JP2002053572A - Method for producing optically active pyran analogue - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an optically active pyran analogue which is industrially useful. SOLUTION: Aldehydes or ketones are reacted with dienes in the presence of a catalyst containing a binaphthol-phosphoric acid derivative, and an aluminosilicate.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an optically active pyran analog. Optically active pyran analogs are compounds useful as intermediates in the synthesis of medicines and pesticides.

[0002]

2. Description of the Related Art Conventionally, in the presence of a chiral Lewis acid catalyst,
A method for obtaining an optically active pyran analog by reacting a diene such as Danishefsky's Diene with a compound having a carbon-hetero element double bond (asymmetric hetero-Diels-Alder cyclization reaction, hereinafter referred to as asymmetric HDA reaction) Abbreviated) are known in many respects. Mik
ami et. al. J. et al. Am. Chem.
Soc. , 1994, 116, 2812. Etc. are known.

[0003]

In the conventional asymmetric HDA reaction, however, a catalyst is usually used for the compound having a carbon-hetero element double bond used for the reaction.
It was necessary to use 0 mol%, which was not an industrially satisfactory production method.

[0004]

Means for Solving the Problems The present inventors have proposed asymmetric HD
As a result of intensive studies on the development of a more industrial production method of the reaction A, as a catalyst, binaphthol represented by the following general formula (1), general formula (2), general formula (3) or general formula (4) was used.
Phosphate derivatives

[0005]

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[0006]

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[In the general formula (1) or the general formula (2),
R ₁ , R ₂ , R ₃ , and R ₄ each independently represent hydrogen, carbon atom 1
Straight-chain or branched alkyl group of -20, carbon number 1
A branched or straight-chain alkenyl group having 20 to 20 carbon atoms, a branched or straight-chain alkynyl group having 1 to 20 carbon atoms, a phenyl group, a branched or straight-chain alkyl group having 1 to 10 carbon atoms and a nucleus of 1 to 4 Substituted phenyl group, having 1 to 1 carbon atoms
10 branched or straight-chain alkenyl groups having 1 to 1 nucleus
It represents a 4-substituted phenyl group, a phenyl group, a naphthyl group, or a cycloalkyl group having 3 to 8 carbon atoms, wherein the nucleus is substituted by 1 to 4 branched or straight-chain alkynyl groups having 1 to 10 carbon atoms. However, R _{1 to} R ₄ are not simultaneously hydrogen. M represents a metal element capable of forming a trivalent metal ion. ]

[0008]

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[0009]

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[In the general formula (3) or the general formula (4),
R ₅ , R ₆ , R ₇ and R ₈ are each independently hydrogen, carbon atom 1
Straight-chain or branched alkyl group of -20, carbon number 1
A branched or straight-chain alkenyl group having 1 to 20 carbon atoms, an alkynyl group or a phenyl group having 1 to 20 carbon atoms, a branched or straight-chain alkyl group having 1 to 10 carbon atoms and a nucleus of 1 to 4 Substituted phenyl group, having 1 to 1 carbon atoms
10 branched or straight-chain alkenyl groups having 1 to 1 nucleus
It represents a 4-substituted phenyl group, a phenyl group, a naphthyl group, or a cycloalkyl group having 3 to 8 carbon atoms, wherein the nucleus is substituted by 1 to 4 branched or straight-chain alkynyl groups having 1 to 10 carbon atoms. M represents a metal element capable of forming a trivalent metal ion. The present inventors have found that the amount of the catalyst can be greatly reduced by carrying out an asymmetric HDA reaction in the presence of an aluminosilicate using an asymmetric synthesis catalyst containing .

That is, the present invention provides a method for producing an optically active pyran analog by reacting a diene with a compound having a carbon-hetero element double bond in the presence of a catalyst. Optical activity characterized by reacting in the presence of an asymmetric synthesis catalyst containing a binaphthol-phosphate derivative represented by the general formula (2), (3) or (4) and an aluminosilicate This is a method for producing a pyran analog.

The present invention will be described in detail below.

The asymmetric synthesis catalyst used in the present invention is not particularly limited as long as it contains the binaphthol-phosphate derivative represented by the above general formulas (1) to (4). However, specifically, gadolinium tris (R)-(−)-6,6′-di-n-octyl-
1,1′-binaphthyl-2,2′-diyl phosphate, gadolinium tris (S)-(+)-6,6′-di-n-
Octyl-1,1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (R)-(-)-6,6 '
-Di-n-octenyl-1,1'-binaphthyl-2,
2'-diyl phosphate, gadolinium tris (S)-
(+)-6,6'-di-n-octenyl-1,1'-binaphthyl-2,2'-diyl phosphate, ytterbium tris (R)-(-)-6,6'-di-n- Octyl-
1,1′-binaphthyl-2,2′-diyl phosphate, ytterbium tris (S)-(+)-6,6′-di-n
-Octyl-1,1'-binaphthyl-2,2'-diylphosphate, scandium tris (R)-(-)-6,
6'-di-n-octyl-1,1'-binaphthyl-2,
2'-diyl phosphate, scandium tris (S)-
(+)-6,6'-di-n-octyl-1,1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (R)-(-)-6,6'-di (2 " , 6 "-dimethylphenyl) -1,1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (S)-(+)-6,
6'-di (2 ", 6" -dimethylphenyl) -1,1 '
-Binaphthyl-2,2'-diyl phosphate, ytterbium tris (R)-(-)-6,6'-di (2 ", 6"
-Dimethylphenyl) -1,1'-binaphthyl-2,
2'-diyl phosphate, ytterbium tris (S)-
(+)-6,6′-di (2 ″, 6 ″ -dimethylphenyl-1,1′-binaphthyl-2,2′-diylphosphate,
Scandium tris (R)-(-)-6,6'-di (2 ", 6" -dimethylphenyl) -1,1'-binaphthyl-2,2'-diyl phosphate, scandium tris (S)-( +)-6,6'-di (2 ", 6" -dimethylphenyl) -1,1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (R)-(-)-5,
6,7,8,5 ', 6', 7 ', 8'-octahydro-
1,1′-binaphthyl-2,2′-diyl phosphate, gadolinium tris (S)-(+)-5,6,7,8,
5 ', 6', 7 ', 8'-octahydro-1,1'-binaphthyl-2,2'-diyl phosphate, ytterbium tris (R)-(-)-5,6,7,8,5' , 6 ',
7 ', 8'-octahydro-1,1'-binaphthyl-
2,2′-diyl phosphate, ytterbium tris (S)-(+)-5,6,7,8,5 ′, 6 ′, 7 ′,
8'-octahydro-1,1'-binaphthyl-2,2 '
-Diyl phosphate, scandium tris (R)-(-)
-5,6,7,8,5 ', 6', 7 ', 8'-octahydro-1,1'-binaphthyl-2,2'-diyl phosphate, scandium tris (S)-(+)-5 , 6,7,
8,5 ′, 6 ′, 7 ′, 8′-octahydro-1,1 ′
-Binaphthyl-2,2'-diyl phosphate, gadolinium tris (R)-(-)-3,3'-diethenyl-1,
1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (S)-(+)-3,3'-diethenyl-
1,1′-binaphthyl-2,2′-diyl phosphate, ytterbium tris (R)-(−)-3,3′-diethenyl-1,1′-binaphthyl-2,2′-diyl phosphate, ytterbium Tris (S)-(+)-3,3'-
Diethenyl-1,1′-binaphthyl-2,2′-diyl phosphate, scandium tris (R)-(−)-3,
3'-diethenyl-1,1'-binaphthyl-2,2'-
Diyl phosphate, scandium tris (S)-(+)-
3,3′-diethenyl-1,1′-binaphthyl-2,
2'-diyl phosphate, gadolinium tris (R)-
(-)-1,1'-binaphthyl-2,2'-diyl phosphate, gadolinium tris (S)-(+)-1,1'-
Binaphthyl-2,2'-diyl phosphate, ytterbium tris (R)-(-)-1,1'-binaphthyl-2,
2'-diyl phosphate, ytterbium tris (S)-
(+)-1,1'-binaphthyl-2,2'-diyl phosphate, scandium tris (R)-(-)-1,1'-
Binaphthyl-2,2'-diyl phosphate, scandium tris (S)-(+)-1,1'-binaphthyl-2,2
'-Diyl phosphate and the like, and those phosphates which are retained as crystals in the form of crystals having 0 to 10 molecules of water of crystallization and those which contain 0 to 10 mol of water as resinous substances Is also included.

The above general formulas (1) to (4) of the present invention.
Can be prepared by reacting the corresponding binaphthol-phosphate derivative with a trivalent metal salt.

As the trivalent metal salt, a metal salt of any metal element capable of stably forming a trivalent metal salt is applicable, and is not particularly limited. Preferred are lanthanoid series elements, specifically, scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium. The selected element may be mentioned.

In the present invention, the asymmetric synthesis catalyst can be used in any ratio with respect to the compound having a carbon-hetero element double bond and the diene used in the reaction, but the excessive use is economical. is not. If the amount is too small, the reaction may not proceed smoothly, or the reaction may not proceed at all because the catalyst is deactivated due to the presence of a trace amount of impurities in the system.
Preferably, of the compounds having a carbon-hetero element double bond and dienes, 0.01 to 0.01
The range is 100 mol%, preferably 0.1 to 50 mol%, and more preferably 0.1 to 10 mol%.

In the present invention, the optical absolute configuration developed by the reaction using the above asymmetric synthesis catalyst generally depends on the optical absolute configuration of binaphthols constituting the asymmetric synthesis catalyst. For example, when (R) -binaphthol is used and the optical absolute configuration of the asymmetric carbon of the product gives the (R) form, if (S) -binaphthol of the enantiomer is used, the asymmetric carbon of the product is obtained. The optical absolute configuration of (S)
There is a relationship that gives the body. As for the optical absolute configuration of the asymmetric carbon of the product, when the binaphthol is (R),
The optical absolute configuration of the product differs depending on the type of the substrate, the type of the binaphthols, the type of the phosphate-forming element, etc., rather than providing (R).

In the present invention, it is essential to carry out the reaction in the presence of the asymmetric synthesis catalyst and aluminosilicates.

In the present invention, the aluminosilicate to be added at the time of the reaction is not particularly limited. For example, A-type zeolites represented by molecular sieves 3A, 4A and 5A, molecular sieves 13X, Y-type, L
And zeolite such as β-type.

In the present invention, the aluminosilicates can be used in any ratio with respect to the catalyst used in the reaction, but using too much is not economical. Although not particularly limited, usually 0.1% by weight based on the catalyst
-100% by weight.

The handling of the aluminosilicate is not particularly limited. However, since the catalyst and the inside of the system can be dehydrated or dried, water and the like are removed by hot drying or other methods. It is preferred to use At this time, the mixture mixed with binaphthol phosphate may be dried while heating.

In the present invention, a diene is reacted with a compound having a carbon-hetero element double bond in the presence of the asymmetric synthesis catalyst and the aluminosilicate.

The diene applicable to the present invention is not particularly limited. For example, the following general formula (5)

[0024]

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Wherein R ₉ , R ₁₀ , R ₁₁ and R ₁₂ are each independently hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, or a branched alkyl group having 1 to 20 carbon atoms. Or a straight-chain alkenyl group, a branched or straight-chain alkynyl group having 1 to 20 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, a branched or straight-chain alkyloxy group having 1 to 20 carbon atoms, Represents a branched or straight-chain dialkylamino group having 1 to 20 carbon atoms, or a branched or straight-chain trialkylsilyloxy group having 1 to 20 carbon atoms. And specific examples thereof include 1,3-butadiene, 1,3-pentadiene, cyclopentadiene, and the like.
1-methoxy-3- (trimethylsilyloxy) -1,
3-butadiene (Danishefsky's die)
ne), 1,3-bis (trimethylsilyloxy)-
1,3-butadiene, 1-methoxy-3- (trimethylsilyloxy) -1,3-pentadiene, 1-methoxy-2-acetoxy-3- (trimethylsilyloxy)-
1,3-butadiene, 1-methoxy-2-methyl-3-
(Trimethylsilyloxy) -1,3-butadiene, 1
-Tert-butoxy-3- (trimethylsilyloxy) -1,3-butadiene, 1-methoxy-3- (triethylsilyloxy) -1,3-butadiene, 1-te
rt-butoxy-3- (triethylsilyloxy)-
1,3-butadiene and the like can be mentioned.

The compound having a carbon-hetero element double bond is not particularly limited, but may be, for example, a compound represented by the following general formula (6):

[0027]

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Wherein R ₁₃ is hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms,
Linear or branched alkynyl group, phenyl group,
A phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms, or a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkenyl group having 1 to 10 carbon atoms A phenyl group having a nucleus 1-4 substituted by a branched or linear alkynyl group having 1 to 10 carbon atoms;
A phenyl group, a naphthyl group, a cycloalkyl group having 3 to 8 carbon atoms, a C1 to C10 alkyl having a phenyl group, wherein the nucleus is substituted by a branched or linear alkoxy group having 1 to 4 carbon atoms, Represents an alkyl group having a phenyl group in which a nucleus is substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms and a nucleus of 1 to 4;

R ₁₄ represents a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms, or a linear or branched alkynyl group having 1 to 20 carbon atoms. Group, phenyl group, carbon number 1-10
A phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group; a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkenyl group having 1-10 carbon atoms; A phenyl group whose nucleus is substituted by 1 to 4 branched or straight-chain alkynyl groups;
0 branched or straight-chain alkoxy group having 1 to 4 nuclei
A phenyl group, a naphthyl group, a cycloalkyl group having 3 to 8 carbon atoms, an alkyl group having 1 to 10 carbon atoms having a phenyl group, a branched or straight-chain alkyl group having 1 to 10 carbon atoms and a nucleus of 1 An alkyl group having a substituted or unsubstituted phenyl group; a linear or branched alkylcarbonyl group having 1 to 19 carbon atoms; a linear or branched alkenylcarbonyl group having 1 to 19 carbon atoms; A straight-chain or branched alkynylcarbonyl group, a phenylcarbonyl group, a phenylcarbonyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group having 1 to 9 carbon atoms, a branched phenylcarbonyl group having 1 to 9 carbon atoms or A phenylcarbonyl group whose nucleus is substituted by 1 to 4 straight-chain alkenyl groups,
A phenylcarbonyl group, a naphthylcarbonyl group, a cycloalkylcarbonyl group having 3 to 8 carbon atoms, and a phenyl group having 1 to 4 carbon atoms, wherein the nucleus is substituted by a branched or linear alkynyl group having 1 to 9 carbon atoms and a alkynyl group having 1 to 4 carbon atoms An alkylcarbonyl group having 9 alkylcarbonyl groups, an alkylcarbonyl group having a phenyl group whose nucleus is substituted by 1 to 4 carbon atoms with a branched or straight-chain alkyl group having 1 to 9 carbon atoms, a linear or branched alkyl having 1 to 19 carbon atoms Represents an oxycarbonyl group, a phenyloxycarbonyl group, or a phenyloxycarbonyl group having 1 to 4 nuclei substituted by a linear or branched alkyl group having 1 to 9 carbon atoms, and R ₁₃ and R ₁₄ are not equal.

A represents an oxygen atom, a sulfur atom, a selenium atom, a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms, 20 straight-chain or branched alkynyl groups, phenyl groups, phenyl groups having 1 to 4 carbon atoms and a nucleus substituted by a branched or straight-chain alkyl group having 1 to 4 carbon atoms, branched or straight-chain alkyl groups having 1 to 10 carbon atoms; A phenyl group having 1 to 4 nuclei substituted by a chain alkenyl group;
10 branched or straight-chain alkynyl groups having 1 to 1 nucleus
It has a 4-substituted phenyl group, a phenyl group, a naphthyl group, a cycloalkyl group having 3 to 8 carbon atoms, and a phenyl group, wherein the nucleus is substituted by a branched or straight-chain alkoxy group having 1 to 10 carbon atoms and 1 to 4 carbon atoms. An alkyl group having 1 to 10 carbon atoms,
An alkyl group having a phenyl group whose nucleus is substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms, a straight-chain or branched alkenylcarbonyl group having 1 to 19 carbon atoms, A linear or branched alkynylcarbonyl group, a phenylcarbonyl group, a phenylcarbonyl group having a nucleus 1-4 substituted with a branched or linear alkyl group having 1 to 9 carbon atoms, A branched or straight-chain alkenyl group having 1 nucleus
A substituted or unsubstituted phenylcarbonyl group having 1 to 9 carbon atoms, a phenylcarbonyl group having 1 to 4 nuclei, a naphthylcarbonyl group,
A cycloalkylcarbonyl group having 3 to 8 carbon atoms, an alkylcarbonyl group having 1 to 9 carbon atoms having a phenyl group, a branched or straight-chain alkyl group having 1 to 9 carbon atoms and a nucleus of 1
An alkylcarbonyl group having a substituted or unsubstituted phenyl group, a linear or branched alkyloxycarbonyl group having 1 to 19 carbon atoms, a phenyloxycarbonyl group, and a linear or branched alkyl group having 1 to 9 carbon atoms Represents a nitrogen atom having one kind of substituent selected from the group consisting of a phenyloxycarbonyl group whose nucleus is substituted by 1 to 4. And a compound having a carbon-hetero element double bond, preferably an aldehyde or a ketone.

The aldehydes applicable to the present invention are not particularly limited, but specific examples include ethyl formate, methoxycarbonyl aldehyde, acetaldehyde, propionaldehyde, n-butanal, isobutanal, n-pentanal, and acrolein. Crotonaldehyde, cyclohexylaldehyde, benzaldehyde, 4-methoxybenzaldehyde, 4-methylbenzaldehyde, 3,5-dimethylbenzaldehyde, 4-
Phenylbenzaldehyde, 4-chlorobenzaldehyde, 4-nitrobenzaldehyde, naphthyl-2-aldehyde, 2-furfural, cinnamaldehyde, 3-phenylpropanal, 2-benzyloxyacetaldehyde, and the like.
Primary amines and aldimine type compounds such as sulfonamides are exemplified.

The ketones applicable to the present invention are not particularly limited, but include acetophenone,
(4-methylphenyl) acetophenone, (3-methylphenyl) acetophenone, (2-methylphenyl) acetophenone, (4-ethylphenyl) acetophenone, (3-ethylphenyl) acetophenone, (2-ethylphenyl) acetophenone, (4 -I-propylphenyl) acetophenone, (3-i-propylphenyl) acetophenone, (2-i-propylphenyl) acetophenone, 1-phenylpropan-1-one, 1-
(4-methylphenyl) propan-1-one, 1- (3
-Methylphenyl) propan-1-one, 1- (2-methylphenyl) propan-1-one, 1-phenyl-n
-Butan-1-one, 1- (4-methylphenyl) -n
-Butan-1-one, 1- (3-methylphenyl) -n
-Butan-1-one, 1- (2-methylphenyl) -n
-Butan-1-one, 1-phenyl-2-methylpropan-1-one, 1- (4-phenyl) -2-methylpropan-1-one, 1- (3-phenyl) -2-methylpropane- 1-one, 1- (2-phenyl) -2-methylpropan-1-one, 1-phenyl-n-pentane-1
-One, 1-phenyl-n-hexane-1-one, 1-
Phenyl-n-heptan-1-one, 1-phenyl-n
-Octane-1-one, 1-phenyl-n-nonane-1
-One, 1-phenyl-n-decane-1-one, 1-phenyl-n-undecane-1-one, 1-phenyl-n
-Dodecane-1-one, 1-phenyl-n-tridecane-1-one, 1-phenyl-n-tetradecane-1-one, 1-phenyl-n-pentadecane-1-one, 1-
Phenyl-n-hexadecane-1-one, methyl-te
rt-butyl ketone, ethyl glyoxylate, ethyl phenyl glyoxylate, methyl phenyl glyoxylate, ethyl i-propyl glyoxylate,
Ethyl phenylethenyl glyoxylate, ethyl
Cyclohexylglyoxylate and the like can be mentioned.

The optically active pyran analog obtained by the method of the present invention can be produced by any combination of the compound having a carbon-hetero element double bond and a diene, and is not particularly limited. For example, the following general formula (7)

[0034]

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(Wherein * represents an asymmetric carbon atom, R ₁₀ ,
R ₁₂ , R ₁₃ , R ₁₄ and A have the same definitions as above. )), Specifically, 2-phenyl-
2,3-dihydro-4H-pyran-4-one, 2-benzyloxymethyl-2,3-dihydro-4H-pyran-4-one, 2-tert-butyldimethylsilyloxymethyl-2,3-dihydro- 4H-pyran-4-
On, 1-phenyl-2-phenyl-1,2,3,4-
And tetrahydropyridin-4-one. The steric shape of the carbon to which the substituents R ₁₂ , R ₁₃ and R ₁₄ are bonded differs depending on the type of catalyst and the type of reaction substrate.

In the reaction of this reaction, the compound having a carbon-hetero element double bond and the diene are usually reacted in equimolar amounts.
Compounds having a hetero element double bond may be used in a molar ratio of 0.6 to 1.5 with respect to the diene.

In the reaction of the present invention, a ligand may be added to the reaction system. Specifically, diethylamine, triethylamine, n-propylamine, di-n-propylamine, tri-n-propylamine, tert-butylamine, di-tert-butylamine, cyclohexylamine, N, N-dimethylcyclohexylamine , Piperidine, 1-methylpiperidine, 2,6-dimethylpiperidine, 1,2,6-trimethylpiperidine, 2,2,
6,6-tetramethylpiperidine, piperazine, N,
N'-dimethylpiperazine, pyridine, aniline, N,
N-dimethylaniline, 2-picoline, 2-ethylpyridine, 2,4-lutidine, 2,6-lutidine, 3,5-
Lutidine, 2,6-di-tert-butylpyridine,
2,6-bis (phenylethyl) pyridine, 2,4,6
Amines such as collidine and quinaldine, triphenylphosphine oxide, tri (2-methylphenyl)
Phosphine oxide, tri (3-methylphenyl)
Phosphine oxide, tri (4-methylphenyl)
Phosphine oxide such as phosphine oxide, methyldiphenylphosphine oxide, methoxymethyl (diphenyl) phosphine oxide, tri-n-butylphosphine oxide, tri-n-octylphosphine oxide, and tri (cyclohexyl) phosphine oxide. , Hexamethylphosphoric triamide,
Phosphoric acid triamides such as tripiperidinophosphine oxide, 1,3-dimethyl-2-imidazolidinone,
Examples thereof include 2,6-lutidine-N-oxide and the like, and if necessary, may be added in an amount of 0 to 5 times the molar amount of the salt-forming element.

As the solvent applicable to the present invention, any solvent can be applied as long as it is a solvent inert to the reaction.
Although not particularly limited, specifically, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-
Examples thereof include halogenated solvents such as trichloroethane, bromoform, and dibromomethane; ether solvents such as THF and diethyl ether; aromatic hydrocarbon solvents such as benzene and toluene; and aliphatic hydrocarbon solvents such as hexane.

In the present invention, the reaction temperature is not particularly limited since it differs depending on the substrate used in the reaction, but it can be usually carried out in the range of -78 ° C to 100 ° C. It gives high yield and high optical purity in the temperature range of 20 ° C to 50 ° C.

In the present invention, the substrate concentration is not particularly limited, but is usually 0.1% by weight based on the solvent.
The reaction is carried out in the range of ５０50% by weight.

In the present invention, the reaction time is not particularly limited because it varies depending on the type of the substrate and the type of the catalyst used in the reaction, but the reaction is usually completed within 96 hours.

In the present invention, the post-treatment operation after completion of the reaction is not particularly limited, but as a specific example, after adding an appropriate amount of trifluoroacetic acid, then adding pyridine and water and extracting with dichloromethane. , Drying over magnesium sulfate and concentrating to obtain a crude target product. In purifying the target substance, a method using silica gel thin layer chromatography or a separation column, or a general method such as distillation or recrystallization can be used.

[0043]

According to the present invention, it is possible to reduce the amount of a binaphthol-phosphoric acid catalyst used as a catalyst, which is industrially extremely significant.

[0044]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited only to these examples.

(Measurement of optical rotation) SORI manufactured by HORIBA
Use -300.

(Measurement of melting point) MP-500 manufactured by Yanaco Co., Ltd.
Use D.

(Measurement of ¹ H-NMR and ¹³ C-NMR) V
arian Gemini-200 (200MH
z).

(Measurement of MASS) Hitachi M-80B was used.

(IR measurement) A 2000FT-IR manufactured by Perkin Elmer was used.

(Test of Optical Purity) The test was performed by high performance liquid chromatography equipped with a chiral column OD-H of Daicel Co., Ltd., elution solvent: Hexane / i-PrOH.
= 2/1 to 100/1 (vol / vol) at a flow rate of 0.5 to 1 ml / min.

Example 1 Preparation of 2-phenyl-2,3-dihydro-4H-pyran-4-one A catalyst (scandium tris (R)-(-)-) was placed in a 5 ml round bottom flask containing a magnetic stirrer. 5,6,7,
8,5 ′, 6 ′, 7 ′, 8′-octahydro-1,1 ′
-Binaphthyl-2,2'-diyl phosphate tetrahydrate)
6.6 mg (5.9 μmol), molecular sieves 4A (20 mg) and 0.6 ml of dichloromethane were added, followed by benzaldehyde (20 μl, 0.2 mmol).
l), 1-methoxy-3-trimethylsilyloxy-
1,3-butadiene (purity: 90%, 60.0 μl,
0.3 mmol) and reacted at room temperature for 16 hours. After completion of the reaction, two drops of trifluoroacetic acid were added with a microsyringe and then three drops of pyridine were added with a microsyringe, and the reaction solution was directly purified on a thin-layer silica gel plate for separation (hexane / ethyl acetate = 2/1). As a result, 29.8 mg of the desired product (R) -2-phenyl-2,3-dihydro-4H-pyran-4-one was obtained. As a result of analysis, the yield was 87% and the optical purity was 95% (R).

Comparative Example 1 Production of 2-phenyl-2,3-dihydro-4H-pyran-4-one A catalyst (scandium tris (R)-(-)-) was placed in a 5 ml round bottom flask containing a magnetic stirrer. 5,6,7,
8,5 ′, 6 ′, 7 ′, 8′-octahydro-1,1 ′
-Binaphthyl-2,2'-diyl phosphate tetrahydrate)
6.6 mg (5.9 μmol), dichloromethane 0.6
ml, followed by benzaldehyde (20 μl,
0.2 mmol), 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (purity: 90%, 60.
0 μl, 0.3 mmol) and reacted at room temperature for 16 hours. After completion of the reaction, two drops of trifluoroacetic acid were added with a microsyringe and then three drops of pyridine were added with a microsyringe, and the reaction solution was directly purified on a thin-layer silica gel plate for separation (hexane / ethyl acetate = 2/1). To obtain the desired product (R) -2-phenyl-2,3
24.7 mg of -dihydro-4H-pyran-4-one were obtained. As a result of analysis, the yield was 72% and the optical purity was 87% (R)
Met.

Examples 2 to 4 Using the same reactor as in Example 1, the reaction was carried out under the conditions shown in Table 1. The results are shown in Table 1. The reaction was performed under the same conditions as in Example 1 except for the conditions described in Table 1.

[0054]

[Table 1]

Comparative Examples 2 to 4 Using the same reactor as in Comparative Example 1, the reaction was carried out under the conditions shown in Table 2. The results are shown in Table 2. The reaction was performed under the same conditions as in Comparative Example 1 except for the conditions described in Table 2.

[0056]

[Table 2]

Example 5 Preparation of 2-phenyl-2,3-dihydro-4H-pyran-4-one A catalyst (scandium tris (R)-(-)-) was placed in a 5 ml round bottom flask containing a magnetic stirrer. Tetrahydrate of 1,1′-binaphthyl-2,2′-diylphosphate) 2
1.7 mg (19.8 μmol), molecular sieves 4A (40 mg), dichloromethane 2.0 ml, 2,
6-Lutidine in dichloromethane solution (0.515M) 2
0 μl (19.8 μmol) was added, followed by benzaldehyde (20 μl, 0.2 mmol) and 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (purity: 90%, 60.0 μl, 0.3 mmol). The mixture was added and reacted at room temperature for 16 hours. After completion of the reaction, two drops of trifluoroacetic acid were added with a microsyringe and then three drops of pyridine were added with a microsyringe, and the reaction solution was directly purified on a thin-layer silica gel plate for separation (hexane / ethyl acetate = 2/1). (R)
-2-phenyl-2,3-dihydro-4H-pyran-
32.2 mg of 4-one were obtained. As a result of analysis, the yield was 94.
% And an optical purity of 81% (R).

Comparative Example 5 Production of 2-phenyl-2,3-dihydro-4H-pyran-4-one A catalyst (scandium tris (R)-(-)-1) was placed in a 5 ml round bottom flask containing a magnetic stirrer. , 1'-binaphthyl-2,2'-diylphosphate tetrahydrate) 21.
7 mg (19.8 μmol), molecular sieves 4
A (40 mg) and 2.0 ml of dichloromethane were added,
Subsequently, benzaldehyde (20 μl, 0.2 mmol
l), 1-methoxy-3-trimethylsilyloxy-
1,3-butadiene (purity: 90%, 60.0 μl,
0.3 mmol) and reacted at room temperature for 16 hours. After completion of the reaction, two drops of trifluoroacetic acid were added with a microsyringe and then three drops of pyridine were added with a microsyringe, and the reaction solution was directly purified on a thin-layer silica gel plate for separation (hexane / ethyl acetate = 2/1). As a result, 30.5 mg of the desired product (R) -2-phenyl-2,3-dihydro-4H-pyran-4-one was obtained. As a result of analysis, the yield was 89% and the optical purity was 56% (R).

Claims (2)

[Claims] 1. A method for producing an optically active pyran analog by reacting a diene with a compound having a carbon-hetero element double bond in the presence of a catalyst, comprising the following general formula (1): (2), general formula (3) or general formula (4)
Binaphthol-phosphate derivative represented by the formula Embedded image [In the above general formula (1) or general formula (2), R ₁ , R ₂ , R
₃ and R ₄ are each independently hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a branched or linear alkenyl group having 1 to 20 carbon atoms, or a branched chain having 1 to 20 carbon atoms. Or a straight-chain alkynyl group, a phenyl group, a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms, a branched or straight-chain alkenyl having 1 to 10 carbon atoms A phenyl group in which the nucleus is substituted by 1 to 4 carbon atoms, a phenyl group in which the nucleus is substituted by the branched or straight-chain alkynyl group having 1 to 10 carbon atoms, a naphthyl group, or a cycloalkyl having 3 to 8 carbon atoms. Represents an alkyl group.
However, R _{1 to} R ₄ are not simultaneously hydrogen. M is 3
Represents a metal element capable of forming a multivalent metal ion. ] Embedded image [In the general formula (3) or the general formula (4), R ₅ , R ₆ , R
₇ and R ₈ are each independently hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a branched or linear alkenyl group having 1 to 20 carbon atoms, or a branched chain having 1 to 20 carbon atoms. Alkynyl group, phenyl group, branched or straight-chain phenyl group having 1 to 10 carbon atoms and a nucleus substituted by an alkyl group, branched or straight-chain alkenyl having 1 to 10 carbon atoms A phenyl group in which the nucleus is substituted by 1 to 4 carbon atoms, a phenyl group in which the nucleus is substituted by the branched or straight-chain alkynyl group having 1 to 10 carbon atoms, a naphthyl group, or a cycloalkyl having 3 to 8 carbon atoms. Represents an alkyl group.
M represents a metal element capable of forming a trivalent metal ion. ]
A method for producing an optically active pyran analog, comprising reacting in the presence of an asymmetric synthesis catalyst containing aluminosilicate. 2. A diene compound represented by the following general formula (5): [Wherein, R ₉ , R ₁₀ , R ₁₁ and R ₁₂ each independently represent hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a branched or linear alkyl group having 1 to 20 carbon atoms, An alkenyl group, a branched or straight-chain alkynyl group having 1 to 20 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms,
A branched or straight-chain alkyloxy group having 20 carbon atoms, a branched or straight-chain dialkylamino group having 1 to 20 carbon atoms, or a branched or straight-chain trialkylsilyloxy group having 1 to 20 carbon atoms. And a compound having a carbon-hetero element double bond is represented by the following general formula (6): [Wherein, R ₁₃ represents hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms, or Branched alkynyl group, phenyl group, carbon number 1-1
A phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group of 0, a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkenyl group having 1-10 carbon atoms, A phenyl group whose nucleus is substituted with 1 to 10 branched or straight-chain alkynyl groups,
0 branched or straight-chain alkoxy group having 1 to 4 nuclei
A phenyl group, a naphthyl group, a cycloalkyl group having 3 to 8 carbon atoms, an alkyl group having 1 to 10 carbon atoms having a phenyl group, a branched or straight-chain alkyl group having 1 to 10 carbon atoms and a nucleus of 1 Represents an alkyl group having a -4-substituted phenyl group. R ₁₄ is a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched alkenyl group having 1 to 20 carbon atoms, a linear or branched alkynyl group having 1 to 20 carbon atoms, phenyl Group, carbon number 1
10 to 10 branched or linear alkyl groups having 1 to 1 nucleus
A 4-substituted phenyl group, a phenyl group substituted with 1 to 4 nuclei by a branched or straight-chain alkenyl group having 1 to 10 carbon atoms, a nucleus represented by a branched or straight-chain alkynyl group having 1 to 10 carbon atoms, 1-4 substituted phenyl group, carbon number 1
10 to 10 branched or linear alkoxy groups having 1 nucleus
4 to 4 substituted phenyl group, naphthyl group, 3 to 8 carbon atoms
Having 1 to 1 carbon atoms having a cycloalkyl group and a phenyl group
An alkyl group having 0, an alkyl group having a phenyl group whose nucleus is substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms, and a straight-chain or branched alkylcarbonyl group having 1 to 19 carbon atoms. A straight-chain or branched alkenylcarbonyl group having 1 to 19 carbon atoms,
9 linear or branched alkynylcarbonyl groups,
A phenylcarbonyl group, a phenylcarbonyl group in which the nucleus is substituted by 1 to 4 carbon atoms with a branched or straight-chain alkyl group having 1 to 9 carbon atoms; 4-substituted phenylcarbonyl group, C1-C9 branched or straight-chain alkynyl group, phenylcarbonyl group whose nucleus is substituted by 1-4, naphthylcarbonyl group, C3-C8 cycloalkylcarbonyl group, An alkylcarbonyl group having 1 to 9 carbon atoms having a phenyl group, an alkylcarbonyl group having a phenyl group having 1 to 4 carbon atoms and a nucleus substituted by a branched or straight-chain alkyl group, 1 to 19 carbon atoms; A linear or branched alkyloxycarbonyl group, a phenyloxycarbonyl group, a linear or branched alkyl group having 1 to 9 carbon atoms It represents a 1-4-substituted phenyloxy group, R ₁₃ and R ₁₄ are not equal. A represents an oxygen atom, a sulfur atom, a selenium atom, or a C1-20
A linear or branched alkyl group having 1 to 20 carbon atoms
Linear or branched alkenyl group having 1 to 2 carbon atoms
0 straight-chain or branched alkynyl group, phenyl group, phenyl group having 1 to 10 carbon atoms and a nucleus substituted by 1 to 4 branched or straight-chain alkyl groups, 1 to 10 carbon atoms
A phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkenyl group; a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkynyl group having 1-10 carbon atoms; A phenyl group, a naphthyl group, a nucleus of which is substituted by 1 to 4 nuclei with 10 branched or linear alkoxy groups;
A cycloalkyl group having 3 to 8 carbon atoms, an alkyl group having 1 to 10 carbon atoms having a phenyl group, and a phenyl group having a nucleus 1-4 substituted by a branched or straight-chain alkyl group having 1 to 10 carbon atoms. Having an alkyl group, a linear or branched alkenylcarbonyl group having 1 to 19 carbon atoms, a linear or branched alkynylcarbonyl group having 1 to 19 carbon atoms, a phenylcarbonyl group, a branched or straight-chain having 1 to 9 carbon atoms. A phenylcarbonyl group whose nucleus is substituted by 1 to 4 carbon atoms with a chain alkyl group; a phenylcarbonyl group whose nucleus is substituted by 1 to 4 carbon atoms with a branched or straight-chain alkenyl group having 1 to 9 carbon atoms; A phenylcarbonyl group, a naphthylcarbonyl group, a cycloalkylcarbonyl group having 3 to 8 carbon atoms, wherein the nucleus is substituted by a branched or straight-chain alkynyl group by 1 to 4 groups; An alkylcarbonyl group having 1 to 9 carbon atoms having a phenyl group, an alkylcarbonyl group having a phenyl group having 1 to 4 carbon atoms and a nucleus substituted by a branched or straight-chain alkyl group, 1 to 19 carbon atoms; Selected from the group consisting of a straight-chain or branched alkyloxycarbonyl group, a phenyloxycarbonyl group, and a phenyloxycarbonyl group having a nucleus 1-4 substituted by a straight-chain or branched alkyl group having 1 to 9 carbon atoms. Represents a nitrogen atom having a kind of substituent. And an optically active pyran analog represented by the following general formula (7): (In the formula, * represents an asymmetric carbon atom, and R ₁₀ , R ₁₂ , R ₁₃ ,
R ₁₄ and A have the same definition as above. The method according to claim 1, wherein: