JPH1180179A - Phosphine compound and rhodium complex containing the same as ligand - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new 1,2-bis(t-butylmethylphosphino)ethane useful as a ligand for rhodium complexes excellent in asymmetric selectivity and catalytic activity and used as catalysts for the asymmetric hydrogenation of unsaturated carboxylic acids or the like. SOLUTION: A new 1,2-bis(t-butylmethylphosphino)ethane of formula I (t-Bu is t-butyl ; Me is methyl). The compound of formula I is used as a ligand for rhodium complexes excellent in asymmetric selectivity and catalytic activity and useful as catalysts for the asymmetric hydrogenation of unsaturated carboxylic acids and the like. The phosphine compound of formula I is obtained by reacting phosphorus trichloride with t-butylmagnesium chloride and subsequently with 2 equivalents of methylmagnesium bromide, treating the reaction product with borane-tetrahydrofuran complex, reacting the obtained t- butyldimethylphosphine of formula II with butyl lithium and subsequently with copper chloride in the presence of a sparteine, and further reacting the dimer of formula III with CF3 SO3 H and subsequently with KOH.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel phosphine compound, a rhodium complex having the ligand as a ligand, and a method for asymmetric hydrogenation of an unsaturated carboxylic acid using the complex as a catalyst.

[0002]

2. Description of the Related Art Organic synthesis reactions using a metal complex as a catalyst have been known for a long time. In particular, many research results have been reported because asymmetric synthesis using a chiral compound as a ligand is very useful. For example, J. D. Morrison, Asymmetric Synthesis, Volume 5 (issued in 1985, Acsdem
ic Press Inc.) and “Asymmetric Catalysisi” by R. Noyori
As described in n Organic Synthesis, a number of phosphine compounds with various structures have been developed to enhance catalytic performance, and their metal complexes are reported to be useful as asymmetric catalysts for asymmetric synthesis reactions. Have been.

[0003] In many chiral ligands, asymmetry on the skeletal carbon atom creates an asymmetric environment by inducing the non-equivalence of the two phenyl groups on the phosphorus atom. Therefore, it is considered that a ligand having a directly asymmetric phosphorus atom can achieve better results, and such a ligand includes 1,2-bis [(o-methoxyphenyl) phenylphosphino]. Ethane (hereinafter referred to as diPAMP) is known (US Pat. No. 4,008,281, JP-A-50-113489).

The most commonly used methods for producing an optically active carboxylic acid include a method for oxidizing a naturally occurring optically active alcohol or aldehyde, and a method for converting a racemic carboxylic acid into an optically active carboxylic acid. There are a method of optical resolution using amines, and a method of partially hydrolyzing a racemic carboxylic acid ester using an enzyme or a microorganism. In addition, asymmetric hydrogenation of α, β-unsaturated carboxylic acids can also be used, but it is known that the result largely depends on the structure of the phosphine compound used as the asymmetric ligand of the catalyst. Many phosphine compounds having both selectivity and catalytic activity have not been known yet.

[0005]

As described above, phosphine has been developed to provide a catalyst which achieves higher performance as a catalyst for an asymmetric synthesis reaction.
Depending on the target substrate or the like, these may not be sufficiently satisfactory in terms of selectivity and catalytic activity. Accordingly, an object of the present invention is to provide a phosphine compound that provides higher catalytic performance than a conventional catalyst.

The present inventor has conducted intensive studies to achieve the above object, and as a result, a rhodium having an optically active phosphine compound having an asymmetric source on a phosphorus atom represented by the following formula (I) as a ligand: The complex is compared to a conventionally known rhodium complex of an optically active phosphine compound having an asymmetric source on a phosphorus atom,
The inventors have found that the selectivity and the catalytic activity are excellent, and have completed the present invention.

[0007]

Accordingly, the present invention provides a compound of the formula (I)

Embedded image 1,2-bis (t-butylmethylphosphino) having
About ethane. Furthermore, the present invention relates to the above 1,2-bis (t
-Butylmethylphosphino) ethane as a ligand.

The present invention further relates to a compound of the general formula (II)

Embedded image (Wherein, X represents a borotrihydride group, an oxygen atom or a sulfur atom,

Embedded image Represents a single bond when X represents a borotrihydride group and a double bond when X represents an oxygen atom or a sulfur atom).

The present invention also relates to a compound of the formula (III) using the above rhodium complex as a catalyst.

Embedded image Wherein R ¹ , R ² and R ³ are the same or different and represent a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group, and R ⁴ represents an optionally substituted alkyl, aryl or aralkyl group or a group represented by the formula -CH
₂ COOR ⁵ (wherein R ⁵ represents a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group) or NHR ⁶ (where R ⁶ represents a formyl group or an optionally substituted alkyl or aryl group) Asymmetric hydrogenation of an unsaturated carboxylic acid or an ester thereof having 基 which means a group represented by the formula (I)
V)

Embedded image Wherein R ¹ , R ² , R ³ and R ⁴ have the same meaning as described above, or a method for producing a saturated carboxylic acid or an ester thereof.

The phosphine compound (I) of the present invention has optical isomers, ie, (S, S) -form, (R, R) -form and meso-form, and the present invention relates to all of these optical isomers. Is included. The phosphine compounds (I) of the present invention can be prepared, for example, as shown in the reaction scheme by DAEvans et al. In Journal of Chemical Society, Vol. 117, No. 9
After preparing the four-coordinate phosphorus compound (II ') according to the method disclosed on pages 075 to 9076, the method disclosed in T. Livinghouse et al. In Tetrahedron Letters, Vol. 35, No. 9319-9322, is used. Manufactured.

[0011]

Embedded image

That is, t-butylmagnesium chloride is reacted with phosphorus trichloride, followed by reaction with 2 equivalents of methylmagnesium bromide, and then treated with a borane-tetrahydrofuran complex to obtain t-butyldimethylphosphine-borane (V). Get. Compound (V) is treated with butyllithium in the presence of spartin, and then treated with copper (II) chloride to obtain bisphosphine borane (II '). The resulting compound (IV) is made optically pure by recrystallization, reacted with trifluoromethanesulfonic acid, and then treated with potassium hydroxide to produce the phosphine compound (I) of the present invention.

In the four-coordinate phosphorus compound (II) of the present invention, the compound wherein X is a borotrihydride group is produced as described above. In the four-coordinate phosphorus compound (II) of the present invention, when X is an oxygen atom, the compound (II ') is prepared by T. Imamoto et al. In Main Group Chemistry Volume 1, as shown in the reaction scheme. Compounds (I) prepared by the method disclosed on pages 331 to 338, or
Can be obtained by oxidizing with an oxidizing agent such as hydrogen peroxide or m-chloroperbenzoic acid, and can also be obtained by reducing with a reducing agent such as hexachlorodisilane at the time of use.

[0014]

Embedded image

In the four-coordinate phosphorus compound (II) of the present invention, when X is a sulfur atom, the compound (II ') is converted to a main group by T. Imamoto et al. As shown in the reaction scheme.・ Chemistry Volume 1 331-3
Compounds prepared by the method disclosed on page 38 and compounds
It is obtained by reacting (I) with sulfur and can be obtained by reducing it with a reducing agent such as hexachlorodisilane at the time of use.

[0016]

Embedded image

In order to obtain a rhodium complex from the phosphine compound (I) of the present invention obtained as described above, for example,
Experimental Chemistry Lecture, 4th Edition (edited by The Chemical Society of Japan, published by Maruzen Co., Ltd.), vol. 18, pages 327 to 353, that is, the reaction of compound (I) with [RhX (diene) ₂ ] Where X is a halogen, an anion, tetrafluoroborate (BF ₄ ), hexafluorophosphate (PF ₆ ), perchlorate ion (Cl
O ₄₎ represents the like, Diene is 1,5-cyclooctadiene (COD) or bicyclo [2,2,1] hepta-2,5
Represents a bidentate compound such as -diene (NBD). The molar ratio of the phosphine compound (I) to rhodium in the rhodium complex of the present invention is 1-2: 1, preferably 1: 1.

The step of asymmetrically hydrogenating an unsaturated carboxylic acid or its ester (III) using the rhodium complex of the present invention as a catalyst to produce a saturated carboxylic acid or its ester (IV) can be carried out according to a conventional method. Can be. That is, the α, β-unsaturated carboxylic acid or ester is placed in a pressure vessel with the above rhodium catalyst and solvent in a nitrogen atmosphere, filled with hydrogen and the reaction is started. The rhodium complex is preferably used in an isolated state, but can also be synthesized in a reaction system and used.

The amount of the catalyst used is 0.02 to 0.000 per mole of the α, β-unsaturated carboxylic acid or ester.
The amount is 0.01 mol, preferably 0.01 to 0.0001 mol. As the solvent, methanol, ethanol, isopropyl alcohols or tetrahydrofuran, benzene, toluene or the like, which is generally used as a solvent, is used alone or as a mixture. The amount used is 0.5 to 20 per mole of the α, β-unsaturated carboxylic acid or ester.
0. The reaction hydrogen pressure is usually carried out at a partial pressure of 0.1 to 100 kg / cm ² . Reaction temperature is 5 to 70
° C, preferably 10 to 50 ° C.

The substituents R ^{1 to} R ^{6 of the} formula (III) or (IV)
The alkyl, aryl and aralkyl groups in the definition of are preferably (C ₁ -C ₁₀ ) alkyl, (C ₆ -C ₁₂ ) aryl and (C ₁ -C ₆ ) alkyl- (C ₆ -C ₁₂ ) aryl. May be substituted with a hydrogen-inactive group, for example, an alkyl group, a halogen, an alkoxy group, an ester group and the like. Examples of the alkyl group include methyl, ethyl, propyl, butyl, pentyl, octyl, decyl, and the like.Examples of the aryl include phenyl and naphthyl.Examples of the aralkyl group include benzyl, phenethyl, and naphthyl. Methyl and the like.

[0021]

Next, the present invention will be described more specifically with reference to examples. Example 1 t-butyldimethylphosphine borane (V)
Synthesis of 0.1 mmol of phosphorus trichloride in 100 ml of tetrahydrofuran under argon in a 1 liter three-necked flask and cooling the solution to -78 ° C, whereupon a solution of t-magnesium chloride in ether (1.43 M, 0.11mm
ol) was added dropwise over 1 hour. After returning the reaction solution to room temperature, it was cooled again to 0 ° C., and an ether solution of methylmagnesium bromide in 260 ml (1.0 M, 0.21 mmol) was added thereto.
Was added dropwise in 30 minutes. The reaction solution was warmed to room temperature and cooled to 0 ° C., and 150 ml of a borane-tetrahydrofuran complex solution in tetrahydrofuran (1.0 M, 15 M) was added.
0 mmol) was added dropwise. The reaction was treated with a mixture consisting of ice (500 g), ethyl acetate (20 ml) and concentrated hydrochloric acid (20 ml). The organic layer was separated, the aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine and then dried over anhydrous sodium sulfate. The obtained solution was concentrated under reduced pressure and distilled to obtain colorless crystals. The crystals were recrystallized from hexane to obtain the desired compound (V). 160-163 ° C ¹ H-NMR (δ, CDCL ₃ ): 0.4 (dq, J = 9)
5 Hz, J = 15 Hz, 3H), 1.16 (d, J = 1
3.7 Hz, 9H), 1.23 (d, J = 9.8 Hz, 6
H)

Example 2 1,2-bis [(t-butyl)
Synthesis of dimethylphosphino] ethane-borane (II '): under argon, sparteine dissolved in 8 ml of ether
After cooling to 78 ° C, 1.7 ml of sec-butyllithium (1.06 M solution in cyclohexane, 2.2 mmol) was added thereto. After 10 minutes the compound was dissolved in 8 ml of ether
(V) was added dropwise thereto. After stirring at −78 ° C. for 3 hours,
Copper (II) chloride (2.5 mmol) was added and the mixture was gradually warmed to room temperature with vigorous stirring. After completion of the reaction, the reaction solution was treated with ammonium chloride, then with hydrochloric acid and with a saline solution. After the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.
Recrystallization from toluene gave optically pure (S, S) -1,2-bis [(t-butyl) dimethylphosphino] ethane borane (II '). Melting point 169-171 ° C ¹ H-NMR (δ, CDCL ₃ ): 0.0-0.8 (br)
p, 6H), 1.18 (d, J = 13.9 Hz, 18
H), 1.22 (d, J = 9.5 Hz, 6H), 1.57
１1.66 (m, 2H), 1.96 to 2.04 (m, 2
H) [α] _D = -9.1

Example 3 1,2-bis [(t-butyl)
Synthesis of dimethylphosphino] ethane (I): under argon
Compound (II ') (2.00 mmol) in toluene solution (5 ml)
Was cooled to −78 ° C., and trifluoromethanesulfonic acid (1.5 g, 10.0 mmol) was added thereto. The solution was warmed to room temperature and stirred for another hour. Chloroform (10 ml) was added to the reaction solution, and the mixture was concentrated under reduced pressure. Under argon, a 10% ethanol solution of potassium hydroxide was added to the crystals, and the mixture was stirred at 50 ° C. for 3 hours. After the reaction mixture was extracted with ether, the organic layer dried over anhydrous sodium sulfate was passed through an alumina column, and the solvent was distilled off to obtain the desired phosphine (I). 23.5-25.5 ° C. ¹ H-NMR (δ, CDCL ₃ ): 0.832 (d, J =
7.6 Hz, 3H), 0.940 (d, J = 11.5H)
z, 9H), 0.7-1.7 (m, 4H)

Example 4 Synthesis of a rhodium complex and asymmetric hydrogenation reaction Under argon, bis (bicyclo [2,2,1] hept-2,
5-diene) rhodium (I) tetrafluoroborate salt (0.080 g, 0.21 mmol) and the phosphine compound
(I) (0.031 g, 0.21 mmol) was reacted in a mixed solvent of tetrahydrofuran-isopropyl alcohol (21 ml). On the other hand, α-acetamidocinnamic acid methyl ester (0.219 g, 1 mmol) and 5 ml of isopropyl alcohol are added to a pressure-resistant reaction vessel and heated to 50 ° C., and the reaction vessel is purged with hydrogen. 0.1 ml of the above reaction solution (rhodium complex solution) was withdrawn and dropped into the asymmetric hydrogenation reactor. The hydrogen pressure in the reaction vessel was increased to 3 kg / cm ² , and after 5 minutes, the inside of the system was replaced with argon. The product was analyzed by high performance liquid chromatography (column: Chiral Cell OJ manufactured by Daicel, solvent: isopropyl alcohol / hexane = 1/9). The product (N-acetylphenylalanine methyl ester) was 99.7% ee. It was confirmed that it was obtained with an optical purity of. When the phosphine compound (I) having a configuration of (S, S) was used, the configuration of the product was S.

When the rhodium complex of the present invention was subjected to the asymmetric hydrogenation reaction of α-acetamidocinnamic acid methyl ester by the method described in JP-A-50-113489, the enantioselectivity was 99.7%. And the reaction time was 5 minutes. In contrast, according to the above publication, diPA
When using the MP-rhodium complex, the enantioselectivity is 96% and the reaction time is 50 minutes.

[0026]

According to the present invention, a rhodium complex having 1,2-bis (t-butylmethylphosphino) ethane as a ligand is provided. The rhodium complex of the present invention is useful as a catalyst in asymmetric hydrogenation, and has extremely excellent stereospecificity and catalytic activity as compared with conventionally known rhodium complexes of optically active phosphine compounds having an asymmetric source on a phosphorus atom. I have.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 69/035 C07C 69/035 C07F 15/00 C07F 15/00 B

Claims (4)

[Claims] (1) Formula (I) 1,2-bis (t-butylmethylphosphino) having
Ethane. 2. A rhodium complex having 1,2-bis (t-butylmethylphosphino) ethane according to claim 1 as a ligand. 3. A compound of the general formula (II) (Wherein, X represents a borotrihydride group, an oxygen atom or a sulfur atom, Is a single bond when X represents a boron trihydride group, and represents a double bond when X represents an oxygen atom or a sulfur atom). 4. A compound represented by the general formula (III) using the rhodium complex according to claim 2 as a catalyst. Wherein R ¹ , R ² and R ³ are the same or different and represent a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group, and R ⁴ represents an optionally substituted alkyl, aryl or aralkyl group or a group represented by the formula -CH
₂ COOR ⁵ (wherein R ⁵ represents a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group) or NHR ⁶ (where R ⁶ represents a formyl group or an optionally substituted alkyl or aryl group) Asymmetric hydrogenation of an unsaturated carboxylic acid or an ester thereof having 基 which means a group represented by the formula (I)
V) Wherein R ¹ , R ² , R ³ and R ⁴ have the same meaning as described above, or a saturated carboxylic acid or an ester thereof.