WO2001025183A1

WO2001025183A1 - Process for preparing carboxylic esters of optically active 1-perfluoroalkylated alcohols, optically active 1-perfluoroalkylated alcohols and process for the preparation thereof

Info

Publication number: WO2001025183A1
Application number: PCT/JP2000/006866
Authority: WO
Inventors: Katsuhiko Iseki; Yoshichika Kuroki; Daisuke Asada; Yuko Sakamaki
Original assignee: Daikin Industries Ltd.
Priority date: 1999-10-01
Filing date: 2000-10-02
Publication date: 2001-04-12
Also published as: JP2001097923A

Abstract

Optically active 1-perfluoroalkylated alcohols can be prepared by subjecting a 1-perfluoroalkylated unsaturated ester to asymmetric hydrogenation with an optically active ruthenium complex catalyst to thereby obtain a carboxylic ester of 1-perfluoroalkylated alcohol as represented by general formula (III) (wherein Rf is perfluoroalkyl; and R?1 and R2¿ are each hydrogen, alkyl, aryl, or the like), and hydrolyzing this ester to thereby obtain an optically active 1-perfluoroalkylated alcohol corresponding thereto. The present invention provides optically active 1-perfluoroalkylated alcohols such as 1-trifluoromethylated alcohols useful as important intermediates for the preparation of medicines, agricultural chemicals, liquid crystals, or other functional or physiologically active materials; precursors thereof; and a process for preparing the same easily in high yield.

Description

Method for producing carboxylic acid ester of optically active 1_ (perfluoroalkyl) alcohol, optically active 1- (perfluoroalkyl) alcohol and method for producing the same

^ De no ll ll ffl <Tr

The present invention relates to a method for producing a carboxylic acid ester of an optically active (optically chiral) alcohol (perfluoroalkyl) alcohol, and an optically active method.

1 A (perfluoroalkyl) alcohol and a method for producing the same. Conventional ^ technique

In general, a compound obtained by replacing a hydrogen atom with a fluorine atom from a known compound having a functional property or a biological activity has a function or a physiological activity enhanced by a specific electronic effect of the fluorine atom. It is known to exert new functions and physiological activities.

For this reason, fluorine-building blocks having a structure similar to the raw materials of known compounds have been designed and synthesized ["Biologically active substances in the 1990s" supervised by Nobuyuki Ishikawa, published by CMC (1991)), “Latest Trends in Fluorine Materials” edited by Masaaki Yamabe and Matsuo, published by CMC (1994)].

One of the typical examples is the optically active 1- (trifluoromethyl) alcohol ("Chemistry of Fluorine", Tomoya Kitazume, Takashi Ishihara, Takashi Taro Take chopsticks, published by Kodansha (1993) )). This is a compound that has attracted attention in the field of liquid crystal materials, for example, and is widely used as an optically active material for ferroelectric liquid crystals and antiferroelectric liquid crystals. However, it is very difficult to produce this optically active 11- (trifluoromethyl) alcohol, despite the fact that extreme synthesis methods are known.

For example, a method of synthesizing a racemate and then performing optical resolution (Japanese Unexamined Patent Publication No. 3-31238), or synthesizing an optically active trifluoropropenoxide by ffl of g ginseng, and then obtaining the desired product Derivation method CTetraheron Lett. (1990) 31, 7031], or a method for deriving a target product from another optically active compound, or a synthesis method using a stoichiometric enentio-selective reduction reaction [J. 0rg. Chem. (1995) 60, 41)], but by optical resolution of racemic bodies, by-products such as half are produced, and optical purity is insufficient with other methods. However, there are problems that cannot be overlooked anyway because of the use of expensive reagents or the use of expensive reagents. On the other hand, recently, a catalytic enantioselective synthesis method has been reported or disclosed [Angew. Chem. Int. Ed. Engl. (1996) 35, 448; Chem. Lett. (1996) 861 JP-A-7-252174, JP-A-7-118188]. However, the catalytic activity and optical purity of these synthetic methods are insufficient, leaving much room for improvement. .

In addition, by performing a catalytic asymmetric hydrogenation reaction on 3,3,3-trifluoro-2-acetoxy-1-propene using optically active rhodium gold bending, a high degree of non-uniformity can be achieved. It has been reported that the yield is high J. Org. Chem. (1980) 45, 2362; J. Am. Chem. Soc. (1991) 113, 8519].

However, such high asymmetric efficiency is limited only to the propene compounds described above, and remains unknown for compounds with 3 i-exchange or higher. The present invention was made in view of the above Φ information. Its purpose is to use optically active materials, which are important as bioactive or functional materials such as pharmaceuticals and agricultural chemicals and liquid crystals. An object of the present invention is to provide a 1- (trifluoromethyl) alcohol and other 11- (perfluoroalkyl) alcohols and their precursors, and a production method capable of easily synthesizing these in high yield.

Ming composition,

That is, the present invention provides a compound of the general formula (I): RuL '[wherein, in the general formula (I), L' represents an optically active ligand. Using an optically active ruthenium complex represented by

^^ Formula (II):

[However, in the above general formula (Π), R _f is a perfluoroalkyl group, R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, an alkenyl group, an alkynyl group. , An alkoxy group, an aryloxy group, an alkylthioxy group, an arylthio group, an amino group, an amide group or a phosphono group, and R ³ represents an alkyl group, an aryl group, an aralkyl group, an alkenyl group, an alkynyl group. , An alkoxy group, an aryloxy group, an alkylthioxy, an aryloxy group or an amino group. By subjecting the 1- (perfluoroalkyl) unsaturated ester compound represented by

^^ Formula (III):

[However, in the general formula (III), R _f , R ′, R ² and R ³ are the same as those described above. The present invention relates to a method for producing a carboxylic acid ester of optically active 1- (perfluoroalkyl) alcohol, comprising a carboxylic acid ester of an optically active 1- (perfluoroalkyl) alcohol represented by the formula:

The optically active (perfluoroalkyl) alcohol of the present invention is represented by the following general formula (IV).

Formula (IV):

[However, in the general formula (IV), R _f is a perfluoroalkyl group, R ¹ and R ² are independently a hydrogen atom (however, it is possible that R ¹ and R ² are hydrogen atoms at the same time. ), An alkyl group, an aryl group, an aralkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, an alkyloxy group, an aryloxy group, an amino group, an amide group or a phosphono group. ].

The optical activity of 1- (perfluoroalkyl) alcohol The production method comprises asymmetric hydrogenation of an optically active 1- (perfluoroalkyl) unsaturated ester compound represented by the general formula (II) using a ruthenium complex represented by the general formula (I) as a catalyst. According to the general formula

An optically active 1- (perfluoroalkyl) alcohol carboxylic acid ester represented by the formula (III) is obtained, and further, by hydrolysis or reduction of the ester, the optically active 1- (perfluoroalkyl) alcohol represented by the following general formula (IV) is obtained. Perfluoroalkyl) 'Alcohol is obtained.

^^ Formula (IV):

[However, R _f , R ′ and R ² are the same as defined in the general formula (II). ]

According to the study of the present inventor, the 1- (perfluoroalkyl) unsaturated ester compound represented by the above general formula (Π) is asymmetrically prepared by using the optically active ruthenium lead compound represented by the general formula (I) as a catalyst. when the hydrogenated response, unexpectedly, optically active 1 one (per full O b alkyl) can be synthesized inexpensively in large quantities under high asymmetric yield carbonic phosphate esters of an alcohol _(such The optically active ruthenium lead was used as a catalyst for the hydroperoxidation of 1- (perfluoroalkyl) unsaturated ester compounds as a catalyst, and the effect was more than expected. It has uniqueness and its features.

This carboxylic acid ester of an optically active 1- (perfluoroalkyl) alcohol is, for example, an optically active 1- (perfluoroalkyl) alcohol. It is important as an intermediary or precursor for the production of metal.

According to the study by the present inventors, the carboxylic acid ester of the optically active mono (perfluoroalkyl) alcohol can be easily hydrolyzed, and as a result of the hydrolysis, the optically active 1_ (perfluoroalkyl) alcohol (Alkyl) alcohol can be efficiently and easily produced.

The optically active 1- (perfluoroalkyl) alcohols obtained in this way, and in particular, 11- (trifluoromethyl) alcohol, are particularly important for pharmaceuticals, agricultural chemicals, liquid crystals and other functional materials. Known, and until now its synthesis has been very difficult. As described above, this study has established a method that can easily supply a large amount of it.

In the present invention, the alkyl group in the general formulas (11), (III) and (IV) is, for example, a carbon atom having 1 to 20 carbon atoms which may have an iS substitution of a halogen atom ^. An alkyl group or a cycloalkyl group which may be branched. Examples of the aryl group include a phenyl group, a naphthyl group and an anthryl group which may have a substituent. Examples of the substituent include an alkyl group having 1 to 10 carbon atoms which may be branched, an alkoxy group, and a halogen atom. Examples of the aralkyl group include a benzyl group, a 'p-methylbenzyl group, a naphthylmethyl ^, a furfuryl group, a hyphenethyl group and the like. Examples of the alkenyl group include a vinyl group, a styryl group, a 1-probenyl group, a 1-butenyl group, a 1-hexenyl ^, a 1-decenyl group, a cyclohexenyl group, an aryl group, a cinnamyl group and a 2-butenyl group. , 2-decenyl group and the like. Examples of the alkynyl group include an ethynyl group, a phenylethynyl group, and a 2-propynyl group.

In the present invention, as the carboxylic acid ester of the optically active 1- (perfluoroalkyl) alcohol represented by the general formula (I), the R _f is A perfluoroalkyl group such as CF or C ₂ F or C ₃ F ₇ , with CF ₃ being particularly preferred.

Further, in the present invention, a catalyst used for an asymmetric hydrogenation reaction of a 1 _ (perfluoroalkyl) unsaturated ester compound of the general formula (II),

(I): As the optically active ruthenium complex represented by RuL *, those having an optically active phosphine ligand are preferable.

The optically active ruthenium-phosphine complexes represented by the general formula (II) include, for example, Japanese Patent Publication No. 7-57758, Hei 5-111, No. 19, No. 4-81 596, 5 _ 1 2 3 5 3, No. 4 _ 2 1 0 6 966, USP 5 1 9 8 5 6 1, USP 5 2 0 2 4 7 3, EP 0, 4 0 8, 3 4 0, B 1, J. Am. Chem. Soc. (1987) 109,5856, J. Am. Chem. Soc. (1995) 117,4423, and Tetrahedron Lett. (1999) 40, 3175. The types of phosphine ligands are, for example, (R) _ (+) — 2,2, _bis (diphenylphosphino) -1,1,1-binaphthyl ((R) —BI NAP) ,

(R) ― (+) — 2, 2, 1-bis (di-p-tolylphosphino) 1 1, 1, 1-binaphthyl ((R) — Tol—BI NAP), (-) — 1, 2 ' -Bis ((2R, 5R) -1,2,5-dimethylphosphorano) 'benzene ((R, R) —Me DUPHS), (1-1) 1,1,2-bis ((2R, 5R ) -2,5-Dimethylphosphorano) ene ((R, R) -Me-BPE), (S, S) -1,2, enediylbis [(ο-Methoxyphenyl) phenylphosphine]

((S, S) i D i PAMP) ヽ (2 R, 3 R)-(+) —bis (diphenylphosphino) butyl ((R, R) — CH I RAPH〇 S), (2 S , 4 S) — tert-butyl 4- (diphenylphosphino) 1-2- (diphenylphosphinomethyl) _ 1-pyrrolidinecarboxylate ((S, S) -BPPM), (2R, 3 R) one (one) one 2,3-bis (diphenylphosphine Ino) Bicyclo [2,2,1] hepucan 5-ene ((R, R) -NORP H〇S), (4R, 5R)-(-) —◦—Isopropylidene 1, 2,3 —Dihydroxy 1,4-bis (diphenylphosphino) butane ((R, R) — DI OP), (S)-(-) —2,2,1-bis (diphenylphosphino) — 1,1,1-Binaphthyl ((S) — BI NAP) ヽ (R)-(6,6'-Dimethyl-1,2'-biphenylylene) Bis (diphenylphosphine) ((R) — BI PHEMP), (R) -12,2'-bis (dicyclohexylphosphino) -1,6,6,1-dimethyl-1,1, _biphenyl ((R) -BI CHEP) and the like.

The ligand of the optically active ruthenium complex used in the present invention is not limited to the above phosphine.

In the above-mentioned hydrogen reaction, the optically ruthenium complex is usually used in an amount of 0.00000001-1 mol 1% based on the reaction substrate.

The solvent used at this time is not particularly limited, and examples thereof include alcohol solvents such as methanol and ethanol, ether solvents such as getyl ether and tetrahydrofuran, and ester solvents such as ethyl acetate. Examples include a halogen-based solvent such as methylene chloride, a hydrocarbon-based solvent such as hexane and toluene, acetonitril, dimethylformamide, and the like, and preferably an alcohol-based solvent such as methanol and ethanol. The pressure of hydrogen used for the reaction can be appropriately selected from 1 atm to 200 atm, but is preferably from 1 atm to 100 atm.

The reaction temperature is preferably in the range of 0 ° C to 100 ° C, at which the temperature can be appropriately selected from the temperature range M of 100 ° C to 200 ° C.

The starting material, the 11- (perfluoroalkyl) unsaturated ester compound of the general formula (II) can be prepared, for example, by a known method as described below. For example, according to U.S. Pat. No. 4,149,010), it can be easily synthesized from trifluoromethylketone.

Furthermore, this trifluoromethyl ketone is also known (J. Am. Chem.

Soc. (1956) 78, 2268, J, Org. Chem. (1987) 52, 5026] From the use of trifluoroacetic acid or trifluoroacetic acid ester and an organometallic reagent such as a Grignard reagent or alkyllithium. Can be synthesized as follows.

The acid pay de can synthesis from pyridine and preparative Rifuruoro acetic anhydride (Tetrahedron (1995) 51,2573) ₀

Trifluoromethylketone can also be synthesized from trifluoromethyltrimethylsilane (Ruppert trial build) (Angew. Chem. Int. Ed. (1998) 37,820).

Also, as shown below, trifluoroacetate and the corresponding ester From this, a ketoester is synthesized using LDA, and then treated with an acid to allow the decarboxylation reaction to proceed to synthesize the desired trifluoromethylketone (Tetrahedron (1993) 49, 1725) ₀

In the present invention, the carboxylic acid ester of 1- (perfluoroalkyl) alcohol represented by the general formula (III) obtained by the asymmetric hydrogenation reaction is easily converted to the general formula (IV) by hydrolysis. It can be converted to the optically active 1- (perfluoroalkyl) alcohol represented. In this case, it is preferable that R ¹ and R ² do not simultaneously form a hydrogen atom (arbitrary conditions can be selected for the hydrolysis as long as an ester group can be eliminated, and hydrochloric acid, sulfuric acid, acetic acid, or the like can be used. Acid hydrolysis, alkali hydrolysis using sodium hydroxide, potassium hydroxide, potassium carbonate, or the like can be used.

Further, instead of the hydrolysis, the carboxylic acid ester of the 1- (perfluoroalkyl) alcohol is subjected to a reduction reaction using a lithium hydride λaluminum or the like to thereby form the 1- (perfluoroalkyl) alcohol. It can also be converted to alcohol.

Invitation ΙΠΊΐ ^ 'Ι:

As described above, according to the present invention, in obtaining the carboxylic acid ester (alcohol precursor) of the 11- (perfluoroalkyl) alcohol represented by the general formula (III), An optically active ruthenium complex is prepared by converting the 1- (perfluoroalkyl) unsaturated ester compound of the general formula (II) into an optically active ruthenium complex. The asymmetric hydrogenation reaction is carried out by using as a catalyst, so that the carboxylic acid ester of an optically active (perfluoroalkyl) alcohol of the general formula (III) can be easily synthesized in a high yield, and this is further hydrolyzed. By decomposing or reducing, important intermediates of pharmaceuticals, agricultural chemicals, liquid crystals, and functional materials represented by optically active (trifluoromethyl) alcohol can be provided easily and in large quantities at low cost. . Further, according to the present invention, it is possible to provide a novel optically active (perfluoroalkyl) alcohol in which R ¹ and R ² in the formula (IV) are not simultaneously hydrogen atoms.

Prestigious example

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Example 1

(1) Synthesis of 1,1,1,1-trifluoro-2-acetoxdodecane>

[RuCl (p-cymene) ((R) -BINAP) Cl (1.9 mg), anhydrous degassed methanol (1 m 1) was placed in a 100 ml stainless steel autoclave in a dry box. ) And substrate (560 mg). After seven vacuum / hydrogen cycles, the tube was pressurized to an initial pressure of 4 atm hydrogen (9.99.999%). The reaction was stirred at 50 ° C. for 42 hours. The reaction product was concentrated, the residue was poured onto a short SiO ₂ column, and the reaction product was eluted with ethyl acetate / hexane to obtain 542 mg of the product (96% yield, 99.7% ee). ). Optical purity was determined using an optical resolution gas chromatograph (WCOT FUSED SILICA 50M x 0.25MM COATED WITH CP-CYCLODES B 236MDF = 0.25UM).

1.60-1.82 (m, 2H), 2.15 (s, 3H), 5.20-5.39 (m, lH) ppm

^{_{19 F -NMR (CDC 1 3)}} : Beauty - 77.73 (d, J = 6.8Hz , 3F) ppm

IR (neat): 2927, 1763, 1281, 1220, 1178, 1148cm "'

Example 2

<(R)-(-)-11,1,1-Trifluoro-2-acetoxydeca Synthesized in the same manner as in Example 1 (99% yield, 99% e e).

^{_{1 H - NMR (CDC 1 3}} ): Beauty 0.8 0.92 (m, 3H), 1.20-1.40 (m, 12H),

1.65-1.80 (m, 2H), 2.14 (s, 3H), 5.20-5.34 (m, lH) ppm

¹⁹ F-NMR (CDC 13): 77-77 (d, J = 6.8Hz, 3F) ppm

IR (neat): 2930, 1763, 1283, 1222,1176,1148cm- ¹

The same starting material as in Example 1 (1 mm 0 1), R u C 1 2 [(S) - BI NAP] (1 mo 1%) Likewise 1 8 more hours, to asymmetric hydrogenation using a As a result, the corresponding (+)-1,1,1-trifluoro-2-acetoxdodecane was obtained in 98% yield and 99% ee).

[0 0 0 1]

<Synthesis of 1,1,1-Trifluoro-2-acetoxy_3-cyclohexylpropane> It was synthesized as in Example 1 (79% yield, 95% ee).

¹ H-NMR (CD C 13): σθ.75-1.40 (m, 6H), 1.48-1.88 (m, 12H),

2.14 (s 3H 5.31-5.50 (m, lH) ppm

^{1 F - NMR (CD C 1} 3): Beauty - 78.10 (d, J two 6.6 Hz, 3F) ppm

IR (neat): 2928, 1762, 1285,1225,1176,1138cm " ¹

Presidency 5

It was synthesized as in Example 1 (99% yield, 99% e e).

¹ H-NMR (CDC 13): σθ.81-0.95 (m, 3H), 1.15-1.50 (m, 12H), 1.81-1.95 (m, 2H), 5.47-5.64 (m, lH), 7.43-7.68 (m, 3H), 8.06-8.1Z

(m, 2H) ppm

¹⁹ F-NMR (CDC 1): -77.54 (d, J2 6.0 Hz, 3F) ppm

IR (neat): 2927, 1739, 1262,1179,1108,710cm- '

Example 6

(―) ー 1,1, 1-Trifluoro-2-acetoxy dodecane (250 mg) was added to a methanol solution (15 ml) of ^ acid potassium (1.2 g), and the mixture was added at room temperature. I asked at 1 o'clock. After the reaction solution was filtered, water was added, and the mixture was extracted with ether. After drying and distilling off the residue, the residue is purified by silica gel chromatography to obtain 209 mg of the desired compound (98% yield). Obtained.

^{1 H-NMR (CD C 1} 3): Beauty 0.82- 0.96 (m, 3H), 1.03-1.78 (m, 18H), 2.08-2.18 (m, lH), 3.80-4.01 (m, lH) ppm

¹⁹ F-NMR (CDC1,): -80.59 (d, J2 6.9Hz, 3F) ppm

IR (neat): 3365,2926,1279,1172,1141cm " ¹

Example 7

<Synthesis of ('+)-1- (trifluoromethyl) octanol> The compound was synthesized in the same manner as in Example 6.

¹ H-NMR (CD C 1): 0.81-0.93 (m, 3H), 1.15-1.45 (m, 12H), 1.48-1.80 (m, 2H), 2.11 (d, J = 6. Hz, 1H ), 3.80-4.01 (m, lH) ppm

^{1 9 F - NMR (CDC 13} ): Beauty - 80.58 (d, J = 6.7Hz , 3F) ppm

IR (neat): 3374,2928,1279,1170,1142cm "'

rnmm 8

Synthesized in the same manner as in Example 6.

^{1 H-NMR (CD C 1} 3): σθ.85-1.33 (m, 6H), 1. '48 -1.82 (m, 7H), 1.94 (d, J = 6.3Hz, lH), 3.99-4.07 ( m, lH) ppm

^{19 F - NMR (CD C 1} 3): Beauty - 80.85 (d, J = 6.8Hz , 3F) ppm

IR (neat): 3391,2926, 1280, 1165, 1132cm- '

Participant example 1

<1, 1, 1 _ Trifluoro- 2-acetoxy 2- Synthesis of dodecene

>

Acetic anhydride (6.9 ml) was added to a pyridine solution (5.9 ml) of trifluoromethyldehydroquinone (3.5 g) at room temperature, and the mixture was stirred for 20 hours. 0 ° C in 2 NHC 1 aqueous solution was added, was extracted with pentane, the organic layer was washed with saturated N a HC 0 ₃ water. After drying and distilling off the solvent, the residue was distilled under reduced pressure to obtain 3.2 g (yield: 78%) of a target compound.

^{! H-NMR (CD C 1} 3): Beauty 0.8 0.95 (m, 3H), 1.20-1.51 (m, 14H), 1.91-2.07 (m, 2H), 2.24 (s, 3H), 5.99-6.11 (m , lH) ppm

^{_{19 F -NMR (CDC 1 3)}} : Beauty - 71.37 (s, 3F) ppm

IR (neat): 2928, 1773, 1303, 1192,859cm- ¹

Boiling point 9 8—10 1 ° C / 0.6 mmH g

II? '

Synthesis of 1,1,1-tritrifluoro-2-acetoxy-2-decene> It was synthesized in the same manner as in Reference Example 1 (72% yield).

^{1 H - NMR (CDC 1,} ): or0.88 (t, J = 7.1Hz, 3H), 1.21- 1, 33 (m, 8H), 1.38-1.45 (m, 2H), 1.96-2.05 (m, 2H), 2.24 (s, 3H), 6.05 (tJ = 7.5Hz, lH) ppm

^{_{19 F -NMR (CD C 1 3}} ): Beauty - 71.35 (s, 3F) ppm

IR (neat): 2930, 1788, 1335, 1198, 1136, 842cm " ¹

Boiling point 7 2— 7 3 ° C / 5 mmH g

It was synthesized in the same manner as in Reference Example 1 (79% yield).

¹ H-NMR (CDC 1): 1.03- 1.31 (m, 6H), 1.61-1.78 (m, 4H), 2.05-2.13 (m, lH), 2.25 (s, 3H), 5.88 (t, J = 10.Hz, 1H) ppm

¹⁹ F -NMR (CDC 1): Beauty - 71.19 (s, 3F) ppra

IR (neat): 2932, 1785, 1327, 1193, 1134, 829cm " ¹

Boiling point 6 6— 7 2 ° C / 2 mmH g Participant example 4

<Synthesis of 1,1,1,1-trifluoro-2-benzoyloxy-12-dodecene> A benzoyl alcohol was used in place of acetic anhydride in Reference Example 1 to synthesize (65% yield).

¹ H-NMR (CD C 13): σθ.81-0.97 (m, 3H), 1.12-1.53 (m, 14H), 1.98-2.15 (m, 2H), 6.10-6.23 (m, lH), 7.41- 7.71 (m, 3H), 8.08-8.19 (m, 2H) PPm

¹⁹ F -NMR (CDC 13): Beauty - 71.37 (s, 3F) ppm

IR (neat): 2927, 1757, 1242, 1136, 704cm ' ¹

Boiling point 1 5 3— 1 5 4 ° C / 1.2 mmH g

Claims

The scope of the claims

1. General formula (I): RuL * [However, in the above general formula (I),

1 represents an optically active ligand. Using an optically active ruthenium complex represented by

Formula (II):

[However, in the above general formula (Π), R _f is a perfluoroalkyl group,

R ¹ and R ² independently represent a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, an alkylthioxy group, an arylthiooxy group, an amino group, R ³ represents an alkyl group, an aryl group, an aralkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, an alkylthioxy group, an arylthiooxy group or an amino group. Express. By subjecting the 1- (perfluoroalkyl) unsaturated ester compound represented by

General formula (III):

[However, in the general formula (III), R _f , RR ² and R ³ are as described above. Is the same as A process for producing a carboxylic acid ester of an optically active (perfluoroalkyl) alcohol, which obtains a carboxylic acid ester of an optically active (perfluoroalkyl) alcohol represented by the formula:

2. Using ruthenium chiral phosphine, which is an optically active phosphine ligand, as the ruthenium complex,

Equation (ΙΙΓ):

(Wherein, in the general formula (ΠΓ), I ¹ , R ² and R ³ are the same as described above) to obtain a carboxylic acid ester of optically active 1 _ (trifluoromethyl) alcohol represented by the following formula: 4. The process for producing a carboxylic acid ester of optically active (perfluoroalkyl) alcohol as described in item 1 of the range of packing.

3. The process for producing a carboxylic acid ester of optically active 1- (perfluoroalkyl) alcohol according to claim ^1, wherein R ¹ and R ² are not simultaneously hydrogen atoms.

4. Claims 1- (Perfluoro) represented by the general formula (II) described in claim 1 using a ruthenium lead compound represented by the general formula (I) described in the first item of the ffl as a catalyst. Asymmetric hydrogenation reaction of an alkyl) unsaturated ester compound to obtain a carboxylic acid ester of an optically active (perfluoroalkyl) alcohol represented by the general formula (III) described in Packing 1; By hydrolysis or reduction of this ester, an optically active 1- (perfluoroalkyl) alcohol represented by the following general formula (IV) is obtained. Method for producing optically active 1- (perfluoroalkyl) alcohol <

General formula (IV):

(However, in the general formula (IV), R _f , R ¹ and R ² are the same as described above.)

5. As the ruthenium complex represented by the general formula (I), use is made of ruthenium chiral phosphine in which L * is an optically active phosphine ligand,

Equation (ΙΓ):

(However, in the general formula (ΙΙ ′), R ′, R ² and R ³ are the same as described above.) The asymmetric hydrogenation reaction of the 1- (trifluoromethyl) unsaturated ester compound represented by Let me

"^ Formula (ΙΙΙ '):

(However, in the general formula (ΙΙΙ ′), R ′, R ² and: R ³ are as defined above. Is the same as The optically active carboxylic acid ester of 11- (trifluoromethyl) alcohol represented by the following formula (IV) is obtained by hydrolysis or reduction of this ester. 5. The method for producing 11- (perfluoroalkyl) alcohol according to claim 4, wherein the alcohol is obtained.

Formula (IV):

6. The optical activity according to claim 4, wherein in the general formulas (1), (11), (ΠΙ), and (IV), R ¹ and R ² are not simultaneously hydrogen atoms. 1— (Perfluoroalkyl) alcohol production method.

7. An optically active (perfluoroalkyl) alcohol represented by the following general formula (IV), obtained by the production method according to claim 4.

^: Formula (IV):

[However, in the general formula (IV), R _f is a perfluoroalkyl group, R ¹ ′ and R ² are each independently a hydrogen atom (provided that R ¹ and: ² are hydrogen atoms simultaneously. ), Alkyl, aryl, aralkyl, alkenyl, alkynyl, alkoxy, aryloxy, alkyl Represents a thioxy group, an aryloxy group, an amino group, an amide group or a phosphono group. ]

8. An optically active 1- (trifluoromethyl) alcohol represented by the following general formula (IV '), which is obtained by the production method according to claim 5, wherein the alcohol is represented by the following general formula (IV'): Optically active (perfluoroalkyl) alcohols described in (1).

"^ Formula '(ιν'):