JPH02188591A - 2-(diphenylphosphino)-cycloalkane derivative, production thereof and catalyst for asymmetric synthesis - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R is -N(R<1>)R<2> (R<1> and R<2> are 1-4C alkyl or phenyl) or -COR<3> (R<3> is OH or 1-4c alkoxy); n is 2-4]. EXAMPLE:(2-Dimethylamino)-1-diphenylphosphinocyclobutane. USE:A catalyst for asymmetric syntheses. Usable for asymmetric synthesis reaction such as asymmetric hydrogenating reaction, asymmetric hydrosililating reaction, asymmetric hydroformylating reaction, asymmetric cyclopropanating reaction, asymmetric epoxidizing reaction and cross coupling reaction. PREPARATION:A compound shown by formula II is reduced in a sealed tube in the presence of a solvent such as anhydrous benzene and trichlorosilane at 100-150 deg.C for 5-20 hours.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a 2-(diphenylphosphino)-cycloalkane derivative, a method for producing the same, and a catalyst for asymmetric synthesis containing a complex of the compound and a transition metal as a catalyst component. Regarding.

Conventional techniques and their problems Most natural products, pharmaceuticals, etc. that have asymmetric atoms in their molecules exist in the form of optically active substances and have a certain steric configuration. In addition, its physiological activity is often markedly different from that of its normal counterpart. For example, the teratogenicity of thalidomide, the hormonal activity of estrone, the addictiveness of benzomorphans, and the carcinogenic effects of benz[α]pyrene derivatives are all found in specific enantiomers.

Therefore, it is desired to establish a technique for efficiently synthesizing only optically active substances having a certain steric configuration.

In particular, the catalytic asymmetric synthesis reaction that synthesizes a large amount of optically active substances using a small amount of optically active substances is one of the effective means, and is used in the synthetic chemical industry including the pharmaceutical industry and the fragrance industry. There are many cases where this is required.

Conventionally, a complex of an optically active phosphine and a transition metal has been used as a catalyst for asymmetric synthesis. However, the optically active phosphine, which is one of the ligands of the complex, is either a natural product or difficult to manufacture.
Unable to provide stable supply. Therefore, it is very difficult to scale up an asymmetric synthesis reaction using such a complex to an industrial scale, and the cost becomes extremely high.

Problems to be Solved by the Invention The objects of the present invention are to provide a novel optically active phosphine compound useful as a ligand for a catalyst for asymmetric synthesis, a method for producing the optically active phosphine in high yield at low cost, and a stable method for producing the optically active phosphine. The object of the present invention is to provide a catalyst for asymmetric synthesis that can be supplied and applied on an industrial scale.

Means for Solving the Problems The object of the present invention is to represent a group of the general formula - or which is different from an alkyl group having 1 to 4 carbon atoms or a phenyl group) or a group -COR3 (R3 is a hydroxyl group or a group having 1 to 4 carbon atoms). (indicates an alkoxy group). n represents an integer of 2 to 4. This is achieved by a 2-(diphenylphosphino)-cycloalkane derivative represented by the following, a method for producing the same, and a catalyst for asymmetric synthesis containing a complex of the derivative and a transition metal as a catalyst component.

The 2-(diphenylphosphino)-cycloalkane derivative represented by the above general formula (1) (hereinafter referred to as compound (1)) is a novel optically active phosphine compound that has not been described in any literature, and the combination of this compound and a transition metal. The complexes are useful as catalysts for asymmetric synthesis.

According to the present invention, the above-mentioned compound (1) can be produced in high yield, so it is possible to stably supply a catalyst for asymmetric synthesis which is a complex of compound (1) and a transition metal, and it is also possible to scale up to an industrial scale. It is possible. Moreover, the cost is significantly lower than that of the conventional method.

The compound (1) of the present invention can be produced according to the following reaction scheme-1.

[Reaction Scheme-1] (2) O [In the formula, R and n are the same as above. ] The reduction reaction of compound (2) is carried out by heating in a sealed tube in the presence of an appropriate solvent and trichlorosilane. Examples of the solvent include anhydrous benzene and anhydrous toluene. The amount of trichlorosilane used is as follows: Compound (4)
The amount may be generally about 2 to 20 times, preferably about 2 to 5 times, by mole. The reaction temperature is usually 100 to 150
It may be about ℃. The reaction takes about 5 to 20 hours to complete.

The above compound (2) is a new compound that has not been described in any literature. Among compound (2), compound (2a) in which R is a group can be produced, for example, according to the following reaction scheme-2.

[Reaction Scheme-2] (2a) 0 [In the formula, R1, R2 and n are the same as above. ] Compound (3
) and compound (4) is carried out in the absence of a solvent or in the presence of a solvent. Compound (3) is a known compound, and can be produced, for example, according to the method described in JP-A-60-156696. Examples of the dialkyl secondary amine as compound (4) include dimethylamine, diethylamine,
Di-n-propylamine, diisopropylamine, di-
Examples include n-butylamine, diisobutylamine, and diphenylamine. As the solvent, any inert solvent that does not have an adverse effect on reaction 14 can be used, for example,
Examples include ethers such as diethyl ether and diisopropyl ether, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, and tetrahydrofuran. The amount of compound (4) to be used relative to compound (3) is not particularly limited and is appropriately selected from a wide range, but usually the latter is about 1 to 50 times the former by molar amount, preferably 2 to 50 times the molar amount of the latter.
It is best to set it to about 25 times the molar amount of gold. Further, the reaction temperature is also not particularly limited, but it is usually about -30 to 30°C, preferably about -10 to 10°C. The reaction time is
Usually it takes about 10 to 20 hours.

Further, in compound (2), compound (2b) in which R is a group -00R3 (R3 is the same as above) can be produced, for example, according to the following reaction scheme-3.

[Reaction scheme-3] [In the formula, R4 represents an alkyl group having 1 to 4 carbon atoms.

n is the same as above. ] The reaction between compound (5) and 1,3-dithiane is carried out by first dissolving 1,3-dithiane in a suitable solvent and cooling it usually to 0°C, preferably below -20°C, and then dissolving 1,3-dithiane in a suitable solvent. A hexane solution of n-butyllithium in an equimolar amount and compound (5) are added one after another, and the reaction is carried out at a temperature of usually 0° C. or lower, preferably -20° C. or lower, for about 1 to 10 hours while stirring. Compound (6) is obtained. The amount of 1,3-dithiane to be used is not particularly limited and can be selected from a wide range, but it is usually about 1 to 10 times the mole of compound (5),
Preferably, the amount may be about 1.2 to 3 times the mole. Examples of the solvent include ethers such as diethyl ether and diisopropyl ether, and tetrahydrofuran.

The compound where n=2 in compound (5) is a known compound,
For example, it is described in JP-A-60-152493.

Furthermore, the compounds where n=3 and 4 are new compounds, and can be produced using cyclohexylbromide or cyclopentylbromide as a raw material according to the method described in JP-A-60-152493.

Oxidation of compound (6) is carried out in a lower alcohol such as methanol or ethanol by heating to reflux in the presence of sodium hydroxide. The amount of sodium hydroxide used is usually about 1 to 20 times the mole of compound (6), preferably about 2 to 10 times the mole. Sodium hydroxide is usually used in the form of an aqueous solution. Reaction time is 1-10
It may be about an hour.

Removal of the propylenethiomethyl group and formylation of compound (7) obtained by oxidation of compound (6) can be carried out by removing cerium ammonium nitrate, copper chloride-copper oxide, mercury chloride-mercury oxide, etc. in an appropriate solvent. It is carried out at room temperature with stirring in the presence of a thioacecooling agent. Examples of the solvent include nitriles such as acetonitrile, ketones such as acetone, and the like. The amount of dethioacetalizing agent used is
The amount may be generally about 1 to 10 times the amount of compound (7), preferably about 2 to 4 times the amount of the compound (7). Also, the reaction time is 1
It may be about 0 minutes to 2 hours.

Oxidation of the compound (8) thus obtained can be carried out in a suitable solvent in the presence of an oxidizing agent.

Known oxidizing agents can be used, such as potassium permanganate, hydrogen peroxide, and the like. The amount of the oxidizing agent to be used is generally about 1 to 10 times the mole of compound (8), preferably about 2 to 5 times the mole. Examples of the solvent include ketones such as acetone, methylethimeketone, and methylisobutylketone, and halogenated hydrocarbons such as methylene chloride. The reaction may be carried out at room temperature for about 15 to 30 minutes while stirring or for about 2 to 5 hours while refluxing.

The alkylation reaction of the compound (9) obtained above is carried out by allowing sulfuric acid to act on the compound (9) in a solvent and refluxing it to obtain the compound (2b).

Examples of the solvent include methanol, ethanol, n-
Examples include lower alcohols such as propyl alcohol, isopropyl alcohol, n-butyl alcohol, and isobutyl alcohol. The amount of sulfuric acid used is for compound (9)
, usually about 1 to 20% by weight, preferably 2 to 1% by weight.
It may be about 0% by weight. The reaction is carried out at a temperature of about 50 to 150°C for about 1 to 10 hours.

In the above reaction scheme-3, in place of compound (5) which is the starting compound, (1-cycloalkane)triphenylphosphonium verchlorate such as (1-cyclobutenyl)triphenylphosphonium verchlorate (the number of carbon atoms in cycloalkyl is 4 to 6), the compound (2
b) can be obtained.

Furthermore, in the present invention, the present compound (1a) in which R is an alkyl group having 1 to 4 carbon atoms can be dealkylated as shown in the following reaction scheme-4.
b) can be obtained.

[Reaction Scheme-4] (1a) [In the formula, R4 and n are the same as above. ] The above dealkylation reaction is carried out by reacting compound (1a) with sodium hydroxide in a suitable solvent with stirring. Examples of the solvent include ethers such as diethyl ether and diisopropyl ether, and tetrahydrofuran. The amount of sodium hydroxide to be used is usually about 1 to 20 times the mole, preferably about 1.5 to 3 times the mole of compound (1a). Sodium hydroxide is used in the form of an aqueous solution. The reaction is completed at room temperature for about 3 to 10 hours.

The target products obtained in each of the above steps can be easily separated and purified using conventional purification methods such as concentration, solvent extraction, crystallization, silica gel column chromatography, etc.

The catalyst for asymmetric synthesis of the present invention can be produced using the compound of the present invention and a transition metal according to a conventional method.

For example, a complex of the compound of the present invention and rhodium can be prepared by adding the rhodium compound to a suspension of the compound of the present invention in a solvent, stirring the mixture at room temperature for about 1 to 3 hours, and then adding an aqueous solution of sodium borofluoride and leaving the mixture at room temperature for 1 to 3 hours. It can be produced by stirring and reacting for about 3 hours. Examples of the solvent include anhydrous lower alcohols such as anhydrous methanol and anhydrous ethanol. As the rhodium compound, any compound commonly used in this field can be used, such as rhodium (1,5-cyclooctadiene) chloride dimer, R
h4 (Co) 12, Rh203, RhCR” 3
Examples include H20, (acac)RhCO2, and the like. The amount of the compound of the present invention to be used is usually 1.
The amount may be about 5 to 2.5 times the mole. In addition, the amount of sodium borofluoride used is usually 1 to
It may be about 3 times the mole.

Further, the palladium complex can be produced by adding a palladium compound to a solvent solution of the compound of the present invention and stirring the mixture at room temperature for about 1 to 3 hours to react. As a solvent,
For example, halogenated hydrocarbons such as methylene chloride and chloroform can be used. As a palladium compound,
Examples include palladium chloride, palladium bromide, palladium acetate, and the like. The amount of the compound of the present invention to be used is usually about 1.5 to 2.5 times the mole of the palladium compound, preferably equimolar. Nickel complexes can also be produced in a similar manner.

The catalyst for asymmetric synthesis of the present invention obtained in this manner can be used for asymmetric hydrogenation reactions, asymmetric hydrosilylation reactions, asymmetric hydroformyl reactions, asymmetric cyclopropanation reactions, asymmetric epoxidation reactions, cross force/twisting reactions, etc. It can be used in general asymmetric synthesis reactions such as reactions.

Effects of the Invention According to the present invention, a novel 2-(diphenylphosphino)-cycloalkane derivative useful as a ligand for a catalyst for asymmetric synthesis can be produced in an efficient manner (and at a low cost). It is possible to stably supply catalysts for asymmetric synthesis, which are complexes with

EXAMPLES Examples will be given below to further clarify the present invention.

Example 1 Preparation of a,2-(dimethylamino)-1-diphenylphosphinylcyclobutane Robenyl) diphenylphosphine oxyto 3-90
g (15 mmol) was dissolved. After cooling the resulting solution to 0° C. in a water bath, 50 g of a 30% aqueous dimethylamine solution was added. After stirring this at 0° C. for 1 day, the solvent was concentrated under reduced pressure and methylene chloride was added. After separating the methylene chloride layer, the aqueous layer was further extracted with methylene chloride, and the methylene chloride layer was separated. After drying the combined methylene chloride over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, leaving a residue of 4.43
, obtained. This was purified using silica gel column chromatography using chloroform-methanol (15:1) as a developing solvent to obtain 4.12 g (2-dimethylamino)-1-diphenylphosphinylcyclobutane (yield 9).
o%) was obtained.

b. Preparation of (2-dimethylamino)-1-diphenylphosphinocyclobutane (2-dimethylamino)-1-diphenylphosphinylcyclobutane 0. 71 g (2.4 mmol), 15 anhydrous benzene, and 2.3 mmol of trichlorosilane were placed in a sealed tube and heated at 110° C. for 5 hours. The contents were transferred to an eggplant-shaped flask, and the solvent and unreacted trichlorosilane were distilled off under reduced pressure. 20 parts of benzene and 20 parts of a 25% aqueous sodium hydroxide solution were added to the resulting residue, and the mixture was stirred for 1 hour. The benzene layer was separated, the aqueous layer was further extracted with benzene, and the benzene layer was separated. The combined benzene was washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 0.65 g of a crude product. This was purified using silica gel column cloning and Togelafy using chloroform-method seal (15:1) as a developing solvent, and (2-dimethylamino)-1-diphenylphosphinocyclobutane 0.0. 58 g (yield: 86%) was obtained.

[Analysis value]

I R(neat) cm-' 2950.2900.2850.2800.1590.
1480.1465.1440.1100.740.7
00'H-NMR (CDCE) + ) δ 1.10 1.76 (m, 4H, CH2), 1.80
-2.36 (m, 2H, CH), 2.14 (s, 6
H, CH3), 7.00-7.60 (m, IOH, phenylH)
"C-NMR (CDCQ3) δ 23, 75 (d, 2 Jop = 16.33 Hz), 2
7, 89 (d, 3Jo, -12,04Hz), 29
, 01 (d, 'Jop=12.89Hz), 59
．． 16,45.27 (sSCH3) Example 2 a, Preparation of 2-(propylene dithiomethyl) cyclobutyl diphenylphosphine oxide e
e 4.81 g (40 mmol) of 1,3-dithiane was dissolved in anhydrous tetrahydrofuran 50111Q.

The resulting solution was cooled to -20°C, 25.611tQ (40 mmol) of a 15% hexane solution of n-butyllithium was added, stirred for 2 hours, and (1-cyclobutenyl)
Triphenylphosphonium tetrafluoroborate 8.
04g (20 mmol) was added and stirred for 2 hours. 2
After terminating the reaction by adding N-hydrochloric acid, the reaction mixture was extracted with methylene chloride.

The methylene chloride layer was washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 10.90 g of a residue. This residue was dissolved in 20 parts of methanol, 8.07 g (0.2 moles) of sodium hydroxide was dissolved therein, 25 parts of water was further added, and the mixture was heated under reflux for 3 hours. The solvent was concentrated under reduced pressure, made acidic by adding hydrochloric acid, and then extracted with methylene chloride. After separating the methylene chloride layer, the aqueous layer was further extracted with methylene chloride, and the methylene chloride layer was separated.

After drying the combined methylene chloride over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 9.84 g of a crude product.

This was carried out using silica gel column chromatography.
Purification was performed using chloroform as a developing solvent to obtain 7.48 g (yield 100%) of (2-propylene dithiomethyl)cyclobutyldiphenylphosphine oxide as white crystals.

b. Preparation of (2-carboxyl)cyclobutyldiphenylphosphine oxide 7.48 g (20 mmol) of diphenylphosphine oxide was dissolved in 100 mQ of acetonitrile and 10 mQ of water, and further 32.89 g of larylammonium nitrate was added.
(60 mmol) was added and stirred at room temperature for 15 minutes. After concentrating the solvent under reduced pressure, chloroform was added. The chloroform layer was taken out, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel column chromatography using chloroform-ethyl acetate (1:1) as a developing solvent to obtain 5.69 g (yield 100%) of (2-formyl)cyclobutyldiphenylphosphine oxide. Ta.

(2-formyl)cyclobutyldiphenylphosphine oxide obtained above5. 69g (20 mmol)
was dissolved in 100 g of acetone, 5 g of water, 9.48 g (60 mmol) of potassium permanganate and 2.5 g of sulfuric acid were added thereto, stirred at room temperature for 15 minutes, and then heated under reflux for 3 hours. The precipitate was filtered off using a glass filter packed with Celite, and the resulting filtrate was concentrated under reduced pressure, and methylene chloride was added. The organic layer was taken out, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was crystallized by adding hexane to give (2-carboxyl)cyclobutyldiphenylphosphine oxide 5.
．． 87 g (yield 98%) was obtained as white crystals. Melting point = 218-220°C.

c. Production of (2-methoxycarbonyl)cyclobutyldiphenylphosphine (2-carboxyl)cyclobutyldiphenylphosphine oxide2. 0.7 g (6.9 mmol) was dissolved in 25 ml of methanol, 1 portion of sulfuric acid was added thereto, and the mixture was heated under reflux for 2 hours. After concentrating the solvent, methylene chloride was added, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 2.11 g of a crude product. This was purified using silica gel column chromatography using chloroform-ethyl acetate (1:1) as a developing solvent to obtain (2-methoxycarbonyl)cyclobutyldiphenylphosphine oxide2. 07g (yield 95%) was obtained.

0.44 g (2-methoxycarbonyl)cyclobutyldiphenylphosphine oxide obtained above (1,4
Place 10 ml of anhydrous benzene and 1.4 flQ (14 mmol) of trichlorosilane in a sealed tube,
Heated at ℃ for 6 hours. Transfer the contents to an eggplant-shaped flask,
Benzene and unreacted trichlorosilane were distilled off under reduced pressure, and benzene and water were added. After filtration using a glass filter packed with Celite, the benzene layer was taken out, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.36 g of a crude product. This was purified using silica gel column chromatography using ether-hexane (1:3) as a developing solvent to give (2-methoxycarbonyl)cyclobutyldiphenylphosphine 0. 30 g (yield 72%) was obtained.

d. Preparation of (2-carboxyl)cyclobutyldiphenylphosphine 0.13 g (0.42 mmol) of (2-methoxycarbonyl)cyclobutyldiphenylphosphine was mixed with 10 mQ of purified tetrahydrofuran and 0.1 sodium hydroxide.
Add 10 g of water in which 7 g (4.2 mmol) was dissolved,
Stirred at room temperature for 4 hours. Add benzene to wash the aqueous layer, take out the aqueous layer, add 2N hydrochloric acid until it becomes weakly acidic, extract with methylene chloride, dry the organic layer over anhydrous sodium sulfate, and evaporate the solvent under reduced pressure. , (2-carboxyl)
Cyclobutyldiphenylphosphine 0.11g (89%
) was obtained.

I R(neat) cm -' 2900.1700.1585.1480.1430.
740.695'H-NMR (CDC93) δ 1.50 2.40 (m, 4H, CH2), 2.4
0-3.90 (br, m, 2H, CH), 7
．． 00-7.80 (m, IOH, phenylH)
, 10.82 (s, IH, C00H)”C
-NMR (CDCQ 3 ) δ22.92 (d
, 2J = 20.63Hz), p 23.63 (d, 3J -19,77Hz)
, p 34.44 (d, 'J = 16.33Hz
), p 41.09 (d, 2J = 13.75Hz
), p 179, 93 mass m/e (as CH7HI702 P) Calculated value 284.0966 Theoretical value 284.0961 (M”) (±)-(d) (-)-pbA→ (
±)-(d) ・(-)-PEA→ (+)-(d
) (±)-(2-Carboxyl)cyclobutyldiphenylphosphine 2.20 g (7.7 mmol) was dissolved in acetone 50IIIQ, heated under reflux for 30 minutes, and L-
A solution of 0.85 g (7.0 mmol) of (-)-phenylethylamine in 5Tn12 in acetone was added all at once, heated under reflux for an additional 30 minutes, cooled to room temperature, and left in the refrigerator overnight. The precipitated white crystals were collected and recrystallized with acetone for 10 minutes to obtain 0.50 g of white crystals with a melting point of 158.5 to 160°C. Specific optical rotation [α] = 59°3°
(CC06, CH2CQ2).

The white crystals were treated with dilute hydrochloric acid-chloroform to obtain 0.37 g of optically active (+)-(2-carboxyl)cyclobutyldiphenylphosphine.

Specific optical rotation [α] = 85.4° (δ7.4, CH2C
(22) Optical purity 82%ee (HPLC area ratio) Example 3 (Rhodium(I)-((±)-(2-dimethylamino)
Preparation of cyclobutyldiphenylphosphine](1,5-cyclooctadiene))tetrafluoroborate Under nitrogen atmosphere, (±)-(2-dimethylamino)cyclobutyldiphenylphosphine 0. 57 g (2,0 mmol) of rhodium (1,5-cyclooctadiene) chloride dimer was suspended in anhydrous methanol 3-.
．． 49 g (1.0 mmol) was added, resulting in a red solution. After stirring in this state for 1 hour, a solution of 0.16 g of sodium borofluoride dissolved in 31 TIQ of water was added, and the mixture was further stirred for 1 hour. The precipitated crystals were collected, washed twice with 3-dose water, dried in vacuum, and obtained the desired product at 0.95 sr (
81%).

Example 4 Using the complex obtained in Example 3, phenylethanol was synthesized via hydrosilylation of acetophenone in the following manner.

In a 20 eggplant-shaped flask of 3011Q, under a nitrogen atmosphere, 20 mg (3.4 x 10 mol) of the complex of Example 3, 0.37 g (3.1 mmol) of acetophenone, 5 m12 of anhydrous benzene, and 0.6 formula (3.2 mmol) of diphenylsilane were added. ) and stirred at room temperature for 28 hours. After concentrating the solvent under reduced pressure, acetone 51110 and 10% hydrochloric acid 1Tll
12 was added and stirred for 5 hours. After adding ethyl acetate to separate the organic layer, it was washed with water, washed with saturated brine, and dried by adding anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 1.29 g of a crude product. This was purified using thin layer chromatography using chloroform as a developing solvent.
-0.26 g (yield 70%) of phenylethanol was obtained.

Example 5 - Production of aminophosphine paradiuro complex Aminophosphine 567a+g (2 mmol) was placed in an eggplant-shaped flask, purified dichloromethane solvent was added thereto to dissolve it, and further 355 mg (2 mmol) of palladium chloride was added.

After stirring at room temperature for one week, the solvent of the resulting orange synovial fluid was distilled off to obtain 0.80 g of aminophosphine-palladium complex.

Example 6 a. Preparation of Grignard reagent P h M e C) (CQ 4P h M e C)
(316 mg (13 mmol) of M g CQ magnesium was placed in a third flask, the container was dried, and a small amount of dry ether was added. To this, 1-chloroethylbenzene 1
．． Put 41 g (10 mmol) into the dropping funnel and add 10
The mixture was diluted with mG of dry ether and added dropwise little by little. After the dropwise addition was completed, the mixture was heated under reflux for 1 hour to prepare a Grignard reagent.

b, Cross-coupling reaction P h M e CHM g CQ + CH2= C
HB r-PhMeCHCH=CH2 23 mg (0.05 mmol) of the aminophosphine palladium complex obtained in Example 6 was placed in a dry 2-day flask, 3 parts of dry ether was added, and 0.35 mQ of vinyl bromide was added at -78°C. (5 mmol) was added. The Grignard reagent prepared in step a above was added dropwise, and after stirring at 0°C for 2 days, an aqueous ammonium chloride solution was added, followed by extraction with ether.

After drying, the solvent was distilled off and purified by column chromatography using hexane as a developing solvent. Both obtained solvents were distilled off and the target product 3-phenyl-1-butene was analyzed by IH-NMR and gas chromatography. was obtained with a yield of 20%.

The obtained optically active (+)-(2-carboxyl)cyclobutyldiphenylphosphine (10 mol) (3,5 x 10-5 mol) and rhodium (1,5-cycloocta 8 mg (1°6 x 10-5 mol) of diene) chloride dimer was dissolved in benzene 5111Q, then 0.48 g of acetophenone
(4.0 mmol) was added, and then 0.74119 (4.0 mmol) of diphenylsilane was added, and the mixture was heated at room temperature for 2 hours.
The mixture was stirred for several days. To this, methanol 5 precepts and 10% hydrochloric acid 2
III2 was added and further stirred for 5 hours. Ethyl acetate was added to separate the organic layer, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 1.40 g of a crude product. This was produced by thin layer chromatography using benzene as a developing solvent, and 0.20 g of 1-phenylethanol (yield 41%)
I got it.

The specific optical rotation [α] of this material is 2.73° (C3,8
, CH2CΩ2), and the optical yield calculated from the specific optical rotation was 5%ee.

Example 7 (2-carboxyl)cyclopentyldiphenylphosphine was obtained in the same manner as in Example 2 except that (1-cyclopentenyl)triphenylphosphonium fluoroborate was used as the raw material. The complex of the obtained compound and rhodium (I) showed catalytic activity in the hydrosilylation reaction of acetophenone.

Example 8 Example 2 except that (1-cyclohexenyl)triphenylphosphonium verchlorate was used as the raw material.
In the same manner as above, (2-carboxyl)cyclohexyldiphenylphosphine was obtained.

The complex of the obtained compound and rhodium (I) showed catalytic activity in the hydrosilylation reaction of acetophenone.

Claims (1)

[Claims] 1 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R is a group ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R
^1 and R^2 are the same or different and represent an alkyl group or phenyl group having 1 to 4 carbon atoms) or a group -COR^3 (
R^3 represents a hydroxyl group or an alkoxy group having 1 to 4 carbon atoms. n represents an integer of 2 to 4. ] 2-(diphenylphosphino)-cycloalkane derivative represented by these. 2 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R is a group ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R
^1 and R^2 are the same or different and represent an alkyl group or phenyl group having 1 to 4 carbon atoms) or a group -COR^3 (
R^3 represents a hydroxyl group or an alkoxy group having 1 to 4 carbon atoms. n represents an integer of 2 to 4. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by reducing the compound represented by ▼ [In the formula, R and n are the same as above. ] A method for producing a 2-(diphenylphosphino)-cycloalkane derivative represented by: 3 General formula ▲ Numerical formula, chemical formula, table, etc. are available ▼ [In the formula, R^4 represents an alkyl group having 1 to 4 carbon atoms. n
represents an integer from 2 to 4. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by dealkylating a 2-(diphenylphosphino)-cycloalkane derivative represented by same. ] A method for producing 1-carboxyl-2-(diphenylphosphino)-cycloalkane represented by: 4. A catalyst for asymmetric synthesis comprising a complex of the compound of claim 1 and a transition metal as a catalyst component.