DESCRIPTION
TITLE OF THE INVENTION: NOVEL COMPOUND AND FRAGRANCE COMPOSITION CONTAINING SAME 5
TECHNICAL FIELD
[0001]
The present invention relates to a novel compound having a 3,5,5-trimethylheptane structure, a flavor composition and/or fragrance composition containing the compound, a 10 fragrance or cosmetic, toiletry product, bathing agent, beverage, food, quasi drug, or drug
containing the flavor composition and/or fragrance composition, and a method for strengthening a scent of a flavor and/or fragrance.
BACKGROUND ART 15 [0002]
In recent years, with the diversification of various food ingredients, food additives, beverages, foods (including favorite foods), fragrances or cosmetics, sanitation materials, sundries, drugs, and the like, formerly unknown new demands have been increasing for a flavor and/or fragrance used therein, and development of flavor substance and/or fragrance substance
2 0 having a highly preferred unique aroma has been requested. In particular, recently, due to the
rise in the nature-oriented style of people, with respect to highly preferred floral-like fragrance or green-like fragrance by which the natural environment can be characteristically imaged, development of new fragrance material derived from a natural compound or identical or similar to the natural compound has been strongly desired also from the standpoint of safety. 25 [0003]
As a fragrance ingredient having a floral note, homoallylic alcohols (see, for example, Patent Document 1) which are useful as a fragrance can be exemplified.
PRIOR ART DOCUMENT
3 0 PATENT DOCUMENT
[0004]
Patent Document 1: JP-T-2011-504469
SUMMARY OF THE INVENTION 3 5 PROBLEMS THAT THE INVENTION IS TO SOLVE
[0005]
1

However, floral- and green-based flavors and/or fragrances conventionally used are
insufficient for expressing scent responding to diversified customer needs, and development of
flavor material and/or fragrance material having higher preference has been strongly desired.
[0006]
5 Therefore, an object of the present invention is to provide a novel compound capable of
imparting floral-like and green-like scents which can satisfy the requirement described above and a flavor composition and/or fragrance composition containing the compound.
Also, another object of the present invention is to provide a product, for example, a fragrance or cosmetic, toiletry product, bathing agent, beverage, food, quasi drug, or drug, which 10 has been imparted with floral-like and green-like scents.
Further, a still another object of the present invention is to provide a method for strengthening floral-like and green-like scents of a flavor and/or fragrance.
MEANS FOR SOLVING THE PROBLEMS
15 [0007]
As a result of the intensive investigations in such circumstances described above, the
inventors of the present invention have found that a novel compound having a 3,5,5-
trimethylheptane structure has strong floral-like and green-like scents and is able to be a useful
scent-imparting agent to complete the present invention. 20 [0008]
Specifically, the present invention is achieved by [1] to [7] described below.
[1] Aracemic or optically active compound represented by the general formula (1) shown
below:
[0009]
25 [Chem. 1]
[0010]
(in the formula (1), a double line composed of a solid line and a dotted line represents a double bond or a single bond; Y is CHO, CHtOR^OR2), CH2OH, CH2OR3, COOR4, CH=NR5,
3 0 CN, or CH2SR6; both R1 and R2 are alkyl groups having a carbon number of from 1 to 4 or R1 and R2 may be combined with each other to fonn a ring; R3 is a hydrogen atom or an acyl group having a carbon number of from 1 to 8; R4 is a hydrogen atom or an alkyl group having a carbon number of from 1 to 4; R5 is a hydroxyl group or a phenyl group which may have a substituent; R6 is a hydrogen atom, an alkyl group having a carbon number of from 1 to 4 or an acyl group
3 5 having a carbon number of from 1 to 8; and * represents an asymmetric carbon atom).
2

[2] A flavor composition and/or fragrance composition containing the racemic or optically
active compound represented by the general formula (1) as described in [1] above.
[3] A product imparted with a scent, in which the flavor composition and/or fragrance
composition as described in [2] above is combined with at least one product selected from the 5 group consisting of beverages, foods, flagrances or cosmetics, toiletry products, air care products,
daily necessities and household goods, compositions for oral use, hair care products, skin care
products, body care products, detergents for clothing, soft finishing agents for clothing, quasi
drugs, and drugs.
[4] A method for improving a scent of a flavor and/or fragrance, including adding the
10 racemic or optically active compound represented by the general formula (1) as described in [ 1 ]
above.
[5] A method of producing a racemic or optically active aldehyde represented by the
formula (la) shown below:
[0011]
15 [Chem.2]
CHO (1a)
[0012]
(in the formula (la), * represents an asymmetric carbon atom);
the method including subjecting a triene represented by the formula (2) shown below to 2 0 an amination in the presence of an alkali metal salt of an amine to obtain an allylamine represented by the general formula (3) shown below: [0013]
[Chem. 3]
(2)
7 s (3) NR7R8
2 5 [0014]
(in the formula (3), R7 and R8 each independently is a hydrogen atom, an alkyl group having a carbon number of from 1 to 20 which may have a substituent, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, or an aralkyl group which
3 0 may have a substituent, provided that the case where both R and R are hydrogen atoms is
excluded, and R7 and R8 may be connected to each other to form a ring);
3

subsequently performing an isomerization to obtain a racemic or optically active enamine represented by the general formula (4) shown below: [0015]
[Chem. 4]
(4) NR7RQ
5
[0016]
(in the formula (4), R7 and R8 have the same meanings as defined above; and * represents an asymmetric carbon atom);
and further performing a solvolysis.
10 [6] An allylamine represented by the general formula (3) shown below:
[0017]
[Chem. 5]
7 « ^
NR7R8
[0018]
15 (in the formula (3), R and R each independently is a hydrogen atom, an alkyl group
having a carbon number of from 1 to 20 which may have a substituent, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, or an aralkyl group which may have a substituent, provided that the case where both R7 and Rs are hydrogen atoms is
7 ft
2 0 excluded, and R and R may be connected to each other to form a ring).
[7] A racemic or optically active enamine represented by the general formula (4) shown
below:
[0019]
[Chem. 6]
NR7R8
25
[0020]
1 ft
(in the formula (4), R and R each independently is a hydrogen atom, an alkyl group having a carbon number of from 1 to 20 which may have a substituent, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, an aryl group which may 3 0 have a substituent, a heterocyclic group which may have a substituent, or an aralkyl group which may have a substituent, provided that the case where both R7 and R8 are hydrogen atoms is
4

excluded, and R7 and R8 may be connected to each other to form a ring; and * represents an asymmetric carbon atom).
ADVANTAGE OF THE INVENTION 5 [0021]
The racemic or optically active compound represented by general formula (1) according to the present invention is an extremely useful flavor material and/or fragrance material which is highly preferred, excellent in a scent imparting property and excellent in diffusibility and a flavor and/or fragrance remaining property. By blending the compound, a preferred scent imparting 10 agent can be provided.
MODE FOR CARRYING OUT THE INVENTION [0022]
The compound according to the present invention is a racemic or optically active 15 compound represented by general formula (1) shown below (hereinafter, also referred to as a "compound having a 3,5,5-trimethylheptane structure of the present invention"). [0023]
[Chem. 7]
20 [0024]
(In the formula (1), a double line composed of a solid line and a dotted line represents a double bond or a single bond, Y is CHO, CHP^XOR2), CH2OH, CH2OR3, COOR4, CH-NR5, CN, or CH2SR6, both R1 and R2 are alkyl groups having a carbon number of from 1 to 4 or R and R2 may be combined with each other to form a ring, R3 is a hydrogen atom or an acyl group
2 5 having a carbon number of from 1 to 8, R4 is a hydrogen atom or an alkyl group having a carbon
number of from 1 to 4, R5 is a hydroxyl group or a phenyl group which may have a substiluent, R6 is a hydrogen atom, an alkyl group having a carbon number of from 1 to 4 or an acyl group having a carbon number of from 1 to 8, and * represents an asymmetric carbon atom.) [0025]
3 0 The compound represented by general formula (1) is preferably that having a (5S)
configuration or a (5R) configuration. [0026]
The compound having a 3,5,5-trimethylheptane structure of the present invention can be synthesized, for example, according to the methods illustrated in Scheme 1 and Scheme 2 3 5 shown below. However, the synthesis method tiiereof should not be construed as being limited to the methods of Scheme 1 and Scheme 2 below.
5

[0027] (Scheme 1) [0028]
[Chem. 8]
Amination \ / | Iscmerization
^_ — ft*
7^8
NR'R
(2) (3)
Soivolysis | Hydrogenation
■NR7R8 ^>\^k/CHO \^A^CHO
{A) <1a) (1al)
5
[0029]
(In formula (3) and formula (4), R7 and R8 each independently is a hydrogen atom, an alkyl group having a carbon number of from 1 to 20 which may have a substituent, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, an aryl group which
10 may have a substituent, a heterocyclic group which may have a substituent or an aralkyl group which may have a substituent, provided that the case where both R7 and R8 are hydrogen atoms is excluded, and R7 and R8 may be connected to each other to form a ring. In formula (4) and formula (la), * represents an asymmetric carbon atom.) [0030]
15 In Scheme 1, an amination of triene, for example, one represented by formula (2) is
performed in the presence of an alkali metal salt of an amine to obtain an allylamine represented by general formula (3) (hereinafter, also referred to as an "allylamine (3)"), an isomerization is then performed to obtain a racemic or optically active enamine represented by general formula (4) (hereinafter, also referred to as an "enamine (4)"), then a soivolysis is performed to obtain a
2 0 racemic or optically active terminal unsaturated aldehyde represented by formula (la)
(hereinafter, also referred to as a "terminal unsaturated aldehyde (la)"), and a hydrogenation is performed to obtain a saturated aldehyde represented by formula (la') (hereinafter, also referred to as a "saturated aldehyde (la')"). [0031]
2 5 (Scheme 2) [0032]
6

[Chem. 9]

Acetalization

CH(0R1)(OR2) (1b, b')

fmination

CHO (1a.a')

Reduction

(1c, C)

OH

Esterification
Sulfurization

<1d, d'}

ORJ

(U n

CH=NRS

COOR4 (1e, e'}

<1h, h')

SRE


CN
d9. 9l)
[0033]
(In the formulae, a double line composed of a solid line and a dotted line represents a 5 double bond or a single bond, and * represents an asymmetric carbon atom. In formula (lb, b'), both R1 and R2 are alkyl groups having a carbon number of from 1 to 4 or R1 and R2 may be combined with each other to form a ring. In formula (Id, d'), R is a hydrogen atom or an acyl group having a carbon number of from 1 to 8. In formula (le, e'), R4 is a hydrogen atom or an alkyl group having a carbon number of from 1 to 4. In formula (If, f'),R5 is a hydroxyl group
10 or a phenyl group which may have a substituent. In formula (lh, h'), R is a hydrogen atom, an alkyl group having a carbon number of from 1 to 4 or an acyl group having a carbon number of from 1 to 8.) [0034]
In Scheme 2, by an acetalization of the aldehyde of formula (la) or (la') obtained by
15 the method described in Scheme 1, a corresponding acetal of formula (lb) or (lb') can be
obtained. Also, by a reduction of an aldehyde portion of the aldehyde of formula (la) or (la'), a corresponding alcohol of formula (lc) or (lc') can be obtained. By an esterification ofthe alcohol thus-obtained, a corresponding ester of formula (Id) or (Id') can be obtained. Moreover, by a conversion of an alcohol portion ofthe alcohol of formula (lc) or (lc') to
2 0 mercaptan, a corresponding sulfur-containing compound of formula (lh) or (lh') can be obtained.

On the other hand, by an oxidation of the aldehyde of formula (la) or (la'), a corresponding carboxylic acid or a carboxylic acid ester of formula (le) or (le') can be obtained.
Furthermore, by a condensation of the aldehyde of formula (la) or (la') with an amine compound, a corresponding imine of formula (If) or (If) can be obtained. Also, by a 5 dehydration treatment of an oxime in which R5 in formula (If) or (If) represents a hydroxyl group, a corresponding nitrile of formula (Ig) or (lg') can be obtained. [0035]
Hereinafter, Scheme 1 and Scheme 2 are specifically described.
The triene represented by formula (2) which is a raw material for producing the 10 compound having a 3,5,5-trimethylheptane structure of the present invention is a known
compound and can be produced by a known method, for example, a method described in Yasushi KAJIHARA and other three persons, "Monoterpenoid Synthesis by Transition Metal Catalyzed Coupling of Enediylmagnesium with Cs-Organic Halides", The Chemical Society of Japan, 53, 3035-3036(1980). 15 [0036]
An amine which is used for production of the compound having a 3,5,5-trimethylheptane structure of the present invention is described below.
The amine for use in the present invention is represented by general formula (5) shown
below.
20 HNR7R8 (5)
(In formula (5), R7 and R8 each independently is a hydrogen atom, an alkyl group having a carbon number of from 1 to 20 which may have a substituent, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, or an aralkyl group which
2 5 may have a substituent, provided that the case where both R7 and R8 are hydrogen atoms is
excluded, and R and R may be connected to each other to form a ring.) [0037]
The alkyl group having a carbon number of from 1 to 20 represented by R7 or Rs in general formula (5) includes, for example, a methyl group, an ethyl group, a n-propyl group, an
3 0 isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-
pentyl group, an iso-pentyl group, a neopentyl group, a hexyl group, a heptyl group, an octyl
group, a nonyl group, a decyl group, an undecyl group, a dodecyl group, a tridecyl group, a
tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group,
a nonadecyl group, and an eicosyl group.
3 5 The cycloalkyl group having a carbon number of from 3 to 8 represented by R7 or R8 in
general formula (5) includes, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.
8

The aryl group represented by R7 or R8 in general formula (5) includes, for example, an
aromatic monocyclic or polycyclic group, such as a phenyl group, a naphthyl group, an anthryl
group, a phenanthryl group, or an indenyl group. Other examples include a metallocenyl group
such as a ferrocenyl group.
5 The heterocyclic group represented by R7 or R8 in general formula (5) includes, for
example, an oxiranyl group, an aziridinyl group, a 2-oxopyrrolidyl group, a piperidyl group, a piperazinyl group, a morpholino group, a tetrahydrofuryl group, a tetrahydropyranyl group, and a tetrahydrothienyl group.
The aralkyl group represented by R7 or R8 in general formula (5) includes, for example, 10 a benzyl group, a 1-phenylethyl group and a 2-phenylethyl group. [0038]
In the case where R7 and R8 in general formula (5) are connected to each other to form a ring, it includes, for example, a cyclic amine such as piperidine, pyrrolidine, morphoHne, indoline, or isoindoline. 15 [0039]
The alkyl group having a carbon number of from 1 to 20, cycloalkyl group having a carbon number of from 3 to 8, aryl group, heterocyclic group, and aralkyl group described above may have a substituent., and the substituent includes, for example, an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, a halogen atom, a hydroxyl group, an alkoxy group, a tri-2 0 substituted organosiiyi group, a carboxyl group, an acyl group, an acyloxy group, a substituted amino group, a heterocyclic group, and a nitro group. [0040]
The alkyl group as the substituent includes, for example, an alkyl group having a carbon number of from I to 6 such as a methyl group, an ethyl group, a n-propyl group, an
2 5 isopropyl group, a sec-butyl group, a tcrt-butyl group, a pentyl group, or a hexyl group.
[0041]
The aryl group as the substituent includes, for example, an aryl group having a carbon number of from 6 to 14 such as a phenyl group, an a~naphthyl group, a j3-naphthyl group, an anthryl group, a phenanthryl group, or a biphenyl group. 30 [0042]
The aralkyl group as the substituent includes an aralkyl group having a carbon number of from 7 to 12 such as a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, an a-naphthylmethyl group, or a p-naphthylmethyl group. [0043]
3 5 The cycloalkyl group as the substituent includes an alicyclic group having a carbon
number of from 5 to 8 such as a cyclopentyl group, a cyclohexyl group, a methylcyclohexyl
group, a cycloheptyl group, or a cyclooctyl group.
[0044]
9

The halogen atom as the substituent includes a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. [0045]
The alkoxy group as the substituent includes an alkoxy group having a carbon number 5 of from 1 to 4 such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group, or a tert-butoxy group. [0046]
The tri-substituted organosilyl group as the substituent includes a tri(Cl to C6 alkyl)silyl group such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a 10 dimethylisopropylsilyl group, a diethylisopropylsilyl group, a dimethyl(2,3-dimethyl-2-butyl)silyl group, a tert-butyldimethylsilyl group, or a dimethylhexylsilyl group. [0047]
The carboxyl group as the substituent includes an alkoxycarbonyl group having a carbon number of from 2 to 6 such as a methoxycarbonyl group or an ethoxycarbonyl group and 15 an arylcarboxyl group having a carbon number of from 6 to 11 such as a phenoxycarbonyl group. [0048]
The acyl group as the substituent includes an acyl group having a carbon number of from 1 to 8 such as a formyl group, an acetyl group, a propionyl group, a n-butyroyl group, an isobutyroyl group, or a benzoyl group. 20 [0049]
The acyloxy group as the substituent includes an acyloxy group having a carbon number of from 1 to 8 such as a formyloxy group, an acyloxy group, a propionyloxy group, a n-butyroyloxy group, an isobutyroyloxy group, or a benzoyloxy group. [0050]
2 5 The substituted amino group as the substituent includes a dialkylamino group having
alkyl groups each having a carbon number of from 1 to 12 as substituents, such as a dimethylamino group, a diethylamino group, a diisopropylamino group, a piperidyl group, or a piperidyl group. [0051]
3 0 The heterocyclic group as the substituent includes an aliphatic heterocyclic group and
an aromatic heterocyclic group. The aliphatic heterocyclic group includes a 5- to 8-membered, preferably 5~ or 6-membered, monocyclic, polycyclic or condensed-cyclic aliphatic heterocyclic group having a carbon number of from 2 to 14 and including, as a heteroatom, at least one, preferably from 1 to 3 heteroatoms, for example, a nitrogen atom, an oxygen atom or a sulfur 3 5 atom. Specific examples of the aliphatic heterocyclic group include a 2~oxopyrrolidyl group, a piperidyl group, a piperazinyl group, a morpholmo group, a tetrahydrofuryl group, a tetrahydropyranyl group and a tetrahydrothienyl group. On the other hand, the aromatic heterocyclic group includes a 5- to 8-membered, preferably 5- or 6~membered, monocyclic,
10

polycyclic or condensed-cyclic aromatic heterocyclic (heteroaryl) group having a carbon number
of from 2 to 15 and including, as a heteroatom, at least one, preferably from 1 to 3 heteroatoms
such as a nitrogen atom, an oxygen atom or a sulfur atom. Specific examples of the aromatic
heterocyclic group include a furyl group, a thienyl group, a pyridyl group, a pyridinyl group, a 5 pyrazinyl group, a pyradazinyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group,
a benzofuryl group, a benzothienyl group, a quinolyl group, an isoquinolyl group, a quinoxalinyl
group, a phthalazinyl group, a quinazolinyl group, a naphthyridinyl group, a cinnolinyl group, a
benzimidazolyl group, a benzoxazolyl group, and a benzothiazolyl group.
[0052]
10 Specific examples of the amine for use in the present invention include dimethylamine,
diethylamine, di-n-propylamine, diisopropylamine, cyclohexylamine, piperidine, pyrrolidine,
and morpholine.
[0053]
The used amount of the triene represented by formula (2) relative to the amine is from 1 15 to 100 times by mole, preferably from 1 to 10 times by mole, of the triene represented by
formula (2), relative to the amine.
[0054]
The alkali metal salt of an amine which can be used in the present invention can be
obtained by allowing the amine described above to react with an alkali metal catalyst. As the 2 0 alkali metal catalyst, an organic lithium compound, lithium metal, an organic sodium compound,
sodium metal, an orgamc potassium compound, or potassium metal can be used, and an organic
lithium compound or lithium metal can be preferably used.
[0055]
The alkali metal salt of an amine which can be used in the present invention can be
2 5 prepared by using any method. Examples thereof include a method in which one selected from
an organic lithium compound, an organic sodium compound and an organic potassium compound is allowed to react with an amine, and a method in which one selected from lithium metal, sodium metal and potassium metal is allowed to react with an amine in the presence of a hydrogen acceptor olefin such as isoprene or styrene.
3 0 The organic lithium compound includes, for example, methyllithium, n-butyllithium,
sec-butyl lithium, t-butyllithium, and phenyllithium. The organic sodium compound includes, for example, methylsodium, n-butylsodium, sec-butylsodium, t-butylsodium, and phenylsodium. The organic potassium compound includes, for example, methylpotassium, n-butyrpotassium, sec-butylpotassium, t-butylpotassium, and phenylpotassium. 3 5 [0056]
The amount of the alkali metal catalyst used in the animation is from 0.001 to 1 time by mole, preferably from 0.05 to 0.5 times by mole, relative to the amine used in the reaction. [0057]
11

The amination reaction is performed in an inert atmosphere with or without using a
solvent. In the case of using a solvent, a solvent capable of dissolving the alkali metal catalyst is
used. The solvent which can be used includes, for example, a hydrocarbon solvent such as
benzene or toluene, and an ether solvent such as tetrajhydrofiiran.
5 As to the reaction temperature, it cannot be said definitely depending on the raw
material and reagent used, and is ordinarily from 0 to 150°C and preferably from 50 to 100°C.
As to the reaction time, it cannot be said definitely, and is ordinarily from several
minutes to 24 hours and preferably from 1 to 10 hours.
[0058]
10 After the completion of the reaction, to the reaction mixture obtained by performing the
amination of the triene represented by formula (2) in the presence of the alkali metal salt of an amine under the reaction conditions described above is added water, ethanol, carbon dioxide, or the like to deactivate the alkali metal catalyst as the catalyst, and then the oil layer is subjected to a purification treatment, for example, by distillation or column chromatography, thereby 15 obtaining the allylamine represented by general formula (3). [0059]
The allylamine is a compound having isomers of (E)-from and (Z)-form.
In the aUylamine obtained by the synthesis method of the present invention described above, the (2E)-allylamine (3) which is the (E)-form has an extremely high chemical purity as 20 the (E)-rrom/(Z)-from ratio of 95/5 to 100/0. Thus, it may be used for the isomerization in the subsequent step without being subjected to fine distillation. [0060]
The racemic enamine represented by general formula (4) can be obtained by performing the isomerization of the allylamine (3) obtained by the amination reaction described
2 5 above.
As a method for isomerization of the allylamine (3), a method for isomerization using a transition metal phosphine complex as a catalyst can be adopted. [0061]
As the transition metal phosphine complex which can be used in the present invention, 30 a complex containing a transition metal complex and a phosphine ligand is preferably used.
The phosphine ligand which can be used in the transition metal phosphine complex for isomerization of the allylamine (3) of the present invention includes, for example, a monodentate phosphine ligand, a bidentate phosphine ligand and a polydentate phosphine ligand. [0062]
3 5 The monodentate phosphine ligand includes a monodentate phosphine ligand
represented by general formula (6) shown below. [0063]
12

[Chem. 10] R9
I (6)
[0064]
(In formula (6), R9to R11 each independently represents an alkyl group having a carbon 5 number of from 1 to 10, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent or an aromatic group which may have a substituent, or any two of R , R and R11 may be connected to each other together with the phosphorus atom bound thereto to form a ring.) [0065]
10 In the general formula (6), R9 to R1' each independently represents an alkyl group
having a carbon number of from 1 to 10, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent or an aromatic group which may have a substituent, or any two ofR9,R10andRn may be connected to each other together with the phosphorus atom bound thereto to form a ring.
15 [0066]
The alkyl group having a carbon number of from 1 to 10 represented by any ofR9to R11 in general formula (6) includes, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a neopentyl group, a hexyl group, a heptyl group, an
2 0 octyl group, a nonyl group, and a decyl group.
In the cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent, represented by any of R9to R11 in general formula (6), the cycloalkyl group includes, for example, a cyciopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.
2 5 In the aromatic group which may have a substituent, represented by any of R to R in
general formula (6), the aromatic group includes a hydrocarbon aromatic group such as a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, or an indenyl group; a heteroaromatic group such as a pyrrolyl group, a pyridyl group, a pyrazyl group, a quinolyl group, an isoquinolyl group, or an imidazolyl group; and a metallocenyl group such as a
3 0 ferrocenyl group.
[0067]
Specific examples of the substituent include an alky] group having a carbon number of from 1 to 12 such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an 3 5 isopentyl group, a neopentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group,
13

a decyl group, an undecyl group, or a dodecyl group; a lower alkoxy group having a carbon number of from 1 to 4 such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group, or a tert-butoxy group; an aryl group such as a phenyl group, an a-naphthyl group, a p-naphthyl group, or a 5 phenanthiyl group; an aralkyl group having a carbon number of from 7 to 13 such as a benzyl group, an a-phenylethyl group, a p-phenylethyl group, an a-phenylpropyl group, a p-phenylpropyl group, a 7-phenylpropyl group, or a naphthylmethyl group; a tri-substituted organosilyl group including, a tri(C 1 to C6 alkyl)silyl group such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a diniethylisopropylsilyl group, a 10 diethylisopropylsilyl group, a drmethyl(2,3-dimcthyl-2-butyl)silyl group, a tert-
butyldimethylsilyl group, or a dimethylhexylsilyl group, a di(Cl to C6 alkyl) (C6 to CI8 aryl)silyl group such as a dimethylcumylsilyl group, a di(C6 to CI 8 aryl) (CI to C6 alkyl)silyl group such as a tert-butyldiphenylsilyl group or a diphenylmethylsilyl group, a tri(C6 to C18 aryl)silyl group such as a triphenylsilyl group, and a tri(C7 to 19 aralkyl)silyl group such as a 15 tribenzylsilyl group or a tri-p-xylylsilyl group; a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom; and a nitro group. [0068]
In the case where any two of R9, R10 and Rn are connected to each other together with the phosphorus atom bound thereto to form a ring, the ring in which R9and R)0, R10and Rn, or 20 RuandR9 are connected together with the phosphorus atom bound thereto includes rings of a 4-membered ring, a 5-membered ring and a 6-membered ring. Specific rings include a phosphetane ring, a phospholane ring, a phosphorinane ring, a 2,4-dimethylphosphetane ring, a 2,4-diethylphosphetane ring, a 2,5-dimethylphospholane ring, a 2,5-diethylphospholane ring, a 2,6-dimethylphosphane ring, and a 2,6-diethylphosphorinane ring. 2 5 [0069]
Specific examples of the monodentate phosphinc ligand represented by the general formula (6) include trimethylphosphine, triethylphosphine, tributylphosphine, triphenyiphosphine, tritolylphosphine, tri(3,5-xylyl)phosphine, methyldiphenylphosphine, dimethylphenylphosphine, and phenylphosphorane. 30 [0070]
The bidentate phosphine ligand includes a bidentate phosphine ligand represented by general formula (7) shown below. [0071]
[Chem. 11]
R12 R14
I I (7)
R13 \A^ \R15
35
14

[0072]
(In formula. (7), R12 to R15 each independently represents an alkyl group having a carbon number of from 1 to 10, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent or an aromatic group which may have a substituent, or R and R ' or R1 and 5 R15 may be connected to each other together with the phosphorus atom bound thereto to form a ring, and A represents an alkylene chain which may have a substituent, a cycloalkanediyl group which may have a substituent, an alaryldiyl group which may have a substituent, or an aryldiyl group which may have a substituent.) [0073]
10 In the general formula (7), R32 to R15 each independently represents an alkyl group
having a carbon number of from 1 to 10, a cycloalkyl group having a carbon number of from 3 to 8 which may have a substituent or an aromatic group which may have a substituent, or R12 and RI3orR14andR15 may be connected to each other together with the phosphorus atom bound thereto to form a ring, and A represents an alkylene chain which may have a substituent, a
15 cycloalkanediyl group which may have a substituent, an alaiyldiyl group which may have a substituent, or an aryldiyl group which may have a substituent. [0074]
The alkyl group having a carbon number of from 1 to 10 represented by any of R to Ri5 in general formula (7) includes the same as that exemplified in general formula (6).
2 0 In the cycloalkyl group having a carbon number of from 3 to 8 which may have a
substituent, represented by any of R!2to R15in general formula (7), the cycloalkyl group includes the same as that exemplified in general formula (6).
In the aromatic group which may have a substituent, represented by any of R12 to Ri5 in general formula (7), the aromatic group includes the same as that exemplified in general formula 25 (6).
Specific examples of the substituent described above in general formula (7) include the same as those exemplified in general formula (6).
In the case where R12 and R13 or R14 and R15 is connected to each other together with the phosphorus atom bound thereto to form a ring in general formula (7), the ring formed
3 0 includes the same as those exemplified in general formula (6).
[0075]
The alkylene chain represented by A in general fonnula (7) includes, for example, a
methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a
pentamethylene group, and a hexamethylene group.
3 5 The cycloalkanediyl group represented by A in general formula (7) includes, for
example, a cyclobutanediyl group, a cyclopentancdiyl group, a cyclohexanediyl group, and a cycloheptanediyl group.
15

The alaryldiyl group represented by A in general formula (7) includes, for example, a toluene-2,a-diyl group, a l,2-xylene-a,a'-diyl group and a l,3-xylene-a,a'-diyl group.
The aryldiyl group represented by A in general formula (7) includes, for example, a benzenediyl group, a naphthaienediyl group, an anthracenediyl group, a phenanthrenediyl group, 5 a biphenyldiyl group, a binaphthyldiyl group, 4,4'-bi(l,3-benzodioxole)diyl group, and a ferrocenediyl group. [0076]
Each of the alkylene chain, the cycloalkanediyl group, the alaryldiyl group, and the aryldiyl group represented by A in general formula (7) may have a substituent. Examples of the 10 substituent include an alkyl group, an alkoxy group, an aryl group, and a heterocyclic group. . The alkyl group as the substituent includes a straight-chain or branched alkyl group having, for example, a carbon number of from 1 to 15, preferably a carbon number of from 1 to 10, more preferably a carbon number of from 1 to 6, and specific examples thereof include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, a s-butyl 15 group, an isobutyl group, a t-butyi group, a n-pentyl group, a neopentyl group, and a n-hexyl group.
The alkoxy group as the substituent includes a straight-chain or branched alkoxy group having, for example, a carbon number of from 1 to 6, and specific examples thereof include a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n~butoxy group, a 2 0 s-butoxy group, an isobutoxy group, a t-butoxy group, a n-pentyloxy group, a neopentyloxy group, and a n-hexyloxy group.
The aryl group as the substituent includes an aryl group having, for example, a carbon number of from 6 to 14, and specific examples thereof include a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, and a biphenyl group.
2 5 The heterocyclic group as the substituent includes an aliphatic heterocyclic group and
an aromatic heterocyclic group. The aliphatic heterocyclic group includes a 5- to 8-membered, preferably 5- or 6-membered, monocyclic, polycyclic or condensed-cyclic aliphatic heterocyclic group having, for example, a carbon number of from 2 to 14 and including, as a heteroatom, at least one, preferably from 1 to 3 heteroatoms, for example, a nitrogen atom, an oxygen atom or a
3 0 sulfur atom. Specific examples of the aliphatic heterocyclic group include a 2-oxopyrroIidyl
group, a piperidino group, a piperazinyl group, a morpholino group, a tetrahydrofuryl group, a tetrahydropyranyl group, and a tetrahydrothienyl group. On the other hand, the aromatic heterocyclic group includes a 5- to 8-membered, preferably 5- or 6-membered, monocyclic, polycyclic or condensed-cyclic aromatic heterocyclic (heteroaryl) group having, for example, a 35 carbon number of from 2 to 15 and including, as a heteroatom, at least one, preferably from 1 to 3 heteroatoms such as a nitrogen atom, an oxygen atom or a sulfur atom. Specific examples thereof include a furyl group, a thienyl group, a pyridyl group, a pyrimidinyl group, a pyrazinyl group, apyridazinyl group, apyrazolyl group, an imidazolyl group, an oxazolyl group, a
16

thiazolyl group, a benzofuryl group, a benzothienyl group, a quinolyl group, an isoquinolyl
group, a quinoxalyl group, a phthalazinyl group, a quinazolinyl group, a naphthyridinyl group, a
cinnolinyl group, a benzimidazolyl group, a benzoxazolyl group, and a benzothiazolyl group.
[0077]
5 Specific examples of the bidentate phosphine ligand represented by general formula (7)
include bis(diphenylphosphino)methane, l,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane, 1,6-bis(diphenylphosphino)hexane, 1,2-bis(diphenylphosphino)benzene, l,2-bis(anisylphenylphosphino)ethane, 2,3-
10 bis(diphenylphosphino)butane, 1,2-bis(diphenylphosphino)propane, 2,3 -
bis(diphenylphosphino)-5-norbornene, 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane, l-cyclohexyl-l,2-bis(diphenylphosphino)ethane, 2,4-bis-(diphenylphosphino)pentane, 2,2'-bis(diphenylphosphino)-l ,1 '-bicyclopentane, 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl, 2,2'-bis(diphenylphosphino)-l,r-(5,5',6,6',7,7',8,8'-
15 octahydrobinaphthyl), 2,2'-bis(di-p-tolylphosphino)-l5l'-binaphthyl, 2,2'-bis(di(3,5-
dimethylpheny!)phosphino)-l, 1 '-binaphthyl, 2,2'-bis(diphenylphosphino)-6,6'-dimethyl-1,1'-biphenyl, (4,4'-bi-l,3-benzodioxole)-5,5'-diylbis(diphenylphosphine), (4,4'-bi-l,3-benzodioxole)-5,5'-diylbis[bis(3,5-dimethylphenyl)phosphine], [(4S)-[4,4'-bi-l,3-benzodioxole]-5,5'-diyl]bis[bis[3,5-bis(l,l-dimethylethyl)-4-methoxyphenyl]phosphine], 2,2'-
2 0 bis(diphenylphosphino)benzophenone, and 2,2'-bis(di(3,5-
dimethylphenyl)phosphino)benzophenone. The bidentate phosphine ligand may be a racemic
form or an optically active form.
[0078]
In the present invention, the optically active enamine represented by general formula
2 5 (4) can be obtained by performing the asymmetric isomerization of the (E)-allylamine (3)
particularly obtained by the amination reaction described above.
In the present invention, as a method for asymmetric isomerization of the (E)-allylamine (3), a method for asymmetric isomerization using an optically active transition metal phosphine complex as a catalyst can be adopted. 30 [0079]
As the optically active transition metal phosphine complex which can be used in the present invention, a complex containing a transition metal complex and an optical phosphine ligand is preferably used.
The phosphine ligand which can be used in the optically active transition metal
3 5 phosphine complex for asymmetric isomerization of (E)-allylamine (3) of the present invention
includes, for example, an optically active monodentate phosphine ligand, an optically active bidentate phosphine ligand and an optically active polydentate phosphine ligand, and the optically active bidentate phosphine ligand is preferred.
17

[0080]
The optically active bidentate phosphine ligand includes an optically active bidentate phosphine ligand represented by general formula (8) shown below. [0081]

[Chem, R20 .12]
R2; M^l
R22- ■\^" _pR16R17
R22_ "rV _pR1SR19
R21' ^T^

(8)

R20
[0082]
»16*„ jyl9.
(hi formula (8), R to R each independently represents an aromatic group which may have a substituent or a cycloalkyl group having a carbon number of from 3 to 10 which may
10 have a substituent, or each of R16 and R17 and R18 and R19may be connected to each other together with the adjacent phosphorus atom to form a heterocyclic ring; R20and R21 each independently represents a hydrogen atom, an alkyl group having a carbon number of from 1 to 5, an alkoxy group having a carbon number of from 1 to5,adi(Cl toC5 alkyl)amino group, a 5-to 8-membered cyclic amino group, or a halogen atom; and R22 represents an alkyl group having
15 a carbon number of from 1 to 5, an alkoxy group having a carbon number of from 1 to 5, adi(Cl to C5 alkyl)amino group, a 5- to 8-membered cyclic amino group, or a halogen atom; plural R20s toR22s may be the same as or different from each other; or each of R20 and R21 and R21 and R22 may be connected to each other to form a condensed benzene ring, a condensed substituted benzene ring, a trimethylene group, a tetramethylene group, a pentamethylene group, a
2 0 methylenedioxy group, an ethylenedioxy group, or a trimethylenedioxy group.) [0083]
In the general formula (8), R16to R19each independently represents an aromatic group which may have a substituent or a cycloalkyl group having a carbon number of from 3 to 10 which may have a substituent, or each of Ri6and R17and R18and Rl9may be connected to each
2 5 other together with the adjacent phosphorus atom to form a heterocyclic ring.
[0084]
In the aromatic group which may have a substituent, the aromatic group includes, for example, a hydrocarbon aromatic group such as a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, or an indenyl group; a heteroaromatic group such as a pyrrolyl
3 0 group, a pyridyl group, a pyrazyl group, a quinolyl group, an isoquinolyl group, or an imidazolyl
group; and a metallocenyl group such as a ferrocenyl group.

[0085]
In the cycloalkyl group having a carbon number of from 3 to 10 which may have a substituent, specific examples of the cycloalkyl group include a cyclopentyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a 5 cyclononyl group, a cyclodecyl group, and a octahydronaphthyl group. [0086]
Specific examples of the substituent, which the aromatic group or the cycloalkyl group having a carbon number of from 3 to 10 may have in formula (8), include an alkyl group having a carbon number of from 1 to 12 such as a methyl group, an ethyl group, a n-propyl group, an 10 isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopenlyl group, a neopentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, or a dodecyl group; a lower alkoxy group having a carbon number of from 1 to 4 such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group, or a tert-15 butoxy group; an aryl group such as a phenyl group, an a-naphthyl group, a p-naphthyl group, or a phenanthryl group; an aralkyl group having a carbon number of from 7 to 13 such as a benzyl group, an a-phenylethyl group, a [3-phenylethyl group, an a-phenylpropyl group, a (3-phenylpropyl group, a y-phenylpropyl group, or a naphthylmethyl group; a tri-substituted organosilyl group including, a tri(C 1 to C6 alkyl)silyl group such as a trimethylsilyl group, a 2 0 triethylsilyl group, a triisopropylsilyl group, a dimethylisopropylsilyl group, a diethylisopropylsilyl group, a dimethyl(2,3-dimethyl-2-butyl)silyl group, atert-butyldimethylsilyl group, or a dimethylhexylsilyl group, a di(Cl to C6 alkyl) (C6 to CI 8 aryl)silyl group such as a dimethylcumylsilyl group, a di(C6 to CI 8 aryl) (CI to C6 alkyl)silyl group such as a tert-butyldiphenylsilyl group or a diphenylmethylsilyl group, a tri(C6 to C18
2 5 aryl)silyl group such as a triphenylsilyl group, and a tri(C7 to 19 aralkyl)silyl group such as a
tribenzylsilyl group or a tri-p-xylylsilyl group; a halogen atom such as a fluorine atom, a chlorine
atom, a bromine atom, or an iodine atom; and a nitro group.
[0087]
In the case where each of R16 and R17 and R18 and R19 are connected to each other
3 0 together with the adjacent phosphorus atom to form a heterocyclic ring, specific examples of the
heterocyclic group include phosphole, terrahydrophosphole and phosphorinane. The heterocyclic ring may have one to four functional groups which are inactive in the reaction of the present invention as substituents. Examples of the substituent include an alkyl group having a carbon number of from 1 to 4, an alkoxy group having a carbon number of from 1 to 4 and a 3 5 halogen atom. [0088]
In general formula (8), R20 and R21 each independently is a hydrogen atom, an alkyi group having a carbon number of from 1 to 5, an alkoxy group having a carbon number of from
19