JP2002275112A - Binaphthol compound and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new compound which can favorably be synthesized and is useful as a ligand for asymmetric synthesis catalysts, and to provide a method for producing the same. SOLUTION: The binaphthol compound represented by the general formula [I] (R1 and R2 are each H, a halogen or a 1 to 3C haloalkyl; R3 and R4 are each H, a 1 to 3C alkyl, a 1 to 3C alkoxy or benzyloxy which may be substituted; R5 to R8 are each H, a halogen, a 1 to 6C alkyl or an aryl; or R5 and R6 may together form a saturated or unsaturated carbon ring), and a method for producing the same.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel binaphthol compound useful as a ligand of an asymmetric synthesis catalyst and a method for producing the same.

[0002]

BACKGROUND ART Chiral zirconium catalysts having a compound similar to the compound of the present invention as a ligand include, for example,
JP-A-11-33407, JP-A-11-2538
No. 13, the asymmetric imino aldol reaction,
It is described that it is useful for asymmetric cyanation reaction and the like.
Further, a method for producing a binaphthol compound similar to the compound of the present invention is described in Tetrahedron Lett. , 40 , 2
161-2164 (1999), Tetrahedro
n Lett. , 39 , 7917-7920 (199).
8).

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel compound which can be synthesized industrially advantageously and which is useful as a ligand of an asymmetric synthesis catalyst, and a process for producing the same.

[0004]

SUMMARY OF THE INVENTION The present invention firstly provides a compound of the general formula
[I]

[0005]

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(Where R₁, R₂Are each independently
Hydrogen atom, halogen atom or C₁~ C ₃Haloalkyl group
And R₃, R₄Is independently a hydrogen atom, C
₁~ C ₃Alkyl group, C₁~ C₃Alkoxy group or substitution
Represents a benzyloxy group which may be₅, R₆, R
₇, R₈Are each independently a hydrogen atom, a halogen atom
Child, C₁~ C₆Represents an alkyl group or an aryl group. Ma
R₅And R₆Are saturated or unsaturated bonds together
May be formed. Binaf represented by)
A toll compound is provided. In addition, the present invention secondly provides a general
Formula [II]

[0007]

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(Wherein R ₁ and R ₂ have the same meanings as described above, and L represents a hydroxyl-protecting group), and a compound represented by the general formula [III]

[0009]

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Wherein R ₅ , R ₆ , R ₇ and R ₈ have the same meanings as described above, and L ′ represents a hydroxyl-protecting group. [IV]

[0011]

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(Wherein R ₁ , R ₂ , R ₅ , R ₆ , R ₇ ,
R ₈ , L and L ′ represent the same meaning as described above. The present invention provides a method for producing a binaphthol compound represented by the formula:

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION In the general formula [I],
R ₁ , R ₂ , R ₅ , R ₆ , R ₇ and R ₈ are not particularly limited as long as they do not inhibit the function as an asymmetric catalyst when used as ligands of the asymmetric catalyst. Absent. As preferred specific examples thereof, R ₁ and R ₂ each independently represent a hydrogen atom; a halogen atom such as fluorine, bromine, chlorine and iodine; and C _{1 to} C ₃ such as a trifluoromethyl and pentafluoroethyl group. A haloalkyl group; R ₃ and R ₄ each independently represent a hydrogen atom; C such as methyl, ethyl, propyl, isopropyl, etc.
₁ -C ₃ alkyl group; methoxy, ethoxy, n- propoxy, _C 1 -C ₃ alkoxy groups such as an isopropoxy group;
Or a benzyloxy group which may be substituted; Examples of the substituent of the benzyloxy group include a halogen atom such as fluorine, chlorine, and bromine; a C _{1 to} C ₆ alkyl group such as a methyl and ethyl group; methoxy, ethoxy, n-
A C ₁ -C ₆ alkoxy group such as a propyl and isopropyl group; a nitro group; and the like. Further, the benzoyloxy group may have a plurality of the same or different substituents.

R ₅ , R ₆ , R ₇ and R ₈ are each independently a hydrogen atom; a halogen atom such as fluorine, bromine, chlorine and iodine; methyl, ethyl, propyl, isopropyl, n-butyl, And C ₁ -C ₆ alkyl groups such as tertiary butyl and n-hexyl groups; and aryl groups such as phenyl and naphthyl groups. Also, R ₅ and R
_{6 together, -CH 2 -CH 2 -CH 2 -CH} 2
A carbon ring having 5 to 8 carbon atoms (including carbon atoms of an aromatic ring) represented by-or -CH = CH-CH = CH- or the like may be formed.

The compound of the present invention represented by the general formula [I] is as follows:
As shown in the above reaction formula, R₃And R ₄Depending on the group represented by
It can be produced by appropriately selecting a reaction method. 1) Production method 1: R₃And R₄Is a hydrogen atom
Manufacture

[0016]

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(Wherein, R ₁ , R ₂ , R ₅ , R ₆ , R ₇ and R ₈ have the same meanings as described above, and L and L ′ each represent a leaving group for a hydroxyl group. Is an alkoxyalkyl group such as methoxymethyl or 2- (2-ethoxy) ethyl group; an oxygen-containing heterocyclic group such as tetrahydrofuranyl group or tetrahydropyranyl group; a trityl group; a trimethylsilyl group or a t-butyldimethylsilyl group. A silyl group; and the like.)

Among the compounds represented by the general formula [I], R ₃
And compound [I-1] wherein R ₄ is a hydrogen atom, can be obtained by reacting compound [II] and compound [III] in an organic solvent in the presence of a base at −100 ° C. to 50 ° C. for 1 hour to several tens of hours. The compound represented by the formula [VI] can be obtained by reacting for a period of time, followed by hydrolysis to remove the protecting group, followed by reduction.

The organic solvents used in this reaction include:
There is no particular limitation as long as the solvent is inert to the reaction. For example, diethyl ether, tetrahydrofuran (THF)
Ether solvents such as n-pentane, n-hexane and cyclohexane; aromatic hydrocarbon solvents such as benzene, toluene and xylene; N, N-dimethylformamide (DMF), N, N- Amide solvents such as dimethylacetamide; and the like.

As the base, organic lithium such as methyllithium, ethyllithium, n-butyllithium, sec-butyllithium, t-butyllithium, lithium diisopropylamide and lithium hexamethyldisilazide can be used. .

The hydrolysis reaction for removing the protecting group is carried out by using a mineral acid such as hydrochloric acid, sulfuric acid or nitric acid in an organic solvent such as an alcohol-based solvent, an ether-based solvent, a hydrocarbon-based solvent or a halogen-based solvent at 0 ° C. to room temperature. The reaction is performed by Examples of the alcohol-based solvent include methanol, ethanol, propyl alcohol and the like. Examples of the ether solvent include diethyl ether, THF, 1,
2-dimethoxyethane and the like. Examples of the hydrocarbon solvent include n-hexane, cyclohexane, benzene, toluene and the like. Examples of the halogen-based solvent include dichloromethane, chloroform, carbon tetrachloride and the like. ,

The reduction reaction is carried out at 0 ° C. in a solvent such as trifluoroacetic acid using a reducing agent such as lithium aluminum hydride, sodium borohydride or borane as a reducing agent.
To room temperature.

2) Production method 2: R ₃ and R ₄ are C ₁ -C ₃
Preparation of a compound that is an alkoxy group or an optionally substituted benzyloxy group

[0024]

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Among the compounds represented by the general formula [I], R
Compounds in which ₃ and R ₄ are a C ₁ -C ₃ alkoxy group or an optionally substituted benzyloxy group ([I-3], [I-
4]) converts the compound represented by the general formula [IV] obtained above into an alkyl halide in an organic solvent in the presence of a base,
After reacting with a compound represented by the formula R ₉ -X (R ₉ represents a C ₁ -C ₃ alkoxy group or an optionally substituted benzyloxy group, and X represents a halogen atom) such as benzyl halide. , By hydrolysis to remove the protecting group.

The solvent used in this reaction is n-
Aliphatic hydrocarbon solvents such as pentane, n-hexane, n-heptane and cyclohexane; aromatic hydrocarbon solvents such as benzene, toluene, xylene, dichlorobenzene;
Ether solvents such as diethyl ether, THF, 1,2-dimethoxyethane and dioxane; DMF, N, N-
Amide solvents such as dimethylacetamide; dimethylsulfoxide (DMSO), acetonitrile and the like.

Examples of the base include organic bases such as triethylamine, diisopropylethylamine, piperidine, pyridine, toluidine and picoline; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metals such as magnesium hydroxide and calcium hydroxide. Alkali metal carbonates such as sodium carbonate and potassium carbonate; alkaline earth metal carbonates such as magnesium carbonate and calcium carbonate; and the like.

After completion of the reaction, the desired product can be obtained by ordinary purification means. The structure of the compound of the present invention is represented by NMR
It can be determined by spectrum, IR spectrum, MS spectrum, elemental analysis (EA) and the like.

The compounds of the present invention are useful as ligands for asymmetric catalysts. For example, according to the method described in JP-A-11-33407, zirconium may be used as an asymmetric zirconium catalyst as an active center atom, or an asymmetric synthesis catalyst may be obtained by using it as a ligand of another metal compound.

[0030]

The compounds of the present invention are described in more detail with reference to the following examples. Example 1 Production of (R) -3- (2 ″ -hydroxy-3 ″ -isopropylphenyl) methyl-1,1′-bi-2-naphthol (Compound No. 5)

[0031]

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(Wherein MOM represents a methoxymethyl group) (R) -2,2'-bis (methoxymethyloxy)-
In a solution of 1,1′-binaphthalene (8.92 mmol) in diethyl ether (150 ml), 1.56 M hexane solution of n-butyllithium (10.8 mmol) and N, N, N ′, N′-tetramethylethylenediamine (TMEDA, 10.9 mmol) was added at room temperature and stirred for 1 hour. The solution was cooled to -78 ° C and
A solution of-(methoxymethyloxy) -3-isopropylbenzaldehyde (5.09 mmol) in diethyl ether (15 ml) was added dropwise. Further, the mixture was added to -7
The mixture was stirred overnight while gradually warming from 8 ° C. to room temperature.
Thereafter, a saturated aqueous ammonium chloride solution (120 ml) was added, and the organic layer was separated.
ml) twice. All organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain compound [I] at a yield of 58%.

A solution of compound [I] (2.74 mmol) in dichloromethane (3 ml) was cooled to 0 ° C., and saturated HCl / methanol (2 ml) was added thereto. The mixture was stirred for 2 hours, and saturated aqueous sodium hydrogen carbonate solution (20 m
l) was added. This is diluted with dichloromethane (20 ml)
After extraction, the organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained crude product [II] was dissolved in dichloromethane (10 ml). Thereto, sodium borohydride (27.5 mmol) was added, and 0 ° C.
And the suspension was added to trifluoroacetic acid (TFA, 1
(0 ml) in dichloromethane (10 ml) was slowly added dropwise, and the mixture was stirred overnight while gradually warming to room temperature. Thereafter, the mixture was cooled again to 0 ° C., a saturated aqueous sodium hydrogen carbonate solution (40 ml) was added, and the mixture was added with dichloromethane (20 ml).
Extracted. All organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography and recrystallization to give the title compound in a yield of 5%.
5% (two steps).

When a ketone is used in place of benzaldehyde, a compound in which R ₃ and R ₄ are alkyl groups can be synthesized in the same manner.

Example 2 3- (S)-[1- (2-hydroxy-3-isopropylphenyl) -1-methoxymethyl]-(R) -1,
Production of 1'-bi-2-naphthol (Compound Nos. 13, 14)

[0036]

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Compound D of compound [I] (0.956 mmol)
The MF (10 ml) solution was cooled to 0 ° C., sodium hydride (3.3 mmol) was added, and the mixture was stirred at room temperature for 30 minutes.
The solution was cooled again to 0 ° C and methyl iodide (10.7
mmol) was added dropwise. After further stirring at the same temperature for 1.5 hours, a saturated aqueous ammonium chloride solution (40 ml) was added.
Extracted three times with diethyl ether (40 ml). All the organic layers were combined, washed with water and saturated saline, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product of compound [III]. This crude product was dissolved in dichloromethane (14ml) and cooled to 0 ° C. Thereto, saturated HCl / methanol (4 ml) was added dropwise.
The mixture was stirred at the same temperature for 5 hours. A saturated aqueous sodium hydrogen carbonate solution (30 ml) was added to the reaction mixture, and dichloromethane (3
0 ml). All organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography to obtain a diastereomer in a combined yield of 75% (two steps). Table 1 shows typical examples of the compounds of the present invention including the above Examples. Table 2 shows physical property data. The abbreviations in the table represent the following meanings. Me: methyl, Et: ethyl, Ph: phenyl, tB
u: tert-butyl, i-Pr: isopropyl, B
n: benzyl

[0038]

[Table 1]

[0039]

[Table 2]

[0040]

[Table 3]

[0041]

The following is an example of performing asymmetric synthesis using the compound of the present invention as a ligand of an asymmetric synthesis catalyst. (Reference Example 1)

[0042]

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Zr (Ot-Bu) ₄ (0.0454 mm
ol), the compound obtained in Example 1 as a ligand (Li
gand, 0.0681 mmol) and N-methylimidazole (NMI, 0.135 mmol) were mixed in toluene (1 ml) at room temperature and stirred for 1 hour to prepare a catalyst. Thereafter, the solution was cooled to -20 ° C,
A solution of imine (VII, 0.454 mmol) in toluene (0.5 ml) and ketene silyl acetal (VIII,
0.564 mmol) of a toluene solution (0.5 ml) was added and reacted at the same temperature for 20 hours. A saturated aqueous sodium hydrogen carbonate solution (15 ml) was poured into the reaction mixture, and the mixture was extracted three times with dichloromethane (15 ml). All organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was cooled in an ice bath, and thereto was added 10 ml of a 1N-HCl / THF = 1/20 solution,
The reaction was performed at 0 ° C. for 1.5 hours. A saturated aqueous sodium hydrogen carbonate solution (15 ml) was poured into the reaction mixture, and the mixture was extracted three times with dichloromethane (15 ml). All the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 128.7 mg (yield: 95%) of a product. Obtained. The enantiomeric excess of the product was determined by liquid chromatography (Daicel; Chiralc).
el AD, n-hexane / 2-propanol = 9 /
As a result of analysis from 1), it was 94% ee (S). (Reference Example 2)

[0044]

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Zr (Ot-Bu) ₄ (0.0422 mm)
ol), the compound ligand obtained in Example 1 (Ligan
d, 0.0845 mmol) and N-methylimidazole (NMI, 0.128 mmol) in benzene (1 m
In 1), the mixture was mixed at room temperature and stirred for 1 hour to prepare a catalyst. Imine (VII, 0.422 m
mol) of benzene (0.5 ml) and a benzene solution (0.5 ml) of ketene silyl acetal (VIII, 0.550 mmol) were added at room temperature, and reacted at the same temperature for 20 hours. A saturated aqueous sodium hydrogen carbonate solution (15 ml) was poured into the reaction mixture, and the mixture was diluted with dichloromethane (15 ml).
Extracted. The organic layers were combined, dried over anhydrous sodium carbonate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was cooled in an ice bath, 10 ml of a 1N-HCl / THF = 1/20 solution was added thereto, and the mixture was reacted at 0 ° C. for 2 hours. A saturated aqueous sodium hydrogen carbonate solution (15 ml) was poured into the reaction mixture,
Extracted three times with dichloromethane (15 ml). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the product (120.5 mg) in a yield of 95%. The enantiomeric excess of the product was determined by liquid chromatography (Daicel; Chiralc).
el AD, n-hexane / 2-propanol = 9 /
As a result of analysis from 1), it was 92% ee (S).

As described above, the compound of the present invention can be easily produced and is useful as an asymmetric synthesis catalyst.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) C07C 43/178 C07C 43/178 D 43/23 43/23 C // B01J 31/22 B01J 31/22 Z F term ( Reference) 4G069 AA06 AA08 BA27B BC51B BE13B BE36B BE38B CB57 DA02 FA01 4H006 AA01 AA02 AB40 AC41 FC52 FC54 FE11 FE13 GP01 GP03

Claims (2)

[Claims] 1. A compound of the formula [I](Where R₁, R₂Are each independently a hydrogen atom,
Logen atom or C₁~ C ₃Represents a haloalkyl group,
R₃, R₄Is independently a hydrogen atom, C₁~ C ₃
Alkyl group, C₁~ C₃Alkoxy or substituted
Represents a good benzyloxy group,₅, R₆, R₇And R
₈Is independently a hydrogen atom, a halogen atom, C₁
~ C₆Represents an alkyl group or an aryl group. Also, R₅When
R₆Is a coal having a saturated or unsaturated bond
It may form a ring. Binaphthol compound represented by)
object. 2. A compound of the formula [II](Where R₁, R₂Are each independently a hydrogen atom,
Logen atom or C₁~ C ₃Represents a haloalkyl group, and L is
Represents a protecting group for a hydroxyl group. ) And a compound of the formula [II
I](Where R₅, R₆, R₇And R₈Are independent
And a hydrogen atom, a halogen atom, C₁~ C₃Alkyl group
Represents an aryl group, and L 'represents a hydroxyl-protecting group. Ma
R₅And R₆Are saturated or unsaturated bonds together
May be formed. Compound represented by)
With the general formula [IV] characterized by reacting(Where R₁, R₂, R₅, R₆, R₇, R₈, L and
L 'has the same meaning as described above. Binaf represented by)
A method for producing a tall compound.