
In the case where 285 mg (0.64 mmol) of
(R)-3,3'-dibromo-1,1'-bi-2-naphthol was used and 9-hour
stirring for cyclization was performed, the substrate
conversion rate was 42.8%, the isopulegol selectivity was 92.7%,
the enantioselectivity for 1-citronellal was 23.3%e.e. , and the
enantioselectivity for 1-n-isopulegol was 42.6%e.e.
(Example 23) Synthesis of d-isopulegol from racemic citronellal
In a 50-ml Schlenk flask, 214 mg (0.3 mmol) of
(R)-3,3'-bis(triphenylsilyl)-1,1'-bi-2-naphthol was placed
and the air in the flask was replaced with nitrogen gas. Then,
7 ml of toluene and 0.3 ml (0.3 mmol) of a toluene solution of
triethylaluminum (1.0 mol/L) were successively added thereto
and the mixture was stirred at room temperature for 1 hour, to
give a catalyst solution. After the catalyst solution was
cooled to a temperature of 0 to 5°C, 2.31 g (15 mmol) of racemic
citronellal was added dropwise thereto, and the mixture was
stirred at a temperature of 0 to 5°C for 1 hour. After completion
of the reaction, 2 ml of water was added thereto, and the organic
layer was analyzed by GC. According to the analysis results,
the substrate conversion rate was 55.3%, the isopulegol
selectivity was 71.9%, the enantioselectivity for
d-citronellal was 7.20%e.e., and the enantioselectivity for
d-n-isopulegol was 14.6%e.e.
In the case where 386 mg (0.48 mmol) of
(R)-3,3'-bis(triphenylsilyl)-1,1'-bi-2-naphthol was used and
1-hour stirring for cyclization was performed, the substrate
conversion rate was 55.0%, the isopulegol selectivity was 70.3%,
the enantioselectivity for d-citronellal was 6 . 43%e.e. , and the
enantioselectivity for d-n-isopulegol was 17.0%e.e.
(Comparative Examples 1 to 4) Isopulegol production by
cyclization of citronellal using lithium aluminum hydride as
aluminum compound
In a 50-ml Schlenk flask, 229 mg (0.8 mmol, 1.6eq) or 300
mg (1.05 mmol, 2.1eq) of (R)-1,1'-bi-2-naphthol was placed and
the air in the flask was replaced with nitrogen gas. Then, 4.6
ml of a given solvent and 19 mg (0.5 mmol) of lithium aluminum
hydride were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of d-citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 1 hour. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC. The analysis results are shown below. In
the table, conv. represents the conversion rate of
d-citronellal, and sel. represents the selectivity for
1-isopulegol.
(Comparative Example 5) 1-isopulegol synthesis with
simultaneous addition of ligands
In a 50-ml Schlenk flask, 143 mg (0.5 mmol) of
(R)-1,1'-bi-2-naphthol and 55.9 mg (0.3 mmol) of 2,2' -biphenol
were placed and the air in the flask was replaced with nitrogen
gas. Then, 4.6 ml of methylene chloride and 0.5 ml (0.5 mmol)
of a toluene solution of triethylaluminum (1.0 mol/L) were
successively added thereto and the mixture was stirred at room
temperature for 2 hours, to give a catalyst solution. After
the catalyst solution was cooled to a temperature of 0 to 5°C,
1.54 g (10 mmol) of d-citronellal was added dropwise thereto,
and the mixture was stirred at a temperature of 0 to 5°C for
1 hour. After completion of the reaction, 2 ml of water was
added thereto, and the organic layer was analyzed by GC.
According to the analysis results, the substrate conversion
rate was 42.3%, the 1-isopulegol selectivity was 96.2%, and the
ratio of 1-isopulegol to the other isomers was 87.2:12.8.
(Comparative Example 6) 1-isopulegol synthesis using racemic
1,1'-bi-2-naphthol as aluminum catalyst
In a 50-ml Schlenk flask, 229 mg (0.8 mmol) of
1,1' -bi-2-naphthol was placed and the air in the flask was
replaced with nitrogen gas. Then, 4.6 ml of toluene and 0.5
ml (0.5 mmol) of a toluene solution of triethylaluminum (1.0
mol/L) were successively added thereto and the mixture was
stirred at room temperature for 1 hour, to give a catalyst
solution. After the catalyst solution was cooled to a
temperature of 0 to 5°C, 1.54 g (10 mmol) of d-citronellal was
added dropwise thereto, and the mixture was stirred at a
temperature of 0 to 5°C for 1 hour. After completion of the
reaction, 2 ml of water was added thereto, and the organic layer
was analyzed by GC. According to the analysis results, the
substrate conversion rate was 22.7%, the 1-isopulegol
selectivity was 62.8%, and the ratio of 1-isopulegol to the
other isomers was 70.2:29.8.
CLAIMS
1. An aluminum complex obtainable by a reaction of 1 Eq of an
aluminum compound represented by the following general formula
(1):
Al(Lg)3 (1)
(in the formula (1), Lg represents an alkyl group, an alkoxy
group or a halogen atom) and 1.5 Eq or more of a biaryldiol
compound represented by the following general formula (2):

(in the formula (2) , R1, R2, R3, R1' , R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxyl group, a halogen atom,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4' , R4' and R3', R3' and R2', or R2' and R1'
may bind to each other to form a ring), or
by a reaction of 1 Eq of the aluminum compound represented by
the above general formula (1), 1.1 to 1.3 Eq of the biaryldiol
compound represented by the above general formula (2) and 0.4
Eq or more of a biaryldiol compound represented by the following
general formula (3):

(in the formula (3), R5, R6, R7, R8, R5', R6', R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8' ,
R8' and R7' , R7' and R6' , or R6' and R5' may bind to each other to
form a ring).
2. The aluminum complex according to Claim 1, wherein the
biaryldiol compound represented by the general formula (2) is
an optically active compound having a chiral axis.
3. The aluminum complex according to Claim 2, wherein both of
the biaryldiol compound represented by the general formula (2)
and the biaryldiol compound represented by the general formula
(3) are optically active compounds having a chiral axis.
4. The aluminum complex according to any of Claims 1 to 3, which
is represented by the following general formula (1'):
[Al2(L1)n(L2)3-n]m (1')
(in the formula (1'), n represents an integer of 2 or 3; m
represents a natural number; L1 represents a ligand represented
by the following formula (2'); and L2 represents a ligand
represented by the following formula (3'):

(in the formula (2'), R1, R2, R3, R1', R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxy 1 group, a halogen atom,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4', R4' and R3' , R3' and R2' , or R2' and R1'
may bind to each other to form a ring, and
in the formula (3'), R5, R6, R7, R8, R5', R6' . R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8' ,
R8' and R7', R7' and R6' , or R6' and R5' may bind to each other to
form a ring)).
5. A process for preparing an optically active compound,
comprising performing, in the presence of an aluminum complex,
cyclization of a compound having, in a molecule, a formyl group
and a double bond which allow carbonyl-ene cyclization, the
compound existing as a mixture of optical isomers thereof, to
increase the ratio of a particular optical isomer in a cyclized
compound or an unreacted compound, the aluminum complex being
obtainable by a reaction of 1 Eq of an aluminum compound
represented by the following general formula (1):
Al(Lg)3 (1)
(in the formula (1), Lg represents an alkyl group, an alkoxy
group or a halogen atom) and 1.0 Eq or more of an optically active
biaryldiol compound having a chiral axis represented by the
following general formula (2):

(in the formula (2), R1, R2, R3, R1', R2' and R3' independently
represent a hydrogen atom, a halogen atom, a hydroxyl group,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, a nitro group, an
acyl group, a substituted silyl group or a polymer chain; R4
and R4' independently represent a hydroxyl group, a halogen atom,
a saturated or unsaturated carbon chain, an optionally
substituted aryl group, an optionally substituted heterocyclic
group, an alkoxy group, an aryloxy group, an aralkyloxy group,
a carboxyl group which may be protected by a protecting group,
an amino group, a substituted amino group, an acyl group, a
substituted silyl group or a nitro group; and R1 and R2, R2 and
R3, R3 and R4, R4 and R4' , R4' and R3' , R3' and R2' , or R2' and R1'
may bind to each other to form a ring), or
by a reaction of 1 Eq of the aluminum compound represented by
the above general formula (1), 1.0 to 1.3 Eq of the optically
active biaryldiol compound having a chiral axis represented by
the above general formula (2) and 0.4 Eq or more of a biaryldiol
compound represented by the following general formula (3):

(in the formula (3), R5, R6, R7, R8, R5', R6', R7' and R8'
independently represent a hydrogen atom, a hydroxyl group, a
halogen atom, a saturated or unsaturated carbon chain, an
optionally substituted aryl group, an optionally substituted
heterocyclic group, an alkoxy group, an aryloxy group, an
aralkyloxy group, a carboxyl group which may be protected by
a protecting group, an amino group, a substituted amino group,
a nitro group, an acyl group, a substituted silyl group or a
polymer chain; and R5 and R6, R6 and R7, R7 and R8, R8 and R8' ,
R8' and R7' , R7' and R6' , or R6' and R5' may bind to each other to
form a ring).
6 . The process according to Claim 5 , wherein the compound having,
in a molecule, a formyl group and a double bond which allow
carbonyl-ene cyclization is represented by the following
general formula (4):
(in the formula (4), n2 represents an integer of 1 or 2; R ,
R10 and R12 independently represent a hydrogen atom or an
optionally substituted alkyl group; R11 represents an
optionally substituted alkyl group or a hydroxyl group which
may be protected by a protecting group; R13, R14 and R15
independently represent a hydrogen atom or an optionally
substituted alkyl group; and the wavy line represents
configuration E or Z).
7. The process according to Claim 5, wherein the cyclized
compound is represented by the following general formula (5):

(in the formula (5), n2 represents an integer of 1 or 2; R9,
R10 and R12 independently represent a hydrogen atom or an
optionally substituted alkyl group; R11 represents an
optionally substituted alkyl group or a hydroxyl group which
may be protected by a protecting group; R13, R14 and R15
independently represent a hydrogen atom or an optionally
substituted alkyl group; and the wavy line represents
configuration E or Z).
8. The process according to Claim 5, wherein the compound having,
in a molecule, a formyl group and a double bond which allow
carbonyl-ene cyclization is racemic citronellal or optically
active citronellal, and the cyclized compound is optically
active isopulegol.
9. The process according to Claim 8, wherein the optically
active isopulegol is 1-isopulegol.
10. The process according to Claim 8, wherein the optically
active citronellal is 1-citronellal.

Provided is a method for enriching the proportions of the optical isomers not only of a compound produced by ring
closure but also of the remaining compound which has not undergone ring closure when a mixture of optical isomers of a compound
having a formyl group and a double bond which can undergo an intra-molecular carbonyl-ene ring-closing reaction is subjected
to a ring-closing reaction. The method for the enrichment of the proportions of the optical isomers, wherein a mixture of
optical isomers of a compound having a formyl group and a double bond which can undergo an intra-molecular carbonyl-ene ring-
closing reaction is subjected to a ring-closing reaction, is carried out in the presence of a specified aluminum complex of general
formula [Al2(L1)n(L2)3-n]m