A β-chiral tertiary amine compound and its preparation method

Abstract

This invention relates to the field of organic chemical synthesis technology, and discloses a β-chiral tertiary amine compound and its preparation method. The compound has the following structure: wherein Ar is a heterocyclic or aryl group, and contains N, O, S, Si, B, or a halogen, and contains 6 to 18 carbon atoms. This invention starts with aryl diazo or aryl hydrazone compounds and tertiary amines, and utilizes the excellent selectivity and enantioselectivity of axially chiral iridium porphyrin catalysis by Carbinberg C(sp...) 3 A series of β-chiral tertiary amine compounds were synthesized by alkylation with aryl tertiary amines without sterically hindered groups at the para position or by unactivated N-methyl groups. Complex natural products and drug molecules containing N-methyl structures can also be well modified to obtain highly diastereoselective target products. For example, the natural product paeonol is also suitable for this method. Its high diastereoselectivity provides a favorable approach for the modification of natural products containing N-methyl tertiary amine structures.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis technology, specifically to a β-chiral tertiary amine compound and its preparation method. Background Technology

[0002] Tertiary amines are ubiquitous in pharmaceuticals, alkaloid natural products, functional materials, and photocatalysts. Direct functionalization of the CH bond near nitrogen in amines offers endless opportunities for the synthesis of tertiary amines. This can be achieved by constructing complex amines from simple amines, or by later modification of complex amines (such as alkaloids).

[0003] To date, the α-alkylation of tertiary amines has seen rapid development. Among these, the C(sp) group in tertiary amines... 3 Metal-catalyzed carbonylation of the α-H bond has become an important strategy for realizing the functionalization of tertiary amines, especially in asymmetric synthesis. However, some challenges remain: (1) The nitrogen lone pair electrons themselves act as nucleophiles on the carbene center, forming N-ylides, making the reaction pathway uncontrollable. (2) Different types of CH bonds, such as primary and secondary carbon bonds, can cause selectivity problems. (3) If aromatic amines are involved, the para-C(sp) of the nitrogen on the phenyl ring... 2 The -H bond is activated, leading to new site selectivity issues. To overcome these challenges, it is essential to develop novel catalysts that can subtly differentiate the energy barriers between different types of CH 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 pioneering study, both amine compounds had to employ an N-boc protection strategy to overcome the selectivity challenges encountered during N-ylide formation.

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

[0006] In addition, Davies’ group disclosed in “Chem. Comm. 2006, 29, 3110” that CH functionalization of methylamines protected by a bulky trimethylsilyl group was achieved under dirhodium catalysis, forming a series of chiral β-amino acid compounds. Summary of the Invention

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

[0008] To achieve the above objectives, the present invention provides a β-chiral tertiary amine compound having the following structure:

[0009] ,

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

[0011] R 1 Alkyl groups containing 1 to 19 carbon atoms;

[0012] R 2 It is a heterocyclic group or an aryl group, and the R 2 It contains 14 to 18 carbon atoms, and the heterocyclic group contains N, O or S;

[0013] R 3 It is an ester group containing 1 to 16 carbon atoms;

[0014] The method for preparing the β-chiral tertiary amine compound includes: reacting a diazo compound or 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 following structural formula:

[0016] ,

[0017] Among them, R 4 It is 4-OTfC6H5;

[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 following structural formula:

[0023] ;

[0024] In the above structural formula, Ar and R 1 R 2 R 3 The definitions are the same as those in the β-chiral tertiary amine compounds;

[0025] The additive is selected from 5Å molecular sieves.

[0026] Preferably, the solvent is selected from at least one of toluene, dichloromethane, dichloroethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, chlorobenzene, and trifluorotoluene.

[0027] In a preferred embodiment, the molar ratio of the diazo compound, the tertiary amine, and the iridium porphyrin catalyst is 1:0.5~5:0.01~0.02.

[0028] 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.

[0029] Preferably, the amount of solvent used is 1 mL relative to 0.1 mmol of diazo compound or hydrazone compound.

[0030] More preferably, the amount of the additive is 100 mg relative to 0.1 mmol of diazo compound or hydrazone compound.

[0031] More preferably, the reaction conditions are: room temperature and a reaction time of 24 hours.

[0032] A 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.

[0033] The β-chiral tertiary amine compound provided by this invention has at least the following beneficial effects:

[0034] (1) The synthesis reaction conditions of the β-chiral tertiary amine compounds provided by the present invention are mild and simple, and the range of applicable substrates is wide.

[0035] (2) The β-chiral tertiary amine compounds provided by the present invention have high yields and are easy to separate and purify. They can be scaled up to the gram scale and are expected to be industrialized.

[0036] (3) The method for synthesizing β-chiral tertiary amine compounds provided by the present invention has high chemoselectivity, high regioselectivity and high enantioselectivity.

[0037] (4) This invention starts with aryl diazo or aryl hydrazone compounds and tertiary amines, and exhibits excellent selectivity and enantioselectivity of axially chiral iridium porphyrin catalysis for Cabinber C(sp) 3 A series of β-chiral tertiary amine compounds were synthesized by alkylation with alkylation of the aryl tertiary amine with sterically hindered groups at the para position or by unactivated N-methyl groups (Scheme 1). Complex natural products and drug molecules containing N-methyl structures can also be well modified to obtain highly diastereoselective target products. For example, the natural product paeonol 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 Implementation

[0038] The endpoints and any values ​​of the ranges disclosed herein 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 the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0039] The present invention will be described in detail below through examples. In the following examples, unless otherwise specified, the raw materials are all commercially available products.

[0040] In the following examples, unless otherwise specified, the room temperature is 25±2℃.

[0041] In the following examples, the synthesis methods and steps of the iridium porphyrin catalyst [Ir] are carried out according to the methods 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−H Alkylation, Angew. Chem. Int. Ed. 2024, 63, e202404329."

[0042] In the following examples, unless otherwise specified, 5Å MS refers to a 5Å molecular sieve with the structural formula Ca. n Na 12-2n [(AlO2) 12 (SiO2) 12]xH2O.

[0043] In the following examples, unless otherwise specified, tertiary amine 2e is an alkaloid and tertiary amine 2n is the N-methyl natural product paeonolide.

[0044] Example 1

[0045]

[0046] Under an 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), and 5 Å MS (100 mg) were added to a reaction tube, followed by 1 mL of dichloromethane. A stir bar was added to keep the reaction under stirring. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the mixture was filtered through a diatomaceous earth-lined sand core funnel and washed with 10 mL of dichloromethane. The filtrate was collected and subjected to reduced pressure to remove the solvent, yielding a crude product. The crude product was then separated by column chromatography to obtain the target product, denoted as 3a.

[0047] 3a, colorless liquid. Optical rotation -31.9 (concentration = 0.8, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.38 – 7.30 (m, 5H), 7.27 – 7.23 (m, 2H), 6.77 – 6.72 (m, 3H), 4.73 (d, J =12.0 Hz, 1H), 4.68 (d, J = 11.9 Hz, 1H), 4.21 (dd, J = 14.1, 8.5 Hz, 1H), 4.15 (dd, J = 8.4, 5.0 Hz, 1H), 3.65 (dd, J = 14.2, 5.0 Hz, 1H), 2.84 (s,3H). 13 C NMR (100 MHz, CDCl3) d 171.6, 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] + calcd for C 18 H19 Cl3NO2 + : 386.0476, found: 386.0469. FT-IR (film): 3027, 1751,1598, 1505, 1453, 1341, 1136, 1029, 988, 801, 746, 691 cm ‐1 .

[0048] Example 2

[0049]

[0050] The procedure was carried out according to Example 1, except that diazo compound 1b was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1b was 34.2 mg, and the remaining steps and parameters were the same as in Example 1.

[0051] The target product obtained, denoted as 3b, has the following structural formula:

[0052] .

[0053] 3b, colorless liquid. Optical rotation -25.3 (concentration = 1.0, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.85 – 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 = 12.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.35 – 4.28(m, 2H), 3.74 (dd, J = 17.8, 9.2 Hz, 1H), 2.84 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 171.5, 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] + calcd for C 22H 21 Cl3NO2 + : 436.0632, found: 436.0626. FT-IR(film): 1751, 1511, 1361, 1245, 1139, 1038, 812, 734 cm ‐1 .

[0054] Example 3

[0055]

[0056] The procedure was carried out according to Example 1, except that diazo compound 1c was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1c was 33.4 mg, and the remaining steps and parameters were the same as in Example 1.

[0057] The target product obtained, denoted as 3c, has the following structural formula:

[0058] .

[0059] 3c, colorless liquid. Optical rotation -45.6 (concentration = 1.2, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.95 – 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, 9.4 Hz, 1H), 2.82 (s, 3H), 2.60 (s, 3H). 13 C NMR (100 MHz, CDCl3) d HRMS (ESI‐MS) m / z [M+H] + calcd for C 20 H 21 Cl3NO3 +: 428.0582, found:428.0573. FT-IR (film): 1751, 1748, 1598, 1505, 1355, 1266, 1144, 960, 746,714 cm ‐1 .

[0060] Example 4

[0061]

[0062] The procedure was carried out according to Example 1, except that diazo compound 1d was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1d was 36.0 mg, and the remaining steps and parameters were the same as in Example 1.

[0063] The target product obtained, denoted as 3d, has the following structural formula:

[0064] .

[0065] 3d, colorless liquid. Optical rotation -24.2 (concentration = 0.9, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.62 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.28 – 7.24 (m, 2H), 6.77(t, J = 7.3 Hz, 1H), 6.73 – 6.70 (m, 2H), 4.74 (d, J = 11.9 Hz, 1H), 4.70 (d, J = 12.0 Hz, 1H), 4.27 – 4.21 (m, 2H), 3.67 (dd, J = 17.7, 9.4 Hz, 1H), 2.83(s, 3H). 13 C NMR (150 MHz, CDCl3) d 170.8, 148.3, 140.2, 130.4 (q, J = 31.5Hz), 129.5, 128.9, 125.9 (q, J = 6.0 Hz), 124.1 (q, J= 270.0 Hz), 117.4,112.7, 94.7, 74.4, 56.7, 49.7, 39.6. 19 F NMR (376 MHz, CDCl3) d -62.6. HRMS(ESI‐MS) m / z [M+H] + calcd 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 .

[0066] Example 5

[0067]

[0068] The procedure was carried out according to Example 1, except that diazo compound 1e was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1e was 35.0 mg, and the remaining steps and parameters were the same as in Example 1.

[0069] The target product obtained, denoted as 3e, has the following structural formula:

[0070] .

[0071] 3e, colorless liquid. Optical rotation -22.7 (concentration = 1.4, chloroform). 1 H NMR (400 MHz, CDCl3) d 8.08 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.7 Hz, 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, 9.6 Hz, 1H), 2.84 (s, 3H). 13CNMR (100 MHz, CDCl3) d 171.1, 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] + calcd for C 20 H 21 Cl3NO4 + : 444.0531, found: 444.0518. FT-IR(film): 2949, 1753, 1719, 1598, 1499, 1433, 1277, 1104, 798, 717 cm ‐1 .

[0072] Example 6

[0073]

[0074] The procedure was carried out according to Example 1, except that diazo compound 1f was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1f was 34.8 mg, and the remaining steps and parameters were the same as in Example 1.

[0075] The target product obtained, denoted as 3f, has the following structural formula:

[0076] .

[0077] 3f, colorless liquid. Optical rotation -24.4 (concentration = 1.2, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.28 – 7.23 (m, 4H), 7.13 – 7.10 (m, 2H), 6.76 – 6.71 (m, 3H), 4.72 (d, J =12.0 Hz, 1H), 4.67 (d, J = 11.9 Hz, 1H), 4.19 (dd, J = 14.3, 8.6 Hz, 1H), 4.11 (dd, J = 8.5, 5.2 Hz, 1H), 3.64 (dd, J= 14.3, 5.2 Hz, 1H), 2.85 (s,3H), 2.46 (d, J = 7.2 Hz, 2H), 1.89 – 1.79 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H). 13 C NMR (100 MHz, CDCl3) d HRMS (ESI‐MS)m / z [M+H] + calcd for C 22 H 27 Cl3NO2 + : 442.1102, found: 442.1103. FT-IR (film):2954, 2028, 1751, 1598, 1499, 1367, 1326, 1139, 795, 711 cm ‐1 .

[0078] Example 7

[0079]

[0080] The procedure was carried out according to Example 1, except that 1g of diazo compound was used instead of diazo compound 1a in the same molar amount, wherein the amount of 1g of diazo compound was 41.6mg, and the remaining steps and parameters were the same as in Example 1.

[0081] The target product obtained, denoted as 3g, has the following structural formula:

[0082] .

[0083] 3g, colorless liquid. Optical rotation -46.7 (concentration = 1.0, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.29 – 7.22 (m, 4H), 7.18 (d, J = 8.2 Hz, 2H), 6.75 – 6.71 (m, 3H), 4.73 (d, J = 12.0 Hz, 1H), 4.63 (d, J= 11.9 Hz, 1H), 4.18 (dd, J = 14.1, 8.8 Hz, 1H), 4.11 (d, J = 8.8, 4.7 Hz, 1H), 3.63 (dd, J = 14.1, 4.7 Hz, 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 = 7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) d 171.8, 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] + calcd for C 27 H 35 Cl3NO2 + : 510.1728, found: 510.1730. FT-IR (film): 2920, 1751,1598, 1505, 1445, 1329, 1139, 798, 714, 694 cm ‐1 .

[0084] Example 8

[0085]

[0086] The procedure was carried out according to Example 1, except that diazo compound 1h was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1h was 38.8 mg, and the remaining steps and parameters were the same as in Example 1.

[0087] The target product obtained, denoted as 3h, has the following structural formula:

[0088] .

[0089] 3h, colorless liquid. Optical rotation -133.9 (concentration = 0.8, chloroform). 1H NMR (400 MHz, CDCl3) d 7.45 – 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, 8.0 Hz, 1H), 4.14 (dd, J = 8.1, 5.6 Hz, 1H), 3.62 (dd, J = 14.1, 5.6 Hz, 1H), 2.80 (s, 3H), 0.25 (s, 9H). 13 C NMR (100 MHz, CDCl3) d HRMS (ESI‐MS) m / z [M+H] + calcd for C 23 H 27 Cl3NO2Si + : 482.0871, found: 482.0872. FT-IR (film): 2957, 2158,1751, 1598, 1499, 1245, 1133, 861, 836, 743, 688 cm ‐1 .

[0090] Example 9

[0091]

[0092] The procedure was carried out according to Example 1, except that diazo compound 1i was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1i was 41.8 mg, and the remaining steps and parameters were the same as in Example 1.

[0093] The target product obtained, denoted as 3i, has the following structural formula:

[0094]

[0095] 3i, colorless liquid. Optical rotation -22.9 (concentration = 1.0, chloroform). 11H NMR (600 MHz, CDCl3) d 7.79 (d, J J = 7.9 Hz, 2H), 7.73 – 7.71 (m, 1H), 7.51 (d, J J = 8.0 Hz, 1H), 7.38(d, J J = 7.9 Hz, 1H), 7.26 (d, J J = 8.0 Hz, 1H), 6.76 – 6.71 (m, 3H), 4.73 (d, J J = 11.9 Hz, 1H), 4.67 (d, J J = 12.0 Hz, 1H), 4.22 (dd, J J = 14.5, 8.3 Hz, 1H),4.17 (dd, J J = 8.4, 5.6 Hz, 1H), 3.64 (dd, J J = 14.5, 5.5 Hz, 1H), 2.82 (s,3H), 1.35 (s, 18H). 13 13C NMR (150 MHz, CDCl3) d 171.3, 148.4, 139.3, 137.1,136.4, 135.5, 129.5, 127.8, 117.1, 112.6, 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] + calcd for C 24 H 30 BCl3NO4 + :512.1328, found: 512.1325. FT‐IR (film): 2978, 2920, 1751, 1583, 1505, 1355,1139, 1087, 960, 856, 717 cm ‐1 .

[0096] Example 10

[0097]

[0098] The procedure was carried out according to Example 1, except that diazo compound 1j was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1j was 47.6 mg, and the remaining steps and parameters were the same as in Example 1.

[0099] The target product obtained, denoted as 3j, has the following structural formula:

[0100]

[0101] 3j, white solid (melting point 104–106 °C). Optical rotation -31.5 (concentration = 1.0, chloroform). 1 H NMR (600MHz, CDCl3) d 8.29 (s, 1H), 8.13 (s, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.57 (dd, J = 8.5, 1.9 Hz, 1H), 7.52 (d, J = 8.3 Hz, 1H),7.32 – 7.29 (m, 2H), 6.81 – 6.78 (m, 3H), 4.80 (d, J = 11.9 Hz, 1H), 4.73 (d, J = 11.9 Hz, 1H), 4.37 – 4.32 (m, 2H), 3.76 (dd, J = 20.1, 8.5 Hz, 1H), 2.87(s, 3H). 13 C NMR (150 MHz, CDCl3) d 171.4, 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] + calcd forC 24 H 20 BrCl3NO2S +: 569.9458, found: 569.9442. FT-IR (film): 1748, 1598, 1505,1424, 1263, 1141, 1069, 1017, 795, 737 cm ‐1 .

[0102] Example 11

[0103]

[0104] The procedure was carried out according to Example 1, except that diazo compound 1k was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1k was 45.7 mg, and the remaining steps and parameters were the same as in Example 1.

[0105] The target product obtained, denoted as 3k, has the following structural formula:

[0106] .

[0107] 3K, colorless liquid. Optical rotation -57.7 (concentration = 0.9, chloroform). 1 H NMR (600 MHz, CDCl3) d 8.21 (s, 1H) 8.18 (d, J = 8.0 Hz, 1H), 7.65 – 7.63 (m, 2H), 7.59 – 7.58 (m,2H), 7.50 (t, J = 7.4 Hz, 1H), 7.46 – 7.41 (m, 4H), 7.35 – 7.31 (m, 3H), 6.83– 6.79 (m, 3H), 4.84 (d, J = 12.0 Hz, 1H), 4.72 (d, J = 12.0 Hz, 1H), 4.41 –4.36 (m, 2H), 3.80 (dd, J = 18.8, 9.4 Hz, 1H), 2.92 (s, 3H). 13 C NMR (150 MHz, CDCl3) d172.1, 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] + calcd forC 30 H 26 Cl3N2O2 + : 551.1054, found: 551.1053. FT-IR (film): 1748, 1598, 1499, 1450,1266, 1231, 1130, 732, 697 cm ‐1 .

[0108] Example 12

[0109]

[0110] The procedure was carried out according to Example 1, except that diazo compound 1l was used instead of diazo compound 1a in the same molar amount, wherein the amount of diazo compound 1l was 34.3 mg, and the remaining steps and parameters were the same as in Example 1.

[0111] The target product obtained, denoted as 3l, has the following structural formula:

[0112] .

[0113] 3L, colorless liquid. Optical rotation -35.1 (concentration = 1.0, chloroform). 1 H NMR (600 MHz, CDCl3) d 8.94 (d, J = 4.5 Hz, 1H), 8.13 (t, J = 9.6 Hz, 2H), 7.81 – 7.76 (m, 2H), 7.43(dd, J = 8.2, 4.2 Hz, 1H), 7.29 – 7.26 (m, 2H), 6.79 – 6.75 (m, 3H), 4.76 (d, J = 11.9 Hz, 1H), 4.72 (d, J= 12.0 Hz, 1H), 4.37 (dd, J = 14.4, 5.4 Hz, 1H), 4.33 (dd, J = 14.3, 8.2 Hz, 1H), 3.77 (dd, J = 14.2, 5.5 Hz, 1H), 2.83 (s,3H). 13 C NMR (150 MHz, CDCl3) d 171.2, 151.0, 148.4, 148.0, 136.1, 134.6,130.4, 129.7, 129.5, 128.4, 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] + calcd for C 21 H 20 Cl3N2O2 + : 437.0585, found:437.0552. FT-IR (film): 2926, 1753, 1600, 1502, 1370, 1260, 1144, 1032, 795,737, 691 cm ‐1 .

[0114] Example 13

[0115]

[0116] The procedure was carried out according to Example 2, except that tertiary amine 2b was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2b was 39.8 mg, and the remaining steps and parameters were the same as in Example 2.

[0117] The target product obtained, denoted as 3m, has the following structural formula:

[0118]

[0119] 3m, colorless liquid, the reaction can be scaled up to the gram scale. Optical rotation -83.1 (concentration = 1.0, chloroform). 1 HNMR (600 MHz, CDCl3) d7.85 – 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 = 11.9 Hz, 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 C NMR (150MHz, CDCl3) d 171.3, 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] + calcd for C 22 H 20 BrCl3NO2 + : 513.9738, found: 513.9736. FT-IR(film): 3059, 1748, 1589, 1495, 1371, 1136, 859, 808, 725 cm ‐1 .

[0120] Example 14

[0121]

[0122] The procedure was carried out according to Example 2, except that tertiary amine 2c was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2c was 32.6 mg, and the remaining steps and parameters were the same as in Example 2.

[0123] The target product obtained, denoted as 3n, has the following structural formula:

[0124]

[0125] 3n, white solid (melting point 103–106 °C). Optical rotation -120.6 (concentration = 0.8, chloroform). 1 H NMR (400 MHz, CDCl3) d7.91 – 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, 1H), 4.38 (dd, J = 14.4, 7.9Hz, 1H), 4.31 (dd, J = 8.0, 5.8 Hz, 1H), 3.84 (dd, J = 14.4, 5.8 Hz, 1H), 2.89 (s, 3H), 2.53 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 196.5, 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] + calcd for C 24 H 23 Cl3NO3 + : 478.0738, found: 478.0727. FT-IR (film): 1647, 1593,1359, 1287, 1264, 1188, 1066, 943, 821, 733 cm ‐1 .

[0126] Example 15

[0127]

[0128] The procedure was carried out according to Example 2, except that tertiary amine 2a was replaced with the same molar amount of tertiary amine 2d, wherein the amount of tertiary amine 2d was 32.6 mg, and the remaining steps and parameters were the same as in Example 2.

[0129] The target product obtained, denoted as 3o, has the following structural formula:

[0130] .

[0131] 3°C, white solid (melting point 103–106 °C). Optical rotation -22.9 (concentration = 1.0, chloroform). 1 H NMR (600MHz, CDCl3) d 7.72 – 7.69 (m, 4H), 7.40 – 7.36 (m, 3H), 6.72 (t, J = 8.7 Hz, 2H), 4.64 (d, J = 12.0 Hz, 1H), 4.59 (d, J = 12.0 Hz, 1H), 4.04 (dd, J = 9.9, 5.6 Hz, 1H), 3.82 (dd, J = 13.1, 9.9 Hz, 1H), 3.44 (dd, J = 13.1, 5.4 Hz,1H), 2.73 (s, 3H), 2.15 (s, 3H), 2.10 (s, 3H), 2.04 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 171.9, 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] + calcd for C 25 H 27 Cl3NO2:478.1102, found: 478.1105. FT-IR (film): 2917, 1752, 1490, 1375, 1140, 854,789, 716 cm ‐1 .

[0132] Example 16

[0133]

[0134] The procedure was carried out according to Example 2, except that tertiary amine 2e was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2e was 34.2 mg, and the remaining steps and parameters were the same as in Example 2.

[0135] The target product obtained, denoted as 3p, has the following structural formula:

[0136] .

[0137] 3p, colorless liquid. Optical rotation -62.1 (concentration = 0.9, chloroform). 1 H NMR (600 MHz, CDCl3) d 7.86 – 7.80 (m, 4H), 7.74 (d, J = 9.1 Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.65(d, J = 8.3 Hz, 1H), 7.55 – 7.53 (m, 1H), 7.50 – 7.48 (m, 2H), 7.38 (t, J =7.5 Hz, 1H), 7.24 – 7.22 (m, 1H), 7.18 (dd, J = 9.1, 2.6 Hz, 1H), 6.93 (d, J = 2.6 Hz, 1H), 4.79 (d, J = 12.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.44(dd, J = 14.6, 8.1 Hz, 1H), 4.38 (dd, J = 8.1, 5.6 Hz, 1H), 3.84 (dd, J =14.6, 5.7 Hz, 1H), 2.93 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 171.5, 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] + calcd for C 26 H23 Cl3NO2 + : 486.0797, found:486.0789. FT-IR (film): 3055, 1745, 1625, 1598, 1505, 1367, 1260, 1141, 1104,965, 818, 801, 732 cm ‐1 .

[0138] Example 17

[0139]

[0140] The procedure was carried out according to Example 2, except that tertiary amine 2f was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2f was 27.0 mg, and the remaining steps and parameters were the same as in Example 2.

[0141] The target product obtained, denoted as 3q, has the following structural formula:

[0142] .

[0143] 3q, colorless liquid. Optical rotation -47.1 (concentration = 0.8, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.86 – 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 = 12.0 Hz, 1H), 4.70 (d, J = 12.0 Hz, 1H), 4.30 (dd, J =8.2, 5.0 Hz, 1H), 4.24 (dd, J = 14.2, 8.2 Hz, 1H), 3.70 (dd, J = 14.2, 5.0Hz, 1H), 3.39 – 3.19 (m, 2H), 1.02 (t, J = 7.0 Hz, 3H). 13 C NMR (100 MHz, CDCl3) d171.7, 147.3, 133.7, 133.5, 133.0, 129.6, 128.8, 128.0, 127.8,127.6, 126.5, 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] + calcd for C 23 H 23 Cl3NO2 + : 450.0789, found: 450.0778. FT-IR (film): 2966, 1748, 1595, 1502, 1370, 1346, 1266, 1136, 859, 795, 749 cm ‐1 .

[0144] Example 18

[0145]

[0146] The procedure was carried out according to Example 2, except that tertiary amine 2g was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2g was 39.4 mg, and the remaining steps and parameters were the same as in Example 2.

[0147] The target product obtained, denoted as 3r, has the following structural formula:

[0148] .

[0149] 3r, colorless liquid. Optical rotation -33.4 (concentration = 1.0, chloroform). 1 H NMR (600 MHz, CDCl3) d 7.84 – 7.79 (m, 4H), 7.50 – 7.47 (m, 3H), 7.24 – 7.21 (m, 4H), 7.17 (t, J =7.3 Hz, 1H), 7.09 – 7.08 (m, 2H), 6.77 – 6.74 (m, 3H), 4.67 (d, J = 11.9 Hz,1H), 4.60 – 4.56 (m, 2H), 4.43 – 4.36 (m, 3H), 3.89 (dd, J = 12.9, 3.4 Hz, 1H). 13C NMR (150 MHz, CDCl3) d 171.5, 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] + calcdfor C 28 H 25 Cl3NO2 + : 512.0945, found: 512.0938. FT-IR (film): 2923, 2851, 1753,1600, 1502, 1450, 1372, 1147, 740 cm ‐1 .

[0150] Example 19

[0151]

[0152] The procedure was carried out according to Example 2, except that tertiary amine 2h was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2h was 29.4 mg, and the remaining steps and parameters were the same as in Example 2.

[0153] The target product obtained, denoted as 3s, has the following structural formula:

[0154] .

[0155] 3s, colorless liquid. Optical rotation -33.5 (concentration = 1.0, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.78 – 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), 4.67 (d, J = 12.0 Hz, 1H), 4.62 (d, J = 11.9 Hz, 1H), 4.27 (dd, J= 8.3, 4.9 Hz, 1H), 4.20 (dd, J =14.3, 8.3 Hz, 1H), 3.88 – 3.82 (m, 1H), 3.71 – 3.66 (m, 2H). 13 C NMR (100 MHz, CDCl3) d 171.6, 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] + calcd for C 24 H 23 Cl3NO 2+ : 462.0789, found:462.0795. FT-IR (film): 3061, 1744, 1595, 1509, 1343, 1138, 988, 865, 742 cm ‐1 .

[0156] Example 20

[0157]

[0158] The procedure was carried out according to Example 2, except that tertiary amine 2i was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2i was 29.8 mg, and the remaining steps and parameters were the same as in Example 2.

[0159] The target product obtained, denoted as 3t, has the following structural formula:

[0160] .

[0161] 3t, colorless liquid. Optical rotation -17.4 (concentration = 1.1, chloroform). 1 H NMR (600 MHz, CDCl3) d 7.86 – 7.82 (m, 4H), 7.54 (dd, J = 8.5, 1.8 Hz, 1H), 7.51 – 7.47 (m, 2H), 7.12 – 7.10 (m, 1H), 6.97 (dd, J= 7.4, 1.5 Hz, 1H), 6.68 (d, J = 8.2 Hz,1H), 6.65 – 6.62 (m, 1H), 4.79 (d, J = 11.9 Hz, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.35 (dd, J = 8.0, 5.9 Hz, 1H), 4.23 (dd, J = 14.8, 8.0 Hz, 1H), 3.67(dd, J = 14.8, 5.9 Hz, 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 (150 MHz, CDCl3) d 171.7, 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] + calcd for C 24 H 23 Cl3NO2 + : 462.0789, found: 462.0786. FT-IR(film): 3061, 2920, 1748, 1598, 1500, 1448, 1263, 1133, 908, 732 cm ‐1 .

[0162] Example 21

[0163]

[0164] The procedure was carried out according to Example 2, except that tertiary amine 2j was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2j was 26.6 mg, and the remaining steps and parameters were the same as in Example 2.

[0165] The target product obtained, denoted as 3u, has the following structural formula:

[0166] .

[0167] 3u, colorless liquid. Optical rotation -14.7 (concentration = 1.2, chloroform). 1 H NMR (600 MHz, CDCl3) d 7.89 (s, 1H), 7.86 – 7.82 (m, 3H), 7.57 (dd, J = 8.4, 1.8 Hz, 1H), 7.50 –7.48 (m, 2H), 7.10 – 7.06 (m, 2H), 6.67 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 7.9Hz, 1H), 4.79 (d, J = 12.0 Hz, 1H), 4.70 (d, J = 12.0 Hz, 1H), 4.29 (dd, J =9.9, 5.4 Hz, 1H), 4.11 (dd, J = 13.7, 9.9 Hz, 1H), 3.51 (dd, J = 15.3, 8.7Hz, 1H), 3.37 (dd, J = 13.6, 5.5 Hz, 1H), 3.32 (dd, J = 17.3, 8.5 Hz, 1H),2.95 – 2.92 (m, 2H). 13 C NMR (150 MHz, CDCl3) d 171.4, 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] + calcd for C 23 H 21 Cl3NO2 +: 448.0632, found: 448.0633. FT-IR (film): 2931, 2848,1748, 1603, 1485, 1372, 1266, 1139, 856, 737 cm ‐1 .

[0168] Example 22

[0169]

[0170] The procedure was carried out according to Example 2, except that tertiary amine 2k was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2k was 24.4 mg, and the remaining steps and parameters were the same as in Example 2.

[0171] The target product obtained, denoted as 3v, has the following structural formula:

[0172] .

[0173] 3V, colorless liquid. Optical rotation -18.7 (concentration = 0.8, chloroform). 1 H NMR (400 MHz, CDCl3) d 8.23 – 8.21 (m, 1H), 7.84 – 7.79 (m, 4H), 7.55 (dd, J = 8.6, 1.7 Hz, 1H),7.49 – 7.44 (m, 3H), 6.62 – 6.58 (m, 1H), 6.46 (d, J = 8.6 Hz, 1H), 4.75 (d, J = 12.0, 1H), 4.71 (d, J = 11.9, 1H), 4.55 (dd, J = 8.3, 6.2 Hz, 1H), 4.40(dd, J = 14.0, 8.3 Hz, 1H), 4.02 (dd, J = 13.9, 6.2 Hz, 1H), 2.91 (s, 3H). 13 CNMR (100 MHz, CDCl3) d171.8, 158.3, 148.2, 137.4, 134.0, 133.6, 133.0,128.6, 128.0, 127.8, 127.6, 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] + calcd for C 21 H 20 Cl3N2O2 + : 437.0582,found: 437.0582. FT-IR (film): 2931, 2853, 1751, 1595, 1491, 1421, 1323,1130, 772, 714 cm ‐1 .

[0174] Example 23

[0175]

[0176] The procedure was carried out according to Example 2, except that tertiary amine 2a was replaced with the same molar amount of tertiary amine 2l, wherein the amount of tertiary amine 2l was 25.4 mg. The resulting product was further reduced to the corresponding alcohol product, and the remaining steps and parameters were the same as in Example 2.

[0177] The target product obtained is denoted as 3w.

[0178] 3w, colorless liquid. Optical rotation -7.6 (concentration = 0.8, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.81 – 7.77 (m, 3H), 7.60 (s, 1H), 7.48 – 7.41 (m, 2H), 7.31 (dd, J = 8.5, 1.8 Hz, 1H), 4.10 (t, J = 10.4 Hz, 1H), 3.93 (dt, J = 10.5, 3.1 Hz, 1H), 3.41– 3.35 (m, 1H), 3.17 (t, J = 12.2 Hz, 1H), 2.85 (dt, J= 12.5, 2.9 Hz, 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 (100 MHz, CDCl3) d 138.4,133.6, 132.6, 128.3, 127.7, 127.7, 126.4, 126.3, 125.9, 125.7, 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] + calcd for C 22 H 27 Cl3NO2 + : 442.1102, found: 442.1098. FT-IR (film): 3520, 2923, 2853, 1450, 1043, 896, 850, 812, 737 cm ‐1 Example 24

[0179]

[0180] The procedure was carried out according to Example 2, except that tertiary amine 2a was replaced with the same molar amount of tertiary amine 2m, wherein the amount of tertiary amine 2m was 23.0 mg. The resulting product was further reduced to the corresponding alcohol product, and the remaining steps and parameters were the same as in Example 2.

[0181] The target product obtained is denoted as 3x.

[0182] 3x, brown liquid. Optical rotation -17.3 (concentration = 0.7, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.81 – 7.78 (m, 3H), 7.60 (d, J = 1.8 Hz, 1H), 7.49 – 7.42 (m, 2H), 7.32 (dd, J = 8.4, 1.8 Hz, 1H), 4.09 (t, J = 10.4 Hz, 1H), 3.93 (dt, J= 10.5, 3.1 Hz,1H), 3.40 – 3.34 (m, 1H), 3.13 (t, J = 12.3 Hz, 1H), 2.91 – 2.78 (m, 3H), 2.52 – 2.44 (m, 2H), 1.15 (t, J = 7.1 Hz, 6H). 13 C NMR (100 MHz, CDCl3) d 138.3, 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] + calcd for C 17 H 24 NO + : 258.1852, found: 258.1849. FT-IR (film): 2974, 1468, 1387, 1121, 1162, 945, 815 cm ‐1 .

[0183] Example 25

[0184]

[0185] The procedure was carried out according to Example 2, except that tertiary amine 2n was used instead of tertiary amine 2a in the same molar amount, wherein the amount of tertiary amine 2nb was 67.4 mg, and the remaining steps and parameters were the same as in Example 2.

[0186] The target product obtained, denoted as 3y, has the following structural formula:

[0187] .

[0188] 3y, brown liquid. Diastereoselectivity dr > 20:1, optical rotation -17.3 (concentration = 0.7, chloroform). 1 H NMR (400 MHz, CDCl3) d 7.81 – 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= 3.9 Hz, 2H), 6.15 (d, J = 5.8 Hz, 2H), 5.89 (d, J = 5.1 Hz, 2H), 5.59 (d, J = 4.5 Hz, 1H), 4.91 (d, J = 12.1 Hz, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.18 (dd, J = 10.4, 4.7 Hz, 1H), 4.07 (d, J =4.8 Hz, 1H), 3.52 (dd, J = 13.0, 10.4 Hz, 1H), 3.03 – 2.93 (m, 2H), 2.89 –2.80 (m, 2H), 2.41 – 2.33 (m, 1H). 13 C NMR (100 MHz, CDCl3) d 171.5, 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, HRMS (ESI‐MS)m / z [M+H] + calcd 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, 846 cm ‐1 .

[0189] Comparative Example 1

[0190] The procedure was carried out according to Example 1, except that no iridium porphyrin catalyst [Ir] was added, and the remaining steps and parameters were the same as in Example 1.

[0191] Comparative Example 2

[0192] The procedure was carried out according to Example 1, except that 5 Å MS was not added, and the remaining steps and parameters were the same as in Example 1.

[0193] The separation yield and enantiomeric excess percentage of the target product obtained in the above embodiments were calculated, and the results are shown in Table 1.

[0194] The enantiomeric excess percentage was determined by chiral high-performance liquid chromatography (HPLC).

[0195] Table 1

[0196]

[0197] As can be seen from the results in Table 1, the product prepared using the embodiments of the present invention... β - The separation yield and enantiomeric excess percentage of chiral tertiary amine compounds were both high.

[0198] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A process for the preparation of a β-chiral tertiary amine compound, characterized in that, The beta-chiral tertiary amine compound has a structure as shown in the following formula: ， wherein Ar is a heterocyclic group or an aryl group, and contains N, O, S, Si or B in the heterocyclic group, and contains 6-18 carbon atoms in the Ar; R 1 R is alkyl containing 1 to 19 carbon atoms; R 2 is heterocyclyl or aryl, and said R 2 contains 14 to 18 carbon atoms, and N, O or S in the heterocyclyl group; R 3 R is an ester group containing 1 to 16 carbon atoms; The method for preparing the beta-chiral tertiary amine compound comprises: reacting a diazo compound or a hydrazone compound, 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 a structure as shown in the following formula: ， wherein R 4 is 4-OTfC6H5; The diazo compound has a structure as shown in the following formula: ； The hydrazone compound has a structure as shown in the following formula: ； The tertiary amine has a structure as shown in the following formula: ； wherein, in the above structural formula, Ar, R 1 , R 2 , R 3 are defined respectively the same as in the β-chiral tertiary amine compound. The additive is a 5A molecular sieve.

2. The method of claim 1, wherein, The solvent is selected from at least one of toluene, dichloromethane, dichloroethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, chlorobenzene, and trifluorotoluene.

3. The method of claim 1, 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. The molar ratio of the hydrazone compound, the tertiary amine, and the iridium porphyrin catalyst is 1:0.5-5:0.01-0.

02.

4. The method of claim 1, wherein, The amount of the solvent is 1 mL relative to 0.1 mmol of the diazo compound or the hydrazone compound.

5. The method of claim 1, wherein, The amount of the additive is 100 mg relative to 0.1 mmol of the diazo compound or the hydrazone compound.

6. The method of claim 1, wherein, The reaction condition is room temperature, and the reaction time is 24 h.

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