阅读说明：本技术 苯并环庚烯酮类化合物的合成方法 (Method for synthesizing benzocycloheptenone compounds ) 是由 刘丙贤 王娟娟 杨凌云 石雨佳 于 2021-08-19 设计创作，主要内容包括：本发明公开了一种过渡金属催化合成苯并环庚烯酮类化合物的方法,属于有机合成技术领域。以2-联苯硼酸类化合物和二取代环丙烯酮类化合物为起始原料,在过渡金属铑催化剂和银盐氧化剂作用下,有机溶剂中加热搅拌反应得到苯并环庚烯酮类化合物。本发明具有起始原料简单易制备、底物适用范围广和操作简单等优点,环丙烯酮三元环在反应过程中开环重新生成七元环,为一步合成复杂多环化合物提供了有益的借鉴。(The invention discloses a method for synthesizing benzocycloheptenone compounds by transition metal catalysis, belonging to the technical field of organic synthesis. The preparation method comprises the steps of taking 2-biphenyl boric acid compounds and disubstituted cyclopropenone compounds as initial raw materials, and heating and stirring the initial raw materials in an organic solvent to react under the action of a transition metal rhodium catalyst and a silver salt oxidant to obtain the benzocycloheptenone compounds. The invention has the advantages of simple and easy preparation of the starting material, wide application range of the substrate, simple operation and the like, and the ring-opening of the three-membered ring of the cyclopropenone in the reaction process regenerates the seven-membered ring, thereby providing a beneficial reference for synthesizing the complex polycyclic compound in one step.)

1. A method for synthesizing benzocycloheptenone compounds is characterized by comprising the following steps: taking a 2-biphenyl boric acid compound 1 and a disubstituted cyclopropenone compound 2 as starting raw materials, and heating and reacting in an organic solvent under the action of a transition metal rhodium catalyst and a silver salt oxidant to obtain a benzocycloheptone compound 3;

wherein: r¹One or more selected from C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group and C1-C4 alkoxycarbonyl; r²Is selected from C1-C6 alkyl, phenyl or substituted phenyl, wherein the substituent in the substituted phenyl is one or more of C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group, C1-C4 alkylsulfonyl and C1-C4 alkoxycarbonyl.

2. The method for synthesizing benzocycloheptenone compounds according to claim 1, characterized in that: the R is²Is phenyl, 3-chlorophenyl, 2-methylphenyl, 2-chlorophenyl, 2-bromophenyl or propyl.

3. The method for synthesizing benzocycloheptenone compounds according to claim 1, characterized in that: the rhodium catalyst is [ Cp^*RhCl₂]₂。

4. The method for synthesizing benzocycloheptenone compounds according to claim 1, characterized in that: the silver salt oxidant is one or more of silver acetate, silver carbonate, silver benzoate, silver sulfate, silver nitrate and silver oxide.

5. The method for synthesizing benzocycloheptenone compounds according to claim 1, characterized in that: the organic solvent is an aprotic polar solvent.

6. The method for synthesizing benzocycloheptenone compounds according to claim 5, characterized in that: the aprotic polar solvent is selected from ethyl acetate, toluene, dichloroethane or acetone.

7. The method for synthesizing benzocycloheptenone compounds according to claim 1, characterized in that: the molar ratio of the compound 1, the compound 2, the rhodium catalyst and the silver salt oxidant is 1.0-1.5:1.0:0.02-0.10: 0.5-2.0.

8. The method for synthesizing the benzocycloheptenone compounds represented by the formula 3 according to claim 1, characterized in that: the heating temperature is 40-80 ℃.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing benzocycloheptenone compounds.

Background

Cycloheptenone and its derivatives are widely present in natural products and drug molecules as important organic frameworks. The benzocycloheptenone compounds are special compounds containing a seven-membered ring structure, and most of the structures have biological activities of resisting fungi, bacteria, viruses, tumors and the like.

At present, research and development on cycloheptenone and derivatives are relatively insufficient, so that the development of a high-efficiency synthesis method of the benzocycloheptenone compounds plays an important role in screening of drug lead compounds.

Disclosure of Invention

In order to overcome the technical defects, the invention provides a benzocycloheptenone compound and a preparation method thereof. The compound benzocycloheptenone compound has a novel structure, can be finished in one step by taking a 2-biphenyl boric acid compound and a disubstituted cyclopropenone compound as starting raw materials in the presence of a rhodium catalyst and a silver salt oxidant, and can be obtained with high yield. The synthesis method is not reported at present. The method has the following advantages: the method has the advantages of universality, mild reaction conditions, low cost, high reaction yield, less generated by-products, reasonable reaction path and capability of efficiently preparing the compound.

The benzocycloheptenone compound has the following specific structure:

wherein: r¹One or more selected from C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group and C1-C4 alkoxycarbonyl; r²Is selected from C1-C6 alkyl, phenyl or substituted phenyl, and the substituent is one or more of C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group, C1-C4 alkylsulfonyl and C1-C4 alkoxycarbonyl.

The invention also provides a synthesis method of the benzocycloheptenone compound, which comprises the following steps: taking 2-biphenyl boric acid compounds 1 and disubstituted cyclopropenone compounds 2 as initial raw materials, and heating and stirring the initial raw materials in an organic solvent to react under the action of a transition metal rhodium catalyst and a silver salt oxidant to obtain benzocycloheptenone compounds 3.

The synthetic route is as follows:

wherein: r¹One or more selected from C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group and C1-C4 alkoxycarbonyl; r²Is selected from C1-C6 alkyl, phenyl or substituted phenyl, wherein the substituent in the substituted phenyl is one or more of C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro, nitrile group, C1-C4 alkylsulfonyl and C1-C4 alkoxycarbonyl.

Further, in the above technical scheme, the rhodium catalyst is [ Cp ]^*RhCl₂]₂。

Further, in the above technical solution, the silver salt oxidant is one or more of silver acetate, silver carbonate, silver benzoate, silver sulfate, silver nitrate, and silver oxide.

Further, in the technical scheme, the molar ratio of the compound 1, the compound 2, the rhodium catalyst and the silver salt oxidant is 1.0-1.5:1.0:0.02-0.10: 0.5-2.0.

Further, in the above technical solution, the organic solvent is selected from aprotic polar solvents. The aprotic polar solvent is preferably selected from ethyl acetate, toluene, dichloroethane or acetone.

Further, in the above technical scheme, the heating reaction temperature is 40-80 ℃.

Furthermore, in the technical scheme, the reaction can be directly carried out in the air without the protection of inert gas.

From the experimental results, the possible reaction mechanism is presumed as follows:

further, in the above technical scheme, the obtained product is further derived as follows (taking 3aa as an example):

advantageous effects of the invention

The invention can synthesize the benzocycloheptenone compound with high selectivity, and has the advantages that: the compound is synthesized for the first time, the reaction condition is mild, the efficiency is high, the reaction path is reasonable, and the post-treatment is simple.

Detailed Description

The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.

Reaction condition optimization test

Exploration test of reaction conditions: (taking the example of the rhodium-catalyzed formation of 3aa from 1a and 2 a) in a typical procedure, compounds 1a (0.12mmol,1.5eq), [ Cp ]^*RhCl₂]₂(4.0 mol%), a compound 2a (0.1mmol,1.0eq) and various silver salts and corresponding common solvents, sealing a reaction tube, heating to 40-80 ℃ for reaction, and monitoring the complete disappearance of the raw material 2a by a thin-layer plate (TLC) (12 h); the solvent was spin dried and column chromatographed (eluent: petroleum ether/dichloromethane volume ratio 1:1) to give 3aa of a white solid. The reaction equation is as follows:

^areaction conditions are as follows: 1a (0.1mmol),2a (0.1mmol), [ Cp ]^*RhCl₂]₂(4 mol%), an oxidizing agent (x eq), a solvent (1mL), and an air atmosphere at 60 ℃ for 12 hours, and the yield was isolated.

Based on the above optimization experiments, the general synthesis method of the benzocycloheptenone compound 3 typically operates as follows:

in a reaction tube, Compound 1, Compound 2 (Compound 1 to Compound 2 molar ratio 1.2:1.0), and [ Cp^*RhCl₂]₂(4 mol%) under the condition of air, adding 1.0mL of ethyl acetate, sealing the vacuum sealed tube, placing the tube in an oil bath at 60 ℃, stirring until the reaction is finished, adding water for quenching, extracting with diethyl ether, combining diethyl ether layers, removing the organic solvent under reduced pressure to obtain a crude product, and purifying by PE/DCM silica gel column chromatography to obtain a compound 3.

Example 1

2-Biphenylboronic acid 1a (0.15mmol,30.0mg), 2, 3-diphenylcyclopropane-2-en-1-one 2a (0.1mmol,20.6mg) and [ Cp ] were sequentially added to a 25mL pressure-resistant tube^*RhCl₂]₂(0.004mmol,2.5mg), AgOAc (0.2mmol,33.4mg) and ethyl acetate (1.0mL), the reaction tube was sealed, and the mixture was then heated at 60 ℃ with stirring for 12 h. Cool to room temperature and spin dry the solvent. Adding deionized water and ethyl acetate, extracting the aqueous phase for three times, combining the organic phases, back-extracting with saturated saline solution once, and drying with anhydrous sodium sulfate. Separation by spin-dry column chromatography (petroleum ether/dichloromethane ═ 1:1) gave 3aa (32.2mg, 90%) as a white solid.¹H NMR(600MHz,CDCl₃)δ7.88(d,J＝7.8Hz,1H),7.72(dd,J＝8.0,1.1Hz,1H),7.65–7.63(m,1H),7.45–7.43(m,1H),7.40–7.37(m,1H),7.34(dd,J＝7.6,1.2Hz,1H),7.26–7.20(m,3H),7.14–7.08(m,7H),6.99–6.96(m,2H).¹³C NMR(150MHz,CDCl₃)δ197.9,144.2,142.6,141.8,141.1,137.8,137.2,136.4,136.1,134.2,133.8,131.7,131.4,131.0,130.8,130.1,129.4,129.2,129.1,128.9,128.7,128.5,128.4,127.8,127.7,127.6,125.7.[M+Na]⁺Calcd for C₂₇H₁₈NaO⁺381.1250,Found:381.1245.

Example 2

By usingWhite solid 3ab (24.5mg, 62%, m.p.224-225 ℃ C.) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)δ7.90(d,J＝7.9Hz,1H),7.74(dd,J＝7.9,0.9Hz,1H),7.69–7.66(m,1H),7.49–7.46(m,1H),7.45–7.41(m,1H),7.35(dd,J＝7.6,1.0Hz,1H),7.28–7.20(m,3H),7.10(dd,J＝8.0,1.0Hz,1H),6.98–6.91(m,2H),6.90–6.78(m,4H).¹³C NMR(150MHz,CDCl₃)δ198.7,162.1(d,J＝247.3Hz,1C),161.9(d,J＝247.9Hz,1C),144.4,141.9,141.0,137.7,137.1(d,J＝3.7Hz,1C),136.8,136.4,132.8(d,J＝7.9Hz,1C),132.0(d,J＝7.9Hz,1C),131.8,131.7(d,J＝3.3Hz,1C),131.2,130.9,128.8,128.4(d,J＝7.5Hz,1C),127.4,125.6,115.2(d,J＝21.8Hz,1C),114.9(d,J＝21.1Hz,1C).¹⁹F NMR(376MHz,CDCl₃)δ-114.15/-114.22(m),-114.44/-114.51(m).[M+Na]⁺Calcd for C₂₇H₁₆F₂NaO⁺417.1563,Found:417.1561.

Example 3

By usingWhite solid 3ac (30.8mg, 80%) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)for the diastereoisomersδ7.89(m,2H),7.80–7.77(m,1H),7.75–7.74(m,1H),7.70–7.68(m,3H),7.53–7.50(m,2H),7.48–7.40(m,4H),7.29–7.17(m,5H),7.14–7.00(m,8H),7.00–6.91(m,4H),6.87–6.80(m,2H),6.74(s,1H),2.50(s,2.5H),1.85(s,2.5H),1.67(s,3H),1.65(s,3H).¹³C NMR(150MHz,CDCl₃)for the diastereoisomersδ198.3,197.6,171.3,145.1,144.3,143.8,143.3,140.2,139.3,137.7,137.4,137.3,137.0,136.4,136.2,136.1,135.7,135.6,135.0,132.8,132.0,131.2,131.1,130.8,130.7,130.6,130.2,130.1,130.0,129.6,129.0,128.6,128.5,128.4,128.1,128.0,127.7,127.6,127.4,126.5,125.8,125.2,125.0,124.8,60.5,21.3,21.2,19.9,19.7,14.4.[M+Na]⁺Calcd for C₂₉H₂₂NaO⁺409.1563,Found:409.1561.

The isomers are diastereoisomers, each beingThe isomer ratio is 1: 1.2, main compound structures cannot be distinguished, and the separation cannot be realized through column chromatography.

Example 4

By usingWhite solid 3ad (33.6mg, 79%) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)for the diastereoisomersδ7.90–7.89(m,1H),7.81–7.74(m,2H),7.74–7.70(m,1H),7.59–7.50(m,2H),7.48–7.44(m,2H),7.36–7.16(m,5H),7.12–7.00(m,4H).¹³C NMR(150MHz,CDCl₃)for the diastereoisomersδ196.9,195.3,144.4,143.6,143.1,142.5,142.2,141.9,139.4,138.2,138.03,137.96,137.1,136.9,135.8,135.2,134.6,134.3,134.2,133.7,133.0,132.9,132.8,131.5,131.3,131.1,130.3,130.1,130.0,129.4,129.33,129.29,129.21,129.15,129.1,128.9,128.8,128.6,128.4,128.3,127.8,127.6,127.2,126.6,126.5,126.3,125.54,125.49.[M+Na]⁺Calcd for C₂₇H₁₆Cl₂NaO⁺449.0470, Found:449.0467 the product is a similar diastereomer to example 3, in a ratio of 1: 1.9, cannot be separated by column chromatography.

Example 5

By usingThe procedure described in example 1 was followed to give 3ae (34.5mg, 67%) as a white solid.

¹H NMR(400MHz,CDCl₃)for the diastereoisomersδ7.90–7.87(m,1H),7.80–7.75(m,1H),7.72–7.68(m,1H),7.63–7.37(m,5H),7.35–7.14(m,4H),7.09–6.95(m,3H).¹³C NMR(100MHz,CDCl₃)for the diastereoisomersδ196.8,194.9,144.7,144.1,143.8,143.7,143.1,141.2,139.7,139.3,138.5,138.3,137.3,137.1,137.0,135.9,134.7,134.6,133.7,133.3,132.7,132.5,132.4,131.52,131.46,131.2,131.0,130.14,130.05,129.8,129.4,129.33,129.30,129.23,129.18,129.0,128.7,128.6,128.4,128.33,128.25,127.8,127.6,127.3,127.0,126.9,126.8,126.03,125.96,124.5,124.2,123.3,122.7.[M+Na]⁺Calcd for C₂₇H₁₆Br₂NaO⁺538.9440, Found:538.9438 the product is a similar diastereomer to example 3, in a ratio of 1: 1.9, isomers cannot be separated by column chromatography.

Example 6

By usingThe procedure described in example 1 gave 3af (30.6mg, 57%, m.p.139 ℃ -140 ℃ C.) as a white solid.

¹H NMR(400MHz,CDCl₃)δ7.83(d,J＝7.8Hz,1H),7.68(d,J＝7.8Hz,1H),7.64–7.60(m,1H),7.48–7.34(m,2H),7.30(d,J＝7.5Hz,1H),7.23–7.18(m,1H),7.10–6.98(m,5H),6.92(s,1H),6.83(d,J＝7.3Hz,1H).¹³C NMR(150MHz,CDCl₃)δ197.9,144.2,142.6,141.8,141.1,137.8,137.2,136.4,136.1,134.2,133.8,131.7,131.4,131.0,130.8,130.1,129.4,129.2,129.1,128.9,128.7,128.5,128.4,127.8,127.7,127.6,125.7.[M+Na]⁺Calcd for C₂₇H₁₄Cl₂NaO⁺449.0470,Found:449.0472.

Example 7

By usingThe procedure described in example 1 was followed to give 3ag as a white solid (28.4mg, 98%, m.p.55-57 ℃ C.).

¹H NMR(400MHz,CDCl₃)δ7.73(d,J＝7.8Hz,1H),7.65–7.54(m,3H),7.49–7.42(m,2H),7.40–7.32(m,2H),2.73–2.48(m,4H),1.54–1.27(m,4H),0.91(t,J＝7.3Hz,3H),0.76(t,J＝7.4Hz,3H).¹³C NMR(100MHz,CDCl₃)δ201.9,145.0,144.4,140.6,137.01,136.96,136.6,131.0,130.7,128.2,127.9,127.6,127.5,127.1,125.3,34.9,34.2,22.9,22.3,14.4,14.0.[M+Na]⁺Calcd for C₂₁H₂₂Na O⁺313.1563,Found:313.1563.

Example 8

By usingThe procedure described in example 1 was followed to give 3ba (23.7mg, 60%, m.p.184-185 ℃ C.) as a white solid.

¹H NMR(400MHz,CDCl₃)δ7.44–7.40(m,1H),7.35–7.31(m,1H),7.25–7.19(m,3H),7.15–7.10(m,7H),7.05–6.95(m,3H),6.91(d,J＝8.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ197.9,161.4(d,J＝1.7Hz,1C),160.3(d,J＝243.3Hz,1C),159.9(d,J＝244.9Hz,1C),158.9,147.8(d,J＝1.6Hz,1C),144.1,139.9(d,J＝2.2Hz,1C),139.8(d,J＝1.8Hz,1C),140.1,134.9,131.0,130.7(d,J＝8.4Hz,1C),130.0,129.2(d,J＝9.1Hz,1C),128.0(d,J＝11.0Hz,1C),127.6(d,J＝4.3Hz,1C),126.9(d,J＝3.0Hz,1C),120.0,119.9(d,J＝2.9Hz,1C),117.9(d,J＝22.1Hz,1C),117.1(d,J＝15.7Hz,1C),115.1(d,J＝1.0Hz,1C),114.9(d,J＝1.3Hz,1C).¹⁹F NMR(376MHz,CDCl₃)δ-108.46/-108.50(m),-108.60/-108.64(m),-108.75/-108.79(m),-108.89/-108.93(m).[M+Na]⁺Calcd for C₂₇H₁₆F₂NaO⁺417.1061,Found:417.1055.

Example 9

By usingThe procedure described in example 1 was followed to give 3ca as a white solid (37.1mg, 96%, m.p.166 ℃ -168 ℃).

¹H NMR(600MHz,CDCl₃)δ7.67(s,1H),7.52(s,1H),7.24–7.22(m,4H),7.09–7.07(m,6H),7.01(dd,J＝8.2,1.3Hz,1H),6.98–6.93(m,3H),2.51(s,3H),2.41(s,3H).¹³C NMR(150MHz,CDCl₃)δ198.7,142.21,142.20,141.8,141.6,141.2,138.0,137.7,136.6,136.3,134.6,132.0,131.10,131.08,130.4,129.2,129.0,128.2,127.8,127.6,127.01,126.98,125.9,21.9,21.5.[M+Na]⁺Calcd for C₂₉H₂₂NaO⁺409.1563,Found:409.1554.

Example 10

By usingThe procedure described in example 1 was followed to give 3da (20.0mg, 51%) as a white solid.

¹H NMR(400MHz,CDCl₃)for the regioismersδ7.52–7.26(m,3H),7.18–6.91(m,10H),6.91–6.73(m,3H).¹³C NMR(100MHz,CDCl₃)for the regioismersδ198.2,194.7,164.2(d,J＝250.8Hz),161.4(d,J＝249.5Hz),161.2(d,J＝252.8Hz),156.4(d,J＝253.0Hz),144.5,142.7(d,J＝0.9Hz,1H),141.4(d,J＝2.9Hz),140.5,140.2(d,J＝3.0Hz),138.9(d,J＝2.6Hz),138.8(d,J＝2.8Hz),138.7,138.4(d,J＝3.2Hz),138.3(d,J＝3.1Hz),134.5,134.4,134.2,134.0(d,J＝3.3Hz),133.9,131.7(d,J＝17.3Hz),131.4(d,J＝8.5Hz),131.2,130.1,130.0,129.6(d,J＝10.3Hz),129.5(d,J＝2.1Hz),128.2,128.0,127.8(d,J＝9.3Hz),127.70(d,J＝7.4Hz),127.68,127.4(d,J＝42.2Hz),126.0(d,J＝3.2Hz),125.8(d,J＝11.0Hz),124.3(d,J＝3.6Hz),116.7(d,J＝22.7Hz),116.2(d,J＝23.0Hz),115.71(d,J＝40.2Hz),115.71(d,J＝2.7Hz),115.4(d,J＝4.0Hz),115.1(d,J＝5.7Hz).¹⁹F NMR(376MHz,CDCl₃)δ-101.40/-101.44(m),-108.27/-108.33(m),-112.44/-112.50(m),-119.17/-119.20(m).(The fluorine spectru m shows that the ratio of products is 1:1.1)[M+Na]⁺Calcd for C₂₇H₁₆F₂NaO⁺417.1061, Found:417.1054 the product is a regioisomer with a ratio of 1: 1.1, cannot be separated by column chromatography.

Example 11

By usingWhite solid 3ea (42.3mg, 99%) was obtained as described in example 1.

¹H NMR(400MHz,CDCl₃)δ7.85(d,J＝1.8Hz,1H),7.69(d,J＝2.1Hz,1H),7.44(dd,J＝8.2,1.8Hz,1H),7.29(d,J＝8.2Hz,1H),7.26–7.18(m,3H),7.17–7.09(m,6H),7.06(d,J＝8.6Hz,1H),6.95–6.93(m,2H).¹³C NMR(150MHz,CDCl₃)δ197.3,143.0,142.8,140.9,140.7,137.8,137.3,136.7,135.9,135.4,134.0,133.7,131.0,130.2,130.1,129.0,128.5,128.1,128.0,127.8,127.6,127.5,127.4.[M+Na]⁺Calcd for C₂₇H₁₆Cl₂NaO⁺449.0470,Found:449.0460.

Example 12

By usingWhite solid 3fa (48.9mg, 99%, m.p.162-163 ℃) was obtained as described in example 1.

¹H NMR(400MHz,CDCl₃)δ8.24(s,1H),8.06(s,1H),7.83(d,J＝7.9Hz,1H),7.59(d,J＝8.1Hz,1H),7.53(d,J＝7.9Hz,1H),7.40–7.31(m,3H),7.24–7.21(m,6H),7.05–7.04(m,2H).¹³C NMR(100MHz,CDCl₃)δ197.4,147.0,144.2,140.7,140.1,136.8,135.7,134.7,133.2(q,J＝32.9Hz,1C),132.9,131.0,130.1,130.3(q,J＝32.9Hz,1C),128.3,128.0,127.9,127.4(q,J＝3.9Hz,1C),126.4,125.7(q,J＝3.5Hz,1C),125.6(q,J＝3.7Hz,1C),124.6(q,J＝3.5Hz,1C),123.8(q,J＝272.9Hz,1C).¹⁹F NMR(376MHz,CDCl₃)δ-62.55,-62.63.[M+Na]⁺Calcd for C₂₉H₁₆F₆NaO⁺517.0998,Found:517.1000.

Example 13

By usingThe procedure described in example 1 was followed to give 3ga (46.5mg, 99%, m.p.200-201 ℃ C.) as a white solid.

¹H NMR(400MHz,CDCl₃)δ7.85(d,J＝8.3Hz,1H),7.73–7.66(m,2H),7.43(dd,J＝8.3,2.0Hz,1H),7.39(d,J＝2.0Hz,1H),7.33(d,J＝3.6Hz,1H),7.31(d,J＝2.4Hz,1H),7.17–7.08(m,7H),7.00(d,J＝3.6Hz,1H),6.98(d,J＝2.3Hz,1H),1.35(s,9H),1.16(s,9H).¹³C NMR(150MHz,CDCl₃)δ199.3,151.1,149.6,144.0,142.8,142.2,141.7,136.7,136.5,134.9,133.9,131.1,130.6,130.2,129.1,128.5,128.4,127.7,127.6,126.98,126.96,125.3,122.5,35.0,34.6,31.4,31.1.[M+Na]⁺Calcd for C₃₅H₃₄NaO⁺493.2502,Found:493.2495.

Example 14

By usingWhite solid 3ha (48.9mg, 99%) was obtained as described in example 1.

¹H NMR(400MHz,CDCl₃)δ8.03(d,J＝8.3Hz,1H),7.92(d,J＝8.3Hz,1H),7.85(d,J＝8.3Hz,1H),7.71–7.60(m,2H),7.41(s,1H),7.28–7.23(m,2H),7.21–7.07(m,6H),6.96–6.94(m,2H).¹³C NMR(150MHz,CDCl₃)δ196.9,144.8,144.0,141.0,139.9,139.3,138.30,138.26,134.9,131.5,131.3(q,J＝33.8Hz,1C),130.9,130.4(q,J＝32.9Hz,1C),130.2,129.6,129.0(q,J＝3.6Hz,1C),128.4,128.0,127.9,127.7(q,J＝3.3Hz,1C),124.7(q,J＝3.4Hz,1C),123.7(q,J＝272.6Hz,1C),123.6(q,J＝272.4Hz,1C),123.0(q,J＝3.9Hz,1C).¹⁹F NMR(376MHz,CDCl₃)δ-62.59,-62.93.[M+Na]⁺Calcd for C₂₉H₁₆F₆NaO⁺517.0998,Found:517.0997.

Example 15

By usingYellow liquid 3ia (37.0mg, 96%) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)δ7.78(d,J＝8.1Hz,1H),7.63(d,J＝8.1Hz,1H),7.46(d,J＝8.0Hz,1H),7.28–7.27(m,2H),7.22(d,J＝8.0Hz,1H),7.17(s,1H),7.14–7.11(m,6H),7.00–6.99(m,2H),6.92(s,1H),2.39(s,3H),2.24(s,3H).¹³C NMR(150MHz,CDCl₃)δ198.8,159.2,157.8,144.8,142.19,142.17,141.3,137.9,136.3,131.7,131.0,130.7,130.4,130.0,129.5,127.9,127.6,127.2,127.1,118.7,116.5,114.6,108.8,55.7,55.3.[M+Na]⁺Calcd for C₂₉H₂₂NaO⁺409.1563,Found:409.1563.

Example 16

By usingYellow liquid 3ja (35.8mg, 86%) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)δ7.75(d,J＝8.7Hz,1H),7.61(d,J＝8.8Hz,1H),7.27–7.24(m,2H),7.18(dd,J＝8.7,2.8Hz,1H),7.12–7.10(m,6H),6.99–6.95(m,3H),6.84(d,J＝2.8Hz,1H),6.59(d,J＝2.7Hz,1H),3.80(s,3H),3.62(s,3H).¹³C NMR(150MHz,CDCl₃)δ198.8,159.2,157.8,144.8,142.19,142.17,141.3,137.9,136.3,131.7,131.0,130.7,130.4,130.0,129.5,127.9,127.6,127.2,127.1,118.7,116.5,114.6,108.8,55.7,55.3.[M+Na]⁺Calcd for C₂₉H₂₂NaO₃ ⁺441.1461,Found:441.1459.

Example 17

By usingThe colorless liquid 3ka (42.3mg, 99%) was obtained as described in example 1.

¹H NMR(600MHz,CDCl₃)δ7.79(d,J＝8.5Hz,1H),7.66–7.60(m,2H),7.38(dd,J＝8.5,2.2Hz,1H),7.34(d,J＝2.2Hz,1H),7.25–7.24(m,2H),7.19–7.09(m,7H),7.00–6.94(m,2H).¹³C NMR(150MHz,CDCl₃)δ197.1,145.2,143.4,140.9,140.2,138.7,135.2,135.03,134.97,133.9,133.7,131.9,131.6,131.2,131.0,130.2,130.0,128.5,128.2,127.9,127.7,127.6,125.4.[M+Na]⁺Calcd for C₂₇H₂₁Cl₂NaO⁺449.0470,Found:449.0467.

Example 34

The reaction was scaled up using a scale-up test, referring to the reaction conditions of example 1, with only scale-up of the reaction, and the results were as follows:

example 35

Derivatization procedures for compounds 3aa to 4:

3aa (35.8mg, 0.1mmol) was dissolved in dry DCM (1.0mL) and LiAlH was added₄(29.0mg, 0.1mmol) and the reaction mixture was stirred at 80 ℃ for 4h and then quenched by slow addition of water (2.0 mL). The reaction mixture was first filtered through celite, rotary evaporated and column chromatographed to give 35.5mg of 4 as a colorless oily liquid in 99% yield.¹H NMR(400MHz,CDCl₃)for major productδ7.77(dd,J＝7.9,1.1Hz,1H),7.74–7.68(m,1H),7.45–7.41(m,3H),7.20–7.16(m,4H),7.09-7.07(m,2H),7.03–6.99(m,3H),6.96-6.92(m,2H),6.86–6.79(m,2H),5.09(d,J＝6.9Hz,1H),2.14(d,J＝7.4Hz,1H).¹³C NMR(151MHz,CDCl₃)for mixturesδ145.6,144.6,144.0,142.9,142.8,141.7,141.5,139.7,139.0,138.8,138.2,136.0,135.9,135.7,135.2,134.3,131.6,131.5,131.4,131.1,130.7,130.3,130.0,129.6,129.0,128.9,128.00,127.95,127.9,127.8,127.6,127.42,127.38,127.2,127.0,126.8,126.60,126.58,126.4,120.4,79.0,70.6.[M+Na]⁺Calcd for C₂₇H₂₀NaO⁺383.1406, Found:383.1406 the product is a diastereomer, in a ratio of 1: 3, cannot be separated by column chromatography.

Derivatization procedures for compounds 3aa to 5:

5aa (35.8mg, 0.1mmol), mCPBA (83.0mg, 0.5mmol), CF₃COOH (16. mu.L, 0.2mmol) was dissolved in CH₂Cl₂(1.0mL), heated and stirred at 80 ℃ for 15 hours, then cooled to room temperature. After rotary evaporation, column chromatography gave 20.1mg of yellow oily liquid 5 in 54% yield.¹H NMR(600MHz,CDCl₃)δ8.37(d,J＝8.0Hz,1H),7.71–7.68(m,1H),7.63–7.61(m,1H),7.59(d,J＝7.6Hz,1H),7.55(d,J＝7.7Hz,1H),7.51–7.46(m,2H),7.40–7.33(m,4H),7.28(d,J＝7.8Hz,1H),7.19–7.15(m,4H),7.11(d,J＝7.8Hz,1H),6.66(d,J＝7.9Hz,1H).¹³C NMR(150MHz,CDCl₃)δ197.1,168.0,141.8,140.2,137.8,135.5,134.9,133.6,133.0,131.9,130.0,129.94,129.87,129.5,129.2,129.0,128.9,128.6,128.4,128.2,128.1,127.5,127.1,91.8.[M+Na]⁺Calcd for C₂₇H₁₈NaO₃ ⁺413.1148,Found:413.1146.

The foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and the embodiments and descriptions are only illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the scope of the principles of the present invention, and the changes and modifications are within the scope of the present invention.