JPH10287691A - Asymmetric wacker type cyclizing reaction using palladium complex catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new complex, comprising an optically active biaryl type oxazoline-palladium complex having axial asymmetry and useful as a catalyst, for an asymmetric Wacker type cyclizing reaction capable of efficiently providing an optically active heterocyclic compound from olefin compounds. SOLUTION: This new optically active biaryl type oxazoline-palladium complex having the axial asymmetry is represented by formula I [A<1> to A<4> are each H, a 1-6C (substituted)alkyl, a 2-6C (substituted)alkenyl, a 1-6C (substituted) alkoxy, cyano, nitro, a halogen, etc.; A<3> and A<4> , together with the benzene ring to which they are bonded, may form a naphthyl ring; W<1> and W<2> are each H (not simultaneously H), a 1-6C (substituted)alkyl, a (substituted)phenyl, a (substituted)benzyl, etc.; X is acetoxy, trifluoroacetic acid, a halogen, etc.; *stands for asymmetric carbon] and is useful as a catalyst, etc., for an asymmetric Wacker type cyclizating reaction. The complex is obtained by reacting binaphthyloxazoline compound represented by formula II, etc., with bis(acetonitrile)palladium(II) chloride, etc., in a solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an optically active biaryl-type oxazoline-palladium complex having axial asymmetry and an asymmetric Wacker-type cyclization reaction of an olefin compound using the complex. 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-palladium complex having axial asymmetry is used as a catalyst, an olefin compound can be efficiently used. The present inventors have found that an asymmetric Wacker-type cyclization reaction can be performed, and have completed the present invention.

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

[0007]

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[Wherein A¹, A^Two, A^ThreeAnd A^FourIndependently
Hydrogen atom, C₁~ C₆Alkyl group, C_Two~ C₆Alkenyl
Group, C_Two~ C₆Alkynyl group, C₁~ C₆An alkoxy group (the
Alkyl, alkenyl, alkynyl and alkoxy
The group is a halogen atom, a hydroxyl group, a tri-C₁~ C₆Alkyl
Silyl group, C₁~ C₆Alkyldiphenylsilyl group, diC
₁~ C₆Alkylphenylsilyl group, C₁~ C₆Alkoxy
Group, C₆~ C_TenOptionally substituted with an aromatic group or a heterocyclic group
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
It means a rubamoyl group.

A ³ and A ⁴ may form a naphthyl ring together with the benzene ring to which they are bonded. The naphthyl ring may be unsubstituted or one or more C ₁ -C ₆ alkyl groups, C ₂ -C ₆ alkenyl group, C ₂ -C ₆ alkynyl group, C
₁ -C ₆ alkoxy group (said alkyl group, alkenyl group, alkynyl group and alkoxy groups, halogen atom, hydroxyl group, tri C ₁ -C ₆ alkylsilyl group, C ₁ -C ₆ alkyl butyldiphenylsilyl, di C ₁ ~ C ₆ alkylphenyl silyl group, C ₁ -C ₆ alkoxy group, may be optionally substituted with C ₆ -C ₁₀ aromatic group and a heterocyclic group.), a cyano group, a nitro group, a halogen atom, C ₂ -C ₁₀ alkoxycarbonyl group, C ₂ -C ₁₀ alkanoyl group and phenyl group (the phenyl group is optionally a C ₁ -C ₆ alkyl group, a C ₁ -C ₆ alkoxy group, a cyano group, a nitro group and a halogen atom. May be substituted.). ｝.

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

X represents an acetoxy group, a trifluoroacetic acid group, a trifluoromethanesulfonyl group, a cyano group or a halogen atom. * Means asymmetric carbon, and the absolute configuration of carbon atom indicates R or S. In the presence of an optically active biaryl-type oxazoline-palladium complex having axial asymmetry represented by the formula (2):

[0012]

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Wherein Z is an oxygen atom, a sulfur atom and N
H means a group. R represents a hydrogen atom, a C ₁ -C ₁₀ alkyl group, a C ₃ -C ₁₀ cycloalkyl group (the alkyl group and the cycloalkyl group may be a halogen atom, a C ₆ -C ₁₀ aromatic group or a heterocyclic group, May be substituted.), C ₆
To a C ₁₀ aromatic group and a heterocyclic group (the aromatic group and the heterocyclic group are optionally substituted with a C ₁ -C ₁₀ alkyl group, a C ₁ -C ₁₀ alkoxy group, a halogen atom, a nitro group and a cyano group. May be used).

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, the alkoxy group and the cycloalkyl group may be optionally substituted with a halogen atom, a C ₆ -C ₁₀ aromatic group and a heterocyclic group), C ₆
-C ₁₀ aromatic group and heterocyclic group (the aromatic group and heterocyclic group are a C ₁ -C ₁₀ alkyl group, a C ₁ -C ₁₀ alkoxy group, a halogen atom, a nitro group, a cyano group, a C ₂ -C 10 Optionally substituted with a ₁₀ alkoxycarbonyl group and a C ₂ -C ₁₀ alkanoyl group), a halogen atom, a nitro group,
A cyano group, C ₂ -C ₁₀ alkoxycarbonyl group and a C ₂ ~
Means C ₁₀ alkanoyl group.

N represents an integer of 1 to 3. Wherein the olefin compound represented by formula (3) is oxidized.

[0016]

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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:

[0018]

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 ,
A ^4, X, for W ¹ and W ² will be described. Examples of the C ₁ -C ₆ alkyl group include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, and 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.

C ₁ -C ₁₀ alkyl groups include methyl, ethyl, n-propyl, i-propyl, 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 and 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, and 2-thienyl group.
-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.

Examples of the non-aromatic heterocyclic ring include 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 ₆ alkoxy group includes methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, sec-butoxy, t-butoxy, n-pentyloxy and n-hexyloxy group and the like, preferably methoxy group, ethoxy group, n
-A propoxy group, an i-propoxy group, an n-butoxy group,
and a sec-butoxy group and a t-butoxy 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.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. C ₂ ~C
₁₀ alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl, sec-butoxycarbonyl, t-butoxycarbonyl, n-pentyloxycarbonyl Group, n
-Hexyloxycarbonyl group, n-heptyloxycarbonyl group, n-octyloxycarbonyl group, n-nonyloxycarbonyl group and the like.

Examples of 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-di C 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.

The optically active biaryl-type oxazoline-palladium complex having axial asymmetry of the formula (1) is a substituted or unsubstituted optically active biphenyl-type oxazoline-palladium complex or a substituted or unsubstituted optically active binaphthyl-type oxazoline-palladium complex. Includes palladium complexes, wherein the aryl-aryl bond is in the R or S configuration. The optically active biaryl oxazoline-palladium complex having axial asymmetry of the formula (1) can be produced from an optically active biaryl oxazoline compound and a divalent palladium salt.

The optically active biaryl oxazoline compounds include the following compounds and their enantiomers.

[0038]

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As the divalent palladium salt, palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium sulfate,
Examples include palladium nitrate, palladium cyanide, and palladium trifluoromethanesulfonate, and preferably, palladium acetate and palladium trifluoroacetate.

The reaction molar ratio of the optically active biaryl type oxazoline compound and the divalent palladium salt is 0.1:
It is 1: 10: 1, preferably 0.5: 1-4: 1. The reaction temperature is usually from -100 ° C to the reflux temperature of the reaction solvent used, preferably from -20 to -20 ° C.
50 ° C. The reaction solvent may be any solvent that does not participate in the reaction, and is generally a hydrocarbon solvent such as benzene, toluene, and hexane, an ether solvent such as tetrahydrofuran, diethyl ether, and 1,4-dioxane, methanol, ethanol, and 1-. Alcoholic solvents such as propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, cyclohexanol, formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoric acid Amide solvents such as 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 others, such as acetonitrile, propionitrile, and dimethyl sulfoxide. Medium, or,
These mixed solvents can be exemplified, and preferably, methanol, tetrahydrofuran, methylene chloride, and dimethylformamide are exemplified.

The optically active biaryl-type oxazoline-palladium complex having axial asymmetry of the formula (1) thus produced can be used in an asymmetric Wacker-type cyclization reaction as it is or as a reaction solution. Next, the asymmetric Wacker-type cyclization reaction will be described. Examples of the olefin compound of the formula (2) include the following o-allylphenol derivatives, o-homoallylphenol derivatives, o-allylthiophenol derivatives, o-homoallylthiophenol derivatives, o-allylaniline derivatives, o-homoallyl derivatives Aniline derivatives and the like (R ¹ , R ² , R ³ and R ⁴ are as defined above).

[0042]

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The amount of the optically active biaryl-type oxazoline-palladium complex having axial asymmetry of the formula (1) is 0.1 to 50 relative to the olefin compound of the formula (2).
Mol%, preferably in the range of 0.1 to 20 mol%. Examples of the oxidizing agent include benzoquinone, copper-oxygen chloride (II) -oxygen, copper-oxygen acetate (II), tert-butyl hydroperoxide, cumene hydroperoxide and the like, and preferably benzoquinone and the like.

The reaction solvent may be the same as or different from the solvent used in the production of the optically active biaryl-type oxazoline-palladium complex having axial asymmetry of the formula (1), and may be a carbonized solvent such as benzene, toluene and hexane. Hydrogen solvent, tetrahydrofuran, diethyl ether, 1,4-
Ether solvents such as dioxane, alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, cyclohexanol, formamide, N, N-dimethylformamide, N, N -Dimethylacetamide, N
-Amide solvents such as methylpyrrolidone and hexamethylphosphoric acid 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 acetonitrile and propionitrile And a solvent such as dimethyl sulfoxide, or a mixed solvent thereof, preferably, methanol, tetrahydrofuran, benzene, or methylene chloride.

The reaction temperature is usually from -100 ° C. to the reflux temperature of the reaction solvent used, and is preferably
-20 to 70 ° C. The reaction time is usually 0.1 to 10
00 hours. After completion of the reaction, for example, water is added to the reaction solution to quench the reaction, followed by extraction with an appropriate solvent, concentration of the solvent under reduced pressure, and separation and purification by silica gel column chromatography or distillation to obtain the formula (3) Can be obtained.

The optical purity of the obtained optically active heterocyclic compound of the formula (3) can be analyzed by an optically active chromatography column or optical rotation.

[0047]

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 (Synthesis of optically active biaryl-type oxazoline-palladium complex)

[0048]

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152 mg (0.586 mmol) of bis (acetonitrile) palladium (II) chloride was added to and dissolved in 5 ml of dichloromethane, and a solution of 323 mg (0.678 mmol) of the binaphthyloxazoline compound (1) in 5 ml of dichloromethane was added dropwise at a temperature of 5 ° C. After vigorous stirring for 5 minutes, insolubles were filtered off and the filtrate was concentrated under reduced pressure.

To the concentrate, 3 ml of dichloromethane and 6 ml of hexane were added to precipitate crystals. After filtering the crystals,
After drying, 275 mg (72% yield) of an optically active biaryl-type oxazoline-palladium complex (2) was obtained. The analytical values are shown below. Melting point: 243-264 ° C. (decomposition) ¹ H-NMR (270 MHz, CD ₂ Cl ₂ ) 0.013 (3H, d, J = 6.93 Hz), 0.741 (1H, dtt, J = 7.59, 6.93, 6.60)
Hz), 1.263 (3H, d, J = 6.60Hz), 3.466 (1H, dd, J = 8.60,6.26H
z), 4.171 (1H, dd, J = 9.90,8.60Hz), 4.800 (1H, ddd, J = 9.90,
7.59,6.27Hz), 7.011 (1H, bd, J = 8.58Hz), 7.339 (1H, bt, J =
8.58Hz), 7.584 (1H, bt, J = 7.92Hz), 7.785 (1H, bd, J = 8.25H
z), 7.990 (1H, bd, J = 7.92 Hz), 8.152 (1 H, bd, J = 8.25 Hz) Optical rotation [α] _D ²⁰ -54.1 (c 0.10, CH ₂ C
l ₂ ) Example 2 (Synthesis of optically active biaryl-type oxazoline-palladium complex)

[0051]

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Binaphthyl oxazoline compound (1) 47
7 mg (1.0 mmol) and trifluoroacetic acid (II)
330 mg (0.99 mmol) of palladium was added to and dissolved in 20 ml of methanol, followed by vigorous stirring at 25 ° C. for 5 minutes. Next, the reaction solution was concentrated to about 10 ml, and 20 ml of benzene was added to precipitate crystals.
After drying, 565 mg (70% yield) of an optically active biaryl-type oxazoline-palladium complex (3) was obtained.

The analytical values are shown below. Melting point: 227 to 243 ° C. (decomposition) ¹ H-NMR (270 MHz, CD ₂ Cl ₂ ) 0.020 (3H, d, J = 6.59 Hz), 0.677 (1 H, dtt, J = 7.59, 6.60, 6.59)
Hz), 1.191 (3H, d, J = 6.60Hz), 3.560 (1H, ddd, J = 9.24,7.59,
6.27Hz), 3.597 (1H, dd, J = 8.91,6.27Hz), 4.190 (1H, dd, J =
9.24,8.91Hz), 7.005 (1H, bd, J = 8.25Hz), 7.353 (1H, bt, J =
7.26Hz), 7.963 (1H, bd, J = 8.58Hz), 8.043 (1H, bd, J = 8.25H
z), 8.248 (1H, bd, J = 8.57 Hz) Optical rotation [α] _D ²⁰ −24.4 (c 0.11, CH ₂ C
l ₂ ) X-ray data C ₃₆ H ₃₂ O ₆ N ₂ PdF ₆ lattice constant: a = 16.25 (1) １b = 15.207 (6) ６c = 14.316 (5) ５ space group: P2 _{1 2 1 2 1 (# 19} ) R = 6.5%

[0054]

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Example 3 (Asymmetric Wacker-type cyclization of o-allylphenol)

[0056]

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12.1 mg (0.015 mmol) of optically active biaryl-type oxazoline-palladium complex (3)
Was added to and dissolved in 0.1 ml of methanol, and the mixture was stirred at 25 ° C. Next, p-benzoquinone 65 mg (0.60 m
mol) and 0.1 ml of methanol, and the mixture was stirred well, and then 26.4 mg (0.4 ml) of o-allylphenol (4) was added.
15 mmol) and 0.1 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).
Optically active dihydrobenzofuran compound (5) 19.6m
g (75% yield). The optical purity was 96% ee by gas chromatography using an optically active substance separation column (Cyclodex β236M).

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 ) Example 4 ( Asymmetric Wacker-type cyclization of o-homoallylphenol)

[0060]

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O-Allylphenol (4) is replaced with o
Example 3 except that homoallylphenol (6) was used
When the reaction and operation were carried out in the same manner as in the above, 16.9 mg of the optically active dihydrobenzopyran compound (7) (yield: 60)
%). 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 (1H, d, J = 7.3 Hz), 7.11 (1H, t, J = 7.3 Hz) Mass: 188 (M +), 173 (bp), 145,107 Optical rotation [α] _D ²⁰ -34.2 (c0. 24, CHCl ₃ )

[0062]

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-palladium complex having axial asymmetry.

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

Claims (10)

[Claims] (1) Formula (1)[Where A¹, A^Two, A^ThreeAnd A^FourIs independently a hydrogen atom, C
₁~ C₆Alkyl group, C_Two~ C₆Alkenyl group, C_Two~ C₆A
Rukinyl group, C₁~ C₆An alkoxy group (the alkyl group,
Lucenyl, alkynyl and alkoxy groups are
Atom, hydroxyl group, tri-C₁~ C₆Alkylsilyl group, C₁
~ C₆Alkyldiphenylsilyl group, diC ₁~ C₆Archi
Ruphenylsilyl group, C₁~ C₆Alkoxy group, C₆~ C
_TenOptionally 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, 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
Ill group. A^ThreeAnd A^FourIs their binding Ben
A naphthyl ring may be formed together with the zen ring.
The naphthyl ring may be unsubstituted as well as one or more₁~ C₆A
Alkyl group, C_Two~ C₆Alkenyl group, C_Two~ C₆Alkynyl
Group, C₁~ C₆An alkoxy group (the alkyl group, the alkenyl
Group, alkynyl group and alkoxy group are a halogen atom,
Hydroxyl group, tri-C₁~ C₆Alkylsilyl group, C₁~ C₆Al
Kildiphenylsilyl group, di C₁~ C₆Alkylphenyl
Silyl group, C₁~ C₆Alkoxy group, C₆~ C_TenAromatic group
And a heterocyclic group. ), Shea
Group, nitro group, halogen atom, C_Two~ C_TenAlkoxy
Carbonyl group, C_Two~ C_TenAlkanoyl group and phenyl
Group (the phenyl group is C₁~ C₆Alkyl group, C₁~ C₆A
Designated with lucoxy, cyano, nitro and halogen atoms
It may be replaced at will. )
Is also good. ｝. W¹And W^TwoIs independently a hydrogen atom (however,
W¹And W^TwoAre not simultaneously hydrogen atoms. ), C₁~ C₆
Alkyl group, phenyl group (the phenyl group is₁~ C₆A
Alkyl group, C₁~ C₆Alkoxy group, cyano group, nitro group
And a halogen atom. )
And a benzyl group, wherein the benzyl group is C₁~ C₆Alkyl group,
C₁~ C₆Alkoxy, cyano, nitro and halogen
And may be optionally substituted with a substituent atom. ).
X represents an acetoxy group, a trifluoroacetic acid group,
Methanesulfonyl group, cyano group and halogen atom
To taste. * Means asymmetric carbon, and the absolute configuration of carbon atoms is
Indicates R or S. An optically active polymer having axial asymmetry represented by
Aryl-type oxazoline-palladium complex. 2. The optically active biaryl-type oxazoline-palladium complex having axial asymmetry according to claim 1, wherein A ³ and A ^{4 form} a substituted or unsubstituted naphthyl ring. 3. The method according to claim 2, wherein X is a trifluoroacetic acid group.
An optically active biaryl-type oxazoline-palladium complex having the axial asymmetry described. 4. The axially chirally active biaryl-type oxazoline-palladium complex according to claim 2, wherein X is a chlorine atom. 5. The optically active biaryl-type oxazoline-palladium complex having axial asymmetry according to claim 3, wherein W ¹ is an isopropyl group. 6. The optically active biaryl-type oxazoline-palladium complex having axial asymmetry according to claim 3, wherein W ¹ is a phenyl group. 7. The optically active biaryl-type oxazoline-palladium complex having axial asymmetry according to claim 3, wherein W ¹ is a benzyl group. 8. The formula (2) [In the formula, Z means an oxygen atom, a sulfur atom, and an NH group. R represents a hydrogen atom, a C ₁ -C ₁₀ alkyl group, a C ₃ -C ₁₀
Cycloalkyl group (the alkyl group and cycloalkyl group may be substituted with a halogen atom, may be optionally substituted with C ₆ -C ₁₀ aromatic group and a heterocyclic group.), C ₆ ~C ₁₀ aromatic group and the heterocyclic A cyclic group (the aromatic group and the heterocyclic group are C ₁ -C ₁₀
Alkyl group, C ₁ -C ₁₀ alkoxy group, halogen atom,
It may be optionally substituted with a nitro group and a cyano group. ). R ¹ , R ² , R ³ and R ⁴ represent a hydrogen atom, a C ₁ -C ₁₀ alkyl group, a C ₁ -C ₁₀ alkoxy group,
₃ -C ₁₀ cycloalkyl group (said alkyl group, alkoxy group and cycloalkyl group, a halogen atom, C ₆ -C ₁₀
It may be optionally substituted with an aromatic group and a heterocyclic group. ), A C ₆ -C ₁₀ aromatic group and a heterocyclic group (the aromatic group and the heterocyclic group are a C ₁ -C ₁₀ alkyl group, a C ₁ -C ₁₀ alkoxy group, a halogen atom, a nitro group, a cyano group, C ₂ ~
Optionally may be substituted with C ₁₀ alkoxycarbonyl group and C ₂ -C 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 means the integer of 1-3. Wherein the olefin compound represented by formula (3) is oxidized in the presence of the optically active biaryl-type oxazoline-palladium complex having axial asymmetry according to claim 1. [In the formula, * means asymmetric carbon, and the absolute configuration of carbon atom indicates R or S. Z, R, R ¹ , R ² , R ³ , R ⁴ and n
Is the same as above. ] The method for producing an optically active heterocyclic compound represented by the formula: 9. The method for producing an optically active heterocyclic compound according to claim 8, wherein Z is an oxygen atom. 10. The oxidizing agent is benzoquinone.
The production method of the optically active heterocyclic compound according to the above.