JPH0516414B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula (In the formula, R ¹ and R ² are an alkyl group, an aryl group, an aralkyl group, or an alkenyl group, and Z' is a protected hydroxyl group, an alkoxy group, a substituted amino group, or a hydroxyl group.) .

According to the method of the present invention, pharmaceuticals, chiral modifiers (Terashima et al., Chem.Pharm.Bull. 25 ,
1273 (1977)), optical resolving agents (R. Kelly et al.
Synthetic intermediates for threo-2-amino alcohols and amino sugars such as pseudoephedrin, N-methyl pseudoephedrin , and chloramphenicol, which are useful as (2S ^* ,3S ^* )-5-phenyl-4
-Threo isomers of 1,2-diols such as pentene-2,3-diol can be synthesized with high selectivity (see Reference Examples below).

Conventional methods for synthesizing alcohols represented by the above general formula [] include (a) reduction of ketones with sodium borohydride, lithium aluminum hydride, aluminum triisopropoxide, sodium bis(2-methoxyethoxy)aluminum hydride, etc. A method of reducing threo-1,2-diol or threo-2-aminoalcohol by reducing it with a reagent (J.
D.Morrison and H.S.Mosher “Asymmetric
Organic Reactions” Prentice Hall, Inc., US
A., M. Tramontini, Synthesis, 1982 , 605.
T. Nakata et al., Tetrahedron Lett., 24 ,
2653 (1983)), (b) A method of oxidizing trans-olefin with osmium tetroxide, osmium tetroxide-chlorate or osmium tetroxide-hydrogen peroxide to give threo-1,2-diol (c) cis - Method of forming threo-1,2-diol by epoxidizing olefin and then ring-opening addition of water; (d) The above general formula of tartaric acid, threonine, etc.
A method of deriving from a compound having the same partial structure as the alcohol represented by is known. However, in method (a), a considerable proportion of unnecessary stereoisomers are produced as by-products, making it difficult to synthesize with high selectivity a compound having the same steric configuration as the alcohol represented by the above general formula []. . Methods (b) and (c) are applicable only to the synthesis of 1,2-diols and cannot be applied to the production of threo-1,2-amino alcohols. Furthermore, since the raw material olefin must be produced stereoselectively, it has drawbacks such as being difficult to produce in many cases. Method (d) has drawbacks such as being limited by the carbon skeleton of the compound that can be produced.

As a result of research to overcome these conventional drawbacks, the present inventors discovered a method for highly selectively producing the alcohol represented by the general formula (),
The invention has been completed.

In the present invention, in the presence of a fluorine anion in an aprotic polar solvent, the general formula (wherein R ¹ and R ² are an alkyl group, an aryl group, an aralkyl group, or an alkenyl group, and Z is a protected hydroxyl group, an alkoxy group, or a substituted amino group.) and a ketone of the general formula HSiR ³ R ⁴ R ⁵ - [] (In the formula, R ³ is an alkyl group, aryl group, aralkyl group, or alkoxy group, and R ⁴ and R ⁵ are an alkyl group, aryl group, aralkyl group, alkoxy group, or a hydrogen atom.) The alcohol represented by the general formula [] is produced by reacting with the hydrosilane represented by the following and then hydrolyzing with an acid or an alkali.

The ketones represented by the general formula [] that are raw materials of the present invention include 2-acetoxy-1-phenyl-1-propanone, 2-acetoxy-1-phenyl-1-butanone, 2-benzoyloxy-
1-phenyl-1-propanone, 2-(1'-ethoxyethoxy)-1-phenyl-1-propanone,
2-t-butoxy-1-phenyl-1-propanone, 2-(benzenesulfonyloxy)-1-phenyl-1-propanone, 2-acetoxy-3-heptanone, 4-(1'-ethoxyethoxy)-1- Phenyl-1-penten-3-one, 2-dimethylamino-1-phenyl-1-propanone, 2-dimethylamino-1-phenyl-1-butanone, 2
-dimethylamino-1-(4-methoxyphenyl)
-1-propanone, 2-dimethylamino-1-
(3,4-dimethoxyphenyl)-1-propanone, 2-dimethylamino-1-(2,5-dimethoxyphenyl)-1-propanone, 2-(ethoxycarbonylamino)-1-phenyl-1-propanone , 3-benzyloxymethyl-2-dimethylamino-1-phenyl-1-propanone, 3-acetoxy-1-phenyl-2-butanone, 1-acetoxy-1-phenyl-2-propanone, 2-
Acetoxy-1,3-diphenyl-3-propanone, 2-acetoxy-1-phenyl-3-buten-1-one, 1-phenyl-4-acetoxy-1
-Penten-3-one etc. can be used.
These raw materials include (i) a method utilizing the substitution reaction of the corresponding α-haloketone with primary and secondary amines or carboxylic acid salts; (ii) a method using α-hydroxy such as (S)-lactic acid and (S)-alanine; Alternatively, it is a compound that can be easily synthesized by a method derived from α-amino acids (see Reference Examples). The above general formula () which is one raw material
Hydrosilanes represented by are industrially easily available compounds, such as dimethylphenylsilane,
Methyldiphenylsilane, triphenylsilane,
Triethylsilane, benzyldimethylsilane, ethoxydimethylsilane, ethoxydiphenylsilane, triethoxysilane, methylphenylsilane, diphenylsilane, benzylphenylsilane, phenylethoxysilane, butylethoxysilane, dibutylsilane, β-naphthylsilane, phenylsilane , benzylsilane, t-butoxysilane, etc. can be used. Hydrosilane can be used in an amount ranging from 0.3 molar equivalent to a large excess, but in order to carry out the reaction efficiently, it is preferably used in an equimolar amount to 2 molar equivalents.

The present invention requires that the reaction be carried out in the presence of fluorine anions. As the fluoride anion source, fluorides such as tetrabutylammonium fluoride, benzyltrimethylammonium fluoride, potassium fluoride, and cesium fluoride can be used. A so-called catalytic amount is sufficient for the amount used.

Further, the present invention requires that the reaction be carried out in an aprotic polar solvent. As the aprotic polar solvent, for example, amides such as hexamethylphosphoric acid triamide (HMPA) and dimethylformamide, ureas such as N,N'-dimethylpropylene urea, and sulfoxides such as dimethyl sulfoxide can be used. Furthermore, these aprotic polar solvents may be used in combination with diethyl ether, dioxane, tetrahydrofuran, dichloromethane, benzene, and the like.

The reaction proceeds at -50°C to 100°C, but in order to conduct it efficiently and with high selectivity, it is necessary to heat the reaction at -20°C to 30°C.
is preferred.

The present invention will be explained in more detail below using Examples and Reference Examples.

Reference example 1 2-Bromo-1-phenyl-1-propanone
Dissolve 1.32g (6.22mmol) in 5ml of dimethylformamide (DMF) and add 1.20g of potassium acetate.
(12.2 mmol) was added and stirred at 50°C for 1.5 hours.
After adding 30 ml of ether and washing with water (30 ml x 3),
The organic layer was dried over anhydrous magnesium sulfate. After removing the desiccant, the liquid was concentrated under reduced pressure to obtain a crude product. Purification by column chromatography (silica gel, methylene chloride) yielded 1.04 g of 2-acetoxy-1-phenyl-1-propanone as a colorless oil.
Yield 87%.

¹ H-NMR (CDCl ₃ ): δ1.49 (d, J=7Hz,
3H), 2.11 (s, 3H), 5.94 (q, J=7Hz,
1H), 7.3-7.7 (m, 3H), 7.8-8.1 (m,
2H). IR (neat): 1742, 1700, 1233, ^{704cm -1} . Reference example 2 2-Bromo-1-phenyl-1- in 10ml DMF
Propanone 2.35g (11.1mmol), benzoic acid 1.89g
(15.5mmol), anhydrous potassium carbonate 1.09g
(7.85 mmol) were added one after another and stirred at 80°C for 1 hour. Add 50ml of ether and wash with water (30ml x 3 times)
After that, the organic layer was dried over anhydrous magnesium sulfate. After removing the desiccant, concentrate under reduced pressure and recrystallize from ether-hexane to obtain 2.06 g of 2-benzoyl-1-phenyl-1-propanone.
was obtained as colorless crystals. Yield 73%.

mp: 109-110℃ ¹ H-NMR (CDCl ₃ ): δ1.65 (d, J = 7Hz,
3H), 6.20 (q, J=7Hz, 1H), 7.2~7.7
(m, 6H), 7.8-8.2 (m, 4H). IR (KBr): 1727, 1696, 1276, 1126, 972,
718,706cm ^-1 ． Reference example 3 (S)-2-acetoxypropanoyl chloride
Add 3.01 g ([α] ^20/D −36.1○ (neat, = 1), optical purity 89%) (20.0 mmol) and 30 ml of dichloromethane to 200 ml of benzene, and after cooling to −15°C, 5.61 g (42.0 mmol) of aluminum chloride mmol) were added all at once. -15℃
After stirring for 18 hours, 50 ml of 1M hydrochloric acid was added to separate the organic layer and aqueous layer. The organic layer was washed with water (50 ml) and saturated aqueous sodium hydrogen carbonate solution (50 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure.
A crude product was obtained. Purified by column chromatography (silica gel, dichloromethane - dichloromethane: ethyl acetate = 2:1) to obtain (S) as a colorless oil.
3.13 g of -2-acetoxy-1-phenyl-1-propanone was obtained. Yield 82%.

Optical purity was assayed using Eu(TFC) ₃ (0.3 molar equivalent, CCl ₄ ) and found to be 88% ee.

[α] ^20/D −41.5○ (c 1.036, CHCl ₃ ) Reference example 4 20 ml of phenylmagnesium bromide (0.6M tetrahydrofuran (THF) solution) was added dropwise to 1.89 g (10.0 mmol) of (S)-N,N-dimethyl-2-(1-ethoxyethoxy)propanamide over 5 minutes under ice cooling. did. After stirring for 30 minutes at 0°C, 50 ml of saturated ammonium chloride aqueous solution was added, and dichloromethane extraction (50 ml
×2 times). After drying the organic layer with anhydrous maglucium sulfate, column chromatography (silica gel, dichloromethane:hexane = 1:1 ~
(S)-2- as a colorless oil.
1.62 g of (1-ethoxyethoxy)-1-phenyl-1-propanone was obtained. Yield 73%.

^1H -NMR ( _CDCl3 ) (diastereomer mixture with ethoxyethyl group): δ0.95-1.55
(m, 9H), 3.30~3.70 (m, 2H), 4.60~5.20
(m, 2H), 7.3~7.7 (m, 3H), 7.85~8.20
(m, 2H), IR (neat): 1690, 1450, 1271, 1130, 972,
704cm ^-1 ． Reference example 5 (S)-N,N-dimethyl-2-(1-ethoxyethoxy)propanamide 1.89g (10.0mmol)
Butyllithium (1.74M,
6.32 ml (11.0 mmol) of hexane solution was added dropwise.
After stirring at 0° C. for 30 minutes, the same post-treatment as in Reference Example 4 was carried out to obtain 1.49 g of (S)-2-(1-ethoxyethoxy)heptan-3-one as a colorless oil. Yield 74
%.

¹ H-NMR (CDCl ₃ ) (diastereomer mixture with ethoxyethyl group): δ0.7-1.0 (m,
3H), 1.0~1.8 (m, 13H), 2.3~2.7 (m,
2H), 3.3-3.7 (m, 2H), 3.8-4.3 (m, 1H)
4.4-4.8 (m, 1H). IR (neat): 2980, 2950, 1720, 1127, 1086,
1060cm ^-1 ． Mass [m/z (relative intensity)]: 202 (M ⁺ ), 157 (7),
85(9), 74(5), 73(100), 69(5), 57(15), 45(68),
44(6), 43(14), 41(11), 29(13), 27(8). Reference example 6 (S)-N,N-dimethyl-2-t-butoxypropanamide (1.02 g (5.91 mmol)) was added with 1M bromide 2 at 0°C.
- 12 ml of phenylethenylmagnesium was slowly added. After stirring at room temperature for 1 hour, 20 ml of saturated ammonium chloride aqueous solution was added, and dichloromethane (20 ml
3 times). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting reaction mixture was purified by column chromatography (silica gel, dichloromethane), and (S)-2-1
-butoxy-5-phenyl-4-pentene-3-
1.06 g of on was obtained as colorless crystals. Yield 78%.

mp: 64-66℃ [α] ^20/D −106○ (c 0.218, CHCl ₃ ) ¹ H-NMR (CDCl ₃ ): δ1.22 (s, 9H), 1.31
(d, J=7Hz, 3H), 4.14 (q, J=7Hz,
1H), 7.24 (d, J = 16Hz, 1H), 7.3-7.45
(m, 3H), 7.5-7.65 (m, 2H), 7.70 (d,
J=16Hz, 1H). IR (KBr): 1694, 1613, 1339, 1200, 1086,
1000, 950, 772cm ^-1. Mass [m/z (relative intensity)]: 217 (M ⁺ -15),
176(5), 132(11), 131(100), 103(21), 101(44),
77(12), 58(5), 57(92), 51(5), 41(15), 29(10). Reference example 7 2-Bromo-1-phenyl-1-propanone
10 ml of dimethylamine (50% aqueous solution) was added to a solution of 5.25 g (24.7 mmol) in 20 ml of ether, and the mixture was stirred at room temperature for 3 days. After adding phosphoric acid to adjust the pH to below 1, the organic layer was separated. After adding potassium carbonate to the aqueous layer to make it alkaline, ether extraction (30ml x
3 times). The extract was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then distilled under reduced pressure to obtain 2-dimethylamino-1- as a colorless oil.
2.15 g of phenyl-1-propanone was obtained. Yield 49
%.

bp: 120℃/3mm (Kugel) ¹ H-NMR (CDCl ₃ ): δ1.25 (d, J = 7Hz,
3H), 2.30 (s, 6H), 4.03 (q, J=7Hz,
1H), 7.3-7.6 (m, 3H), 8.0-8.2 (m,
2H). Example 1 Under nitrogen atmosphere, 59.1 mg (0.308 mmol) of 2-acetoxy-1-phenyl-1-propanone and 52 mg (0.38 mmol) of dimethylphenylsilane in HMPA1.
0.03 ml of tetrabutylammonium fluoride (TBAF) (0.5 MTHF solution) was added dropwise to the ml solution under ice cooling, and the mixture was further stirred in an ice bath for 20 hours. Add 2 ml of 1M sodium hydroxide methanol solution and stir at room temperature.
After stirring for an hour, 5 ml of water was added and ether extraction (10 ml x 3) was performed. The extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. Purification was performed by thin layer chromatography (silica gel, ethyl acetate:hexane = 1:1) to obtain 44.4 mg of 1-phenyl-1,2-propanediol as a colorless oil. Yield 95%.

¹ H-NMR (90MHz) analysis revealed that the threo/erythro ratio was 93:7.

¹ H-NMR of threo form (CDCl ₃ ): δ1.00 (d, J
=6.5Hz, 3H), 3.55 (broad s, 2H), 3.79
(dq, J = 7.2Hz, 6.5Hz, 1H), 4.28 (d, J
=7.2Hz, 1H), 7.29(s, 5H). Example 2 Diphenylsilane 0.370ml under nitrogen atmosphere
(2.00 mmol) of TBAF in 2 ml solution of HMPA
Add 0.4ml (0.5MTHF solution) and (S)-2 at 0℃.
-acetoxy-1-phenyl-1-propanone ([α] ^20/D -41.5○ (c 1.036, CHCl ₃ ), 88%ee)
A 2 ml solution of 384 mg (2.00 mmol) of HMPA was added dropwise over 3.5 hours. After further stirring at 0°C for 30 minutes,
10 ml of 1M sodium hydroxide in methanol was added. Thereafter, 163 mg of 1-phenyl 1,2-propanediol was obtained by the same operation as in Example 1. Yield 53.6%. (1S, 2S): (1R, 2S) = 92:8.

After diacetylated with acetic anhydride-pyridine, the optical purity of the (1S, 2S) form was assayed using Eu(TFC) ₃ and found to be 88% ee.

Example 3 Under nitrogen atmosphere, 56.2 mg (0.293 mmol) of 2-acetoxy-1-phenyl-1-propanone and 70 mg (0.354 mmol) of methyldiphenylsilane.
TBAF (0.5M THF solution) in HMPA0.3ml solution
0.030 ml was added dropwise and stirred at room temperature for 14 hours. below,
By the same operation as in Example 1, 1-phenyl-
39.4 mg of 1,2-propanediol was obtained. Yield 89
%. Treo:Erythro=92:8.

Example 4 7.5mg of cesium fluoride under nitrogen atmosphere
Dissolve in 2 ml of HMPA and cool to 0°C, then add 202 mg of 2-acetoxy-1-phenyl-1-propanone.
(1.05mmol), dimethylphenylsilane 0.19ml
(1.2 mmol) was added. After stirring at 0°C for 13 hours, 5 ml of 1M potassium hydroxide in methanol was added. Hereinafter, 1-phenyl-
115 mg of 1,2-propanediol was obtained. Yield 72
%. Treo: Etrillo = 95:5.

Example 5 3 potassium fluoride in 2 ml of HMPA under nitrogen atmosphere
mg was dissolved with heating. After cooling to 0℃, 2-
Acetoxy-1-phenyl-1-propanone 202
mg (1.05 mmol), dimethylphenylsilane 0.19 ml
(1.2 mmol) was added, and the mixture was stirred at 0°C for 12 hours and at room temperature for 48 hours. Hereinafter, 112 mg of 1-phenyl-1,2-propanediol was prepared in the same manner as in Example 1.
I got it. Yield 70%. Treo: Erythro = 95:5.

Example 6 Under a nitrogen atmosphere, 127 mg (0.500 mmol) of 2-benzoyloxy-1-phenyl-1-propanone and 0.092 ml (0.60 mmol) of dimethylphenylsilane were added.
Add TBAF (0.5MTHF) to 0.5ml HMPA solution under ice cooling.
Solution) 0.050 ml was added dropwise, and the mixture was further stirred in an ice bath for 6 hours. Add 1 ml of 1M sodium hydroxide methanol solution, stir overnight at room temperature, then add 5 ml of water.
Ether extraction (5 ml x 3) was performed. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained crude product was subjected to thin layer chromatography (silica gel, ethyl acetate:hexane = 1:
By purifying in step 1), 62 mg of 1-phenyl-1,2-propanediol was obtained as a colorless oil.
Yield 82%. Treo:Erythro=96:4.

Example 7 2-(1-ethoxyethoxy)- under nitrogen atmosphere
1-phenyl-1-propanone 111 mg
(0.500mmol), dimethylphenylsilane 84mg
(0.62 mmol) in 0.5 ml solution of HMPA under ice cooling.
0.050 ml of TBAF (0.5 MTHF solution) was added dropwise, and the mixture was further stirred at 0°C for 18 hours. Add 0.5 ml of 1M hydrochloric acid (methanol solution), stir at room temperature for 1 hour, then add 5 ml of water.
ml was added, and ether extraction (10 ml x 2) was performed. After drying the organic layer with anhydrous maglucium sulfate,
The mixture was filtered and concentrated under reduced pressure. The resulting reaction mixture was purified by thin layer chromatography (silica gel, ethyl acetate:hexane = 1:1), and a colorless oil, 1
42 mg of -phenyl-1,2-propanediol was obtained. Yield 55%. Treo: Erythro = 90:10.

Example 8 trans-1-phenyl-4- under nitrogen atmosphere
Acetoxy-1-penten-3-one 10.9mg
(0.050mmol), dimethylphenylsilane 8.4mg
(0.062 mmol) in 0.05 ml solution of HMPA, TBAF
(0.5 MTHF solution) 0.005 ml was added dropwise under ice cooling, and the mixture was further left in an ice bath for 12 hours. Add 0.1ml of 1M sodium hydroxide (methanol solution) and stir at room temperature.
I left it for a while. Add 3 ml of water and extract with ether (5 ml).
ml x 3 times). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting reaction mixture was purified by thin layer chromatography (silica gel, ethyl acetate:hexane = 1:1) to obtain 5-phenyl-4-pentene-
8.5 mg of 2,3-diol was obtained. Yield 95%.
HPLC analysis revealed that threo:erythro=84:16.

¹ H-NMR (CDCl ₃ -TMS): From threo/erythro mixture Threo body: δ1.17 (d, J = 6.2Hz, 3H), 2.40
(broad s, 2H), 3.68 (q, d, J=6.2Hz,
7.0Hz, 1H), 3.96 (d=d, 7.0Hz, 6.6Hz,
1H), 6.13 (d=d, J=6.6Hz, 16.2Hz,
1H), 6.55 (d, J=16.2Hz, 1H), 7.1~7.4
(m, 5H). Erythro body: δ1.14 (d, J = 6.2Hz, 3H), 2.40
(broad s, 2H), 3.89 (d=d, J=6.2Hz,
3.1Hz, 1H), 4.19 (d=d, J=3.1Hz, 6.6
Hz, 1H), 6.20 (d=d, J=6.6Hz, 16.2Hz,
1H), 6.55 (d, J=16.2Hz, 1H), 7.1~7.4
(m, 5H). Example 9 Trans-1-phenyl-4-(1-ethoxyethoxy)-1-penten-3-one 248mg
(1.00mmol), dimethylphenylsilane 164mg
(1.20 mmol) of TBAF in 1 ml solution of HMPA
0.1 ml (0.5 MTHF solution) was added dropwise under ice cooling, and the mixture was further stirred for 12 hours under ice cooling. After adding 1 ml of 1M hydrochloric acid (methanol solution) and stirring at room temperature for 10 minutes,
10 ml of water was added and ether extraction (5 ml x 3) was performed. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting reaction mixture was purified by thin layer chromatography (silica gel, ethyl acetate:hexane = 1:1) to obtain 5 as a colorless oil.
-phenyl-4-pentene-2,3-diol
Got 100mg. Yield 57%. Treo: Elytro =
88:12.

Example 10 175 mg (0.989 mmol) of 2-dimethylamino-1-phenyl-1-propanone and 159 mg (1.17 mmol) of dimethylphenylsilane in 1 ml of HMPA solution.
Add 0.1ml of TBAF (0.5MTHF solution) dropwise at room temperature.
Stirred for 10 hours. After adding 10 ml of ether and 10 ml of 2M hydrochloric acid and shaking for a while, the organic layer and the aqueous layer were separated. Potassium carbonate was added to the aqueous layer to make it alkaline, and then extracted with ether (3 ml x 5 times). After drying with anhydrous maglucium sulfate,
It was concentrated under reduced pressure to obtain a crude product. Purified by thin-layer chromatography (silica gel, ethyl acetate), 1-phenyl-2-dimethylamino-1-
146 mg of propanol was obtained. Yield 83%. ^1H -NMR
When observed, the production of erythro bodies could not be detected.

^1H -NMR of threo body: δ0.70 (d, J = 6.7Hz,
3H), 2.29 (s, 6H), 2.53 (q=d, J=6.7
Hz, 9.9Hz), 4.15 (d, J=9.9Hz, 1H), 4.85
(broad s, 1H), 7.1-7.4 (m, 5H). Example 11 2-dimethylamino-1-phenyl-1-propanone 176 mg (0.994 mmol), diphenylsilane
203 mg (1.10 mmol) of TBAF in 1 ml of HMPA solution
(0.5MTHF solution) 0.1ml was added dropwise. At this time, a considerable fever was observed. After stirring at room temperature for 12 hours, the same procedure as in Example 10 was performed to obtain 173 mg of 1-phenyl-2-dimethylamino-1-propanol.
Yield 97%. Treo: Eretro = 98:2.

Example 12 In a 1 ml solution of HMPA containing 180 mg (1.02 mmol) of 2-dimethylamino-1-phenyl-1-propanone and 217 mg (1.10 mmol) of methyldiphenylsilane,
Add 0.1ml of TBAF (0.5MTHF solution) dropwise at room temperature.
Stirred for 10 hours. By the same operation as in Example 10,
Colorless oily 1-phenyl-2-dimethylamino-
122 mg of 1-propanol was obtained. Yield 67%. ¹ H−
When observed by NMR, the formation of erythro form could not be detected.

5-phenyl-4-pentene-2,3-diol [(2S ^* ,3S ^* )/(2S ^* ,3R ^* )=88/12 mixture] 92.1mg (0.517mmol), 1,1-dimethoxycyclohexane 86.7mg (0.602 mmol) was dissolved in 1 ml of dichloromethane and dissolved in 4A-molecular sieve.
0.5 g and 0.025 ml of bistrimethylsilyl sulfate (1M dichloromethane solution) were added, and the mixture was stirred at room temperature for 3 hours. Two drops of triethylamine were added, and the molecular sieve was separated and thoroughly washed with dichloromethane. After concentration under reduced pressure, thin layer chromatography (silica gel, dichloromethane:hexane = 1:1)
trans-3,4-(cyclohexylidenedioxy)-1-phenyl-1-
Pentene 116.1 mg (2S ^* , 3S ^* ) and (2S ^* ,
3R ^* ) was obtained as a mixture. Yield 87%.

¹ H−NMR (CDCl ₃ −TMS) (2S ^* , 3S ^* ) body:
δ1.27 (d, J=5.7Hz, 3H), 1.2~1.8 (m,
10H), 3.82 (dq, J=7.8Hz, 5.7Hz, 1H),
4.03 (dd, J = 6.9Hz, 7.8Hz, 1H), 6.08 (dd,
J=6.9Hz, 16.2Hz, 1H), 6.58(d, J=16.2
Hz, 1H), 7.1-7.4 (m, 5H). IR (neat, cm ^-1 ): 2950, 1448, 1110, 968,
944, 750, 696 Mass [m/z (relative intensity)]: 258 (M ⁺ , 6),
215(28), 214(100), 186(12), 185(29), 160(19),
145(12), 144(47), 143(41), 131(22), 130(11),
129(50), 128(23), 126(17), 118(11), 117(64),
116(16), 115(39), 109(10), 105(14), 104(17), 98
(17), 91(17), 81(94), 67(10), 55(44), 43(37), 42
(12), 41(24), 39(10).

Reference example 9 Trans-3,4-(cyclohexylidenedioxy)-1-phenyl-1-pentene 120mg
(0.465 mmol) in 2.5 ml of dioxane solution, 1 ml of water,
Sodium metaperiodate 200mg (0.935mmol),
0.05 ml of osmium tetroxide (0.5 MTHF solution) was added, and the mixture was stirred at room temperature for 2 hours. After adding 2 ml of water, ether extraction (5 ml x 3) was performed. The extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. Distillation under reduced pressure yielded 66.8 mg of colorless oily trans-(2,3-cyclohexylidenedioxy)butanal. Yield 78.1
%.

^1H -NMR ( _CDCl3 ): δ1.2-1.8 (m, 13H),
3.4-4.2 (m, 2H), 9.71 (d, J=2Hz,
1H). The reaction that leads trans-(2,3-cyclohexylidenedioxy)butanal to donosamine is known.

[T. Mukaiyama, Y. Goto, S. Shoda, Chem. Lett., 671 (1983), C. Fuganti, P. Grasselli, G. Pedrocchi−
Fantoni, Tetrahedron Lett., 22 , 4017 (1981)]

Claims (1)

[Claims] 1. In a non-brotic polar solvent, in the presence of a fluorine anion, the general formula It consists of reacting a ketone of the formula with a hydrosilane of the general formula HSiR ³ R ⁴ R ⁵ and then hydrolyzing it with an acid or an alkali.
general formula A method for producing alcohol represented by (where R ¹
and R ² is an alkyl group, aryl group, aralkyl group or alkenyl group, Z is a protected hydroxyl group, alkoxy group or substituted amino group,
Z' is Z or a hydroxyl group. Further, R ³ is an alkyl group, aryl group, aralkyl group, or alkoxy group, and R ⁴ and R ⁵ are an alkyl group, aryl group, aralkyl group, alkoxy group, or a hydrogen atom. ).