A rapid synthesis method of axially chiral aromatic amine compounds without metal catalysis

Abstract

The present invention discloses a rapid synthesis method for axially chiral aromatic amine compounds using metal-free catalysis. 1-substituted tetrahydro-2-naphthalenone and a cheap and readily available chiral amine are used as raw materials. Axial chiral aromatic amines are prepared by reaction under the action of a catalyst, and a wide range of substrates can be selected. Compared with traditional synthesis methods, the method of the present invention uses metal-free catalysis, has the advantages of simple conditions, convenient operation, relatively high yield, low environmental pollution, and ease of industrial production. The synthesis method of the present invention can simultaneously obtain two axially chiral aromatic amine compounds, and the yield range is 20%-70%.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a rapid synthesis method of axial chiral aromatic amine compounds without metal catalysis. Background Art

[0002] Axially chiral compounds have attracted attention in chiral catalytic reactions. Most axially chiral compounds have biaryl skeletons; among them, axially chiral aromatic amines are the core structures of drugs, natural products and optoelectronic materials, and are also widely used in the development of chiral ligands and chiral catalysts. Traditional methods for constructing this type of compound include metal-mediated asymmetric cross-coupling, selective conversion of point chirality to axial chirality, chiral construction of aromatic rings, and kinetic resolution / desymmetrization of biaryl compounds [(a) Kozlowski, M.; Morgan, BJ; Linton, E.C. Chem. Soc. Rev. 2009, 38, 3193. (b) Wencel-Delord, J., Panossian, A.; Leroux, FR; Colobert, F. Chem. Soc. Rev. 2015, 44, 3418. (c) Bringmann, G. Angew. Chem. Int. Ed. 2005, 44, 5384. (d) Ma, G.; Sibi, M.P. Chem. Eur. J. 2015, 21, 11644.].

[0003] Currently, the main limitation of the synthesis of axially chiral aromatic amines lies in chiral resolution, which often requires complex operational procedures, and product yield and selectivity still need to be improved. In recent years, asymmetric catalytic synthesis methods have also made some progress in the synthesis of axially chiral aromatic amines, but they generally require the participation of metal catalysts, and the chiral ligands used are often complex, making large-scale preparation difficult. [(a) Chang, X.; Zhang, Q.; Guo, C. Org. Lett. 2019, 21, 4915. (b) Moustafa, G.A.I.; Oki, Y.; Akai, S. Angew. Chem. Int. Ed. 2018, 57, 10278.] Summary of the Invention

[0004] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide a metal-free catalytic method for the rapid synthesis of axially chiral aromatic amine compounds, so as to solve the technical problems in the prior art such as the need for transition metal catalysts, complex reaction operation procedures, and low atom economy.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention discloses a method for rapidly synthesizing an axially chiral aromatic amine compound without metal catalysis, comprising: mixing a 1-substituted tetrahydro-2-naphthalenone compound with a chiral amine compound, and reacting the mixture under the action of a catalyst and an additive to obtain the axially chiral aromatic amine compound; wherein:

[0007] The structural formula of the 1-substituted tetrahydro-2-naphthalenone compound is as follows:

[0008]

[0009] The structural formula of the chiral amine compound is as follows:

[0010] R*NH2

[0011] wherein R is selected from (hetero)aryl or alkyl;

[0012] The structural formula of the obtained axial chiral aromatic amine compound is as follows:

[0013]

[0014] Among them, R 1 、R 2 is selected from alkyl, alkoxy, halogen, substituted aryl or ester group; R 3 Selected from alkyl, alkoxy, halogen, substituted aryl or ester group.

[0015] Preferably, the catalyst is selected from methyltriphenylphosphine iodide, tetraethylammonium iodide, tetrapropylammonium iodide, benzyltrimethylammonium iodide, tetraheptylammonium iodide, tetrabutylammonium iodide, magnesium iodide or sodium iodide.

[0016] Preferably, the additive is selected from N,N-diisopropylethylamine, 2,6-lutidine, N,N-dimethylaniline, sodium bicarbonate or ammonium acetate.

[0017] Preferably, the molar ratio of the 1-substituted tetrahydro-2-naphthalenone compound to the catalyst is 4:1 to 2:1.

[0018] Preferably, the reaction temperature is 60-100°C.

[0019] Preferably, the solvent used in the reaction is selected from 1,2-dichloroethane, 1,2-dibromoethane, dichloromethane, chloroform, carbon tetrachloride, ethyl acetate, methyl acetate, butyl acetate, acetone, nitromethane, acetonitrile, toluene, benzene, chlorobenzene, n-hexane, tetrahydrofuran, 1,4-dioxane, diethyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, methanol or ethanol.

[0020] Preferably, the concentration of the solvent is 0.5 to 2 mol / L.

[0021] Preferably, the reaction molar ratio of the 1-substituted tetrahydro-2-naphthalenone compound to the chiral amine compound is 3:1 to 1:3.

[0022] Preferably, the molar amount of the additive is 5% to 25% of the amount of the 1-substituted tetrahydro-2-naphthalenone compound.

[0023] Preferably, the axially chiral aromatic amine compound is separated by column chromatography.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The present invention discloses a rapid, metal-free synthesis method for axially chiral aromatic amine compounds. The method uses a 1-substituted tetrahydro-2-naphthalenone derivative and a readily available, inexpensive chiral amine as raw materials. The axially chiral aromatic amine is prepared by reacting in the presence of a catalyst, allowing for a wide range of substrates to be selected. Compared with traditional synthesis methods, the method utilizes metal-free catalysis, resulting in simpler conditions, easier operation, relatively higher yields, less environmental pollution, and ease of industrial production. The method can simultaneously produce two axially chiral aromatic amine compounds with yields ranging from 20% to 70%. The axially chiral aromatic amine compounds synthesized by the method can be hydrogenated to synthesize commonly used ligand compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 A roadmap for the synthesis of axially chiral aromatic amine compounds. DETAILED DESCRIPTION

[0027] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0028] It should be noted that the terms "first", "second", etc. in the description and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that the numbers used in this way can be interchanged where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0029] The present invention is described in further detail below with reference to the accompanying drawings:

[0030] Example 1

[0031] Synthesis of methyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)-L-phenylalaninate

[0032]

[0033] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 86.3mg of L-phenylalanine methyl ester hydrochloride, MS 150 mg, ammonium acetate 30.8 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (35.7 mg) and IV (46.4 mg), respectively, for a total of 82.1 mg, with an overall yield of 89%.

[0034] III: 1 H NMR(400MHz, CDCl3)δ8.01(d,J=9.0Hz,1H),7.91(d,J=8.2Hz,1H),

[0035] 7.81(d,J=8.9Hz,1H),7.76–7.74(m,1H),7.42(d,J=9.1Hz,1H),7.36(ddd,J=8.1,5.7,1.2Hz,1H),7.23–7.03(m,6H),6.97–6.93(m,3 H),6.68–6.66(m,2H),4.45(dt,J=9.0,6.0Hz,1H),3.98(d,J=9.2Hz,1H),3.66(s,3H),3.57(s,3H),2.85(qd,J=13.4,6.0Hz,2H)ppm; 13C NMR(100MHz,CDCl3)δ173.5,155.7,141.9,136.0,134.1,133.9,130.2,129.7,129.3,129.1,128.3,128.14,128.09,127.8,126.8,126.7,126.4,125.3,124.49,124.0,122.1,118.3,114.7,114.6,113.6,57.6,56.8,52.0,39.2.ppm;FTIR(neat)υ2943,2342,1740,1599,1501,1260,1198,811,746;HRMS(ESI)m / z:Calcd.For C 31 H 28 NO3 + :462.2064,Found:462.2064(M+H + ).IV: 1 H NMR(400MHz,CDCl3)δ8.02(d,J=9.0Hz,1H),7.85(dd,J=16.4,8.5Hz,2H),7.77–7.75(m,1H),7.45(d,J=9.1Hz,1H),7.32(ddd,J=8.1,6.7,1.2Hz,1H),7.18(dddd,J=8.2,6.8,2.5,1.3Hz,2H),7.14–7.08(m,6H),6.91–6.87(m,3H),4.44(t,J=6.5Hz,1H),3.69(s,3H),3.43(s,3H),2.90(d,J=6.4Hz,2H)ppm; 13 CNMR(100MHz,CDCl3)δ173.5,155.6,142.2,136.3,134.1,133.9,130.3,129.6,129.3,129.0,128.4,128.1,128.0,126.8,126.7,126.4,125.4,124.5,124.0,122.3,118.3,115.1,114.1,58.4,56.8,51.9,39.2ppm;FTIR(neat)υ2988,2008,1401,1191,1121,833,776,701,471;HRMS(ESI)m / z:Calcd.For C 31 H 28 NO3 + :462.2064,Found:462.2064(M+H + ).

[0036] Example 2

[0037] Synthesis of methyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)-L-valinate

[0038]

[0039] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 67.1mg of L-valine methyl ester hydrochloride, MS 150 mg, ammonium acetate 30.8 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (37.2 mg) and IV (30.5 mg), respectively, for a total of 67.7 mg, with an overall yield of 82%.

[0040] III: 1 H NMR (400MHz, CDCl3) δ8.01 (d, J=9.0Hz, 1H), 7.85 (dd, J=12.9, 8.6Hz, 2H),

[0041] 7.77–7.75(m,1H),7.49(d,J=9.1Hz,1H),7.32(ddd,J=8.1,6.6,1.3Hz,1H),7.21–7.13(m,5H),6.94(dd,J=8.2,1.0Hz,1H),3.98(d,J =6.0Hz,1H),3.77(s,3H),3.63(s,3H),1.82(dq,J=13.4,6.7Hz,1H),0.85(ddd,J=16.0,8.1,3.0Hz),0.67(dd,J=14.4,6.8Hz,6H)ppm; 13C NMR(100MHz,CDCl3)δ173.9,155.8,142.6,134.1,133.9,130.3,129.6,129.3,128.1,127.7,126.8,126.4,125.3,124.4,123.9,122.0,118.4,114.5,114.4,114.0,62.5,56.9,51.8,31.8,18.8,18.6ppm;FTIR(neat)υ3407,2954,1725,1602,1503,1257,1153,814,749;HRMS(ESI)m / z:Calcd.For C 27 H 28 NO3 + :414.2064,Found:414.2064(M+H + ).

[0042] IV: 1 H NMR(400MHz,CDCl3)δ8.02(d,J=9.0Hz,1H),7.86(dd,J=14.9,8.6Hz,2H),

[0043] 7.76(d,J=7.5Hz,1H),7.47(d,J=9.1Hz,1H),7.33(ddd,J=8.1,6.7,1.2Hz,1H),7.25–7.10(m,5H),6.91(d,J=8.4Hz,1H),3.98(dd,J=9.6,6.3Hz,1H),3.85(d,J=9.6Hz,1H),3.77(s,3H),3.43(s,3H),1.92–1.80(m,1H),0.80(dd,J=6.8,1.6Hz,6H)ppm; 13 C NMR(100MHz,CDCl3)δ173.7,155.7,142.8,134.2,134.1,130.3,129.6,129.3,128.1,128.0,127.8,126.8,126.4,125.5,124.4,124.0,122.1,118.4,114.8,114.3,114.1,63.1,56.8,51.6,31.6,18.9,18.7ppm;FTIR(neat)υ2924,2874,1737,1595,1507,1266,1154,810,748;HRMS(ESI)m / z:Calcd.For C 27 H 28 NO3 +:414.2064,Found:414.2072(M+H + ).

[0044] Example 3

[0045] Synthesis of methyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)-L-alloisoleucinate

[0046]

[0047] Take a 25 mL reaction tube and add 14.8 mg of tetrabutylammonium iodide, 60.4 mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 72.7 mg of L-isoleucine methyl ester hydrochloride. MS 150 mg, ammonium acetate 30.8 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (29.7 mg) and IV (25.8 mg), respectively, for a total of 55.5 mg, with an overall yield of 65%.

[0048] III: 1 H NMR (400MHz, CDCl3) δ8.00 (d, J=9.1Hz, 1H), 7.85 (dd, J=10.7, 8.7Hz, 2H),

[0049] 7.77–7.75(m,1H),7.48(d,J=9.1Hz,1H),7.32(ddd,J=8.1,6.7,1.2Hz,1H),7 .22–7.11(m,5H),6.94(d,J=8.3Hz,1H),4.07(dd,J=9.2,6.1Hz,1H),3.94(d, J=9.3Hz,1H),3.77(s,3H),3.62(s,3H),1.57(dq,J=8.7,6.6Hz,1H),1.29–1. 24(m,1H),0.92–0.83(m,1H),0.70(t,J=7.4Hz,3H),0.59(d,J=6.8Hz,3H)ppm; 13C NMR(100MHz,CDCl3)δ173.8,155.9,142.6,134.2,133.9,130.3,129.6,129.3,128.1,127.7,126.7,126.4,125.3,124.5,123.9,122.0,118.5,114.6,114.5,114.0,61.2,56.9,51.8,38.2,25.5,15.2,11.3ppm;FTIR(neat)υ2958,1737,1600,1503,1341,1259,1155,810,747;HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0050] IV: 1 H NMR(400MHz,CDCl3)δ8.01(d,J=9.0Hz,1H),7.86(dd,J=13.3,8.6Hz,2H),

[0051] 7.76(d,J=8.2Hz,1H),7.46(d,J=9.1Hz,1H),7.35–7.31(m,1H),7.25–7.10(m,5H),6.91(d,J=8.4Hz,1H),4.07(dd,J=9.6,6.3Hz,1H),3.88(d,J=9.6Hz,1H),3.76(s,3H),3.43(s,3H),1.68–1.61(m,1H),1.41(tdd,J=11.3,7.2,4.3Hz,1H),1.03(dt,J=15.5,7.3Hz,1H),0.81(t,J=7.4Hz,3H),0.72(d,J=6.8Hz,3H)ppm; 13C NMR (400MHz, CDCl3) δ173.6,155.6,142.7,134.2,134.1,130.3,129.6,129. 3,128.1,128.0,127.8,126.8,126.4,125.4,124.4,124.0,122.1,118.4,114 .7,114.3,114.0,61.7,56.7,51.6,38.0,25.6,15.3,11.5ppm; FTIR(neat)υ 2928,1733,1597,1498,1344,1254,1156,806,747; HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0052] Example 4

[0053] Synthesis of methyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)-L-leucinate

[0054]

[0055] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 72.7mg of L-leucine methyl ester hydrochloride, MS 150 mg, ammonium acetate 30.8 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (30.1 mg) and IV (21.4 mg), respectively, for a total of 51.5 mg, with an overall yield of 60%.

[0056] III: 1 H NMR (400MHz, CDCl3) δ8.01 (d, J=9.0Hz, 1H), 7.86 (t, J=8.3Hz, 2H),

[0057] 7.76(d,J=7.6Hz,1H),7.48(d,J=9.1Hz,1H),7.34–7.30(m,1H),7.23–7.11(m,5H),6.94(d,J=8.3Hz,1H),4.18(dd,J=15.5,7.2Hz,1H),3.78(s,3H),3.74(d,J=9.0Hz,1H),3.64(s,3H),1.41–1.25(m,3H),0.72(t,J=6.3Hz,6H)ppm; 13 C NMR(100MHz,CDCl3)δ175.0,155.9,142.5,134.1,133.9,130.3,129.59,129.3,128.1,127.9,126.8,126.4,125.3,124.5,123.9,122.1,118.4,114.7,114.5,114.1,56.9,55.6,52.1,42.4,24.7,22.6,22.3ppm;FTIR(neat)υ2954,1738,1594,1506,1267,1149,808,747;HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0058] IV: 1 H NMR(400MHz,CDCl3)δ8.02(d,J=9.0Hz,1H),7.87(dd,J=12.7,8.6Hz,2H),

[0059] 7.76(d,J=7.6Hz,1H),7.46(d,J=9.1Hz,1H),7.34(ddd,J=8.1,6.7,1.2Hz,1H),7.26–7.09(m,5H),6.87(d,J=8.4Hz,1H),4.23(t,J=7.2Hz,1H),3.76(s,3H),3.49(s,3H),1.59–1.37(m,4H),0.84(dd,J=18.8,6.5Hz,6H)ppm; 13C NMR (100MHz, CDCl3) δ174.7,155.7,142.7,134.12,130.32 129.6,129.4,128.1,128.0,127.9,126.8,126.4,125.5,124.5,124.1,122.2,118.4,114.8,114.2,114.1,56.7,56.0,51 .9,42.3,25.0,22.7,22.4ppm; FTIR(neat)υ2916,1735,1659,1503,1327,1252,1196,1143,802; HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0060] Example 5

[0061] Synthesis of methyl(2S)-2-((2'-methoxy-[1,1'-binaphthalen]-2-yl)amino)-3,3-dimethylbutanoate

[0062]

[0063] Take a 25 mL reaction tube and add 14.8 mg of tetrabutylammonium iodide, 60.4 mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 72.7 mg of L-tert-leucine methyl ester hydrochloride. MS 150 mg, ammonium acetate 30.8 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (34.4 mg) and IV (21.0 mg), respectively, for a total of 55.4 mg, with an overall yield of 65%.

[0064] III: 1 H NMR (400MHz, CDCl3) δ8.01 (d, J=9.0Hz, 1H), 7.85 (dd, J=16.0, 8.5Hz, 2H),

[0065] 7.77–7.74(m,1H),7.49(d,J=9.1Hz,1H),7.33(ddd,J=8.1,6.6,1.3Hz,1H),7.24–7.12(m,5H),6.99–6.96(m,1H),3.78(s,3H),3.62(s,3H),1.54(s,1H),0.68(s,3H)ppm; 13 C NMR(100MHz,CDCl3)δ173.6,155.7,142.8,134.2,133.9,130.3,129.6,129.3,128.1,127.7,126.7,126.4,125.4,124.4,123.9,122.0,118.5,114.5,114.3,113.7,65.1,56.9,51.5,34.6,26.4ppm;FTIR(neat)υ2953,1735,1598,1501,1342,1258,1150,808,745;HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0066] IV: 1 H NMR(400MHz,CDCl3)8.01(d,J=9.0Hz,1H),7.85(dd,J=15.4,8.5Hz,2H),

[0067] 7.77–7.75(m,1H),7.47(d,J=9.1Hz,1H),7.33(ddd,J=8.1,6.7,1.2Hz,1H),7.24–7.11(m,5H),6.96–6.93(m,1H),3.96–3.90(d,J=5.7Hz,2H),3.77(s,3H),3.35(s,,3H),0.78(s,9H)ppm; 13C NMR (100MHz, CDCl3) δ173.1,155.8,143.1,134.2,134.1,130.3,129.6,12 9.3,128.1,128.0,127.8,126.7,126.4,125.5,124.5,124.0,122.1,118. 6,114.9,114.3,114.1,66.1,56.8,51.3,34.5,26.5ppm; FTIR(neat)υ2954,1735,1594,1504,1263,1151,1082,808,739; HRMS(ESI)m / z:Calcd.For C 28 H 30 NO3 + :428.2220,Found:428.2220(M+H + ).

[0068] Example 6

[0069] Synthesis of (2R)-2-((2'-methoxy-[1,1'-binaphthalen]-2-yl)amino)-2-phenylethan-1-ol

[0070]

[0071] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)-2-tetralone, 54.9mg of D-phenylglycinol, MS 150 mg, ammonium acetate 15.4 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (30.0 mg) and IV (20.1 mg), respectively, for a total of 50.1 mg, with an overall yield of 60%.

[0072] III: 1 H NMR(400MHz, CDCl3)δ8.04(d,J=9.0Hz,1H),7.91(d,J=8.1Hz,1H),

[0073] 7.74(t,J=8.6Hz,2H),7.51(d,J=9.1Hz,1H),7.39–7.35(m,1H),7.23–7.07(m,10H),6.87(d,J=8.4Hz,1H),4.74(dd,J=7.4,4.1Hz,1H),4.11(s,1H),3.77(d,J=15.0Hz,4H),3.42(dd,J=11.1,7.8Hz,1H),2.15(s,1H)ppm; 13 C NMR(100MHz,CDCl3)δ155.4,143.2,140.4,134.1,134.0,130.5,129.9,129.2,128.7,128.2,128.1,127.8,127.6,126.9,126.7,126.4,125.5,124.4,124.3,122.2,118.9,115.4,114.7,67.3,60.5,57.3ppm;FTIR(neat)υ3387,2930,1602,1499,1340,1257,1078,811,744,701;HRMS(ESI)m / z:Calcd.For C 29 H 26 NO2 + :420.1958,Found:420.1958(M+H + ).

[0074] IV: 1 H NMR(400MHz,CDCl3)δ8.03(d,J=9.0Hz,1H),7.90(d,J=8.1Hz,1H),

[0075] 7.72(d,J=8.4Hz,1H),7.49(d,J=9.1Hz,1H),7.36(ddd,J=8.1,6.7,1.3Hz,1H),7.36–7.12(m,9H),7.04(d,J=9.0Hz,1H),6.93–6.91(m,1H),4.69(dd,J=7.0,4.2Hz,1H),4.16(s,1H),3.77(s,3H),3.69–3.63(m,1H),3.45–3.41(m,1H),1.48(d,J=5.2Hz,1H)ppm; 13C NMR (100MHz, CDCl3) δ155.5,142.9,140.5,134.0,130.4,129.7,129.1,1 28.8,128.3,128.1,127.8,127.6,127.1,126.8,126.3,125.1,124.3,12 4.1,122.1,118.4,115.2,114.8,113.9,67.1,59.9,56.5ppm; FTIR(neat)υ2927,1602,1500,1343,1260,1076,810,748; HRMS(ESI)m / z:Calcd.For C 29 H 26 NO2 + :420.1958,Found:420.1958(M+H + ).

[0076] Example 7

[0077] Synthesis of (2S)-2-((2'-methoxy-[1,1'-binaphthalen]-2-yl)amino)-3-phenylpropan-1-ol

[0078]

[0079] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)-2-tetralone, and 60.5mg of L-phenylalaninol, MS 150 mg, ammonium acetate 15.4 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (29.1 mg) and IV (19.8 mg), respectively, for a total of 48.9 mg, with an overall yield of 56%.

[0080] III: 1 H NMR(400MHz, CDCl3)δ8.03(d,J=9.1Hz,1H),7.92(d,J=8.2Hz,1H),

[0081] 7.85(d,J=9.0Hz,1H),7.77(d,J=7.9Hz,1H),7.47(d,J=9.1Hz,1H),7.41–7.37(m,1H),7.27–7.10(m,,8H),6.94(dd,J=6.5,2.9Hz,2H),6.83(d,J=8.4Hz,1H),3.89(s,1H),3.70(d,J=14.7Hz,4H),3.48(s,1H),3.26–3.21(m,1H),2.66(dd,J=13.3,5.3Hz,1H),2.56–2.49(m,2H)ppm; 13 C NMR(100MHz,CDCl3)δ154.8,143.0,138.1,134.3,134.1,130.5,130.0,129.3,128.4,128.2,128.1,127.9,127.2,126.5,126.4,125.4,124.5,124.3,122.3,119.2,115.6,114.8,114.7,62.6,57.4,56.8,38.0ppm;FTIR(neat)υ2928,2357,1598,1498,1255,1035,810,742;HRMS(ESI)m / z:Calcd.For C 30 H 28 NO2 + :434.2115,Found:434.2115(M+H + ).

[0082] IV: 1 H NMR(400MHz,CDCl3)δ8.02(d,J=9.0Hz,1H),7.88(d,J=8.9Hz,2H),

[0083] 7.79(d,J=7.5Hz,1H),7.48(d,J=9.1Hz,1H),7.35–7.30(m,2H),7.24–7.14(m,7H),7.06–7.04(m,2H),6.92(d,J=8.4Hz,1H),3.86(dd,J=8.5,4.1Hz,1H),3.74(s,1H),3.48(d,J=9.7Hz,2H),3.20(dd,J=11.0,5.3Hz,1H),2.83(dd,J=13.5,5.2Hz,1H),2.55(dd,J=13.5,8.3Hz,1H),1.48(s,1H)ppm; 13C NMR (100MHz, CDCl3) δ155.5,142.9,138.2,134.1,133.9,130.4,129.6,129. 4,129.3,128.5,128.4,128.1,128.0,127.2,126.5,126.4,124.6,124.4,12 4.1,122.4,118.2,115.6,115.3,114.0,63.06,57.1,56.6,38.2ppm; FTIR(n eat)υ2936,1737,1599,1501,1338,1259,809,745; HRMS(ESI)m / z:Calcd.For C 30 H 28 NO2 + :434.2115,Found:434.2115(M+H + ).

[0084] Example 8

[0085] Synthesis of (2R)-2-((2'-methoxy-[1,1'-binaphthalen]-2-yl)amino)-3-methylbutan-1-ol

[0086]

[0087] Take a 25mL reaction tube, add 14.8mg of tetrabutylammonium iodide, 60.4mg of 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone, and 41.3mg of D-valinol, MS 150 mg, ammonium acetate 15.4 mg, 1,2-dichloroethane 1 mL, stirred at 100°C for 24 hours. After the reaction, ethyl acetate 10 mL was added and washed with saturated sodium carbonate solution 5 mL. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were separated by column chromatography using a developing solvent of petroleum ether:ethyl acetate in a ratio of 40:1 to 10:1 to obtain the pure products III (19.0 mg) and IV (14.8 mg), respectively, for a total of 33.8 mg, with an overall yield of 44%.

[0088] III: 1 H NMR(400MHz, CDCl3)δ8.02(d,J=9.1Hz,1H),7.87(dd,J=17.7,8.6Hz,2H),

[0089] 7.77(d,J=8.0Hz,1H),7.49(d,J=9.1Hz,1H),7.39–7.35(m,1H),7.30–7.22(m,2H),7.19–7.15(m,2H),7.13–7.09(m,1H),6.81(d,J=8.4Hz),3.74(d,J=15.1Hz,4H),3.45(s,1H),3.30(ddd,J=11.2,6.7,4.7Hz,2H),2.66(dd,J=8.6,4.8Hz,1H),1.52(dq,J=13.5,6.8Hz,1H),0.70(dd,J=8.6,6.8Hz,6H)ppm; 13 C NMR(100MHz,CDCl3)δ154.9,144.2,134.3,134.2,130.4,130.0,129.3,128.1,127.6,127.0,126.4,125.5,124.4,124.2,122.0,119.4,115.4,114.7,113.9,63.3,61.5,57.3,30.3,19.3,19.2ppm;FTIR(neat)υ2953,1600,1501,1339,1255,1150,1071,810,744;HRMS(ESI)m / z:Calcd.ForC 26 H 28 NO2 + :386.2115,Found:386.2115(M+H + ).

[0090] IV: 1 H NMR(400MHz,CDCl3)δ8.02(d,J=9.0Hz,1H),7.87(dd,J=16.6,8.5Hz,2H),

[0091] 7.78–7.76(m,1H),7.48(d,J=9.1Hz,1H),7.37–7.23(m,3H),7.20–7.11(m,3H),6.90(d,J=8.3Hz,1H),3.77(s,3H),3.56(ddd,J=10.8,9.0,3.9Hz,1H),3.49(s,1H),3.30(s,1H),3.19(ddd,J=10.6,7.5,3.0Hz,1H),1.70–1.57(m,2H),0.78(dd,J=6.8,4.9Hz,6H)ppm; 13C NMR (100MHz, CDCl3) δ155.4,144.0,134.2,134.0,130.4,129.6,129.2,1 28.4,128.1,127.8,127.3,126.4,124.7,124.3,124.1,122.1,118.3,115 .1,114.6,113.7,62.7,61.3,56.3,30.6,18.9,18.8ppm; FTIR(neat)υ2951,1594,1500,1336,1255,1150,1050,807,737; HRMS(ESI)m / z:Calcd.For C 26 H 28 NO2 + :386.2115,Found:386.2115(M+H + ).

[0092] The axial chiral aromatic amine compound synthesized by the present invention is subjected to palladium-carbon hydrogenation to remove the benzyl group or direct reduction to remove the alkyl group to obtain a binaphthyl ligand. The reaction mechanism is shown in the following equation:

[0093]

[0094] Therefore, it can be shown that the axially chiral aromatic amine compound synthesized by the method of the present invention can be used to synthesize commonly used ligand compounds.

[0095] The above content is only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A method for the rapid synthesis of axially chiral aromatic amine compounds without metal catalysis, characterized in that: include: A 1-substituted tetrahydro-2-naphthalenone compound is mixed with a chiral amine compound, and reacted under the action of a catalyst and an additive to prepare an axial chiral aromatic amine compound; wherein: The structural formula of the 1-substituted tetrahydro-2-naphthalenone compound is as follows: ； The 1-substituted tetrahydro-2-naphthalenone compound is specifically selected from 1-(2-methoxynaphthyl)tetrahydro-2-naphthalenone; The structural formula of the chiral amine compound is as follows: The chiral amine compound is specifically selected from L -Phenylalanine methyl ester hydrochloride, L-valine methyl ester hydrochloride, L -Isoleucine methyl ester hydrochloride, L -Leucine methyl ester hydrochloride, L -tert-Leucine methyl ester hydrochloride, D -phenylglycinol, L -phenylalaninol and D -Valinol; The structural formula of the obtained axial chiral aromatic amine compound is as follows: or The obtained axial chiral aromatic amine compounds are specifically: methyl (2'-methoxy-[1,1'-binaphthyl]-2-yl)-L-phenylalaninate, methyl (2'-methoxy-[1,1'-binaphthyl]-2-yl)-L-valine ester, methyl (2'-methoxy-[1,1'-binaphthyl]-2-yl)-L-alloleucine ester, methyl (2'-methoxy-[1,1'-binaphthyl]-2-yl)-L-leucine ester, methyl (2S)-2-[(2'-methyl (2R)-2-[(2'-methoxy-[1,1'-binaphthyl]-2-yl)amino]-3,3-dimethylbutyrate, (2R)-2-[(2'-methoxy-[1,1'-binaphthyl]-2-yl)amino]-2-phenylethanol, (2S)-2-[(2'-methoxy-[1,1'-binaphthyl]-2-yl)amino]-3-phenylpropan-1-ol, or (2R)-2-[(2'-methoxy-[1,1'-binaphthyl]-2-yl)amino]-3-methylbutan-1-ol; The catalyst is selected from methyltriphenylphosphine iodide, tetraethylammonium iodide, tetrapropylammonium iodide, benzyltrimethylammonium iodide, tetraheptylammonium iodide, and tetrabutylammonium iodide; The additive is selected from N , N -Diisopropylethylamine, 2,6-lutidine, N , N -dimethylaniline, sodium bicarbonate or ammonium acetate; the solvent used in the reaction is 1,2-dichloroethane.

2. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: The molar ratio of the 1-substituted tetrahydro-2-naphthalenone compound to the catalyst is 4:1 to 2:

1.

3. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: The reaction temperature is 60~100℃.

4. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: The concentration of the solvent is 0.5~2mol / L.

5. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: The reaction molar ratio of the 1-substituted tetrahydro-2-naphthalenone compound to the chiral amine compound is 3:1 to 1:

3.

6. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: The molar amount of the additive is 5% to 25% of the amount of the 1-substituted tetrahydro-2-naphthalenone compound.

7. The method for rapid synthesis of axially chiral aromatic amine compounds without metal catalysis according to claim 1, characterized in that: Axially chiral aromatic amine compounds were separated by column chromatography.

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