JP2981621B2 - Biphenyl bisphosphine complex - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a biphenylbisphosphine complex used as a catalyst for an asymmetric hydrogenation reaction or the like.

(Prior Art) Conventionally, asymmetric hydrogenation catalysts are extremely important for the synthesis of optically active amino acids, the synthesis of various reagents and the synthesis of intermediates, and many studies have been made. For example, a ruthenium complex coordinated with 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (hereinafter abbreviated as BINAP) (JP-A-64-68387) or a rhodium complex (JP-A-55 -61937).

Also, in the 37th Symposium on Organometallic Chemistry, pp. 370-372 (1990), a rhodium complex coordinated with 2,2′-bis (dicyclohexylphosphino) -6,6′-dimethylbiphenyl (BICHEP and Are abbreviated).

Conventionally, both complexes in which a ruthenium or rhodium metal is coordinated to a bisphosphine ligand do not always show excellent catalytic activity and enantioselectivity.

(Problems to be Solved by the Invention) An object of the present invention is to provide a biphenylbisphosphine complex in which both ruthenium and rhodium metals can be used while maintaining high catalytic activity and enantioselectivity.

(Means for Solving the Problems) As a result of intensive studies on a hydrogenation catalyst having high catalytic activity and enantioselectivity, the present inventors have found that, in the biphenylbisphosphine complex, the 4-, 4 'of the biphenyl group is present.
By introducing specific substituents at the-, 5-, 5 '-, 6- and 6'-positions, both ruthenium and rhodium complexes (general formula (I)) can exhibit excellent catalytic activity and enantioselectivity. The present inventors have found what has been shown, and have made the present invention based on this finding.

That is, the present invention [Wherein, A represents an arene or an olefin group, X represents a halogen atom or an olefin group, Y represents a halogen atom,
Represents boron tetrafluoride, tetraphenyl boron, phosphorus hexafluoride, perchloric acid, Z represents ruthenium, rhodium atom,
R ¹ represents a cyclohexyl group, a phenyl group (which may be substituted with an alkyl group or an alkoxy group), R ² represents a lower alkyl group or a lower haloalkyl group, R ³ represents a lower alkoxy group, R ⁴ represents a lower alkyl group, Shows a lower haloalkyl group. And a biphenylbisphosphine complex represented by the following formula:

The compound represented by the general formula (I) of the present invention can be easily produced according to the following scheme 1.

The dihalobiphenyl compound of the general formula (II) is reacted with t-butyllithium and a chlorodisubstituted phosphine oxide in a tetrahydrofuran solvent at -70 ° C for 30 minutes to obtain a general formula (III) (method A).

Alternatively, the general formula (III) is obtained by reacting the dihalogenated biphenyl compound of the general formula (II) with chlorodisubstituted phosphine in a tetrahydrofuran solvent and then oxidizing with hydrogen peroxide or the like (method) B).

Thus, the obtained racemic biphenylbisphosphoryl compound of the general formula (III) is converted to (-) or (+)
Optical resolution by a method using -dibenzoyltartaric acid gives the (R) -form or the (S) -form general formula (III).

The (R) or (S) -biphenylbisphosphine compound of the general formula (IV) is a compound of the general formula (II) in the (R) or (S) form.
It is obtained by reducing I) by a method using trichlorosilane-tertiary amine.

The thus obtained (R) or (S) -biphenylbisphosphine compound of the general formula (IV) and the general formula [ZAXl] mYn (V) (wherein Z represents a ruthenium or rhodium atom, and A represents Arenes, olefin groups, X represents a halogen atom or an olefin group, Y represents a halogen atom, boron tetrafluoride, tetraphenyl boron, phosphorus hexafluoride, perchloric acid
3, n represents an integer of 0 to 1. The compound represented by the general formula (I) can be obtained by reacting the compound represented by the formula (1) with an inert solvent such as alcohols and halogenated hydrocarbons.

General formula (V) can be easily obtained according to a conventional method.

In addition, as the arenes described above, p-cymene,
Examples of m-cymene, o-cymene, benzene and the like and olefin groups include norbornadiene, 1,5-hexadiene, 1,5
-Cyclooctadiene, 1,3-butadiene, 1,3-cyclohexadiene, two molecules of ethylene and the like may be used. In the general formula (V), when Z is ruthenium, A
Is an arene, X is a halogen atom, l and m are 2, n
Represents an integer of 0. When Z is rhodium, A and X each represent an olefin group, l is 3, m and n are complexes derived from a compound represented by an integer of 1 [general formula (I)] is asymmetric hydrogenation. It shows good results as a catalyst for use.

In addition, a complex represented by the general formula (I) wherein Y is a halogen ion is converted into an alcohol or a halogenated hydrocarbon solvent,
A boron tetrafluoride ion or tetraphenyl boron ion complex can be easily produced by reacting with silver tetrafluoride or silver tetraphenyl boride according to a conventional method.

Represented by the general formula (II) which is a starting compound of the above reaction
2,2'-dibromo-5,5'-dimethoxy-4,4 ', 6,6'-
Tetramethylbiphenyl ・ 2,2′-diiodo-4,4 ′, 6,
6'-Tetra (trifluoromethyl) biphenyl is also a novel compound, and is produced from 2,6-dimethylnitrobenzene / 2,4-bis (trifluoromethyl) bromobenzene according to the following reaction formula.

a: I ₂ , HIO ₄ / AcOH b: 1.Fe, H ₂ SO ₄ / H ₂ O; 2.dry-HCl / MeOH c: 1.Iosamyl Nitrite / 1,4-magnesium, AcOH; 2.MeO
H d: Cu / Sulfolane e: Br ₂ , AcOH f: HNO ₃ , H ₂ SO ₄ g: Cu / Sulfolane h: Pd-C / AcOH i: 1.NaNO ₂ , H ₂ SO ₄ / AcOH; 2. KI / H ₂ O (Effect of the Invention) The biphenylbisphosphine complex of both ruthenium and rhodium represented by the general formula (I) exhibits excellent catalytic activity and enantioselectivity, and thus can be widely used as a hydrogenation catalyst. Moreover, the catalyst can be easily prepared, and exhibits high activity without purification. Therefore, the present invention was able to provide a novel chemical substance having excellent versatility and excellent properties.

(Examples) Hereinafter, the present invention will be specifically described with reference to Examples, Reference Examples, and Test Examples.

Example 1 (R) -2,2'-bis (diphenylphosphino) -5,5 '
Synthesis of -dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl (Compound 1) In a pressure tube, 30 ml of dried and degassed chlorobenzene was synthesized in Reference Example 5 using (R) -2,2'-bis ( 671 mg (0.001 mol) of diphenylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl was dissolved. Next, 4.86 g (0.048 mol) of triethylamine was added, and 5.42 g (0.04 mol) of trichlorosilane was added under ice-cooling. After purging with argon, the tube was sealed and stirred at 140 ° C. for 5 hours. The yellow reaction solution was ice-cooled again, a degassed 30% aqueous sodium hydroxide solution was added until the white suspension of the reaction solution was dissolved, and the mixture was purged with argon and stirred at 70 ° C. for 30 minutes. After cooling to room temperature, 70 ml of chlorobenzene was added, and the separated organic layer was washed with 30 ml of water.
The mixture was washed successively with 30 ml of a saturated saline solution, dried with anhydrous magnesium sulfate after purging with argon. After chlorobenzene was distilled off under reduced pressure, the white solid residue was separated and purified by silica gel chromatography (chloroform solvent) to give (R) -2,
428 mg of 2'-bis (diphenylphosphino) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl (compound 1) was obtained. The yield was 67%. Table 1 shows the results.

Examples 2 to 8 The same procedures as in Example 1 were carried out, except that the starting material 2,2-bis (diphosphoryl) biphenyl [general formula (III)] was variously changed. Table 1 shows the results.

Test examples are shown below.

Test Example 1 Asymmetric hydrogenation of methyl acetoacetate using ruthenium complex 1-1) Preparation of catalyst 2.4 μg (2.5 × 10 ⁻³ mmol) of di-μ-iodo-bis [(p-cymene) iodolthenium (II)] ) And (R) -2,2'-bis (diphenylphosphino) -5,
5'-Dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl (Compound 1) was dried and degassed in 6 x 10 ^-3 mmol of methanol / dichloromethane = 1: 1 (4 ml) in a mixed solvent of argon under a stream of argon. The mixture was stirred at 50 ° C. for 30 minutes to prepare a ruthenium (II) cationic complex. Still further, (R) -2,2'-bis (diphenylphosphino) -5,5'-dimethoxy-4,
A ruthenium (II) cationic complex was prepared in the same manner as described above, except that compounds 2 to 8 synthesized in Examples were used instead of 4 ', 6,6'-tetramethylbiphenyl (compound 1).

1-2) Asymmetric hydrogenation reaction The autoclave was charged with 581 mg (5 mmol) of methyl acetoacetate, the catalyst solution prepared in 1-1), and dried and degassed methanol / dichloromethane = 1: 1 (6 ml).
The mixture was stirred at 90 atm and 30-40 ° C for 40 hours. After the reaction, the reaction conversion was measured by gas chromatography (column: PEG-20M). After the solvent was distilled off under reduced pressure, the residue was distilled under reduced pressure to a boiling point of 75.
The rotation of the fraction at 8080 ° C./20 mmHg was measured, and the absolute configuration was determined by the sign of the rotation. A part of the product was taken, benzoyl chloride in pyridine was added, and the mixture was stirred at room temperature for 1 hour. After treatment according to a conventional method, the obtained methyl 3-benzoyloxybutyrate was subjected to high performance liquid chromatography (254 nm, 2 nm) using an optically active column (Daicel: Chiralcel OB).
-Propanol: n-hexane = 1: 9), and the optical purity was measured. Table 2 shows the results.

Comparative Test Examples 1-2 1) Preparation of Comparative Catalyst Instead of Compound 1, (R) -2,2'-bis (diphenylphosphino) -1,1-binaphthyl (BINAP) was used.
Others were prepared similarly.

2) Comparison of asymmetric hydrogenation reactions The same operation as above was performed except for using a comparative catalyst. Table 2 shows the results.

BINAP: (R) -2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (described in JP-A-64-68387) Test Example 2 α-piperonylidene using rhodium complex Asymmetric hydrogenation of succinic acid monomethyl ester 2-1) Preparation of catalyst [Bis (1,5-dichlorooctadiene) rhodium (I) perchlorate] 2.1 mg (5.0 × 10 ⁻³ mmol) and (R) ) -2,2'-Bis (diphenylphosphino)-
3.5 mg (5.5 × 10 ⁻³ mmol) of 5,5′-dimethoxy-4,4 ′, 6,6′-tetramethylbiphenyl (compound 1) was dried,
The mixture was stirred in 4 ml of degassed dichloromethane under a stream of argon at room temperature for 3 hours to prepare a rhodium (I) cationic complex. It was concentrated under reduced pressure and dissolved in 4 ml of dry and degassed methanol.

2-2) Asymmetric hydrogenation reaction The α-piperonylidene succinic acid monomethyl ester was converted to 1.
A catalyst solution prepared by 32 g (5 mmol), 506 mg (5 mmol) of triethylamine and 2-1) and 6 ml of dry and degassed methanol were put into an autoclave, and the mixture was stirred for 20 hours at 30 at 30 ° C. and an initial hydrogen pressure of 5 atm. After the reaction, the solution was distilled off under reduced pressure.
The residue was dissolved in 10 ml of a 0.5N aqueous sodium hydroxide solution under ice cooling. After filtration, the filtrate was acidified with 6N hydrochloric acid under ice-cooling again, and extracted with 40 ml of diethyl ether. The separated organic layer was washed three times with 20 ml of water and 20 ml of saturated saline and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the reaction conversion was measured by ¹ H-NMR analysis. Further, the specific rotation was measured, and the value was compared with literature values to determine the optical purity and the absolute configuration. When the conversion did not reach 100%, the measured specific rotation was corrected for concentration to calculate the optical purity.

Here, COD indicates 1,5-cyclooctadiene.

Reference Example 1 (RS) -2,2'-bis (diphenylphosphoryl) -5,5 '
Synthesis of -dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl (Method A) 2,2'-Dibromo-5,5'-dimethoxy-4,4', 6,6 ' 4.28 g (0.01 mol) of tetramethylbiphenyl were completely dissolved and cooled to -70 ° C. t-Butyllithium (1.5 mol / n-pentane solution: 28 ml, 0.042 mol) was added, and the mixture was stirred at the same temperature for 30 minutes. After the reaction changed from colorless and transparent to yellow, chlorodiphenylphosphine oxide was dissolved in 10 ml of dried tetrahydrofuran. Add 10.41 g (0.044 mol) and add 1 at the same temperature
The mixture was stirred for another 15 hours, and the mixture was stirred while gradually returning to room temperature over 15 hours.

Tetrahydrofuran was distilled off under reduced pressure, and the residue was dissolved in dichloromethane (100 ml) and water (10 ml). The mixture was washed successively with 1N-sodium hydroxide aqueous solution (50 ml) and water (30 ml) three times, and saturated saline (30 ml), and dried over anhydrous sodium sulfate. After distilling off dichloromethane under reduced pressure, the yellow syrup residue was separated and purified by silica gel chromatography (developing solvent, chloroform: acetone = 9: 1) to obtain 4.34 g of a white solid. Reconstituted with methanol, racemic colorless scaly crystals, 2,2'-bis (diphenylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-
3.42 g of tetramethylbiphenyl was obtained. The yield is 51%,
Melting point was above 320 ° C. The confirmation data is shown in Table 4.

Reference Example 2 Synthesis of (RS) -2,2'-bis [di (4-methoxyphenyl) phosphoryl] -5,5'-dimethoxy-4,6 ', 6,6'-tetramethylbiphenyl (Method B) Completely dissolve 4.28 g (0.01 mol) of 2,2'-dibromo-5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl in 90 ml of dried tetrahydrofuran and cool to -79 ° C did. t-Butyllithium (1.5 mol / n-pentane solution: 28 ml, 0.042 mol) was added, and the mixture was stirred at the same temperature for 30 minutes, and then the reaction solution changed from colorless and transparent to yellow was dried with 10 ml of chlorodi (4) dissolved in tetrahydrofuran. Then, 10.10 g (0.036 mol) of -methoxyphenyl) phosphine was added, and the mixture was stirred at the same temperature for 1 hour, and further stirred for 15 hours while gradually returning to room temperature. Tetrahydrofuran was distilled off under reduced pressure, the residue was dissolved in 100 ml of dichloromethane and 10 ml of water, and 11 ml (0.01 mol) of 31% aqueous hydrogen peroxide was added under ice-cooling, followed by stirring at room temperature for 3 hours. The organic layer was separated, washed successively with 50 ml of a 1N aqueous solution of sodium hydroxide and 30 ml of water three times with 30 ml of saturated saline, and dried over anhydrous sodium sulfate. Dichloromethane was distilled off under reduced pressure, followed by vacuum drying to obtain a white solid. After reconstitution with ethanol, a racemic colorless prism crystal, 2,2'-bis [di (4-methoxyphenyl) phosphoryl] -5,5 '
4.43 g of dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl was obtained. The yield was 56% and the melting point was 270-271 ° C.

 The confirmation data is shown in Table 4.

Reference Examples 3 to 4 Various methods A and B were selected and (RS) -2,2'-bis (dicyclohexylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl And (RS)-
2,2'-bis (diphenylphosphoryl) -4,4 ', 6,6'-
Tetra (trifluoromethyl) biphenyl was synthesized.
Table 4 shows the confirmation data.

Reference Example 5 (R) -2,2'-bis (diphenylphosphoryl) -5,5 '
Synthesis of -dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl Racemic 2,2' synthesized in Reference Example 1 with chloroform
-Bis (diphenylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl 6.71 g (0.01 mol) and (-)-dibenzoyltartaric acid hydrate 4.14 g
(0.011 mol) was dissolved by heating, and 20 ml of hot ethyl acetate was added under heating. Allow to cool to room temperature and add a small amount of (R) -2,
2'-Bis (diphenylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl was added, 10 ml of hot ethyl acetate was added under heating, and the mixture was left at room temperature for 15 hours. The precipitated crystals are filtered by suction, and chloroform 5 ml is again formed.
Then, recrystallization was performed by repeating the operation of adding 10 ml of hot ethyl acetate with heating to obtain 2.42 g of a complex. The obtained complex is dichloromethane 150 ml.
, 50 ml of a 1N aqueous solution of sodium hydroxide was added, and the mixture was stirred at room temperature for 30 minutes. Separate the organic layer, 3 times with 50 ml of water,
After sequentially washing with 50 ml of a saturated saline solution, the mixture was dried over anhydrous magnesium sulfate. After drying dichloromethane under reduced pressure, vacuum drying,
1.58 g of a white solid (R) -2,2'-bis (diphenylphosphoryl) -5,5'-dimethoxy-4,4 ', 6,6'-tetramethylbiphenyl was obtained. The yield was 47%. Table 5 shows the results.

Reference Examples 6 to 12 Raw materials and (-)-dibenzoyltartaric acid or (+)-
Dibenzoyltartaric acid was selected according to the purpose, and the other procedures were the same as in Reference Example 5. Table 5 shows the results.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ identification code FI C07F 9/50 C07F 9/50 (58) Fields investigated (Int. Cl. ⁶ , DB name) CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] (1) General formula [Wherein, A represents an arene or an olefin group, X represents a halogen atom or an olefin group, Y represents a halogen atom,
Represents boron tetrafluoride, tetraphenyl boron, phosphorus hexafluoride, perchloric acid, Z represents ruthenium, rhodium atom,
R ¹ represents a cyclohexyl group, a phenyl group (which may be substituted with an alkyl group or an alkoxy group), R ² represents a lower alkyl group or a lower haloalkyl group, R ³ represents a lower alkoxy group, R ⁴ represents a lower alkyl group, Shows a lower haloalkyl group. ] The biphenylbisphosphine complex represented by these.