Beta-chiral tertiary amine compound and preparation method thereof

Abstract

The invention relates to the technical field of organic chemical synthesis, and discloses a beta-chiral tertiary amine compound and a preparation method thereof. The compound has the following structure: # imgabs0 #, Ar is a heterocyclic group or an aryl group, the Ar contains N, O, S, Si, B or halogen, and the Ar contains 6-18 carbon atoms. Starting from an aryl diazo or aryl hydrazone compound and tertiary amine, a series of beta-chiral tertiary amine compounds are synthesized through excellent selectivity and enantioselectivity carbene C (sp3)-H alkylation catalyzed by axial chiral iridium porphyrin, and the para-position of aryl tertiary amine is not blocked by a large-steric-hindrance group or N-methyl is not activated aliphatic tertiary amine. A complex natural product, a drug molecule and the like containing an N-methyl structure can also be well modified to obtain a target product with high diastereoselectivity, for example, the natural product dicentrine is also suitable for the method, and a favorable method is provided for modification of the natural product containing an N-methyl tertiary amine structure due to high diastereoselectivity.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical synthesis, and in particular to a beta-chiral tertiary amine compound and a preparation method thereof. Background Art

[0002] Tertiary amines are ubiquitous in pharmaceuticals, alkaloid natural products, functional materials, photosynthesis, and catalysis. Direct functionalization of the CH bond near the nitrogen in amines provides unlimited opportunities for the synthesis of tertiary amines. This can be achieved by building complex amines from simple amines or by modifying complex amines (such as alkaloids) at a later stage.

[0003] So far, the α-alkylation of tertiary amines has developed rapidly. 3 Metal-catalyzed carbonylation of )-H bonds has become an important strategy for functionalizing tertiary amines, especially in asymmetric synthesis. However, there are still some challenges: (1) The nitrogen lone pair itself acts as a nucleophile to the carbene center to form N-ylide, making the reaction path uncontrollable. (2) Different types of C-H bonds, such as primary and secondary carbon bonds, will cause selectivity problems. (3) If aromatic amines are involved, the C(sp) 2 )-H bonds will be activated, thus giving rise to new site selectivity issues. To overcome the above challenges, it is necessary to develop new catalysts that can subtly distinguish the energy barriers between different types of C-H bonds.

[0004] Davies and Winkler disclosed the asymmetric CH functionalization of cyclic amines with carbenes in "J. Am. Chem. Soc. 1999, 121, 6509." In their seminal study, both amines had to use an N-boc protection strategy to overcome the selectivity challenges faced in the formation of N-ylides.

[0005] In addition, Ge, ZL et al. in "Chem. Eur. J. 2023, 29. e202202820.", Xu, B. et al. in "Am. Chem. Soc. 2015, 137, 8700.", Davies, HML et al. in "Org. Lett. 2004, 6, 1769." all disclosed that if the reactant is an aromatic amine and is accompanied by C (sp 2 )-H bond activation, which requires the use of blocking groups at the para position or bulky groups nearby to avoid unwanted reactions.

[0006] In addition, the Davies group disclosed in "Chem. Comm. 2006, 29, 3110" that, under the catalysis of double rhodium, methylamine protected by a bulky trimethylsilyl group was functionalized to form a series of chiral β-amino acid compounds. Summary of the invention

[0007] The purpose of the present invention is to provide a β-chiral tertiary amine compound and a preparation method thereof based on the above technical problems.

[0008] In order to achieve the above object, the first aspect of the present invention provides a β-chiral tertiary amine compound having the structure shown below:

[0009]

[0010] Wherein, Ar is a heterocyclic group or an aromatic group, and Ar contains N, O, S, Si, B or halogen, and Ar contains 6 to 18 carbon atoms;

[0011] R 1 is an alkyl group, an alkene group, a benzyl group, an aryl group or an ester group having 1 to 19 carbon atoms; or R 1 is a heterocyclic group or an aryl group, and said R 1 contains 14 to 18 carbon atoms, and the R 1 Contains N, O, S or halogen;

[0012] R 2 is an alkyl group, an alkene group, a benzyl group, an aryl group or an ester group having 1 to 19 carbon atoms; or R 2 is a heterocyclic group or an aryl group, and said R 2 contains 14 to 18 carbon atoms, and the R 2 Contains N, O, S or halogen;

[0013] R 3 is an alkyl group or an ester group containing 1 to 16 carbon atoms; or R 3 is an alkyl group, a heterocyclic group or an aryl group, and in said R 3 contains 4 to 18 carbon atoms, and in the R 3 Contains N, O, S, Si, B or halogen.

[0014] The second aspect of the present invention provides a method for preparing a β-chiral tertiary amine compound, the method comprising: reacting a diazo compound or a hydrazone compound and a tertiary amine in an argon atmosphere in the presence of an iridium porphyrin catalyst, an additive and a solvent;

[0015] The iridium porphyrin catalyst has the structural formula described below:

[0016]

[0017] Among them, R 4 is an alkyl group containing 1 to 16 carbon atoms; or R 4 is aryl or benzyl, and said R 4 contains 4 to 10 carbon atoms, and the R 4 Contains N, O, S or F;

[0018] The diazo compound has the following structural formula:

[0019]

[0020] The hydrazone compound has the following structural formula:

[0021]

[0022] The tertiary amine has the structural formula described below:

[0023]

[0024] Among them, in the above structural formula, Ar, R 1 , R 2 , R 3 The definitions are respectively the same as those described in the first aspect of the present invention.

[0025] According to a particularly preferred embodiment, the tertiary amine is the N-methyl natural product bicuculline.

[0026] Preferably, the additive is selected from Molecular sieves, Molecular sieves, At least one of molecular sieve, anhydrous sodium sulfate, and anhydrous magnesium sulfate.

[0027] Preferably, the solvent is selected from at least one of toluene, dichloromethane, dichloroethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, chlorobenzene and trifluorotoluene.

[0028] Preferably, the molar ratio of the diazo compound, the tertiary amine and the iridium porphyrin catalyst is 1:0.5-5:0.01-0.02.

[0029] More preferably, the molar ratio of the hydrazone compound, the tertiary amine and the iridium porphyrin catalyst is 1:0.5-5:0.01-0.02.

[0030] Preferably, the amount of the solvent used is 1 mL relative to 0.1 mmol of the diazo compound or hydrazone compound.

[0031] More preferably, the amount of the additive is 100 mg relative to 0.1 mmol of the diazo compound or hydrazone compound.

[0032] More preferably, the reaction conditions at least meet: room temperature, reaction time is 24h.

[0033] The third aspect of the present invention provides a β-chiral tertiary amine compound prepared by the method described in the second aspect of the present invention.

[0034] The β-chiral tertiary amine compound provided by the present invention has at least the following beneficial effects:

[0035] (1) The synthesis reaction conditions of the β-chiral tertiary amine compound provided by the present invention are mild and simple, and the synthetic substrate has a wide range of applicability.

[0036] (2) The β-chiral tertiary amine compound provided by the present invention has a high yield and is easy to separate and purify. It can be scaled up to the gram level and is expected to be industrially produced.

[0037] (3) The synthesis method of the β-chiral tertiary amine compound provided by the present invention has high chemical selectivity, high regioselectivity, and high enantioselectivity.

[0038] (4) The present invention starts from aromatic diazo or aromatic hydrazone compounds and tertiary amines, and the axial chiral iridium porphyrin catalyzes the excellent selectivity and enantioselectivity of carbinol C (sp 3 )-H alkylation and the aromatic tertiary amine is not blocked by a large steric group or the N-methyl is not activated by aliphatic tertiary amine (Scheme 1) to synthesize a series of β-chiral tertiary amine compounds. Complex natural products and drug molecules containing N-methyl structures can also be well modified to obtain highly diastereoselective target products, such as the natural product bicuculline, which is also suitable for this method. The high diastereoselectivity provides a favorable method for the modification of natural products containing N-methyl tertiary amine structures. DETAILED DESCRIPTION

[0039] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0040] The present invention will be described in detail below by way of examples. In the following examples, unless otherwise specified, the raw materials are all commercially available.

[0041] In the following examples, unless otherwise specified, the room temperature is 25±2°C.

[0042] In the following examples, the synthesis method and steps of the iridium porphyrin catalyst [Ir] are carried out according to the method disclosed in the reference “Shanshan Yuan, Jun-Chao Sun, Xiao-Ming Zhao, Jieping Zhu, Sheng-Cai Zheng, Design and Synthesis of C4-Symmetric Axially Chiral β-Aryl Porphyrins and Application for Supporting Ir(III)-Catalyzed Enantioselective C-HAlkylation, Angew. Chem. Int. Ed. 2024, 63, e202404329.”

[0043] In the following examples, unless otherwise specified, MS Molecular sieve, whose structural formula is Ca n Na 12-2n [(AlO2) 12 (SiO2) 12 ]xH2O.

[0044] In the following examples, unless otherwise specified, the tertiary amine 2e is an alkaloid, and the tertiary amine 2n is the N-methyl natural product bicuculline.

[0045] Example 1

[0046]

[0047] Under argon atmosphere, diazo compound 1a (29.4 mg, 0.1 mmol), tertiary amine 2a (22 mg, 0.2 mmol), iridium porphyrin catalyst [Ir] (2 mg, 0.001 mmol), MS (100 mg) was added to the reaction tube, followed by dichloromethane (1 mL), and a stirrer (to keep the reaction in a stirring state). The mixture was stirred at room temperature for 24 h. After the reaction was completed, the mixture was filtered using a sand core funnel covered with diatomaceous earth, and 10 mL of dichloromethane was added for washing. The filtrate was taken and decompressed to remove the solvent to obtain a crude product. The crude product was separated by column chromatography to obtain the target product, which was recorded as 3a.

[0048] 3a, colorless liquid, optical rotation -31.9 (concentration = 0.8, chloroform). 1H NMR (400MHz, CDCl3) δ7.38–7.30(m,5H),7.27–7.23(m,2H),6.77–6.72(m,3H),4.73(d,J=12.0Hz,1H),4.68(d,J= 11.9Hz, 1H), 4.21 (dd, J=14.1, 8.5Hz, 1H), 4.15 (dd, J=8.4, 5.0Hz, 1H), 3.65 (dd, J=14.2, 5.0Hz, 1H), 2.84 (s, 3H). 13 C NMR (100MHz, CDCl3) δ171.6,148.5,136.3,129.4,129.0,128.4,128.1,117.1,112.6,94.9,74.3,56.7,49.9,39.4.HRMS(ESI-MS)m / z[M+H] + calcdfor C 18 H 19 Cl3NO2 + :386.0476,found:386.0469.FT-IR(film):3027,1751,1598,1505,1453,1341,1136,1029,988,801,746,691cm -1 .

[0049] Example 2

[0050]

[0051] The method of Example 1 was followed, except that the diazo compound 1a was replaced by the diazo compound 1b in the same molar amount, wherein the amount of the diazo compound 1b was 34.2 mg, and the remaining steps and parameters were the same as those of Example 1.

[0052] The obtained target product, denoted as 3b, has the following structural formula:

[0053]

[0054] 3b, colorless liquid, optical rotation -25.3 (concentration = 1.0, chloroform). 1H NMR (400MHz, CDCl3) δ7.85–7.80(m,4H),7.53–7.47(m,3H),7.39–7.24(m,2H),6.78–6.75(m,3H),4.77( d,J=12.0Hz,1H),4.68(d,J=12.0Hz,1H),4.35–4.28(m,2H),3.74(dd,J=17.8,9.2Hz,1H),2.84(s,3H). 13 C NMR (100MHz, CDCl3) δ171.5,148.5,133.7,133.6,133.0,129.5,128.8,128.0,127.8,127. 6,126.5,126.4,126.0,117.2,112.7,94.9,74.4,56.7,50.1,39.5.HRMS(ESI-MS)m / z[M+H] + Calculate for C 22 H 21 Cl3NO2 + :436.0632,found:436.0626.FT-IR(film):1751,1511,1361,1245,1139,1038,812,734cm -1 .

[0055] Example 3

[0056]

[0057] The method of Example 1 was followed, except that the diazo compound 1c was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 1c was 33.4 mg, and the remaining steps and parameters were the same as those of Example 1.

[0058] The obtained target product, denoted as 3c, has the following structural formula:

[0059]

[0060] 3c, colorless liquid, optical rotation -45.6 (concentration = 1.2, chloroform). 1 H NMR (400MHz, CDCl3) δ7.95–7.93(m,2H),7.48–7.46(m,2H),7.24–7.28(m,2H),6.78–6.71(m, 3H),4.72(s,2H),4.28–4.21(m,2H),3.67(dd,J=17.4,9.4Hz,1H),2.82(s,3H),2.60(s,3H).13 C NMR (100MHz, CDCl3) δ197.6,170.8,148.3,141.5,136.8,129.5,129.0,128. 8,117.4,112.7,94.7,74.4,56.6,49.9,39.6,26.7.HRMS(ESI-MS)m / z[M+H] + Calculate for C 20 H 21 Cl3NO3 + :428.0582,found:428.0573.FT-IR(film):1751,1748,1598,1505,1355,1266,1144,960,746,714cm -1 .

[0061] Example 4

[0062]

[0063] The method of Example 1 was followed, except that the diazo compound 1a was replaced by the diazo compound 1d in the same molar amount, wherein the amount of the diazo compound 1d was 36.0 mg, and the remaining steps and parameters were the same as those of Example 1.

[0064] The target product obtained is denoted as 3d and has the following structural formula:

[0065]

[0066] 3d, colorless liquid, optical rotation -24.2 (concentration = 0.9, chloroform). 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.1Hz,2H),7.50(d,J=8.1Hz,2H),7.28–7.24(m,2H),6.77(t,J=7.3Hz,1H),6.73–6.7 0(m,2H),4.74(d,J=11.9Hz,1H),4.70(d,J=12.0Hz,1H),4.27–4.21(m,2H),3.67(dd,J=17.7,9.4Hz,1H),2.83(s,3H). 13 C NMR (150MHz, CDCl3) δ170.8, 148.3, 140.2, 130.4 (q, J = 31.5Hz), 129.5, 128.9, 125 .9(q,J=6.0Hz),124.1(q,J=270.0Hz),117.4,112.7,94.7,74.4,56.7,49.7,39.6.19 F NMR(376MHz, CDCl3)δ-62.6.HRMS(ESI-MS)m / z[M+H] + Calculate for C 19 H 18 Cl3F3NO2 + :454.0350,found:454.0345.FT-IR(film):2917,1751,1600,1508,1323,1162,1118,1066,1017,841,795,746cm -1 .

[0067] Example 5

[0068]

[0069] The method of Example 1 was followed, except that the diazo compound 1e was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 1e was 35.0 mg, and the remaining steps and parameters were the same as those of Example 1.

[0070] The obtained target product, denoted as 3e, has the following structural formula:

[0071]

[0072] 3e, colorless liquid, optical rotation -22.7 (concentration = 1.4, chloroform). 1 H NMR (400MHz, CDCl3) δ8.08(s,1H),8.00(d,J=7.8Hz,1H),7.57(d,J=7.8Hz,1H),7.43(t,J=7.7Hz,1H),7.28–7.24( m,2H),6.78–6.72(m,3H),4.71(s,2H),4.28–4.20(m,2H),3.92(s,3H),3.67(dd,J=19.2,9.6Hz,1H),2.84(s,3H). 13 CNMR (100MHz, CDCl3) δ171.1,166.8,148.4,136.7,133.0,131.0,129.5,129.5,129 .3,129.1,117.3,112.7,94.7,74.4,56.6,52.4,49.7,39.5.HRMS(ESI-MS)m / z[M+H] + Calculate for C 20 H 21 Cl3NO4 +:444.0531,found:444.0518.FT-IR(film):2949,1753,1719,1598,1499,1433,1277,1104,798,717cm -1 .

[0073] Example 6

[0074]

[0075] The method of Example 1 was followed, except that the diazo compound 1a was replaced by the diazo compound 1f in the same molar amount, wherein the amount of the diazo compound 1f was 34.8 mg, and the remaining steps and parameters were the same as those of Example 1.

[0076] The obtained target product, denoted as 3f, has the following structural formula:

[0077]

[0078] 3f, colorless liquid, optical rotation -24.4 (concentration = 1.2, chloroform). 1 H NMR (400MHz, CDCl3) δ7.28–7.23(m,4H),7.13–7.10(m,2H),6.76–6.71(m,3H),4.72(d,J=12.0Hz,1H),4.67(d,J=11.9Hz,1H),4.19(dd,J=14.3,8 .6Hz,1H),4.11(dd,J=8.5,5.2Hz,1H),3.64(dd,J=14.3,5.2Hz,1H),2.8 5(s,3H),2.46(d,J=7.2Hz,2H),1.89–1.79(m,1H),0.88(d,J=6.6Hz,6H). 13 C NMR (100MHz, CDCl3) δ171.8,148.6,141.6,133.5,129.7,129.4,128.1,117.0, 112.6,94.9,74.3,56.6,49.6,45.2,39.4,30.3,22.5.HRMS(ESI-MS)m / z[M+H] + Calculate for C 22 H 27 Cl3NO2 + :442.1102,found:442.1103.FT-IR(film):2954,2028,1751,1598,1499,1367,1326,1139,795,711cm -1 .

[0079] Example 7

[0080]

[0081] The method of Example 1 is followed, except that the diazo compound 1a is replaced by the diazo compound 1g in the same molar amount, wherein the amount of the diazo compound 1g is 41.6 mg, and the remaining steps and parameters are the same as those of Example 1.

[0082] The target product obtained is recorded as 3g and has the following structural formula:

[0083]

[0084] 3g, colorless liquid. Optical rotation -46.7 (concentration = 1.0, chloroform). 1 H NMR(400MHz, CDCl3)δ7.29–7.22(m,4H),7.18(d,J=8.2Hz,2H),6.75–6.71(m,3H), 4.73(d,J=12.0Hz,1H),4.63(d,J=11.9Hz,1H),4.18(dd,J=14.1,8.8Hz,1H),4.11 (d,J=8.8,4.7Hz,1H),3.63(dd,J=14.1,4.7Hz,1H),2.86(s,3H),2.49–2.41(m,1H ),1.88–1.84(m,4H),1.48–1.18(m,7H),1.08–1.00(m,2H),0.90(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ171.8,148.6,147.8,133.5,129.4,128.2,127.5,117.1,112.7,94.9 ,74.3,56.7,49.6,44.4,39.9,39.4,37.2,34.4,33.7,20.2,14.6.HRMS(ESI-MS)m / z[M+H] + Calculate for C 27 H 35 Cl3NO2 + :510.1728,found:510.1730.FT-IR(film):2920,1751,1598,1505,1445,1329,1139,798,714,694cm -1 .

[0085] Example 8

[0086]

[0087] The method of Example 1 was followed, except that the diazo compound 1a was replaced by the diazo compound 1h in the same molar amount, wherein the amount of the diazo compound 1h was 38.8 mg, and the remaining steps and parameters were the same as those of Example 1.

[0088] The target product obtained is denoted as 3h and has the following structural formula:

[0089]

[0090] 3h, colorless liquid. Optical rotation -133.9 (concentration = 0.8, chloroform). 1 H NMR (400MHz, CDCl3) δ7.45–7.43(m,2H),7.31–7.23(m,4H),6.77–6.69(m,3H),4.74–4.67(m,2H),4.21(dd ,J=14.1,8.0Hz,1H),4.14(dd,J=8.1,5.6Hz,1H),3.62(dd,J=14.1,5.6Hz,1H),2.80(s,3H),0.25(s,9H). 13 C NMR (100MHz, CDCl3) δ171.1,148.4,136.6,132.6,129.5,128.4,123.0,117.2,1 12.6,104.6,95.1,94.8,74.3,56.6,49.8,39.6,0.090.HRMS(ESI-MS)m / z[M+H] + calcdfor C 23 H 27 Cl3NO2Si + :482.0871,found:482.0872.FT-IR(film):2957,2158,1751,1598,1499,1245,1133,861,836,743,688cm -1 .

[0091] Example 9

[0092]

[0093] The method of Example 1 was followed, except that the diazo compound 1i was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 1i was 41.8 mg, and the remaining steps and parameters were the same as those of Example 1.

[0094] The target product obtained is denoted as 3i and has the following structural formula:

[0095]

[0096] 3i, colorless liquid, optical rotation -22.9 (concentration = 1.0, chloroform). 1 H NMR(600MHz, CDCl3)δ7.79(d,J=7.9Hz,2H),7.73–7.71(m,1H),7.51(d,J=8.0 Hz,1H),7.38(d,J=7.9Hz,1H),7.26(d,J=8.0Hz,1H),6.76–6.71(m,3H),4.73( d,J=11.9Hz,1H),4.67(d,J=12.0Hz,1H),4.22(dd,J=14.5,8.3Hz,1H),4.17(d d,J=8.4,5.6Hz,1H),3.64(dd,J=14.5,5.5Hz,1H),2.82(s,3H),1.35(s,18H). 13 C NMR (150MHz, CDCl3) δ171.3,148.4,139.3,137.1,136.4,135.5,129.5,127.8,117.1,11 2.6,99.0,94.8,84.2,84.1,74.3,56.6,50.1,39.5,25.0,24.9.HRMS(ESI-MS)m / z[M+H] + Calculate for C 24 H 30 BCl3NO4 + :512.1328,found:512.1325.FT-IR(film):2978,2920,1751,1583,1505,1355,1139,1087,960,856,717cm -1 .

[0097] Example 10

[0098]

[0099] The method of Example 1 was followed, except that the diazo compound 1j was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 1j was 47.6 mg, and the remaining steps and parameters were the same as those of Example 1.

[0100] The target product obtained is denoted as 3j and has the following structural formula:

[0101]

[0102] 3j, white solid (melting point 104-106°C), optical rotation -31.5 (concentration = 1.0, chloroform). 1 H NMR (600MHz, CDCl3) δ8.29(s,1H),8.13(s,1H),7.84(d,J=8.3Hz,1H),7.71(d,J=8.5Hz,1H),7.57(dd,J=8.5,1.9Hz,1H),7.52(d,J=8.3Hz,1H),7 .32–7.29(m,2H),6.81–6.78(m,3H),4.80(d,J=11.9Hz,1H),4.73(d,J=1 1.9Hz,1H),4.37–4.32(m,2H),3.76(dd,J=20.1,8.5Hz,1H),2.87(s,3H). 13 C NMR (150MHz, CDCl3) δ171.4,148.4,139.8,138.6,137.1,135.1,133.0,130.0,129.5,127.7,124. 8,124.3,123.4,121.6,118.6,117.3,112.7,94.8,74.4,57.0,49.8,39.6.HRMS(ESI-MS)m / z[M+H] + Calculate for C 24 H 20 BrCl3NO2S + :569.9458,found:569.9442.FT-IR(film):1748,1598,1505,1424,1263,1141,1069,1017,795,737cm -1 .

[0103] Embodiment 11

[0104]

[0105] The method of Example 1 was followed, except that the diazo compound 1k was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 1k was 45.7 mg, and the remaining steps and parameters were the same as those of Example 1.

[0106] The target product obtained is denoted as 3k and has the following structural formula:

[0107]

[0108] 3k, colorless liquid, optical rotation -57.7 (concentration = 0.9, chloroform).1 H NMR(600MHz, CDCl3)δ8.21(s,1H)8.18(d,J=8.0Hz,1H),7.65–7.63(m,2H),7.59–7.58(m,2H),7.50(t,J=7.4Hz,1H),7.46–7.41(m,4H),7.35– 7.31(m,3H),6.83–6.79(m,3H),4.84(d,J=12.0Hz,1H),4.72(d,J=12.0Hz,1H),4.41–4.36(m,2H),3.80(dd,J=18.8,9.4Hz,1H),2.92(s,3H). 13 C NMR (150MHz, CDCl3) δ172.1,148.6,141.4,140.6,137.6,130.1,129.5,127.8,127.7,127.2,126.4,126.2,123. 9,123.2,120.5,120.3,120.1,117.0,112.6,110.2,110.0,95.0,74.3,57.1,49.9,39.5.HRMS(ESI-MS)m / z[M+H] + Calculate for C 30 H 26 Cl3N2O2 + :551.1054,found:551.1053.FT-IR(film):1748,1598,1499,1450,1266,1231,1130,732,697cm -1 .

[0109] Example 12

[0110]

[0111] The method of Example 1 was followed, except that the diazo compound 11 was used in the same molar amount to replace the diazo compound 1a, wherein the amount of the diazo compound 11 was 34.3 mg, and the remaining steps and parameters were the same as those of Example 1.

[0112] The target product obtained is denoted as 31 and has the following structural formula:

[0113]

[0114] 3l, colorless liquid. Optical rotation -35.1 (concentration = 1.0, chloroform). 1H NMR (600MHz, CDCl3) δ8.94 (d, J=4.5Hz, 1H), 8.13 (t, J=9.6Hz, 2H), 7.81–7. 76(m,2H),7.43(dd,J=8.2,4.2Hz,1H),7.29–7.26(m,2H),6.79–6.75(m,3H) ,4.76(d,J=11.9Hz,1H),4.72(d,J=12.0Hz,1H),4.37(dd,J=14.4,5.4Hz,1 H), 4.33 (dd, J=14.3, 8.2Hz, 1H), 3.77 (dd, J=14.2, 5.5Hz, 1H), 2.83 (s, 3H). 13 CNMR (150MHz, CDCl3) δ171.2,151.0,148.4,148.0,136.1,134.6,130.4,129.7,129.5,1 28.4,127.5,121.7,117.3,112.7,94.8,74.4,56.8,49.8,39.6.HRMS(ESI-MS)m / z[M+H] + Calculate for C 21 H 20 Cl3N2O2 + :437.0585,found:437.0552.FT-IR(film):2926,1753,1600,1502,1370,1260,1144,1032,795,737,691cm -1 .

[0115] Example 13

[0116]

[0117] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2b in the same molar amount, wherein the amount of the tertiary amine 2b was 39.8 mg, and the remaining steps and parameters were the same as those of Example 2.

[0118] The target product obtained is denoted as 3m and has the following structural formula:

[0119]

[0120] 3m, colorless liquid, the reaction can be scaled up to gram scale. Optical rotation -83.1 (concentration = 1.0, chloroform). 1HNMR(600MHz, CDCl3)δ7.85–7.79(m,4H),7.50–7.48(m,3H),7.33–7.32(m,2H),6.60–6.59(m,2H), 4.78(d,J=11.9Hz,1H),4.68(d,J=12.0Hz,1H),4.30–4.25(m,2H),3.73–3.68(m,1H),2.79(s,3H). 13 CNMR (150MHz, CDCl3) δ171.3,147.4,133.5,133.3,133.0,132.1,128.9,128.0,127.8,127. 6,126.6,126.5,125.9,114.2,109.1,94.8,74.4,56.6,49.8,39.6.HRMS(ESI-MS)m / z[M+H] + Calculate for C 22 H 20 BrCl3NO2 + :513.9738,found:513.9736.FT-IR(film):3059,1748,1589,1495,1371,1136,859,808,725cm -1 .

[0121] Embodiment 14

[0122]

[0123] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2c in the same molar amount, wherein the amount of the tertiary amine 2c was 32.6 mg, and the remaining steps and parameters were the same as those of Example 2.

[0124] The target product obtained is denoted as 3n and has the following structural formula:

[0125]

[0126] 3n, white solid (melting point 103-106°C), optical rotation -120.6 (concentration = 0.8, chloroform). 1H NMR (400MHz, CDCl3) δ7.91–7.79(m,6H),7.51–7.48(m,3H),6.71–6.69(m,2H),4.80(d,J=12.0,1H),4.69(d,J=11.9,1 H),4.38(dd,J=14.4,7.9Hz,1H),4.31(dd,J=8.0,5.8Hz,1H),3.84(dd,J=14.4,5.8Hz,1H),2.89(s,3H),2.53(s,3H). 13 C NMR (100MHz, CDCl3) δ196.5,171.1,151.7,133.5,133.1,133.0,130.8,129.0,128.0,127.9,127. 6,126.7,126.6,126.3,125.7,111.1,94.7,74.4,56.0,49.8,39.8,26.2.HRMS(ESI-MS)m / z[M+H] + Calculate for C 24 H 23 Cl3NO3 + :478.0738,found:478.0727.FT-IR(film):1647,1593,1359,1287,1264,1188,1066,943,821,733cm -1 .

[0127] Embodiment 15

[0128]

[0129] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2d in the same molar amount, wherein the amount of the tertiary amine 2d was 32.6 mg, and the remaining steps and parameters were the same as those of Example 2.

[0130] The target product obtained is denoted as 3o and has the following structural formula:

[0131]

[0132] 3o, white solid (melting point 103-106°C), optical rotation -22.9 (concentration = 1.0, chloroform). 1H NMR (600MHz, CDCl3) δ7.72–7.69(m,4H),7.40–7.36(m,3H),6.72(t,J=8.7Hz,2H),4.64(d,J=12.0Hz,1H),4.59(d,J=12.0Hz,1H),4.04 (dd,J=9.9,5.6Hz,1H),3.82(dd,J=13.1,9.9Hz,1H),3.44(dd,J=13.1,5.4Hz,1H),2.73(s,3H),2.15(s,3H),2.10(s,3H),2.04(s,3H). 13 C NMR (100MHz, CDCl3) δ171.9,146.2,137.0,136.9,134.9,133.9,133.5,133.0,129.9,129.8,128.5,128.0, 127.8,127.5,126.4,126.3,126.2,94.9,74.6,59.9,52.5,41.3,20.8,19.1,19.0.HRMS(ESI-MS)m / z[M+H] + Calculate for C 25 H 27 Cl3NO2:478.1102,found:478.1105.FT-IR(film):2917,1752,1490,1375,1140,854,789,716cm -1 .

[0133] Example 16

[0134]

[0135] The method of Example 2 was followed, except that the tertiary amine 2e was used in the same molar amount to replace the tertiary amine 2a, wherein the amount of the tertiary amine 2e was 34.2 mg, and the remaining steps and parameters were the same as those of Example 2.

[0136] The target product obtained is denoted as 3p and has the following structural formula:

[0137]

[0138] 3p, colorless liquid, optical rotation -62.1 (concentration = 0.9, chloroform). 1H NMR (600MHz, CDCl3) δ7.86–7.80(m,4H),7.74(d,J=9.1Hz,1H),7.71(d,J=8.1Hz,1H),7.65(d,J= 8.3Hz,1H),7.55–7.53(m,1H),7.50–7.48(m,2H),7.38(t,J=7.5Hz,1H),7.24–7.22(m,1H),7.18( dd,J=9.1,2.6Hz,1H),6.93(d,J=2.6Hz,1H),4.79(d,J=12.0Hz,1H),4.68(d,J=12.0Hz,1H),4.4 4(dd,J=14.6,8.1Hz,1H), 4.38(dd,J=8.1,5.6Hz,1H), 3.84(dd,J=14.6,5.7Hz,1H), 2.93(s,3H). 13 C NMR (100MHz, CDCl3) δ171.5,146.4,135.1,133.6,133.6,133.1,129.2,128.8,128.0,127.8,127.7,127.6,127. 1,126.6,126.5,126.4,126.4,126.0,122.5,116.1,106.9,94.9,74.4,56.9,50.1,39.8.HRMS(ESI-MS)m / z[M+H] + Calculate for C 26 H 23 Cl3NO2 + :486.0797,found:486.0789.FT-IR(film):3055,1745,1625,1598,1505,1367,1260,1141,1104,965,818,801,732cm -1 .

[0139] Embodiment 17

[0140]

[0141] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2f in the same molar amount, wherein the amount of the tertiary amine 2f was 27.0 mg, and the remaining steps and parameters were the same as those of Example 2.

[0142] The target product obtained is denoted as 3q and has the following structural formula:

[0143]

[0144] 3q, colorless liquid. Optical rotation -47.1 (concentration = 0.8, chloroform). 1 H NMR (400MHz, CDCl3) δ7.86–7.81(m,4H),7.54–7.47(m,3H),7.28–7.24(m,2H),6.76–6.72(m,3H),4.77(d,J=12.0Hz,1H),4.70(d,J=12.0 Hz,1H),4.30(dd,J=8.2,5.0Hz,1H),4.24(dd,J=14.2,8.2Hz,1H),3.70(dd,J=14.2,5.0Hz,1H),3.39–3.19(m,2H),1.02(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ171.7,147.3,133.7,133.5,133.0,129.6,128.8,128.0,127.8,127.6,1 26.5,126.4,126.0,116.9,113.0,94.8,74.4,54.6,50.4,46.2,12.0.HRMS(ESI-MS)m / z[M+H] + Calculate for C 23 H 23 Cl3NO2 + :450.0789,found:450.0778.FT-IR(film):2966,1748,1595,1502,1370,1346,1266,1136,859,795,749cm -1 .

[0145] Embodiment 18

[0146]

[0147] The method of Example 2 was followed, except that the same molar amount of tertiary amine 2g was used to replace tertiary amine 2a, wherein the amount of tertiary amine 2g was 39.4 mg, and the remaining steps and parameters were the same as in Example 2.

[0148] The target product obtained is denoted as 3r and has the following structural formula:

[0149]

[0150] 3r, colorless liquid, optical rotation -33.4 (concentration = 1.0, chloroform). 1H NMR (600MHz, CDCl3) δ7.84–7.79(m,4H),7.50–7.47(m,3H),7.24–7.21(m,4H),7.17(t,J=7.3Hz,1H),7.09–7.08(m, 2H),6.77–6.74(m,3H),4.67(d,J=11.9Hz,1H),4.60–4.56(m,2H),4.43–4.36(m,3H),3.89(dd,J=12.9,3.4Hz,1H). 13 C NMR (150MHz, CDCl3) δ171.5,147.7,138.6,133.6,133.5,133.0,129.6,128.8,128.7,128.0,127.8,127. 6,126.9,126.6,126.6,126.4,126.0,117.4,113.0,94.8,74.3,55.5,55.3,50.3.HRMS(ESI-MS)m / z[M+H] + Calculate for C 28 H 25 Cl3NO2 + :512.0945,found:512.0938.FT-IR(film):2923,2851,1753,1600,1502,1450,1372,1147,740cm -1 .

[0151] Embodiment 19

[0152]

[0153] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2h in the same molar amount, wherein the amount of the tertiary amine 2h was 29.4 mg, and the remaining steps and parameters were the same as those of Example 2.

[0154] The target product obtained is denoted as 3s and has the following structural formula:

[0155]

[0156] 3s, colorless liquid. Optical rotation -33.5 (concentration = 1.0, chloroform). 1H NMR (400MHz, CDCl3) δ7.78–7.73(m,4H),7.46–7.39(m,3H),7.19–7.15(m,2H),6.69–6.66(m,3H),5.67–5.59(m,1H),5.01–4.95(m,2H),4.6 7(d,J=12.0Hz,1H),4.62(d,J=11.9Hz,1H),4.27(dd,J=8.3,4.9Hz,1H),4.20(dd,J=14.3,8.3Hz,1H),3.88–3.82(m,1H),3.71–3.66(m,2H). 13 C NMR (100MHz, CDCl3) δ171.6,147.6,133.9,133.7,133.6,133.0,129.5,128.8,128.0,127.8,127. 6,126.6,126.4,126.0,117.3,116.4,113.0,94.8,74.4,54.8,54.2,50.5.HRMS(ESI-MS)m / z[M+H] + Calculate for C 24 H 23 Cl3NO 2+ :462.0789,found:462.0795.FT-IR(film):3061,1744,1595,1509,1343,1138,988,865,742cm -1 .

[0157] Embodiment 20

[0158]

[0159] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2i in the same molar amount, wherein the amount of the tertiary amine 2i was 29.8 mg, and the remaining steps and parameters were the same as those of Example 2.

[0160] The target product obtained is denoted as 3t and has the following structural formula:

[0161]

[0162] 3t, colorless liquid, optical rotation -17.4 (concentration = 1.1, chloroform). 1H NMR (600MHz, CDCl3) δ7.86–7.82(m,4H),7.54(dd,J=8.5,1.8Hz,1H),7.51–7.47(m,2H),7.12–7. 10(m,1H),6.97(dd,J=7.4,1.5Hz,1H),6.68(d,J=8.2Hz,1H),6.65–6.62(m,1H),4.79(d,J=11.9H z,1H),4.71(d,J=12.0Hz,1H),4.35(dd,J=8.0,5.9Hz,1H),4.23(dd,J=14.8,8.0Hz,1H),3.67(dd ,J=14.8,5.9Hz,1H),3.29–3.25(m,1H),3.06–3.02(m,1H),2.70–2.67(m,2H),1.81–1.73(m,2H). 13 C NMR (150MHz, CDCl3) δ171.7,144.6,133.8,133.5,133.0,129.6,128.8,128.0,127.8,127.6,127.3,126 .5,126.3,126.1,123.0,116.5,110.7,94.9,74.3,55.6,50.8,49.8,28.1,22.2.HRMS(ESI-MS)m / z[M+H] + Calculate for C 24 H 23 Cl3NO2 + :462.0789,found:462.0786.FT-IR(film):3061,2920,1748,1598,1500,1448,1263,1133,908,732cm -1 .

[0163] Embodiment 21

[0164]

[0165] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2j in the same molar amount, wherein the amount of the tertiary amine 2j was 26.6 mg, and the remaining steps and parameters were the same as those of Example 2.

[0166] The target product obtained is denoted as 3u and has the following structural formula:

[0167]

[0168] 3u, colorless liquid, optical rotation -14.7 (concentration = 1.2, chloroform).1 H NMR (600MHz, CDCl3) δ7.89 (s, 1H), 7.86–7.82 (m, 3H), 7.57 (dd, J = 8.4, 1.8Hz, 1H), 7.50–7.48 ( m,2H),7.10–7.06(m,2H),6.67(t,J=7.3Hz,1H),6.62(d,J=7.9Hz,1H),4.79(d,J=12.0Hz,1H), 4.70(d,J=12.0Hz,1H),4.29(dd,J=9.9,5.4Hz,1H),4.11(dd,J=13.7,9.9Hz,1H),3.51(dd,J=1 5.3,8.7Hz,1H),3.37(dd,J=13.6,5.5Hz,1H),3.32(dd,J=17.3,8.5Hz,1H),2.95–2.92(m,2H). 13 CNMR (150MHz, CDCl3) δ171.4,152.0,133.5,133.4,133.1,129.8,128.8,128.0,127.8,127.5,127.4, 126.6,126.4,126.0,124.7,118.1,107.0,94.9,74.4,54.1,53.7,51.2,28.8.HRMS(ESI-MS)m / z[M+H] + Calculate for C 23 H 21 Cl3NO2 + :448.0632,found:448.0633.FT-IR(film):2931,2848,1748,1603,1485,1372,1266,1139,856,737cm -1 .

[0169] Embodiment 22

[0170]

[0171] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2k in the same molar amount, wherein the amount of the tertiary amine 2k was 24.4 mg, and the remaining steps and parameters were the same as those of Example 2.

[0172] The target product obtained is denoted as 3v and has the following structural formula:

[0173]

[0174] 3v, colorless liquid, optical rotation -18.7 (concentration = 0.8, chloroform).1 H NMR (400MHz, CDCl3) δ8.23–8.21(m,1H),7.84–7.79(m,4H),7.55(dd,J=8.6,1.7Hz,1H),7.49–7.44(m,3H),6.62–6.58(m,1H),6.46(d,J=8.6Hz,1H ),4.75(d,J=12.0,1H),4.71(d,J=11.9,1H),4.55(dd,J=8.3,6.2Hz,1H) ,4.40(dd,J=14.0,8.3Hz,1H),4.02(dd,J=13.9,6.2Hz,1H),2.91(s,3H). 13 C NMR (100MHz, CDCl3) δ171.8,158.3,148.2,137.4,134.0,133.6,133.0,128.6,128.0,127.8,1 27.6,126.4,126.3,126.2,112.3,106.0,94.9,74.4,54.4,50.3,38.2.HRMS(ESI-MS)m / z[M+H] + Calculate for C 21 H 20 Cl3N2O2 + :437.0582,found:437.0582.FT-IR(film):2931,2853,1751,1595,1491,1421,1323,1130,772,714cm -1 .

[0175] Embodiment 23

[0176]

[0177] The method of Example 2 was followed, except that the same molar amount of tertiary amine 21 was used to replace tertiary amine 2a, wherein the amount of tertiary amine 21 was 25.4 mg, and the obtained product was further reduced to the corresponding alcohol product. The remaining steps and parameters were the same as those of Example 2.

[0178] Among them, the target product obtained is recorded as 3w.

[0179] 3w, colorless liquid, optical rotation -7.6 (concentration = 0.8, chloroform). 1H NMR (400MHz, CDCl3) δ7.81–7.77(m,3H),7.60(s,1H),7.48–7.41(m,2H),7.31(dd,J =8.5,1.8Hz,1H),4.10(t,J=10.4Hz,1H),3.93(dt,J=10.5,3.1Hz,1H),3.41–3.35(m ,1H),3.17(t,J=12.2Hz,1H),2.85(dt,J=12.5,2.9Hz,1H),2.59–2.54(m,1H),2.42 (s,3H),1.87–1.80(m,3H),1.68–1.64(m,1H),1.39–1.21(m,5H),1.16–1.08(m,1H). 13 C NMR (100MHz, CDCl3) δ138.4,133.6,132.6,128.3,127.7,127.7,126.4,126.3,125.9,12 5.7,70.6,63.9,61.7,43.4,37.7,28.7,27.9,26.3,26.1,26.0.HRMS(ESI-MS)m / z[M+H] + Calculate for C 22 H 27 Cl3NO2 + :442.1102,found:442.1098.FT-IR(film):3520,2923,2853,1450,1043,896,850,812,737cm -1 .

[0180] Embodiment 24

[0181]

[0182] The method of Example 2 was followed, except that the same molar amount of tertiary amine 2m was used to replace tertiary amine 2a, wherein the amount of tertiary amine 2m was 23.0 mg, and the obtained product was further reduced to the corresponding alcohol product. The remaining steps and parameters were the same as those of Example 2.

[0183] Among them, the target product obtained is recorded as 3x.

[0184] 3x, brown liquid, optical rotation -17.3 (concentration = 0.7, chloroform). 1H NMR (400MHz, CDCl3) δ7.81–7.78(m,3H),7.60(d,J=1.8Hz,1H),7.49–7.42(m,2H),7.32(dd,J=8.4,1.8Hz,1H),4.09(t,J=10.4Hz,1H) ,3.93(dt,J=10.5,3.1Hz,1H),3.40–3.34(m,1H),3.13(t,J=12.3Hz,1H),2.91–2.78(m,3H),2.52–2.44(m,2H),1.15(t,J=7.1Hz,6H). 13 C NMR (100MHz, CDCl3) δ138.3,133.6,132.6,128.4,127.8,127.7,126.3,126.3,125.9,125.8,70.4,61.0,47.5,43.7,11.7.HRMS(ESI-MS)m / z[M+H] + Calculate for C 17 H 24 NO + :258.1852,found:258.1849.FT-IR(film):2974,1468,1387,1121,1162,945,815cm -1 .

[0185] Embodiment 25

[0186]

[0187] The method of Example 2 was followed, except that the tertiary amine 2a was replaced by the tertiary amine 2n in the same molar amount, wherein the amount of the tertiary amine 2nb was 67.4 mg, and the remaining steps and parameters were the same as those of Example 2.

[0188] The target product obtained is denoted as 3y and has the following structural formula:

[0189]

[0190] 3y, brown liquid, diastereoselectivity dr>20:1, optical rotation -17.3 (concentration = 0.7, chloroform). 1H NMR (400MHz, CDCl3) δ7.81–7.77(m,4H),7.49–7.44(m,3H),6.82(d,J=7.9Hz,1H),6.56(s,1H ),6.36(t,J=3.9Hz,2H),6.15(d,J=5.8Hz,2H),5.89(d,J=5.1Hz,2H),5.59(d,J=4.5Hz,1H),4 .91(d,J=12.1Hz,1H),4.71(d,J=12.0Hz,1H),4.18(dd,J=10.4,4.7Hz,1H),4.07(d,J=4.8Hz ,1H),3.52(dd,J=13.0,10.4Hz,1H),3.03–2.93(m,2H),2.89–2.80(m,2H),2.41–2.33(m,1H). 13 C NMR (100MHz, CDCl3) δ171.5,167.2,149.3,147.1,145.9,144.8,140.6,133.6,133.5,133.0,129.4,128.6,128.0,127.8,127.3,126.5,126 .3,126.1,123.9,115.9,113.3,109.7,109.1,108.0,103.4,101.0,95.1,83.9,74.4,64.1,58.3,51.5,46.1,24.4.HRMS(ESI-MS)m / z[M+H] + Calculate for C 34 H 27 Cl3NO8 + :682.0797,found:682.0782.FT-IR(film):2917,2848,1759,1499,1473,1384,1245,1214,1133,1032,965,846cm -1 .

[0191] Comparative Example 1

[0192] The method of Example 1 was followed, except that no iridium porphyrin catalyst [Ir] was added, and the remaining steps and parameters were the same as in Example 1.

[0193] Comparative Example 2

[0194] The method of Example 1 was followed, except that no MS, the remaining steps and parameters are the same as in Example 1.

[0195] The separation yield and enantiomeric excess percentage of the target product obtained in the above example were calculated, and the results are shown in Table 1.

[0196] The enantiomeric excess percentage was determined by chiral high performance liquid chromatography (HPLC).

[0197] Table 1

[0198]

[0199]

[0200] It can be seen from the results in Table 1 that the separation yield and enantiomeric excess percentage of the β-chiral tertiary amine compound prepared by the embodiment of the present invention are both high.

[0201] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A β-chiral tertiary amine compound, characterized in that: The compound has the following structure: Wherein, Ar is a heterocyclic group or an aromatic group, and Ar contains N, O, S, Si, B or halogen, and Ar contains 6 to 18 carbon atoms; R 1 is an alkyl group, an alkene group, a benzyl group, an aryl group or an ester group having 1 to 19 carbon atoms; or R 1 is a heterocyclic group or an aryl group, and said R 1 contains 14 to 18 carbon atoms, and the R 1 Contains N, O, S or halogen; R 2 is an alkyl group, an alkene group, a benzyl group, an aryl group or an ester group having 1 to 19 carbon atoms; or R 2 is a heterocyclic group or an aryl group, and said R 2 contains 14 to 18 carbon atoms, and the R 2 Contains N, O, S or halogen; R 3 is an alkyl group or an ester group containing 1 to 16 carbon atoms; or R 3 is an alkyl group, a heterocyclic group or an aryl group, and in said R 3 contains 4 to 18 carbon atoms, and in the R 3 Contains N, O, S, Si, B or halogen.

2. A method for preparing a β-chiral tertiary amine compound, characterized in that: The method comprises: reacting a diazo compound or a hydrazone compound and a tertiary amine in the presence of an iridium porphyrin catalyst, an additive and a solvent under an argon atmosphere; The iridium porphyrin catalyst has the structural formula described below: Among them, R 4 is an alkyl group containing 1 to 16 carbon atoms; or R 4 is aryl or benzyl, and said R 4 contains 4 to 10 carbon atoms, and the R 4 Contains N, O, S or F; The diazo compound has the following structural formula: The hydrazone compound has the following structural formula: The tertiary amine has the structural formula described below: Among them, in the above structural formula, Ar, R 1 , R 2 , R 3 The definitions are the same as those in claim 1 or 2.

3. The method according to claim 2, wherein: The tertiary amine is the N-methyl natural product bicuculline.

4. The method according to claim 2 or 3, wherein: The additive is selected from Molecular sieves, Molecular sieves, At least one of molecular sieve, anhydrous sodium sulfate, and anhydrous magnesium sulfate.

5. The method according to claim 2 or 3, wherein: The solvent is selected from at least one of toluene, dichloromethane, dichloroethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, chlorobenzene and trifluorotoluene.

6. The method according to claim 2 or 3, wherein: The molar ratio of the diazo compound, the tertiary amine and the iridium porphyrin catalyst is 1:0.5-5:0.01-0.02; And / or, the molar ratio of the hydrazone compound, the tertiary amine and the iridium porphyrin catalyst is 1:0.5-5:0.01-0.

02.

7. The method according to claim 2 or 3, wherein: The amount of the solvent used is 1 mL relative to 0.1 mmol of the diazo compound or hydrazone compound.

8. The method according to claim 2 or 3, wherein: The amount of the additive used is 100 mg relative to 0.1 mmol of the diazo compound or the hydrazone compound.

9. The method according to claim 2 or 3, wherein: The reaction conditions at least meet the following requirements: room temperature and a reaction time of 24 hours.

10. A β-chiral tertiary amine compound prepared by the method according to any one of claims 2 to 9.

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