JPH10287663A - Asymmetric wacker type cyclization reaction - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently obtain a compound useful for producing functional material compounds, etc., by an asymmetric Wacker type cyclization reaction using a specified oxazollne compound and a palladium salt. SOLUTION: (A) An olefin compound of formula I [Z is 0, S, NH; R is H, a 1-10C alkyl, a 3-10C cycloalkyl, etc.; R<1> -R<4> are each H, a 1-10C alkyl, a 1-10C alkoxy, a 3-10C cycloalkyl, etc.; (n) is 1-31 is oxidized in the presence of (B) an optically active biaryl type oxazoline compound of formula II (A<1> -A<4> are each H, a 1-6C alkyl, a 2-6C alkenyl, a 2-6C alkinyl; W<1> , W<2> are each H, a 1-6C alkyl, phenyl, benzyl, etc.; the * mark expresses an asymmetric carbon atom) having an axial asymmetry and (C) a divalent palladium salt [preferably palladium (II) di(trifluoroacetate)] to obtain the objective compound of formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an asymmetric Wacker-type cyclization reaction of an olefin compound using a divalent palladium salt as a catalyst. By the asymmetric Wacker-type cyclization reaction of the present invention, an optically active heterocyclic compound useful for producing an optically active intermediate for producing a pharmaceutical or agricultural chemical or an optically active functional material compound can be efficiently obtained.

[0002]

2. Description of the Related Art Optically active heterocyclic compounds obtained by an asymmetric Wacker-type cyclization reaction include optically active dihydrobenzofuran compounds, optically active tetrahydrobenzopyran compounds, optically active indoline compounds, optically active tetrahydroquinoline compounds, and optically active tetrahydroquinoline compounds. And dihydrobenzothiophene compounds.

[0003] Conventionally, a method for producing an optically active heterocyclic compound by an asymmetric Wacker-type cyclization reaction is described in J. Am. Am. Che
m. Soc. , 103 , 2318 (1981) and J. Amer.
Org. Chem. , 50 , 1282 (1985), only a method for producing an optically active dihydrobenzofuran compound in an oxygen atmosphere using copper acetate as an oxidizing agent using an optically active π-allyl palladium complex as a catalyst is known.

[0004]

In the above-mentioned asymmetric Wacker-type cyclization reaction, the optically active dihydrobenzofuran compound obtained has an optical purity of up to 29% ee, which is not satisfactory.

[0005]

The present inventors have conducted intensive studies to solve the above-mentioned problems. As a result, when an optically active biaryl-type oxazoline compound having axial asymmetry and a divalent palladium salt are used, an olefin compound can be obtained. The inventors have found that an asymmetric Wacker-type cyclization reaction can be performed efficiently, and have completed the present invention.

That is, the present invention provides the following formula (1)

[0007]

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[Wherein, Z is an oxygen atom, a sulfur atom, NH
Means a group. R represents a hydrogen atom, a C ₁ -C ₁₀ alkyl group, a C ₃ -C ₁₀ cycloalkyl group, wherein the alkyl group and the cycloalkyl group are a halogen atom, a C ₆ -C ₁₀ aromatic group or a heterocyclic group, May be substituted.), C ₆
To C ₁₀ aromatic groups and heterocyclic groups (the aromatic groups and heterocyclic groups are optionally substituted with C ₁ -C ₁₀ alkyl groups, C ₁ -C ₁₀ alkoxy groups, halogen atoms, nitro groups or cyano groups) May be performed).

R ¹ , R ² , R ³ and R ⁴ are a hydrogen atom, C ₁
-C ₁₀ alkyl group, C ₁ -C ₁₀ alkoxy group, C ₃ -C ₁₀
Cycloalkyl group (the alkyl group, alkoxy group, and cycloalkyl group may be optionally substituted with a halogen atom, a C ₆ -C ₁₀ aromatic group or a heterocyclic group), and C _6-
C ₁₀ aromatic groups and heterocyclic groups (the aromatic groups and heterocyclic groups are
_It may be optionally substituted with a ₁ to ₁₀ alkyl group, a ₁ to ₁₀ alkoxy group, a halogen atom, a nitro group, a cyano group, a ₂ to ₁₀ alkoxycarbonyl group or a ₂ to ₁₀ alkanoyl group. . ), Halogen atom, means a nitro group, a cyano group, C ₂ -C ₁₀ alkoxycarbonyl group and a C ₂ -C ₁₀ alkanoyl group.

N represents an integer of 1 to 3. The olefin compound represented by the formula (2)

[0011]

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[Wherein A¹, A^Two, A^ThreeAnd A^FourIs independent
, A hydrogen atom, C₁~ C₆Alkyl group, C _Two~ C₆Alkene
Group, C_Two~ C₆Alkynyl group, C₁~ C₆Alkoxy group
(The alkyl group, alkenyl group, alkynyl group and ruco
The xy group is a halogen atom, a hydroxyl group, a tri-C₁~ C₆Archi
Lucyl group, C₁~ C₆Alkyldiphenylsilyl group, di
C₁~ C₆Alkylphenylsilyl group, C₁~ C₆Alkoki
Si group, C₆~ C_TenOptionally substituted with an aromatic or heterocyclic group
It may be. ), Cyano group, nitro group, halogen source
Child, C_Two~ C_TenAlkoxycarbonyl group, C_Two~ C_TenAl
Canoyl group, formyl group, tri-C₁~ C₆Alkylsilyl
Group, C₁~ C₆Alkyldiphenylsilyl group, diC₁~ C₆
Alkylphenylsilyl group, N-mono C₁~ C_TenArchi
Rucarbamoyl group and N, N-diC₁~ C_TenAlkylka
A rubamoyl group;^ThreeAnd A^FourJoin them
May form a naphthyl ring together with a benzene ring
｛The naphthyl ring is unsubstituted or one or more C₁~
C₆Alkyl group, C_Two~ C₆Alkenyl group, C_Two~ C₆Al
Quinyl group, C₁~ C₆An alkoxy group (the alkyl group,
Kenyl, alkynyl and alkoxy groups are halogen
Hydroxyl group, tri-C1-C6 alkylsilyl group, C₁~
C₆Alkyldiphenylsilyl group, diC₁~ C₆Alkyl
Phenylsilyl group, C₁~ C₆Alkoxy group, C₆~ C_Ten
Optionally substituted with an aromatic group or a heterocyclic group
No. ), Cyano group, nitro group, halogen atom, C_Two~ C
_TenAlkoxycarbonyl group, C_Two~ C_TenAlkanoyl group
And a phenyl group, wherein the phenyl group is₁~ C₆Alkyl
Group, C₁~ C₆Alkoxy, cyano, nitro or halo
It may be optionally substituted with a logen atom. ) Optionally
It may be replaced. ｝.

W ¹ and W ² are independently a hydrogen atom (provided that
W ¹ and W ² are not simultaneously hydrogen atoms. ), A C ₁ -C ₆ alkyl group, a phenyl group (the phenyl group is optionally substituted with a C ₁ -C ₆ alkyl group, a C ₁ -C ₆ alkoxy group, a cyano group, a nitro group or a halogen atom. And a benzyl group (the benzyl group is a C ₁ -C ₆ alkyl group,
_It may be optionally substituted with a ₁ to ₆ alkoxy group, a cyano group, a nitro group or a halogen atom. ).

* Represents an asymmetric carbon, and the absolute configuration of the carbon atom means R or S. Wherein the compound is oxidized in the presence of an optically active biaryl-type oxazoline compound having axial asymmetry and a divalent palladium salt represented by the formula (3):

[0015]

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Wherein Z, R, R ¹ , R ² , R ³ , R ⁴ , n
And * are the same as above. ] The method for producing an optically active heterocyclic compound represented by the formula:

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. First, R, R ¹ , R ² , R ³ , R ⁴ , A ¹ , A ² , A ³ ,
It will be described A ^4, W ¹ and W ^2. As the C ₁ -C ₆ alkyl group, a methyl group, an ethyl group, an n-propyl group, i
-Propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, 1-pentyl group, 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, t-pentyl Group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-1-ethyl-n-pentyl group, 1,1,2-trimethyl-n-propyl group,
1,2,2-trimethyl-n-propyl group, 3,3-dimethyl-n-butyl group, 1-heptyl group, 2-heptyl group, 1-ethyl-1,2-dimethyl-n-propyl group and 1 -Ethyl-2,2-dimethyl-n-propyl group and the like, preferably a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group,
s-butyl group, t-butyl group, 1-pentyl group and 1-
Hexyl group and the like.

As the C ₁ -C ₁₀ alkyl group, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-
Butyl, i-butyl, s-butyl, t-butyl, 1-pentyl, 2-pentyl, 3-pentyl, i-pentyl, neopentyl, t-pentyl, 1-hexyl A 2-hexyl group, a 3-hexyl group, a 1-methyl-1-ethyl-n-pentyl group,
1,2-trimethyl-n-propyl group, 1,2,2-trimethyl-n-propyl group, 3,3-dimethyl-n-butyl group, 1-heptyl group, 2-heptyl group, 1-ethyl-1 , 2-dimethyl-n-propyl group, 1-ethyl-
2,2-dimethyl-n-propyl group, 1-octyl group,
3-octyl group, 4-methyl-3-n-heptyl group, 6
-Methyl-2-n-heptyl group, 2-propyl-1-n
-Heptyl group, 2,4,4-trimethyl-1-n-pentyl group, 1-nonyl group, 2-nonyl group, 2,6-dimethyl-4-n-heptyl group, 3-ethyl-2,2- Dimethyl-3-n-pentyl group, 3,5,5-trimethyl-1
-N-hexyl group, 1-decyl group, 2-decyl group, 4-
Decyl group, 3,7-dimethyl-1-n-octyl group, 3,7-dimethyl-3-n-octyl group and the like,
Preferably a methyl group, an ethyl group, an n-propyl group, i-
Propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, 1-pentyl group, 1-hexyl group,
1-heptyl group, 1-octyl group, 1-nonyl group and 1
-Decyl group and the like.

The C ₃ -C ₁₀ cycloalkyl group includes cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, 4-methylcyclohexyl,
Examples thereof include a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group and a cyclodecyl group, and preferably a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group.

Examples of the C ₂ -C ₆ alkenyl group include an ethenyl group, a 1-propenyl group, a 2-propenyl group, a 1-methylvinyl group, a 1-butenyl group, a 2-butenyl group and a 3-butenyl group. , 1-methyl-1-propenyl group, 1-methyl-
2-propenyl group, 2-methyl-2-propenyl group, 1
-Ethyl-2-vinyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1,
2-dimethyl-1-propenyl group, 1,2-dimethyl-
2-propenyl group, 1-ethyl-1-propenyl group, 1
-Ethyl-2-propenyl group, 1-methyl-1-butenyl group, 1-methyl-2-butenyl group, 2-methyl-1-
Butenyl group, 1-i-propylvinyl group, 2,4-pentadienyl group, 1-hexenyl group, 2-hexenyl group,
Examples include a 3-hexenyl group, a 4-hexenyl group, a 5-hexenyl group, a 2,4-hexadienyl group, and a 1-methyl-1-pentenyl group, preferably an ethenyl group,
Propenyl group, 3-butenyl group, 1-methyl-1-propenyl group, 1-pentenyl group, 4-pentenyl group, 1-
A hexenyl group and a 5-hexenyl group.

The C ₂ -C ₆ alkynyl groups include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl and 2-pentynyl. , 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-
A hexynyl group, a 4-hexynyl group and a 5-hexynyl group, and the like, preferably an ethynyl group, a 1-propynyl group, a 1-butynyl group, a 1-pentynyl group, a 4-pentynyl group, a 1-hexynyl group and a 5-hexynyl group; And the like.

The C ₆ -C ₁₀ aromatic groups include phenyl, 1-indenyl, 2-indenyl, 3-indenyl, 4-indenyl, 5-indenyl, 6-indenyl, 7-indenyl. Group, 1-naphthyl group, 2-
Naphthyl group, 1-tetrahydronaphthyl group, 2-tetrahydronaphthyl group, 5-tetrahydronaphthyl group and 6
-Tetrahydronaphthyl group and the like, preferably,
Examples include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-tetrahydronaphthyl group, and a 2-tetrahydronaphthyl group.

Examples of the heterocyclic group include an aromatic heterocyclic group and a non-aromatic heterocyclic group. As the aromatic heterocyclic group, a 5- to 7-membered monocyclic heterocyclic group having 8
And 10 to 10 condensed bicyclic heterocyclic groups, and may contain 1 to 3 oxygen atoms, nitrogen atoms and sulfur atoms alone or in combination. Examples of the non-aromatic heterocyclic group include a 5- to 7-membered monocyclic heterocyclic group and a condensed bicyclic heterocyclic group having 6 to 10 constituent atoms, and include an oxygen atom, a nitrogen atom, and a sulfur atom. Can be included alone or in combination with one to three atoms.

Examples of the aromatic heterocyclic group include 2-thienyl group, 3-thienyl group, 2-furyl group, 3-furyl group, 2
-Pyranyl group, 3-pyranyl group, 4-pyranyl group, 2-
Benzofuranyl, 3-benzofuranyl, 4-benzofuranyl, 5-benzofuranyl, 6-benzofuranyl, 7-benzofuranyl, 1-isobenzofuranyl, 4-isobenzofuranyl, 5-isobenzofuranyl Group, 2-benzothienyl group, 3-benzothienyl group,
4-benzothienyl group, 5-benzothienyl group, 6-benzothienyl group, 7-benzothienyl group, 1-isobenzothienyl group, 4-isobenzothienyl group, 5-isobenzothienyl group, 2-chromenyl group, 3-chromenyl group, 4-chromenyl group, 5-chromenyl group, 6-chromenyl group, 7-chromenyl group, 8-chromenyl group, 1-pyrrolyl group, 2-pyrrolyl group, 3-pyrrolyl group, 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, 1-pyrazolyl group, 3-pyrazolyl group, 4-pyrazolyl group, 2-thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 3-isothiazolyl group, 4-isothiazolyl group, 5-isothiazolyl group, 2-oxazolyl group, 4
-Oxazolyl group, 5-oxazolyl group, 3-isoxazolyl group, 4-isoxazolyl group, 5-isoxazolyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-pyrazinyl group, 2-pyrimidinyl group, 4 −
Pyrimidinyl group, 5-pyrimidinyl group, 3-pyridazinyl group, 4-pyridazinyl group, 1-indolizinyl group, 2
-Indolizinyl group, 3-indolizinyl group, 5-indolizinyl group, 6-indolizinyl group, 7-indolizinyl group, 8-indolizinyl group, 1-isoindolyl group, 4-isoindolyl group, 5-isoindolyl group, 1
-Indolyl group, 2-indolyl group, 3-indolyl group, 4-indolyl group, 5-indolyl group, 6-indolyl group, 7-indolyl group, 1-indazolyl group, 2-
Indazolyl group, 3-indazolyl group, 4-indazolyl group, 5-indazolyl group, 6-indazolyl group, 7-
Indazolyl group, 1-purinyl group, 2-purinyl group, 3
-A purinyl group, a 6-purinyl group, a 7-purinyl group, 8-
Purinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl Isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group, 8-isoquinolyl group, 1-phthalazinyl group, 5-phthalazinyl group, 6-phthalazinyl group, 2-naphthyridinyl group, 3-
Naphthyridinyl group, 4-naphthyridinyl group, 2-quinoxalinyl group, 5-quinoxalinyl group, 6-quinoxalinyl group, 2-quinazolinyl group, 4-quinazolinyl group, 5-
Quinazolinyl group, 6-quinazolinyl group, 7-quinazolinyl group, 8-quinazolinyl group, 3-cinnolinyl group, 4-
Cinnolinyl group, 5-cinnolinyl group, 6-cinnolinyl group, 7-cinnolinyl group, 8-cinnolinyl group, 2-
Examples include a ptenidinyl group, a 4-ptenidinyl group, a 6-ptenidinyl group, a 7-ptenidinyl group, and a 3-flazanyl group.

The non-aromatic heterocyclic ring includes a 1-pyrrolidinyl group, a 2-pyrrolidinyl group, a 3-pyrrolidinyl group,
A pyrrolinyl group, a 2-pyrolinyl group, a 3-pyrolinyl group,
4-pyrrolinyl group, 5-pyrrolinyl group, 1-imidazolidinyl group, 2-imidazolidinyl group, 4-imidazolidinyl group, 1-imidazolinyl group, 2-imidazolinyl group, 4-imidazolinyl group, 1-pyrazolidinyl group, 3
-Pyrazolidinyl group, 4-pyrazolidinyl group, 1-pyrazolinyl group, 2-pyrazolinyl group, 3-pyrazolinyl group, 4-pyrazolinyl group, 5-pyrazolinyl group, 1-piperidyl group, 2-piperidyl group, 3-piperidyl group, 4
-Piperidyl group, 1-piperazinyl group, 2-piperazinyl group, 3-piperazinyl group, 1-indolinyl group, 2-
Indolinyl group, 3-indolinyl group, 4-indolinyl group, 5-indolinyl group, 6-indolinyl group, 7-
Indolinyl group, 1-isoindolinyl group, 2-isoindolinyl group, 4-isoindolinyl group, 5-isoindolinyl group, 2-quinuclidinyl group, 3-quinuclidinyl group, 4-quinuclidinyl group, 2-morpholinyl group,
Examples thereof include a 3-morpholinyl group, a 4-morpholinyl group, a 1-azetidinyl group, a 2-azetidinyl group, a 3-azetidinyl group, a 1-azetidinonyl group, a 3-azetidinonyl group, and a 4-azetidinonyl group.

The C ₁ -C ₁₀ alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, sec-butoxy, t-butoxy, n-pentyloxy, n-hexyloxy group,
n-heptyloxy group, n-octyloxy group, n-nonyloxy group, n-decyloxy group and the like, preferably methoxy group, ethoxy group, n-propoxy group,
Examples thereof include an i-propoxy group, an n-butoxy group, a sec-butoxy group, and a t-butoxy group.

[0027] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. C ₁ -C ₆
Examples of the alkoxy group include a methoxy group, an ethoxy group, and n-
Propoxy group, i-propoxy group, n-butoxy group, s
ec-butoxy group, t-butoxy group, n-pentyloxy group, n-hexyloxy group and the like, preferably methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, sec. -Butoxy group and t-butoxy group.

The C ₂ -C ₁₀ alkoxycarbonyl group includes a methoxycarbonyl group, an ethoxycarbonyl group, n
-Propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, sec-butoxycarbonyl group, t-butoxycarbonyl group, n-pentyloxycarbonyl group, n-hexyloxycarbonyl group,
Examples include an n-heptyloxycarbonyl group, an n-octyloxycarbonyl group, and an n-nonyloxycarbonyl group.

The C ₂ -C ₁₀ alkanoyl groups include acyl, ethylcarbonyl, n-propylcarbonyl, i-propylcarbonyl, n-butylcarbonyl, i-butylcarbonyl, sec-butylcarbonyl, Examples include a t-butylcarbonyl group, n-pentylcarbonyl group, n-hexylcarbonyl group, n-heptylcarbonyl group, n-octylcarbonyl group and n-nonylcarbonyl group.

The tri C ₁ -C ₆ alkylsilyl group includes
A silyl group tri-substituted by the above-mentioned C ₁ -C ₆ alkyl is shown. For example, a trimethylsilyl group, a triethylsilyl group, a tri-n-propylsilyl group, a tri-n-butylsilyl group, a tri-n-pentylsilyl group, a tri-n-hexylsilyl group, and the like are preferable, and a trimethylsilyl group and the like are preferable. No.

The C ₁ -C ₆ alkyldiphenylsilyl group is the above-mentioned diphenylsilyl group mono-substituted with the C ₁ -C ₆ alkyl. Examples include a methyldiphenylsilyl group, an ethyldiphenylsilyl group, an n-butyldiphenylsilyl group, a t-butyldiphenylsilyl group, and the like, and preferably a t-butyldiphenylsilyl group.

The di C ₁ -C ₆ alkylphenylsilyl group is
The phenylsilyl group di-substituted by the above-mentioned C ₁ -C ₆ alkyl is shown. Examples include a dimethylphenylsilyl group, a diethylphenylsilyl group, a di-n-butylphenylsilyl group, a di-t-butylphenylsilyl group, and the like, and preferably a dimethylphenylsilyl group, a di-t-butylphenylsilyl group, and the like. Is mentioned.

The N-mono C ₁ -C ₁₀ alkylcarbamoyl group includes N-monomethylcarbamoyl, N-monoethylcarbamoyl, N-monon-propylcarbamoyl, N-monoi-propylcarbamoyl, Mono-n-butylcarbamoyl group, N-monoi-butylcarbamoyl group, N-monosec-butylcarbamoyl group,
N-mono-t-butylcarbamoyl group, N-monon-pentylcarbamoyl group, N-monon-hexylcarbamoyl group, N-monon-heptylcarbamoyl group, N-monon-octylcarbamoyl group, N-monon- A nonylcarbamoyl group and an N-mono-n-decylcarbamoyl group.

Examples of the N, N-diC ₁ -C ₁₀ alkylcarbamoyl group include an N, N-dimethylcarbamoyl group,
N-diethylcarbamoyl group, N, N-di-n-propylcarbamoyl group, N, N-dii-propylcarbamoyl group, N, N-din-butylcarbamoyl group, N, N-dii-butylcarbamoyl group, N, N-disec-butylcarbamoyl group, N, N-dit-butylcarbamoyl group, N, N-din-pentylcarbamoyl group, N, N-
Di-n-hexylcarbamoyl group, N, N-di-n-heptylcarbamoyl group, N, N-di-n-octylcarbamoyl group, N, N-di-n-nonylcarbamoyl group and N, N
-Di-n-decylcarbamoyl group and the like.

Next, the reaction conditions will be described in detail.
Examples of the olefin compound of the formula (1) include the following o-allylphenol derivatives, o-homoallylphenol derivatives, o-allylthiophenol derivatives, o-homoallylthiophenol derivatives, o-allylaniline derivatives and o-homoallyl derivatives. Aniline derivatives and the like (wherein,
R ¹ , R ² , R ³ and R ⁴ are the same as described above. ).

[0036]

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The optically active biaryl type oxazoline compound having axial asymmetry of the formula (2) includes a substituted or unsubstituted optically active biphenyl type oxazoline compound and a substituted or unsubstituted optically active binaphthyl type oxazoline compound, The aryl-aryl bond is in the R or S configuration. Examples of the optically active biaryl type oxazoline compound of the formula (2) include the following compounds and their enantiomers.

[0038]

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The amount of the optically active biaryl type oxazoline compound of the formula (2) to be used is in the range of 0.1 to 50 mol%, preferably, to the olefin compound of the formula (1).
It is in the range of 0.1 to 20 mol%. Examples of the divalent palladium salt include palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium sulfate, palladium nitrate, palladium cyanide and palladium trifluoromethanesulfonate, preferably. Examples include palladium acetate and palladium trifluoroacetate.

The amount of the divalent palladium salt used is 0.1 to 50 mol% based on the olefin compound of the formula (1).
, Preferably in the range of 0.1 to 20 mol%. Oxidizing agents include benzoquinone, a combination of copper (II) chloride and oxygen, a combination of copper (II) acetate and oxygen, ter
Examples include t-butyl hydroperoxide and cumene hydroperoxide, and preferably benzoquinone.

The oxidizing agent is used in an amount of 0.01 to 20 equivalents, preferably 0.1 to 10 equivalents, based on the olefin compound of the formula (1). The reaction solvent may be any solvent that does not participate in the reaction, such as benzene,
Hydrocarbon solvents such as toluene and hexane, ether solvents such as tetrahydrofuran, diethyl ether and 1,4-dioxane, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, cyclobutane Alcohol solvents such as hexanol, amide solvents such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphoric triamide;
Halogen solvents such as chloroform, methylene chloride, and ethylene dichloride; ketone solvents such as acetone, methyl ethyl ketone and methyl-i-butyl ketone; and other solvents such as acetonitrile, propionitrile, and dimethyl sulfoxide, or mixtures thereof. And preferably, methanol, tetrahydrofuran, benzene, methylene chloride and the like.

The reaction temperature is usually from -100.degree. C. to the reflux temperature of the reaction solvent used.
20-70 ° C. The reaction time is usually 0.1 to 100
0 hours. After the completion of the reaction, for example, after quenching the reaction by adding water to the reaction solution, extraction with a suitable solvent,
When the solvent is concentrated under reduced pressure and separated and purified by silica gel column chromatography, distillation or the like, the optically active heterocyclic compound of the formula (3) can be obtained.

The optical purity of the obtained optically active heterocyclic compound can be analyzed by an optically active chromatography column or optical rotation.

[0044]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. Example 1

[0045]

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22.4 mg (47 μmol) of the optically active binaphthyl oxazoline compound (2) and 15.0 mg (45 μmol) of palladium trifluoroacetate (II) were added to 0.3 ml of methanol and dissolved at 25 ° C., and 194 mg of p-benzoquinone (194 mg) was added. 1.8 mmol), 79.3 mg (0.45 mmol) of o-allylphenol (1) and 0.6 ml of methanol were added at 25 ° C, and the mixture was stirred at 60 ° C for 24 hours.

After completion of the reaction, the reaction mixture was purified by silica gel column chromatography (eluent: benzene) to obtain an optically active dihydrobenzofuran compound (3).
8 mg (yield 75%) and o-allylphenol (1)
9.5 mg (12% recovery) were obtained. The optical purity of the product was measured using an optically active substance separation column (Cyclodex β23).
As a result of gas chromatography analysis using 6M), it was 96% ee.

The analysis values are shown below. ¹ H-NMR (270 MHz, CDCl ₃ ) 1.55 (3 H, s), 1.82 (3 H, brs), 3.01 (1 H, d, J = 16.2 Hz), 3.26 (1
H, d, J = 16.2Hz), 4.84 (1H, brs), 5.09 (1H, brs), 6.79 (1H, br
d, J = 7.8Hz), 6.82 (1H, t, J = 7.3Hz), 7.11 (1H, brt, J = 7.2H)
z), 7.13 (1H, brd, J = 7.3 Hz) Mass: 174 (M +), 159 (bp), 141,131 Optical rotation [α] _D ²⁰ -83.1 (c 0.23, CHCl ₃ ) The reaction and operation were carried out in the same manner as in Example 1 except that 5 o-allylphenol (1) was changed to the following substrate, and the results in the following table were obtained.

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[0050]

[Table 1] Table 1 ─────────────────────────────────── Yield Substrate recovery rate Optical purity Example Substrate (%) (%) (% ee) ─────────────────────────────────── 2 R ^{1 = H, R 2 = F,} R 3 = H, R 4 = H 82 8 92 3 R 1 = H, R 2 = Me, R 3 = H, R 4 = H 86 8 94 4 R 1 = H, R ^{2 = H, R 3 = H} , R 4 = Me 71 7 94 5 R 1 = H, R 2 = Ph, R 3 = H, R 4 = H 62 19 90 ─────────── ──────────────────────── Examples 6 to 8 Same as Example 1 except that the optically active binaphthyl oxazoline compound was changed as follows. The reaction and operation were performed to obtain the results shown in the following table.

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Table 2 ──────────────────────────────── Yield Substrate recovery Optical purity Example Substrate ( (%) (%) (% Ee) ──────────────────────────────── 6 W ¹ s = Ph, W ¹ _R = H 71 10 937 W ¹ s = CH ₂ Ph, W ¹ _R = H 5 922 948 W ¹ s = H, W ¹ _R = i-Pr 378 18 ────────── Example 9 Same as Example 1 except that palladium (II) trifluoroacetate was replaced with palladium (II) acetate. As a result of the reaction and the operation, the yield of the optically active dihydrobenzofuran compound (3) was 44%, the optical purity was 54% ee, and o-
The recovery of allylphenol (1) was 33%. Example 10 A reaction and operation were carried out in the same manner as in Example 1 except that methanol was replaced with tetrahydrofuran. The yield of the optically active dihydrobenzofuran compound (3) was 8%, the optical purity was 6% ee, and o -The recovery of allylphenol (1) was 71%. Example 11 A reaction and operation were carried out in the same manner as in Example 1 except that methanol was replaced with benzene. As a result, the yield of the optically active dihydrobenzofuran compound (3) was 11% and the optical purity was 17%.
In ee, the recovery of o-allylphenol was 72%. Example 12

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The reaction was carried out in the same manner as in Example 1 except that o-allylphenol (1) was replaced by o-homoallylphenol (4) and optically active binaphthyl oxazolidine compound (2) was replaced by optically active binaphthyl oxazolidine compound (5). After that, 16.9 mg (60% yield) of an optically active dihydrobenzopyran compound (6) was obtained. The optical purity was 97% ee.

The analytical values are shown below. ¹ H-NMR (270 MHz, CDCl ₃ ) 1.46 (3H, s), 1.78 (3H, brs), 1.77-1.87 (1 H, m), 2.13 (1 H, d
t, J = 4.9,13.9Hz), 2.63-2.68 (2H, m), 4.84 (1H, brs), 4.94
(1H, brs), 6.78 (1H, d, J = 7.3Hz), 6.82 (1H, t, J = 7.3Hz), 7.0
0 (1 H, d, J = 7.3 Hz), 7.11 (1 H, t, J = 7.3 Hz) Mass: 188 (M +), 173 (bp), 145,107 Optical rotation [α] _D ²⁰ -34.2 (c0. 24, CHCl ₃ )

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According to the present invention, an optically active heterocyclic compound can be efficiently produced from an olefin compound in the presence of an optically active biaryl-type oxazoline compound having axial asymmetry and a divalent palladium salt.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07M 7:00

Claims (9)

[Claims] (1) Formula (1)Wherein Z represents an oxygen atom, a sulfur atom and an NH group
You. R is a hydrogen atom, C₁~ C_TenAlkyl group, C_Three~ C_Ten
Cycloalkyl group, (the alkyl group, the cycloalkyl group
Is a halogen atom, C₆~ C_TenAromatic or heterocyclic group
It may be arbitrarily substituted. ), C₆~ C_TenAromatic group
And a heterocyclic group (the aromatic group and the heterocyclic group are₁~ C_TenA
Alkyl group, C₁~ C_TenAlkoxy group, halogen atom, d
It may be optionally substituted with a toro group or a cyano group. )
Means R¹, R^Two, R^ThreeAnd R^FourIs a hydrogen atom, C₁
~ C_TenAlkyl group, C₁~ C_TenAlkoxy group, C_Three~ C_Ten
Cycloalkyl group (the alkyl group, the alkoxy group,
A loalkyl group is a halogen atom, C₆~ C_TenAromatic group
May be optionally substituted with a heterocyclic group. ), C₆~
C_TenAn aromatic group or a heterocyclic group (the aromatic group or the heterocyclic group is
₁~ C_TenAlkyl group, C₁~ C_TenAlkoxy group, halogen
Atom, nitro group, cyano group, C_Two~ C_TenAlkoxycal
Bonyl group or C_Two~ C_TenOptionally substituted with alkanoyl groups
It may be. ), Halogen atom, nitro group, cyano
Group, C_Two~ C_TenAn alkoxycarbonyl group and C_Two~ C_TenA
It means a lucanoyl group. n represents an integer of 1 to 3
You. An olefin compound represented by the formula (2):[Where A¹, A^Two, A^ThreeAnd A^FourIs independently a hydrogen atom,
C₁~ C₆Alkyl group, C _Two~ C₆Alkenyl group, C_Two~ C₆
Alkynyl group, C₁~ C₆An alkoxy group (the alkyl group,
Alkenyl, alkynyl and alkoxy groups are halogenated
Atom, hydroxyl group, tri-C₁~ C₆Alkylsilyl group, C₁
~ C₆Alkyldiphenylsilyl group, diC₁~ C₆Archi
Ruphenylsilyl group, C₁~ C₆Alkoxy group, C₆~ C
_TenMay be optionally substituted with an aromatic or heterocyclic group
No. ), Cyano group, nitro group, halogen atom, C_Two~ C
_TenAlkoxycarbonyl group, C_Two~ C_TenAlkanoyl
Group, formyl group, tri-C₁~ C₆Alkylsilyl group, C₁
~ C₆Alkyldiphenylsilyl group, diC₁~ C₆Archi
Ruphenylsilyl group, N-mono C₁~ C_TenAlkyl cal
Bamoyl group and N, N-di C₁~ C_TenAlkyl carbamo
Il group, A^ThreeAnd A^FourTogether with their attached benzene rings
To form a naphthyl ring.
Or one or more C₁~ C₆Alkyl group, C_Two~ C₆
Alkenyl group, C_Two~ C₆Alkynyl group, C₁~ C₆Arco
A xy group (the alkyl group, the alkenyl group, the alkynyl group,
The alkoxy group is a halogen atom, a hydroxyl group, a tri-C 1 -C
6 alkylsilyl group, C₁~ C₆Alkyl diphenyl silyl
Le group, di C₁~ C₆Alkylphenylsilyl group, C₁~ C₆
Alkoxy group, C₆~ C_TenAny aromatic or heterocyclic group
May be substituted. ), Cyano group, nitro group, ha
Logen atom, C_Two~ C_TenAlkoxycarbonyl group, C_Two~
C_TenAn alkanoyl group and a phenyl group (the phenyl group is
C₁~ C₆Alkyl group, C₁~ C₆Alkoxy group, cyano
Group, nitro group or halogen atom
Is also good. ) May be optionally substituted. ｝. W¹Passing
And W^TwoIs independently a hydrogen atom (however, W¹And W^TwoAre simultaneous
Is not a hydrogen atom. ), C₁~ C₆Alkyl group, phenyl
Group (the phenyl group is a C₁~ C₆Alkyl group, C₁~ C₆
With an alkoxy, cyano, nitro or halogen atom
It may be arbitrarily substituted. ) And a benzyl group (the
The radical is a C₁~ C₆Alkyl group, C₁~ C₆Alkoxy
Group, cyano group, nitro group or halogen atom
It may be. ). * Indicates asymmetric carbon
And the absolute configuration of the carbon atom means R or S. ]so
Optically active biaryl oxazo with axial asymmetry expressed
Oxidizes in the presence of phosphorus compounds and divalent palladium salts
Equation (3) characterized by the following:[Wherein, Z, R, R¹, R^Two, R^Three, R^Four, N and * are before
Same as above. Production of an optically active heterocyclic compound represented by the formula
Law. 2. The method according to claim 1, wherein Z in the formula (1) is an oxygen atom.
The production method of the optically active heterocyclic compound according to the above. 3. The compound according to claim 1, wherein A ³ and A ^{4 in} the formula (2) form a substituted or unsubstituted naphthyl ring.
The production method of the optically active heterocyclic compound according to the above. 4. The method for producing an optically active heterocyclic compound according to claim ¹ , wherein W ^{1 in the} formula (2) is an isopropyl group. 5. The method for producing an optically active heterocyclic compound according to claim ¹ , wherein W ^{1 in the} formula (2) is a phenyl group. 6. The method for producing an optically active heterocyclic compound according to claim ¹ , wherein W ^{1 in the} formula (2) is a benzyl group. 7. The method for producing an optically active heterocyclic compound according to claim 1, wherein the divalent palladium salt is palladium (II) trifluoroacetate. 8. The process for producing an optically active heterocyclic compound according to claim 1, wherein the divalent palladium salt is palladium (II) acetate. 9. The method for producing an optically active heterocyclic compound according to claim 1, wherein the oxidizing agent is benzoquinone.