A method for the synthesis of axially chiral biaryl compounds by palladium-catalyzed asymmetric hydrogenolysis

Abstract

The present invention discloses a method for palladium-catalyzed asymmetric hydrogenolysis to synthesize axially chiral biaryl compounds, which realizes the palladium-catalyzed asymmetric hydrogenolysis of aryl trifluoromethanesulfonates through kinetic resolution, thereby enabling the facile construction of a series of axially chiral biaryl compounds with excellent selectivity factors (the highest s value reaches 70). Additionally, some chiral monophosphine ligands were prepared from these axially chiral biaryl compounds as raw materials and applied to palladium-catalyzed asymmetric allylic alkylation reactions, obtaining products of allylic alkylation with excellent enantioselectivity and regioselectivity, demonstrating the potential utility of this method. The method of the present invention is simple, practical, the catalyst is commercially available, the reaction conditions are mild, the energy consumption is low, and it is environmentally friendly.

Description

Technical Field

[0001] The present invention belongs to the field of asymmetric catalytic synthesis, and relates to a method for asymmetric hydrogenolysis of aryl trifluoromethanesulfonates catalyzed by palladium to synthesize a series of axially chiral biaryl compounds through kinetic resolution. Technical Background

[0002] Hydrogenolysis is an attractive synthetic method widely used in organic synthesis and industrial processes (References: a) J. Newham, Chem. Rev. 1963, 63, 123; b) A. R. Pinder, Synthesis 1980, 425; c) T. Turek, D. L. Trimm, A. W. Cant, Catal. Rev. 1994, 36, 645; d) C. Bianchini, A. Meli, Acc. Chem. Res. 1998, 31, 109; e) A. Wilsily, Y. Nguyen, E. Fillion, J. Am. Chem. Soc. 2009, 131, 15606; f) A. Martin, U. Armbruster, I. Gandarias, P. L. Arias, Eur. J. Lipid Sci. Technol. 2013, 115, 9; g) R. R. Chianelli, Catal. Rev. 1984, 26, 361; b) M. L. Poutsma, Energy Fuels 1990, 4, 113; h) A. N. Startsev, Russ. Chem. Rev. 1992, 61, 175; i) K. Ichimura, Y. Inoue, I. Yasumori, Catal. Rev. 1992, 34, 301; j) A. M. Ruppert, K. Weinberg, R. Palkovits, Angew. Chem. Int. Ed. 2012, 51, 2564; k) Y. Wang, J. Zhou, X. Guo, RSC Adv. 2015, 5, 74611; l) K. Tomishige, Y. Nakagawa, M. Tamura, Green Chem. 2017, 19, 2876.). However, hydrogenolysis mainly focuses on the synthesis of racemic or achiral compounds, and relatively few studies have been conducted on the asymmetric form. The main reasons are as follows: 1) Severe side reactions; 2) Difficulty in coordinating the substrate with the chiral catalyst; 3) Poor chemical and stereoselectivity control. In recent years, some examples have been achieved in the asymmetric hydrogenolysis of carbon-oxygen bonds. In 1991, Chan reported the homogeneous asymmetric hydrogenolysis of sodium cis-epoxysuccinate using a chiral rhodium complex as the catalyst, obtaining moderate enantioselectivity (References: (a) A. S. C. Chan, J. P. Coleman, J. Chem. Soc., Chem. Commun. 1991, 535.).Subsequently, Bakos also carried out asymmetric hydrogenolysis of this compound using the same rhodium catalyst system containing a water-soluble sulfonated ligand (Reference III: (a) J. Bakos, á. Orosz, S. Cserépi, I. Tóth, D. Sinou, J. Mol. Catal. A 1997, 116, 85.). In 2016, Zhang et al. developed the enantioselective hydrogenolysis of palladium-catalyzed α-acyloxy ketones with ortho-substituted aryl C-O bonds through kinetic resolution (Reference III: (a) J. Chen, Z. Zhang, D. Liu, W. Zhang, Angew. Chem. Int. Ed. 2016, 55, 8444.). At the same time, the desymmetrization of meso-dihalides or the formal asymmetric hydrogenolysis of racemic tertiary alcohol compounds were also studied.(Reference 4: a) E.P. Kündig, P.D. Chaudhuri, D. House, G. Bernardinelli, Angew. Chem. Int. Ed. 2006, 45, 1092; b) A. Mercier, W.C. Yeo, J. Chou, P.D. Chaudhuri, G. Bernardinelli, E.P. Kündig, Chem. Commun. 2009, 5227; c) A. Mercier, X. Urbaneja, W.C. Yeo, P.D. Chaudhuri, G.R. Cumming, D. House, G. Bernardinelli, E.P. Kündig, Chem. Eur. J. 2010, 16, 6285; d) A. Mercier, W.C. Yeo, X. Urbaneja, E.P. Kündig, Chimia 2010, 64, 177; e) M. Hirai, S. Terada, H. Yoshida, K. Ebine, T. Hirata, O. Kitagawa, Org. Lett. 2016, 18, 5700; f) M.-W. Chen, Q.-A. Chen, Y. Duan, Z.-S. Ye, Y.-G. Zhou, Chem. Commun. 2012, 48, 1698; g) J.-Q. Zhou, W.-J. Sheng, J.-H. Jia, Q. Ye, J.-R. Gao, Y.-X. Jia, Tetrahedron Lett. 2013, 54, 3082; h) Q. Yin, S.-G. Wang, S.-L. You, Org. Lett. 2013, 15, 2688; i) C.-B. Yu, Y.-G. Zhou, Angew. Chem. Int. Ed. 2013, 52, 13365; j) B. Song, C.-B. Yu, W.-X. Huang, M.-W. Chen, Y.-G. Zhou, Org. Lett. 2015, 17, 190; k) J. Zheng, J. Jongcharoenkamol, B.B.C. Peters, J. Guhl, S. Ponra, M.S.G. Ahlquist, P.G. Andersson, Nat. Catal. 2019, 2, 1093.) Despite considerable efforts in this area, the incompatibility of substrates under hydrogenolysis conditions is not conducive to the construction of chiral versions. Therefore, the development of new catalyst systems and the expansion of substrate scope will further promote the application of asymmetric hydrogenolysis in organic synthesis.

[0003] Axially chiral biaryl structures are an important class of skeletons that widely exist in natural products, drugs, and ligands. (References V: a) G. Bringmann, D. Menche, Acc. Chem. Res. 2001, 34, 615; b) P. M. Chem. Rev. 2003, 103, 3213; c) J. Clayden, W. J. Moran, P. J. Edwards, S. R. LaPlante, Angew. Chem. Int. Ed. 2009, 48, 6398; d) M. C. Kozlowski, B. J. Morgan, E. C. Linton, Chem. Soc. Rev. 2009, 38, 3193.). The synthesis of axially chiral biaryl compounds through the strategy of kinetic or dynamic kinetic resolution is one of the very important methods. Therefore, it is very meaningful to develop a method for constructing axially chiral biaryl compounds through kinetic resolution. Based on this, the present invention provides a method for the asymmetric hydrogenolysis of aryl triflates catalyzed by palladium to synthesize axially chiral biaryl compounds through kinetic resolution, and successfully applies it to the synthesis and application of monophosphine ligands. Summary of the Invention

[0004] The object of the present invention is to provide a method for the asymmetric hydrogenolysis of palladium-catalyzed synthesis of axially chiral biaryl compounds. The method of the present invention is simple, practical, with easily available raw materials, a high selectivity factor, and can rapidly synthesize chiral monophosphine ligands.

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

[0006] A method for realizing the asymmetric hydrogenolysis of palladium-catalyzed synthesis of axially chiral biaryl compounds through the strategy of kinetic resolution. The method uses a chiral bisphosphine complex of palladium as a catalyst, aryl triflate as a substrate, and a reducing agent as a hydrogen source to synthesize a series of axially chiral biaryl compounds through asymmetric hydrogenolysis. The reaction formula of the method is as follows:

[0007]

[0008] In the formula:

[0009] R is methoxy, benzyloxy, isopropoxy, cyclopentylamino, or dimethylamino;

[0010] Ar is a benzene ring, a naphthalene ring, or an aromatic ring with substituents, and the substituents are one of fluorine, methyl, methoxy, ethyl, isopropyl, tert-butyl, and phenyl;

[0011] The catalyst is a complex of a metal palladium precursor and a chiral bisphosphine ligand.

[0012] Based on the above technical solutions, preferably, the reaction solvent is an organic solvent, and the organic solvent is one of N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), tetrahydrofuran (THF), and methanol (MeOH).

[0013] Based on the above technical solutions, preferably, the reaction temperature is -50°C - 30°C, preferably -20°C or -40°C; the reaction time is 0.5 - 36 hours, preferably 3 hours.

[0014] Based on the above technical solutions, preferably, the hydrogen source is a reducing reagent, and the reducing reagent is one of sodium borohydride (NaBH4), sodium borodeuteride (NaBD4), lithium borohydride (LiBH4), lithium borodeuteride (LiBD4), potassium borohydride (KBH4), and potassium borodeuteride (KBD4), preferably sodium borohydride or sodium borodeuteride.

[0015] Based on the above technical solutions, preferably, the molar ratio of the palladium metal precursor to the chiral bisphosphine ligand is 1:1 - 1:3.

[0016] Based on the above technical solutions, preferably, the molar ratio of the aryl trifluoromethanesulfonate, the palladium metal precursor to the chiral bisphosphine ligand in the reaction is 1:0.005:0.0006 - 1:0.05:0.100, preferably 1:0.05:0.075.

[0017] Based on the above technical solutions, preferably, the palladium metal precursor is one of palladium trifluoroacetate (Pd(TFA)2) and palladium acetate (Pd(OAc)2).

[0018] Based on the above technical solutions, preferably, the chiral bisphosphine ligand is one of (R)-SegPhos, (S)-SegPhos, (R)-DM-SegPhos, (S)-DM-SegPhos, (R)-DTBM-SegPhos, (S)-DTBM-SegPhos, (R)-DifluorPhos, (S)-DifluorPhos, (R)-3,5-t-Bu-4-MeO-MeOBIPHEP, and (S)-3,5-t-Bu-4-MeO-MeOBIPHEP.

[0019] Based on the above technical solutions, preferably, the preparation method of the catalyst is as follows: Under nitrogen protection, the palladium metal precursor and the chiral bisphosphine ligand are stirred in the reaction solvent at 30°C in an oil bath for 10 - 60 minutes to obtain.

[0020] Based on the above technical solutions, preferably, the specific reaction steps of the method are as follows:

[0021] Under a nitrogen atmosphere, a palladium metal precursor and a chiral bisphosphine ligand are stirred in a reaction solvent in an oil bath at 30 °C for 10 to 60 minutes, and then aryl trifluoromethanesulfonate is added. After addition, the reaction system is stirred at -50 to 30 °C for 20 minutes, and then a hydrogen source is added. After addition, the reaction vessel is sealed and maintained at this temperature for a certain period of time. The reaction is monitored by TLC. After the reaction is completed, water is added to quench the reaction, and then the product is obtained by purification.

[0022] Based on the above technical solution, preferably, the purification step is as follows: after quenching with water, extract three times with ethyl acetate, combine the organic phases, then dry with anhydrous sodium sulfate, filter, remove the solvent by rotary evaporation under reduced pressure, and separate the product by column chromatography.

[0023] Based on the above technical solution, preferably, the ratio of the aryl trifluoromethanesulfonate to the solvent is 0.35 mmol: 3.5 mL.

[0024] Based on the above technical solution, preferably, under a nitrogen atmosphere, the palladium metal precursor and the chiral bisphosphine ligand are added to a Schlenk tube, and then the solvent is added and stirred at room temperature for ten minutes. Then aryl trifluoromethanesulfonate is added. After addition, the mixture is stirred at -20 °C or -40 °C for 20 minutes, and then a hydrogen source is added. After addition, the reaction vessel is sealed and reacted for a certain period of time. Water is added to quench the reaction, and the mixture is extracted three times with ethyl acetate, then dried with anhydrous sodium sulfate, filtered, the solvent is removed by rotary evaporation under reduced pressure, and the product is obtained by column chromatography. The selectivity factor and enantiomeric excess of the product are determined by nuclear magnetic resonance spectrometer and high performance liquid chromatography respectively.

[0025] The present invention also relates to the use of the axially chiral biaryl compound synthesized by the above method in the synthesis of chiral monophosphine ligands, and this method is successfully used in the synthesis of chiral monophosphine ligands.

[0026] The present invention also relates to the use of the above chiral monophosphine ligands in palladium-catalyzed asymmetric allylic alkylation reactions. These synthesized chiral monophosphine ligands are applied to palladium-catalyzed asymmetric allylic alkylation reactions, and excellent results are obtained, thus demonstrating the practicality of the chiral monophosphine ligands and the asymmetric hydrogenolysis method of the present invention.

[0027] Through the kinetic resolution method of the present invention, the palladium-catalyzed asymmetric hydrogenolysis reaction of aryl trifluoromethanesulfonate can be realized, and a series of axially chiral biaryl compounds with optical purity can be obtained with a relatively high selectivity factor (the s value can reach up to 70 at most). The present invention has a relatively high selectivity factor, is simple and practical to operate, the raw materials are easily available, the catalyst is commercially available, the reaction conditions are mild, the energy consumption is low, and it is environmentally friendly. In addition, some chiral monophosphine ligands are prepared from these axially chiral biaryl compounds as raw materials and applied to palladium-catalyzed asymmetric allylic alkylation reactions, and allylic alkylation products with excellent enantioselectivity and regioselectivity are obtained, demonstrating the potential use of this method.

[0028] Beneficial effects

[0029] (1) The raw materials are simple and easily available, the catalyst preparation is convenient, and the reaction operation is simple and practical.

[0030] (2) The reaction activity is high, and high-purity products can be obtained.

[0031] (3) Axially chiral biaryl compounds can be rapidly constructed, and further very useful chiral monophosphine ligands can be synthesized. Specific embodiments

[0032] The present invention will be described in detail below by way of examples, but the present invention is not limited to the following examples.

[0033] The references for the ortho-substituted aryl bromides S1-S3, the synthetic raw materials in the following examples, are as follows: (a) D. Schaarschmidt, M. Grumbt, A. Hildebrandt, H. Lang, Eur. J. Org. Chem. 2014, 6676-6685. (b) K. Yang, Y. Mao, J. Xu, H. Wang, Y. He, W. Li, Q. Song, J. Am. Chem. Soc. 2021, 143, 10048-10053.

[0034] The ortho-substituted aryl bromide S4, the synthetic raw material in the following examples, is a commercially available raw material.

[0035] The references for the ortho-substituted aryl bromides S5 and S6, the synthetic raw materials in the following examples, are as follows: (a) B. Xu, M.-L. Li, X.-D. Zuo, S.-F. Zhu, Q.-L. Zhou, J. Am. Chem. Soc. 2015, 137, 8700-8703. (b) M. Aki, T. Ogura, Y. Naruta, T. H. Le, T. Sato, T. Kitagawa, J. Phys. Chem. A 2002, 106, 3436-3444. S5 and S6 are specifically prepared through the following steps:

[0036]

[0037] 1-Bromo-2-naphthylamine (commercially available raw material) (10 mmol, 2.221 g), 1,4-dibromobutane (10 mmol, 2.159 g), potassium iodide (22 mmol, 3.652 g), potassium carbonate (22 mmol, 3.041 g) and acetonitrile (20 mL) were added to a reaction flask and stirred at 90 °C for 48 h. At the end of the reaction, the reaction solution was filtered, and then the filtrate was concentrated under reduced pressure to obtain a crude product. Finally, it was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (100 / 1) as the eluent to obtain the desired intermediate S5.

[0038] 2-Bromo-3-methylphenol (commercially available raw material) (10 mmol, 1.870 g), benzyl bromide (15 mmol, 1.8 mL), potassium carbonate (20 mmol, 2.764 g) and acetone (15 mL) were added to a reaction flask and stirred at 90 °C for 19 h. When the reaction was monitored by TLC to be complete, the reaction solution was filtered, and then the filtrate was concentrated under reduced pressure to obtain a crude product. Finally, it was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (100 / 1) as the eluent to obtain the desired intermediate S6.

[0039] The synthesis of aryl trifluoromethanesulfonates rac-1a - rac-1m in the following examples refers to the following references: (a) M. Bartoszek, M. Beller, J. Deutsch, M. Klawonn, A. N. Nemati, A. Pews-Davtyan, Tetrahedron 2008, 64, 1316; (b) K. Mori, Y. Ichikawa, M. Kobayashi, Y. Shibata, M. Yamanaka, T. Akiyama, Chem. Sci. 2013, 4, 4235; (c) D.-Y. Zhang, D.-S. Wang, M.-C. Wang, C.-B. Yu, K. Gao, Y.-G. Zhou, Synthesis 2011, 17, 2796; (d) D. A. B. L. Rejc, A. A. Molecules 2016, 21, 267; (e) H. Yang, J. L. Petersen, K. K. Wang, Tetrahedron 2006, 62, 8133. Among them:

[0040] The synthetic routes for the synthesis of aryl trifluoromethanesulfonates (rac-1a, rac-1d, rac-1i and rac-1j) are as follows:

[0041]

[0042] The detailed procedure for synthesizing aryl trifluoromethanesulfonate (rac-1b) is as follows:

[0043] Under nitrogen protection, 1-bromo-N,N-dimethyl-2-naphthylamine (S1) (5 mmol, 1.250 g), 2-hydroxy-5-fluorophenylboronic acid (6 mmol, 0.936 g), palladium acetate (0.15 mmol, 0.034 g), bis(1-adamantyl)butylphosphine (0.22 mmol, 0.079 g), potassium carbonate (20 mmol, 2.764 g) and ethylene glycol dimethyl ether / water (32 mL, 3 / 1) were successively added to the reaction flask. After addition, the mixture was stirred at 90 °C for 4 hours. The reaction was monitored by TLC until completion, and then the reaction was stopped and cooled to room temperature. The two phases were separated, and the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Column chromatography was performed on silica gel using petroleum ether / ethyl acetate (50 / 1) as the eluent to obtain the pure intermediate, which was directly used in the next reaction.

[0044] Under nitrogen protection, the above intermediate (4 mmol, 1.116 g) was dissolved in tetrahydrofuran (30 mL) and stirred at 0 °C. Then sodium hydride (8 mmol, 0.320 g, 60% dispersed in mineral oil) was added, and the reaction continued for 1 hour. Subsequently, N-phenyl-bis(trifluoromethylsulfonyl)imide (8 mmol, 2.858 g) was added to the reaction system. After addition, the reaction was transferred to room temperature and allowed to react overnight. At the end of the reaction, water was slowly added to the reaction system under ice bath conditions. The organic phase was separated, and the aqueous phase was extracted 3 times with ethyl acetate (10 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (100 / 1) as the eluent to obtain the desired substrate rac-1b.

[0045] Using a similar procedure to synthesize rac-1b above, substrates rac-1a, rac-1d, rac-1i and rac-1j can be prepared.

[0046] The synthetic routes for synthesizing aryl trifluoromethanesulfonates (rac-1c, rac-1e-1h) are as follows:

[0047]

[0048] The detailed procedure for synthesizing aryl trifluoromethanesulfonate (rac-1f) is as follows:

[0049] Under nitrogen protection, 1-bromo-N,N-dimethylnaphthalen-2-amine (50 mmol, 12.505 g) was dissolved in tetrahydrofuran (200 mL), placed in a -78 °C cold bath, and n-butyllithium (60 mmol, 24 mL, 2.5 M solution in tetrahydrofuran) was slowly added, followed by stirring the reaction for 1 hour. Then trimethyl borate (60 mmol, 6.7 mL) was added. After addition, the reaction mixture was transferred to room temperature and reacted overnight. At the end of the reaction, saturated ammonium chloride solution was slowly added, and the mixture was stirred for 1 hour. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by recrystallization to obtain pure (2-(dimethylamino)naphthalen-1-yl)boronic acid (7.557 g, 70% yield, yellow solid).

[0050] Under a nitrogen atmosphere, (2-(dimethylamino)naphthalen-1-yl)boronic acid (5.2 mmol, 1.118 g), 2-bromo-4-isopropylphenol (4 mmol, 0.804 g), palladium acetate (0.12 mmol, 0.027 g), bis(1-adamantyl)butylphosphine (0.176 mmol, 0.063 g), potassium carbonate (16 mmol, 2.211 g), and 1,2-dimethoxyethane / water (24 mL, 3 / 1) were added to a reaction flask, and the mixture was refluxed in an oil bath at 90 °C for 4 hours. When the reaction was monitored by TLC to be complete, the reaction was stopped and cooled to room temperature. The organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (50 / 1) as the eluent to obtain a pure intermediate, which was directly used in the next reaction.

[0051] Under nitrogen protection, the above intermediate (3.5 mmol, 1.060 g) was dissolved in tetrahydrofuran (25 mL), and the mixture was stirred at 0 °C. Then sodium hydride (7 mmol, 0.280 g, 60% dispersed in mineral oil) was added. After stirring the reaction for 1 hour, N-phenyl-bis(trifluoromethanesulfonimide) (7 mmol, 2.501 g) was added. After addition, the reaction mixture was transferred to room temperature and reacted overnight. At the end of the reaction, water was slowly added to the reaction system under ice bath conditions. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (100 / 1) as the eluent to obtain the product rac-1f.

[0052] Using a similar procedure to the above synthesis of rac-1f, the substrates rac-1c, rac-1e, rac-1g, and rac-1h can be prepared.

[0053] The synthetic route for the synthesis of aryl trifluoromethanesulfonates (rac-1k - 1m) is as follows:

[0054]

[0055] The detailed steps for synthesizing aryl trifluoromethanesulfonate (rac-1k) are as follows:

[0056] Under nitrogen protection, 1-bromo-2-isopropoxynaphthalene (5 mmol, 1.326 g), 2-hydroxyphenylboronic acid (6 mmol, 0.828 g), tetrakis(triphenylphosphine)palladium (1.5 mmol, 1.733 g), potassium phosphate (20 mmol, 4.245 g), and ethylene glycol dimethyl ether / water (55 mL, 8 / 3) were added to a reaction flask and stirred at 100 °C overnight. When the reaction was completed monitored by TLC, the reaction was stopped and cooled to room temperature. The organic phase was separated, then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (50 / 1 to 20 / 1) as the eluent to obtain the pure intermediate, which was directly used in the next step of the reaction.

[0057] Under nitrogen protection, the above intermediate (4.9 mmol, 1.372 g) was dissolved in tetrahydrofuran (40 mL), stirred at 0 °C, and then sodium hydride (9.8 mmol, 0.392 g, 60% dispersed in mineral oil) was added. After stirring for 1 hour, N-phenyl-bis-(trifluoromethanesulfonimide) (9.8 mmol, 3.501 g) was added to the above reaction system. Then, it was transferred to room temperature and reacted overnight. At the end of the reaction, water was slowly added to the mixture under ice bath conditions. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (100 / 1) as the eluent to obtain the desired substrate rac-1k.

[0058] Using a similar procedure to synthesize rac-1k above, substrates rac-1l and rac-1m can be prepared.

[0059] The reference for the synthesis of the known compound rac-1n in the following examples is as follows: C. Yao, P. Wu, Y. Huang, Y. Chen, L. Lia and Y.-Mi. Li, Org. Biomol. Chem. 2020, 18, 9712.

[0060] The reference for the synthesis of the synthetic raw material biaryl diphenol S7 in the following examples is as follows: K. Mori, Y. Ichikawa, M. Kobayashi, Y. Shibata, M. Yamanaka, T. Akiyama, Chem. Sci. 2013, 4, 4235;

[0061] The detailed steps for preparing substrate 3 in the following examples are as follows:

[0062]

[0063] Under a nitrogen atmosphere, the above compound S7 (0.6 mmol, 0.160 g) was dissolved in tetrahydrofuran (10 mL), then sodium hydride (2.4 mmol, 0.096 g, 60% dispersed in mineral oil) was added, and the reaction was stirred for 1 hour. Subsequently, N-phenyl-bis(trifluoromethanesulfonimide) (1.8 mmol, 0.643 g) was added, and then the reaction was carried out at room temperature for 2 hours. When the reaction was monitored by TLC to be complete, water was slowly added to the reaction system under ice bath conditions to quench the reaction. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (8 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using petroleum ether / ethyl acetate (40 / 1) as the eluent to obtain the desired substrate 3.

[0064] The references for the synthesis of rac-6 in the following examples are as follows: E. C.K. Claverie, C. Bour, D.J. Cárdenas, A.M. Echavarren, Angew. Chem. Int. Ed. 2008, 47, 7892;

[0065] The references for the synthesis of rac-9 in the following examples are as follows: A.J. Argüelles, S. Sun, B.G. Budaitis, P. Nagorny, Angew. Chem. Int. Ed. 2018, 57, 5325;

[0066] The references for the synthesis of NaCMe(CO2Me)2 in the following examples are as follows: T. Hayashi, M. Kawatsura, Y. Uozumi, J. Am. Chem. Soc. 1998, 120, 1681 - 1687.

[0067] Examples 1 - 14

[0068] Condition optimization: changing the types of organic solvents, palladium precursors, hydrogen sources, and chiral ligands

[0069] Under a nitrogen atmosphere, palladium acetate (0.005 mmol) and a chiral ligand (0.0075 mmol) were added to a reaction tube, followed by N,N-dimethylformamide (0.6 mL). After stirring at 30 °C for 10 minutes, aryl trifluoromethanesulfonate rac-1a (0.1 mmol) and N,N-dimethylformamide (0.4 mL) were added. Then, the mixture was placed in a -20 °C cold bath and stirred for 20 minutes. After that, sodium borohydride (0.15 mmol) was added, and the reaction was carried out for 3 hours. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate (2×15 mL), the organic phases were combined, washed once with water, then dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure by rotary evaporation. The pure product was obtained by column chromatography separation.

[0070] The types of organic solvents, palladium precursors, hydrogen sources, and chiral ligands are shown in Table 1. ee represents enantioselectivity.

[0071]

[0072] Table 1. Optimization of the reaction conditions for the asymmetric hydrogenolysis of aryl trifluoromethanesulfonate 1a

[0073]

[0074]

[0075] Examples 15 - 29

[0076] Asymmetric hydrogenolysis of aryl trifluoromethanesulfonate rac-1

[0077] Under a nitrogen atmosphere, palladium acetate (0.0175 mmol) and chiral ligand L1 (0.02625 mmol) were added to a reaction tube, followed by N,N-dimethylformamide (2.1 mL). After stirring at 30 °C for 10 minutes, aryl trifluoromethanesulfonate rac-1 (0.35 mmol) and N,N-dimethylformamide (1.4 mL) were added. Then, the mixture was placed in a -20 °C or -40 °C cold bath and stirred for 20 minutes. After that, sodium borohydride (0.525 mmol) was added, and the reaction was carried out for a certain time. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate (2×15 mL), the organic phases were combined, washed once with water, then dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure by rotary evaporation. The pure product was obtained by column chromatography separation.

[0078] The aryl trifluoromethanesulfonate was rac-1. By changing the type of rac-1 in the reaction, 14 different axially chiral biaryl compounds (-)-1 and compound 2 examples were obtained. The specific types of changes are as follows:

[0079]

[0080] The reaction temperature for rac-1a - rac-1i is -20 °C, and the reaction temperature for rac-1j - rac-1n is -40 °C.

[0081] The structure of (-)-1n was determined by comparison with the literature. (References: L. Byrne, C. P. Norrby, R. H. Munday, A. R. Turner, P. D. Smith, Adv. Synth. Catal. 2021, 363, 259 - 267.).

[0082] Examples 30 - 31

[0083] Hydrogenolysis and desymmetrization of aryl triflate 3

[0084] Under a nitrogen atmosphere, palladium acetate (0.01 mmol), chiral ligand L1 (0.015 mmol), and N,N-dimethylformamide (1.6 mL) were added to a reaction tube. After stirring at 30 °C for 10 minutes, aryl triflate 3 (0.2 mmol) and N,N-dimethylformamide (0.4 mL) were added. Then, it was placed in a -40 °C cold bath and stirred for 20 minutes, followed by the addition of sodium borohydride or sodium borodeuteride (0.3 mmol), and the reaction was carried out for 2 hours. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate (2 × 15 mL), the organic phases were combined, washed once with water, then dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. The pure product was obtained by column chromatography.

[0085]

[0086] Note: The deuterium incorporation rate is greater than 99% in the above.

[0087] Examples 32 - 35

[0088] Synthesis of axially chiral monophosphine ligand

[0089] Under a nitrogen atmosphere, palladium acetate (33.7 mg, 0.15 mmol) and chiral ligand L1 (265.4 mg, 0.225 mmol) were added to a reaction tube, along with N,N-dimethylformamide (18 mL). After stirring at 30 °C for 10 minutes, aryl triflate 1l (1.375 g, 3 mmol) and N,N-dimethylformamide (12 mL) were added. Then, it was placed in a -40 °C cold bath and stirred for 20 minutes, followed by the addition of sodium borohydride (170.2 mg, 4.5 mmol), and the reaction was carried out for 12 hours. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate (2 × 15 mL), the organic phases were combined, washed once with water, then dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. The pure product (-)-1l (0.350 g, 25% yield, >99% ee) was obtained by column chromatography.

[0090] Under a nitrogen atmosphere, (-)-1l (1.0 equivalent, >99% ee), arylphosphine oxide Ar2P(O)H (1.2 equivalents), Ni(COD)2 (1.0 equivalent), DPPF (1.0 equivalent), sodium carbonate (1.0 equivalent), and 1,4-dioxane (the concentration of the starting material (-)-1l in dioxane was 0.1 M) were added to a reaction tube. After the addition, the reaction was carried out at 70 °C for 10 hours. After the reaction was completed, it was filtered through diatomaceous earth and the solvent was removed by rotary evaporation under reduced pressure. The pure product 4 was obtained by column chromatography separation.

[0091] Specifically, when synthesizing 4a, the amounts of each reactant used were (-)-1l (0.334 g, 0.73 mmol), Ph2P(O)H (0.177 g, 0.87 mmol), Ni(COD)2 (0.201 g, 0.73 mmol), DPPF (0.405 g, 0.73 mmol), sodium carbonate (0.077 g, 0.73 mmol), and 1,4-dioxane (7.3 mL).

[0092] When synthesizing 4b, the amounts of each reactant used were (-)-1l (0.339 g, 0.74 mmol), (4-MeOC6H4)2P(O)H (0.233 g, 0.89 mmol), Ni(COD)2 (0.204 g, 0.74 mmol), DPPF (0.410 g, 0.74 mmol), sodium carbonate (0.078 g, 0.74 mmol), and 1,4-dioxane (7.4 mL).

[0093] When synthesizing 4c, the amounts of each reactant used were (-)-1l (0.333 g, 0.73 mmol), (4-MeC6H4)2P(O)H (0.200 g, 0.87 mmol), Ni(COD)2 (0.201 g, 0.73 mmol), DPPF (0.405 g, 0.73 mmol), sodium carbonate (0.077 g, 0.73 mmol), and 1,4-dioxane (7.3 mL).

[0094] When synthesizing 4d, the amounts of each reactant used were (-)-1l (0.320 g, 0.70 mmol), (2-naphthyl)2P(O)H (0.253 g, 0.84 mmol), Ni(COD)2 (0.193 g, 0.70 mmol), DPPF (0.388 g, 0.70 mmol), sodium carbonate (0.075 g, 0.70 mmol), and 1,4-dioxane (7.0 mL).

[0095] Under a nitrogen atmosphere, the above compound 4 (1.0 equivalent), triethylamine (5.0 equivalents) and toluene (10 ml) were added to a reaction tube. Trichlorosilane (5.0 equivalents) was added under an ice bath condition. After the addition, the reaction was carried out at 100 °C overnight. After the reaction was completed, water was added to quench the reaction under an ice bath, and then the pure product 5 was obtained by column chromatography separation.

[0096] Specifically, when synthesizing 5a, the amounts of each reactant used were 4a (0.170 g, 0.33 mmol), triethylamine (0.32 mL, 2.31 mmol), toluene (10 mL), and trichlorosilane (0.16 mL, 1.66 mmol).

[0097] When synthesizing 5b, the amounts of each reactant used were 4b (0.195 g, 0.34 mmol), triethylamine (0.33 mL, 2.38 mmol), toluene (10 mL), and trichlorosilane (0.17 mL, 1.71 mmol).

[0098] When synthesizing 5c, the amounts of each reactant used were 4c (0.240 g, 0.45 mmol), triethylamine (0.44 mL, 3.15 mmol), toluene (10 mL), and trichlorosilane (0.22 mL, 2.25 mmol).

[0099] When synthesizing 5d, the amounts of each reactant used were 4d (0.200 g, 0.33 mmol), triethylamine (0.32 mL, 2.31 mmol), toluene (10 mL), and trichlorosilane (0.16 mL, 1.65 mmol).

[0100]

[0101] Table 2. Synthesis of Axially Chiral Monophosphine Ligands

[0102]

[0103] Examples 36 - 40

[0104] Application of Axially Chiral Monophosphine Ligands

[0105] Under a nitrogen atmosphere, [PdCl(C3H5)]2 (0.002 mmol, 0.7 mg), chiral monophosphorus ligand 5 (0.004 mmol) and tetrahydrofuran (0.5 mL) were added to a reaction flask and stirred at 30 °C for 30 min. Then, rac-6 (0.2 mmol, 41.2 mg) and tetrahydrofuran (0.5 mL) were added and stirred for another 30 minutes. Then it was cooled to -20 °C or -40 °C, and NaCMe(CO2Me)2 (0.4 mmol, 67.2 mg) was added. The reaction continued for 57 hours. Saturated ammonium chloride solution was added to the mixture to quench the reaction. The mixture was diluted with ethyl acetate and transferred to a round-bottom flask. Then it was dried over anhydrous sodium sulfate, filtered and the solvent was removed by rotary evaporation under reduced pressure. Column chromatography was used to separate the products (7 and 8).

[0106] Under a nitrogen atmosphere, allylpalladium(II) chloride dimer ([PdCl(C3H5)]2) (0.005 mmol, 1.8 mg), chiral monophosphoric acid ligand 5a (0.022 mmol, 10.9 mg) and toluene (0.5 mL) were added to a reaction flask and stirred at 30 °C for 30 min. Then, rac-9 (0.25 mmol, 63.1 mg) and toluene (0.5 mL) were added and stirred for another 30 minutes. Subsequently, dimethyl malonate (0.75 mmol, 85.7 μL), N,O-bis(trimethylsilyl)acetamide (0.75 mmol, 183.0 μL) and lithium acetate (0.0075 mmol, 0.5 mg) were added. The reaction was stirred at 60 °C for 3 hours. At the end of the reaction, saturated ammonium chloride solution was added to the mixture to quench the reaction. The mixture was diluted with ethyl acetate and transferred to a round-bottom flask, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and column chromatography was used to separate the chiral product 10.

[0107]

[0108] Example 41

[0109] Synthesis of chiral compound (-)-1h

[0110] Under a nitrogen atmosphere, palladium acetate (33.7 mg, 0.15 mmol) and chiral ligand L1 (265.4 mg, 0.225 mmol) were added to a reaction tube, followed by N,N-dimethylformamide (18 mL). After stirring at 30 °C for 10 minutes, aryl trifluoromethanesulfonate 1h (1.414 g, 3 mmol) and N,N-dimethylformamide (12 mL) were added. Then, the mixture was placed in a -20 °C cold bath and stirred for 20 minutes. Sodium borohydride (170.2 mg, 4.5 mmol) was added, and the reaction was carried out for 160 minutes. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate (2 × 15 mL), the organic phases were combined, washed once with water, dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. The pure product (-)-1h (0.406 g, 29% yield, >99% ee) was obtained by column chromatography separation.

[0111] Synthesis of chiral compound 11

[0112] Under a nitrogen atmosphere, compound (-)-1h (0.2 mmol, 94.3 mg), palladium (II) dichloride [1,3-bis(diphenylphosphino)propane] (PdCl2(dppp)) (0.012 mmol, 7.1 mg), phenylmagnesium bromide (1.2 mmol, 1.2 mL, 1.0 M solution in tetrahydrofuran) and diethyl ether (1.5 mL) were added to a reaction flask. After addition, the mixture was stirred at 40 °C for 68 hours. At the end of the reaction, water was slowly added to the mixture to quench the reaction. The two phases were separated, and the aqueous phase was extracted twice with ethyl acetate (10 mL × 2).

[0113] The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Subsequently, the product 11 was obtained by column chromatography separation.

[0114]

[0115] 1-(1-Bromonaphthalen-2-yl)pyrrolidine (S5):

[0116] 1.653 g, 60% yield, yellow oil, new compound, R f = 0.62 (hexanes / ethylacetate 50 / 1). 1 H NMR (400 25.5.HRMS Calculated for C 14 H 15 BrN[M+H] + 276.0382( 79 Br) and 278.0362( 81Br), found: 276.0383( 79 Br) and 278.0363( 81 Br).

[0117] 1-(Benzyloxy)-2-bromo-3-methylbenzene (S6):

[0118] 99% yield, colorless oil, new compound, R f = 0.81 (hexanes / ethyl acetate 20 / 1). 1 H NMR (400 MHz, 111.1, 70.9, 23.5. HRMS Calculated for C 14 H 17 BrNO + [M + NH4] + 294.0488( 79 Br) and 296.0468( 81 Br), found: 294.0487( 79 Br) and 294.0468( 81 Br).

[0119] 2-(2-(Dimethylamino)naphthalen-1-yl)phenyl trifluoromethanesulfonate (rac-1a):

[0120] 1.585 g, 76% yield, yellow solid, mp = 168 - 169℃, new compound, R f = 0.60 (hexanes / ethyl acetate MHz, CDCl3) δ - 74.97. HRMS Calculated for C 19 H 17 F3NO3S + [M + H] + 396.0876, found: 396.0878.

[0121] 2-(2-(Dimethylamino)naphthalen-1-yl)-4-fluorophenyl trifluoromethanesulfonate (rac-1b):

[0122] 1.534 g, 73% yield, white solid, mp = 108 - 109 °C, new compound, R f = 0.70 (hexanes / ethyl acetate 20 / 1). (m, 3H), 7.40 - 7.35 (m, 2H), 7.29 - 7.25 (m, 1H), 7.24 - 7.16 (m, 1H), 2.61 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 162.5, 160.0, 150.3, 144.1 (d, J = 2.0 Hz), 135.1 (d, J = 8.0 Hz), 133.0, 130.6, 130.1, 128.2, 126.8, 124.4 (d, J = 4.0 Hz), 123.6 (d, J = 9.0 Hz), 122.7, 120.9 (d, J = 23.0 Hz), 119.5, 118.3 (q, J = 318.0 Hz), 115.7 (d, J = 24.0 Hz), 44.1. 19 F NMR (376 MHz, CDCl3) δ -74.84, -113.27. HRMS Calculated for C 19 H 16 F4NO3S + [M + H] + 414.0782, found: 414.0785.

[0123] 2-(2-(Dimethylamino)naphthalen-1-yl)-4-methoxyphenyl trifluoromethanesulfonate (rac-1c):

[0124] 0.898 g, 71% yield, yellow solid, mp = 103 - 104 °C, new compound, R f = 0.47 (hexanes / ethyl acetate -74.96. HRMS Calculated for C 20 H 19 F3NO4S + [M + H] + 426.0981, found: 426.0984.

[0125] 2-(2-(Dimethylamino)naphthalen-1-yl)-4-methylphenyl trifluoromethanesulfonate(rac-1d):

[0126] 1.619 g, 80% yield, yellow solid, mp = 98 - 99 °C, new compound, R f = 0.75 (hexanes / ethyl acetate 20 / 1). 410.1032, found: 410.1033.

[0127] 2-(2-(Dimethylamino)naphthalen-1-yl)-4-ethylphenyl trifluoromethanesulfonate(rac-1e):

[0128] 1.247 g, 73% yield, yellow solid, mp = 96 - 97 °C, new compound, R f = 0.77 (hexanes / ethyl acetate 20 / 1). -75.00. HRMS Calculated for C 21 H 21 F3NO3S + [M + H] + 424.1189, found: 424.1191.

[0129] 2-(2-(Dimethylamino)naphthalen-1-yl)-4-isopropylphenyl trifluoromethanesulfonate(rac-1f):

[0130] 1.349 g, 67% yield, yellow solid, mp = 92 - 93 °C, new compound, R f = 0.87 (hexanes / ethyl acetate 20 / 1). CDCl3) δ -75.01. HRMS Calculated for C 22 H 23 F3NO3S + [M + H] + 438.1345, found: 438.1348.

[0131] 4-(tert-Butyl)-2-(2-(dimethylamino)naphthalen-1-yl)phenyltrifluoromethanesulfonate(rac-1g):

[0132] 1.647 g, 90% yield, yellow solid, mp = 103 - 104 °C, new compound, R f = 0.76 (hexanes / ethyl acetate 128.1, 126.5, 125.8, 124.8, 124.2, 124.1, 121.3, 119.5, 118.4 (q, J = 318.0 Hz), 43.9, 34.9, 31.4. 19 F NMR (376 MHz, CDCl3) δ -75.00. HRMS Calculated for C 23 H 25 F3NO3S + [M+H] + 452.1502, found: 452.1503.

[0133] 3-(2-(Dimethylamino)naphthalen-1-yl)-[1,1'-biphenyl]-4-yltrifluoromethanesulfonate(rac-1h):

[0134] 1.032 g, 52% yield, white solid, mp = 142 - 143 °C, new compound, R f = 0.67 (hexanes / ethyl acetate 20 / 1). δ -74.86. HRMS Calculated for C 25 H 21 F3NO3S + [M+H] + 472.1189, found: 472.1193.

[0135] 2-(2-(Pyrrolidin-1-yl)naphthalen-1-yl)phenyl trifluoromethanesulfonate(rac-1i):

[0136] 0.796 g, 77% yield, yellow solid, mp = 111 - 112 °C, new compound, R f = 0.72 (hexanes / ethyl acetate for C 21 H 19 F3NO3S + [M + H] + 422.1032, found: 422.1034.

[0137] 2-(2-Methoxynaphthalen-1-yl)phenyl trifluoromethanesulfonate (rac-1j):

[0138] 1.418 g, 81% yield, yellow solid, mp = 77 - 78 °C, new compound, R f = 0.70 (hexanes / ethyl acetate 10 / 1). HRMS Calculated for C 18 H 14 F3O4S + [M + H] + 383.0559, found: 383.0557.

[0139] 2-(2-Isopropoxynaphthalen-1-yl)phenyl trifluoromethanesulfonate (rac-1k):

[0140] 1.813 g, 89% yield, yellow oil, new compound, R f = 0.61 (hexanes / ethylacetate 50 / 1). 1 H NMR (400 J = 318.3 Hz), 115.5, 71.4, 22.5, 22.2. 19 F NMR (376 MHz, CDCl3) δ -74.76. HRMS CalculatedforC 20 H 18 F3O4S + [M + H] + 411.0872, found: 411.0870.

[0141] 2-(2-(Benzyloxy)naphthalen-1-yl)phenyl trifluoromethanesulfonate(rac-1l):

[0142] 1.810 g, 80% yield, white solid, mp=93 - 94℃, new compound, R f =0.51(hexanes / ethyl acetate 50 / 1). (q, J=318.0 Hz), 114.7, 71.1. 19 F NMR(376 MHz, CDCl3)δ - 74.62. HRMS Calculated for C 24 H 18 F3O4S + [M + H] + 459.0872, found: 459.0873.

[0143] 2'-(Benzyloxy)-6'-methyl-[1,1'-biphenyl]-2-yl trifluoromethanesulfonate(rac-1m):

[0144] 1.823 g, 76% yield, white solid, mp=64 - 65℃, new compound, R f =0.60(hexanes / ethyl acetate 50 / 1). 318.3 Hz), 109.9, 70.2, 20.1. 19 F NMR(376 MHz, CDCl3)δ - 74.62. HRMS Calculated for C 21 H 18 F3O4S + [M + H] + 423.0872, found: 423.0880.

[0145] 2'-Methoxy-[1,1'-binaphthalen]-2-yl trifluoromethanesulfonate(rac-1n):

[0146] 1.764 g, 41% yield, white solid, known compound, 2e R f= 0.50 (hexanes / ethylacetate 20 / 1). 1 1H NMR 127.00, 126.96, 124.9, 123.8, 119.7, 118.4 (q, J = 318.0 Hz), 115.2, 113.0, 56.3. 19 19F NMR (376 MHz, CDCl3) δ -74.92.

[0147] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)phenyl trifluoromethanesulfonate ((-)-1a):

[0148] Conversion: 53%, s 17.6, 58.2 mg, 42% yield, 83.8% ee, [α] 20 D = -70.47 (c 0.84, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 8.5 min (major) and 9.9 min.

[0149] N,N-Dimethyl-1-phenylnaphthalen-2-amine (2a):

[0150] 43.5 mg, 50% yield, white solid, known compound, 3a R f = 0.68 (hexanes / ethylacetate 20 / 1). 1 1H NMR

[0151] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)-4-fluorophenyltrifluoromethanesulfonate ((-)-1b):

[0152] Conversion: 50%, s 15.0, 71.2 mg, 49% yield, 74.4% ee, [α] 20 D=-41.00(c 0.60, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 8.2 min (major) and 9.3 min.

[0153] 1-(3-Fluorophenyl)-N,N-dimethylnaphthalen-2-amine (2b):

[0154] 45.7 mg, 49% yield, yellow oil, new compound, R f = 0.46 (hexanes / dichloromethane 5 / 1). 1 H NMR (400

[0155] C 18 H 17 FN + [M + H] + 266.1340, found: 266.1341.

[0156] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)-4-methoxyphenyltrifluoromethanesulfonate ((-)-1c):

[0157] Conversion: 41%, s 15.1, 87.8 mg, 59% yield, 55.2% ee, [α] 20 D =-48.89 (c 1.54, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 11.7 min (major) and 13.0 min.

[0158] 1-(3-Methoxyphenyl)-N,N-dimethylnaphthalen-2-amine (2c):

[0159] 35.1 mg, 36% yield, yellow oil, new compound, R f= 0.17 (hexanes / dichloromethane 2 / 1). 1 H NMR(400

[0160] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)-4-methylphenyltrifluoromethanesulfonate ((-)-1d):

[0161] Conversion: 52%, s 18.7, 67.8 mg, 47% yield, 82.5% ee, [α] 20 D = -88.21 (c 0.84, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 8.5 min (major) and 9.5 min.

[0162] N,N-Dimethyl-1-(m-tolyl)naphthalen-2-amine (2d):

[0163] 47.0 mg, 51% yield, yellow oil, new compound, R f = 0.24 (hexanes / dichloromethane 5 / 1). 1 H NMR(400

[0164] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)-4-ethylphenyltrifluoromethanesulfonate ((-)-1e):

[0165] Conversion: 51%, s 63.8, 71.0 mg, 48% yield, 93.4% ee, [α] 20 D = -79.58 (c 0.96, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 8.0 min (major) and 8.5 min.

[0166] 1-(3-Ethylphenyl)-N,N-dimethylnaphthalen-2-amine(2e):

[0167] 48.1mg, 50% yield, yellow oil, new compound, R f =0.34(hexanes / dichloromethane 5 / 1). 1 H NMR(400

[0168] (-)-2-(2-(Dimethylamino)naphthalen-1-yl)-4-isopropylphenyltrifluoromethanesulfonate((-)-1f):

[0169] Conversion: 52%, s 68.8, 71.1mg, 47% yield, 96.4% ee, [α] 20 D =-105.69(c1.00, CHCl3). HPLC: Chiralpak IB column, 230nm, 30℃, n-Hexane / i-PrOH=99.5 / 0.5, flow=0.5mL / min, retention time 7.8min(major) and 8.8min.

[0170] 1-(3-Isopropylphenyl)-N,N-dimethylnaphthalen-2-amine(2f):

[0171] 51.0mg, 50% yield, colorless oil, new compound, R f =0.25(hexanes / dichloromethane 5 / 1). 1 H NMR

[0172] (-)-4-(t-Butyl)-2-(2-(dimethylamino)naphthalen-1-yl)phenyltrifluoromethanesulfonate((-)-1g):

[0173] Conversion: 49%, s 45.2, 78.0 mg, 49% yield, 85.2% ee, [α] 20 D = -90.49 (c 1.20, CHCl3). HPLC: Chiralpak IB column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 7.4 min (major) and 8.0 min.

[0174] 1-(3-(tert-Butyl)phenyl)-N,N-dimethylnaphthalen-2-amine (2 g):

[0175] 50.3 mg, 47% yield, yellow oil, new compound, R f = 0.36 (hexanes / dichloromethane 5 / 1). 1 H NMR (400

[0176] (-)-3-(2-(Dimethylamino)naphthalen-1-yl)-[1,1'-biphenyl]-4-yltrifluoromethanesulfonat ((-)-1h):

[0177] Conversion: 53%, s 70.0, 75.4 mg, 46% yield, 98.4% ee, [α] 20 D = -156.49 (c 0.80, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.5 mL / min, retention time 9.8 min (major) and 10.5 min.

[0178] 1-([1,1'-Biphenyl]-3-yl)-N,N-dimethylnaphthalen-2-amine (2h):

[0179] 58.4 mg, 52% yield, yellow oil, new compound, R f= 0.29 (hexanes / dichloromethane 5 / 1). 1 H NMR (400

[0180] (-)-2-(2-(Pyrrolidin-1-yl)naphthalen-1-yl)phenyl trifluoromethanesulfonate ((-)-1i):

[0181] Conversion: 65%, s 11.2, 48.1 mg, 33% yield, 95.9% ee, [α] 20 D = -127.88 (c 0.71, CHCl3). HPLC: Chiralpak OD-3 column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.0 / 1.0, flow = 0.7 mL / min, retention time 8.0 min and 10.1 min (major).

[0182] 1-(1-Phenylnaphthalen-2-yl)pyrrolidine (2i):

[0183] 57.8 mg, 60% yield, yellow oil, new compound, R f = 0.81 (hexanes / acetone 50 / 1). 1 H NMR (400 MHz,

[0184] (-)-2-(2-Methoxynaphthalen-1-yl)phenyl trifluoromethanesulfonate ((-)-1j):

[0185] Conversion: 55%, s 13.0, 57.6 mg, 43% yield, 82.7% ee, [α] 20 D = -82.96 (c 0.91, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 98.0 / 2.0, flow = 0.7 mL / min, retention time 6.7 min (major) and 7.8 min.

[0186] 2-Methoxy-1-phenylnaphthalene(2j):

[0187] 43.2mg, 53% yield, colorless oil, known compound, 3b R f = 0.50(hexanes / ethyl acetate 50 / 1). 1 H NMR 123.6, 114.0, 56.9.

[0188] (-)-2-(2-Isopropoxynaphthalen-1-yl)phenyl trifluoromethanesulfonate((-)-1k):

[0189] Conversion: 53%, s 18.8, 64.0mg, 45% yield, 84.9% ee, [α] 20 D = -88.97(c 0.88, CHCl3). HPLC: Chiralpak IA column, 230nm, 30℃, n-Hexane / i-PrOH = 99.0 / 1.0, flow = 0.6mL / min, retention time 7.1min(major) and 7.9min.

[0190] 2-Isopropoxy-1-phenylnaphthalene(2k):

[0191] 46.2mg, 50% yield, colorless oil, new compound, R f = 0.68(hexanes / ethylacetate 50 / 1). 1 H NMR(400

[0192] (-)-2-(2-(Benzyloxy)naphthalen-1-yl)phenyl trifluoromethanesulfonate((-)-1l):

[0193] Conversion: 44%, s 16.7, 84.3mg, 53% yield, 62.6% ee, [α] 20 D=-53.95 (c 1.24, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.0 / 1.0, flow = 0.6 mL / min, retention time 10.7 min (major) and 15.4 min.

[0194] 2-(Benzyloxy)-1-phenylnaphthalene (2l):

[0195] 44.8 mg, 41% yield, colorless oil, new compound, R f = 0.63 (hexanes / ethylacetate 50 / 1). 1 H NMR (400 C 23 H 19 O + [M + H] + 311.1430, found: 311.1430.

[0196] (-)-2'-(Benzyloxy)-6'-methyl-[1,1'-biphenyl]-2-yl trifluoromethanesulfonate ((-)-1m):

[0197] Conversion: 40%, s 5.3, 84.1 mg, 57% yield, 38.3% ee, [α] 20 D =-25.00 (c 1.28, CHCl3). HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.0 / 1.0, flow = 0.6 mL / min, retention time 7.5 min (major) and 9.4 min.

[0198] 2-(Benzyloxy)-6-methyl-1,1'-biphenyl (2m):

[0199] 36.4 mg, 38% yield, colorless oil, new compound, R f = 0.70 (hexanes / ethylacetate 50 / 1). 1 H NMR (400 for C 20 H 22 NO + [M+NH4] + 292.1696, found: 292.1703.

[0200] (R)-(-)-2'-Methoxy-[1,1'-binaphthalen]-2-yl trifluoromethanesulfonate ((-)-1n):

[0201] Conversion: 65%, s 3.7, 49.1mg, 33% yield, 62.7% ee, [α] 20 D = -74.15 (c 0.53, CHCl3), [lit. 3c :[α] 20 D = -94.10 (c 1.00, CHCl3) for >99% ee (R)]. HPLC: Chiralpak IB column, 230nm, 30℃, n-Hexane / i-PrOH = 99.0 / 1.0, flow = 0.7mL / min, retention time 7.8min (minor) and 8.3min (major).

[0202] (R)-(-)-2-Methoxy-1,1'-binaphthalene (2n):

[0203] 60.0mg, 60% yield, white solid, known compound, R f = 0.58 (hexanes / ethylacetate 20 / 1), 34.8% ee, [α] 20 D = -18.25 (c 0.80, CHCl3), [lit. 4a :[α] 20 D = -42.20 (c 1.23, CHCl3) for 97% ee (R)]. 11H NMR (400 MHz, CDCl3) δ 8.04 - 7.95 (m, 3H), 7.89 (d, J = 8.1 Hz, 1H), 7.68 - 7.61 (m, 1H), 7.52 - 7.44 (m, 3H), 7.39 - 7.29 (m, 3H), 7.27 - 7.22 (m, 1H), 7.18 (d, J = 8.5 Hz, 1H), 3.78 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 154.7, 134.7, 134.4, 133.8, 133.1, 129.6, 129.1, 128.6, 128.4, 127.92, 127.86, 126.5, 126.3, 126.0, 125.8, 125.7, 125.6, 123.7, 123.3, 113.9, 56.8. HPLC: Chiralpak AD - H column, 230 nm, 30 °C, n - Hexane / i - PrOH = 99.0 / 1.0, flow = 0.6 mL / min, retention time 10.0 min (major) and 12.6 min.

[0204] 2 - (2 - Methoxynaphthalen - 1 - yl)-1,3 - phenylene bis(trifluoromethanesulfonate) (3):

[0205] 0.271 g, 85% yield, white solid, mp = 95 - 96 °C, new compound, R f = 0.67 (hexanes / ethyl acetate 10 / 1). 19 19F NMR (376 MHz, CDCl3) δ - 74.54. HRMS Calculated for C 19 H 13 F6O7S2 + [M + H] + 531.0001, found: 531.0002.

[0206] (+)-(2-(2-(Benzyloxy)naphthalen - 1 - yl)phenyl)diphenylphosphine oxide (4a):

[0207] 0.227 g, 61% yield, white solid, mp = 144 - 145 °C, new compound, Rf = 0.19 (hexanes / ethyl acetate 2 / 1), NMR (100 MHz, CDCl3) δ 153.3, 141.2, 141.1, 137.7, 134.5, 134.4, 134.0, 133.8, 133.7, 133.2, 133.0, 132.9, 132.7, 132.2, 132.0, 131.92, 131.86, 131.8, 131.5, 131.4, 131.03, 131.00, 130.72, 130.70, 129.9, 128.6, 128.4, 127.8, 127.7, 127.5, 127.4, 127.3, 127.1, 126.7, 126.0, 125.7, 123.82, 123.78, 123.4, 114.0, 70.3. 31 P NMR (162 MHz, CDCl3) δ 27.8. HRMS Calculated for C 35 H 28 O2P + [M + H] + 511.1821, found: 511.1819. HPLC: Chiralpak IA column, 230 nm, 30 °C, n - Hexane / i - PrOH = 80 / 20, flow = 1.0 mL / min, retention time 15.7 min (major) and 21.9 min (minor).

[0208] (+)-(2-(2-(Benzyloxy)naphthalen - 1 - yl)phenyl)bis(4 - methoxyphenyl)phosphine oxide (4b):

[0209] 0.274 g, 65% yield, white solid, mp = 135 - 136 °C, new compound, R f = 0.14 (hexanes / ethyl acetate 1 / 1), 1313C NMR (100 MHz, CDCl3) δ 161.8, 161.7, 161.11, 161.08, 153.1, 140.54, 140.45, 137.6, 134.8, 134.6, 134.5, 134.0, 133.9, 133.8, 133.2, 133.1, 132.8, 132.6, 131.63, 131.60, 129.6, 128.7, 128.5, 127.6, 127.5, 127.4, 127.3, 126.8, 126.0, 125.8, 125.6, 124.5, 124.4, 124.29, 124.26, 123.4, 123.3, 114.2, 113.4, 113.2, 112.6, 112.5, 70.5, 55.2, 55.1. 31 31P NMR (162 MHz, CDCl3) δ 28.4. HRMS Calculated for C 37 19 32 H31O4P + [M + H]+ + 571.2033, found: 571.2029. HPLC: Chiralpak IA column, 230 nm, 30 °C, n - Hexane / i - PrOH = 60 / 40, flow = 0.7 mL / min, retention time 20.1 min (major) and 27.9 min.

[0210] (+)-(2-(2-(Benzyloxy)naphthalen - 1 - yl)phenyl)di - p - tolylphosphine oxide (4c):

[0211] 0.244 g, 62% yield, white solid, mp = 69 - 70 °C, new compound, R f = 0.31 (hexanes / ethyl acetate 1 / 1), 3H), 7.14 - 7.04 (m, 3H), 7.03 - 6.95 (m, 2H), 6.80 (dd, J = 8.0, 2.2 Hz, 2H), 6.65 (dd, J = 8.0, 2.3 Hz, 2H), 5.06 - 4.96 (m, 2H), 2.22 (s, 3H), 2.15 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 153.3, 141.22, 141.19, 140.9, 140.78, 140.75, 137.8, 134.6, 134.5, 134.4, 133.8, 133.5, 132.9, 132.8, 132.0, 131.9, 131.7, 131.6, 131.5, 131.4, 130.7, 129.8, 129.7, 129.4, 128.7, 128.6, 128.5, 128.4, 127.9, 127.8, 127.5, 127.4, 127.3, 127.2, 126.7, 125.9, 125.8, 124.1, 124.0, 123.3, 114.1, 70.5, 21.54, 21.45. 31 31P NMR (162 MHz, CDCl3) δ 28.3. HRMS Calculated for C 37 H 32 O2P + [M + H] + 539.2134, found: 539.2139. HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 60 / 40, flow = 0.7 mL / min, retention time 16.5 min (major) and 28.2 min.

[0212] (+)-(2-(2-(Benzyloxy)naphthalen-1-yl)phenyl)di(naphthalen-2-yl)phosphine oxide (4d):

[0213] 0.261 g, 61% yield, white solid, mp = 72 - 73 °C, new compound, R f = 0.30 (hexanes / ethyl acetate 1 / 1), 4.95 (s, 2H). 1313C NMR (100 MHz, CDCl3) δ 153.2, 141.1, 141.0, 137.7, 134.7, 134.6, 134.40, 134.37, 134.2, 134.1, 134.0, 133.9, 133.7, 133.4, 133.3, 133.2, 133.0, 132.9, 132.3, 132.2, 132.0, 131.9, 131.8, 131.1, 130.3, 130.0, 129.8, 129.3, 129.0, 128.5, 128.3, 127.8, 127.67, 127.65, 127.63, 127.58, 127.5, 127.2, 127.1, 127.0, 126.8, 126.74, 126.66, 126.62, 126.56, 126.4, 126.1, 126.0, 125.4, 123.7, 123.6, 123.4, 113.8, 70.5. 31 31P NMR (162 MHz, CDCl3) δ 28.0. HRMS Calculated for C 43 H 32 O2P + [M + H] + 611.2134, found: 611.2137. HPLC: Chiralpak IA column, 230 nm, 30 °C, n - Hexane / i - PrOH = 60 / 40, flow = 0.7 mL / min, retention time 19.3 min (major) and 27.1 min (minor).

[0214] ( - )-(2-(2-(Benzyloxy)naphthalen - 1 - yl)phenyl)diphenylphosphane (5a):

[0215] 0.154 g, 94% yield, white solid, new compound, R f = 0.61 (hexanes / ethylacetate 20 / 1), [α] 20 D = - 18.20 (c 128.0, 127.9, 127.8, 127.7, 127.3, 126.5, 126.1, 125.52, 125.48, 125.4, 123.5, 114.7, 70.3. 3131P NMR (162 MHz, CDCl3) δ -13.7. HRMS Calculated for C 35 H 28 OP + [M + H] + 495.1872, found: 495.1869.

[0216] (−)-(2-(2-(Benzyloxy)naphthalen-1-yl)phenyl)bis(4-methoxyphenyl)phosphane (5b):

[0217] 0.180 g, 95% yield, white solid, new compound, R f = 0.50 (hexanes / ethylacetate 20 / 1), [α] 20 D = -18.00 (c 133.6, 131.41, 131.35, 129.4, 128.9, 128.8, 128.6, 128.53, 128.47, 128.4, 128.3, 127.7, 127.6, 127.3, 126.4, 126.0, 125.6, 125.5, 125.4, 123.5, 114.7, 113.9, 113.82, 113.79, 113.7, 70.4, 55.20, 55.16. 31 31P NMR (162 MHz, CDCl3) δ -16.5. HRMS Calculated for C 37 H 32 O3P + [M + H] + 555.2084, found: 555.2087.

[0218] (−)-(2-(2-(Benzyloxy)naphthalen-1-yl)phenyl)di-p-tolylphosphane (5c):

[0219] 0.218 g, 93% yield, white solid, new compound, R f = 0.65 (hexanes / ethylacetate 20 / 1), [α] 20 D = -21.20 (c 0.50, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.86 - 7.71 (m, 2H), 7.50 - 7.43 (m, 1H), 7.41 - 7.34 (m, 1H), 7.34 - 7.05 (m, 11H), 7.04 - 6.81 (m, 8H), 4.88 (dd, J = 91.2, 12.6 Hz, 2H), 2.25 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 153.3, 143.1, 142.8, 139.6, 139.5, 138.1, 138.0, 137.7, 134.4, 134.3, 134.2, 134.0, 133.9, 133.8, 133.7, 133.5, 131.4, 131.3, 129.4, 129.0, 128.94, 128.91, 128.86, 128.3, 127.8, 127.7, 127.3, 126.4, 126.1, 125.61, 125.58, 123.4, 114.7, 70.4, 21.4. 31 31P NMR (162 MHz, CDCl3) δ -15.4. HRMS Calculated for C 37 H 32 OP + [M + H] + 523.2185, found: 523.2200.

[0220] (-)-(2-(2-(Benzyloxy)naphthalen-1-yl)phenyl)di(naphthalen-2-yl)phosphane (5d):

[0221] 0.188 g, 96% yield, white solid, new compound, R f = 0.47 (hexanes / ethylacetate 20 / 1), [α] 20 D = -15.60 (c 130.4, 130.3, 130.2, 129.6, 129.3, 128.9, 128.4, 128.2, 128.1, 127.9, 127.73, 127.72, 127.69, 127.65, 127.6, 127.5, 127.39, 127.37, 126.50, 126.46, 126.3, 126.1, 126.03, 126.00, 125.5, 125.4, 123.5, 114.7, 70.4. 311P NMR (162 MHz, CDCl3) δ -12.4. HRMS Calculated for C 43 H 32 OP + [M + H] + 595.2185, found: 595.2185.

[0222] 54.0 mg, 93% yield, known compounds, 4e 7:8 = 16.7:1, 92% ee, R f =0.38 (hexanes / ethyl acetate 20 / 1). HPLC: Chiralpak AD-H column, 220 nm, 30℃, n-Hexane / i-PrOH = 97 / 3, flow = 0.7 mL / min, retention time 10.1 min (major) and 11.4 min.

[0223] The 1 1H NMR data of the branched compound 7: 1 1H NMR (400 MHz, CDCl3) δ 7.21 - 7.08 (m, 2H), 6.88 - 6.74 (m, 2H), 6.34 - 6.17 (m, 1H), 5.20 - 5.00 (m, 2H), 4.10 (d, J = 8.6 Hz, 1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.62 (s, 3H), 1.42 (s, 3H).

[0224] The 1 1H NMR data of the linear compound 8: 1 1H NMR (400 MHz, CDCl3) δ 7.21 - 7.08 (m, 2H), 6.88 - 6.74 (m, 2H), 6.42 - 6.35 (m, 1H), 5.97 - 5.88 (m, 1H), 3.79 (s, 3H), 3.73 (s, 6H), 2.74 (d, J = 7.0 Hz, 2H), 1.44 (s, 3H).

[0225] (+)-dimethyl (R,E)-2-(1,3-diphenylallyl)malonate (10):

[0226] 78.0 mg, 96% yield, known compound, R f= 0.27 (hexanes / ethyl acetate 20 / 1), 94% ee, [α] 20 D = +21.00 (c 1.00, CHCl3), [lit. 5b : [α] 20 D = +6.1 (c 1.00, CHCl3) for 50% ee (R)]. 1 1H NMR (400 MHz, CDCl3) δ 7.35 - 7.16 (m, 10H), 6.48 (d, J = 15.8 Hz, 1H), 6.33 (dd, J = 15.7, 8.6 Hz, 1H), 4.27 (dd, J = 10.8, 8.7 Hz, 1H), 3.96 (d, J = 10.9 Hz, 1H), 3.70 (s, 3H), 3.51 (s, 3H). HPLC: Chiralpak AD-H column, 254 nm, 30 °C, n-Hexane / i-PrOH = 95 / 5, flow = 1.0 mL / min, retention time 15.9 min (major) and 22.3 min (minor).

[0227] (−)-1-([1,1':4',1″-Terphenyl]-2'-yl)-N,N-dimethylnaphthalen-2-amine (11):

[0228] 54.3 mg, 68% yield, white solid, mp = 65 - 66 °C, new compound, R f = 0.56 (hexanes / ethyl acetate 40 / 1), 98% ee, [α] 20 D = −41.60 (c 1.00, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.88 - 7.79 (m, 2H), 7.78 - 7.68 (m, 5H), 7.63 (d, J = 7.7 Hz, 1H), 7.51 - 7.44 (m, 2H), 7.44 - 7.32 (m, 3H), 7.13 - 6.99 (m, 4H), 6.97 - 6.90 (m, 2H), 2.26 (s, 6H). 1313C NMR (100 MHz, CDCl3) δ 148.7, 141.8, 141.7, 140.8, 139.6, 137.6, 134.4, 131.4, 130.8, 129.9, 129.3, 129.0, 128.7, 128.6, 128.1, 127.4, 127.2, 127.1, 126.3, 126.2, 126.0, 125.4, 123.7, 119.8, 43.3. HRMS Calculated for C 30 H 26 N [M+H] + 400.2060, found: 400.2061. HPLC: Chiralpak IA column, 230 nm, 30 °C, n-Hexane / i-PrOH = 99.5 / 0.5, flow = 0.6 mL / min, retention time 7.4 min and 7.9 min (major).

Claims

1. A method for the synthesis of axially chiral biaryl compounds by palladium-catalyzed asymmetric hydrogenolysis through kinetic resolution, characterized in that, The method uses a chiral bisphosphine complex of palladium as a catalyst, aryl trifluoromethanesulfonate as a substrate, and a reducing agent as a hydrogen source to synthesize axially chiral biaryl compounds through asymmetric hydrogenolysis; The reaction formula is as follows: In the formula: R is methoxy, benzyloxy, isopropoxy, cyclopentylamino or dimethylamino; Ar is a benzene ring or an aromatic ring with substituents; When Ar is an aromatic ring with substituents, the aryl trifluoromethanesulfonate substrate is selected from one of the following structures: The catalyst is a complex of a metal palladium precursor and a chiral bisphosphine ligand; The metal palladium precursor is one of palladium trifluoroacetate and palladium acetate; the chiral bisphosphine ligand is one of (R)-DTBM-SegPhos and (S)-DTBM-SegPhos; The reducing agent is one of sodium borohydride, lithium borohydride and potassium borohydride; The reaction solvent is an organic solvent, and the organic solvent is N,N-dimethylformamide.

2. The method according to claim 1, characterized in that, The reaction temperature is -50°C - 30°C; the reaction time is 0.5 - 36 hours.

3. The method according to claim 1, wherein: The molar ratio of the metal palladium precursor to the chiral bisphosphine ligand is 1:1 - 1:

3.

4. The method according to claim 1, characterized in that: The preparation method of the catalyst is: under nitrogen protection, the metal palladium precursor and the chiral bisphosphine ligand are stirred in a reaction solvent at 30°C for 10 minutes - 60 minutes to obtain.

5. The method according to claim 1, characterized in that, The molar ratio of the aryl trifluoromethanesulfonate, the metal palladium precursor to the chiral bisphosphine ligand is 1:0.005:0.0006 - 1:0.05:0.

100.

6. The method according to claim 1, characterized in that, The specific reaction steps of the method are: Under nitrogen protection, the metal palladium precursor and the chiral bisphosphine ligand are stirred in a reaction solvent at 30°C for 10 minutes - 60 minutes, then aryl trifluoromethanesulfonate is added, the reaction system is stirred at -50 - 30°C for 20 minutes, then the hydrogen source is added, and the reaction is carried out at this temperature to obtain axially chiral biaryl compounds.

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