JPH08157481A - Optically active oxazaboranaphthalenes - Google Patents

Abstract

PURPOSE: To obtain the subject new compounds useful as an asymmetric reducing agent capable of efficiently synthesizing optically active amines in high optical purity. CONSTITUTION: The optically active oxazaboranaphthalenes of formula I (R<1> is an alkyl, an aryl or an aralkyl; R<2> is an alkyl, an aryl or an aralkyl; R<3> is H, an alkyl or an alkoxy; * indicates asymmetric carbon), e.g. 2,4- dimethyl-2,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene. The compounds of the formula are obtained by reacting, e.g. optically active O-hydroxybenzylamines of formula II with a boron derivative of the formula R<1> -B(OH)2 or a boroxine derivative of formula III. An asymmetric reducing agent is obtained from the compounds of the formula I and a boron hydride compound.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the general formula [I] (In the formula, R ¹ represents an alkyl group, an aryl group or an aralkyl group, R ² represents an alkyl group, an aryl group or an aralkyl group, R ³ represents a hydrogen atom, an alkyl group or an alkoxy group, and * represents an asymmetric carbon atom. Represented by the formula (1), a process for producing the same, an asymmetric reducing agent obtained from the optically active oxazaboranaphthalenes [I] and a borohydride compound, and a general formula using the reducing agent. [VI]

[0002] (Wherein R ⁴ and R ⁵ are different from each other and represent an alkyl group, an aryl group or an aralkyl group, and * represents an asymmetric carbon).

[0003]

BACKGROUND OF THE INVENTION Optically active cyclic boron compounds include, for example, optically active 1,3,2- (2,5-diphenyl-3,4-
Dimethyl) oxazaborolidine is known (Te
trahedron Lett. 30 5551-54, (1989)). However, when the oxime derivative is reduced using an asymmetric reducing agent obtained from the oxazaborolidine derivative and the borohydride compound, there is a problem that the optical purity of the optically active amine derivative produced is low.

The present inventors have synthesized various optically active cyclic boron compounds and have conducted extensive studies. As a result, the optically active oxazaboranaphthalenes represented by the general formula [I] having no substituent on the nitrogen atom and hydrogen have been obtained. An asymmetric reducing agent obtained from a boron bromide compound efficiently gives optically active amines with high optical purity and is an optically active O-hydroxybenzyl which is a ligand of optically active oxazaboranaphthalenes [I]. It was found that separation of amines [II] and reduction products was extremely easy, and various studies were conducted to complete the present invention.

[0005]

That is, the present invention has the general formula [I] (In the formula, R ¹ , R ² and R ³ have the same meanings as described above, and * represents an asymmetric carbon), and the optically active oxazaboranaphthalene and its production method, and the optically active oxazbora. The invention provides an asymmetric reducing agent obtained from naphthalene and a borohydride compound, and a method for producing an optically active amine using the same.

Hereinafter, the present invention will be described in detail. R ¹ in the optically active oxazaboranaphthalenes represented by the above general formula [I] of the present invention represents an alkyl group, an aryl group or an aralkyl group. Examples of the alkyl group include methyl, ethyl, Propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 1-iodoethyl, 2-fluoroethyl, 3-chloropropyl And an alkyl group having 1 to 8 carbon atoms which may be substituted with halogen such as 3-trifluoropropyl.

Examples of the aryl group include a phenyl group, a substituted phenyl group, a 1-naphthyl group and a 2-naphthyl group. Examples of the substituted phenyl group include o-, m-,
p-methylphenyl, o-, m-, p-ethylphenyl, o-, m
-, P-propylphenyl, o-, m-, p-butylphenyl,
A phenyl group substituted with an alkyl group having 1 to 8 carbon atoms such as 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-dimethylphenyl, o -, M-, p-methoxyphenyl, o-, m-, p-ethoxyphenyl, o-, m-, p-propoxyphenyl, 2,3-, 2,4
-, 2,5-, 2,6-, 3,4-, 3,5-, 3,6-dimethoxyphenyl and other phenyl groups substituted with an alkoxy group having 1 to 8 carbon atoms, o-, m- , P-chlorophenyl, o-, m-, p-bromophenyl, o-, m-, p-fluorophenyl, and the like. Examples of the aralkyl group include benzyl, o-, m-, p-tolylmethyl, o
-, M-, p-ethylbenzyl, o-, m-, p-methoxybenzyl, o-, m-, p-ethoxybenzyl, 2,3-, 2,4-, 2,5-,
2,6-, 3,4-, 3,5-, 3,6-dimethylbenzyl, phenylethyl, phenylpropyl, phenylpentyl, phenylhexyl, (2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-, 3,
Examples thereof include those having 7 to 12 carbon atoms such as 6-dimethylphenyl) ethyl.

R ² represents an alkyl group, an aryl group or an aralkyl group, and examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, 1-8 carbon atoms such as pentyl, hexyl, heptyl, octyl
Alkyl groups of Examples of the aryl group include a phenyl group, a phenyl group substituted with an alkyl group similar to the above, a phenyl group substituted with an alkoxy group, and the like. Examples of the aralkyl group include the same aralkyl groups as described above.

R ³ represents a hydrogen atom, an alkyl group or an alkoxy group, and examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl and hexyl. , Heptyl, octyl, and other alkyl groups having 1 to 8 carbon atoms. Examples of the alkoxy group include alkoxy groups having 1 to 8 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, pentyloxy and hexyloxy.

Specific examples of the optically active oxazaboranaphthalene represented by the general formula [I] include 2,4-dimethyl-2,4-
Dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-
Ethyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza
-2 Boranaphthalene, 2-propyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-butyl
-4-Methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-phenyl-4-methyl-3,4-dihydro-2
H-1-oxa-3-aza-2-boranaphthalene, 2-o-fluorophenyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-m -Fluorophenyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-p-fluorophenyl-4-methyl-3,4-dihydro
-2H-1-oxa-3-aza-2-boranaphthalene, 2-o-chlorophenyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-m -Chlorophenyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-p-chlorophenyl-4-methyl-3,4-dihydro-2H-
1-oxa-3-aza-2-boranaphthalene, 2-o-methoxyphenyl-4-methyl-3,4-dihydro-2H-1-oxa-3-aza
-2-boranaphthalene, 2-m-methoxyphenyl-4-methyl
-3,4-Dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-p-methoxyphenyl-4-methyl-3,4-dihydro-2
H-1-oxa-3-aza-2-boranaphthalene,

2-o-tolyl-4-methyl-3,4-dihydro-2H
-1-oxa-3-aza-2-boranaphthalene, 2-m-tolyl-4-
Methyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-p-tolyl-4-methyl-3,4-dihydro-2H-
1-oxa-3-aza-2-boranaphthalene, 2- (2,4-dimethylphenyl) -4-methyl-3,4-dihydro-2H-1-oxa-3
-Aza-2-boranaphthalene, 2- (2,6-dimethylphenyl) -4-methyl-3,4-dihydro-2H-1-oxa-3-aza-2-
Boranaphthalene, 2- (2,5-dimethylphenyl) -4-methyl
-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4,7-trimethyl-3,4-dihydro-2H-1-oxa-3-
Aza-2-boranaphthalene, 2,4-dimethyl-7-ethyl-3,4-
Dihydro-2H-1-oxa-3-aza-2-boranaphthalene,
2,4,6-Trimethyl-3,4-dihydro-2H-1-oxa-3-aza
-2-Boranaphthalene, 2,4-Dimethyl-6-ethyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4,
8-Trimethyl-3,4-dihydro-2H-1-oxa-3-aza-2-
Boranaphthalene, 2,4-Dimethyl-8-ethyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4,5-Trimethyl-3,4-dihydro-2H- 1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-5-ethyl-3,4-dihydro-2
H-1-oxa-3-aza-2-boranaphthalene,

2,4,5,7-Tetramethyl-3,4-dihydro-2H-
1-oxa-3-aza-2-boranaphthalene, 2,4,6,7-tetramethyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4,6 , 8-Tetramethyl-3,4-dihydro-2H-1-
Oxa-3-aza-2-boranaphthalene, 2,4,5,8-tetramethyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4,5,6 -Tetramethyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-7-methoxy-3,4-dihydro-2H-1-oxa-3-aza -2-Boranaphthalene, 2,4-dimethyl-6-methoxy-3,4-dihydro-2
H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-
8-Methoxy-3,4-dihydro-2H-1-oxa-3-aza-2-
Boranaphthalene, 2,4-dimethyl-5-methoxy-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-6-ethoxy-3,4-dihydro- 2H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-6-propoxy-
3,4-Dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-6-butoxy-3,4-dihydro-2H-1-oxa-3-aza-2-bora Naphthalene, 2-methyl-4-ethyl
-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-methyl-4-propyl-3,4-dihydro-2H-1-oxa
-3-aza-2-boranaphthalene, 2-methyl-4-butyl-3,4
-Dihydro-2H-1-oxa-3-aza-2-boranaphthalene,
2-Methyl-4-hexyl-3,4-dihydro-2H-1-oxa-3
-Aza-2-boranaphthalene, 2,4-dimethyl-6-fluoro
-3,4-Dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2,4-dimethyl-6,8-chloro-3,4-dihydro-2H-1-oxa-3-aza- 2-Boranaphthalene, 2-Methyl-4-phenyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-Methyl-4-p-tolyl-3,4-dihydro- 2H-1-oxa-3-aza-2-boranaphthalene, 2-methyl-4-p-chlorophenyl-3,4-dihydro-2H-1-oxa-3-aza-2-boranaphthalene, 2-benzyl- 4-Methyl-3,4-dihydro-2H-
Examples thereof include optically active oxazaboranaphthalenes such as 1-oxa-3-aza-2-boranaphthalene.

Optically active oxazaboranaphthalenes [I]
Is a general formula [II]

The optically active O-hydroxybenzylamines represented by the formula (wherein R ² , R ³ and * have the same meanings as described above) are represented by the general formula [III] R ¹ -B (OH) ₂ [III [Wherein R ¹ has the same meaning as described above] or a boronic acid derivative represented by the general formula [IV]

[0015] (In the formula, R ¹ has the same meaning as described above.) It can be easily produced by acting a boroxine derivative.

Here, as a typical example of the optically active O-hydroxybenzylamines [II], for example, optically active 1-hydroxybenzylamines
(2-Hydroxy-3-ethylphenyl) ethylamine, 1-
(2-Hydroxy-3-methylphenyl) ethylamine, 1-
(2-hydroxy-3-methoxy-phenyl) ethylamine, 1- (2-hydroxy-3-ethoxyphenyl) ethylamine, 1- (2-hydroxy-5-methoxyphenyl) ethylamine, 1- (2-hydroxy-5- Ethoxyphenyl) ethylamine, 1- (2-hydroxyphenyl) propylamine, 1- (2-hydroxy-3-methylphenyl) propylamine, 1- (2-hydroxy-3-methoxyphenyl) propylamine, 1- (2 -Hydroxy-5-ethylphenyl) -propylamine, 1- (2-hydroxy-5-ethoxyphenyl)
Propylamine, 1- (2-hydroxy-4-methylphenyl) ethylamine, 1- (2-hydroxy-6-methoxyphenyl) ethylamine, 1- (2-hydroxy-6-methylphenyl) ethylamine, 1- (2- Hydroxy-4-ethoxyphenyl) ethylamine, 1- (2-hydroxy-4-methoxyphenyl) ethylamine, 1- (2-hydroxy-5-methylphenyl) ethylamine, 1- (2-hydroxyphenyl)
Ethylamine, 1- (2-hydroxy-4,5-dimethylphenyl) ethylamine, 1- (2-hydroxy-4-chlorophenyl) ethylamine, 1- (2-hydroxy-4-methoxyphenyl) ethylamine, 1- (2- Hydroxy-5-fluorophenyl) ethylamine, 1- (2-hydroxy-4,5-dichlorophenyl) ethylamine, and the like.

In the boronic acid derivative [III], R ¹ has the same meaning as described above, but specific compounds include, for example, methylboronic acid, ethylboronic acid, propylboronic acid, butylboronic acid, pentylboronic acid and hexylboron. Acid, phenylboronic acid, α, β-naphthylboronic acid, o-, m-, p-methylphenylboronic acid, mesitylboronic acid, o-, m-, p-fluorophenylboronic acid, o-, m-, p -Chlorophenylboronic acid, o-, m-, p-bromophenylboronic acid, o-, m-, p-methoxyphenylboronic acid, benzylboronic acid and the like can be mentioned.

In the boroxine derivative [IV], R ¹ has the same meaning as described above, but specific compounds include, for example, trimethylboroxine, triethylboroxine,
Tripropylboroxine, tributylboroxine, triisobutylboroxine, tripentylboroxine, trihexylboroxine, trioctylboroxine, triphenylboroxine, tris (2-methylphenyl) boroxine, tris (3-methylphenyl) Boroxine, tris
(4-methylphenyl) boroxine, tris (2-ethylphenyl) boroxine, tris (3-ethylphenyl) boroxine, tris (4-ethylphenyl) boroxine, tris (2-methoxyphenyl) boroxine, tris (3-methoxyphenyl) ) Boroxin, Tris (4-methoxyphenyl) boroxine, Tris (2-chlorophenyl) boroxine, Tris (3-chlorophenyl) boroxine, Tris (4
-Chlorophenyl) boroxine, tris (2-fluorophenyl) boroxine, tris (3-fluorophenyl) boroxine, tris (4-fluorophenyl) boroxine,
Examples include trisbenzylboroxine.

Optically Active Oxazaboranaphthalenes [I]
Can be produced by reacting the optically active O-hydroxybenzylamines [II] with a boronic acid derivative [III] or a boroxine derivative [IV]. When a boronic acid derivative [III] is used, The amount is optically active
For O-hydroxybenzylamines [II],
It is 1 to 5 equivalents, preferably 1 to 2 equivalents. When the boroxine derivative [IV] is used, its amount is 0.3 to 1 equivalent, preferably 0.3 to 0.8 equivalent. The reaction is usually performed in the presence of a solvent. The solvent used is not particularly limited as long as it is an aprotic solvent, and examples thereof include aromatic hydrocarbons such as toluene and benzene, aliphatic hydrocarbons such as hexane and heptane, halogenated hydrocarbons such as chloroform and chlorobenzene. Used. The reaction temperature is usually 0 to
At 150 ℃, preferably 10 ~ 120 ℃, the reaction time is usually 10
Minutes to 8 hours. The optically active oxazaboranaphthalenes [I] can be isolated from the reaction mixture, if necessary, by a conventional means such as concentration or distillation.

Thus, the optically active oxazaboranaphthalenes [I] of the present invention can be obtained. The optically active borohydride compound obtained from the optically active oxazaboranaphthalenes [I] and the borohydride compound is It is useful as an asymmetric reducing agent and reduces a prochiral compound to give an optically active substance. For example, the general formula [V] (In the formula, R ⁶ represents a hydrogen atom, an alkyl group, an aralkyl group or an alkyl-substituted silyl group. R ⁴ and R ⁵ have the same meanings as described above.)

By reacting the oxime derivative represented by the formula (1) with an anti-form or a syn-form or a mixture rich in one of them, a compound of the general formula [VI] (In the formula, R ⁴ and R ⁵ have the same meanings as described above, and * represents an asymmetric carbon.) The optically active amines represented by the formula can be produced.

The oxime derivative represented by the general formula [V] may be an anti-form, a syn-form or a substance rich in any of these. R ⁶ represents a hydrogen atom, an alkyl group, an aralkyl group or an alkyl-substituted silyl group, and examples of the alkyl group include methyl, ethyl, propyl,
Examples thereof include those having 1 to 10 carbon atoms such as butyl, pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl, cycloheptyl, octyl, cyclooctyl, nonyl and decyl. Examples of the aralkyl group include benzyl, β-phenethyl, naphthylmethyl and the like having 7 to 12 carbon atoms.
The following are listed. As the alkyl-substituted silyl group,
Examples thereof include those having 3 to 12 carbon atoms such as trimethylsilyl, dimethyl-t-butylsilyl, tri-n-propylsilyl and tri-n-butylsilyl.

R ⁴ and R ⁵ are different from each other and represent an alkyl group, an aryl group or an aralkyl group. Examples of the alkyl group include methyl, ethyl, propyl,
C1-C6 alkyl groups such as butyl, pentyl, cyclopentyl, hexyl, cyclohexyl, chloromethyl, dichloromethyl, trichloromethyl, tribromomethyl, trifluoromethyl, 2-chloroethyl, 3-chloropropyl, 4-chlorobutyl, etc. And a halogenated alkyl group having 1 to 6 carbon atoms. The aryl group, a phenyl group, a substituted phenyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, α-naphthyl group, β
An aryl group having 5 to 17 carbon atoms such as a naphthyl group. The substituted phenyl group, for example, o-, m-,
p-chlorophenyl, o-, m-, p-bromophenyl, 2,3-, 2,
4-, 2,5-, 2,6-, 3,4-, 3,5-dichlorophenyl and other halogen-substituted phenyl groups, o-, m-, p-methylphenyl, o-, m
-, p-ethylphenyl, o-, m-, p-butylphenyl, 2,3-,
Phenyl groups substituted with alkyl groups having 1 to 6 carbon atoms such as 2,4-, 2,5-, 2,6-, 3,4-, 3,5-dimethylphenyl,
o-, m-, p-methoxyphenyl, o-, m-, p-ethoxyphenyl, o-, m-, p-propoxyphenyl and the like having 1 to 6 carbon atoms
Phenyl group substituted with alkoxy group, o-, m-, p-benzyloxyphenyl, 2-benzyloxy-3-methylphenyl, 2-benzyloxy-4-methylphenyl, 2-benzyloxy-5-methyl Phenyl, 2-benzyloxy-5-t-
Butylphenyl, 2-benzyloxy-3-methoxyphenyl, 2-benzyloxy-4-methoxyphenyl, 2-benzyloxy-5-methoxyphenyl, 2-benzyloxy-3,5
-A phenyl group substituted with a benzyloxy group such as dichlorophenyl and a phenyl group substituted with a cyano group such as o-, m-, p-cyanophenyl and the like.

Examples of the aralkyl group include benzyl, o-, m-, p-tolylmethyl, o-, m-, p-ethylbenzyl,
o-, m-, p-methoxybenzyl, o-, m-, p-ethoxybenzyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5 Examples include aralkyl groups having 7 to 11 carbon atoms such as -dimethylbenzyl, 2-phenylethyl, and 2- (o-, m-, p-tolyl) ethyl.

Representative oximes [V] include, for example, acetophenone, propiophenone, butyrophenone, chloromethyl (phenyl) ketone, bromomethyl (phenyl) ketone, 2-acetylpyridine, o-methoxyacetophenone, o-ethoxy. Acetophenone, o-propoxyacetophenone, o-benzyloxyacetophenone, α-acetonaphthone, β-acetonaphthone, (p-chlorophenyl) methyl ketone, (p-bromophenyl) methyl ketone, 2,4-dichloroacetophenone, phenylbenzyl ketone, phenyl (o -Tolylmethyl) ketone, phenyl (m-tolylmethyl) ketone, phenyl (p-tolylmethyl) ketone, phenyl (2-phenylethyl) ketone, 2-butanone, 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 3-heptanone, 3- Kutanon,
O-Methyl, o-octyl, o-cyclohexyl, o-benzyl, such as cyclohexyl methyl ketone, cyclohexyl ethyl ketone, cyclohexyl benzyl ketone, α-phenylacetone, (2-phenylethyl) methyl ketone and (2-phenylethyl) ethyl ketone. Examples include oxime derivatives such as o-trimethylsilyl, and anti-forms or syn-forms thereof or a mixture rich in one of them can be used.

The oxime [V] can be easily produced from the corresponding ketone by a known method. When one of the anti isomer and the syn isomer is used, the remaining separated isomers can be converted into the necessary isomers by performing an anti isomer / syn isomerization reaction. It can be used effectively.

The asymmetric reduction reaction proceeds by reacting an oxime [V] with an optically active oxazaboranaphthalene [I] and a borohydride compound. The order of addition is not particularly limited, and for example, a method of preparing a reducing agent from an optically active oxazaboranaphthalene [I] and a borohydride compound and then adding an oxime [V], an oxime [V] and an optical method. A method of adding an active oxazaboranaphthalene [I] and then adding a borohydride compound can be mentioned.

Here, the amount of the optically active oxazaboranaphthalenes [I] used is usually in the amount of oximes [V].
The molar ratio is 0.05 mol or more, preferably 0.1 to 1.5 mol.
Examples of the borohydride compound include diborane, borane-tetrahydrofuran complex, borane-dimethyl sulfide complex and the like, and the amount thereof is usually 0.5 to 8 mol times with respect to the oxime [V], and preferably It is 0.7 to 5 mol times.

The asymmetric reduction reaction is usually carried out in the presence of a solvent. Examples of such solvents include ethers such as dioxane, tetrahydrofuran, diglyme, and triglyme, sulfides such as dimethyl sulfide and diethyl sulfide, a mixture of ethers and sulfides,
And a mixed solvent of this mixture and benzene, toluene, xylene, chlorobenzene, 1,2-dichloroethane, etc., and the amount thereof is usually 2 to 2 with respect to the oxime derivative.
It is about 50 times the weight. The reaction temperature for the asymmetric reduction reaction is usually 150 ° C. or lower, preferably −20 to 100 ° C., and can be further heated if necessary. The progress of the reaction can be confirmed by an analytical means such as gas chromatography.

After completion of the reaction, for example, the reducing agent is decomposed by adding an acid such as hydrochloric acid to the reaction solution, made alkaline with an alkaline aqueous solution such as caustic soda, and then extracted with an organic solvent to remove the organic layer from the organic layer. The objective optically active amines [VI] can be isolated and recovered, and the aqueous layer is neutralized to isolate optically active O-hydroxybenzylamines [II] as a raw material of oxazaboranaphthalenes [I]. Can be recovered. The optically active amine [VI] thus obtained can be further purified, if necessary, by a purification means such as distillation or column chromatography.

[0031]

EFFECT OF THE INVENTION By using the asymmetric reducing agent obtained from the optically active oxazaboranaphthalenes [I] of the present invention and a borohydride compound, optically active amines [VI] with high optical purity and efficiency can be obtained. ] Can be manufactured. Further, the optically active oxazaboranaphthalenes [I]
The optically active O-hydroxybenzylamines [II], which are the ligands, are easy to separate from the objective optically active amines [VI] and can be easily recovered and recycled. The invention is industrially advantageous.

[0032]

EXAMPLES The present invention will be further described below with reference to examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 (S) -2-hydroxyphenylethylamine under nitrogen atmosphere
0.35 g (2.55 mmol) was dissolved in 33 ml of toluene, 0.225 g (1.79 mmol) of trimethylboroxine was added thereto, and the mixture was stirred at 75 ° C for 1 hour and further at 110 ° C for 1 hour. Then, after distilling off the toluene, it is distilled to give a value of 0.
41 g of (S) -2,4-dimethyl-3,4-dihydro-1-oxazaboranaphthalene were obtained. The yield was 97.7% based on (S) -2-hydroxyphenylethylamine. ¹¹ B-NMR; 31.9 ppm (BF ₃ / Et ₂ O is 0 ppm.)

Example 2 Example 2 was repeated except that 0.386 g (2.56 mmol) of (S) -2-hydroxy-3-methylphenylethylamine was used in place of (S) -2-hydroxyphenylethylamine. By carrying out in accordance with 1., 0.31 g of (S) -2,4,
8-Trimethyl-3,4-dihydro-1-oxazaboranaphthalene was obtained. The yield was 69.4% based on (S) -2-hydroxy-3-methylphenylethylamine. ¹¹ B-NMR; 32.0 ppm (BF ₃ / Et ₂ O is 0 ppm.)

Example 3 Example 3 was repeated except that 0.427 g (2.55 mmol) of (S) -2-hydroxy-5-methoxyphenylethylamine was used in place of (S) -2-hydroxyphenylethylamine. By carrying out in accordance with 1., 0.38 g of (S) -2,
4-Dimethyl-6-methoxy-3,4-dihydro-1-oxazaboranaphthalene was obtained. The yield was 77.9% based on (S) -2-hydroxy-5-methoxyphenylethylamine. ¹¹ B-NMR; 31.8 ppm (BF ₃ / Et ₂ O is 0 ppm.)

Example 4 (S) -2,4-Dimethyl-3,4-dihydro at room temperature under nitrogen atmosphere
-1- Oxazaboranaphthalene 0.186 mmol (0.03 g) and toluene 0.5 ml was added with 1 M borane tetrahydrofuran complex 0.38 mmol (0.38 ml). Then, a solution consisting of 0.186 mmol (0.045 g) of anti-phenyl (p-tolylmethyl) ketone (o-methyloxime) and 1 ml of toluene was added, and the mixture was stirred at 25 ° C for 16 hours. Then, 1 g of 10% hydrochloric acid was added, the mixture was stirred at the same temperature for 1 hour, and the reaction solution was concentrated under reduced pressure. An aqueous solution of sodium hydroxide was added to the mixture to make it basic, which was then extracted with hexane, and the separated hexane layer was concentrated to obtain 1-phenyl-2- (p-tolyl) ethylamine. When acetic anhydride and triethylamine were added to form an N-acetyl derivative and analyzed by gas chromatography, the reaction rate was 69.6%, and the amine compound ratio (selectivity) in the product was 64.3%. The enantiomeric ratio of the amine compound was determined by high performance liquid chromatography analysis using an optically active column to give the R compound.
It was 4.4% and S body 15.6%.

Example 5 In Example 4, (S) -2,4-dimethyl-3,4-dihydro-1
-(S) -2,4,8-trimethyl-3,4-dihydro-1-oxazaboranaphthalene 0.14 instead of oxazaboranaphthalene 0.14
mmol and borane-tetrahydrofuran complex 0.28 mmol were used, and the procedure of Example 4 was repeated. Reaction rate is 52.9%
And the ratio (selectivity) of amines in the product is 62.2%.
Met. The enantiomeric ratio of the amine form is 60.3 R form.
% And S body 39.7%.

Example 6 In Example 4, (S) -2,4-dimethyl-3,4-dihydro-1
-Compared with Example 4, except that 0.186 mmol of (S) -2,4-dimethyl-6-methoxy-3,4-dihydro-1-oxazaboranaphthalene was used in place of oxazaboranaphthalene. . The reaction rate was 64.5%, and the ratio (selectivity) of the amine compound in the product was 65.6%. The enantiomer ratio of the amine form was R-form 70.5% and S-form 29.5%.

Comparative Example 1 In Example 4, (S) -2,4-dimethyl-3,4-dihydro-1
-(4S) (5R) -1,3,2 instead of oxazaboranaphthalene
It was carried out in accordance with Example 4 except that 0.186 mmol of-(2,5-diphenyl-3,4-dimethyl) oxazaborolidine was used and the mixture was stirred at 25 ° C for 48 hours. The reaction rate was 81%, and the ratio (selectivity) of the amine compound in the product was 51.1%. The enantiomer ratio of the amine form was 42.5% for R form and 57.5% for S form.

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Claims (4)

[Claims] 1. A general formula [I] (In the formula, R ¹ represents an alkyl group, an aryl group or an aralkyl group, R ² represents an alkyl group, an aryl group or an aralkyl group, R ³ represents a hydrogen atom, an alkyl group or an alkoxy group, and * represents an asymmetric carbon atom. Represents an optically active oxazaboranaphthalene. 2. General formula [II] (Wherein R ² , R ³ and * have the same meanings as described above) and the optically active O-hydroxybenzylamines represented by the general formula [III] R ¹ -B (OH) ₂ [III] Wherein R ¹ has the same meaning as described above), or a boronic acid derivative represented by the general formula [IV] The method for producing an optically active oxazaboranaphthalene [I] according to claim 1, wherein a boroxine derivative represented by the formula (wherein R ¹ has the same meaning as described above) is allowed to act. 3. An asymmetric reducing agent obtained from the optically active oxazaboranaphthalenes [I] according to claim 1 and a borohydride compound. 4. The asymmetric reducing agent according to claim 3 is replaced by a compound represented by the general formula [V] (In the formula, R ⁶ represents a hydrogen atom, an alkyl group, an aralkyl group or an alkyl-substituted silyl group. R ⁴ and R ⁵ are different from each other and represent an alkyl group, an aryl group or an aralkyl group.) General formula [VI] characterized by acting on an anti-form, a syn-form or a mixture rich in one of them (In the formula, R ⁴ , R ⁵ and * have the same meanings as described above.) A process for producing an optically active amine.