Method for synthesizing chiral dihydronaphthalene compound

Abstract

The invention discloses a method for synthesizing a chiral dihydronaphthalene compound, which comprises the following steps: in an organic solvent, catalyzing by a rhodium catalytic system, and carrying out asymmetric ring-opening reaction on a carboxylic ester compound I and an oxabicyclo olefin compound II to obtain a chiral dihydronaphthalene compound III, the rhodium catalytic system is composed of rhodium salt and a chiral ligand, and the chiral ligand has a structure as shown in a formula IV.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis and relates to a method for synthesizing chiral dihydronaphthalene compounds. Background Art

[0002] Chiral dihydronaphthalene compounds are widely present in biologically active molecules and natural products, and can be used as precursors of many natural products and drug molecules. They are also important raw materials in the field of organic synthesis and fine chemicals, such as SF 2315B. However, this type of compound is difficult to obtain only through natural separation and biosynthesis, and has the disadvantages of low content and high cost.

[0003] In recent decades, transition metal-catalyzed asymmetric ring-opening reactions have become a powerful tool for the construction and transformation of new complex molecules. With the advantage of high step economy, they have become a universal method for the construction of various complex cyclic compounds. Moreover, through the combination of chiral ligands and metals, multiple chiral centers can be controlled in one step, completing the asymmetric and efficient construction of the core skeleton of natural products.

[0004] Therefore, developing asymmetric ring-opening reactions based on transmetallation catalysis to achieve efficient and highly selective construction of complex cyclic molecules has potential application value and important methodological significance, but is also full of challenges. Summary of the invention

[0005] In order to overcome the shortcomings of the prior art, one of the purposes of the present invention is to provide a method for preparing chiral dihydronaphthalene compounds. The present invention uses a simple transition metal catalyst and a simple and easy-to-synthesize chiral ligand as a catalytic system to achieve efficient asymmetric synthesis of chiral dihydronaphthalene compounds.

[0006] The technical solution of the present invention is as follows:

[0007] A method for preparing chiral dihydronaphthalene compounds comprises the following steps:

[0008] In an organic solvent, a carboxylate compound I and an oxabicycloolefin compound II are subjected to an asymmetric ring-opening reaction under the catalysis of a rhodium catalyst system to obtain a chiral dihydronaphthalene compound III; the rhodium catalyst system is composed of a rhodium salt and a chiral ligand IV, and the chiral ligand has a structure shown in formula IV;

[0009]

[0010] Wherein in compound I, R1 is 4-methoxyphenyl, 2-chlorophenyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 4-boronic acid pinacol ester phenyl, 4-iodophenyl, 4-(N,N-dimethyl)phenyl, 4-biphenyl, 2-furyl, 2-naphthyl, 2-thienyl;

[0011] R2 is methyl, phenyl, hydrogen, or cyano;

[0012] R3 is methyl, phenyl, hydrogen, or cyano;

[0013] R4 is 4-nitrophenyl, 3-fluoro-4-nitrophenyl, 3-methoxy-4-nitrophenyl, or 2,3,4,5,6-pentafluorophenyl;

[0014] In compound II, R5 is hydrogen, methyl, or methoxy;

[0015] R6 is hydrogen, methyl, methoxy or fluoro;

[0016] R7 is hydrogen, methyl, methoxy or fluoro;

[0017] R8 is hydrogen, methyl or methoxy;

[0018] In compound III, substituents R1, R2, R3, and R4 are respectively the same as R1, R2, R3, and R4 in compound I; substituents R5, R6, R7, and R8 are the same as R5, R6, R7, and R8 in compound II.

[0019] Preferably according to the present invention, the solvent is one or more of acetonitrile, tetrahydrofuran, dioxane, ether, dichloromethane, ethyl acetate, toluene, 1,2-dichloroethane, DMF, DMSO or ethylene glycol dimethyl ether; the ratio of the volume of the solvent to the molar number of the carboxylate compound I is 1 mL: 0.1 mmol; and the solvent is anhydrous.

[0020] Preferably according to the present invention, the rhodium catalyst is (1,5-cyclooctadiene)chlororhodium (I) dimer; the molar ratio of the rhodium catalyst to the carboxylate compound I is 0.02:0.1; and the molar ratio of the rhodium in the rhodium catalyst to the chiral ligand IV is 1:2.5.

[0021] Preferably according to the present invention, the rhodium catalyst is prepared according to the following method: under nitrogen protection, rhodium salt and chiral ligand IV are added to a solvent, stirred at room temperature for 30 minutes, and the resulting solution is a rhodium catalyst system.

[0022] Preferably according to the present invention, the asymmetric ring-opening reaction is carried out under an inert gas atmosphere, and the inert gas is nitrogen.

[0023] Preferably according to the present invention, the temperature of the asymmetric ring-opening reaction is 70° C.; the time of the asymmetric ring-opening reaction is 2 to 7 hours.

[0024] According to the present invention, after the carboxylate compound I and the oxabicycloolefin compound II undergo an asymmetric ring-opening reaction, the product can be separated and characterized by a conventional separation and purification method. The specific post-reaction treatment steps are as follows: the reaction solution is freed of solvent, and the obtained crude product is separated by silica gel column chromatography to obtain a chiral dihydronaphthalene compound III, and the eluent is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the mixed solvent of ethyl acetate and petroleum ether in the mixed solvent is 0.05-0.2:1.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The present invention uses carboxylic acid ester compounds I substituted with different substituents and oxygen-heterobicycloolefin compounds II substituted with different substituents as raw materials, uses a catalyst and a chiral ligand that are simple and easily available and novel in structure as a catalytic system, and prepares dihydronaphthalene compounds through an asymmetric ring-opening reaction. The method of the present invention can generate dihydronaphthalene compounds with high stereoselectivity and regioselectivity, and perform efficient asymmetric synthesis of chiral dihydronaphthalene compounds.

[0027] The catalyst used in the method of the present invention is a commercially available rhodium catalyst and a chiral ligand IV; the catalyst has the advantages of low catalyst cost, high efficiency, etc., and the amount of the catalyst used is small and can be reduced to 2%; the method of the present invention for preparing dihydronaphthalene compounds through an asymmetric ring-opening reaction of a metal catalyst has the advantages of convenient operation, wide application range of substrates, cheap and easy-to-obtain reaction raw materials, etc. DETAILED DESCRIPTION

[0028] The present invention will be further described below in conjunction with specific implementation modes, but is not limited thereto.

[0029] Meanwhile, the experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents, materials and equipment described are all commercially available unless otherwise specified.

[0030] The yields described in the examples are molar yields.

[0031] The reaction route is as follows:

[0032] Example 1

[0033]

[0034] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 1a (51.4 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 1c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 88% and the ee value was 98%.

[0035] 1 H NMR(CDCl3,400MHz)δ8.18-8.13(m,2H),7.36-7.31(m,1H),7.28-7.21(m,6H),7.19(d,J=7.2Hz,1H),7.14(d,J=7.2Hz,1H),6 .96-6.90(m,2H),6.67(d,J=10.0Hz,1H),6.41(d,J=7.6Hz,1H),6.00(dd,J=10.0&3.2Hz,1H),5.26-5.21(m,1H),3.68(s,2H);

[0036] 13 C NMR (CDCl3, 100MHz) δ171.1,162.6,142.0,133.5,132.1,131.4,130.9,129. 3,128.7,128.6,127.4,127.3,126.9,126.1,123.7,115.6,75.4,72.7,41.6;

[0037] Example 2

[0038]

[0039] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 2a (55.0 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 2c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 72% and the ee value was 97%.

[0040] 1H NMR(CDCl3,400MHz)δ8.20-8.14(m,2H),7.37-7.31(m,1H),7.28-7.17(m,4H),7.14(d,J=7.6Hz,1H),6.97-6.89( m,4H),6.67(d,J=9.6Hz,1H),6.39(d,J=7.6Hz,1H),6.01(dd,J=9.6&3.2Hz,1H),5.26-5.20(m,1H),3.64(s,2H);

[0041] 13 C NMR(CDCl3,100MHz)δ171.0,162.2(d,J=244.8Hz),162.5,142.0,132.1,131.2,130.9(d,J=17.2Hz), 130.8,129.4,129.3(d,J=2.7Hz),128.7,127.4,126.9,126.1,123.6,115.7,115.5,75.2,72.7,40.6;

[0042] Example 3

[0043]

[0044] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 3a (58.2 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 3c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 81% and the ee value was 96%.

[0045] 1 H NMR(CDCl3,400MHz)δ8.20-8.14(m,2H),7.37-7.31(m,1H),7.29-7.12(m,7H),6.94-6.88(m,2H),6.66 (d,J=10.0Hz,1H),6.40(d,J=8.0Hz,1H),5.99(dd,J=10.0&2.8Hz,1H),5.24-5.19(m,1H),3.64(s,2H);

[0046] 13C NMR (CDCl3, 100MHz) δ170.7,162.5,142.0,133.5,132.2,132.0,131.2,131. 0,129.4,128.9,128.7,127.4,126.8,126.1,123.6,115.5,75.4,72.9,40.9;

[0047] Example 4

[0048]

[0049] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 4a (57.4 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 4c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 88% and the ee value was 98%.

[0050] 1 H NMR(CDCl3,400MHz)δ8.17-8.11(m,2H),7.36-7.31(m,1H),7.28-7.22(m,1H),7.21-7.12(m,4H),6.93-6.89(m,2H),6.78-6.74(m, 2H),6.66(dd,J=17.6&1.2Hz,1H),6.40(d,J=8.0Hz,1H),5.99(dd,J=9.6&3.2Hz,1H),5.25-5.22(m,1H),3.75(s,3H),3.61(s,2H);

[0051] 13 C NMR (CDCl3, 100MHz) δ171.4,162.6,158.9,141.9,132.1,131.5,130.8,130.3,129. 2,128.6,127.3,126.8,126.0,125.5,123.8,115.5,114.1,75.6,72.7,55.3,40.7;

[0052] Example 5

[0053]

[0054] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 5a (51.4 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 5c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 57% and the ee value was >99%.

[0055] 1 H NMR(CDCl3,400MHz)δ8.21-8.16(m,2H),7.37-7.32(m,2H),7.28-7.17(m,6H),7.01-6.98(m,2H),6.67(d d,J=9.6&1.2Hz,1H),6.43(d,J=7.6Hz,1H),6.01(dd,J=9.6&3.2Hz,1H),5.29-5.24(m,1H),3.82(s,2H);

[0056] 13 C NMR (CDCl3, 100MHz) δ170.2,162.6,142.0,134.6,132.2,132.0,131.6,131.3,131. 0,129.7,129.4,129.1,128.7,127.4,127.1,126.1,123.6,115.6,75.2,72.9,39.4;

[0057] Example 6

[0058]

[0059] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 6a (65.0 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 6c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 64% and the ee value was 98%.

[0060] 1H NMR(CDCl3,400MHz)δ8.18-8.13(m,2H),7.53-7.47(m,2H),7.43(d,J=7.6Hz,1H),7.40-7.32(m,2H),7.28-7.23(m,1H),7.22-7.14( m,2H),6.95-6.91(m,2H),6.68(d,J=10.0Hz,1H),6.40(d,J=7.6Hz,1H),6.01(dd,J=9.6&3.6Hz,1H),5.24-5.20(m,1H),3.74(s,2H);

[0061] 13 C NMR(CDCl3,100MHz)δ170.3,162.5,142.0,134.5,132.8,132.1,131.1(q,J=19.6Hz),131.0,129.5,12 9.2,128.7,127.5,127.0,126.1,125.4,124.4,123.9(q,J=132.5Hz),123.4,115.5,75.1,72.9,41.2;

[0062] Example 7

[0063]

[0064] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 7a (51.4 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 7c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 70% and the ee value was >99%.

[0065] 1H NMR(CDCl3,400MHz)δ8.14-8.10(m,2H),7.35-7.30(m,1H),7.27-7.23(m,1H),7.18(d,J=7.6Hz,2H),7.08(d,J=8.8Hz,2H),6.88(d,J=9.2Hz,2H ),6.65(d,J=10.0Hz,1H),6.56(d,J=8.4Hz,2H),6.41(d,J=8.4Hz,1H),5 .98(dd,J=9.6&3.2Hz,1H),5.24-5.21(m,1H),3.57(s,2H),2.89(s,6H);

[0066] 13 C NMR (CDCl3, 100MHz) δ171.8,162.7,149.8,141.8,132.2,131.7,130.7,129.9,129. 1,128.7,127.3,126.8,125.9,123.9,121.1,115.5,112.6,75.9,72.6,40.7,40.5;

[0067] Example 8

[0068]

[0069] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 8a (54.8 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 8c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 81% and the ee value was 98%.

[0070] 1 H NMR(CDCl3,400MHz)δ8.22-8.17(m,2H),7.37-7.26(m,3H),7.23-7.17(m,2H),7.04-6.99(m,2H),6.68(d,J=9.6Hz,1H),6.42(d ,J=7.6Hz,1H),6.30(dd,J=3.2&2.4Hz,1H),6.20(d,J=3.2Hz,1H),6.03(dd,J=9.6&3.2Hz,1H),5.29-5.25(m,1H),3.73(s,2H);

[0071] 13 C NMR (CDCl3, 100MHz) δ169.0,162.7,147.1,142.4,142.1,132.2,131.1,129. 4,128.8,127.4,127.2,126.1,123.6,115.7,110.7,108.5,75.1,73.0,34.3;

[0072] Example 9

[0073]

[0074] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 9a (52.6 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 9c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 77% and the ee value was >99%.

[0075] 1 H NMR(CDCl3,400MHz)δ8.20-8.15(m,2H),7.37-7.32(m,1H),7.29-7.24(m,1H),7.22-7.15(m,3H),7.00-6.95(m,2H),6.93-6 .88(m,2H),6.69(dd,J=9.6&1.2Hz,1H),6.41(d,J=7.2Hz,1H),6.03(dd,J=10.0&3.2Hz,1H),5.28-5.24(m,1H),3.88(s,2H);

[0076] 13 C NMR (CDCl3, 100MHz) δ170.0,162.6,142.0,134.4,132.2,131.1,129.4,128. 7,127.4,127.2,127.1,127.0,126.1,125.4,123.5,115.6,75.1,72.9,35.7;

[0077] Example 10

[0078]

[0079] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 10a (33.3 mg, 0.1 mmol) and 1b (17.3 mg, 0.12 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 10c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 64% and the ee value was 98%.

[0080] 1 H NMR(CDCl3,400MHz)δ8.16-8.12(m,2H),7.33-7.22(m,11H),7.22-7.14(m,2H),7.04(d,J=7.6Hz,1H),6.93-6.87(m,2H ),6.63(d,J=10.0Hz,1H),6.54(d,J=8.8Hz,1H),5.97(dd,J=10.0&2.8Hz,1H),5.27(dt,J=8.4&2.0Hz,1H),5.09(s,1H);

[0081] 13 C NMR(CDCl3,100MHz)δ172.1,162.5,142.0,138.2,132.1,131.5,130.7,129.2,1 28.8,128.7,128.6,127.6,127.3,126.5,126.1,123.8,115.5,75.9,73.2,57.3;

[0082] Embodiment 11

[0083]

[0084] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 11a (29.6 mg, 0.1 mmol) and 1b (17.3 mg, 0.12 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 11c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1), and the yield was 47%.

[0085] 1H NMR(CDCl3,400MHz,2:3dr)δ8.24-8.18(m,0.8H),8.13-8.07(m,1.2H),7.51-7.46(m,1H ),7.44-7.40(m,1H),7.36-7.24(m,4H),7.19-7.09(m,3H),7.00-6.94(m,1H),6.71-6.69 (m,1H),6.61-6.52(m,1.6H),6.47-6.42(m,0.4H),5.98(dd,J=9.6&2.8Hz,0.4H),5.86( dd,J=10.0&2.4Hz,0.6H),5.36-5.31(m,0.4H),5.21-5.16(m,0.6H),1.99&1.96(2s,3H);

[0086] 13 C NMR(CDCl3,100MHz,2:3dr)δ167.6,167.5,162.3,162.0,142.3,142.0,135.3,132.0,130.7,130.5,129.4,129.3,129.2,129.1,128.9,12 8.6,127.4,127.3,126.2,126.0,125.9,125.7,125.6,123.7,123.6, 119.2,115.7,115.3,76.5,75.8,75.7,75.4,48.7,48.5,25.0,24.4;

[0087] Example 12

[0088]

[0089] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 12a (54.0 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 12c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 60% and the ee value was >99%.

[0090] 1H NMR(CDCl3,400MHz)δ7.97(d,J=8.8Hz,2H),7.34-7.16(m,8H),7.11(d,J=7.6Hz,1H),6.91(d,J=8.8Hz,2H),6.62( d,J=10.0Hz,1H),6.43(d,J=8.0Hz,1H),6.03(dd,J=10.0,3.2Hz,1H),5.36-5.20(m,1H),3.90(s,3H),3.66(s,2H);

[0091] 13 C NMR (CDCl3, 100MHz) δ171.2,166.9,161.4,133.7,132.2,131.8,130.3,129.3,129. 1,128.7,128.5,127.3,127.2,126.7,124.7,123.3,115.3,75.0,73.1,52.1,41.6;

[0092] Example 13

[0093]

[0094] Under nitrogen atmosphere, an acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 13a (57.4 mg, 0.2 mmol) and 1b (34.6 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 13c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 80% and the ee value was 96%.

[0095] 1 H NMR (CDCl3, 400MHz) δ7.95 (d, J = 9.2Hz, 1H), 7.38-7.31 (m, 1H), 7.28-7.22 ( m,6H),7.20(d,J=7.6Hz,1H),7.15(d,J=7.6Hz,1H),6.68(d,J=10.0Hz,1H) ,6.54(d,J=2.4Hz,1H),6.49(dd,J=9.2,2.4Hz,1H),6.37(d,J=7.6Hz,1H), 5.99(dd,J=10.0,3.2Hz,1H),5.25-5.16(m,1H),3.88(s,3H),3.67(s,2H);

[0096] 13 C NMR (CDCl3, 100MHz) δ171.2,162.7,155.8,133.6,133.4,132.2,131.2,131.0,129. 4,129.3,128.7,128.5,127.4,127.2,123.6,106.0,101.3,74.9,72.4,56.7,41.6;

[0097] Embodiment 14

[0098]

[0099] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 1a (51.4 mg, 0.2 mmol) and 14b (41.3 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 1c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 78% and the ee value was >99%.

[0100] 1 H NMR(CDCl3,400MHz)δ8.20-8.13(m,2H),7.30-7.24(m,5H),6.99-6.93(m,3H),6.86(s,1H),6.62(d,J=10.0Hz,1H), 6.33(d,J=7.6Hz,1H),5.94(dd,J=9.6,3.2Hz,1H),5.22-5.15(m,1H),3.71-3.63(m,2H),2.26(s,3H),2.19(s,3H);

[0101] 13 C NMR(CDCl3,100MHz)δ171.2,162.7,141.9,137.7,137.3,133.7,131.0,129.8,129 .3,128.7,128.6,128.5,127.4,126.0,122.4,115.6,75.2,72.4,41.7,19.8,19.6;

[0102] Embodiment 15

[0103]

[0104] Under nitrogen atmosphere, the acetonitrile solution of (1,5-cyclooctadiene)chlororhodium (I) dimer and Josiphos SL-J002-1 was stirred at room temperature for thirty minutes. 1a (51.4 mg, 0.2 mmol) and 15b (49.0 mg, 0.24 mmol) were added to a 4 mL reaction bottle in sequence, and then the pre-complexed rhodium catalyst was added to the reaction bottle. The mixture was reacted at 70 ° C for 3 h. The reaction solution was spin-dried and separated by silica gel column chromatography to obtain the target product 15c. The eluent was ethyl acetate and petroleum ether (volume ratio of 0.1:1). The yield was 66% and the ee value was 94%.

[0105] 1 H NMR (CDCl3, 400MHz) δ8.20-8.13(m,2H),7.33-7.24(m,6H),7.19-7.13(m,2H),6.90(d,J=9.2Hz,1H),6.80(d,J= 9.2Hz,1H),6.41(s,1H),6.13-6.05(m,1H),4.97(dd,J=5.6,1.6Hz,1H),3.84(s,3H),3.65(s,3H),3.63(s,2H);

[0106] 13 C NMR(CDCl3,100MHz)δ171.7,162.8,152.1,150.0,141.9,133.9,129.3,128.7,126 .6,126.0,122.2,120.8,118.6,115.8,113.0,111.9,70.1,64.6,56.2,55.9,41.4;

[0107] The above are only some embodiments of the present invention, and do not limit the present invention in any form. Any simple modification, equivalent changes and modifications made to the above embodiments based on the technical essence of the invention are within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing chiral dihydronaphthalene compounds, comprising the following steps: In an organic solvent, a carboxylate compound I and an oxabicycloolefin compound II are subjected to an asymmetric ring-opening reaction under the catalysis of a rhodium catalyst system to obtain a chiral dihydronaphthalene compound III; the rhodium catalyst system is composed of a rhodium salt and a chiral ligand IV, and the chiral ligand has a structure shown in formula IV; in, In the formula I compound structure, R1 is selected from phenyl, halogenated phenyl, C1-C8 alkyl substituted phenyl, C1-C8 alkoxy substituted phenyl, trifluoromethyl substituted phenyl, boric acid substituted phenyl, ester substituted phenyl, hydroxy substituted phenyl, cyano substituted phenyl, naphthyl, furanyl, thienyl, quinolyl, hydrogen, C1-C8 alkyl, cyano, indolyl, alkoxy, thiazolyl, C3-C6 cycloalkyl, alkenyl, alkynyl, benzyl, R2 is selected from hydrogen R3 is selected from hydrogen, phenyl, C1-C8 alkyl, C3-C6 cycloalkyl, cyano, R4 is selected from halophenyl, C1-C8 alkyl substituted phenyl, C1-C8 alkoxy substituted phenyl, trifluoromethyl substituted phenyl, ester substituted phenyl, sulfonyl substituted phenyl, cyano substituted phenyl, nitro substituted phenyl, R1, R2, R3, R4 may be the same or different; In the structure of the compound of formula II, R5 is selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, and hydrogen; R6 is selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, and hydrogen; R7 is selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, and hydrogen; R8 is selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, and hydrogen; R5, R6, R7, and R8 may be the same or different; In compound III, substituents R1, R2, R3, and R4 are respectively the same as R1, R2, R3, and R4 in compound I; substituents R5, R6, R7, and R8 are the same as R5, R6, R7, and R8 in compound II.

2. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: In compound I, R1 is 4-methoxyphenyl, 2-chlorophenyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 4-boronic acid pinacol ester phenyl, 4-iodophenyl, 4-(N,N-dimethyl)phenyl, 4-biphenyl, 2-furyl, 2-naphthyl, 2-thienyl; R2 is methyl, phenyl, hydrogen, cyano; R3 is methyl, phenyl, hydrogen, cyano; R4 is 4-nitrophenyl, 3-fluoro-4-nitrophenyl, 3-methoxy-4-nitrophenyl, 2 , 3,4,5,6-pentafluorophenyl; in compound II, R5 is hydrogen, methyl, methoxy; R6 is hydrogen, methyl, methoxy, fluoro; R7 is hydrogen, methyl, methoxy, fluoro; R8 is hydrogen, methyl, methoxy; in compound III, the substituents R1, R2, R3, R4 are respectively the same as R1, R2, R3, R4 in compound I; the substituents R5, R6, R7, R8 are the same as R5, R6, R7, R8 in compound II.

3. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: The solvent is one or more of acetonitrile, tetrahydrofuran, dioxane, ether, dichloromethane, ethyl acetate, toluene, 1,2-dichloroethane, DMF, DMSO or ethylene glycol dimethyl ether; the ratio of the volume of the solvent to the molar number of the carboxylate compound I is 1 mL: 0.1 mmol; and the solvent is anhydrous.

4. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: The rhodium catalyst is (1,5-cyclooctadiene)chlororhodium (I) dimer; the molar ratio of the rhodium catalyst to the carboxylate compound I is 0.02:0.1; and the molar ratio of the rhodium in the rhodium catalyst to the chiral ligand IV is 1:2.

5.

5. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: The rhodium catalyst is prepared according to the following method: under nitrogen protection, rhodium salt and chiral ligand IV are added to a solvent, and stirred at room temperature for 30 minutes. The obtained solution is a rhodium catalyst system.

6. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: The asymmetric ring-opening reaction is carried out under an inert gas atmosphere, and the inert gas is nitrogen.

7. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: The temperature of the asymmetric ring-opening reaction is 70° C.; the time of the asymmetric ring-opening reaction is 2 to 7 hours.

8. The method for synthesizing chiral dihydronaphthalene compounds according to claim 1, characterized in that: After the carboxylic acid ester compound I and the oxabicycloolefin compound II undergo an asymmetric ring-opening reaction, the product can be separated and characterized by conventional separation and purification methods. The specific post-reaction treatment steps are as follows: the reaction solution is freed of solvent, and the obtained crude product is separated by silica gel column chromatography to obtain a chiral dihydronaphthalene compound III, and the eluent is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the mixed solvent of ethyl acetate and petroleum ether in the mixed solvent is 0.05-0.2:1.

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