A method for hydrogenation kinetic resolution of biaryl axial chiral compounds

Abstract

The invention discloses a hydrogenation kinetic resolution method for biaryl axial chiral compounds, wherein the catalyst used is a chiral diphosphine complex of rhodium. By this method, 1-aryl substituted naphthalene compounds with axial chirality (enantiomeric excess can reach 99%) and biphenyl compounds with axial chirality (enantiomeric excess can reach 82%) can be obtained, and the resolution coefficient can reach s=52. The present invention can realize catalytic resolution, is simple and easy to operate, has commercially available catalysts, mild conditions, low energy consumption, is environmentally friendly, has a high resolution coefficient, and has a good yield.

Description

Technical Field

[0001] The invention belongs to the field of asymmetric catalytic synthesis and relates to a method for realizing kinetic resolution of biaryl axial chiral compounds through a rhodium-catalyzed hydrogenation reaction of naphthalene. Background Art

[0002] Axially chiral biaryl compounds are widely present in materials, drugs and natural products, and they play a very important role in the field of organic synthesis as the dominant skeleton of chiral catalysts and ligands. (Reference 1: (a) Bringmann, G.; Gulder, T.; Gulder, TAM; Breuning, M. Chem. Rev. 2011, 111, 563-639. (b) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070. (c) Terada, M. Synthesis 2010, 12, 1929-1982.) Therefore, the synthesis of axially chiral compounds has attracted the attention of many scientists, and a series of synthetic methods have been successfully developed, mainly including traditional chemical resolution, asymmetric coupling, asymmetric functionalization, central chirality to axial chirality transfer, dynamic kinetic resolution and kinetic resolution. (Reference 2: (a) Wencel-Delord, J.; Panossian, A.; Leroux, FR; Colobert, F. Chem. Soc. Rev. 2015, 44, 3418-3430. (b) Bencivenni, G. Synlett 2015, 26, 1915-1922. (c) Kumarasamy, E.; Raghunathan, R.; Sibi, MP; Sivaguru, J. Chem. Rev. 2015, 115, 11239-11300. (d) Ma, G.; Sibi, MP Chem. Eur. J. 2015, 21, 11644-11657.) Among them, kinetic resolution has received widespread attention because it can improve the enantioselectivity of the product or substrate by controlling the conversion rate.

[0003] In recent years, a series of excellent research results have been achieved in the asymmetric hydrogenation of aromatic heterocyclic compounds, but the development of asymmetric hydrogenation of aromatic carbocyclic compounds has been very slow, and there are only a few reports on asymmetric hydrogenation of aromatic carbocyclic compounds. The construction of biaryl axial chiral compounds by hydrogenation kinetic resolution of all-carbon aromatic rings has not been reported. Based on this, the present invention provides a rhodium-catalyzed hydrogenation method of 1-aryl substituted naphthalene compounds to achieve the kinetic resolution of the axial chiral compounds. Summary of the invention

[0004] The present invention provides a hydrogenation kinetic resolution method for biaryl axial chiral compounds. The present invention can realize catalytic resolution, is simple and easy to operate, has commercially available catalysts, mild conditions, low energy consumption, is environmentally friendly, has a high resolution coefficient, and has a good yield.

[0005] The technical solution of the present invention is as follows:

[0006] A method for hydrogenation kinetic resolution of biaryl axial chiral compounds, characterized in that the method uses a chiral diphosphine complex of rhodium as a catalyst and a 2-aryl substituted naphthalene compound as a substrate to synthesize biphenyl derivatives with axial chirality by hydrogenation kinetic resolution;

[0007] The reaction formula is as follows:

[0008]

[0009] Where:

[0010] R is hydrogen, alkyl, phenyl, naphthyl or a benzene ring containing a substituent, wherein the substituent is halogen, alkoxy or C 1 -C 20 At least one of the alkyl groups; including methyl or methoxy.

[0011] R'=N(R 1 )SO 2 R 2 , where R 1 , R 2 Each of them is independently hydrogen, or C1-C10 alkyl or aryl, and C1-C10 alkyl includes one or more substituents of methoxy and halogen;

[0012] Or R'=OSO 2 R 1 , where R 1 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen;

[0013] or R'=OCOR 1 , where R 1 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen;

[0014] Ar is a benzene ring or an aromatic ring containing a substituent, wherein the substituent is a C1-C10 alkyl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen;

[0015] The catalyst is a complex of a metal rhodium precursor and a chiral diphosphine ligand.

[0016] Based on the above technical solution, preferably, the preparation method of the catalyst is: under nitrogen protection, stirring the metal rhodium precursor and the chiral diphosphine ligand in a solvent at room temperature for 10 minutes to 60 minutes.

[0017] Based on the above technical scheme, preferably, the specific reaction steps of the method are: adding 1-aryl substituted naphthalene compound, in-situ prepared catalyst and solvent into a reaction bottle, placing the reaction bottle into an autoclave, and introducing H 2 . After the reaction is completed, hydrogen is released, the solvent is dried, and the pure product is separated by column chromatography. The amount of organic solvent and 1-aryl substituted naphthalene compound is as follows: the amount of organic solvent is 1-4mL; preferably 2mL; the amount of 1-aryl substituted naphthalene compound is 0.1-0.4mmol; preferably 0.2mmol. The molar ratio of the 1-aryl substituted naphthalene compound, the metal rhodium precursor and the chiral bisphosphine ligand is 1:0.01:0.011-1:0.1:0.11; preferably 1:0.05:0.055.

[0018] Based on the above technical solution, preferably, the reaction solvent is an organic solvent, and the organic solvent is dichloromethane.

[0019] Based on the above technical scheme, preferably, the reaction temperature of the method is 25-70°C, preferably 30°C; the hydrogen pressure is 300-800psi, preferably 600psi; and the reaction time is 4-24h, preferably 5 hours.

[0020] Based on the above technical scheme, preferably, the metal rhodium precursor is one of bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt and bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate, preferably bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt. The chiral bisphosphine ligand is (R)-(+)-1-[(R)-2-(2'-diphenylphosphinophenyl)ferrocene]ethyldiphenylphosphine, (2R,2'R,3R,3'R)-4,4'-bis(2,6-dimethoxyphenyl)-3,3'-di-tert-butyl-2,2',3,3'-tetrahydro-2,2'-bis-1,3-benzoxaphosphocyclopentadiene, (2R,2'R,3R,3'R)-4 ,4'-di(9-anthracenyl)-3,3'-di(tert-butyl)-2,2',3,3'-tetrahydro-2,2'-dibenzo[D][1,3]oxy,phosphine pentane conjugated, preferably (2R,2'R,3R,3'R)-4,4'-di(9-anthracenyl)-3,3'-di(tert-butyl)-2,2',3,3'-tetrahydro-2,2'-dibenzo[D][1,3]oxy,phosphine pentane conjugated.

[0021] Based on the above technical scheme, preferably, the solvent used for preparing the catalyst is selected from one or more of chloroform, 1,2-dichloroethane, dichloromethane, ethyl acetate, tetrahydrofuran, toluene and methanol, preferably dichloromethane.

[0022] Beneficial Effects

[0023] The present invention has the following advantages

[0024] 1. High reaction activity, enantioselectivity and resolution coefficient.

[0025] 2. Axially chiral biphenyl compounds and axially chiral 1-aryl substituted naphthalene compounds can be obtained.

[0026] 3. The catalyst is commercially available and the reaction operation is simple.

[0027] 4. Mild reaction conditions and low energy consumption. DETAILED DESCRIPTION

[0028] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0029] References for the synthesis of 1-aryl substituted naphthalene compounds in the following examples: (a) Bartoszek, M.; Beller, M.; Deutsch, J.; Klawonn, M.; Kockritz, A.; Nemati, N.; Pews-Davtyan, A. Tetrahedron 2008, 64, 1316-1322. (b) St-Gelais, A.; Alsarraf, J.; Legault, J.; Gauthier, C.; Pichette, A. Org. Lett. 2018 ,20,7424-7428. (c) Han, B.; Ma, P.; Cong, X.; Chen, H.; Zeng, XJAm.Chem.Soc.2019,141,9018-9026. (d) Zhang, A.; RajanBabu,T VJAm.Chem.Soc.2006,128,54-55.(e)Hu,R.-B.;Zhang,H;Zhang,X.-Y;Yang,S.-D.Chem.Commun.2014,50,2193-2195.Example 1-11

[0030] Condition optimization: changing the types of organic solvent, catalyst precursor and chiral ligand

[0031] Rhodium precursor (5.0 mol%) and chiral ligand (5.5 mol%) were added to the reaction bottle, and 1 mL of solvent was added after nitrogen replacement. The in-situ prepared catalyst was obtained by stirring at room temperature for 10 minutes. The in-situ prepared catalyst and 1 mL of solvent were added to the reaction bottle which was previously placed with substrate 1-aryl substituted naphthalene (0.10 mmol) in the glove box, and then placed in a high pressure reactor, and hydrogen (600 psi) was introduced to react at 30°C for 5 hours. Hydrogen was slowly released, the solvent was removed by rotary evaporation, and the pure product was obtained by column chromatography separation.

[0032] Types of organic solvent, catalyst precursor and chiral ligand. Specific results are shown in Table 1; ee is enantioselectivity.

[0033]

[0034] Table 1.1-Optimization of hydrogenation kinetic resolution conditions for aryl-substituted naphthalene compounds

[0035]

[0036] Examples 12-27

[0037] For the hydrogenation splitting reaction of 1-aryl substituted naphthalene compounds, bis(1,5-cyclooctadiene) rhodium(I) antimony hexafluoride salt (5.0 mol%) and (2R,2'R,3R,3'R)-4,4'-di(9-anthryl)-3,3'-di(tert-butyl)-2,2',3,3'-tetrahydro-2,2'-dibenzo[D][1,3]oxy,phosphine pentane conjugate (5.5 mol%) were added to the reaction flask. After nitrogen substitution, 1 mL of dichloromethane was added and stirred at room temperature for 10 minutes to prepare the catalyst in situ. In the glove box, the reaction flask containing the substrate 1-aryl substituted naphthalene (0.20 mmol) was added with the in situ prepared catalyst and 1 mL of dichloromethane, and then placed in a high pressure reactor, hydrogen (600 psi) was introduced, and the reaction was carried out at 30°C for 5 hours. Slowly release hydrogen, remove the solvent by rotary evaporation, and separate the axial chiral raw material 1 and the pure product 2 by column chromatography (commercial silica gel). It can be used as an axial chiral ligand and catalyst and has application value in organic synthesis. The enantiomeric excess of raw material 1 and product 2 is determined by chiral liquid chromatography, and the s value is calculated by this formula: s = ln [(1-C) (1-ee of 1)] / ln [(1-C) (1 + ee of 1)], Conv. = ee 1a / (ee 1a +ee 2a ). Only by changing the type of raw material 1, 13 different embodiments were obtained. The specific types of changes are shown in Table 2.

[0038]

[0039] Table 2. Hydrogenation and resolution reactions of a series of 1-aryl substituted naphthalene compounds

[0040]

[0041] (+)-2-(2-Methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl benzoate(2a):36.0mg,52%yield,10h,colorless oil,new compound,R f =0.80(hexanes / ethylacetate 20 / 1),77%ee, 135.5,134.4,133.9,133.7,133.2,131.0,129.8,129.6,128.6,128.3,128.3,126.8,126.2,122.8,29.7,27.9,23.5,23.0,20.2. HPLC: Chiralpak AD-H / AD-H column, 254nm, 30℃, n-Hexane / i-PrOH=98 / 2, flow=0.7mL / min, retention time 14.7min and 16.1min(major).HRMS: Calculated for C 24 H 23 O 2 [M+H] + 343.1693,found:343.1691.

[0042] _____________________________________________________________________

[0043] (-)-2-(2-Methylnaphthalen-1-yl)phenyl benzoate(1a):31.0mg,46%yield,91%ee,[α] 20 D = -121.60 (c 0.62, CHCl 3 ).HPLC: Chiralpak IC column, 254nm, 30℃, n-Hexane / i-PrOH=95 / 5, flow=0.7mL / min, retention time 6.5min (minor) and 7.0min (major).

[0044]

[0045] (+)-2-(2-Methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 2-methylbenzoate(2b):

[0046] 36.0mg,50%yield,5h,colorless oil,new compound,R f =0.85(hexanes / ethylacetate 10 / 1),80%ee, 126.2,125.6,123.1,29.8,27.9,23.5,23.0,21.1,20.1.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time 5.7min(minor)and 6.9min(major).HRMS:Calculated for C 25 H 25 O 2 [M+H] + 357.1849,found:357.1846.

[0047] _____________________________________________________________________

[0048] (-)-2-(2-Methylnaphthalen-1-yl)phenyl 2-methylbenzoate(1b):

[0049] 34.0mg,48%yield,82%ee,[α] 20 D =-112.20(c 0.68,CHCl 3 ).HPLC:ChiralpakID,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time 5.0min(major)and 5.5min.

[0050]

[0051] (+)-2-(2-Methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-fluorobenzoate(2c)

[0052] 42.0mg,58%yield,10h,colorless oil,new compound,R f =0.85(hexanes / ethyl acetate 10 / 1),71%ee, =252.8Hz),163.7,148.3,136.3,135.4,134.5,133.8,133.7,132.3(d, 3 J C-F =9.4Hz),130.9,128.6,128.3,126.8,126.3,125.8(d, 4 J C-F =2.9Hz)122.7,115.5(d, 2 J C-F =22.0Hz),29.7,27.9,23.5,23.0,20.1. 19 F NMR(376MHz,CDCl 3 )δ-104.99.HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time 5.6minand 6.2min(major).HRMS:Calculated for C 24 H 22 FO 2 [M+H] + 361.1598,found:361.1595.

[0053] _____________________________________________________________________

[0054] (-)-2-(2-Methylnaphthalen-1-yl)phenyl 4-fluorobenzoate(1c):

[0055] 30.0mg,42%yield,97%ee,[α]20 D =-139.99(c 0.60,CHCl 3 ).HPLC:ChiralpakIA,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time 6.9min(major)and 7.5min.

[0056]

[0057] (+)-2-(2-Methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methoxybenzoate(2d):41.0mg,55%yield,10h,colorless oil,new compound,R f =0.35(hexanes / ethyl acetate 10 / 1),74%ee, CDCl 3 )δ164.4,163.6,148.5,136.5,135.5,134.4,133.9,133.7,131.9,130.9,128.5,128.2,126.7,126.0,122.9,121.9,113.6,55.5,29.8,27.9,23.5,23.0,20.2.HPLC:Chiralpak IA column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time 8.8min(minor)and 9.7min(major).HRMS:Calculated for C 25 H 25 O 3 [M+H] + 373.1798,found:373.1802.

[0058] _____________________________________________________________________

[0059] (-)-2-(2-Methylnaphthalen-1-yl)phenyl 4-methoxybenzoate(1d):

[0060] 32.0mg,43%yield,96%ee,[α] 20 D =-127.94(c 0.78,CHCl 3 ).HPLC:ChiralpakIA column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time11.5min(major)and 14.1min(minor).

[0061]

[0062] (+)-2-(2-Methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2e):

[0063] 43.0mg,55%yield,5h,white solid,mp=90-91℃,new compound,R f =0.55(hexanes / ethyl acetate

[0064] CDCl 3 )δ146.8,144.5,135.9,135.8,134.5,134.2,134.1,133.7,131.8,129.4,128.7,128.6,127.7,127.0,127.0,123.0,29.8,27.7,23.2,22.8,21.7,20.2.HPLC:ChiralcelOJ-H / OJ-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retentiontime 13.3min(minor)and 15.0min(major).HRMS:Calculated for C 24 H 25 O 3 S[M+H] + 393.1519,found:393.1521.

[0065] _____________________________________________________________________

[0066] (-)-2-(2-Methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1e):

[0067] 34.0mg,44%yield,95%ee,[α] 20 D =-97.93(c 0.68,CHCl 3 ).HPLC:Chiralpak ICcolumn,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time13.5min(minor)and 14.9min(major).

[0068]

[0069] (-)-2-(2-Methoxy-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2f):46.0mg,56%yield,10h,colorless oil,new compound,R f =0.25(hexanes / ethyl acetate 10 / 1),63%ee, 147.4,144.3,137.1,133.7,132.5,131.2,129.4,129.4,129.3,128.5,127.8,126.7,124.8,122.7,108.5,55.8,29.3,27.6,23.1,22.9,21.7.HPLC:Chiralpak IA column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time 9.1min(major)and 10.0min.HRMS:Calculated for C 24 H 25 O 4 S[M+H] + 409.1468,found:409.1470.

[0070] _____________________________________________________________________

[0071] (-)-2-(2-Methoxynaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1f):

[0072] 35.0mg,43%yield,84%ee,[α] 20 D =-14.57(c 0.70,CHCl 3 ).HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time11.1min(minor)and 12.5min(major).

[0073]

[0074] (+)-3-Methyl-2-(5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2g):

[0075] 49.0mg,62%yield,5h,colorless oil,new compound,R f =0.80(hexanes / ethylacetate 20 / 1),60%ee, MHz,CDCl 3 )δ146.9,144.5,138.8,137.3,135.6,135.3,134.8,133.6,129.4,128.5,128.4,128.0,128.0,127.2,125.0,119.7,30.0,26.9,23.1,22.9,21.7,20.2.HPLC:ChiralpakAD-H column,230nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time7.6min and 8.1min(major).HRMS:Calculated for C 24 H 28NO 3 S[M+NH 4 ] + 410.1784,found:410.1782.

[0076] _____________________________________________________________________

[0077] (-)-3-Methyl-2-(naphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1g):

[0078] 29mg,37%yield,97%ee,[α] 20 D =-68.96(c 0.58,CHCl 3 ).HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=90 / 10,flow=1.0mL / min,retention time6.1min(major)and 6.7min.

[0079]

[0080] (+)-2-Methyl-6-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2h):

[0081] 43.0mg,53%yield,5h,colorless oil,new compound,R f =0.55(hexanes / ethylacetate 20 / 1),82%ee, 127.0,126.8,126.7,29.7,27.6,23.2,22.8,21.6,20.4,18.2.HPLC:Chiralcel OD-Hcolumn,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time 5.7minand 6.1min(major).HRMS:Calculated for C 25 H 30NO 3 S[M+NH 4 ] + 424.1941,found:424.1942.

[0082] _____________________________________________________________________

[0083] (-)-2-Methyl-6-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1h):

[0084] 37.0mg,46%yield,96%ee,[α] 20 D =-98.64(c 0.74,CHCl 3 ).HPLC:ChiralpakAD-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time7.5min(minor)and 8.4min(major).

[0085]

[0086] (+)-5-Methyl-2-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2i):

[0087] 38.0mg,47%yield,5h,colorless oil,new compound,R f =0.55(hexanes / ethylacetate 20 / 1),81%ee, 146.6,144.4,138.9,136.0,135.9,134.5,134.3,133.8,131.4,131.0,129.3,128.6,127.9,127.6,126.9,123.5,29.8,27.7,23.3,22.8,21.6,21.2,20.2.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time7.0min(major)and 7.6min(minor).HRMS:Calculated for C 25 H 30 NO 3 S[M+NH 4 ] + 424.1941,found:424.1939.

[0088] _____________________________________________________________________

[0089] (-)-5-Methyl-2-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1i):

[0090] 42.0mg,52%yield,74%ee,[α] 20 D =-95.47(c 0.84,CHCl 3 ).HPLC:ChiralpakAD-H column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time13.9min(minor)and 15.0min(major).

[0091]

[0092] (+)-4-Methyl-2-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2j):

[0093] 43.0mg,53%yield,5h,colorless oil,new compound,R f =0.55(hexanes / ethylacetate 20 / 1),80%ee, 126.9,122.7,29.8,27.7,23.3,22.8,21.6,21.0,20.2.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time 8.0min and10.1min(major).HRMS:Calculated for C 25 H 30 NO 3 S[M+NH 4 ] + 424.1941,found:424.1939.

[0094] _____________________________________________________________________

[0095] (-)-4-Methyl-2-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1j):

[0096] 37.0mg,46%yield,92%ee,[α] 20 D =-84.32(c 0.74,CHCl 3 ).HPLC:ChiralpakAS-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time18.2min(major)and 20.1min(minor).

[0097]

[0098] (+)-4-Methoxy-2-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2k):52.0mg,62%yield,10h,colorless oil,new compound,R f =0.30(hexanes / ethyl acetate 10 / 1),60%

[0099] 133.7,129.4,128.8,127.7,127.0,123.9,116.4,113.6,55.6,29.8,27.6,23.2,22.8,21.6,20.2.HPLC:Chiralpak IA column,254nm,30℃,n-Hexane / i-PrOH=90 / 10,flow=1.0mL / min,retention time 6.4min and 7.5min(major).HRMS:Calculated forC 25 H 30 NO 4 S[M+NH 4 ] + 440.1890,found:440.1894.

[0100] _____________________________________________________________________

[0101] (-)-4-Methoxy-2-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1k):

[0102] 31.0mg,37%yield,99%ee,[α] 20 D =-74.83(c 0.62,CHCl 3 ).HPLC:ChiralpakIB,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time 8.3min and8.8min(major).

[0103]

[0104] (+)-4-Fluoro-2-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2l):

[0105] 46.8mg,57%yield,5h,colorless oil,new compound,R f =0.55(hexanes / ethylacetate 20 / 1),73%ee,[α] 20 D =+33.51(c 0.94,CHCl 3 ). 1 H NMR(400MHz,CDCl 3 )δ7.44(dd,J=9.0,4.9Hz,1H),7.22(d,J 115.3(d, 2 J C-F =23.2Hz),29.7,27.6,23.2,22.7,21.7,20.1. 19 F NMR(376MHz,CDCl 3 )δ-114.88.HPLC:Chiralpak IA column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time 5.8min and 6.3min(major).HRMS:Calculated for C 24 H 27 FNO 3 S[M+NH] + 428.1690,found:428.1686.

[0106] _____________________________________________________________________

[0107] (-)-4-Fluoro-2-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1l):

[0108] 35.1mg,43%yield,96%ee,[α] 20 D =-111.99(c 0.70,CHCl 3 ).HPLC:ChiralpakAY-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time12.4min(major)and 14.3min(minor).

[0109]

[0110] (+)-(S)-2-Methoxy-6-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2m):49.8mg,59%yield,5h,colorless oil,newcompound,R f =0.30(hexanes / ethyl acetate 20 / 1),69% 126.9,122.9,111.2,56.1,29.7,27.6,23.2,22.8,21.6,20.2.HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time10.9min(major)and 11.9min(minor).HRMS:Calculated for C 25 H 30 NO 4 S[M+NH 4 ] + 440.1890,found:440.1886.

[0111] _____________________________________________________________________

[0112] (-)-(R)-2-Methoxy-6-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1m):

[0113] 33.6mg,40%yield,99%ee,[α] 20 D =-111.19(c 0.67,CHCl 3 ).HPLC:ChiralpakIA,254nm,30℃,n-Hexane / i-PrOH=90 / 10,flow=1.0mL / min,retention time 8.8minand 10.7min(major).The absolute configuration was determined by X-raydiffraction analysis,and the CCDC number is 2072357.

[0114]

[0115] (+)-2-Fluoro-6-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2n):

[0116] 45.4mg,55%yield,5h(reaction time),colorless oil,new compound,R f =0.50(hexanes / ethyl acetate 135.0(d, 4 J C-F =2.0Hz),134.5,133.9,129.3,129.0,127.6(d, 3 J C-F =7.9Hz),127.3,127.0,126.7(d, 3 J C-F =3.4Hz),115.7(d, 2 J C-F =18.8Hz),29.7,27.7,23.2,22.7,21.6,20.2. 19 FNMR(376MHz,CDCl 3)δ-124.35.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time 10.8min(major)and 11.9min(minor).HRMS:Calculated for C 24 H 27 FNO 3 S[M+NH 4 ] + 428.1690,found:428.1690.

[0117] _____________________________________________________________________

[0118] (-)-2-Fluoro-6-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1n):36.5mg,45%yield,97%ee,[α] 20 D =-87.53(c 0.73,CHCl 3 ).HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time13.1min and 14.4min(major).

[0119]

[0120] (+)-2-Chloro-6-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(2o):46.7mg,55%yield,5h,colorless oil,new compound,R f =0.55(hexanes / ethyl acetate 20 / 1),82%ee, 29.7,27.7,23.2,22.7,21.6,20.3.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time 6.9min(major)and 7.7min.HRMS:Calculated for C 24 H 27 ClNO 3 S[M+NH 4 ] + 444.1395( 35 Cl)and 446.1373( 37 Cl),found:444.1395( 35 Cl)and 446.1371( 37 Cl).

[0121] _____________________________________________________________________

[0122] (-)-2-Chloro-6-(2-methylnaphthalen-1-yl)phenyl 4-methylbenzenesulfonate(1o):

[0123] 38.1mg,45%yield,99%ee,[α] 20 D =-123.68(c 0.76,CHCl 3 ).HPLC:ChiralpakIA column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=1.0mL / min,retention time8.8min(minor)and 9.7min(major).

[0124]

[0125] (+)-(S)-4-Methyl-N-(2-(2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)phenyl)benzenesulfonamide(2p):46.0mg,59%yield,5h,white solid,mp=178-179℃,new compound,Rf =0.40(hexanes / ethyl 144.0,136.5,135.7,135.7,134.9,134.2,134.1,123.0,129.9,129.9,129.7,128.3,127.6,127.3,124.2,117.6,29.7,27.5,23.3,22.6,21.5,19.6.HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=70 / 30,flow=0.7mL / min,retention time6.1min and 8.1min(major).HRMS:Calculated for C 24 H 26 NO 2 S[M+H] + 392.1679,found:392.1678.

[0126] _____________________________________________________________________

[0127] (-)-(R)-4-Methyl-N-(2-(2-methylnaphthalen-1-yl)phenyl)benzenesulfonamide(1p):

[0128] 31.0mg,40%yield,95%ee,[α] 20 D =-83.16(c 0.60,CHCl 3 ).HPLC:Chiralpak IAcolumn,254nm,30℃,n-Hexane / i-PrOH=70 / 30,flow=0.7mL / min,retention time7.0min(major)and 9.7min.The absolute configuration was determined by X-raydiffraction analysis and the CCDC number is 2083665.

[0129]

Claims

1. A method for the hydrogenation kinetic resolution of biaryl axial chiral compounds, characterized in that: The catalyst of the splitting method is a chiral diphosphine complex of rhodium, and the specific reaction formula is as follows: In the formula Selected from: The reaction solvent is selected from dichloromethane; The catalyst is a complex of a metal rhodium precursor and a chiral diphosphine ligand; The metal rhodium precursor is one of bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt and bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; The chiral bisphosphine ligand is (2R,2'R,3R,3'R)-4,4'-di(9-anthryl)-3,3'-di(tert-butyl)-2,2',3,3'-tetrahydro-2,2'-dibenzo[D][1,3]oxy, phosphine pentane conjugated; The organic solvent used in the preparation of the catalyst is selected from dichloromethane.

2. The method according to claim 1, characterized in that: The preparation method of the catalyst is as follows: under the protection of nitrogen or argon, a metal rhodium precursor and a chiral diphosphine ligand are stirred in an organic solvent at room temperature for 10 minutes to 60 minutes.

3. The method according to claim 1, characterized in that The specific reaction steps of the method are: adding 1-aryl substituted naphthalene compound, in-situ prepared catalyst and organic solvent dichloromethane into a reaction bottle, placing the reaction bottle into an autoclave, and introducing H2; after the reaction is completed, releasing hydrogen, spinning the solvent dry, and separating by column chromatography to obtain a pure product; The amount of the reaction solvent used is 1-4 mL per 0.1-0.4 mmol of the 1-aryl substituted naphthalene compound; the molar ratio of the 1-aryl substituted naphthalene compound, the metal rhodium precursor and the chiral diphosphine ligand is 1:0.01:0.011-1:0.1:0.

11.

4. The method according to claim 1, characterized in that: The reaction temperature of the method is 25-70° C., the hydrogen pressure is 300-800 psi, and the reaction time is 4-24 hours.

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