阅读说明：本技术 铑催化合成手性3,3-二取代异吲哚啉酮类化合物的方法 (Method for synthesizing chiral 3, 3-disubstituted isoindolinone compound by rhodium catalysis ) 是由 郑光范 孙佳琼 田荣 李兴伟 哈迪 于 2020-05-29 设计创作，主要内容包括：本发明公开了一种手性3,3-二取代异吲哚啉酮类骨架的合成方法,该方法采用易于制备的手性茂基铑催化剂为催化剂,实现了N-甲氧基苯甲酰胺类化合物与1,3-烯炔类化合物的C-H键活化、烯炔迁移插入、1,4-铑迁移、亲核环化等串联反应,温和条件下即可高收率、高对映选择性构建3,3-二取代手性异吲哚啉酮类骨架化合物。本发明操作简单,催化剂用量低,反应条件温和,底物适用范围广,克服了传统的合成该类化合物需分多步进行,起始原料制备困难,底物适用范围受限等不足,具有很好的发展前景。(The invention discloses a synthesis method of a chiral 3, 3-disubstituted isoindolinone skeleton, which adopts an easily prepared chiral cyclopentadienyl rhodium catalyst as a catalyst to realize the series reactions of C-H bond activation, eneyne migration insertion, 1, 4-rhodium migration, nucleophilic cyclization and the like of an N-methoxybenzamide compound and a 1, 3-eneyne compound, and can construct the 3, 3-disubstituted chiral isoindolinone skeleton compound with high yield and high enantioselectivity under mild conditions. The method has the advantages of simple operation, low catalyst consumption, mild reaction conditions and wide substrate application range, overcomes the defects that the traditional synthesis of the compounds needs to be carried out in multiple steps, the preparation of starting materials is difficult, the substrate application range is limited and the like, and has good development prospect.)

1. A method for synthesizing chiral 3, 3-disubstituted isoindolinone compounds by rhodium catalysis is characterized in that: adding an N-methoxybenzamide compound shown in a formula I or I ', a 1, 3-eneyne compound shown in a formula II, a chiral cyclopentadienyl rhodium catalyst, an oxidant and a carboxylic acid additive into an alcohol solvent, reacting for 60-80 hours at 5-15 ℃, and separating and purifying a product to obtain a chiral 3, 3-disubstituted isoindolinone compound shown in a formula III or III';

in the formula R¹Representative H, C₁～C₄Alkyl radical, C₁～C₄Any one of alkoxy, benzyloxy, phenoxy, phenyl, halogen, nitro, trifluoromethyl, acetyl and methoxycarbonyl, R²Represents C₁～C₂Alkyl radical, R³Represents C₃～C₆Cycloalkyl radical, C₃～C₅Any one of alkyl and phenethyl, Ar represents phenyl or thienyl;

the structural formula of the chiral cyclopentadienyl rhodium catalyst is shown as follows:

wherein R represents methoxy or isopropoxy, and X represents Cl or I;

the oxidant is any one of silver difluoride, copper acetate, copper oxide, silver oxide and silver fluoride;

the carboxylic acid additive is any one of acetic acid, propionic acid, isobutyric acid, pivalic acid, benzoic acid and trimesobenzoic acid.

2. The rhodium-catalyzed process for the synthesis of chiral 3, 3-disubstituted isoindolinones according to claim 1, wherein: the molar ratio of the N-methoxybenzamide compound to the 1, 3-eneyne compound is 1: 1.3-2.0.

3. The rhodium-catalyzed process for the synthesis of chiral 3, 3-disubstituted isoindolinones according to claim 1, wherein: the addition amount of the chiral cyclopentadienyl rhodium catalyst is 3 to 5 percent of the molar amount of the N-methoxybenzamide compound.

4. The rhodium-catalyzed process for the synthesis of chiral 3, 3-disubstituted isoindolinones according to claim 1, wherein: the oxidant is silver difluoride.

5. The rhodium-catalyzed synthesis method of chiral 3, 3-disubstituted isoindolinones according to claim 1 or 4, wherein: the addition amount of the oxidant is 2-3 times of the molar amount of the N-methoxybenzamide compound.

6. The rhodium-catalyzed process for the synthesis of chiral 3, 3-disubstituted isoindolinones according to claim 1, wherein: the carboxylic acid additive is acetic acid.

7. The rhodium-catalyzed synthesis method of chiral 3, 3-disubstituted isoindolinones according to claim 1 or 6, wherein: the addition amount of the carboxylic acid additive is 1.5-2.5 times of the molar amount of the N-methoxybenzamide compound.

8. The rhodium-catalyzed process for the synthesis of chiral 3, 3-disubstituted isoindolinones according to claim 1, wherein: the alcohol solvent is any one of 3-pentanol, methanol, ethanol and isopropanol.

Technical Field

The invention relates to a synthetic method of a chiral 3, 3-disubstituted isoindolinone compound.

Background

3, 3-disubstituted chiral isoindolinone skeletons are widely applied in the fields of medicine, biology, synthetic chemistry and the like, and the exploration of an effective method for synthesizing the indole skeletons becomes an important research field. 3, 3-disubstituted chiral isoindolinone compounds are widely concerned by organic synthesizers due to their unique biological and pharmaceutical activities. The construction of disubstituted chiral isoindolinone skeletons is mainly realized in the existing literature through 3-enantioselective functionalization of isoindolinone, but the strategy inevitably causes the defects of difficult substrate synthesis, low atom and step economy, difficult product diversity and complexity and the like. The development of a new synthetic method is expected, and the construction of the chiral isoindolinone compound is realized with high efficiency and high selectivity from a simple and easily obtained substrate.

The direct functionalization reaction of C-H bond catalyzed by transition metal does not need the preactivation process of substrate to realize the construction of target product, and becomes a hotspot and difficult field of organic synthesis in recent years. Alkynes, as common coupling components, generally participate in cyclization as two-carbon synthons to synthesize important five-or six-membered compounds. The transformations effected by alkynes as one-carbon synthons are very rare. In 2014, the Lam subject group firstly uses an eneyne compound as a one-carbon synthon to realize [5+1] cyclization reaction and construct a lactone compound containing a quaternary carbon center (Angew. chem. int. Ed.,2014,53, 9931). In 2019, the topic group takes N-methoxybenzamide as an aromatic hydrocarbon substrate, and the isoindolone derivative (org. Lett.2019,21,1789) is constructed by the (4 + 1) cyclization reaction of the N-methoxybenzamide and an eneyne compound under the catalysis of rhodium. However, enantioselective [4+1] cyclisation reactions involving enynes have not been achieved. A chiral rhodium catalyst (Angew. chem. int. Ed.2019,58,8902; Angew. chem. int. Ed.2020,59,2890.) is prepared by a chiral cyclopentadienyl ligand which is easy to obtain commercially, C-H bond activation and enantioselective allyl substitution reaction are combined, and the one-step construction of a 3, 3-disubstituted chiral isoindolinone skeleton is realized by an enantioselective [4+1] cyclization reaction from N-methoxybenzamide which is easy to obtain and an eneyne substrate.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a method for constructing a 3, 3-disubstituted chiral isoindolinone compound under mild conditions with high yield and high selectivity by using easily prepared chiral cyclopentadienyl rhodium as a catalyst, silver difluoride as an oxidant and easily prepared stable N-methoxybenzamide and 1, 3-eneyne as raw materials.

The technical scheme for solving the technical problems is as follows: adding an N-methoxybenzamide compound shown in a formula I or I ', a 1, 3-eneyne compound shown in a formula II, a chiral cyclopentadienyl rhodium catalyst, an oxidant and a carboxylic acid additive into an alcohol solvent, reacting for 60-80 hours at 5-15 ℃, and separating and purifying a product to obtain a chiral 3, 3-disubstituted isoindolinone compound shown in a formula III or III'.

In the formula R¹Representative H, C₁～C₄Alkyl radical, C₁～C₄Any one of alkoxy, benzyloxy, phenoxy, phenyl, halogen, nitro, trifluoromethyl, acetyl and methoxycarbonyl, R²Represents C₁～C₂Alkyl radical, R³Represents C₃～C₆Cycloalkyl radical, C₃～C₅Any one of alkyl and phenethyl, and Ar represents phenyl or thienyl.

The structural formula of the chiral cyclopentadienyl rhodium catalyst is shown as follows:

wherein R represents methoxy or isopropoxy, and X represents Cl or I.

The oxidizing agent is any one of silver difluoride, copper acetate, copper oxide, silver oxide and silver fluoride, and preferably silver difluoride.

The carboxylic acid additive is any one of acetic acid, propionic acid, isobutyric acid, pivalic acid, benzoic acid and trimesobenzoic acid, and acetic acid is preferred.

In the method, the molar ratio of the N-methoxybenzamide compound to the 1, 3-eneyne compound is preferably 1: 1.3-2.0, the addition amount of the chiral cyclopentadienyl rhodium catalyst is preferably 3-5% of the molar amount of the N-methoxybenzamide compound, the addition amount of the oxidant is preferably 2-3 times of the molar amount of the N-methoxybenzamide compound, and the addition amount of the carboxylic acid additive is preferably 1.5-2.5 times of the molar amount of the N-methoxybenzamide compound.

The alcohol solvent is preferably any one of 3-pentanol, methanol, ethanol and isopropanol.

The invention has the following beneficial effects:

the invention adopts chiral cyclopentadienyl rhodium which is easy to prepare as a catalyst, silver difluoride and the like as oxidants, adopts simple and easily obtained and relatively stable N-methoxybenzamide compounds and 1, 3-eneyne compounds as raw materials, and constructs the chiral 3, 3-disubstituted isoindolinone skeleton compound with high yield and high selectivity under the conditions of acid catalysis and mild conditions. The method has the advantages of simple operation, stable and easily-prepared raw materials, mild reaction conditions, wide substrate application range, high product yield and enantioselectivity (up to 91% yield and 95% ee), overcomes the defects of poor atom and step economy, complex raw material preparation, poor stability, harsh reaction conditions and the like of the traditional method, and has good application prospect.

Detailed Description

The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.

The structural formulas of chiral cyclopentadienyl rhodium catalysts a and B in the following examples are:

example 1

Adding 15.1mg (0.1mmol) of N-methoxybenzamide, 5.0mg (0.004mmol) of chiral cyclopentadienyl rhodium catalyst A and 35.0mg (0.24mmol) of silver difluoride into a test tube, cooling to-15 ℃, adding 2mL of 3-pentanol and 18.0mg (0.15mmol) of (4-methylpent-3-en-1-ynyl) cyclopropane, adding 200 mu L of a 3-pentanol solution of 1.0mol/L acetic acid, stirring at 10 ℃ for reaction for 72 hours, adding 1.0mL of ethylenediamine for quenching after the reaction is finished, and carrying out spin drying to obtain a crude product, wherein the crude product is rapidly subjected to silica gel column chromatography (petroleum ether: ethyl acetate: 1-5: 1) to obtain 18.8mg of a yellow oily liquid with the structural formula as follows, wherein the yield is 70%, and the ee value is 90% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.84(d,J＝7.8Hz,1H),7.53(td,J＝7.8,1.2Hz,1H),7.46(td,J＝7.2,0.6Hz,1H),7.25(d,J＝7.2Hz,1H),6.61(d,J＝16.2Hz,1H),5.70(d,J＝15.6Hz,1H),5.05(s,1H),5.04(s,1H),4.05(s,3H),1.82(s,3H),1.59–1.54(m,1H),0.74–0.69(m,1H),0.62–0.57(m,1H),0.51–0.46(m,1H),-0.01–-0.06(m,1H).¹³C NMR(150MHz,CDCl₃)δ164.2,143.6,141.0,135.6,131.7,129.7,128.6,127.0,123.8,123.1,118.3,70.1,65.0,18.5,15.9,2.4,0.5；HRMS(ESI-TOF)(m/z):C₁₇H₁₉NNaO₂,([M+Na]⁺) Theoretical 292.1308, found 292.1304; [ alpha ] to]_D ²⁰＝+33.2(c＝0.1,CHCl₃).

Example 2

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-methylbenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 24.5mg of a colorless oily liquid of the formula shown below in a yield of 86%, and an ee value thereof by HPLC analysis was 95%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.72(d,J＝7.8Hz,1H),7.26(d,J＝8.4Hz,1H),7.02(s,1H),6.62(d,J＝16.2Hz,1H),5.69(d,J＝15.6Hz,1H),5.06(s,1H),5.05(s,1H),4.03(s,3H),2.44(s,3H),1.83(s,3H),1.57–1.53(m,1H),0.73–0.68(m,1H),0.60–0.56(m,1H),0.49–0.45(m,1H),-0.02–-0.05(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.6,144.0,142.5,141.1,135.5,129.6,127.4,127.0,123.64,123.59,118.1；[α]_D ²⁰＝+52.8(c＝0.1,CHCl₃).

example 3

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-tert-butylbenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 28.4mg of a colorless oily liquid of the formula shown below in a yield of 87%, and an ee value of 95% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.76(d,J＝8.4Hz,1H),7.49(dd,J＝7.8,1.8Hz,1H),7.20(d,J＝1.2Hz,1H),6.63(d,J＝15.6Hz,1H),5.71(d,J＝16.2Hz,1H),5.06(s,1H),5.05(s,1H),4.03(s,3H),1.84(s,3H),1.60–1.56(m,1H),1.34(s,9H),0.73–0.68(m,1H),0.57–0.53(m,1H),0.49–0.44(m,1H),-0.05–-0.09(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.6,155.8,143.5,141.1,135.5,127.4,127.0,125.9,123.4,119.9,118.1,70.2,65.0,35.3,31.3,18.5,15.8,2.4,0.4；HRMS(ESI-TOF)(m/z):C₂₁H₂₇NNaO₂,([M+Na]⁺) Theoretical 348.1934, found 348.1935; [ alpha ] to]_D ²⁰＝-8.4(c＝0.1,CHCl₃).

Example 4

In this example, equimolar N-methoxy-4-methoxybenzamide was used instead of N-methoxybenzamide in example 1, and the other procedures were the same as in example 1 to give 22.8mg of a colorless oily liquid of the formula shown below in a yield of 76%, and an ee value thereof by HPLC analysis was 95%.

Structural characterization number of the obtained productAccording to the following steps:¹H NMR(600MHz,CDCl₃)δ7.77(d,J＝8.4Hz,1H),6.97(dd,J＝8.4,1.8Hz,1H),6.71(d,J＝1.8Hz,1H),6.61(d,J＝16.2Hz,1H),5.69(d,J＝15.6Hz,1H),5.06(s,1H),5.05(s,1H),4.02(s,3H),3.86(s,3H),1.83(s,3H),1.57–1.53(m,1H),0.72–0.68(m,1H),0.61–0.57(m,1H),0.51–0.46(m,1H),0.03–-0.02(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.8,162.8,146.0,141.0,135.6,127.2,125.4,121.9,118.2,114.3,108.9,69.9,65.1,55.7,18.5,16.0,2.2,0.5；HRMS(ESI-TOF)(m/z):C₁₈H₂₁NNaO₃,([M+Na]⁺) Theoretical 322.1414, found 322.1412; [ alpha ] to]_D ²⁰＝+8.2(c＝0.1,CHCl₃).

Example 5

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-benzyloxybenzamide in an equimolar amount instead of the N-methoxybenzamide in example 1 to give 29.9mg of a colorless oily liquid of the formula shown below in a yield of 80%, and an ee value of 92% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.76(d,J＝8.4Hz,1H),7.42(d,J＝7.2Hz,2H),7.38(t,J＝7.8Hz,2H),7.34–7.32(m,1H),7.04(dd,J＝8.4,2.4Hz,1H),6.78(d,J＝2.4Hz,1H),6.57(d,J＝15.6Hz,1H),5.67(d,J＝15.6Hz,1H),5.10(s,2H),5.04(s,1H),5.02(s,1H),4.01(s,3H),1.81(s,3H),1.55–1.50(m,1H),0.70–0.65(m,1H),0.56–0.52(m,1H),0.48–0.44(m,1H),0.01–-0.04(m,1H)；¹³CNMR(150MHz,CDCl₃)δ164.6,161.8,145.9,140.9,136.0,135.5,128.6,128.2,127.5,127.1,125.3,122.1,118.2,115.2,109.8,70.4,69.8,65.0,18.4,15.9,2.2,0.5；HRMS(ESI-TOF)(m/z):C₂₄H₂₅NNaO₃,([M+Na]⁺) Theoretical 398.1727, found 398.1710; [ alpha ] to]_D ²⁰＝+16.4(c＝0.1,CHCl₃).

Example 6

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-phenoxybenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 29.5mg of a yellow oily liquid of the formula shown below in a yield of 82%, and an ee value thereof was 91% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.70(d,J＝8.4Hz,1H),7.33–7.29(m,2H),7.11(t,J＝7.2Hz,1H),6.97–6.95(m,2H),6.93(dd,J＝8.4,2.4Hz,1H),6.80(d,J＝2.4Hz,1H),6.49(d,J＝16.2Hz,1H),5.61(d,J＝16.2Hz,1H),4.97(s,1H),4.95(s,1H),3.96(s,3H),1.74(s,3H),1.47–1.43(m,1H),0.64–0.59(m,1H),0.50–0.45(m,1H),0.44–0.39(m,1H),-0.03–-0.08(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.1,160.9,155.9,146.0,140.9,135.7,130.0,126.6,125.5,124.3,123.9,119.5,118.4,118.3,113.0,69.8,65.1,18.5,16.0,2.2,0.5；HRMS(ESI-TOF)(m/z):C₂₃H₂₃NNaO₃,([M+Na]⁺) Theoretical 384.1570, found 384.1555; [ alpha ] to]_D ²⁰＝+10.3(c＝0.1,CHCl₃).

Example 7

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-phenylbenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 27.0mg of a colorless oily liquid of the formula shown below in a yield of 78%, and an ee value of 95% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.90(d,J＝7.8Hz,1H),7.68(dd,J＝7.8,1.8Hz,1H),7.60–7.58(m,2H),7.48(t,J＝7.8Hz,2H),7.42–7.39(m,2H),6.67(d,J＝15.6Hz,1H),5.74(d,J＝15.6Hz,1H),5.06(bs,2H),4.07(s,3H),1.84(s,3H),1.63–1.59(m,1H),0.78–0.73(m,1H),0.67–0.62(m,1H),0.54–0.50(m,1H),0.06–0.02(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.2,145.1,144.4,141.0,140.2,135.8,129.0,128.5,128.2,127.8,127.4,127.04 124.2,121.8,118.4,70.2,65.1,18.5,16.0,2.5,0.6；HRMS(ESI-TOF)(m/z):C₂₃H₂₃NNaO₂,([M+Na]⁺) Theoretical 368.1621, found 368.1622; [ alpha ] to]_D ²⁰＝-8.9(c＝0.1,CHCl₃).

Example 8

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-fluorobenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 26.1mg of a colorless oily liquid of the formula shown below in a yield of 91%, and an ee value thereof by HPLC analysis was 90%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.83(dd,J＝8.4,4.8Hz,1H),7.16(td,J＝8.4,2.4Hz,1H),6.96(dd,J＝7.8,2.4Hz,1H),6.58(d,J＝15.6Hz,1H),5.67(d,J＝15.6Hz,1H),5.08(s,1H),5.05(s,1H),4.04(s,3H),1.83(s,3H),1.55–1.50(m,1H),0.75–0.71(m,1H),0.61–0.57(m,1H),0.55–0.51(m,1H),0.07–0.03(m,1H)；¹³C NMR(150MHz,CDCl₃)δ165.1(J＝251.1Hz),163.5,146.5(J＝8.9Hz),140.8,136.1,126.1,126.0(J＝9.5Hz),125.6(J＝2.3Hz),118.7,116.3(J＝23.1Hz),110.7(J＝24.0Hz),69.8,65.1,18.4,16.1,2.2,0.6；HRMS(ESI-TOF)(m/z):C₁₇H₁₈FNNaO₂,([M+Na]⁺) Theoretical 310.1214, found 310.1213; [ alpha ] to]_D ²⁰＝+19.6(c＝0.1,CHCl₃).

Example 9

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-chlorobenzamide in place of N-methoxybenzamide in example 1 in an equimolar amount to give 27.1mg of a yellow solid having the following structural formula, the yield thereof was 89%, and the ee value thereof by HPLC analysis was 88%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.77(d,J＝7.8Hz,1H),7.44(dd,J＝8.4,1.8Hz,1H),7.25(d,J＝1.8Hz,1H),6.58(d,J＝15.6Hz,1H),5.65(d,J＝16.2Hz,1H),5.08(s,1H),5.06(s,1H),4.04(s,3H),1.83(s,3H),1.54–1.50(m,1H),0.76–0.71(m,1H),0.61–0.57(m,1H),0.56–0.51(m,1H),0.08–0.03(m,1H)；¹³C NMR(150MHz,CDCl₃)δ163.3,145.6,140.8,138.2,136.2,129.2,128.0,125.9,125.1,123.5,118.8,69.9,65.1,18.5,16.0,2.3,0.7；HRMS(ESI-TOF)(m/z):C₁₇H₁₈ClNNaO₂,([M+Na]⁺) Theoretical 326.0918, found 326.0917; [ alpha ] to]_D ²⁰＝-18.1(c＝0.1,CHCl₃).

Example 10

In this example, the same procedures used in example 1 were repeated except for using N-methoxy-4-bromobenzamide in an equimolar amount instead of N-methoxybenzamide used in example 1 to give 29.3mg of a yellow solid having the following structural formula, the yield thereof was 84%, and the ee value thereof by HPLC analysis was 90%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.71(d,J＝8.4Hz,1H),7.60(d,J＝7.8Hz,1H),7.41(s,1H),6.59(d,J＝15.6Hz,1H),5.64(d,J＝16.2Hz,1H),5.08(s,1H),5.07(s,1H),4.04(s,3H),1.83(s,3H),1.54–1.49(m,1H),0.76–0.71(m,1H),0.61–0.56(m,1H),0.55–0.51(m,1H),0.08–0.04(m,1H)；¹³C NMR(150MHz,CDCl₃)δ163.4,145.8,140.8,136.2,132.1,128.5,126.5,126.4,125.9,125.3,118.8,69.9,65.1,18.5,16.0,2.3,0.7；HRMS(ESI-TOF)(m/z):C₁₇H₁₈BrNNaO₂,([M+Na]⁺) Theoretical 370.0413, found 370.0413; [ alpha ] to]_D ²⁰＝-5.4(c＝0.1,CHCl₃).

Example 11

In this example, equimolar N-methoxy-4-methoxycarbonylbenzamide was used instead of N-methoxybenzamide in example 1, and the other procedures were the same as in example 1 to give 21.2mg of a colorless oily liquid of the formula shown below in a yield of 65%, and an ee value thereof by HPLC analysis was 90%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ8.15(d,J＝7.8Hz,1H),7.92(s,1H),7.91(d,J＝7.8Hz,1H),6.61(d,J＝16.2Hz,1H),5.67(d,J＝15.6Hz,1H),5.08(s,1H),5.06(s,1H),4.06(s,3H),3.96(s,3H),1.83(s,3H),1.58–1.53(m,1H),0.77–0.72(m,1H),0.64–0.60(m,1H),0.56–0.51(m,1H),0.05–0.02(m,1H)；¹³CNMR(150MHz,CDCl₃)δ166.2,162.9,143.9,140.8,136.2,133.7,133.3,130.0,125.9,124.2,123.8,118.8,70.3,65.1,52.5,18.5,16.0,2.4,0.7；HRMS(ESI-TOF)(m/z):C₁₉H₂₁NNaO₄,([M+Na]⁺) Theoretical 350.1363, found 350.1363; [ alpha ] to]_D ²⁰＝-6.4(c＝0.1,CHCl₃).

Example 12

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-4-acetylbenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 17.5mg of a colorless oily liquid of the formula shown below in a yield of 56%, and an ee value of 92% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ8.04(dd,J＝7.8,1.2Hz,1H),7.94(d,J＝7.8Hz,1H),7.86(s,1H),6.61(d,J＝15.6Hz,1H),5.67(d,J＝15.6Hz,1H),5.08(s,1H),5.06(s,1H),4.07(s,3H),2.66(s,3H),1.82(s,3H),1.58–1.53(m,1H),0.77–0.73(m,1H),0.63–0.59(m,1H),0.56–0.52(m,1H),0.06–0.02(m,1H)；¹³C NMR(150MHz,CDCl₃)δ197.2,162.8,144.2,140.7,139.7,136.3,133.6,129.1,125.8,124.0,122.5,118.8,70.3,65.0,26.9,18.4,16.0,2.4,0.7；HRMS(ESI-TOF)(m/z):C₁₉H₂₁NNaO₃,([M+Na]⁺) Theoretical 334.1414, found 334.1415; [ alpha ] to]_D ²⁰＝-44.2(c＝0.1,CHCl₃).

Example 13

In this example, N-methoxybenzamide from example 1 was replaced with equimolar N-methoxy-4-nitrobenzamide and the procedure was otherwise as in example 1 to give 25.7mg of a yellow solid of the formula shown below in 82% yield with an ee of 77% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ8.36(dd,J＝8.4,1.8Hz,1H),8.15(d,J＝1.8Hz,1H),8.02(d,J＝7.8Hz,1H),6.60(d,J＝15.6Hz,1H),5.65(d,J＝16.2Hz,1H),5.11(s,1H),5.08(s,1H),4.08(s,3H),1.83(s,3H),1.57–1.52(m,1H),0.81–0.76(m,1H),0.65–0.59(m,2H),0.17–0.13(m,1H)；¹³C NMR(150MHz,CDCl₃)δ161.5,150.2,145.4,140.4,137.0,135.1,125.0,124.4,124.2,119.5,118.5,70.3,65.2,18.4,16.2,2.4,0.9；HRMS(ESI-TOF)(m/z):C₁₇H₁₈N₂NaO₄,([M+Na]⁺) Theoretical 337.1159, found 337.1158; [ alpha ] to]_D ²⁰＝-20.1(c＝0.1,CHCl₃).

Example 14

In this example, equimolar N-methoxy-3-methylbenzamide was used instead of N-methoxy benzamide in example 1, and the other procedures were the same as in example 1 to give 22.0mg of a colorless oily liquid of the formula shown below in a yield of 78%, and an ee value of 81% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.65(s,1H),7.33(dd,J＝7.8,1.2Hz,1H),7.12(d,J＝7.8Hz,1H),6.60(d,J＝16.2Hz,1H),5.69(d,J＝16.2Hz,1H),5.04(s,1H),5.03(s,1H),4.04(s,3H),2.42(s,3H),1.82(s,3H),1.58–1.53(m,1H),0.73–0.68(m,1H),0.60–0.56(m,1H),0.48–0.43(m,1H),-0.06–-0.09(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.5,141.0,140.7,138.8,135.4,132.6,129.7,127.5,124.0,123.0,118.1,70.0,65.0,21.3,18.5,15.8,2.5,0.4；HRMS(ESI-TOF)(m/z):C₁₈H₂₁NNaO₂,([M+Na]⁺) Theoretical 306.1465, found 306.1464; [ alpha ] to]_D ²⁰＝-3.6(c＝0.1,CHCl₃).

Example 15

In this example, equimolar N-methoxy-3-bromobenzamide was used instead of N-methoxybenzamide in example 1, and the other procedures were the same as in example 1 to give 24.9mg of a yellow solid of the formula shown below in a yield of 72% with an ee value of 94% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.96(s,1H),7.64(d,J＝8.4Hz,1H),7.13(d,J＝8.4Hz,1H),6.56(d,J＝15.6Hz,1H),5.64(d,J＝15.6Hz,1H),5.05(s,1H),5.03(s,1H),4.03(s,3H),1.80(s,3H),1.54–1.49(m,1H),0.74–0.70(m,1H),0.58–0.53(m,1H),0.52–0.47(m,1H),0.01–-0.03(m,1H)；¹³C NMR(150MHz,CDCl₃)δ162.6,142.4,140.7,136.0,134.7,131.6,126.9,126.1,124.8,122.8,118.7,70.1,65.1,18.4,15.9,2.4,0.6；HRMS(ESI-TOF)(m/z):C₁₇H₁₈BrNNaO₂,([M+Na]⁺) Theoretical 370.0413, found 370.0410; [ alpha ] to]_D ²⁰＝+28.4(c＝0.1,CHCl₃).

Example 16

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-3-trifluoromethylbenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 17.2mg of a yellow oily liquid of the formula shown below in a yield of 51%, and an ee value thereof by HPLC analysis of 90%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ8.12(s,1H),7.80(d,J＝7.8Hz,1H),7.43(d,J＝7.8Hz,1H),6.59(d,J＝16.2Hz,1H),5.67(d,J＝16.2Hz,1H),5.09(s,1H),5.06(s,1H),4.07(s,3H),1.83(s,3H),1.57–1.52(m,1H),0.78–0.73(m,1H),0.63–0.59(m,1H),0.58–0.54(m,1H),0.10–0.06(m,1H)；¹³C NMR(150MHz,CDCl₃)δ162.5,147.4,140.6,136.4,131.3(q,J＝33.0Hz),130.5,128.6(q,J＝3.3Hz),125.4,123.7,123.6(q,J＝271.1Hz),121.1(q,J＝3.9Hz),119.0,70.2,65.1,18.4,16.1,2.3,0.7；HRMS(ESI-TOF)(m/z):C₁₈H₁₈F₃NNaO₂,([M+Na]⁺) Theoretical 360.1182, found 360.1178; [ alpha ] to]_D ²⁰＝+19.2(c＝0.1,CHCl₃).

Example 17

In this example, equimolar N-methoxy-2-methylbenzamide was used instead of N-methoxy benzamide in example 1 and equal volume of ethanol was used instead of 3-pentanol in example 1, and the other steps were the same as in example 1 to give 19.2mg of a colorless oily liquid of the formula shown below in a yield of 68%, and an ee value thereof by HPLC analysis was 96%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.38(t,J＝7.8Hz,1H),7.18(d,J＝7.8Hz,1H),7.05(d,J＝7.8Hz,1H),6.59(d,J＝16.2Hz,1H),5.69(d,J＝16.2Hz,1H),5.04(s,1H),5.03(s,1H),4.03(s,3H),2.71(s,3H),1.82(s,3H),1.56–1.51(m,1H),0.71–0.66(m,1H),0.60–0.56(m,1H),0.49–0.45(m,1H),-0.01–-0.04(m,1H)；¹³C NMR(150MHz,CDCl₃)δ165.7,144.3,141.1,137.9,135.4,131.2,130.6,127.5,126.5,120.6,118.0,69.2,64.9,18.5,17.3,16.0,2.2,0.5；HRMS(ESI-TOF)(m/z):C₁₈H₂₁NNaO₂,([M+Na]⁺) Theoretical 306.1465, found 360.1464; [ alpha ] to]_D ²⁰＝+62.7(c＝0.1,CHCl₃).

Example 18

In this example, equimolar N-methoxy-2-fluorobenzamide was used instead of N-methoxybenzamide in example 1 and equal volume of ethanol was used instead of 3-pentanol in example 1, and the other steps were the same as in example 1 to give 15.9mg of a colorless oily liquid of the formula shown below in 55% yield and 90% ee by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.54–7.50(m,1H),7.10(t,J＝8.4Hz,1H),7.06(d,J＝7.8Hz,1H),6.58(d,J＝16.2Hz,1H),5.67(d,J＝15.6Hz,1H),5.07(s,1H),5.04(s,1H),4.04(s,3H),1.82(s,3H),1.56–1.51(m,1H),0.74–0.70(m,1H),0.61–0.57(m,1H),0.55–0.50(m,1H),0.08–0.04(m,1H).¹³CNMR(150MHz,CDCl₃)δ161.5,158.7(J＝259.8Hz),146.4,140.8,136.0,133.6(J＝7.5Hz),126.2,119.2(J＝4.1Hz),118.6,116.8(J＝12.8Hz),116.0(J＝19.2Hz),69.8,65.0,18.4,16.1,2.1,0.6；HRMS(ESI-TOF)(m/z):C₁₇H₁₈FNNaO₂,([M+Na]⁺) Theoretical 310.1214, found 310.1211; [ alpha ] to]_D ²⁰＝+26.7(c＝0.1,CHCl₃).

Example 19

In this example, equimolar N-methoxy-1-naphthamide was used instead of N-methoxybenzamide in example 1 and equal volume of ethanol was used instead of 3-pentanol in example 1, and the other steps were the same as in example 1 to give 16.8mg of a colorless oily liquid of the formula shown below in a yield of 53%, and an ee value thereof by HPLC analysis was 95%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.20(d,J＝8.4Hz,1H),8.03(d,J＝8.4Hz,1H),7.92(d,J＝8.4Hz,1H),7.70(t,J＝7.8Hz,1H),7.61(t,J＝7.8Hz,1H),7.37(d,J＝8.4Hz,1H),6.67(d,J＝16.2Hz,1H),5.77(d,J＝16.2Hz,1H),5.07(s,1H),5.06(s,1H),4.12(s,3H),1.85(s,3H),1.64–1.59(m,1H),0.76–0.71(m,1H),0.69–0.64(m,1H),0.58–0.54(m,1H),0.15–0.10(m,1H).¹³C NMR(150MHz,CDCl₃)δ166.2,144.3,141.0,136.0,133.1,132.6,129.2,128.19,128.15,127.0,126.9,124.2,123.6,120.2,118.3,69.6,65.1,18.5,16.1,2.3,0.7；HRMS(ESI-TOF)(m/z):Calcd for C₂₁H₂₁NNaO₂,([M+Na]⁺),342.1465,found 342.1463；[α]_D ²⁰＝+93.0(c＝0.1,CHCl₃).

example 20

In this example, the same procedures as in example 1 were repeated except for using N-methoxy-7-benzothiophenecarboxamide in an equimolar amount instead of N-methoxybenzamide in example 1 to give 26.1mg of a colorless oily liquid of the formula shown below in a yield of 80%, and an ee value thereof by HPLC analysis was 96%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝5.4Hz,1H),8.03(d,J＝8.4Hz,1H),7.69(d,J＝5.4Hz,1H),7.22(d,J＝8.4Hz,1H),6.63(d,J＝16.2Hz,1H),5.74(d,J＝15.6Hz,1H),5.05(s,1H),5.03(s,1H),4.08(s,3H),1.82(s,3H),1.62–1.57(m,1H),0.75–0.70(m,1H),0.66–0.62(m,1H),0.53–0.49(m,1H),0.06–0.02(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.8,141.4,141.0,140.9,135.7,135.2,130.2,127.3,125.8,123.4,121.6,118.6,118.2,70.2,65.1,18.5,16.1,2.4,0.6；HRMS(ESI-TOF)(m/z):C₁₉H₁₉NNaO₂S,([M+Na]⁺) Theoretical 348.1029, found 348.1029; [ alpha ] to]_D ²⁰＝+19.0(c＝0.1,CHCl₃).

Example 21

In this example, the same procedure as in example 1 was repeated except for using N-ethoxybenzamide in an equimolar amount instead of N-methoxybenzamide in example 1 to obtain 21.2mg of a white solid having the following structural formula, the yield thereof was 75%, and the ee value thereof by HPLC analysis was 86%.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.84(d,J＝7.8Hz,1H),7.52(td,J＝7.8,0.6Hz,1H),7.45(t,J＝7.8Hz,1H),7.24(d,J＝7.2Hz,1H),6.63(d,J＝16.2Hz,1H),5.70(d,J＝15.6Hz,1H),5.05(s,1H),5.04(s,1H),4.32–4.25(m,2H),1.82(s,3H),1.60–1.55(m,1H),1.37(t,J＝7.2Hz,3H),0.73–0.69(m,1H),0.61–0.56(m,1H),0.49–0.44(m,1H),-0.05–-0.09(m,1H)；¹³C NMR(150MHz,CDCl₃)δ164.5,143.5,141.0,135.5,131.6,129.8,128.5,127.3,123.7,123.2,118.1,73.0,70.0,18.5,15.8,13.9,2.3,0.3；HRMS(ESI-TOF)(m/z):C₁₈H₂₁NNaO₂,([M+Na]⁺) Theoretical 306.1465, found 306.1464; [ alpha ] to]_D ²⁰＝+32.7(c＝0.1,CHCl₃).

Example 22

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 19 was replaced with equimolar 2-methyloct-2-en-4-yne and the procedure was otherwise the same as in example 19 to give 21.1mg of a colorless oily liquid of the formula shown below in a yield of 66% and an ee value of 84% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.16(d,J＝8.4Hz,1H),8.03(d,J＝8.4Hz,1H),7.90(d,J＝8.4Hz,1H),7.68(t,J＝7.8Hz,1H),7.58(t,J＝7.8Hz,1H),7.32(d,J＝8.4Hz,1H),6.47(d,J＝16.2Hz,1H),5.73(d,J＝16.2Hz,1H),5.04(s,1H),5.03(s,1H),4.04(s,3H),2.34–2.29(m,1H),2.15–2.10(m,1H),1.82(s,3H),1.17–1.11(m,1H),0.82(t,J＝7.8Hz,3H),0.64–0.58(m,1H)；¹³C NMR(150MHz,CDCl₃)δ166.8,145.7,141.1,134.4,133.3,133.1,129.5,129.2,128.2,126.8,124.1,123.5,119.1,118.1,69.0,65.0,36.0,18.5,16.4,13.9；HRMS(ESI-TOF)(m/z):C₂₁H₂₃NNaO₂,([M+Na]⁺) Theoretical 344.1621, found 344.1618; [ alpha ] to]_D ²⁰＝+31.1(c＝0.1,CHCl₃).

Example 23

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 19 was replaced with equimolar 2-methyldec-2-en-4-yne and the procedure was otherwise the same as in example 19 to give 20.5mg of a colorless oily liquid of the formula shown below in 59% yield with an ee value of 85% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.17(d,J＝8.4Hz,1H),8.03(d,J＝8.4Hz,1H),7.90(d,J＝7.8Hz,1H),7.68(t,J＝7.8Hz,1H),7.58(t,J＝7.8Hz,1H),7.31(d,J＝8.4Hz,1H),6.45(d,J＝16.2Hz,1H),5.72(d,J＝16.2Hz,1H),5.04(s,1H),5.02(s,1H),4.04(s,3H),2.34–2.29(m,1H),2.17–2.12(m,1H),1.81(s,3H),1.22–1.10(m,5H),0.76(t,J＝6.6Hz,3H),0.58–0.56(m,1H)；¹³C NMR(150MHz,CDCl₃)δ166.7,145.7,141.1,134.4,133.3,133.1,129.6,129.2,128.22,128.20,126.8,124.2,123.6,119.1,118.0,69.0,65.0,33.8,31.7,22.5,22.3,18.5,13.9；HRMS(ESI-TOF)(m/z):C₂₃H₂₇NNaO₂,([M+Na]⁺) Theoretical 372.1934, found 372.1931; [ alpha ] to]_D ²⁰＝+78.0(c＝0.1,CHCl₃).

Example 24

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 19 was replaced with equimolar 2, 7-dimethyloct-2-en-4-yne and the procedure was otherwise as in example 19 to give 17.2mg of a colorless oily liquid of the formula shown below in 51% yield and 80% ee by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.18(d,J＝8.4Hz,1H),8.02(d,J＝8.4Hz,1H),7.90(d,J＝8.4Hz,1H),7.68(t,J＝7.8Hz,1H),7.58(t,J＝7.8Hz,1H),7.34(d,J＝8.4Hz,1H),6.42(d,J＝16.2Hz,1H),5.69(d,J＝16.2Hz,1H),5.03(s,1H),5.01(s,1H),4.06(s,3H),2.34(dd,J＝14.4,4.2Hz,1H),2.08(dd,J＝14.4,6.6Hz,1H),1.81(s,3H),1.30–1.26(m,1H),0.88(d,J＝6.6Hz,3H),0.39(d,J＝6.6Hz,3H)；¹³C NMR(150MHz,CDCl₃)δ166.4,145.7,141.0,134.1,133.1,132.9,130.1,129.3,128.23,128.19,126.8,124.2,123.5,120.0,118.1,68.7,65.0,42.2,24.3,24.1,23.5,18.5；HRMS(ESI-TOF)(m/z):C₂₂H₂₅NNaO₂,([M+Na]⁺) Theoretical 358.1778, found 358.1773; [ alpha ] to]_D ²⁰＝+19.2(c＝0.1,CHCl₃).

Example 25

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 19 was replaced with an equimolar amount of (6-methylhept-5-en-3-yn-1-yl) benzene and the procedure was otherwise as in example 19 to give 26.4mg of a colorless oily liquid of the formula shown below in a yield of 69%, and an ee value of 84% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.19(d,J＝8.4Hz,1H),8.07(d,J＝8.4Hz,1H),7.93(d,J＝7.8Hz,1H),7.70(t,J＝7.8Hz 1H),7.60(t,J＝7.8Hz,1H),7.36(d,J＝8.4Hz,1H),7.20(t,J＝7.8Hz,2H),7.13(t,J＝7.8Hz,1H),7.04–7.02(m,2H),6.48(d,J＝15.6Hz,1H),5.74(d,J＝16.2Hz,1H),5.04(s,1H),5.00(s,1H),4.11(s,3H),2.72–2.64(m,1H),2.48–2.43(m,2H),1.87–1.81(m,1H),1.81(s,3H)；¹³C NMR(150MHz,CDCl₃)δ166.9,145.3,141.2,141.0,134.6,133.6,133.2,129.3,129.2,128.4,128.3,128.2,126.9,126.0,124.2,123.6,119.0,118.3,68.8,65.2,35.8,29.4,18.4；HRMS(ESI-TOF)(m/z):C₂₆H₂₅NNaO₂,([M+Na]⁺) Theoretical value 406.1778, upper measured value 406.1773; [ alpha ] to]_D ²⁰＝+24.2(c＝0.1,CHCl₃).

Example 26

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 19 was replaced with an equimolar amount of (5-methylhexan-4-en-2-yn-1-yl) cyclohexane and the procedure was repeated in the same manner as in example 19 to give 18.3mg of a colorless oily liquid of the formula shown below in 49% yield and 81% ee by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ9.18(d,J＝8.4Hz,1H),8.01(d,J＝8.4Hz,1H),7.91(d,J＝7.8Hz,1H),7.68(t,J＝7.8Hz,1H),7.59(t,J＝7.8Hz,1H),7.33(d,J＝8.4Hz,1H),6.39(d,J＝16.2Hz,1H),5.68(d,J＝16.2Hz,1H),5.02(s,1H),5.00(s,1H),4.05(s,3H),2.27(dd,J＝14.4,3.6Hz,1H),2.09(dd,J＝14.4,6.0Hz,1H),1.80(s,3H),1.67–1.66(m,1H),1.59–1.55(m,1H),1.44–1.42(m,1H),1.32–1.30(m,1H),1.08–0.98(m,4H),0.89–0.87(m,1H),0.83–0.77(m,1H),0.70–0.64(m,1H)；¹³C NMR(150MHz,CDCl₃)δ166.4,145.8,141.0,134.1,133.1,132.8,130.2,129.2,128.2,128.1,126.8,124.2,123.5,119.8,118.0,68.6,65.0,41.0,34.6,32.6,26.1,26.0,25.9,18.5；HRMS(ESI-TOF)(m/z):C₂₅H₂₉NNaO₂,([M+Na]⁺) Theory ofValue 398.2091, found 398.2086; [ alpha ] to]_D ²⁰＝+84.4(c＝0.1,CHCl₃).

Example 27

In this example, (4-methylpent-3-en-1-ynyl) cyclopropane in example 17 was replaced with equimolar 2-methylnon-2-en-4-yne and the procedure was otherwise as in example 17 to give 18.1mg of a colorless oily liquid of the formula shown below in 60% yield and an ee of 91% by HPLC analysis.

The structural characterization data of the obtained product are:¹H NMR(600MHz,CDCl₃)δ7.40(t,J＝7.2Hz,1H),7.17(d,J＝7.2Hz,1H),7.02(d,J＝7.2Hz,1H),6.40(d,J＝16.2Hz,1H),5.69(d,J＝16.2Hz,1H),5.02(s,1H),5.01(s,1H),3.97(s,3H),2.71(s,3H),2.25–2.20(m,1H),2.03–1.98(m,1H),1.80(s,3H),1.29–1.17(m,2H),1.09–1.01(tm,1H),0.78(t,J＝7.2Hz,3H),0.60–0.53(m,1H).¹³C NMR(150MHz,CDCl₃)δ166.2,146.0,141.1,137.8,133.7,131.7,130.3,130.0,126.6,119.5,117.8,68.5,64.8,34.0,24.9,22.6,18.5,17.3,13.8；HRMS(ESI-TOF)(m/z):C₁₉H₂₅NNaO₂,([M+Na]⁺) Theoretical 322.1778, found 322.1780; [ alpha ] to]_D ²⁰＝+28.3(c＝0.1,CHCl₃).

Example 28

In this example, an equimolar chiral cyclopentadienyl rhodium catalyst B was used instead of the chiral cyclopentadienyl rhodium catalyst a in example 1, and the other steps were the same as in example 1, to give 19.1mg of a yellow oily liquid, the yield thereof was 71%, and the ee value thereof was 85% by HPLC analysis.