CN1376659A - Process for preparing chiral desubstituted carbinol with high selectivity - Google Patents

Abstract

The invention is a new method for preparing chiral secondary alcohols with high yield and high stereoselectivity. It uses metal borohydride as a reducing agent, and under the action of Lewis acid and a catalytic amount of chiral ligands, the latent chiral The reduction of ketones to prepare chiral secondary alcohols. The present invention uses cheap, easy-to-obtain and easy-to-preserve metal borohydride as the reducing agent, thereby avoiding the use of highly toxic and expensive borohydride. The chiral ligands used in the present invention are all natural, cheap and easy to obtain. Therefore, the present invention provides an inexpensive and environmentally friendly method for the preparation of chiral secondary alcohols.

Description

A New Method for Highly Selective Preparation of Chiral Secondary Alcohols

technical field

The present invention relates to a method for preparing chiral secondary alcohols with high yield and high stereoselectivity through a novel reduction system. The reduction system is a composite metal complex composed of metal borohydride M(BH ₄ ) _n / Lewisacids/chiral ligands, this reduction system can catalyze latent chiral ketones to prepare chiral secondary alcohols.

technical background

Optically active chiral secondary alcohols are an important class of organic compounds, and they are often used as chiral intermediates, chiral auxiliary reagents or ligands. As a powerful means to prepare chiral secondary alcohols, the asymmetric reduction of latent chiral ketones has always attracted the attention of organic chemists. Now, people have developed a variety of reduction methods. Among them, the chiral oxazoline-catalyzed asymmetric hydroboration reaction developed by Itsuno and Corey is one of the most successful methods. However, since this type of reaction must face the toxicity and high price of borane, people have been paying attention to finding a cheap and non-toxic reduction method.

M(BH ₄ ) _n is a kind of cheap and stable reducing reagent. In organic reactions, it is often used for the reduction of carbonyl compounds and unsaturated carbon nitrogen compounds. For its use in the asymmetric reduction of latent chiral ketones, so far, there is only one case of catalytic reduction reported. In 1995, Japanese chemist T.Mukaiyama et al. reported the method of using KBH ₄ to prepare chiral secondary alcohols under the catalysis of chiral salen-Co(II) (T.Nagata, K.Yorozu, T.Yamada and T Mukaiyama, Angew. Chem. Int. Ed. Engl. 1995, 34, 2145).

Contents of the invention

The purpose of the present invention is to provide a novel reduction system [metal borohydride M(BH ₄ ) _n /lewiic acid NX _m /chiral ligand] to prepare chiral secondary alcohols. The reduction system can catalyze the preparation of chiral secondary alcohols from latent chiral ketones.

Mixing a certain proportion of metal borohydride M(BH ₄ ) _n and Lewis acid NX _m in an organic solvent can obtain a new type of reducing agent, which can produce high yield and high Selective reduction of various latent chiral ketones affords chiral secondary alcohols.

In the present invention, the molar ratio of latent chiral ketone to reducing system is 1:1-8.

The molar ratio of the metal borohydride M(BH ₄ ) _n /Lewiic acid NX _m in the present invention is preferably controlled between 1:8-0.2.

The ratio of the chiral ligand metal borohydride M(BH ₄ ) _n in the present invention is controlled between 1:0.5-200, and the reaction effect between 1:5-100 is the best.

The organic solvent used in the present invention is preferably THF, methylene dichloride and toluene.

The best reaction result can be obtained when the reaction temperature of the present invention is controlled between room temperature and reflux temperature.

The molecular formula of the latent chiral ketone is RCOR ¹ , and the molecular formula of the chiral secondary alcohol is RCOHR ¹ . Wherein R=C _1-12 hydrocarbon group, substituted phenyl PhR ² , phSO ₂ or PhSO ₂ CH ₂ . The hydrocarbon group is linear, branched alkyl, cyclohexyl, phenyl or naphthyl. R ¹ =C _1-12 hydrocarbon group, C _P H _2P+1 NO ₂ , C _p H _2p+1 NR ³ R ⁴ . wherein R ² =NO ₂ , CN, X, OCH ₃ or CF ₃ . P=1-3. R ³ or R ⁴ =H or C _P H _2P+1 .

In the chiral ligand metal borohydride compound M(BH ₄ ) _n , M=monovalent or divalent metal, such as lithium, sodium, potassium, calcium, magnesium, zinc, etc., n=1-2.

In said Lewis acid NX _m , m=Sn, Zr, Ti and Al, X=halogen, m=1-4.

，其中

表示单键、以及R型或S型单键，R或R¹＝CH³或苯基，

等，R⁴＝H、SO₂R⁶、R⁵＝H、NH2、NHCH³或N(CH³)₂，R⁶＝H、CH³或

。手性配体的结构式可以以下为例： The chiral ligand of the present invention has the following molecular formula:

,in

represents a single bond, and an R-type or S-type single bond, R or R ¹ =CH ³ or phenyl,

etc., R ⁴ =H, SO ₂ R ⁶ , R ⁵ =H, NH2, NHCH ³ or N(CH ³ ) ₂ , R ⁶ =H, CH ³ or

. The structural formula of the chiral ligand can be as follows:

Taking the asymmetric reduction of acetophenone as a model reaction, the effects of temperature, solvent, catalyst and the ratio of M(BH ₄ ) _n to NX _m on the reaction were discussed separately.

First, use it as a catalyst to investigate the effects of temperature, solvent, catalyst and the ratio of M(BH ₄ ) _n to NX _m on the reaction. The reaction operation is as follows: add M(BH ₄ ) _n and a certain proportion of NX _m to the reaction solvent under investigation, stir at room temperature for 1 hour, add a catalytic amount of 2 (10mol%), heat and reflux for 0.5 hours, and re- A solution of acetophenone in the reaction solvent was slowly added dropwise. After the reaction is completed, the product can be obtained by conventional treatment. The reaction results are shown in Table-1. From this reaction result we know:

(1) In a certain reaction solution, the stereoselectivity of the reaction increases with the increase of the reaction temperature.

(2) In the same reaction solution and the same reaction temperature, the stereoselectivity of the reaction depends on M(BH ₄ ) _n

Ratio to NX _m .

(3) Different reaction solvents have different effects on the reaction. When the reaction was carried out in THF under reflux,

The best stereoselectivity was obtained, followed by toluene and _worst by _CH2Cl2 .

(4) NX _m has a certain influence on the reaction. Such as SnCl ₂ , SnCl ₄ , ZrCl ₄ , TiCl ₄ and AlCl ₃ can take

Get better results.

Table-1: Effect of temperature, solvent and molar ratio of M(BH ₄ ) _n to Lewis acid on the reaction M(BH ₄ ) _n NX _m molar ratio Solvent Temperature Yield Ee

[M(BH ₄ ) _n /NX _m ] (°C) (%) (%) KBH ₄ SnCl ₂ 8 THF Reflux 80 36KBH ₄ SnCl ₂ 4 THF Reflux 89 57KBH ₄ SnCl ₂ 2 THF Reflux 93 96KBH ₄ SnCl ₂ 1.5 THF Reflux 92 95KBH ₄ SnCl ₂ 1 THF Reflux 94 89KBH ₄ SnCl ₂ 0.5 THF Reflux 90 80KBH ₄ SnCl ₂ 0.2 THF Reflux 93 78KBH ₄ SnCl ₂ 2 THF Room temperature 93 56KBH ₄ SnCl ₂ 2 THF ₂ THF ₄ 90-9 Reflux 92 35KBH ₄ SnCl ₂ 2 Dichloromethane Reflux 94 5KBH ₄ SnCl ₄ 4 THF Reflux 96 92NaBH ₄ SnCl _{2 2 THF Room temperature 98 53NaBH 4 SnCl 2 2 THF} Reflux 98 96NaBH ₄ AlCl ₃ 3 THF SnCl ₂ 2 _THF Reflux NaB 4 5 Reflux 98 95NaBH ₄ TiCl ₄ 4 THF Reflux 97 73LiBH ₄ SnCl _{2 2} THF Reflux 98 97Zn(BH ₄ ) ₂ SnCl ₂ 1 _THF Reflux 97 96LiBH 4 SnCl 2 2 THF Reflux 96 96Ca(BH ₄ ) ₂ THF ₂ THF 95NaBH ₄ LiCl 3 THF Reflux 93 0NaBH ₄ ZnCl ₂ 2 THF Reflux 93 5NaBH ₄ ZrCl _{4 4 THF Reflux 96 60NaBH 4 CuCl 2 2 THF Reflux 0 0KBH 4 TiCl 4 4 THF Reflux 96 68KBH 3} ZnB 4 Al9 ₄ ) ₂ SnCl ₄ 2 THF Reflux 97 93LiBH ₄ SnCl ₄ 4 THF Reflux 96 95

After investigating the effects of temperature, solvent and the molar ratio of M(BH ₄ ) _n /NX _m on the reaction, we studied the effect of different chiral ligands on the reaction (Figure 1). Here again, the asymmetric reduction of acetophenone is selected as the model reaction, and the equivalent ratio of M(BH ₄ ) _n /acetophenone used in the reaction is 1.1:1. Examples of reaction results are shown in Table-2. The amount of catalyst in Table-2 is relative to acetophenone.

     Table-2: Effects of different chiral ligands on the reaction

M(BH ₄ ) _n /NX _m / molar ratio chiral ligand dosage (mol%) yield (%) Ee (%)

KBH ₄ /SnCl ₂ /2 1 10 94 64

KBH ₄ /SnCl ₂ /2 2 10 96 96

KBH ₄ /SnCl ₂ /2 2 20 95 95

KBH ₄ /SnCl ₂ /2 2 40 94 98

KBH ₄ /SnCl ₄ /4 2 100 93 97

KBH ₄ /SnCl ₂ /3 2 200 95 96

LiBH ₄ /SnCl ₂ /2 2 5 96 94

KBH ₄ /SnCl ₂ /2 2 2 98 92

KBH ₄ /SnCl ₂ /2 2 1 96 91

KBH ₄ /SnCl ₂ /2 2 10 95 96

LiBH ₄ /SnCl ₄ /4 2 10 93 93

NaBH ₄ /TiCl ₄ /4 2 20 94 69

NaBH ₄ /AlCl ₃ /3 2 15 96 67

Zn(BH ₄ ) ₂ /SnCl ₂ /1 2 20 94 92

KBH ₄ /SnCl ₂ /2 2 0.5 97 87

KBH ₄ /SnCl ₂ /2 3 10 96 61

KBH ₄ /SnCl ₂ /2 4 10 92 81

KBH ₄ /SnCl ₂ /2 5 10 95 86

KBH ₄ /SnCl ₂ /2 5 1 94 71

NaBH ₄ /SnCl ₂ /2 5 10 94 89

KBH ₄ /SnCl ₂ /2 6 10 96 0

KBH ₄ /SnCl ₂ /2 7 10 95 5

NaBH ₄ /SnCl ₂ /2 8 10 95 95

NaBH ₄ /ZrCl ₄ /4 8 10 94 94

KBH ₄ /SnCl ₂ /2 8 10 97 96

KBH ₄ /SnCl ₂ /2 9 10 94 53

From the reaction results, the chiral β-aminoalcohol ligand can give better stereoselectivity, and the stereoselectivity given is the best (95% ee). However, for chiral diol ligands such as ligands 6 and 7, good results cannot be obtained in this reaction.

The reducing system used in the present invention is composed of industrially readily available metal borohydrides M(BH ₄ ) _n (n=1-2), Lewis acid NX _m and chiral ligands mainly from nature. The raw materials used are stable and cheap. The reaction operation is simple and easy for industrial production.

Detailed ways

The following examples will help to understand the present invention, but do not limit the content of the present invention.

Example 1. Preparation of chiral 1-phenylethanol

(a) Add tin dichloride (0.6mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 98%. [α] _D ²⁰ =+52.4 (c 2.04, CHCl ₃ ), 96%ee; IR: 3354 (OH), 3086, 3029, 1452, 1078; ¹ HNMR (CDCl ₃ , TMS): δ1.39 (3H, d, CH ₃ ), 2.92 (1H, s, OH), 4.74 (1H, q, CHOH), 7.20-7.35 (5H, m, Ph); m/z 122 (M ⁺ ), 107, 79, 78, 77, 51.

(b) Add tin dichloride (0.6mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 8 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 97%. [α] _D ²⁰ = -52.6 (c 2.73, CHCl ₃ ), 96% ee.

(c) Add tin dichloride (0.6mmol), sodium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 98%. [α] _D ²⁰ =+52.9 (c 1.64, CHCl ₃ ), 96% ee.

(d) Add tin tetrachloride (0.3mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =+50.1 (c 1.65, CHCl ₃ ), 92% ee.

(e) Add aluminum trichloride (0.4mmol), sodium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir for 1 hour at room temperature, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =-33.4 (c1.07, CHCl ₃ ), 58% ee.

(f) Add titanium tetrachloride (0.3mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 97%. [α] _D ²⁰ =+42.5 (c1.73, CHCl ₃ ), 73% ee.

(g) Add zirconium tetrachloride (0.3mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir for 1 hour at room temperature, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =+38.2 (c1.34, CHCl ₃ ), 60% ee.

(h) Add tin dichloride (0.6mmol), zinc borohydride (0.6mmol), and tetrahydrofuran (8mL) into the reaction flask, stir for 1 hour at room temperature, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 97%. [α] _D ²⁰ =+53.8 (c 1.78, CHCl ₃ ), 96% ee.

(i) Add tin dichloride (0.6mmol), calcium borohydride (0.6mmol), and tetrahydrofuran (8mL) into the reaction flask, stir for 1 hour at room temperature, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 98%. [α] _D ²⁰ =+51.5 (c 1.89, CHCl ₃ ), 95% ee.

(j) Add tin dichloride (0.6mmol), lithium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.1mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =+52.3 (c1.57, CHCl ₃ ), 97% ee.

(k) Add tin dichloride (0.6mmol), lithium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir at room temperature for 1 hour, then add catalyst 2 (0.05mmol), and heat to reflux for half an hour After that, a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =+50.3 (c1.93, CHCl ₃ ), 94% ee.

(l) Add tin tetrachloride (0.3mmol), potassium borohydride (1.2mmol), and tetrahydrofuran (8mL) into the reaction flask, stir for 1 hour at room temperature, then add catalyst 2 (100mmol), and heat to reflux for half an hour , a solution of acetophenone (1.0 mmol) in tetrahydrofuran (8 mL) was slowly added dropwise. After the addition, return to room temperature, add water to quench the reaction, filter, spin the filtrate to dryness on a rotary evaporator, and perform column chromatography to obtain a colorless oily liquid with a yield of 96%. [α] _D ²⁰ =+52.3 (c1.57, CHCl ₃ ), 97% ee.

Example 2. Preparation of chiral 1-phenylpropanol

The experimental procedure is the same as 1(a). Colorless oily liquid, yield 97%.[α] _D ²⁰ =+52.4 (c 2.32, CHCl ₃ ), 81% ee; IR: 3363(OH), 1062, 898 cm ^-1 ; ¹ H NMR (CDCl ₃ ) : δ0.92 (3H, t, CH ₃ ), 1.65-1.90 (2H, m, CH ₂ ), 1.93 (1H, s, OH), 4.58 (1H, t, CHOH), 7.25-7.35 (5H, m , Ph).

Example 3. Preparation of chiral 1-(4-bromophenyl)ethanol

The experimental procedure is the same as 1(g). Colorless oily liquid, yield 97%.[α] _D ²⁰ =+21.6 (c 1.78, MeOH), 75% ee; IR: 3340 (OH), 1060, 898, 828 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ1.38 (3H, d, CH ₃ ), 3.20 (1H, s, OH), 4.73 (1H, q, CHOH), 7.1-7.4 (4H, m, p-BrC ₆ H ₄ ).

Example 4. Preparation of chiral 1-(4-methoxyphenyl)ethanol

The experimental procedure is the same as 1(a). Colorless oily liquid, yield 97%.[α] _D ²⁰ =+52.4 (c 1.46, CHCl ₃ ), 84%ee; IR: 3380(OH), 1063, 891, 834cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ1.40 (3H, d, CH ₃ ), 2.67 (1H, s, OH), 3.73 (3H, s, OCH ₃ ), 4.78 (1H, q, CHOH), 6.8-7.2 (4H, m , p-MeOC ₆ H ₄ ).

Example 5. Preparation of chiral 1-(4-nitrophenyl)ethanol

The experimental procedure is the same as 1(k). Colorless oily liquid, yield 97%. [α] _D ²⁰ =+32.9 (c 1.24, CHCl ₃ ), 97%ee; IR: 3347(OH), 1073, 902, 829 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ1.33 (3H, d , CH ₃ ), 2.87 (1H, s, OH), 4.75 (1H, q, CHOH), 7.1-7.4 (4H, m, p-NO ₂ C ₆ H ₄ ).

Example 6. Preparation of chiral 1-(2-naphthyl)ethanol

The experimental procedure is the same as 1(b). White solid, yield 97%. [α] _D ²⁰ =+32.6 (c 1.86, EtOH), 96%ee; IR: 3338 (OH), 1064, 891, 832 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ1.65 (3H, d, CH ₃ ), 2.18 (1H, bs, OH), 5.06 (1H, q, CHOH), 7.5-7.9 (7H, m, C ₁₀ H ₇ ).

Example 7. Preparation of chiral 2-chloro-1-phenyl-ethanol

The experimental procedure is the same as 1(a). Colorless oily liquid, yield 97%. [α] _D ²⁰ =+35.9 (c 2.18, n-hexane), 92%ee; IR: 3343 (OH), 1063, 898, 828 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ3.00 (1H, bs, OH), 3.52 (2H, d, _CH2Cl ), 4.79 (1H, t, CHOH), 7.32 (5H, m, Ph).

Example 8. Preparation of chiral 2-bromo-1-phenylethanol

The experimental steps are the same as 1(h). Colorless oily liquid, yield 97%. [α] _D ²⁰ =+41.8 (c 1.64, CHCl ₃ ), 94% ee; IR: 3340(OH), 1057, 893 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ1.43 (2H, d, CH ₂ Br), 2.71 (1H, s, OH), 4.71 (1H, t, CHOH), 7.21-7.32 (5H, m, Ph).

Example 9. Preparation of chiral 3-chloro-1-phenylpropanol

The experimental procedure is the same as 1(a). White solid, yield 97%. [α] _D ²⁰ ＝+17.4(c 1.34, CHCl ₃ ), 81%ee; IR: 3331(OH), 3228, 1069, 912cm ^-1 ; ¹ H NMR(CDCl ₃ ): δ1.98-2.14(2H , m, -CH ₂ -), 2.73 (1H, s, OH), 3.48-3.66 (2H, m, CH ₂ Cl), 7.23-7.35 (5H, m, Ph).

Example 10. Preparation of chiral 3-methyl-2-butanol

The experimental procedure is the same as 1(1). A colorless liquid was obtained by distillation with a yield of 95%. [α] _D ²⁰ =+0.78 (c 5.03, EtOH), 78%ee; IR: 3431 (OH), 1040 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ0.92 (6H, d, CH (CH ₃ ) ₂ ), 1.05(3H, d, CH ₃ ), 1.33(1H, m, OH), 1.65(1H, m, CH), 3.53(1H, m, CHOH).

Example 11. Preparation of chiral 3,3'-dimethyl-2-butanol alcohol

The experimental procedure is the same as 1(a). A colorless liquid was obtained by distillation with a yield of 96%. [α] _D ²⁰ ＝+42.7(c 3.94, CCl ₄ ), 96%ee; IR: 3400(OH), 1100cm ^-1 ; ¹ H NMR(CDCl ₃ ): δ0.82(9H, s, C(CH ₃ ) ₃ ), 1.02 (3H, d, _CH3 ), 2.78 (1H, s, OH), 3.36 (1H, q, CHOH).

Example 12. Preparation of chiral 2-butanol

The experimental procedure is the same as 1(a). A colorless liquid was obtained with a yield of 98%. [α] _D ²⁰ =+4.5 (c 4.64, MeOH), 42%ee; IR: 3420 (OH), 1150 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ0.93 (3H, t, CH ₃ ), 1.21 (3H, d, CH ₃ ), 1.66 (2H, m, -CH ₂ -), 2.64 (1H, s, OH), 3.56 (1H, CHOH).

Example 13. Preparation of Chiral 1-Cyclohexyl Ethanol

The experimental procedure is the same as 1(c). A colorless liquid was obtained with a yield of 98%. [α] _D ²⁰ =+2.8 (c 1.94, CHCl ₃ ), 68%ee; IR: 3620(OH), 3340, 2860, 1450cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ0.73-1.88 (12H , m, cC ₆ H ₁₁ andOH), 1.21 (3H, d, CH ₃ ), 3.56 (1H, CHOH).

Example 14. Preparation of Chiral 1-Phenyl-2-Phenylsulfone-Ethanol

The experimental procedure is the same as 1(a). White solid, yield 97%. [α] _D ²⁰ =+20.9 (c 2.08, CHCl ₃ ), 95% ee; IR: 3343(OH), 1286, 1135 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δδ 3.25 and 3.40 (each 1H, dd, CH ₂ ), 3.69 (1H, s, CHOH), 5.19 (1H, dd, CH), 7.29-7.73 (10H, m, 2Ph).

Example 15. Preparation of chiral 1-(4-methoxyphenyl)-2-phenylthiosulfonyl-ethanol

The experimental procedure is the same as 1(a). White solid, yield 98%. [α] _D ²⁰ =+10.9 (c 1.38, CHCl ₃ ), 91%ee; IR: 3442 (OH), 1302, 1145 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ3.22 and 3.40 (each 1H, dd, CH ₂ ), 3.60 (1H, s, CHOH), 3.70 (3H, s, CH ₃ ), 5.12 (1H, dd, CH), 7.14-7.73 (9H, m, 2Ph).

Example 16. Preparation of Chiral 1-(4-Chlorophenyl)-2-Phenylsulfone-Ethanol

The experimental procedure is the same as 1(1). White solid, yield 96%. [α] _D ²⁰ =+15.3 (c 1.17, CHCl ₃ ), 96%ee; IR: 3363 (OH), 1283, 1155 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ3.21 and 3.42 (each 1H, dd, CH ₂ ), 3.61 (1H, s, CHOH), 3.74 (3H, s, CH ₃ ), 5.15 (1H, dd, CH), 7.24-7.69 (9H, m, 2Ph).

Example 17. Preparation of chiral 1-(4-fluorophenyl)-2-phenylthiosulfonyl-ethanol

The experimental procedure is the same as 1(a). White solid, yield 98%. [α] _D ²⁰ =+20.9 (c 1.43, CHCl ₃ ), 96%ee; IR: 3353 (OH), 1298, 1133 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ3.21 and 3.36 (each 1H, dd, CH ₂ ),

3.62 (1H, s, CHOH), 5.17 (1H, dd, CH), 7.18-7.76 (9H, m, 2Ph).

Example 19. Preparation of chiral 1-cyclohexyl-2-phenylthiosulfonyl-ethanol

The experimental procedure is the same as 1(a). White solid, yield 97%. [α] _D ²⁰ =+23.7 (c 1.19, CHCl ₃ ), 92%ee; IR: 3513, 2926, 1285, 1141 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ0.67-1.18 (5H, m) , 1.29-1.46(1H, m), 1.54-1.67(5H, m), 3.12(1H, s), 3.13(1H, d,), 3.32(1H, d), 3.85(1H, s), 7.31- 7.74(5H, m).

Example 20. Preparation of Chiral 1-Phenylsulfone-3,3'-Dimethyl-2-butanol

The experimental procedure is the same as 1(a). White solid, yield 96%. [α] _D ²⁰ ＝+43.6(c 3.13, CHCl ₃ ), 99%ee; IR: 3530(OH), 1286, 1135cm ^-1 ; ¹ H NMR(CDCl ₃ ): δ0.90(9H, s), 3.02(1H, dd), 3.16(1H, s), 3.19(1H, s), 3.68(1H, d), 7.32-7.55(5H, m).

Example 21. Preparation of chiral 1-phenylthiosulfonyl-2-butanol

The experimental procedure is the same as 1(a). White solid, yield 98%. [α] _D ²⁰ ＝+17.9(c 1.24, CHCl ₃ ), 91%ee; IR: 3503(OH), 2932, 1286, 1145cm ^-1 ; ¹ H NMR(CDCl ₃ ): δ0.92(3H, t ), 1.53-1.63(2H, m), 3.17-3.20(1H, m), 3.37(1H, s), 4.09(1H, m), 7.38-7.82(5H, m).

Example 22. Preparation of chiral 1-phenyl-2-nitro-ethanol

The experimental procedure is the same as 1(k). Pale yellow oily liquid, yield 97%. [α] _D ²⁰ =+25.6 (c 1.16, EtOH), 89%ee; IR: 3352 (OH), 1288, 1135 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ3.42 (2H, d), 3.51 (1H, s), 4.79 (1H, t), 7.32-7.54 (5H, m, Ph).

Example 23. Preparation of chiral 1-phenyl-2-(dimethylamino)-ethanol

The experimental procedure is the same as 1(a). White solid, yield 97%. [α] _D ²⁰ =+15.9 (c 2.13, EtOH), 86%ee; IR: 3343 (OH), 3120, 2934, 1291, 1132 cm ^-1 ; ¹ H NMR (CDCl ₃ ): δ2.34 (6H, s), 2.53-(2H, d), 4.52 (1H, s), 4.79 (1H, d), 7.46 (5H, m, Ph).

Claims (5)

1 one kinds of highly selectives prepare the method for chiral, secondary alcohols, it is characterized in that in organic solvent a certain proportion of metal hydroborates M (BH ₄) _nWith Louis acid NX _m(m=1-4) under the chiral ligand effect of catalytic amount, the reduction prochiral ketone obtains chiral, secondary alcohols, and the mol ratio of prochiral ketone and reduction system is 1: 1-8, metal hydroborates M (BH ₄) _nWith Louis acid NX _mMol ratio be 1: 8-0.2, chiral ligand and metal hydroborates M (BH ₄) _nMol ratio be 1: 0.5-200, temperature of reaction is room temperature-reflux temperature;

Described chiral, secondary alcohols molecular formula is RCOHR ¹, R=C wherein _1-12Alkyl, substituted-phenyl PhR ², phSO ₂Or PhSO ₂CH ₂, described alkyl is alkyl, cyclohexyl, the phenyl or naphthyl of straight chain, side chain, R ¹=C _1-12Alkyl, CPH _2P+1NO ₂, C _pH _2p+1NR ³R ⁴, R wherein ²=NO ₂, CN, X, OCH ₃Or CF ₃, P=1-3.R ³Or R ⁴=H or C _PH _2P+1

Described chiral ligand metal hydroborates M (BH ₄) _nIn, M=monovalence or divalent metal, n=1-2;

Described Louis acid NX _mIn, N=Sn, Zr, Ti or Al, X=halogen, m=1-4;

Described chiral ligand metal hydroborates M (BH ₄) _nMiddle M=Sn, Zr, Ti and Al.n＝n＝1-2，

Described chiral ligand has following molecular formula:

, wherein

Expression singly-bound and R type or S type singly-bound, R or R ¹=CH ³Or phenyl,

Deng, R ⁴=H, SO ₂R ⁶, R ⁵=H, NH2, NHCH ³Or N (CH ³) ₂, R ⁶=H, CH ³Or

2 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that the structural formula of described chiral ligand is as follows:

3 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described chiral ligand and metal hydroborates M (BH ₄) _nMol ratio be 1: 5-100.

4 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described organic solvent is tetrahydrofuran (THF), methylene dichloride and toluene.

5 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described chiral ligand metal hydroborates M (BH ₄) _nIn, M is lithium, sodium, potassium, calcium, magnesium or zinc.