Preparation method of cyclic chiral nitro compound

Abstract

The invention discloses a preparation method of a cyclic chiral nitro compound, which comprises the following steps: S1, in a protective gas atmosphere, adding a rhodium metal precursor and a chiral diphosphine ligand into a solvent, and stirring for reaction to obtain a chiral rhodium catalyst; s2, dissolving cyclic nitroolefin with a structural formula as shown in a formula I or a formula III in an organic solvent, and carrying out asymmetric hydrogenation reaction in a hydrogen atmosphere under the action of a chiral rhodium catalyst, respectively obtaining a cyclic chiral nitro compound as shown in a structural formula II, or a 2-substituted cyclic chiral nitro compound as shown in a structural formula IV and 2-substituted cyclic chiral nitroolefin as shown in a structural formula V; compared with the existing method for synthesizing the annular chiral nitro compound, the preparation method disclosed by the invention has the characteristics of simplicity in operation, high atom economy, environment friendliness and the like, and is suitable for large-scale popularization and application.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing a cyclic chiral nitro compound. Background Art

[0002] Chiral nitro compounds are an important class of intermediates in synthetic chemistry. They can be used to synthesize chiral amines, chiral aldehydes, chiral carboxylic acids and other compounds through simple transformation. Due to this property, chiral nitro compounds are of great value in medicine, pesticides and natural products. Therefore, it is very meaningful to develop a method for synthesizing chiral nitro compounds with high efficiency and high enantioselectivity.

[0003] The asymmetric hydrogenation of prochiral olefins catalyzed by transition metals has always been an important method for synthesizing chiral compounds due to its advantages such as high atom economy and environmental friendliness. At present, there are many literature reports on the synthesis of chiral nitro compounds by transition metal-catalyzed asymmetric hydrogenation. For example, the synthesis method of β-aryl-β-alkyl substituted nitroolefins (Angew. Chemie., Int. Ed. 2012, 51, 8573-8576.; Org. Lett. 2013, 15, 4014-4017.; Adv. Synth. Catal. 2015, 357, 3875-3879.), the synthesis method of β,β-dialkyl substituted nitroolefins (Chem. Commun. 201 6, 52, 4812-4815.); Synthesis of β-acetylaminonitroolefins (Org. Lett. 2013, 15, 5524-5527.; Chem. Commun. 2014, 50, 12870-12872.; Org. Lett. 2016, 18, 40-43.); Synthesis of β-nitroacrylates (Org. Lett. 2015, 17, 3782-3785.), etc. Xumu Zhang et al. (Chem. Commun. 2014, 50, 8878-8881.) reported the asymmetric hydrogenation of α,β-disubstituted nitroolefins catalyzed by rhodium / JosiPhos, and obtained a series of corresponding chiral nitro compounds with moderate to excellent enantioselectivity.

[0004] Compared with the extensive research on β-substituted nitroolefins, there are few reports on the asymmetric hydrogenation of α-substituted nitroolefins to prepare α-chiral nitro compounds. Moreover, the current transition metal-catalyzed asymmetric hydrogenation of nitroolefins is mainly focused on chain substrates, and there are no reports on cyclic substrates. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention aims to provide a method for preparing a cyclic chiral nitro compound.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The first aspect of the present invention provides a method for preparing a cyclic chiral nitro compound, comprising the following steps:

[0008] S1. Under a protective gas atmosphere, a rhodium metal precursor and a chiral diphosphine ligand are added to a solvent, and stirred for reaction to obtain a chiral rhodium catalyst;

[0009] S2, dissolving a cyclic nitroolefin of the structural formula as shown in formula Ⅰ or formula Ⅲ in an organic solvent, and carrying out an asymmetric hydrogenation reaction under the action of a hydrogen atmosphere and a chiral rhodium catalyst to obtain a cyclic chiral nitro compound of the structural formula as shown in formula Ⅱ, or a 2-substituted cyclic chiral nitro compound of the structural formula as shown in formula Ⅳ and a 2-substituted cyclic chiral nitroolefin of formula Ⅴ;

[0010]

[0011] In formula II, * represents a chiral carbon atom;

[0012] In formula I or II, R is selected from any one of H, C1-C6 alkyl, C1-C6 alkoxy, halogen, and nitro;

[0013] In formula III, IV or V, R1 is selected from any one of H, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl and halogen; R2 is selected from C1-C20 alkyl, which may be a linear alkyl, a branched alkyl, a cyclic alkyl, a substituted C1-C20 alkyl, a phenyl, a naphthyl or a substituted phenyl;

[0014] Wherein, the substituted C1-C20 alkyl group is a C1-C20 alkyl group in which one or more H on the C1-C20 alkyl group is replaced by a substituent A; the substituted phenyl group is a phenyl group in which one or more H on the phenyl group is replaced by a substituent A, and the substituent A is selected from C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl, halogen or phenyl.

[0015] Preferably, in step S1, the molar ratio of the rhodium metal precursor to the chiral diphosphine ligand is 0.5:1.1-1.0:2.2; for example, it can be 1:1.1, 1:1.2, 1:1.3 or 1:1.6.

[0016] Preferably, in step S1, the reaction temperature is 15-35° C., and the reaction time is 20-30 min.

[0017] Preferably, the rhodium metal precursor is any one of cyclooctadiene rhodium chloride dimer, bis(1,5-cyclooctadiene) rhodium tetrafluoroborate, and cyclooctadiene iridium chloride dimer.

[0018] Preferably, the chiral bisphosphine ligand is (S,S)-f-spiroPhos, (S)-BINAP, (R,S P )-JosiPhos-1,

[0019] Any one of (S)-MonoPhos, (R,R)-QuinoxP, (S)-DTBM-SegPhos, and (S)-SegPhos.

[0020] Preferably, in step S1, the solvent is one or a combination of two or more of toluene, tetrahydrofuran, 1,2-dichloroethane, methanol, dioxane, diethyl ether and dichloromethane.

[0021] Preferably, the molar ratio of the rhodium metal precursor to the cyclic nitroolefin is 1-2:100.

[0022] Preferably, in step S2, the hydrogen pressure during the reaction is 300-1200 psi, for example, the reaction pressure may be 300 psi, 600 psi, 900 psi or 1200 psi.

[0023] Preferably, in step S2, the reaction temperature is room temperature to 60° C., and the reaction time is 4 to 24 hours.

[0024] Preferably, in step S2, the organic solvent is one or a combination of two or more of toluene, tetrahydrofuran, 1,2-dichloroethane, methanol, dioxane, diethyl ether and dichloromethane.

[0025] The second aspect of the present invention provides a cyclic chiral nitro compound prepared by the above preparation method.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention firstly uses a rhodium metal precursor and a chiral diphosphine ligand as raw materials to prepare a rhodium chiral catalyst, which has the advantages of low toxicity, high atom economy and environmental friendliness; then, under the action of a hydrogen atmosphere and a rhodium chiral catalyst, a cyclic chiral nitro olefin is subjected to an asymmetric hydrogenation reaction to successfully prepare a cyclic chiral nitro compound. The preparation method of the present invention has the characteristics of simple operation, high atom economy, environmental friendliness, etc., and is suitable for large-scale promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 A synthetic route for the preparation of cyclic chiral nitro compounds;

[0030] Figure 2 is the chemical structural formula of a typical chiral bisphosphine ligand in the present invention. DETAILED DESCRIPTION

[0031] In the following description, for the purpose of illustration rather than limitation, specific details such as specific system structures and technologies are provided to provide a thorough understanding of the embodiments of the present invention. However, it should be clear to those skilled in the art that the present invention may also be implemented in other embodiments without these specific details.

[0032] Example 1

[0033] Reference Figure 1-2 , specifically preparing compound 2a, 3-nitrochromane, whose chemical structure is shown below:

[0034]

[0035] Preparation steps: In a glove box filled with nitrogen, cyclooctadiene rhodium chloride dimer and (S,S)-f-spiroPhos are dissolved in dichloromethane, wherein the molar ratio of cyclooctadiene rhodium chloride dimer to (S,S)-f-spiroPhos is 0.5:1.1, and stirred at 25°C for 0.5h to obtain a chiral rhodium catalyst;

[0036] 1.0 mL of the obtained chiral rhodium catalyst was taken and transferred to a dry reaction bottle pre-added with 3-nitro-2H-chromene and dichloromethane (2.0 mL), wherein the molar ratio of 3-nitro-2H-chromene to cyclooctadiene rhodium chloride dimer was 100:0.5. The reaction bottle was moved to a reaction kettle, hydrogen was introduced, and the hydrogen pressure was set to 1200 psi. The reaction was carried out at 60°C for 24 hours. After the reaction was completed, hydrogen was released, and the reaction product was filtered through a silica gel column to remove the chiral rhodium catalyst to obtain a white solid, namely compound 2a; 21.9 mg, yield: 98%; 92% ee; [α] D 25 =-58.5 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =2.3min(minor),2.5min(major); mp86-88℃. 1H NMR (600MHz, CDCl3) δ7.18-7.12(m,2H),6.96(t,J=5.0Hz,1H),6.87(d,J=8.2Hz,1H),4.9-4.91(m,1 H),4.66-4.59(m,1H),4.47-4.42(m,1H),3.55(dd,J=17.0,5.8Hz,1H),3.34(dd,J=17.0,6.0Hz,1H). 13 C NMR (150MHz, CDCl3) δ153.51,129.74,128.42,122.10,117.80,117.22,77.81,66.03,28.48.TOF-HRMS Calcd.for C9H9NO3[M+H + ]:180.0655,found 180.0651.

[0037] Example 2

[0038] The steps are basically the same as those in Example 1, except that the chiral bisphosphine ligand used is different, and the chiral bisphosphine ligand used in this example is (S)-DTBM-SegPhos. Yield: 88%; 29% ee.

[0039] Example 3

[0040] The steps are basically the same as those in Example 1, except that the chiral bisphosphine ligand used is different, and the chiral bisphosphine ligand used in this example is (S)-SegPhos. Yield: 74%; 33% ee.

[0041] Example 4

[0042] The steps are basically the same as those in Example 1, except that the solvent used is different, and the solvent used in this example is toluene. Yield: 99%; 86% ee.

[0043] Example 5

[0044] The steps are basically the same as those in Example 1, except that the solvent used is different, and the solvent used in this example is tetrahydrofuran. Yield: 99%; 75% ee.

[0045] Example 6

[0046] The steps are basically the same as those in Example 1, except that the solvent used is different. The solvent used in this example is 1,2-dichloroethane. Yield: 99%; 53% ee.

[0047] Example 7

[0048] The steps are basically the same as those in Example 1, except that the solvent used is different, and the solvent used in this example is dioxane. Yield: 99%; 66% ee.

[0049] Example 8

[0050] The steps are basically the same as those in Example 1, except that the solvent used is different, and the solvent used in this example is ether. Yield: 99%; 86% ee.

[0051] Example 9

[0052] The steps are basically the same as those in Example 1, except that the hydrogen pressure is different, and the hydrogen pressure in this example is 600 psi. Yield: 99%; 90% ee.

[0053] Example 10

[0054] The steps are basically the same as those in Example 1, except that the reaction temperature is different. The reaction temperature in this example is room temperature. Yield: 99%; 92% ee.

[0055] Embodiment 11

[0056] The steps are basically the same as those in Example 10, except that the type and amount of the rhodium metal precursor used are different. The rhodium metal precursor used in this example is di(1,5-cyclooctadiene)rhodium tetrafluoroborate (Rh(COD)2BF4), and the molar ratio of di(1,5-cyclooctadiene)rhodium tetrafluoroborate to 3-nitro-2H-chromene is 1.0:100. Yield: 91%; 91%ee.

[0057] Example 12

[0058] The steps are basically the same as those in Example 10, except that the rhodium metal precursor used is different. The rhodium metal precursor used in this example is cyclooctadiene iridium chloride dimer ([Ir(COD)Cl]2). Yield: 99%; 22% ee.

[0059] Example 13

[0060] Preparation of 6-methyl-3-nitrochromane:

[0061]

[0062] The experimental conditions were the same as those of Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced by 6-methyl-3-nitro-2H-chromene.

[0063] The specific preparation steps are as follows: in a glove box filled with nitrogen, cyclooctadiene rhodium chloride dimer and (S,S)-f-spiroPhos are dissolved in dichloromethane, wherein the molar ratio of cyclooctadiene rhodium chloride dimer to (S,S)-f-spiroPhos is 0.5:1.1, and the reaction is stirred at 25°C for 0.5h to obtain a chiral rhodium catalyst; 1.0mL of the obtained chiral rhodium catalyst is taken and transferred to a mixture pre-added with 6-methyl-3-nitro-2H-chromene and dichloromethane (2.0mL) L) in a dry reaction bottle, wherein the molar ratio of 6-methyl-3-nitro-2H-chromene to cyclooctadiene rhodium chloride dimer is 100:0.5, the reaction bottle is moved to a reaction kettle, hydrogen is introduced, and the hydrogen pressure is set to 1200psi, and the reaction is carried out at room temperature for 24 hours. After the reaction is completed, hydrogen is released, and the reaction product is filtered through a silica gel column to filter out the chiral rhodium catalyst to obtain a white solid, namely 6-methyl-3-nitrochromene; 23.4mg, yield: 97%; 90%ee; [α] D 25 =-73.4 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flowrate=3.0mL / min, l=210nm)t R =2.6min(minor),2.7min(major); mp90-92℃. 1 H NMR (600MHz, CDCl3) δ6.98-6.90(m,2H),6.76(d,J=8.2Hz,1H),4.97-4.89(m,1H),4.62-4.57(m, 1H), 4.41-4.36 (m, 1H), 3.50 (dd, J=17.1, 5.6Hz, 1H), 3.29 (dd, J=17.1, 6.0Hz, 1H), 2.28 (s, 3H). 13 C NMR (150MHz, CDCl3) δ151.35,131.46,129.95,129.07,117.45,116.93,78.00,66.11,28.44,20.71.TOF-HRMS Calcd.for C 10 H 11 NO3[M+H + ]:194.0812,found194.0808.

[0064] Embodiment 14

[0065] Preparation of 6-nitro-3-nitrochromane:

[0066]

[0067] The experimental conditions were the same as those in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced by 6-nitro-3-nitro-2H-chromene, and a white solid, namely 6-nitro-3-nitrochromene, was finally obtained; 26.6 mg, yield: 95%; 93% ee; [α] D 25 =-56.7 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =5.1min(minor),5.6min(major); mp133-135℃. 1 H NMR (600MHz, CDCl3) δ8.10(s,1H),8.04(dd,J=8.8,3.1Hz,1H),6.96(dd,J=9.0,1.8Hz,1H),5.02(s,1H),4 .89-4.85(m,1H),4.48(dd,J=12.0,3.0Hz,1H),3.65(dd,J=17.5,2.5Hz,1H),3.40(dd,J=17.5,5.7Hz,1H). 13 CNMR(150MHz, CDCl3)δ158.53,142.38,125.92,124.41,118.50,117.94,76.62,66.50,27.84.TOF-HRMS Calcd.for C9H8N2O5[M+H + ]:225.0506,found225.0501.

[0068] Embodiment 15

[0069] Preparation of 6-chloro-3-nitrochromane:

[0070]

[0071] The experimental conditions were the same as those in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced by 6-chloro-3-nitro-2H-chromene, and a white solid, namely 6-chloro-3-nitrochromene, was finally obtained; 26.2 mg, yield: 98%; 93% ee; [α] D 25 =-73.4 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R=3.1min(minor),4.1min(major); mp83-85℃. 1 H NMR (600MHz, CDCl3) δ7.16-7.06(m,2H),6.80(d,J=8.5Hz,1H),4.94-4.91(m,1H),4.67(ddd,J=11 .7,5.2,1.8Hz,1H),4.41-4.36(m,1H),3.53(dd,J=17.4,5.0Hz,1H),3.29(dd,J=17.4,6.0Hz,1H). 13 C NMR (150MHz, CDCl3) δ152.14,129.25,128.49,126.94,119.39,118.63,77.35,66.17,28.04.TOF-HRMS Calcd.for C9H8ClNO3[M+H + ]:214.0265,found 214.0268.

[0072] Example 16

[0073] Preparation of 8-methoxy-3-nitrochromane:

[0074]

[0075] The experimental conditions were the same as those of Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced by 8-methoxy-3-nitro-2H-chromene, and a white solid, namely 8-methoxy-3-nitrochromene, was finally obtained; 25.4 mg, yield: 97%; 93% ee; [α] D 25 =-48.1 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2= 20 / 80, flow rate= 3.0 mL / min, l = 210 nm) t R = 3.4 min (major), 3.5 min (minor); mp102-105℃. 1H NMR (600MHz, CDCl3) δ6.90(t,J=7.9Hz,1H),6.75(dd,J=15.8,8.0Hz,2H),4.96-4.92(m,1H),4.69(dd,J=11.4 ,5.8Hz,1H),4.49(d,J=13.2Hz,1H),3.86(s,3H),3.54(dd,J=17.1,5.6Hz,1H),3.33(dd,J=17.1,5.9Hz,1H). 13 C NMR (150MHz, CDCl3) δ148.58,142.96,121.84,121.30,118.69,110.21,77.63,66.35,56.10,28.34.TOF-HRMS Calcd.forC 10 H 11 NO4[M+H + ]:210.0761,found210.0765.

[0076] Embodiment 17

[0077] Reference Figure 1 The invention discloses a synthetic route for preparing 2-substituted cyclic chiral nitro compounds, specifically preparing compound (R)-3a, (R)-3-nitro-2-phenyl-2H-chromene and compound 4a, (2S,3S)-3-nitro-2-phenylchromene.

[0078]

[0079] The specific steps are as follows: in a glove box filled with nitrogen, cyclooctadiene rhodium chloride dimer and (S,S)-f-spiroPhos are dissolved in dichloromethane, wherein the molar ratio of cyclooctadiene rhodium chloride dimer to (S,S)-f-spiroPhos is 0.5:1.1, and the reaction is stirred at 25°C for 0.5h to obtain a chiral rhodium catalyst; then 1.0mL of the obtained chiral rhodium catalyst is transferred to a dry The reaction flask was dried, wherein the molar ratio of 3-nitro-2-phenyl-2H-chromene to cyclooctadiene rhodium chloride dimer was 100:0.5, the reaction flask was moved to a reaction kettle, hydrogen was introduced, the hydrogen pressure was set to 1200psi, and the reaction was carried out at room temperature for 24h; after the reaction was completed, hydrogen was released, and the reaction mixture was subjected to silica gel column chromatography to obtain a white solid, namely compound 4a, (2S,3S)-3-nitro-2-phenylchromene; 15.0mg, yield: 47%; 97%ee; [α] D 25=+28.7(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =3.5min(major),3.9min(minor); mp142-144℃. 1 HNMR(600MHz, CDCl3)δ7.42-7.36(m,5H),7.24(t,J=7.9Hz,1H),7.18(d,J=7.5H z,1H),7.05-7.00(m,2H),5.43(d,J=2.9Hz,1H),5.22(m,1H),3.45-3.36(m,2H). 13 C NMR (150MHz, CDCl3) δ153.91,135.82,129.36,129.14,128.94,128.37,125.90,122.16,117.69,117.25,82.59,76.36,28.33.TOF-HRMS Calcd.for C 15 H 14 NO3[M+H + ]:256.0968,found 256.0971.

[0080] and yellow solid, namely compound (R)-3a, (R)-3-nitro-2-phenyl-2H-chromene; 15.2 mg, yield: 48%; 95% ee; [α] D 25 =-46.1(c=1.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2= 20 / 80, flow rate = 3.0 mL / min, l = 210 nm) t R = 3.8 min (major), 4.6 min (minor); 1 H NMR (600MHz, CDCl3) δ8.06 (s, 1H), 7.39-7.38 (m, 2H), 7.34-7.31 (m, 5H), 7.00 (t, J = 7.6Hz, 1H), 6.87 (d, J = 8.8Hz, 1H), 6.59 (s, 1H). 13C NMR (150MHz, CDCl3) δ153.75,141.37,136.98,134.50,130.62,129.66,129.46,129.04,127.22,122.72,118.13,117.47,74.45.TOF-HRMS Calcd.for C 15 H 12 NO3[M+H + ]:254.0812,found 254.0807.

[0081] Embodiment 18

[0082] The steps are basically the same as those in Example 17, except that the chiral diphosphine ligands used are different. The chiral phosphine ligands used in this example are (R, S P )-JosiPhos-1. yield((R)-3a):50%; ee((R)-3a):7%; yield(4a):48%; ee(4a):7%.

[0083] Embodiment 19

[0084] The steps are basically the same as those in Example 17, except that the chiral bisphosphine ligand used is different. The chiral bisphosphine ligand used in this example is (S)-SegPhos. yield ((R)-3a): 42%; ee ((R)-3a): 53%; yield (4a): 56%; ee (4a): 41%.

[0085] Embodiment 20

[0086] The steps are basically the same as those in Example 17, except that the solvent used is different. The solvent used in this example is toluene. Yield ((R)-3a): 33%; ee ((R)-3a): 85%; yield (4a): 64%; ee (4a): 47%.

[0087] Embodiment 21

[0088] The steps are basically the same as those in Example 17, except that the solvent used is different. The solvent used in this example is tetrahydrofuran. yield ((R)-3a): 26%; ee ((R)-3a): 93%; yield (4a); 73%; ee (4a): 35%.

[0089] Embodiment 22

[0090] The steps are basically the same as those in Example 17, except that the solvent used is different. The solvent used in this example is methanol. yield (R-3a): 53%; ee (R-3a): 22%; yield (4a): 46%; ee (4a): 26%.

[0091] Embodiment 23

[0092] The steps are basically the same as those in Example 17, except that the solvent used is different. The solvent used in this example is ether. Yield ((R)-3a): 20%; ee ((R)-3a): 64%; yield (4a): 79%; ee (4a): 42%.

[0093] Embodiment 24

[0094] The steps are basically the same as those in Example 17, except that the hydrogen pressure is different. The hydrogen pressure in this example is 600 psi. Yield ((R)-3a): 60%; ee ((R)-3a): 52%; yield (4a): 39%; ee (4a): 80%.

[0095] Embodiment 25

[0096] The steps are basically the same as those in Example 17, except that the type and amount of the rhodium metal precursor used are different. The rhodium metal precursor used in this example is di(1,5-cyclooctadiene)rhodium tetrafluoroborate (Rh(COD)2BF4), and the molar ratio of di(1,5-cyclooctadiene)rhodium tetrafluoroborate to 3-nitro-2-phenyl-2H-chromene is 1.0:100. Yield ((R)-3a): 88%; ee ((R)-3a): 11%; yield (4a): 11%; ee (4a): 91%.

[0097] Embodiment 26

[0098] Preparation of 4-((2S,3S)-3-nitrochroman-2-yl)phenol and (R)-4-(3-nitro-2H-chromen-2-yl)phenol, the structural formulas of which are shown below:

[0099]

[0100] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 4-(3-nitro-2H-chromene-2-yl)phenol, and a white solid, namely 4-((2S,3S)-3-nitrochroman-2-yl)phenol, was finally obtained; 15.3 mg, yield: 45%; 99% ee; [α] D 25=+54.3(c=1.0, CH2Cl2); SFC(Lux5u Amylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =11.1min(major),13.6min(minor); mp189-191℃. 1 H NMR (600MHz, CDCl3) δ7.22(dd,J=8.9,6.7Hz,3H),7.17(dd,J=7.3,2.2Hz,1H),7.05-6.97(m,2H),6.83(dd, J=8.4,1.6Hz,2H),5.40(d,J=2.9Hz,1H),5.18(ddd,J=5.6,4.1,2.7Hz,1H),4.92(s,1H),3.44-3.34(m,2H). 13 C NMR (150MHz, CDCl3) δ156.25,153.97,129.40,128.43,128.10,127.54,122.13,117.62,117.25,115.87,82.67,76.17,28.17.TOF-HRMS Calcd.for C 15 H 14 NO4[M+H + ]:272.0917,found 272.0913.

[0101] and yellow solid, i.e. (R)-4-(3-nitro-2H-chromen-2-yl)phenol; 14.8 mg, yield: 44%; >99% ee; [α] D 25 =-35.2 (c=1.0, CH2Cl2); SFC (Lux 5u Amylose-1, MeOH / CO2=20 / 80, flowrate=3.0mL / min, l=210nm)t R =10.6min(major),11.4min(minor); 1 H NMR (600MHz, CDCl3) δ8.04 (s, 1H), 7.32 (td, J = 7.5, 1.8Hz, 2H), 7.26-7.23 (m, 2H), 7.03-6.98(m,1H),6.87-6.83(m,1H),6.78-6.72(m,2H),6.51(s,1H),4.84(s,1H). 13C NMR (150MHz, CDCl3) δ156.71,153.72,134.47,130.56,129.48,129.30,129.01,122.67,118.19,117.56,115.87,74.12.TOF-HRMS Calcd.for C 15 H 12 NO4[M+H + ]:270.0761,found 270.0758.

[0102] Embodiment 27

[0103] Preparation of (2S,3S)-3-nitro-2-(4-(trifluoromethyl)phenyl)chroman and (R)-3-nitro-2-(4-(trifluoromethyl)phenyl)-2H-chromene, the structural formulas of which are shown below:

[0104]

[0105] The experimental conditions were the same as those of Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 3-nitro-2-(4-(trifluoromethyl)phenyl)-2H-chromene, and a white solid, i.e., (2S,3S)-3-nitro-2-(4-(trifluoromethyl)phenyl)chroman, was finally obtained; 19.0 mg, yield: 47%; 97% ee; [α] D 25 =+85.4(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =3.3min(minor),3.8min(major); mp158-160℃. 1 HNMR(600MHz, CDCl3)δ7.67(d,J=8.6Hz,2H),7.52(d,J=8.0Hz,2H),7.26-7.22(m,1H),7.19(d ,J=7.6Hz,1H),7.04(td,J=7.6,3.7Hz,2H),5.46(s,1H),5.28-5.21(m,1H),3.51-3.37(m,2H). 13 C NMR (150MHz, CDCl3) δ153.56,139.89,131.21(q, 2 J FC =32.5Hz),129.39,128.49,126.38,125.90(q, 3J FC =3.2Hz),124.08(q, 1 J FC =270.8Hz),122.55,117.58,117.27,82.32,75.77,28.44.TOF-HRMS Calcd.forC 16 H 13 F3NO3[M+H + ]:324.0842,found 324.0845.

[0106] and yellow solid, namely (R)-3-nitro-2-(4-(trifluoromethyl)phenyl)-2H-chromene; 19.3 mg, yield: 48%; >99% ee; [α] D 25 =-117.4 (c=1.0, CH2Cl2); SFC (Lux 5u Amylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =2.5min(minor),2.9min(major); 1 H NMR(600MHz, CDCl3)δ8.08(s,1H),7.58(d,J=7.9Hz,2H),7.50(d,J=8.0Hz,2 H),7.38-7.32(m,2H),7.08-6.99(m,1H),6.89(d,J=8.1Hz,1H),6.63(s,1H). 13 C NMR (150MHz, CDCl3) δ153.48,140.83,140.79,134.85,131.73(q, 2 J FC =32.4Hz),130.85,129.93,127.60,126.10(q, 3 J FC =4.1Hz),123.96(q, 1 J FC =270.7Hz),123.15,117.91,117.48,73.66.TOF-HRMSCalcd.for C 16 H 11 F3NO3[M+H + ]:322.0686,found 322.0690.

[0107] Embodiment 28

[0108] Preparation of (2S,3S)-6,8-dibromo-2-(4-bromophenyl)-3-nitrochromene and (R)-6,8-dibromo-2-(4-bromophenyl)-3-nitro-2H-chromene, the structural formulas of which are shown below:

[0109]

[0110] The experimental conditions were the same as those of Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 6,8-dibromo-2-(4-bromophenyl)-3-nitro-2H-chromene, and a white solid, i.e., (2S,3S)-6,8-dibromo-2-(4-bromophenyl)-3-nitrochromene, was finally obtained; 28.2 mg, yield: 46%; >99% ee; [α] D 25 =+74.2(c=2.0, CH2Cl2); SFC(Lux5u Cellulose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =12.0min(major),15.4min(minor); mp197-199℃. 1 H NMR (600MHz, CDCl3) δ7.62 (d, J = 2.3Hz, 1H), 7.58-7.55 (m, 2H), 7.32-7.27 (m, 3H), 5.41 (d, J = 2.6Hz, 1H), 5.21-5.25 (m, 1H), 3.37-3.49 (m, 2H). 13 C NMR (150MHz, CDCl3) δ149.61,134.46,133.84,132.34,131.08,123.55,120.81,114.41,112.30,81.43,76.48,28.61.TOF-HRMS Calcd.for C 15 H 11 Br3NO3[M+H + ]:491.8263,found491.8265.

[0111] and yellow solid, namely (R)-6,8-dibromo-2-(4-bromophenyl)-3-nitro-2H-chromene; 29.4 mg, yield: 48%; 95% ee; [α] D 25 =-170.9 (c=2.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)tR =13.4min(major),15.6min(minor); 1 H NMR (600MHz, CDCl3) δ7.94(s,1H),7.66(dd,J=2.3,1.0Hz,1H),7.48-7.44(m,2H),7.40(dd,J=2.3,1.0Hz,1H),7.25-7.22(m,3H),6.65(s,1H). 13 C NMR (150MHz, CDCl3) δ149.47,142.53,139.42,134.88,132.42,131.79,128.65,127.77,124.36,120.83,115.10,112.65,74.22.TOF-HRMS Calcd.for C 15 H9Br3NO3[M+H + ]:489.8107,found 489.8105.

[0112] Embodiment 29

[0113] Preparation of (2S,3S)-6-methyl-3-nitro-2-phenylchromene and (R)-6-methyl-3-nitro-2-phenyl-2H-chromene, the structural formulas of which are shown below:

[0114]

[0115] The experimental conditions were the same as those of Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 6-methyl-3-nitro-2-phenyl-2H-chromene, and a white solid, i.e., (2S,3S)-6-methyl-3-nitro-2-phenylchromene, was finally obtained; 16.2 mg, yield: 48%; 90% ee; [α] D 25 =+86.2(c=1.0, CH2Cl2); SFC(Lux5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =8.3min(major),9.7min(minor); mp80-82℃. 1H NMR (600MHz, CDCl3) δ7.41-7.34(m,5H),7.03(dd,J=8.3,2.1Hz,1H),6.99-6.97(m,1H),6.91(d,J=8 .3Hz,1H),5.41(d,J=2.8Hz,1H),5.21(ddd,J=5.9,3.8,2.8Hz,1H),3.42-3.32(m,2H),2.31(s,3H). 13 C NMR (150MHz, CDCl3) δ151.80,135.98,131.52,129.64,129.12,128.94,125.95,117.30,117.01,82.73,76.47,28.35,20.81.TOF-HRMS Calcd.for C 16 H 16 NO3[M+H + ]:270.1125,found 270.1128.

[0116] And yellow solid, namely (R)-6-methyl-3-nitro-2-phenyl-2H-chromene; 15.0 mg, yield: 45%; >99% ee; [α] D 25 =-44.4 (c=1.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flowrate=3.0mL / min, l=210nm)t R =4.2min(major),5.6min(minor); 1 H NMR (600MHz, CDCl3) δ8.01 (s, 1H), 7.37-7.35 (m, 2H), 7.32-7.29 (m, 3H), 7.13-7.10 (m, 2H), 6.76 (d, J = 8.2Hz, 1H), 6.55 (s, 1H), 2.29 (s, 3H). 13 C NMR (150MHz, CDCl3) δ151.67,141.41,137.05,135.33,132.21,130.70,129.6 9,129.57,129.00,127.21,117.98,117.23,74.33,20.58.TOF-HRMSCalcd.for C 16 H 14 NO3[M+H + ]:268.0968,found 268.0965.

[0117] Embodiment 30

[0118] Preparation of (2S,3S)-6-methoxy-3-nitro-2-phenylchromene and (R)-6-methoxy-3-nitro-2-phenyl-2H-chromene, the structural formulas of which are shown below:

[0119]

[0120] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 6-methoxy-3-nitro-2-phenyl-2H-chromene, and a white solid, i.e., (2S,3S)-6-methoxy-3-nitro-2-phenylchromene, was finally obtained; 17.1 mg, yield: 48%; 96% ee; [α] D 25 =+65.2(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =5.0min(major),5.6min(minor); mp119-121℃. 1 H NMR(600MHz, CDCl3)δ7.33(td,J=7.8,1.6Hz,1H),7.28-7.24(m,1H),7.23-7.19(m,1H),7.10(dd,J=7.7,1.7Hz,1H),7.00-6.9 0(m,4H),6.08(d,J=5.0Hz,1H),5.30(q,J=5.3Hz,1H),3.88(s,3H),3.55(dd,J=16.8,5.9Hz,1H),3.09(dd,J=16.8,5.1Hz,1H). 13 CNMR (150MHz, CDCl3) δ156.39,153.44,130.35,129.53,128.69,127.57,124.99,121. 69,121.21,117.59,116.90,111.09,80.86,73.37,55.80,27.49.TOF-HRMSCalcd.for C 16 H 16 NO4[M+H + ]:286.1074,found 286.1071.

[0121] And brick red solid, namely (R)-6-methoxy-3-nitro-2-phenyl-2H-chromene; 17.0 mg, yield: 48%; >99% ee; [α]D 25 =-60.2 (c=1.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =4.5min(major),5.8min(minor); 1 H NMR (600MHz, CDCl3) δ8.02(s,1H),7.37-7.34(m,2H),7.32-7.30(m,3H),6.88(dd,J=8.7,3.0Hz,1H),6.83-6.79(m,2H),6.54(s,1H),3.78(s,3H). 13 C NMR (150MHz, CDCl3) δ154.99,147.71,142.06,136.81,129.60,129.56,129.00,127.22,120.86,118.65,118.36,113.91,74.24,56.01.TOF-HRMS Calcd.for C 16 H 14 NO4[M+H + ]:284.0917,found 284.0914.

[0122] Embodiment 31

[0123] Preparation of (2S, 3S)-3-nitro-2-(o-tolyl)chroman and (R)-3-nitro-2-(o-tolyl)-2H-chromene, the structural formulas of which are shown below:

[0124]

[0125] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 3-nitro-2-(o-tolyl)-2H-chromene, and a white solid, i.e., (2S,3S)-3-nitro-2-(o-tolyl)chroman, was obtained; 14.8 mg, yield: 44%; 98% ee; [α] D 25 =+81.5(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =3.7min(major),4.4min(minor); mp118-120℃. 1H NMR (600MHz, CDCl3) δ7.51 (d, J = 6.7Hz, 1H), 7.34-7.27 (m, 2H), 7.25-7.15 (m, 3H), 7. 08-6.95(m,2H),5.45(s,1H),5.20(d,J=5.8Hz,1H),3.53-3.42(m,2H),2.37(s,3H). 13 C NMR (150MHz, CDCl3) δ154.54,133.96,133.58,130.76,129.18,129.01,128.13, 126.90,126.02,122.31,117.97,117.51,81.33,73.69,29.27,19.24.TOF-HRMS Calcd.for C 16 H 16 NO3[M+H + ]:270.1125,found 270.1122.

[0126] and yellow solid, namely (R)-3-nitro-2-(o-tolyl)-2H-chromene; 16.4 mg, yield: 49%; 93% ee; [α] D 25 =-13.3 (c=1.0, CH2Cl2); SFC (Lux 5u Amylose-2, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =3.3min(major),5.1min(minor); 1 HNMR(400MHz, CDCl3)δ8.13(s,1H),7.33(dd,J=7.7,1.7Hz,1H),7.31-7.27(m,1H),7.25-7.20(m,2H),7.11(dd,J=7 .9,1.4Hz,1H),7.04(td,J=7.4,1.6Hz,1H),6.98(t,J=7.5Hz,1H),6.83(s,1H),6.77(d,J=8.2Hz,1H),2.67(s,3H). 13 C NMR (150MHz, CDCl3) δ153.61,141.14,137.40,134.39,134.11,131.50,130.51,1 30.03,129.74,126.54,126.36,122.63,118.24,117.48,71.39,19.42.TOF-HRMS Calcd.for C 16 H14 NO3[M+H + ]:268.0968,found 268.0972.

[0127] Embodiment 32

[0128] Preparation of (2S,3S)-2-(2-methoxyphenyl)-3-nitrochromene and (R)-2-(2-methoxyphenyl)-3-nitro-2H-chromene, the structural formulas of which are shown below:

[0129]

[0130] The experimental conditions were the same as those of Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 2-(2-methoxyphenyl)-3-nitro-2H-chromene, and a white solid, i.e., (2S,3S)-2-(2-methoxyphenyl)-3-nitrochromene, was finally obtained; 16.4 mg, yield: 46%; 95% ee; [α] D 25 =+223.0 (c=1.0, CH2Cl2); HPLC (Lux 5u Amylose-2, n-hexane / i-propanol=90 / 10, flow rate=1.0mL / min, l=210nm)t R =12.9min(major),16.1min(minor); mp181-183℃. 1 H NMR(600MHz, CDCl3)δ7.55(dd,J=7.6,0.9Hz,1H),7.39-7.35(m,1H),7.23-7.18(m,2H),7.04(t,J=7.6Hz,1H),7.03-6 .99(m,2H),6.95(d,J=8.3Hz,1H),5.56(d,J=2.1Hz,1H),5.45(dt,J=6.2,1.9Hz,1H),3.89(s,3H),3.53-3.39(m,2H). 13 C NMR (150MHz, CDCl3) δ155.54,154.50,129.86,129.21,127.96,126.80,124.20, 122.10,121.26,118.39,117.40,110.14,80.74,72.02,55.65,29.04.TOF-HRMS Calcd.for C 16 H 16 NO4[M+H + ]:286.1074,found 286.1071.

[0131] And yellow solid, namely (R)-2-(2-methoxyphenyl)-3-nitro-2H-chromene, 17.0 mg, yield: 48%; >99% ee; [α] D 25 =-34.8 (c=1.0, CH2Cl2); HPLC (Lux 5u Amylose-2, n-hexane / i-propanol=90 / 10, flow rate=1.0mL / min, l=210nm)t R =14.6min(major),25.8min(minor); 1 H NMR (600MHz, CDCl3) δ8.08 (s, 1H), 7.33-7.26 (m, 3H), 7.15 (dd, J = 7.6, 1.7Hz, 1H),7.05(s,1H),6.99-6.94(m,2H),6.81(td,J=7.6,1.1Hz,2H),3.90(s,3H). 13 C NMR (150MHz, CDCl3) δ157.52,153.99,140.96,134.25,131.24,130.37,129.74,1 28.16,124.62,122.38,120.67,118.25,117.44,111.73,69.13,56.07.TOF-HRMS Calcd.for C 16 H 14 NO4[M+H + ]:284.0917,found284.0914.

[0132] Embodiment 33

[0133] Preparation of (2S,3S)-2-isopropyl-3-nitrochromene and (R)-2-isopropyl-3-nitro-2H-chromene, the structural formulas of which are shown below:

[0134]

[0135] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 2-isopropyl-3-nitro-2H-chromene, and a white solid, i.e., (2S,3S)-2-isopropyl-3-nitrochromene, was finally obtained; 13.0 mg, yield: 47%; 99% ee; [α] D 25=-51.2 (c=1.0, CH2Cl2); SFC (Lux 5uAmylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =6.0min(major),6.5min(minor); mp110-112℃. 1 HNMR (600MHz, CDCl3) δ7.19-7.10(m,2H),6.96(td,J=7.4,1.2Hz,1H),6.90(dd,J=8.1,1.2Hz,1H),5.21(dt,J=6.1,1.7Hz,1H),3.63(dt, J=9.9,1.1Hz,1H),3.37(d,J=16.3Hz,1H),3.25(dd,J=18.0,6.1Hz,1H),2.09-2.00(m,1H),1.20(d,J=6.5Hz,3H),1.14(d,J=6.7Hz,3H). 13 C NMR (150MHz, CDCl3) δ154.39,129.08,127.88,121.91,118.36,117.03,81.03,78.49,29.80,29.38,19.82,18.58.TOF-HRMS Calcd.for C 12 H 16 NO3[M+H + ]:222.1125,found 222.1122.

[0136] And yellow solid, i.e. (R)-2-isopropyl-3-nitro-2H-chromene, 13.2 mg, yield: 48%; >99% ee; [α] D 25 =+16.7(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-1, MeOH / CO2=10 / 90, flow rate=3.0mL / min, l=210nm)t R =4.6min(major),4.8min(minor); 1H NMR (600MHz, CDCl3) δ7.85 (s, 1H), 7.37-7.31 (m, 1H), 7.25 (dd, J=7.5, 1.6Hz, 1H), 6.97 (td, J=7.5, 1.1Hz, 1H), 6.93 (d, J = 8.2Hz, 1H), 5.38 (d, J = 6.6Hz, 1H), 2.17-2.06 (m, J = 6.8Hz, 1H), 0.98 (dd, J = 6.8, 5.2Hz, 6H). 13 C NMR (150MHz, CDCl3) δ154.79,141.83,134.21,130.51,129.01,122.33,118.51,116.79,77.70,32.83,18.17,17.72.TOF-HRMS Calcd.for C 12 H 14 NO3[M+H + ]:220.0968,found220.0972.

[0137] Embodiment 34

[0138] Preparation of (2S,3S)-2-heptyl-3-nitrochromene and (R)-2-heptyl-3-nitro-2H-chromene, the structural formulas of which are shown below:

[0139]

[0140] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 2-heptyl-3-nitro-2H-chromene, and a colorless oily liquid, i.e., (2S,3S)-2-heptyl-3-nitrochromene, was finally obtained; 16.3 mg, yield: 47%; >99% ee; [α] D 25 =-47.1 (c=1.0, CH2Cl2); SFC (Lux 5uAmylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =4.2min(major),4.6min(minor); 1H NMR (600MHz, CDCl3) δ7.19-7.11(m,2H),6.99-6.94(m,1H),6.89(d,J=8.2Hz,1H),5.02-4.99(m,1H),4.33-4.24(m,1H),3.38(dd,J=17.6,4 .3Hz,1H),3.26(dd,J=17.6,6.2Hz,1H),1.83-1.74(m,1H),1.66-1.56(m,2H),1.54-1.46(m,1H),1.37-1.26(m,8H),0.90(t,J=6.6Hz,3H). 13 CNMR (150MHz, CDCl3) δ153.44,129.34,128.11,121.86,118.16,117.27,80. 57,74.96,31.93,30.49,29.38,29.28,28.01,25.68,22.81,14.28.TOF-HRMS Calcd.for C 16 H 24 NO3[M+H + ]:278.1751,found 278.1754.

[0141] and yellow oily liquid, i.e. (R)-2-heptyl-3-nitro-2H-chromene, 16.5 mg, yield: 48%; 98% ee; [α] D 25 =+2.2(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-1, MeOH / CO2=10 / 90, flow rate=3.0mL / min, l=210nm)t R =3.8min(major),3.6min(minor); 1 H NMR (600MHz, CDCl3) δ7.78(s,1H),7.36(t,J=7.7Hz,1H),7.27(d,J=6.5Hz,1H),7.00(t,J=7.3Hz,1H),6.94(s,1H),5.52(dd,J=9.9 ,3.1Hz,1H),1.87-1.80(m,1H),1.67-1.60(m,1H),1.58-1.51(m,1H),1.48-1.41(m,1H),1.30-1.23(m,8H),0.87(t,J=6.9Hz,3H). 13C NMR (150MHz, CDCl3) δ153.64,143.10,134.15,130.50,128.39,122.57,118.6 6,117.53,73.33,32.60,31.91,29.26,29.13,25.07,22.79,14.26.TOF-HRMS Calcd.for C 16 H 22 NO3[M+H + ]:276.1594,found276.1597.

[0142] Embodiment 35

[0143] Preparation of (2S,3S)-2-cyclopropyl-3-nitrochromene and (R)-2-cyclopropyl-3-nitro-2H-chromene, the structural formulas of which are shown below:

[0144]

[0145] The experimental conditions were the same as those in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced by 2-cyclopropyl-3-nitro-2H-chromene, and a white solid, i.e., (2S,3S)-2-cyclopropyl-3-nitrochromene, was finally obtained; 13.2 mg, yield: 48%; >99% ee; [α] D 25 =-69.0 (c=1.0, CH2Cl2); SFC (Lux 5uAmylose-1, MeOH / CO2=20 / 80, flow rate=3.0mL / min, l=210nm)t R =4.2min(major),5.4min(minor); mp103-105℃. 1 HNMR(600MHz, CDCl3)δ7.19-7.15(m,1H),7.13(dd,J=7.5,1.4Hz,1H),6.95(td, J=7.4,1.2Hz,1H),6.91(dd,J=8.2,1.2Hz,1H),5.08(td,J=5.9,3.0Hz,1H),3.6 7(dd,J=8.9,2.9Hz,1H),3.52(dd,J=17.4,5.5Hz,1H),3.26(dd,J=17.4,6.1Hz, 1H),1.22-1.12(m,1H),0.74-0.64(m,2H),0.59-0.52(m,1H),0.41-0.33(m,1H). 13C NMR (150MHz, CDCl3) δ153.37,129.44,128.26,121.82,117.80,117.27,80.77,78.99,27.74,11.12,3.56,2.35.TOF-HRMS Calcd.for C 12 H 14 NO3[M+H + ]:220.0968,found 222.0966.

[0146] And yellow solid, namely (R)-2-cyclopropyl-3-nitro-2H-chromene, 13.3 mg, yield: 49%; 91% ee; [α] D 25 =+64.4(c=1.0, CH2Cl2); SFC(Lux 5u Amylose-1, MeOH / CO2=10 / 90, flow rate=3.0mL / min, l=210nm)t R =4.2min(major),4.9min(minor);MP:50-52℃. 1 H NMR (600MHz, CDCl3) δ7.84 (s, 1H), 7.38-7.35 (m, 1H), 7.29 (dd, J = 7.5, 2.0Hz, 1H), 7.04-6. 96(m,2H),5.00(d,J=8.5Hz,1H),1.31-1.24(m,1H),0.70-0.64(m,1H),0.56-0.51(m,3H). 13 C NMR (150MHz, CDCl3) δ154.25,142.32,134.10,130.49,128.41,122.53,118.54,117.44,76.62,14.56,3.39,3.18.TOF-HRMS Calcd.for C 12 H 12 NO3[M+H + ]:218.0812,found 218.0808.

[0147] The present invention is not limited to the above-mentioned specific implementation modes. Various changes made by ordinary technicians in this field based on the above-mentioned concepts without creative work are all within the protection scope of the present invention.

Claims

1. A method for preparing a cyclic chiral nitro compound, characterized in that: The following steps are involved: S1. Under a protective gas atmosphere, a rhodium metal precursor and a chiral diphosphine ligand are added to a solvent, and stirred for reaction to obtain a chiral rhodium catalyst; S2, dissolving a cyclic nitroolefin of the structural formula as shown in formula Ⅰ or formula Ⅲ in an organic solvent, and carrying out an asymmetric hydrogenation reaction under the action of a hydrogen atmosphere and a chiral rhodium catalyst to obtain a cyclic chiral nitro compound of the structural formula as shown in formula Ⅱ, or a 2-substituted cyclic chiral nitro compound of the structural formula as shown in formula Ⅳ and a 2-substituted cyclic chiral nitroolefin of formula Ⅴ; In formula II, * represents a chiral carbon atom; In formula I or II, R is selected from any one of H, C1-C6 alkyl, C1-C6 alkoxy, halogen, and nitro; In Formula III, Formula IV or Formula V, R 1 Any one selected from H, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl, halogen; R 2 Selected from C1-C20 alkyl, substituted C1-C20 alkyl, phenyl, naphthyl or substituted phenyl; Wherein, the C1-C20 alkyl group is a C1-C20 alkyl group in which one or more H on the C1-C20 alkyl group is replaced by a substituent A; the substituted phenyl group is a phenyl group in which one or more H on the phenyl group is replaced by a substituent A, and the substituent A is selected from C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl, halogen or phenyl.

2. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: In step S1, the molar ratio of the rhodium metal precursor to the chiral diphosphine ligand is 0.5:1.1-1.0:2.

2.

3. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: In step S1, the reaction temperature is 15-35°C, and the reaction time is 20-30 minutes.

4. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: The chiral diphosphine ligand is (S,S)-f-spiroPhos, (S)-BINAP, (R,S P Any one of )-JosiPhos-1, (S)-MonoPhos, (R,R)-QuinoxP, (S)-DTBM-SegPhos, and (S)-SegPhos.

5. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: The rhodium metal precursor is any one of cyclooctadiene rhodium chloride dimer, bis(1,5-cyclooctadiene) rhodium tetrafluoroborate, and cyclooctadiene iridium chloride dimer.

6. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: In step S1, the solvent is one or a combination of two or more of toluene, tetrahydrofuran, 1,2-dichloroethane, methanol, dioxane, diethyl ether and dichloromethane.

7. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: The molar ratio of the rhodium metal precursor to the cyclic nitroolefin is 1-2:

100.

8. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: In step S2, the hydrogen pressure during the reaction is 300 to 1200 psi, the reaction temperature is room temperature to 60° C., and the reaction time is 4 to 24 hours.

9. The method for preparing a cyclic chiral nitro compound according to claim 1, characterized in that: In step S2, the organic solvent is one or a combination of two or more of toluene, tetrahydrofuran, 1,2-dichloroethane, methanol, dioxane, diethyl ether and dichloromethane.

10. A cyclic chiral nitro compound obtained by the preparation method according to any one of claims 1 to 9.

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