Achirality and chirality aza-biaryl-oxazoline type ligand and preparation method thereof

Abstract

The invention relates to achiral and chiral aza-biaryl-oxazoline type ligands and a preparation method thereof, and belongs to the technical field of organic chemistry. The preparation method comprises an aromatic cyanidation reaction and a condensation reaction, according to the present invention, the multi-site substituted achiral and chiral aza-biaryl nitrile compound can be efficiently prepared, and the rapid construction of the aza-biaryl-oxazoline type ligand can be further achieved through the one-step reaction. The ligand belongs to a novel pyridine-oxazoline type ligand, the preparation method has the advantages of greenness, environmental protection, high efficiency, rapidness, low cost and the like, and the variety of N, N-bidentate ligand libraries is expanded.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic chemistry, and particularly relates to a kind of achiral and chiral nitrogen hetero-arylcyanide-oxazoline type ligand and its preparation method. BACKGROUND

[0002] Ligands containing chiral oxazolines have become one of the most successful, versatile and most commonly used ligand classes in the field of asymmetric catalysis due to their easy synthesis, modular design and wide application in various metal-catalyzed transformations. Most of these ligands are prepared from readily available chiral β-amino alcohols through simple and efficient synthetic routes. Their stereogenic center is located at the alpha position of the oxazoline nitrogen donor, which can be close to the metal active site, thereby directly regulating the enantioselectivity of the reaction. Among the family of chiral oxazoline ligands, the application of chiral N,N-bidentate ligands is particularly widespread. The pyridine-oxazoline type ligand combines the rigid planar structure of pyridine and the chiral induction ability of oxazoline, exhibits unique electronic properties and spatial structure, and can efficiently coordinate with various metal centers, thereby showing excellent performance in asymmetric transition metal-catalyzed reactions.

[0003] The first application of pyridine-oxazoline type ligand can be traced back to 1986. However, in the subsequent long period of time, its unique properties have not been fully explored, and only a few asymmetric reactions can achieve good results using this type of ligand. In recent years, with the in-depth study of the properties of pyridine-oxazoline type ligand, its application in asymmetric catalysis has rapidly expanded, especially in some new and efficient asymmetric catalytic methods. Recent studies have shown that the use of pyridine-oxazoline type ligand has successfully achieved a variety of challenging asymmetric reactions, fully demonstrating its broad application potential in future new catalytic methods. However, due to the difficulty in obtaining the structural skeleton, especially the axial chiral skeleton, and the high cost of synthesis, the development of new pyridine-oxazoline type ligand is still a significant and challenging task. Compared to the traditional way of obtaining high enantioselective chiral ligand skeleton precursor by chemical resolution, the present application uses transition metal-catalyzed method to construct achiral and chiral nitrogen hetero-arylcyanide compounds, and then only one synthesis step is needed to prepare achiral and chiral nitrogen hetero-arylcyanide-oxazoline type ligand with high yield. The preparation method is novel and easy to operate, and the synthetic route is efficient and short. SUMMARY

[0004] The purpose of the present application is to solve the problems of the prior art, and to provide a kind of achiral and chiral nitrogen hetero-arylcyanide-oxazoline type ligand and its preparation method.

[0005] To achieve the above-mentioned purpose, the technical solutions adopted by the present application are as follows: The achiral and chiral nitrogen hetero-arylcyanide-oxazoline type ligand has the structural formula as shown in formula (I): , formula (I); In formula (I), the carbon atom marked with * is a central chiral center; Het is a heteroaromatic group; In formula (I), according to whether the nitrogen-linked aryl structural unit contains an axial chiral center, it is divided into two structures of formula (II) and formula (III): , formula (II); In formula (II), the carbon atom marked with * is an axial chiral and central chiral center; Het is a heteroaromatic group, including benzo[h]quinoline, pyridine, 3-methylpyridine, phenanthridine, pyrimidine, 1H-pyrazole; R 1 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, benzyl, cyclohexyl or phenyl; R 2 is hydrogen or phenyl; or, R 1 and R 2 together constitute a 1,2-indane group; , formula (III); In formula (III), the carbon atom marked with * is an axial chiral and central chiral center; R 1 is hydrogen, ethyl, isopropyl, tert-butyl or benzyl; R 2 is hydrogen.

[0006] The present application provides a preparation method of the above-mentioned achiral and chiral nitrogen-linked aryl-oxazoline type ligand, which comprises the following steps: Step (1), aromatic cyanation reaction: under an argon atmosphere, a nitrogen-linked aryl triflate compound shown in formula (IV) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition of a palladium catalyst and an achiral ligand as a catalyst, potassium carbonate as a base, to obtain an achiral nitrogen-linked aryl nitrile compound shown in formula (V); Step (2), condensation reaction: under an argon atmosphere, the achiral nitrogen-linked aryl nitrile compound shown in formula (V) is reacted with an amino alcohol compound shown in formula (VI) under the condition of zinc chloride as a Lewis acid, to obtain a nitrogen-linked aryl-oxazoline type ligand shown in formula (II); The reaction formula is as follows: Further, preferably, in step (1), the palladium catalyst is palladium acetate; the achiral ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; and potassium carbonate is used as the base.

[0007] Further, preferably, in step (1), the molar ratio of the azabicyclic aryl triflate compound, potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the achiral ligand, and potassium carbonate is 20:8-10:1:1-1.2:2.5-5; the reaction temperature is 80-85°C; and the reaction time is 12-14 hours.

[0008] Further, preferably, in step (1), the reaction solvent is a mixed solvent of water and tetrahydrofuran, and the volume ratio is 1:1; and the concentration of the azabicyclic aryl triflate compound is 0.1 mol / L.

[0009] Further, preferably, in step (2), the molar ratio of the achiral azabicyclic aryl nitrile compound of formula (V), the amino alcohol compound of formula (VI), and zinc chloride is 1:1.5-2:2-4.

[0010] The solvent used in the condensation reaction is chlorobenzene; the reaction temperature is 120-140°C; and the reaction time is 40-48 hours.

[0011] The present application provides a preparation method of the achiral and chiral azabicyclic aryl-oxazoline ligand, which comprises the following steps: Step (A), asymmetric aromatic cyanation reaction: under an argon atmosphere, the azabicyclic aryl triflate compound or perfluorobutanesulfonate compound of formula (VII) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition of a palladium catalyst and a chiral ligand as a catalyst, and potassium carbonate as a base, to obtain a chiral azabicyclic aryl nitrile compound of formula (VIII); Step (B), condensation reaction: under an argon atmosphere, the chiral azabicyclic aryl nitrile compound of formula (VIII) is reacted with the amino alcohol compound of formula (VI) under the condition of zinc chloride as a Lewis acid, to obtain the azabicyclic aryl-oxazoline ligand of formula (III); The reaction formula is as follows: In formula (VII), LG is a leaving group, including triflate and perfluorobutanesulfonate.

[0012] Further, preferably, in step (A), the palladium catalyst is palladium acetate; the chiral ligand is (R)-(5,5'-dichloro-6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine) or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; and potassium carbonate is used as the base.

[0013] Further, preferably, in step (A), the molar ratio of the azafused aryl triflate compound or the nonaflate compound, potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the chiral ligand, and potassium carbonate is 20:8-10:1:1-1.2:2.5-5; the reaction temperature is 75-80°C; and the reaction time is 12-16 hours. The reaction solvent is a mixture of water and isopropyl alcohol at a volume ratio of 1:1; and the concentration of the azafused aryl triflate compound or the nonaflate compound is 0.05 mol / L.

[0014] Further, preferably, in step (B), the molar ratio of the chiral azafused aryl nitrile compound of formula (VIII), the amino alcohol compound of formula (VI), and zinc chloride is 1:1.5-2:2-4. The condensation reaction is carried out in chlorobenzene; the reaction temperature is 120-140°C; and the reaction time is 40-48 hours.

[0015] The present application can efficiently prepare multi-site substituted achiral and chiral azafused aryl nitrile compounds, and further realize rapid construction of azafused aryl-oxazoline type ligands through one-step reaction. The ligands belong to novel pyridine-oxazoline type ligands, and the preparation method has advantages of green environmental protection, high efficiency, rapidness, and low cost, and expands the types of N,N-bidentate ligand library.

[0016] Compared with the prior art, the present application has the following beneficial effects: The preparation method of the present application uses non-toxic cyan reagent to efficiently synthesize achiral and chiral azafused aryl-oxazoline type ligands, exhibits excellent substrate universality, and can be compatible with various substituents and azaheteroaromatic ring structures. Further, the preparation method constructs multi-type azafused aryl-oxazoline type ligands containing single carbon-central chirality and carbon-central chirality combined with axial chirality through one-step reaction, has high reaction yield, and most importantly, fills the blank of pyridine-oxazoline type ligands with axial chirality skeleton. The preparation method is green, environmentally friendly, efficient, rapid, and low in cost, and greatly enriches the types of pyridine-oxazoline type ligand library. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 is the H NMR spectrum of compound 24 1 is the H NMR spectrum of compound 24 Figure 2 is the H NMR spectrum of compound 24 13 is the H NMR spectrum of compound 24 Figure 3 is the H NMR spectrum of compound 42 1 is the H NMR spectrum of compound 42 Figure 4 is the H NMR spectrum of compound 42 13H NMR spectrum; Figure 5 HPLC spectrum of compound 42; Figure 6 HPLC spectrum of compound (1R, 4S)-61 1 H NMR spectrum; Figure 7 HPLC spectrum of compound (1R, 4S)-61 13 C NMR spectrum. DETAILED DESCRIPTION

[0018] The present application will be further described in conjunction with the following examples.

[0019] Those skilled in the art will appreciate that the following examples are included for illustrative purposes only and should not be viewed as limiting on the scope of the present application. If a specific technique or condition is not mentioned in the examples, it is performed according to the technique or condition described in the literature in the art or according to the product manual. If the manufacturer of the materials or equipment to be used has not been specified, conventional products of a type that can be obtained from a commercial vendor have been used.

[0020] The reaction general formula of the present application is divided into two types as follows: The structures of the achiral and chiral diphosphine ligands used in the examples of the present application are shown as follows: The preparation method of the achiral and chiral azo-linked aryl-oxazoline type ligands shown in formula (II) comprises the following steps: Step (1): Into an oven-dried 10 mL sealed reaction tube, under argon atmosphere, was placed achiral diphosphine ligand (0.005-0.006 mmol, 5.0-6.0 mol%), palladium acetate (1.1 mg, 0.005 mmol, 5.0 mol%) and 0.5 mL of tetrahydrofuran, and a magnetic stir bar. The catalyst / ligand solution was pre-stirred at 25 °C for 30 min. Subsequently, the azafused aryl triflate compound of formula (IV) (0.10 mmol, 1.0 equiv), potassium hexacyanoferrate(II) trihydrate (0.04-0.05 mmol, 0.4-0.5 equiv), potassium carbonate (0.0125-0.025 mmol, 12.5-25.0 mol%) and 0.5 mL of water were added sequentially. The reaction was stirred at 80-85 °C for 12-14 h, then cooled to room temperature. Upon completion of the reaction, water was added to quench the reaction, followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The dried solution was filtered, concentrated, and the crude product was obtained. Finally, the crude product was purified by flash column chromatography on silica gel (200-300 mesh) using petroleum ether / ethyl acetate to give the achiral azafused aryl nitrile compound of formula (V).

[0021] Step (2): Into a 50 mL round bottom flask, zinc chloride (2.0-4.0 equiv) was added, vacuumed and heated with a heat gun until melted. After cooling, argon was backfilled and the oil was allowed to solidify again. Chlorobenzene (1.0 M) was added to the flask. Subsequently, the amino alcohol compound of formula (VI) (1.5-2.0 equiv) and the achiral azafused aryl nitrile compound of formula (V) (1.0 equiv) were added sequentially. The reaction was heated to 120-140 °C under argon atmosphere and refluxed at this temperature for 40-48 h, then cooled to room temperature. Upon completion of the reaction, 10 mL of water was added to dilute the reaction, followed by extraction with dichloromethane. The organic phases were combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The dried solution was filtered, concentrated, and the crude product was obtained. Finally, the crude product was purified by flash column chromatography on silica gel (200-300 mesh) using petroleum ether / ethyl acetate to give the azafused aryl-oxazoline type ligand of formula (II).

[0022] The method for preparing the achiral and chiral azafused aryl-oxazoline type ligand of formula (III) comprises the following steps: Step (A): Into an oven-dried 10 mL sealed reaction tube, under argon, was placed chiral bisphosphine ligand 1 or 2 (0.005-0.006 mmol, 5.0-6.0 mol%), palladium acetate (1.1 mg, 0.005 mmol, 5.0 mol%) and 1.0 mL of isopropanol, and a magnetic stir bar. The catalyst / ligand solution was pre-stirred at 25 °C for 30 min. Subsequently, the azafusarizane triflate compound or the nonaflate compound of formula (VII) (0.10 mmol, 1.0 equiv), potassium hexacyanoferrate(II) trihydrate (0.04-0.05 mmol, 0.4-0.5 equiv), potassium carbonate (0.0125-0.025 mmol, 12.5-25.0 mol%) and 1.0 mL of water were added sequentially. The reaction mixture was continuously stirred at 75-80 °C for 12-16 h, then cooled to room temperature. Upon completion of the reaction, water was added to quench the reaction, followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The dried solution was filtered, concentrated, and the crude product was obtained. Finally, the crude product was purified by flash column chromatography on silica gel (200-300 mesh) (petroleum ether / ethyl acetate) to give the chiral azafusarizane nitrile compound of formula (VIII).

[0023] Step (B): Into a 50 mL round bottom flask, zinc chloride (2.0-4.0 equiv) was added, vacuumed and heated with a heat gun until melted. After cooling, argon was backfilled and the oil was allowed to solidify again. Chlorobenzene (1.0 M) was added to the flask. Subsequently, the amino alcohol compound of formula (VIII) (1.5-2.0 equiv) and the chiral azafusarizane nitrile compound of formula (VI) (1.0 equiv) were added sequentially. The reaction system was heated to 120-140 °C under argon and refluxed for 40-48 h. Upon completion of the reaction, the reaction was diluted with 10 mL of water, followed by extraction with dichloromethane. The organic phases were combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The dried solution was filtered, concentrated, and the crude product was obtained. Finally, the crude product was purified by flash column chromatography on silica gel (200-300 mesh) (petroleum ether / ethyl acetate) to give the azafusarizane-oxazoline ligand of formula (III).

[0024] Example 1 The structural formula is: Compound 1 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 10:1) gave a white solid (19.4 mg, 95% yield). The characterization data of Compound 1 are as follows: 1H NMR (500 MHz, CDCl3) δ 9.10 (dd, J = 4.3, 1.8 Hz, 1H), 8.19 (dd, J= 8.0, 1.8 Hz, 1H), 8.12 (dd, J = 7.4, 1.3 Hz, 1H), 8.08 (dd, J = 8.1, 1.4Hz, 1H), 7.79 – 7.74 (m, 2H), 7.69 (dd, J = 8.1, 7.3 Hz, 1H), 7.60 (dd, J =8.0, 4.3 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 148.55, 144.55, 136.32, 135.79, 134.14,132.82, 130.81, 127.46, 127.33, 127.18, 127.05, 123.14, 120.90. HRMS (ESI) m / z calculated for C 14 H9N2 + [M + H] + : 205.0760, found:205.0761. Example 2 having the structure: Compound 2 was prepared according to step (1). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio of 8:1) gave a white solid (15.7 mg, 87% yield). Compound 2 was characterized by the following data: 1 H NMR (500 MHz, CDCl3) δ 8.78 – 8.76 (m, 1H), 7.85 – 7.77 (m, 4H),7.69 (td, J = 7.7, 1.4 Hz, 1H), 7.50 (td, J = 7.6, 1.3 Hz, 1H), 7.37 – 7.34(m, 1H). 13 C NMR (126 MHz, CDCl3) δ 155.34, 150.05, 143.57, 136.97, 134.24,132.97, 130.09, 128.88, 123.47, 123.37, 118.82, 111.15. HRMS (ESI) m / z calculated for C12 H9N2 + [M + H] + : 181.0760, found:181.0762. Example 3 Its structural formula is: Compound 3 was prepared according to step (1). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (17.6 mg, 82% yield). Characterization data for compound 3 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.77 (dt, J = 4.9, 1.3 Hz, 1H), 7.86 – 7.77(m, 4H), 7.66 (dd, J = 8.5, 2.2 Hz, 1H), 7.38 – 7.36 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 154.24, 150.20, 141.99, 137.10, 135.08,133.75, 133.32, 131.44, 123.74, 123.22, 117.59, 112.56. HRMS (ESI) m / z calculated for C 12 H8ClN2 + [M + H] + : 215.0371, found:215.0370. Example 4 Its structural formula is: Compound 4 was prepared according to step (1). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (21.8 mg, 88% yield). Characterization data for compound 4 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.81 (dt, J = 4.8, 1.3 Hz, 1H), 8.06 (s,1H), 8.02 (d, J = 8.3 Hz, 1H), 7.93 (dd, J = 8.3, 1.8 Hz, 1H), 7.90 – 7.87(m, 1H), 7.84 – 7.82 (m, 1H), 7.43 – 7.41 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 153.91, 150.38, 146.67, 137.22, 131.44 (q, J C-F = 34.0 Hz), 131.19 (q, J C-F = 4.0 Hz), 130.89, 129.60 (q, J C-F = 3.6 Hz),124.24, 123.48, 123.09 (q, J C-F = 272.8 Hz), 117.53, 112.07. 19 F NMR (471 MHz, CDCl3) δ -63.01. HRMS (ESI) m / z calculated for C 13 H8F3N2 + [M + H] + : 249.0697, found:249.0695. Example 5 , which has the structural formula: Compound 5 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave white solid (19.2 mg, 99% yield). The characterization data of compound 5 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.75 (dt, J = 4.9, 1.4 Hz, 1H), 7.82 (td, J= 7.6, 1.8 Hz, 1H), 7.78 (dt, J = 8.0, 1.3 Hz, 1H), 7.67 – 7.65 (m, 2H), 7.35– 7.32 (m, 1H), 7.30 (dd, J = 7.9, 1.7 Hz, 1H), 2.47 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 155.48, 150.01, 143.97, 143.45, 136.88,134.09, 130.82, 129.66, 123.42, 123.35, 119.08, 108.09, 21.92. HRMS (ESI) m / z calculated for C 13 H11 N2 + [M + H] + : 195.0917, found:195.0917. Example 6 Its structural formula is: Compound 6 was prepared according to step (1). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (18.0 mg, 84% yield). Characterization data for compound 6 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.79 (dt, J = 4.8, 1.4 Hz, 1H), 7.85 (td, J = 7.8, 1.8 Hz, 1H), 7.71 (td, J = 8.8, 8.4, 1.2 Hz, 2H), 7.51 (dt, J = 7.8,1.1 Hz, 1H), 7.45 (t, J = 7.9 Hz, 1H), 7.42 – 7.39 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 153.90, 150.05, 142.69, 136.66, 134.36, 131.86, 129.86, 125.11, 123.92, 117.03, 115.02. HRMS (ESI) m / z calculated for C 12 H8ClN2 + [M + H] + : 215.0371, found:215.0368. Example 7 Its structural formula is: Compound 7 was prepared according to step (1). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (18.9 mg, 82% yield). Characterization data for compound 7 are as follows: 1H NMR (500 MHz, CDCl3) δ 8.87 - 8.86 (m, 1H), 7.98 (dd, J = 8.6, 0.8 Hz, 1H), 7.95 - 7.91 (m, 2H), 7.73 - 7.71 (m, 2H), 7.65 - 7.60 (m, 2H), 7.55- 7.52 (m, 1H), 7.48 - 7.45 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 155.42, 150.17, 144.60, 136.89, 135.16, 131.28, 129.55, 128.91, 128.45, 128.05, 126.95, 126.86, 125.78, 123.65, 118.67, 109.88. HRMS (ESI) m / z calculated for C 16 H 11 N2 + [M + H] + : 231.0917, found:231.0920. Example 8 The structural formula of which is: Compound 8 was prepared according to step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) to obtain white solid (21.6 mg, 94% yield). The characterization data of compound 8 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.82 (dt, J = 4.8, 1.4 Hz, 1H), 8.40 (s, 1H), 8.28 (s, 1H), 7.97 - 7.93 (m, 2H), 7.89 - 7.85 (m, 2H), 7.69 - 7.66 (m, 1H), 7.64 - 7.62 (m, 1H), 7.39 - 7.36 (m, 1H). 13C NMR (151 MHz, CDCl3) δ 155.69, 150.08, 137.90, 136.99, 136.70,134.74, 131.99, 129.86, 129.62, 128.71, 128.22, 128.20, 123.49, 123.25,119.13, 108.92. HRMS (ESI) m / z calculated for C 16 H 11 N2 + [M + H] + : 231.0917, found:231.0919. Example 9 Its structural formula is: Compound 9 was prepared according to step (1). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (21.6 mg, 87% yield). Characterization data for compound 9 are as follows: 1 H NMR (600 MHz, CDCl3) δ 9.04 (dt, J = 2.1, 1.0 Hz, 1H), 8.09 (dd, J= 8.2, 2.3 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.88 (dd, J = 7.9, 1.2 Hz, 1H), 7.84 (dd, J = 7.8, 1.3 Hz, 1H), 7.74 (td, J = 7.7, 1.4 Hz, 1H), 7.58 (td, J =7.6, 1.3 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 158.61, 147.00 (q, J C-F = 3.4 Hz), 142.07,134.51, 134.33 (q, J C-F = 2.9 Hz), 133.20, 130.29, 129.81, 126.29 (q, J C-F =33.7, 33.2 Hz), 123.55 (q, J C-F = 272.8, 272.3 Hz), 123.03, 118.42, 111.38. 19F NMR (565 MHz, CDCl3) δ -62.40. HRMS (ESI) m / z calculated for C 13 H8F3N2 + [M + H] + : 249.0634, found:249.0630. Example 10 whose structural formula is: Compound 10 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave a white solid (24.3 mg, 95% yield). The characterization data of compound 10 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.81 (dd, J = 5.1, 0.8 Hz, 1H), 8.01 (dd, J= 1.8, 0.8 Hz, 1H), 7.92 (dd, J = 7.9, 1.4 Hz, 1H), 7.83 (dd, J = 7.7, 1.3Hz, 1H), 7.73 – 7.70 (m, 3H), 7.57 (dd, J = 5.1, 1.7 Hz, 1H), 7.54 – 7.50 (m,3H), 7.48 – 7.45 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 155.82, 150.52, 149.54, 143.75, 138.06,134.21, 133.01, 130.18, 129.43, 129.35, 128.95, 127.35, 121.65, 121.45,118.96, 111.26. HRMS (ESI) m / z calculated for C 18 H 13 N2 + [M + H] + : 257.1073, found:257.1076. Example 11 whose structural formula is: Compound 11 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave a white solid (16.1 mg, 83% yield). The characterization data of compound 11 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.56 (dd, J = 4.8, 1.5 Hz, 1H), 7.78 (d, J =7.7 Hz, 1H), 7.69 – 7.64 (m, 2H), 7.52 – 7.49 (m, 2H), 7.29 (dd, J = 7.8, 4.7Hz, 1H), 2.27 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 155.67, 147.29, 144.52, 138.66, 133.17,132.73, 131.80, 130.11, 128.52, 123.67, 117.99, 112.63, 19.18. HRMS (ESI) m / z calculated for C 13 H 11 N2 + [M + H] + : 195.0917, found:195.0912. Example 12 , and its structural formula is: Compound 12 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave a white solid (22.6 mg, 91% yield). The characterization data of compound 12 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.90 (dd, J = 4.9, 1.5 Hz, 1H), 8.14 (dd, J= 8.0, 1.6 Hz, 1H), 7.79 (dd, J = 7.7, 1.2 Hz, 1H), 7.68 – 7.66 (m, 1H), 7.58– 7.54 (m, 2H), 7.49 (dd, J = 7.5, 1.1 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 154.91, 152.29, 142.37, 134.95 (q, J C-F =5.3, 4.9 Hz), 133.00, 132.18, 129.66, 129.32, 125.83 (q, J C-F= 32.1 Hz), 123.42, 123.22 (q, J C-F = 274.0 Hz), 117.32, 112.83. 19 F NMR (565 MHz, CDCl3) δ -58.58. HRMS (ESI) m / z calculated for C 13 H8F3N2 + [M + H] + : 249.0634, found:249.0635. Example 13 The structural formula of which is: Compound 13 was prepared according to Step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave white solid (22.8 mg, 99% yield). The characterization data of compound 13 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.68 (d, J = 5.6 Hz, 1H), 7.93 (d, J = 8.2Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.77 – 7.72 (m, 4H), 7.67 (d, J = 7.7 Hz,1H), 7.61 (t, J = 7.7 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 157.12, 143.17, 142.39, 136.84, 133.63,132.46, 131.05, 130.61, 129.02, 127.94, 127.40, 126.96, 126.62, 121.45,117.87, 113.38. HRMS (ESI) m / z calculated for C 16 H 11 N2 + [M + H] + : 231.0917, found:231.0922. Example 14 The structural formula of which is: Compound 14 was prepared according to step (1). Purification by flash column chromatography (petroleum ether and ethyl acetate in the volume ratio of 5:1) afforded a white solid (27.4 mg, 98% yield). The characterization data of compound 14 are as follows: 1 H NMR (500 MHz, CDC13) δ 8.73 (d, J = 8.1 Hz, 1H), 8.64 (dd, J = 8.1, 1.4 Hz, 1H), 8.27 (dd, J = 8.0, 1.3 Hz, 1H), 7.91 - 7.87 (m, 2H), 7.81 - 7.71 (m, 5H), 7.65 - 7.61 (m, 2H). 13 C NMR (126 MHz, CDC13) δ 157.67, 143.65, 143.34, 133.61, 133.56, 132.61, 131.18, 130.85, 130.63, 129.25, 129.14, 127.94, 127.86, 127.64, 125.02, 124.25, 122.63, 122.20, 117.74, 113.36. HRMS (ESI) m / z calculated for C 20 H 13 N2 + [M + H] + : 281.1073, found: 281.1076. Example 15 The structural formula of which is: Compound 15 was prepared according to step (1). Purification by flash column chromatography (petroleum ether and ethyl acetate in the volume ratio of 5:1) afforded a white solid (13.0 mg, 72% yield). The characterization data of compound 15 are as follows: 1 H NMR (500 MHz, CDC13) δ 8.92 (d, J = 4.9 Hz, 2H), 8.37 (dd, J = 8.0, 1.3 Hz, 1H), 7.85 (dd, J = 7.7, 1.3 Hz, 1H), 7.71 (td, J = 7.7, 1.4 Hz, 1H), 7.57 (td, J = 7.6, 1.3 Hz, 1H), 7.33 (t, J = 4.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 163.00, 157.49, 140.45, 135.21, 132.70, 130.57, 130.36, 120.28, 119.05, 111.99. HRMS (ESI) m / z calculated for C 11 H8N3 + [M + H] + : 182.0713, found:182.0710. Example 16 , the structure of which is: Compound 16 was prepared according to Step (1). Purification by flash column chromatography (petroleum ether and ethyl acetate in the volume ratio of 5:1) gave a white solid (17.7 mg, 98% yield). The characterization data of compound 16 are as follows: 1 H NMR (500 MHz, CDCl3) δ 9.03 (d, J = 1.5 Hz, 1H), 8.75 (dd, J = 2.6, 1.6 Hz, 1H), 8.65 (d, J = 2.5 Hz, 1H), 7.87 – 7.82 (m, 2H), 7.74 (td, J = 7.7, 1.4 Hz, 1H), 7.58 (td, J = 7.6, 1.2 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 151.24, 144.43, 144.12, 140.14, 134.69, 133.17, 130.01, 129.82, 118.24, 111.53. HRMS (ESI) m / z calculated for C 11 H8N3 + [M + H] + : 182.0713, found:182.0710. Example 17 , the structure of which is: Compound 17 was prepared according to Step (1). Purification by flash column chromatography (petroleum ether and ethyl acetate in the volume ratio of 8:1) gave a light brown liquid (14.5 mg, 85% yield). The characterization data of compound 17 are as follows: 1H NMR (500 MHz, CDC13) δ 8.19 (dd, J = 8.1, 1.2 Hz, 1H), 7.83 - 7.80 (m, 2H), 7.70 (td, J = 7.8, 1.3 Hz, 1H), 7.55 (td, J = 7.7, 1.2 Hz, 1H), 7.37 (s, 1H). 13 C NMR (126 MHz, CDC13) δ 158.87, 139.85, 134.98, 132.99, 130.33, 129.47, 129.25, 128.77, 118.04, 109.94. HRMS (ESI) m / z calculated for C 10 H7N2O + [M + H] + : 171.0553, found: 171.0555. Example 18 The structural formula of compound 18 is: Compound 18 was prepared according to step (1). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) to obtain a light brown liquid (16.4 mg, 97% yield). The characterization data of compound 18 are as follows: 1 H NMR (500 MHz, CDC13) δ 8.14 (d, J = 2.5 Hz, 1H), 7.81 - 7.77 (m, 3H), 7.72 - 7.69 (m, 1H), 7.43 (td, J = 7.6, 1.3 Hz, 1H), 6.54 (dd, J = 2.6, 1.8 Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 142.38, 142.16, 134.57, 134.12, 129.64, 127.35, 124.41, 117.11, 108.61, 105.46. HRMS (ESI) m / z calculated for C 10 H8N3 + [M + H] + : 170.0713, found: 170.0716. Example 19 The structural formula is: Compound 19 was prepared according to Step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq.), ethanolamine (183.2 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (1.09 g, 8.0 mmol, 4.0 eq.) to give a white solid (411.8 mg, 83% yield). The characterization data of compound 19 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.91 (dd, J = 4.3, 1.8 Hz, 1H), 8.07 (dd, J= 8.0, 1.8 Hz, 1H), 7.95 (dd, J = 8.0, 1.3 Hz, 1H), 7.83 (dd, J = 7.2, 1.4Hz, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.68 – 7.62 (m, 2H), 7.43 (dd, J = 8.0,4.3 Hz, 1H), 4.59 (t, J = 9.4 Hz, 2H), 4.20 (t, J = 9.4 Hz, 2H). 13 C NMR (126 MHz, CDCl3) δ 168.67, 148.06, 145.50, 135.44, 134.25,130.26, 129.56, 129.45, 127.75, 127.30, 127.20, 127.09, 126.11, 121.76,68.07, 55.33. HRMS (ESI) m / z calculated for C 16 H 13 N2O + [M + H] + : 249.1022, found:249.1020. Example 20 The structural formula is: Compound 20 was prepared according to Step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq.), 2-amino-2-methyl-1-propanol (267.4 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (1.09 g, 8.0 mmol, 4.0 eq.) to give a white solid (281.7 mg, 51% yield). The characterization data of compound 20 are as follows: 1H NMR (600 MHz, CDCl3) δ 8.92 (dd, J = 4.3, 1.8 Hz, 1H), 8.09 (dd, J= 8.0, 1.8 Hz, 1H), 7.95 (dd, J = 7.9, 1.3 Hz, 1H), 7.82 (dd, J = 7.2, 1.3Hz, 1H), 7.77 (d, J = 8.7 Hz, 1H), 7.68 - 7.64 (m, 2H), 7.45 (dd, J = 8.0,4.3 Hz, 1H), 4.31 (s, 2H), 1.57 (s, 6H). 13 C NMR (151 MHz, CDCl3) δ 166.07, 147.63, 145.77, 135.47, 134.34,130.17, 129.78, 129.61, 127.89, 127.84, 127.24, 127.21, 126.10, 121.79,79.88, 67.67, 28.31. HRMS (ESI) m / z calculated for C 18 H 17 N2O + [M + H] + : 277.1335, found:277.1333. Example 21 having the structure: Compound 21 was prepared according to Step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq), L-aminopropanol (225.3 mg, 3.0 mmol, 1.5 eq) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq) to give a white solid (471.6 mg, 90% yield). The characterization data of compound 21 are as follows: 1H NMR (600 MHz, CDCl3) δ 8.93 (dd, J = 4.3, 1.8 Hz, 1H), 8.11 (dd, J= 8.0, 1.8 Hz, 1H), 7.97 (dd, J = 8.0, 1.4 Hz, 1H), 7.83 (dd, J = 7.2, 1.4Hz, 1H), 7.79 (d, J = 8.7 Hz, 1H), 7.69 – 7.66 (m, 2H), 7.46 (dd, J = 8.0,4.3 Hz, 1H), 4.69 (dd, J = 9.2, 7.8 Hz, 1H), 4.56 – 4.52 (m, 1H), 4.17 (t, J= 7.9 Hz, 1H), 1.56 (d, J = 6.6 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 167.58, 147.77, 145.67, 135.54, 134.33,130.28, 129.67, 129.49, 127.89, 127.53, 127.28, 127.23, 126.17, 121.85,74.74, 62.28, 21.25. HRMS (ESI) m / z calculated for C 17 H 15 N2O + [M + H] + : 263.1179, found:263.1175. Specific rotation [α] 20 D = -89.08 (c = 0.40, CH2Cl2). Example 22 having the structure: Compound 22 was prepared according to Step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq), (S)-2-amino-1-butanol (267.4 mg, 3.0 mmol, 1.5 eq) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq) to give a white solid (440.5 mg, 80% yield). The characterization data of compound 22 are as follows: 1H NMR (500 MHz, CDCl3) δ 8.93 (dd, J = 4.3, 1.8 Hz, 1H), 8.15 (dd, J= 8.1, 1.8 Hz, 1H), 7.99 (dd, J = 8.0, 1.4 Hz, 1H), 7.84 – 7.81 (m, 2H), 7.71– 7.68 (m, 2H), 7.49 (dd, J = 8.0, 4.3 Hz, 1H), 4.67 (dd, J = 9.3, 7.8 Hz,1H), 4.42 – 4.35 (m, 1H), 4.25 (t, J = 8.1 Hz, 1H), 2.01 – 1.97 (m, 1H), 1.86– 1.82 (m, 1H), 1.16 (t, J = 7.5 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 167.75, 147.90, 145.78, 135.59, 134.42,130.34, 129.85, 129.59, 127.99, 127.66, 127.37, 127.30, 126.23, 121.91,73.07, 68.66, 28.73, 10.81. HRMS (ESI) m / z calculated for C 18 H 17 N2O + [M + H] + : 277.1335, found:277.1331. Specific rotation [α] 20 D = -70.93 (c = 0.40, CH2Cl2). Example 23 The structural formula of compound 23 is: Compound 23 was prepared according to step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq.), L-valinol (309.5 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq.) to give a white solid (496.6 mg, 86% yield). The characterization data of compound 23 are as follows: 1H NMR (600 MHz, CDCl3) δ 8.92 (dd, J = 4.3, 1.8 Hz, 1H), 8.15 (dd, J= 8.0, 1.8 Hz, 1H), 7.99 (dd, J = 8.0, 1.4 Hz, 1H), 7.84 – 7.81 (m, 2H), 7.71– 7.68 (m, 2H), 7.49 (dd, J = 8.0, 4.3 Hz, 1H), 4.62 (dd, J = 9.5, 8.1 Hz,1H), 4.35 – 4.32 (m, 1H), 4.25 – 4.18 (m, 1H), 2.12 – 2.06 (m, 1H), 1.18 (d,J = 6.8 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 167.78, 147.97, 145.79, 135.57, 134.44,130.36, 130.01, 129.63, 127.99, 127.74, 127.37, 127.29, 126.22, 121.91,73.39, 71.18, 32.99, 19.73, 19.01. HRMS (ESI) m / z calculated for C 19 H 19 N2O + [M + H] + : 291.1492, found:291.1491. Specific rotation [α] 20 D = -68.73 (c = 0.40, CH2Cl2). Example 24 having the structure: Compound 24 was prepared according to Procedure (2) from compound 1 (918.3 mg, 4.5 mmol, 1.0 equiv), (S)-tert-leucinol (1.05 g, 9.0 mmol, 2.0 equiv), and zinc chloride (1.23 g, 9.0 mmol, 2.0 equiv) to give a white solid (1.22 g, 89% yield). Characterization data for compound 24 are as follows: 1H NMR (600 MHz, CDCl3) δ 8.92 (d, J = 4.2 Hz, 1H), 8.12 (dd, J = 8.1,1.7 Hz, 1H), 7.97 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 7.2 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.69 – 7.67 (m, 2H), 7.47 (dd, J = 8.0, 4.3 Hz, 1H), 4.57 (t, J= 9.2 Hz, 1H), 4.43 (t, J = 8.8 Hz, 1H), 4.24 (t, J = 9.6 Hz, 1H), 1.15 (s,9H). 13 C NMR (151 MHz, CDCl3) δ 167.95, 148.03, 145.73, 135.51, 134.38,130.34, 130.19, 129.62, 127.92, 127.71, 127.32, 127.21, 126.17, 121.86,76.80, 69.45, 33.83, 26.64. HRMS (ESI) m / z calculated for C 20 H 21 N2O + [M + H] + : 305.1648, found:305.1644. Specific rotation [α] 20 D = -67.15 (c = 0.40, CH2Cl2). Example 25 having the structure: Compound 25 was prepared according to Procedure (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 equiv), L-phenylalaninol (453.6 mg, 3.0 mmol, 1.5 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) as a light pink solid (621.7 mg, 92% yield). Characterization data for compound 25 are as follows: 1H NMR (500 MHz, CDC13) δ 8.94 (dd, J = 4.3, 1.8 Hz, 1H), 8.14 (dd, J = 8.1, 1.8 Hz, 1H), 7.98 (dd, J = 8.0, 1.4 Hz, 1H), 7.81 - 7.80 (m, 2H), 7.70- 7.67 (m, 2H), 7.49 (dd, J = 8.0, 4.3 Hz, 1H), 7.38 - 7.33 (m, 4H), 7.27 - 7.23 (m, 1H), 4.79 - 4.72 (m, 1H), 4.55 (t, J = 8.7 Hz, 1H), 4.35 (t, J = 7.9 Hz, 1H), 3.47 - 3.43 (m, 1H), 3.04 (dd, J = 13.6, 8.9 Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 168.23, 147.87, 145.71, 138.75, 135.64, 134.41, 130.39, 129.76, 129.55, 129.46, 128.70, 127.98, 127.47, 127.36, 127.31, 126.51, 126.24, 121.94, 72.72, 68.31, 41.85. HRMS (ESI) m / z calculated for C 23 H 19 N2O + [M + H] + : 339.1492, found:339.1488. Specific rotation [α] 20 D = -60.23 (c = 0.40, CH2Cl2). Example 26 having the structure: Compound 26 was prepared according to Procedure (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 equiv), L-cyclohexylglycinal (515.6 mg, 3.6 mmol, 1.8 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) to give a white solid (452.1 mg, 68% yield). Characterization data for compound 26 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.93 (dd, J = 4.3, 1.8 Hz, 1H), 8.13 (dd, J= 8.0, 1.8 Hz, 1H), 7.97 (dd, J = 8.0, 1.4 Hz, 1H), 7.85 – 7.79 (m, 2H), 7.70– 7.67 (m, 2H), 7.48 (dd, J = 8.0, 4.3 Hz, 1H), 4.60 (dd, J = 9.6, 7.9 Hz,1H), 4.36 (t, J = 8.4 Hz, 1H), 4.23 (q, J = 8.6 Hz, 1H), 2.16 (d, J = 12.6Hz, 1H), 1.87 – 1.80 (m, 3H), 1.78 – 1.72 (m, 2H), 1.41 – 1.18 (m, 5H). 13 C NMR (126 MHz, CDCl3) δ 167.58, 147.90, 145.76, 135.53, 134.38,130.29, 129.98, 129.59, 127.94, 127.74, 127.32, 127.24, 126.17, 121.87,72.37, 71.22, 42.94, 30.16, 29.62, 26.76, 26.45, 26.33. HRMS (ESI) m / z calculated for C 22 H 23 N2O + [M + H] + : 331.1805, found:331.1799. Specific rotation [α] 20 D = -88.10 (c = 0.40, CH2Cl2). Example 27 whose structural formula is: Compound 27 was prepared according to step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 eq.), (S)-2-phenylglycinol (411.5 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq.) to give a white solid (486.3 mg, 75% yield). Characterization data of compound 27 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.91 (s, 1H), 8.18 (dd, J = 8.1, 1.8 Hz,1H), 8.03 (dd, J = 7.9, 1.2 Hz, 1H), 7.95 (dd, J = 7.2, 1.2 Hz, 1H), 7.85 (d,J = 8.8 Hz, 1H), 7.75 – 7.72 (m, 2H), 7.66 – 7.61 (m, 2H), 7.51 (dd, J = 8.0,4.3 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.36 – 7.32 (m, 1H), 5.57 (t, J = 9.6Hz, 1H), 4.98 (dd, J = 9.9, 8.1 Hz, 1H), 4.47 (t, J = 8.7 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 169.41, 147.99, 145.71, 143.33, 135.69,134.48, 130.61, 130.06, 129.64, 128.74, 128.03, 127.47, 127.42, 127.36,127.33, 127.26, 126.32, 122.05, 75.75, 70.59. HRMS (ESI) m / z calculated for C 22 H 17 N2O + [M + H] + : 325.1335, found:325.1330. Specific rotation [α] 20 D = -257.43 (c = 0.40, CH2Cl2). Example 28 which has the structural formula: Compound 28 was prepared according to step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 equiv), (1R,2S)-2-amino-1,2-diphenylethanol (639.8 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (1.09 g, 8.0 mmol, 4.0 equiv) as a light yellow solid (493.3 mg, 62% yield). Characterization data for compound 28 are as follows: 1 H NMR (600 MHz, CDCl3) δ 9.05 (d, J = 2.7 Hz, 1H), 8.17 – 8.13 (m,2H), 8.05 (dd, J = 8.0, 1.3 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.79 (t, J =7.6 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.53 (dd, J = 8.0, 4.3 Hz, 1H), 7.25 –7.24 (m, 2H), 7.15 – 7.12 (m, 4H), 7.08 – 7.04 (m, 3H), 7.03 – 7.00 (m, 1H),6.31 (d, J = 10.3 Hz, 1H), 5.86 (d, J = 10.3 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 169.65, 148.22, 145.81, 138.83, 136.91,135.75, 134.56, 130.75, 130.41, 129.82, 128.35, 128.01, 127.69, 127.66,127.46, 127.42, 127.23, 126.94, 126.79, 126.39, 122.08, 86.29, 74.28. HRMS (ESI) m / z calculated for C 28 H 21 N2O + [M + H] + : 401.1648, found:401.1648. Specific rotation [α] 20 D = -204.13 (c = 0.40, CH2Cl2). Example 29 having the structure: Compound 29 was prepared according to Step (2) from compound 1 (408.1 mg, 2.0 mmol, 1.0 equiv), (1S,2R)-1-amino-2-indanol (447.6 mg, 3.0 mmol, 1.5 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) to give a white solid (532.6 mg, 79% yield). Characterization data for compound 29 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.00 (d, J = 8.0 Hz, 1H), 7.94 (dd, J = 7.9,1.3 Hz, 1H), 7.81 – 7.77 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.68 – 7.58 (m,3H), 7.48 – 7.44 (m, 1H), 7.41 (t, J = 7.4 Hz, 1H), 7.34 (td, J = 7.4, 1.2Hz, 1H), 7.29 – 7.26 (m, 1H), 5.94 (d, J = 8.0 Hz, 1H), 5.65 (dt, J = 8.5,4.2 Hz, 1H), 3.56 (d, J = 4.6 Hz, 2H). 13 C NMR (126 MHz, CDCl3) δ 168.13, 147.30, 145.45, 142.57, 140.65,135.16, 134.18, 130.15, 129.72, 129.42, 128.20, 127.63, 127.53, 127.41,127.14, 126.99, 126.08, 125.96, 125.14, 121.71, 83.61, 77.36, 39.88. HRMS (ESI) m / z calculated for C 23 H 17 N2O + [M + H] + : 337.1335, found:337.1343. Specific rotation [α] 20 D = -109.28 (c = 0.40, CH2Cl2). Example 30 having the structure: Compound 30 was prepared according to Step (2) from compound 2 (360.1 mg, 2.0 mmol, 1.0 equiv), L-aminopropanol (225.3 mg, 3.0 mmol, 1.5 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) as a light brown liquid (374.0 mg, 78% yield). Characterization data for compound 30 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.59 (dd, J = 4.9, 2.2 Hz, 1H), 7.75 (dd, J= 7.7, 1.6 Hz, 1H), 7.64 – 7.60 (m, 1H), 7.52 (dd, J = 7.7, 1.8 Hz, 1H), 7.47– 7.43 (m, 1H), 7.39 – 7.34 (m, 2H), 7.16 – 7.13 (m, 1H), 4.21 – 4.14 (m,2H), 3.63 – 3.57 (m, 1H), 1.20 (d, J = 6.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 164.56, 158.67, 148.92, 140.58, 135.75,130.39, 130.08, 129.76, 128.05, 127.73, 122.98, 121.83, 74.15, 61.93, 21.03. HRMS (ESI) m / z calculated for C 15 H 15 N2O + [M + H] + : 239.1179, found:239.1176. Specific rotation [α] 20 D = -49.90 (c = 0.31, CH2Cl2). Example 31 having the structure: , Compound 31 was prepared from Compound 2 (360.1 mg, 2.0 mmol, 1.0 eq.), (S)-2-amino-1-butanol (267.4 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq.) according to step (2), to give a light yellow liquid (378.5 mg, 75% yield). The characterization data of Compound 31 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.64 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 7.81(dd, J = 7.8, 1.3 Hz, 1H), 7.69 (td, J = 7.7, 1.8 Hz, 1H), 7.57 (dd, J = 7.7,1.3 Hz, 1H), 7.51 (td, J = 7.6, 1.4 Hz, 1H), 7.44 – 7.40 (m, 2H), 7.23 – 7.20(m, 1H), 4.19 (dd, J = 9.4, 8.1 Hz, 1H), 4.13 – 4.07 (m, 1H), 3.75 (t, J =7.7 Hz, 1H), 1.70 – 1.61 (m, 1H), 1.58 – 1.50 (m, 1H), 0.92 (t, J = 7.4 Hz,3H). 13 C NMR (126 MHz, CDCl3) δ 164.79, 158.98, 149.15, 140.82, 135.90,130.58, 130.33, 129.98, 128.27, 127.94, 123.27, 122.00, 72.46, 68.20, 28.49,10.14. HRMS (ESI) m / z calculated for C 16 H 17 N2O + [M + H] + : 253.1335, found:253.1332. Specific rotation [α] 20 D = -70.49 (c = 0.47, CH2Cl2). Example 32 The structural formula of which is: , Compound 32 was prepared from compound 2 (360.1 mg, 2.0 mmol, 1.0 eq.), L-valinol (309.5 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq.) according to step (2), to give a light yellow liquid (468.2 mg, 88% yield). The characterization data of compound 32 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.63 (dt, J = 4.9, 1.3 Hz, 1H), 7.81 (dd, J= 7.6, 1.3 Hz, 1H), 7.67 (td, J = 7.7, 1.8 Hz, 1H), 7.55 (dd, J = 7.8, 1.4Hz, 1H), 7.50 (td, J = 7.5, 1.4 Hz, 1H), 7.43 – 7.39 (m, 2H), 7.22 – 7.19 (m,1H), 4.12 (dd, J = 9.6, 8.2 Hz, 1H), 3.98 – 3.93 (m, 1H), 3.83 (t, J = 8.1Hz, 1H), 1.82 – 1.72 (m, 1H), 0.89 (dd, J = 13.5, 6.7 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 164.66, 159.01, 149.12, 140.82, 135.83,130.52, 130.32, 129.98, 128.23, 127.87, 123.31, 121.95, 72.86, 70.41, 32.71,19.01, 18.36. HRMS (ESI) m / z calculated for C 17 H 19 N2O + [M + H] + : 267.1492, found:267.1494. Specific rotation [α] 20 D = -69.77 (c = 0.30, CH2Cl2). Example 33 The structural formula of which is: Compound 33 was prepared according to step (2) from compound 2 (900.4 mg, 5.0 mmol, 1.0 equiv), (S)-tert-leucinol (879.0 mg, 7.5 mmol, 1.5 equiv) and zinc chloride (1.36 g, 10.0 mmol, 2.0 equiv) to give a white solid (1.28 g, 91% yield). Characterization data for compound 33 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 4.8 Hz, 1H), 7.84 (d, J = 7.6Hz, 1H), 7.68 (td, J = 7.7, 1.8 Hz, 1H), 7.57 – 7.50 (m, 2H), 7.44 – 7.41 (m,2H), 7.22 (dd, J = 7.6, 4.9 Hz, 1H), 4.10 – 4.04 (m, 1H), 3.96 – 3.90 (m,2H), 0.89 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 164.72, 159.15, 149.24, 140.90, 135.85,130.58, 130.49, 130.09, 128.31, 127.85, 123.48, 122.00, 76.57, 68.95, 34.01,26.13. HRMS (ESI) m / z calculated for C 18 H 21 N2O + [M + H] + : 281.1648, found:281.1646. Specific rotation [α] 20 D = -77.48 (c = 0.40, CH2Cl2). Example 34 having the structural formula: Compound 34 was prepared according to step (2) from compound 2 (360.1 mg, 2.0 mmol, 1.0 equiv), L-phenylalaninol (453.6 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) to give a light pink solid (507.3 mg, 81% yield). Characterization data for compound 34 are as follows: 1H NMR (500 MHz, CDC13) δ 8.63 (dt, J = 4.8, 1.5 Hz, 1H), 7.82 (dd, J= 7.7, 1.4 Hz, 1H), 7.61 - 7.55 (m, 2H), 7.49 (td, J = 7.5, 1.4 Hz, 1H), 7.41 (td, J = 7.5, 1.4 Hz, 1H), 7.34 - 7.32 (m, 1H), 7.28 - 7.24 (m, 2H), 7.20 - 7.15 (m, 4H), 4.48 - 4.42 (m, 1H), 4.07 (t, J = 8.9 Hz, 1H), 3.85 (dd, J = 8.5, 7.4 Hz, 1H), 3.07 (dd, J = 13.8, 5.3 Hz, 1H), 2.73 (dd, J = 13.8, 8.3 Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 165.11, 158.66, 148.91, 140.67, 137.85, 135.74, 130.49, 130.13, 129.85, 129.28, 128.35, 128.08, 127.54, 126.32, 123.09, 121.84, 71.74, 67.73, 41.13. HRMS (ESI) m / z calculated for C 21 H 19 N2O + [M + H] + : 315.1492, found:315.1488. Specific rotation [α] 20 D = -63.54 (c = 0.41, CH2Cl2). Example 35 having the structure: Compound 35 was prepared according to Procedure (2) from compound 2 (360.1 mg, 2.0 mmol, 1.0 equiv), L-cyclohexylglycinal (429.7 mg, 3.0 mmol, 1.5 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) to give a light yellow liquid (505.3 mg, 82% yield). Characterization data for compound 35 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.61 (dt, J = 4.8, 1.3 Hz, 1H), 7.79 (dd, J= 7.6, 1.3 Hz, 1H), 7.65 (td, J = 7.7, 1.8 Hz, 1H), 7.53 (dd, J = 7.8, 1.3Hz, 1H), 7.47 (td, J = 7.5, 1.4 Hz, 1H), 7.41 – 7.37 (m, 2H), 7.20 – 7.17 (m,1H), 4.10 (dd, J = 9.5, 8.0 Hz, 1H), 3.95 – 3.90 (m, 1H), 3.84 (t, J = 8.0Hz, 1H), 1.75 – 1.55 (m, 5H), 1.45 – 1.37 (m, 1H), 1.25 – 1.10 (m, 3H), 1.02– 0.89 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 164.38, 158.94, 149.01, 140.76, 135.75,130.40, 130.22, 129.87, 128.12, 127.85, 123.25, 121.83, 71.89, 70.50, 42.65,29.41, 28.97, 26.49, 26.09, 26.07. HRMS (ESI) m / z calculated for C 20 H 23 N2O + [M + H] + : 307.1805, found:307.1801. Specific rotation [α] 20 D = -82.66 (c = 0.43, CH2Cl2). Example 36 whose structural formula is: , Compound 36 was prepared from Compound 2 (360.1 mg, 2.0 mmol, 1.0 eq.), (S)-2- phenylglycinol (411.5 mg, 3.0 mmol, 1.5 eq.) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 eq.) according to Step (2), to give a brown yellow liquid (178.3 mg, 30% yield). The characterization data of Compound 36 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.65 (ddd, J = 4.7, 1.8, 0.9 Hz, 1H), 7.94(dd, J = 7.7, 1.3 Hz, 1H), 7.70 (td, J = 7.7, 1.8 Hz, 1H), 7.60 (dd, J = 7.7,1.5 Hz, 1H), 7.56 (td, J = 7.5, 1.4 Hz, 1H), 7.52 – 7.46 (m, 2H), 7.35 – 7.31(m, 4H), 7.29 – 7.28 (m, 1H), 7.22 (ddd, J = 7.5, 4.9, 1.1 Hz, 1H), 5.28 (dd,J = 10.1, 8.4 Hz, 1H), 4.53 (dd, J = 10.1, 8.3 Hz, 1H), 3.97 (t, J = 8.4 Hz,1H). 13 C NMR (151 MHz, CDCl3) δ 166.30, 159.00, 149.19, 142.54, 141.02,136.13, 130.82, 130.65, 130.06, 128.70, 128.38, 127.69, 127.54, 126.95,123.19, 122.08, 75.11, 70.34. HRMS (ESI) m / z calculated for C 20 H 17 N2O + [M + H] + : 301.1335, found:301.1333. Specific rotation [α] 20 D = -100.45 (c = 0.26, CH2Cl2). Example 37 which has the structural formula: Compound 37 was prepared according to step (2) from compound 2 (360.1 mg, 2.0 mmol, 1.0 equiv), (1S,2R)-1-amino-2-indanol (447.6 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) to give a brown-black liquid (323.3 mg, 52% yield). Characterization data for compound 37 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.33 (dt, J = 4.8, 1.3 Hz, 1H), 7.74 (dd, J = 7.7, 1.4 Hz, 1H), 7.57 (dd, J = 7.8, 1.3 Hz, 1H), 7.48 (td, J = 7.5, 1.4Hz, 1H), 7.43 – 7.35 (m, 3H), 7.29 – 7.23 (m, 3H), 7.12 – 7.09 (m, 2H), 5.64(d, J = 7.8 Hz, 1H), 5.23 (ddd, J = 7.9, 6.7, 1.3 Hz, 1H), 3.26 (dd, J =17.9, 6.8 Hz, 1H), 2.92 (d, J = 17.9 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 165.57, 158.35, 149.17, 141.86, 140.66,140.04, 135.84, 130.63, 130.13, 129.90, 128.46, 128.29, 128.00, 127.57,125.89, 125.17, 123.29, 121.85, 83.63, 77.53, 39.49. HRMS (ESI) m / z calculated for C 21 H 17 N2O + [M + H] + : 313.1335, found:313.1331. Specific rotation [α] 20 D = -103.46 (c = 0.27, CH2Cl2). Example 38 having the structural formula: Compound 38 was prepared according to step (2) from compound 11 (388.2 mg, 2.0 mmol, 1.0 equiv), (S)-tert-leucinol (351.6 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (545.2 mg, 4.0 mmol, 2.0 equiv) as a colorless liquid (564.8 mg, 96% yield). Characterization data for compound 38 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.44 (dd, J = 4.9, 1.6 Hz, 1H), 7.96 (dd, J= 7.8, 1.4 Hz, 1H), 7.51 – 7.48 (m, 2H), 7.42 (td, J = 7.6, 1.4 Hz, 1H), 7.28(dd, J = 7.3, 1.5 Hz, 1H), 7.14 (dd, J = 7.7, 4.8 Hz, 1H), 4.03 (dd, J = 9.9,8.4 Hz, 1H), 3.88 (t, J = 8.3 Hz, 1H), 3.82 (dd, J = 10.0, 8.3 Hz, 1H), 2.09(s, 3H), 0.73 (s, 9H). 13 C NMR (151 MHz, CDCl3) δ 162.84, 159.80, 146.03, 141.08, 136.83,131.60, 130.52, 129.68, 129.58, 127.75, 127.07, 122.03, 76.46, 68.34, 33.73,25.77, 19.29. HRMS (ESI) m / z calculated for C 19 H 23 N2O + [M + H] + : 295.1805, found:295.1806. Specific rotation [α] 20 D = -62.06 (c = 0.44, CH2Cl2). Example 39 having the structural formula: Compound 39 was prepared according to step (2) from compound 14 (840.3 mg, 3.0 mmol, 1.0 eq.), (S)-tert-leucinol (527.4 mg, 4.5 mmol, 1.5 eq.) and zinc chloride (817.8 mg, 6.0 mmol, 2.0 eq.) to give a white solid (1.03 g, 90% yield). Characterization data of compound 39 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.65 (d, J = 8.3 Hz, 1H), 8.60 (dd, J = 8.2,1.4 Hz, 1H), 8.21 (dd, J = 20.1, 8.1 Hz, 1H), 8.10 (dd, J = 8.0, 1.3 Hz, 1H),7.78 – 7.72 (m, 2H), 7.68 – 7.55 (m, 5H), 7.51 – 7.49 (m, 1H), 3.84 – 3.47(m, 3H), 0.45 (s, 9H). 13 C NMR (151 MHz, CDCl3) δ 162.76, 162.11, 143.92, 140.02, 132.66,131.07, 130.79, 130.51, 130.43, 130.24, 129.99, 129.66, 128.62, 128.45,128.15, 127.99, 127.19, 126.78, 126.47, 124.05, 122.00, 76.23, 68.48, 33.55,25.53. HRMS (ESI) m / z calculated for C 26 H 25 N2O + [M + H] + : 381.1961, found:381.1959. Specific rotation [α] 20 D = -77.67 (c = 0.58, CH2Cl2). Example 40 having the structural formula: Compound 40 was prepared according to step (2) from compound 15 (362.1 mg, 2.0 mmol, 1.0 equiv), (S)-tert-leucinol (351.6 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (817.8 mg, 6.0 mmol, 3.0 equiv) to give a white solid (507.5 mg, 90% yield). The characterization data of compound 40 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.75 (d, J = 4.8 Hz, 2H), 7.87 (dd, J = 7.7,1.4 Hz, 1H), 7.82 (dd, J = 7.6, 1.4 Hz, 1H), 7.52 (td, J = 7.6, 1.5 Hz, 1H),7.46 (td, J = 7.5, 1.4 Hz, 1H), 7.17 (t, J = 4.9 Hz, 1H), 4.14 – 4.09 (m,1H), 3.98 – 3.93 (m, 2H), 0.91 (s, 9H). 13 C NMR (151 MHz, CDCl3) δ 166.61, 164.60, 156.74, 138.94, 130.40,130.06, 129.35, 128.46, 119.01, 76.64, 68.91, 33.90, 26.12. HRMS (ESI) m / z calculated for C 17 H 20 N3O + [M + H] + : 282.1601, found:282.1606. Specific rotation [α] 20 D = -76.55 (c = 0.40, CH2Cl2). Example 41 whose structural formula is: Compound 41 was prepared according to step (2) from compound 18 (338.1 mg, 2.0 mmol, 1.0 equiv), (S)-tert-leucinol (351.6 mg, 3.0 mmol, 1.5 equiv) and zinc chloride (817.8 mg, 6.0 mmol, 3.0 equiv) to give a white solid (530.3 mg, 99% yield). The characterization data of compound 41 are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.83 – 7.78 (m, 1H), 7.65 (d, J = 2.5 Hz, 2H), 7.49 – 7.47 (m, 2H), 7.39 – 7.36 (m, 1H), 6.36 (t, J = 2.1 Hz, 1H), 4.11(dd, J = 9.7, 8.0 Hz, 1H), 3.99 – 3.91 (m, 2H), 0.88 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 162.59, 140.64, 139.53, 131.26, 131.03,130.55, 127.80, 126.00, 124.32, 106.56, 76.17, 69.01, 33.87, 25.96. HRMS (ESI) m / z calculated for C 16 H 20 N3O + [M + H] + : 270.1601, found:270.1599. Specific rotation [α] 20 D = -69.95 (c = 0.40, CH2Cl2). Example 42 Its structural formula is: Compound 42 was prepared according to step (A). It was purified by rapid column chromatography (petroleum ether and ethyl acetate, volume ratio = 8:1) to give a white solid (20.6 mg, 74% yield, 90% ee). Characterization data for compound 42 are as follows: 1H NMR (500 MHz, CDC13) δ 8.77 (d, J = 5.7 Hz, 1H), 8.07 (dd, J = 8.6, 0.8 Hz, 1H), 8.00 - 7.97 (m, 2H), 7.86 (dd, J = 5.8, 0.9 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.73 - 7.70 (m, 1H), 7.64 - 7.61 (m, 1H), 7.47 - 7.37 (m, 3H), 7.28 (dd, J = 8.6, 1.1 Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 156.50, 143.42, 142.76, 136.58, 134.95, 131.95, 130.80, 129.73, 129.03, 128.48, 128.10, 128.07, 127.38, 127.06, 126.76, 126.57, 121.63, 118.07, 110.75. HRMS (ESI) m / z calculated for C 20 H 13 N2 + [M + H] + : 281.1073, found: 281.1077. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (major) = 19.2 min, t R (minor) = 24.1 min. Specific rotation [α] 20 D = -44.25 (c = 0.40, CH2Cl2). Example 43 whose structural formula is: , Compound 43 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate = 8:1 by volume) afforded a light brown solid (29.8 mg, 96% yield, 94% ee). Characterization data of Compound 43 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 5.7 Hz, 1H), 7.96 (dt, J = 8.2,0.9 Hz, 1H), 7.85 – 7.84 (m, 2H), 7.72 – 7.69 (m, 1H), 7.56 – 7.53 (m, 1H),7.46 – 7.40 (m, 2H), 7.36 (s, 1H), 7.24 – 7.21 (m, 1H), 7.14 (dd, J = 8.5,1.1 Hz, 1H), 4.08 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 156.17, 145.36, 142.73, 136.53, 136.40,130.77, 129.49, 128.07, 127.94, 127.38, 127.34, 127.02, 126.50, 125.49,121.60, 115.13, 106.89, 104.89, 56.34. HRMS (ESI) m / z calculated for C 21 H 15 N2O + [M + H] + : 311.1179, found:311.1175. HPLC analysis: DAICEL CHIRALPAK ® IG column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 25.3 min, t R (major) = 27.2 min. Specific rotation [α] 20 D = +25.58 (c = 1.21, CH2Cl2). Example 44 having the structure: Compound 44 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio of 8:1) afforded a white solid (30.7 mg, 96% yield, 86% ee). Characterization data for Compound 44 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.76 (d, J = 5.7 Hz, 1H), 8.56 (dt, J = 8.6,0.9 Hz, 1H), 7.97 (dt, J = 8.5, 1.0 Hz, 1H), 7.85 (dd, J = 5.8, 0.8 Hz, 1H),7.73 – 7.66 (m, 2H), 7.57 (d, J = 1.0 Hz, 1H), 7.46 – 7.39 (m, 3H), 7.28 (dt,J = 8.5, 0.9 Hz, 1H), 2.47 – 2.43 (m, 1H), 1.24 – 1.18 (m, 2H), 0.97 – 0.82(m, 2H). 13 C NMR (126 MHz, CDCl3) δ 156.85, 142.80, 141.77, 136.58, 135.32,132.06, 130.77, 128.85, 128.25, 128.03, 127.74, 127.67, 127.36, 126.75,125.02, 124.67, 121.52, 118.32, 110.43, 13.51, 7.06, 6.86. HRMS (ESI) m / z calculated for C 23 H 17 N2 + [M + H] + : 321.1386, found:321.1383. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 17.5 min, t R(major) = 20.2 min. Specific rotation [α] 20 D = +3.99 (c = 1.03, CH2Cl2). Example 45 having the structure: Compound 45 was prepared according to Step (A). Purification by flash column chromatography (volumetric ratio of petroleum ether and ethyl acetate = 8: 1) afforded a white solid (22.4 mg, 72% yield, 90% ee). Characterization data of compound 45 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 5.7 Hz, 1H), 7.93 (dd, J = 18.5, 8.4 Hz, 2H), 7.83 (d, J = 5.8 Hz, 1H), 7.73 (d, J = 8.6 Hz, 1H), 7.71 - 7.68 (m, 1H), 7.45 - 7.42 (m, 1H), 7.40 - 7.38 (m, 1H), 7.24 (d, J = 2.6 Hz, 1H), 7.17 (d, J = 9.2 Hz, 1H), 7.04 (dd, J = 9.2, 2.6 Hz, 1H), 3.92 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 159.89, 156.62, 143.10, 142.65, 136.83, 136.50, 130.72, 128.61, 128.31, 128.01, 127.49, 127.33, 127.30, 126.53, 121.51, 120.91, 118.37, 108.11, 106.28, 55.57. HRMS (ESI) m / z calculated for C 21 H 15 N2O + [M + H] + : 311.1179, found:311.1176. HPLC analysis: DAICEL CHIRALPAK ®ID column, hexane / isopropanol = 70 / 30, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 25.5 min. R (minor) = 25.5 min. Specific rotation [α] 20 D = -44.24 (c = 0.80, CH2Cl2). Example 46 having the structure: Compound 46 was prepared according to Step (A). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave a white solid (22.0 mg, 75% yield, 90% ee). Characterization data of compound 46 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.77 (d, J = 5.7 Hz, 1H), 7.98 – 7.96 (m,2H), 7.85 (dd, J = 5.7, 0.8 Hz, 1H), 7.76 – 7.74 (m, 1H), 7.73 – 7.70 (m,1H), 7.46 – 7.43 (m, 1H), 7.40 – 7.37 (m, 1H), 7.24 (dd, J = 8.6, 1.7 Hz,1H), 7.16 (d, J = 8.6 Hz, 1H), 2.52 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 156.69, 143.22, 142.78, 139.38, 136.55,135.24, 130.74, 130.34, 130.24, 129.01, 128.10, 128.03, 127.48, 127.35,126.90, 126.85, 126.63, 121.55, 118.27, 109.75, 21.90. HRMS (ESI) m / z calculated for C 21 H 15 N2 + [M + H] +: 295.1230, found: 295.1226. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 37.2 min. R (minor) = 37.2 min. Specific rotation [α] 20 D = -64.91 (c = 0.80, CH2Cl2). Example 47 having the structure: Compound 47 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio = 8: 1) gave a white solid (30.3 mg, 85% yield, 71% ee). Characterization data for compound 47 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.80 (d, J = 5.7 Hz, 1H), 8.18 (d, J = 1.8Hz, 1H), 8.12 (dd, J = 8.6, 0.8 Hz, 1H), 8.00 (dt, J = 8.2, 1.0 Hz, 1H), 7.88(dd, J = 5.8, 0.9 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.76 – 7.72 (m, 1H),7.71 – 7.67 (m, 3H), 7.51 – 7.40 (m, 5H), 7.36 (d, J = 8.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.47, 143.30, 142.83, 141.72, 139.96, 136.62, 135.33, 131.09, 130.84, 129.91, 129.18, 128.33, 128.16, 128.11, 127.79, 127.64, 127.58, 127.42, 127.27, 126.61, 126.12, 121.68, 118.14, 110.54. HRMS (ESI) m / z calculated for C 26 H 17 N2 + [M + H] + : 357.1386, found:357.1384. HPLC analysis: DAICEL CHIRALPAK ® IG column, hexane / isopropanol = 70 / 30, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (major) = 27.7 min, t R (minor) = 30.8 min. Specific rotation [α] 20 D = -85.95 (c = 0.89, CH2Cl2). Example 48 , which has the structural formula: Compound 48 was prepared according to Step (A). Purification by flash column chromatography (volume ratio of petroleum ether and ethyl acetate = 8: 1) gave a white solid (24.6 mg, 80% yield, 90% ee). The characterization data of compound 48 are as follows: 1H NMR (500 MHz, CDCl3) δ 10.20 (s, 1H), 8.78 (d, J = 5.7 Hz, 1H),8.49 (d, J = 1.6 Hz, 1H), 8.25 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.3 Hz, 1H),7.92 – 7.85 (m, 3H), 7.76 – 7.73 (m, 1H), 7.49 – 7.45 (m, 1H), 7.41 (d, J =8.8 Hz, 1H), 7.34 (dd, J = 8.4, 1.1 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 191.56, 155.62, 143.59, 142.87, 136.64,135.96, 134.78, 134.39, 133.82, 131.11, 131.00, 128.37, 128.32, 128.10,127.96, 127.57, 126.19, 125.04, 121.99, 117.44, 113.68. HRMS (ESI) m / z calculated for C 21 H 13 N2O + [M + H] + : 309.1022, found:309.1018. HPLC analysis: DAICEL CHIRALPAK ® IG column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (major) = 34.3 min, t R (minor) = 40.0 min. Specific rotation [α] 20 D = -97.42 (c = 0.79, CH2Cl2). Example 49 whose structural formula is: , Compound 49 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate = 5:1 by volume) afforded a light yellow solid (24.4 mg, 80% yield, 80% ee). Characterization data of Compound 49 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 5.7 Hz, 1H), 8.39 (d, J = 1.7Hz, 1H), 8.15 (dd, J = 8.6, 0.9 Hz, 1H), 8.01 (dt, J = 8.4, 0.9 Hz, 1H), 7.93– 7.90 (m, 2H), 7.78 – 7.74 (m, 1H), 7.54 (dd, J = 8.8, 1.7 Hz, 1H), 7.50 –7.48 (m, 1H), 7.41 – 7.39 (m, 1H), 7.33 – 7.31 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 155.13, 143.65, 142.90, 136.68, 134.30,133.80, 133.23, 131.09, 130.10, 128.66, 128.55, 128.51, 127.94, 127.64,126.02, 122.12, 118.22, 117.14, 113.94, 112.73. HRMS (ESI) m / z calculated for C 21 H 12 N3 + [M + H] + : 306.1026, found:306.1021. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 36.2 min, t R (major) = 40.1 min. Specific rotation [α] 20 D= -48.89 (c = 0.62, CH2Cl2). Example 50 having the structure: Compound 50 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio of 8: 1) afforded a light yellow solid (28.2 mg, 92% yield, 80% ee). Characterization data for compound 50 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 5.7 Hz, 1H), 8.02 (dd, J = 8.6,0.9 Hz, 1H), 7.98 (dt, J = 8.2, 1.0 Hz, 1H), 7.88 (d, J = 1.7 Hz, 1H), 7.86(dd, J = 5.7, 0.9 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.73 – 7.71 (m, 1H),7.54 (dd, J = 8.8, 1.8 Hz, 1H), 7.47 – 7.44 (m, 1H), 7.40 – 7.38 (m, 1H),7.23 (d, J = 8.8 Hz, 1H), 6.87 (dd, J = 17.6, 10.8 Hz, 1H), 5.89 (d, J = 17.6Hz, 1H), 5.42 (d, J = 10.9 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 156.43, 143.18, 142.79, 138.07, 136.57,136.07, 135.28, 131.54, 130.79, 129.69, 128.10, 128.07, 127.39, 127.29,126.55, 126.44, 125.49, 121.64, 118.10, 116.79, 110.51. HRMS (ESI) m / z calculated for C 22 H 15 N2 + [M + H] + : 307.1230, found:307.1226. HPLC analysis: DAICEL CHIRALPAK ®ID column, hexane / isopropanol = 70 / 30, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 24.7 min. R (minor) = 24.7 min. Specific rotation [α] 20 D = -114.28 (c = 0.86, CH2Cl2). Example 51 having the structure: Compound 51 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio = 8: 1) afforded a colorless liquid (31.0 mg, 96% yield, 89% ee). Characterization data for compound 51 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 5.7 Hz, 1H), 8.03 – 7.98 (m,2H), 7.93 (d, J = 8.5 Hz, 1H), 7.87 (dd, J = 5.8, 0.9 Hz, 1H), 7.74 – 7.71(m, 2H), 7.55 (dd, J = 8.5, 1.7 Hz, 1H), 7.47 – 7.40 (m, 2H), 7.05 (s, 1H),2.84 – 2.79 (m, 1H), 1.10 (dd, J = 6.9, 2.9 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 156.73, 148.82, 142.91, 142.77, 136.56,133.73, 132.11, 130.76, 129.38, 128.53, 128.10, 127.98, 127.37, 126.70,126.05, 123.56, 121.57, 118.31, 110.70, 34.36, 23.77, 23.56. HRMS (ESI) m / z calculated for C 23 H 19 N2 + [M + H] +: 323.1543, found: 323.1537. HPLC analysis: DAICEL CHIRALPAK ® IG column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 16.1 min. R (minor) = 16.1 min. Specific rotation [α] 20 D = -108.94 (c = 0.99, CH2Cl2). Example 52 having the structure: Compound 52 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio = 8: 1) gave a white solid (28.2 mg, 95% yield, 82% ee). Characterization data for compound 52 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 1.8 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.81 – 7.77 (m, 2H), 7.64 – 7.60 (m, 1H), 7.53 – 7.49 (m, 1H), 7.43 – 7.37 (m, 2H), 7.25 (d, J = 8.4 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 155.34 (d, J C-F = 262.5 Hz), 152.38 (d, J C-F = 5.4 Hz), 142.72, 134.94, 131.96, 131.05, 129.92, 129.32 (d, J C-F = 3.4 Hz), 129.10, 128.95, 128.53, 128.37, 128.18, 127.09 (d, J C-F= 15.4 Hz), 126.83, 126.70, 126.40, 120.33 (d, J C-F = 3.7 Hz), 117.98, 110.95. 19 F NMR (471 MHz, CDCl3) δ -137.88. HRMS (ESI) m / z calculated for C 20 H 11 FN2Na + [M + Na] + : 321.0798, found:321.0793. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 12.7 min, t R (major) = 14.4 min. Specific rotation [α] 20 D = -36.68 (c = 0.40, CH2Cl2). Example 53 , which has the structural formula: Compound 53 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in the volume ratio = 8: 1) gave a light yellow solid (27.0 mg, 87% yield, 87% ee). The characterization data of compound 53 are as follows: 1H NMR (600 MHz, CDCl3) δ 8.77 (d, J = 5.8 Hz, 1H), 8.25 (dd, J = 5.8,1.0 Hz, 1H), 8.06 (dd, J = 8.6, 0.9 Hz, 1H), 7.98 (dt, J = 8.4, 0.9 Hz, 1H),7.78 (d, J = 8.6 Hz, 1H), 7.63 – 7.60 (m, 1H), 7.42 – 7.39 (m, 1H), 7.34 (dd,J = 8.5, 7.7 Hz, 1H), 7.28 (dt, J = 8.6, 1.0 Hz, 1H), 7.02 (d, J = 7.6 Hz,1H), 6.92 (dt, J = 8.5, 0.9 Hz, 1H), 4.07 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 155.78, 155.07, 143.84, 142.48, 134.98,131.97, 129.63, 129.48, 129.00, 128.84, 128.45, 128.14, 128.02, 127.16,126.77, 118.29, 118.13, 116.15, 110.74, 107.88, 55.97. HRMS (ESI) m / z calculated for C 21 H 15 N2O + [M + H] + : 311.1179, found:311.1177. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 22.8 min, t R (major) = 24.1 min. Specific rotation [α] 20 D = -11.19 (c = 1.00, CH2Cl2). Example 54 , compound 54 was prepared according to step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate = 8:1 by volume) gave a white solid (20.1 mg, 68% yield, 83% ee). Characterization data of compound 54 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.72 (d, J = 5.8 Hz, 1H), 8.06 (dd, J = 8.6,0.8 Hz, 1H), 7.98 (dt, J = 8.4, 0.9 Hz, 1H), 7.79 – 7.74 (m, 3H), 7.64 – 7.60(m, 1H), 7.42 – 7.39 (m, 1H), 7.30 – 7.28 (m, 3H), 2.54 (d, J = 1.0 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 156.08, 143.58, 142.83, 141.30, 136.90,134.95, 131.96, 130.40, 129.65, 129.00, 128.45, 128.03, 127.10, 126.76,126.55, 126.36, 126.25, 121.13, 118.13, 110.68, 22.11. HRMS (ESI) m / z calculated for C 21 H 15 N2 + [M + H] + : 295.1230, found:295.1225. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (major) = 20.6 min, t R (minor) = 25.1 min. Specific rotation [α] 20 D ​= -5.82 (c = 0.78, CH2Cl2). Example 55 having the structure: Compound 55 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio = 5:1) afforded a white solid (28.3 mg, 86% yield, 68% ee). Characterization data for compound 55 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.77 (d, J = 8.4 Hz, 1H), 8.71 (dd, J = 8.0,1.5 Hz, 1H), 8.30 (dd, J = 8.0, 1.5 Hz, 1H), 8.10 (d, J = 8.6 Hz, 1H), 8.00(dd, J = 8.3, 1.0 Hz, 1H), 7.89 – 7.86 (m, 1H), 7.84 – 7.77 (m, 3H), 7.65 –7.60 (m, 1H), 7.53 – 7.50 (m, 1H), 7.45 (dd, J = 8.2, 1.3 Hz, 1H), 7.41 –7.37 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 157.24, 143.93, 143.50, 135.01, 133.31,131.94, 131.38, 130.69, 129.81, 129.27, 129.11, 128.51, 128.15, 128.02,127.88, 127.09, 126.84, 125.96, 124.39, 122.62, 122.34, 118.03, 110.64. HRMS (ESI) m / z calculated for C 24 H 15 N2 + [M + H] + : 331.1230, found:331.1230. HPLC analysis: DAICEL CHIRALPAK ® ID column, hexane / isopropanol = 80 / 20, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, tR (minor) = 14.0 min, t R (major) = 16.5 min. Specific rotation [α] 20 D = +8.44 (c = 1.00, CH2Cl2). Example 56 having the structure: Compound 56 was prepared according to Step (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio = 5:1) afforded a colorless liquid (27.4 mg, 97% yield, 71% ee). Characterization data for compound 56 are as follows: 1 H NMR (500 MHz, CDCl3) δ 9.56 (s, 1H), 8.22 (dt, J = 8.6, 0.9 Hz,1H), 8.11 (dd, J = 8.6, 0.9 Hz, 1H), 8.01 (dt, J = 8.4, 0.9 Hz, 1H), 7.97 –7.94 (m, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.67 – 7.64 (m, 1H), 7.54 – 7.50 (m,1H), 7.47 – 7.43 (m, 1H), 7.41 – 7.39 (m, 1H), 7.27 – 7.25 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 165.40, 154.91, 150.85, 140.48, 134.82,134.76, 131.09, 130.53, 129.36, 129.30, 128.70, 128.65, 128.53, 126.68,126.46, 126.19, 124.52, 117.52, 110.33. HRMS (ESI) m / z calculated for C 19 H 11 N3Na + [M + Na] + : 304.0845, found:304.0837. HPLC analysis: DAICEL CHIRALPAK ®ID column, hexane / isopropanol = 65 / 35, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 23.4 min. R (minor) = 23.4 min. Specific rotation [α] 20 D = -27.35 (c = 0.54, CH2Cl2). Example 57 having the structure: Compound 57 was prepared according to procedure (A). Purification by flash column chromatography (petroleum ether and ethyl acetate in a volume ratio of 5:1) gave a white solid (20.8 mg, 74% yield, 75% ee). Characterization data for compound 57 are as follows: 1 H NMR (600 MHz, CDCl3) δ 9.71 (d, J = 0.9 Hz, 1H), 8.13 – 8.11 (m,2H), 8.01 (dt, J = 8.4, 0.9 Hz, 1H), 7.97 – 7.94 (m, 1H), 7.81 – 7.77 (m,2H), 7.66 – 7.63 (m, 1H), 7.45 – 7.42 (m, 1H), 7.40 – 7.38 (m, 1H), 7.30 –7.29 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 157.15, 151.71, 139.81, 134.92, 133.44,133.22, 131.89, 130.49, 129.29, 128.59, 128.40, 127.05, 126.70, 126.67,126.57, 125.27, 117.69, 111.16. HRMS (ESI) m / z calculated for C 19 H 12 N3 + [M + H] + : 282.1026, found:282.1023. HPLC analysis: DAICEL CHIRALPAK® IG column, hexane / isopropanol = 65 / 35, flow rate = 1.0 mL / min, λ = 254 nm, 25 °C, t R (minor) = 34.2 min. R (minor) = 34.2 min. Specific rotation [α] 20 D = -27.32 (c = 0.76, CH2Cl2). Example 58 having the structure: Compound 58 was prepared according to Procedure (B) from racemic compound 42 (280.1 mg, 1.0 mmol, 1.0 equiv), ethanolamine (122.2 mg, 2.0 mmol, 2.0 equiv), and zinc chloride (545.2 mg, 4.0 mmol, 4.0 equiv) as a light yellow solid (108.9 mg, 34% yield). Characterization data for compound 58 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.68 (d, J = 5.8 Hz, 1H), 8.18 (d, J = 8.7Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.92 (dd, J = 15.5, 8.2 Hz, 2H), 7.73 (d,J = 5.8 Hz, 1H), 7.64 (ddd, J = 8.1, 6.6, 1.2 Hz, 1H), 7.50 (ddd, J = 8.0,6.7, 1.1 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.36 – 7.34 (m, 1H), 7.31 – 7.28(m, 1H), 7.18 (d, J = 8.6 Hz, 1H), 3.90 – 3.86 (m, 1H), 3.70 – 3.66 (m, 2H),3.64 – 3.59 (m, 1H). 13C NMR (151 MHz, CDCl3) δ 165.07, 160.09, 142.23, 137.41, 135.90,134.78, 132.73, 130.03, 128.97, 128.82, 128.12, 127.35, 127.31, 127.24,127.05, 126.94, 126.85, 126.27, 125.43, 120.09, 67.75, 54.79. HRMS (ESI) m / z calculated for C 22 H 17 N2O + [M + H] + : 325.1335, found:325.1334. Example 59 Structure: and Compound 59 was prepared according to Step (B) from chiral compound 42 (560.0 mg, 2.0 mmol, 1.0 eq, >99% ee), (S)-2-amino-1-butanol (267.4 mg, 3.0 mmol, 1.5 eq) and zinc chloride (817.8 mg, 6.0 mmol, 3.0 eq) to give a white solid {550.8 mg, 78% yield, (1R,4S)-59: (1S,4S)-59 = 1.2: 1}. Characterization data of compound (1R,4S)-59 are as follows: 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 5.7 Hz, 1H), 8.12 (d, J = 8.6Hz, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.92 (dd, J = 14.7, 8.2 Hz, 2H), 7.73 (d,J = 5.8 Hz, 1H), 7.66 – 7.62 (m, 1H), 7.52 – 7.49 (m, 1H), 7.44 (dd, J = 8.5,1.2 Hz, 1H), 7.37 – 7.34 (m, 1H), 7.32 – 7.29 (m, 1H), 7.24 (dd, J = 8.6, 1.1Hz, 1H), 3.96 (dd, J = 9.4, 7.9 Hz, 1H), 3.91 – 3.84 (m, 1H), 3.19 (t, J =7.8 Hz, 1H), 1.34 – 1.26 (m, 1H), 1.22 – 1.12 (m, 1H), 0.63 (t, J = 7.4 Hz,3H). 13 C NMR (126 MHz, CDCl3) δ 164.03, 159.99, 142.18, 137.29, 135.87,134.70, 132.60, 130.03, 129.01, 128.81, 128.13, 127.27, 127.22, 126.92,126.80, 126.23, 125.91, 120.06, 72.33, 67.72, 28.34, 9.86. HRMS (ESI) m / z calculated for C 24 H 21 N2O + [M + H] + : 353.1648, found:353.1645. Specific rotation [α] 20 D = +65.25 (c = 0.40, CH2Cl2). Compound (1S,4S)-59 was characterized by the following data: 1H NMR (500 MHz, CDC13) δ 8.70 (d, J = 5.7 Hz, 1H), 8.13 (d, J = 8.7 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.94 (dd, J = 8.3, 1.2 Hz, 1H), 7.90 (dt, J = 8.1, 0.9 Hz, 1H), 7.73 (dd, J = 5.8, 0.9 Hz, 1H), 7.63 (ddd, J = 8.1, 6.7, 1.3 Hz, 1H), 7.51 (ddd, J = 8.2, 6.7, 1.3 Hz, 1H), 7.42 - 7.40 (m, 1H), 7.35 - 7.30 (m, 2H), 7.26 (dd, J = 8.5, 1.2 Hz, 1H), 3.86 - 3.81 (m, 1H), 3.76 (dd, J = 9.4, 7.9 Hz, 1H), 3.52 (dd, J = 7.9, 7.0 Hz, 1H), 1.16 - 1.08 (m, 2H), 0.60 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 163.42, 160.11, 142.25, 137.42, 136.07, 134.78, 132.72, 130.00, 128.88, 128.78, 128.10, 127.31, 127.29, 127.16, 126.94, 126.85, 126.80, 126.02, 125.59, 120.04, 72.14, 67.89, 28.44, 9.85. Specific rotation [α] 20 D = -132.50 (c = 0.16, CH2CI2). Example 60 Structure is: and , Compound 60 was prepared according to step (B) from chiral compound 42 (560.0 mg, 2.0 mmol, 1.0 eq, >99% ee), L-valinol (371.4 mg, 3.6 mmol, 1.8 eq) and zinc chloride (817.8 mg, 6.0 mmol, 3.0 eq) to give a white solid {504.3 mg, 75% yield, (1R,4S)-60: (1S,4S)-60 = 15: 1}. Characterization data of compound (1R,4S)-60 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 5.8 Hz, 1H), 8.14 (d, J = 8.6Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.94 – 7.89 (m, 2H), 7.72 (dd, J = 5.8,0.9 Hz, 1H), 7.65 – 7.61 (m, 1H), 7.51 – 7.48 (m, 1H), 7.42 (dt, J = 8.3, 1.0Hz, 1H), 7.36 – 7.32 (m, 1H), 7.31 – 7.28 (m, 1H), 7.20 – 7.18 (m, 1H), 3.94(dd, J = 9.7, 8.3 Hz, 1H), 3.75 – 3.70 (m, 1H), 3.37 (t, J = 8.3 Hz, 1H),1.46 – 1.36 (m, 1H), 0.63 (d, J = 6.8 Hz, 3H), 0.56 (d, J = 6.8 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 163.61, 160.11, 142.21, 137.41, 135.84,134.62, 132.66, 129.97, 129.11, 128.72, 128.08, 127.28, 127.24, 127.21,126.86, 126.74, 126.23, 125.78, 120.04, 72.53, 70.20, 32.49, 18.69, 18.02. HRMS (ESI) m / z calculated for C 25 H 23 N2O + [M + H] +: 367.1805, found: 367.1802. Specific rotation [α] 20 D = +30.40 (c = 0.40, CH2Cl2). Compound (1S,4S)-60 was characterized by the following data: 1 H NMR (500 MHz, CDCl3) δ 8.70 (d, J = 5.7 Hz, 1H), 8.15 (d, J = 8.6 Hz, 1H), 8.03 - 8.01 (m, 1H), 7.93 - 7.87 (m, 2H), 7.72 (dd, J = 5.8, 0.9 Hz, 1H), 7.61 (ddd, J = 8.1, 6.7, 1.2 Hz, 1H), 7.49 (ddd, J = 8.1, 6.6, 1.3 Hz, 1H), 7.40 (dd, J = 8.4, 1.1 Hz, 1H), 7.33 - 7.28 (m, 2H), 7.26 - 7.24 (m, 1H), 3.77 - 3.68 (m, 2H), 3.62 (t, J = 6.9 Hz, 1H), 1.31 - 1.24 (m, 1H), 0.58 (d, J = 6.8 Hz, 3H), 0.53 (d, J = 6.7 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 163.04, 160.12, 142.20, 137.43, 136.00, 134.64, 132.68, 129.90, 128.78, 128.66, 127.98, 127.21, 127.18, 127.05, 126.82, 126.79, 126.71, 125.94, 125.41, 119.94, 72.61, 70.10, 32.65, 18.25, 18.23. Specific rotation [α] 20 D = -196.82 (c = 0.13, CH2Cl2). Example 61 Structure is: and Compound 61 was prepared according to step (B) from chiral compound 42 (840.0 mg, 3.0 mmol, 1.0 eq, >99% ee), (S)-tert-leucinol (527.4 mg, 4.5 mmol, 1.5 eq) and zinc chloride (817.8 mg, 6.0 mmol, 2.0 eq) as a white solid {935.3 mg, 82% yield, (1R,4S)-61 : (1S,4S)-61 = 19: 1}. Characterization data of compound (1R,4S)-61 are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 8.7Hz, 1H), 8.02 (dd, J = 8.7, 0.8 Hz, 1H), 7.94 – 7.89 (m, 2H), 7.72 (dd, J =5.8, 0.8 Hz, 1H), 7.65 – 7.61 (m, 1H), 7.51 – 7.48 (m, 1H), 7.41 (dd, J =8.5, 1.1 Hz, 1H), 7.36 – 7.32 (m, 1H), 7.30 – 7.27 (m, 1H), 7.14 (dd, J =8.6, 1.1 Hz, 1H), 3.93 (dd, J = 10.0, 8.4 Hz, 1H), 3.68 (dd, J = 10.0, 8.5Hz, 1H), 3.54 (t, J = 8.5 Hz, 1H), 0.55 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 163.19, 160.24, 142.23, 137.45, 135.82,134.54, 132.72, 129.97, 129.28, 128.68, 128.05, 127.36, 127.23, 127.18,126.83, 126.70, 126.22, 125.62, 120.09, 76.35, 68.53, 33.52, 25.66. HRMS (ESI) m / z calculated for C 26 H 25 N2O + [M + H] + : 381.1961, found:381.1961. Specific rotation [α] 20 D = +44.58 (c = 0.40, CH2Cl2). Compound (1S,4S)-61 was characterized by the following data: 1 H NMR (500 MHz, CDCl3) δ 8.70 (d, J = 5.7 Hz, 1H), 8.15 (d, J = 8.7Hz, 1H), 8.02 (dd, J = 8.8, 0.7 Hz, 1H), 7.93 (dt, J = 8.2, 0.9 Hz, 1H), 7.90– 7.88 (m, 1H), 7.72 (dd, J = 5.8, 0.9 Hz, 1H), 7.62 – 7.59 (m, 1H), 7.51 –7.48 (m, 1H), 7.39 – 7.37 (m, 1H), 7.32 – 7.28 (m, 2H), 7.22 (dd, J = 8.6,1.1 Hz, 1H), 3.78 – 3.66 (m, 3H), 0.47 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 162.71, 160.31, 142.31, 137.63, 136.13,134.65, 132.79, 129.95, 128.83, 128.67, 128.00, 127.26, 127.21, 127.09,126.86, 126.84, 126.77, 125.93, 125.23, 119.95, 76.39, 68.28, 33.53, 25.49. Specific rotation [α] 20 D = -182.38 (c = 0.20, CH2Cl2). Example 62 Structural formula is: and , Compound 62 was prepared according to step (B) from chiral compound 42 (560.0 mg, 2.0 mmol, 1.0 eq, >99% ee), L-phenylalaninol (453.6 mg, 3.0 mmol, 1.5 eq) and zinc chloride (817.8 mg, 6.0 mmol, 3.0 eq) to give a white solid {695.8 mg, 84% yield, (1R,4S)-62: (1S,4S)-62 = 2.5: 1}. Characterization data of compound (1R,4S)-62 are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.67 (d, J = 5.7 Hz, 1H), 8.13 (d, J = 8.6Hz, 1H), 8.04 (dd, J = 8.7, 0.8 Hz, 1H), 7.96 – 7.93 (m, 2H), 7.73 (dd, J =5.7, 0.9 Hz, 1H), 7.70 – 7.67 (m, 1H), 7.54 – 7.51 (m, 1H), 7.49 – 7.47 (m,1H), 7.42 – 7.39 (m, 1H), 7.34 – 7.31 (m, 1H), 7.28 – 7.26 (m, 1H), 7.20 –7.17 (m, 2H), 7.16 – 7.13 (m, 1H), 6.95 – 6.93 (m, 2H), 4.24 – 4.19 (m, 1H),3.86 (dd, J = 9.2, 8.4 Hz, 1H), 3.33 (dd, J = 8.5, 7.4 Hz, 1H), 2.83 (dd, J =13.8, 5.5 Hz, 1H), 2.16 (dd, J = 13.8, 8.9 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 164.49, 159.94, 142.22, 138.13, 137.43,135.90, 134.73, 132.57, 130.04, 129.09, 129.04, 128.86, 128.46, 128.16,127.34, 127.26, 127.24, 126.97, 126.88, 126.38, 126.11, 125.84, 120.13,72.10, 67.70, 41.63. HRMS (ESI) m / z calculated for C29 H 23 N2O + [M + H] + : 415.1805, found:415.1803. Specific rotation [α] 20 D = +53.15 (c = 0.40, CH2Cl2). Compound (1S,4S)-62 was characterized by the following data: 1 H NMR (600 MHz, CDCl3) δ 8.72 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.6Hz, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2Hz, 1H), 7.73 (d, J = 5.8 Hz, 1H), 7.64 (ddd, J = 8.2, 6.7, 1.2 Hz, 1H), 7.53(ddd, J = 8.1, 6.3, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.38 – 7.30 (m,3H), 7.22 – 7.19 (m, 2H), 7.17 – 7.14 (m, 1H), 6.97 – 6.96 (m, 2H), 4,21 –4.16 (m, 1H), 3.67 – 3.63 (m, 2H), 2.63 (dd, J = 13.9, 5.5 Hz, 1H), 2.08 (dd,J = 13.8, 8.7 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 163.91, 159.97, 142.22, 138.07, 137.53,136.00, 134.80, 132.67, 129.96, 129.08, 128.84, 128.79, 128.39, 128.06,127.35, 127.26, 127.13, 126.94, 126.84, 126.75, 126.31, 125.92, 125.38,120.01, 71.70, 67.70, 41.14. Specific rotation [α]20 D = -151.85 (c = 0.18, CH2Cl2). Example 63 The preparation method of the achiral and chiral nitrogen-linked aryl-oxazoline type ligand comprises the following steps: Step (1), aromatic cyanation reaction: under an argon atmosphere, the nitrogen-linked aryl triflate compound shown in formula (IV) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition that palladium and achiral ligand are used as catalysts and potassium carbonate is used as base, to obtain the achiral nitrogen-linked aryl nitrile compound shown in formula (V); Step (2), condensation reaction: under an argon atmosphere, the achiral nitrogen-linked aryl nitrile compound shown in formula (V) is reacted with the amino alcohol compound shown in formula (VI) under the condition that zinc chloride is used as Lewis acid, to obtain the nitrogen-linked aryl-oxazoline type ligand shown in formula (II); The reaction formula is as follows: In step (1), the palladium catalyst is palladium acetate; the achiral ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; and potassium carbonate is used as base.

[0025] In step (1), the molar ratio of the nitrogen-linked aryl triflate compound shown in formula (IV), potassium hexacyanoferrate(II) trihydrate, palladium catalyst precursor, achiral ligand and potassium carbonate is 20:8:1:1:2.5; the reaction temperature is 80°C; and the reaction time is 12 hours.

[0026] In step (1), the reaction solvent is a mixed solvent of water and tetrahydrofuran, and the volume ratio is 1:1. In step (2), the molar ratio of the achiral nitrogen-linked aryl nitrile compound shown in formula (V), the amino alcohol compound shown in formula (VI) and zinc chloride is 1:1.5:2.

[0027] The condensation reaction adopts chlorobenzene as solvent; the reaction temperature is 120°C; and the reaction time is 40 hours.

[0028] Example 64 The preparation method of the achiral and chiral nitrogen-linked aryl-oxazoline type ligand comprises the following steps: Step (1), aromatic cyanation reaction: under an argon atmosphere, the nitrogen-linked aryl triflate compound shown in formula (IV) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition that palladium and achiral ligand are used as catalysts and potassium carbonate is used as base, to obtain the achiral nitrogen-linked aryl nitrile compound shown in formula (V); Step (2), condensation reaction: under argon atmosphere, the achiral nitrogen-containing biaryl cyanide compound represented by formula (V) is reacted with the amino alcohol compound represented by formula (VI) under the condition of zinc chloride as Lewis acid to obtain the nitrogen-containing biaryl-oxazoline ligand represented by formula (II); The reaction formula is as follows: In step (1), the palladium catalyst is palladium acetate; the achiral ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; and potassium carbonate is used as the base.

[0029] In step (1), the molar ratio of the nitrogen-containing biaryl triflate compound represented by formula (IV), potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the achiral ligand and potassium carbonate is 20:10:1:1.2:5; the reaction temperature is 85℃, and the reaction time is 14 hours.

[0030] In step (1), the reaction solvent is a mixed solvent of water and tetrahydrofuran, and the volume ratio is 1:1; the concentration of the nitrogen-containing biaryl triflate compound is 0.1 mol / L.

[0031] In step (2), the molar ratio of the achiral nitrogen-containing biaryl cyanide compound represented by formula (V), the amino alcohol compound represented by formula (VI) and zinc chloride is 1:2:4.

[0032] The solvent used in the condensation reaction is chlorobenzene; the reaction temperature is 140℃, and the reaction time is 48 hours.

[0033] Example 65 The preparation method of the achiral and chiral nitrogen-containing biaryl-oxazoline ligand comprises the following steps: Step (1), aromatic cyanation reaction: under argon atmosphere, the nitrogen-containing biaryl triflate compound represented by formula (IV) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition of palladium and achiral ligand as catalyst and potassium carbonate as base to obtain the achiral nitrogen-containing biaryl cyanide compound represented by formula (V); Step (2), condensation reaction: under argon atmosphere, the achiral nitrogen-containing biaryl cyanide compound represented by formula (V) is reacted with the amino alcohol compound represented by formula (VI) under the condition of zinc chloride as Lewis acid to obtain the nitrogen-containing biaryl-oxazoline ligand represented by formula (II); The reaction formula is as follows: In step (1), the palladium catalyst is palladium acetate; the achiral ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; and potassium carbonate is used as the base.

[0034] In step (1), the molar ratio of the azafused aryl triflate compound represented by formula (IV), potassium hexacyanoferrate(II) trihydrate, a palladium catalyst precursor, a non-chiral ligand, and potassium carbonate is 20:9:1:1.1:4; the reaction temperature is 82°C, and the reaction time is 13 hours.

[0035] In step (1), the reaction solvent is a mixed solvent of water and tetrahydrofuran, and the volume ratio is 1:1; the concentration of the azafused aryl triflate compound is 0.1 mol / L.

[0036] In step (2), the molar ratio of the non-chiral azafused aryl nitrile compound represented by formula (V), the amino alcohol compound represented by formula (VI), and zinc chloride is 1:1.8:3.

[0037] The solvent used in the condensation reaction is chlorobenzene; the reaction temperature is 130°C, and the reaction time is 45 hours.

[0038] Example 66 The preparation method of the non-chiral and chiral azafused aryl-oxazoline ligand comprises the following steps: Step (A), asymmetric aromatic cyanation reaction: under an argon atmosphere, the azafused aryl triflate compound or perfluorobutanesulfonate compound represented by formula (VII) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition of a palladium catalyst and a chiral ligand as a catalyst, and potassium carbonate as a base, to obtain a chiral azafused aryl nitrile compound represented by formula (VIII); Step (B), condensation reaction: under an argon atmosphere, the chiral azafused aryl nitrile compound represented by formula (VIII) is reacted with the amino alcohol compound represented by formula (VI) under the condition of zinc chloride as a Lewis acid, to obtain the azafused aryl-oxazoline ligand represented by formula (III); The reaction formula is as follows: In formula (VII), LG is a leaving group, including triflate and perfluorobutanesulfonate.

[0039] In step (A), the palladium catalyst is palladium acetate; the chiral ligand is (R)-(5,5'-dichloro-6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine) or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; and potassium carbonate is used as a base.

[0040] In Step (A), the molar ratio of the azabicyclic aryl triflate compound or the nonaflate compound of Formula (VII), potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the chiral ligand, and potassium carbonate is 20:8:1:1:2.5; the reaction temperature is 75°C, and the reaction time is 12 hours. The reaction solvent is a mixture of water and isopropanol at a volume ratio of 1:1. In Step (B), the molar ratio of the chiral azabicyclic aryl nitrile compound of Formula (VIII), the amino alcohol compound of Formula (VI), and zinc chloride is 1:1.5:2. The condensation reaction is carried out in chlorobenzene at a reaction temperature of 120°C for 40 hours.

[0041] Example 67 The preparation method of the non-chiral and chiral azabicyclic aryl-oxazoline ligand comprises the following steps: Step (A), asymmetric aromatic cyanation reaction: under an argon atmosphere, the azabicyclic aryl triflate compound or the nonaflate compound of Formula (VII) is reacted with potassium hexacyanoferrate(II) trihydrate in the presence of a palladium catalyst and a chiral ligand as catalysts and potassium carbonate as base to obtain the chiral azabicyclic aryl nitrile compound of Formula (VIII). Step (B), condensation reaction: under an argon atmosphere, the chiral azabicyclic aryl nitrile compound of Formula (VIII) is reacted with the amino alcohol compound of Formula (VI) in the presence of zinc chloride as Lewis acid to obtain the azabicyclic aryl-oxazoline ligand of Formula (III). The reaction scheme is as follows: In Formula (VII), LG is a leaving group, including triflate and nonaflate.

[0042] In Step (A), the palladium catalyst is palladium acetate; the chiral ligand is (R)-(5,5'-dichloro-6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl) bis(diphenylphosphine) or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; and potassium carbonate is used as the base.

[0043] In Step (A), the molar ratio of the azabicyclic aryl triflate compound or the nonaflate compound of Formula (VII), potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the chiral ligand, and potassium carbonate is 20:10:1:1.2:5; the reaction temperature is 80°C, and the reaction time is 16 hours. The reaction solvent is a mixture of water and isopropanol at a volume ratio of 1:1, and the concentration of the azabicyclic aryl triflate compound or the perfluorobutanesulfonate compound is 0.05 mol / L.

[0044] In step (B), the molar ratio of the chiral azabicyclic aryl nitrile compound represented by formula (VIII), the amino alcohol compound represented by formula (VI), and zinc chloride is 1:2:4. The condensation reaction is carried out in chlorobenzene at a temperature of 140°C for 48 hours.

[0045] Example 68 The preparation method of the non-chiral and chiral azabicyclic aryl-oxazoline ligand comprises the following steps: Step (A), asymmetric aromatic cyanation reaction: under an argon atmosphere, the azabicyclic aryl triflate compound or the perfluorobutanesulfonate compound represented by formula (VII) is reacted with potassium hexacyanoferrate(II) trihydrate in the presence of a palladium catalyst and a chiral ligand as a catalyst, and potassium carbonate as a base, to obtain a chiral azabicyclic aryl nitrile compound represented by formula (VIII); Step (B), condensation reaction: under an argon atmosphere, the chiral azabicyclic aryl nitrile compound represented by formula (VIII) is reacted with the amino alcohol compound represented by formula (VI) in the presence of zinc chloride as a Lewis acid, to obtain the azabicyclic aryl-oxazoline ligand represented by formula (III); The reaction scheme is as follows: In formula (VII), LG is a leaving group, including triflate and perfluorobutanesulfonate.

[0046] In step (A), the palladium catalyst is palladium acetate; the chiral ligand is (R)-(5,5'-dichloro-6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine) or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; and potassium carbonate is used as a base.

[0047] In step (A), the molar ratio of the azabicyclic aryl triflate compound or the perfluorobutanesulfonate compound represented by formula (VII), potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the chiral ligand, and potassium carbonate is 20:9:1:1.1:4; the reaction temperature is 78°C, and the reaction time is 14 hours. The reaction solvent is a mixture of water and isopropanol at a volume ratio of 1:1, and the concentration of the azabicyclic aryl triflate compound or the perfluorobutanesulfonate compound is 0.05 mol / L.

[0048] In step (B), the molar ratio of the chiral azabicyclic aryl nitrile compound of formula (VIII), the amino alcohol compound of formula (VI) and zinc chloride is 1:1.8:3; The solvent used in the condensation reaction is chlorobenzene; the reaction temperature is 130 DEG C, and the reaction time is 45 hours.

[0049] The novel non-chiral and chiral azabicyclic aryl-oxazoline ligands expand the N,N-bidentate ligand library. The ligands have wide application prospects in the field of asymmetric transition metal catalysis, especially in the catalysis of cheap metals such as cobalt, nickel and copper, and are expected to provide a new way for the low-cost synthesis of optically pure drugs and natural products.

[0050] The above shows and describes the basic principles, main features and advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above examples, and the above examples and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. Non-chiral and chiral azabifuryl-oxazoline type ligands, characterized in that, The structural formula is shown as formula (I): , formula (I); In formula (I), the carbon atom marked with * is a central chiral center; Het is a heteroaromatic group; In formula (I), according to whether the nitrogen-linked aryl structure unit contains an axial chiral center, it is divided into two structures of formula (II) and formula (III): , formula (II); In formula (II), the carbon atom marked with * is an axial chiral center and a central chiral center; Het is a heteroaromatic group, including benzo[h]quinoline, pyridine, 3-methylpyridine, phenanthridine, pyrimidine, 1H-pyrazole; R 1 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, benzyl, cyclohexyl or phenyl; R 2 is hydrogen or phenyl; or, R 1 and R 2 together form a 1,2-indanyl group; , formula (III); In formula (III), the carbon atom marked with * is an axial chiral center and a central chiral center; R 1 is hydrogen, ethyl, isopropyl, tert-butyl or benzyl; R 2 is hydrogen.

2. Process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 1, characterized in that, The method comprises the following steps: Step (1), aromatic cyanation reaction: under an argon atmosphere, the nitrogen-linked aryl triflate compound shown as formula (IV) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition that palladium and a non-chiral ligand are used as catalysts and potassium carbonate is used as a base, to obtain a non-chiral nitrogen-linked aryl nitrile compound shown as formula (V); Step (2), condensation reaction: under an argon atmosphere, the non-chiral nitrogen-linked aryl nitrile compound shown as formula (V) is reacted with an amino alcohol compound shown as formula (VI) under the condition that zinc chloride is used as a Lewis acid, to obtain a nitrogen-linked aryl-oxazoline type ligand shown as formula (II); The reaction formula is as follows: 。 3. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 2, characterized in that, In step (1), the palladium catalyst is palladium acetate; the non-chiral ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; and potassium carbonate is used as a base.

4. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 2, characterized in that, In step (1), the molar ratio of the nitrogen-linked aryl triflate compound shown as formula (IV), potassium hexacyanoferrate(II) trihydrate, the palladium catalyst precursor, the non-chiral ligand and potassium carbonate is 20:8-10:1:1-1.2:2.5-5; the reaction temperature is 80-85°C; and the reaction time is 12-14 hours.

5. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 2, characterized in that, In step (1), the reaction solvent is a mixed solvent of water and tetrahydrofuran, and the volume ratio is 1:1; the concentration of the nitrogen-linked aryl triflate compound is 0.1 mol / L.

6. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 2, characterized in that, In step (2), the molar ratio of the non-chiral nitrogen-linked aryl nitrile compound shown as formula (V), the amino alcohol compound shown as formula (VI) and zinc chloride is 1:1.5-2:2-4; The condensation reaction uses chlorobenzene as the solvent; the reaction temperature is 120-140°C; and the reaction time is 40-48 hours.

7. A process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 1, characterized in, that The method comprises the following steps: Step (A), asymmetric aromatic cyanation reaction: under an argon atmosphere, the nitrogen-linked aryl triflate compound or perfluorobutanesulfonate compound shown as formula (VII) is reacted with potassium hexacyanoferrate(II) trihydrate under the condition that palladium and a chiral ligand are used as catalysts and potassium carbonate is used as a base, to obtain a chiral nitrogen-linked aryl nitrile compound shown as formula (VIII); Step (B), condensation reaction: under an argon atmosphere, the chiral nitrogen-linked aryl nitrile compound shown as formula (VIII) is reacted with the amino alcohol compound shown as formula (VI) under the condition that zinc chloride is used as a Lewis acid, to obtain a nitrogen-linked aryl-oxazoline type ligand shown as formula (III); The reaction formula is as follows: In formula (VII), LG is a leaving group, including triflate and nonaflate.

8. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 7, characterized in that, In step (A), palladium catalyst is palladium acetate; chiral ligand is (R)-(5,5'-dichloro-6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine) or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; potassium carbonate is used as base.

9. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 7, characterized in that, In step (A), the molar ratio of azabicycloaryl triflate compound or nonaflate compound represented by formula (VII), potassium hexacyanoferrate(II) trihydrate, palladium catalyst precursor, chiral ligand, potassium carbonate is 20:8~10:1:1~1.2:2.5~5; the reaction temperature is 75~80℃, and the reaction time is 12~16 hours. The reaction solvent is a mixed solvent of water and isopropyl alcohol, and the volume ratio is 1:1; the concentration of azabicycloaryl triflate compound or nonaflate compound is 0.05 mol / L.

10. The process for the preparation of achiral and chiral azadiphenyl-oxazoline type ligands according to claim 7, characterized in that, In step (B), the molar ratio of chiral azabicycloaryl nitrile compound represented by formula (VIII), amino alcohol compound represented by formula (VI) and zinc chloride is 1:1.5~2:2~4. The solvent used in the condensation reaction is chlorobenzene; the reaction temperature is 120~140℃, and the reaction time is 40~48 hours.

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