Process for the preparation of cyclic chiral nitro compounds

Abstract

The application discloses a preparation method of a cyclic chiral nitro compound, and comprises the following steps: S1, adding a rhodium metal precursor and a chiral diphosphine ligand into a solvent under a protective gas atmosphere, and stirring to obtain a chiral rhodium catalyst; and S2, dissolving a cyclic nitro olefin with a structural formula as shown in formula I or formula III into an organic solvent, and performing an asymmetric hydrogenation reaction under the action of hydrogen atmosphere and the chiral rhodium catalyst, so as to obtain a cyclic chiral nitro compound with a structural formula as shown in formula II, or a 2-substituted cyclic chiral nitro compound with a structural formula as shown in formula IV and a 2-substituted cyclic chiral nitro olefin with a structural formula as shown in formula V. Compared with a method for synthesizing the cyclic chiral nitro compound, the preparation method has the characteristics of simple operation, high atomic economy and environmental friendliness, and is suitable for large-scale popularization and application.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of a cyclic chiral nitro compound. BACKGROUND

[0002] As an important intermediate in synthetic chemistry, chiral nitro compounds can be converted into chiral amines, chiral aldehydes, chiral carboxylic acids and other compounds. Due to this property, chiral nitro compounds have important value in medicines, pesticides and natural products. Therefore, it is very meaningful to develop a method for efficiently and highly enantioselectively synthesizing chiral nitro compounds.

[0003] Transition metal-catalyzed asymmetric hydrogenation of prochiral olefins has been an important method for synthesizing chiral compounds due to its high atom economy and environmental friendliness. At present, there are many literatures reported on the synthesis of chiral nitro compounds by transition metal-catalyzed asymmetric hydrogenation. For example, the synthesis method of β-aryl-β-alkyl substituted nitro olefins (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-di-alkyl substituted nitro olefins (Chem. Commun. 2016, 52, 4812-4815.), the synthesis method of β-acetamido nitro olefins (Org. Lett. 2013, 15, 5524-5527.; Chem. Commun. 2014, 50, 12870-12872.; Org. Lett. 2016, 18, 40-43.), the synthesis method of β-nitro acrylates (Org. Lett. 2015, 17, 3782-3785.), and the like. Xumu Zhang et al. (Chem. Commun. 2014, 50, 8878-8881.) reported the rhodium / JosiPhos-catalyzed asymmetric hydrogenation of α, β-disubstituted nitro olefins, and a series of corresponding chiral nitro compounds were obtained with moderate to excellent enantioselectivity.

[0004] Compared with the extensive research on β-substituted nitro olefins, the asymmetric hydrogenation of α-substituted nitro olefins for preparing α-chiral nitro compounds is rarely reported, and at present, the transition metal-catalyzed asymmetric hydrogenation of nitro olefins mainly focuses on chain substrates, and there is no report on cyclic substrates. SUMMARY

[0005] In view of the problems existing in the prior art, the purpose of the present application is to provide a preparation method of a cyclic chiral nitro compound.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A 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 bisphosphine ligand are added to a solvent and stirred to react, thereby obtaining a chiral rhodium catalyst.

[0009] S2. Dissolve the cyclic nitro olefins with the structural formula as shown in Formula I or Formula III in an organic solvent, and carry out an asymmetric hydrogenation reaction under a hydrogen atmosphere and a chiral rhodium catalyst to obtain cyclic chiral nitro compounds with the structural formula as shown in Formula II, or 2-substituted cyclic chiral nitro compounds with the structural formula as shown in Formula IV and 2-substituted cyclic chiral nitro olefins with the structural formula V, respectively.

[0010]

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

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

[0013] In formula III, formula IV or formula 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, and can be straight-chain alkyl, branched alkyl, cyclic alkyl, substituted C1-C20 alkyl, phenyl, naphthyl or substituted phenyl.

[0014] Wherein, the substituted C1-C20 alkyl is a C1-C20 alkyl in which one or more H atoms on the C1-C20 alkyl are replaced by substituent A; the substituted phenyl is a phenyl in which one or more H atoms on the phenyl are replaced by substituent A, wherein 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 bisphosphine 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)tetrafluoroborate rhodium, and cyclooctadiene iridium chloride dimer.

[0018] Preferably, the chiral bisphosphine ligand is (S,S)-f-spiroPhos, (S)-BINAP, or (R,S)-f-spiroPhos. 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 to 1200 psi, for example, the reaction pressure can 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] A second aspect of the present invention provides cyclic chiral nitro compounds prepared by the above-described preparation method.

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

[0027] This invention first prepares a rhodium chiral catalyst using a rhodium metal precursor and a chiral bisphosphine ligand as raw materials. This rhodium chiral catalyst has the advantages of low toxicity, high atom economy, and environmental friendliness. Then, under a hydrogen atmosphere and with the aid of the rhodium chiral catalyst, cyclic chiral nitro compounds are successfully prepared by asymmetric hydrogenation of cyclic nitroolefins. The preparation method of this invention is simple to operate, highly atom-economical, and environmentally friendly, making it suitable for large-scale application. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 Synthetic route for preparing cyclic chiral nitro compounds;

[0030] Figure 2 This is the chemical structural formula of a typical chiral bisphosphine ligand in this invention. Detailed Implementation

[0031] In the following description, specific details such as particular system architectures and techniques are set forth for illustrative purposes and not for limitation, in order to provide a thorough understanding of the embodiments of the invention. However, those skilled in the art will understand that the invention may be implemented in other embodiments without these specific details.

[0032] Example 1

[0033] Reference Figures 1-2 Specifically, compound 2a,3-nitrochromane was prepared, and its chemical structural formula is shown below:

[0034]

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

[0036] Take 1.0 mL of the obtained chiral rhodium catalyst and transfer it to a dry reaction flask pre-filled with 3-nitro-2H-chromene and dichloromethane (2.0 mL), wherein the molar ratio of 3-nitro-2H-chromene to cyclooctadiene rhodium chloride dimer is 100:0.5. Transfer the reaction flask to a reaction vessel, introduce hydrogen gas, set the hydrogen pressure to 1200 psi, and react at 60 °C for 24 h. After the reaction is complete, release the hydrogen gas, filter the reaction product through a silica gel column to remove the chiral rhodium catalyst, and 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 in Example 1, except that the chiral bisphosphine ligand used is different. In this example, the chiral bisphosphine ligand used is (S)-DTBM-SegPhos. Yield: 88%; 29% ee.

[0039] Example 3

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

[0041] Example 4

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

[0043] Example 5

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

[0045] Example 6

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

[0047] Example 7

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

[0049] Example 8

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

[0051] Example 9

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

[0053] Example 10

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

[0055] Example 11

[0056] The steps are basically the same as in Example 10, except that the type and amount of rhodium metal precursor used are different. In this example, the rhodium metal precursor used is rhodium bis(1,5-cyclooctadiene)tetrafluoroborate (Rh(COD)2BF4), and the molar ratio of rhodium bis(1,5-cyclooctadiene)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 in Example 10, except that the rhodium metal precursor used is different. In this example, the rhodium metal precursor used 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 in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced with 6-methyl-3-nitro-2H-chromene.

[0063] Specific preparation steps: In a nitrogen-filled glove box, cyclooctadiene rhodium chloride dimer and (S,S)-f-spiroPhos were dissolved in dichloromethane, wherein the molar ratio of cyclooctadiene rhodium chloride dimer to (S,S)-f-spiroPhos was 0.5:1.1. The mixture was stirred at 25°C for 0.5 h to obtain a chiral rhodium catalyst; 1.0 mL of the obtained chiral rhodium catalyst was taken and transferred to a container pre-filled with 6-methyl-3-nitro-2H-chromene and dichloromethane (2.0 mL). In a dry reaction flask containing 6-methyl-3-nitro-2H-chromene and cyclooctadiene rhodium chloride dimer at a molar ratio of 100:0.5, the flask was transferred to a reaction vessel, hydrogen gas was introduced, and the hydrogen pressure was set to 1200 psi. The reaction was carried out at room temperature for 24 h. After the reaction was completed, the hydrogen gas was released, and the reaction product was filtered through a silica gel column to remove the chiral rhodium catalyst, yielding a white solid, namely 6-methyl-3-nitrochromene; 23.4 mg, 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] Example 14

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

[0066]

[0067] The experimental conditions were the same as in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced with 6-nitro-3-nitro-2H-chromene, ultimately yielding a white solid, namely 6-nitro-3-nitrochromane; 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] Example 15

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

[0070]

[0071] The experimental conditions were the same as in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced with 6-chloro-3-nitro-2H-chromene, ultimately yielding a white solid, namely 6-chloro-3-nitrochromane; 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 in Example 10, except that 3-nitro-2H-chromene in Example 10 was replaced with 8-methoxy-3-nitro-2H-chromene, ultimately yielding a white solid, namely 8-methoxy-3-nitrochromane; 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] Example 17

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

[0078]

[0079] Specific steps: In a nitrogen-filled glove box, cyclooctadiene rhodium chloride dimer and (S,S)-f-spiroPhos were dissolved in dichloromethane, wherein the molar ratio of cyclooctadiene rhodium chloride dimer to (S,S)-f-spiroPhos was 0.5:1.1. The mixture was stirred at 25°C for 0.5 h to obtain a chiral rhodium catalyst. Then, 1.0 mL of the obtained chiral rhodium catalyst was transferred to a dry container pre-added with 3-nitro-2-phenyl-2H-chromene and 2.0 mL of dichloromethane. In a dry reaction flask, the molar ratio of 3-nitro-2-phenyl-2H-chromene to cyclooctadiene rhodium chloride dimer was 100:0.5. The reaction flask was transferred to a reaction vessel, hydrogen gas was introduced, and the hydrogen pressure was set to 1200 psi. The reaction was carried out at room temperature for 24 h. After the reaction was completed, the hydrogen gas 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-phenylchromane; 15.0 mg, 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 a 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] Example 18

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

[0083] Example 19

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

[0085] Example 20

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

[0087] Example 21

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

[0089] Example 22

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

[0091] Example 23

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

[0093] Example 24

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

[0095] Example 25

[0096] The steps are basically the same as in Example 17, except that the type and amount of rhodium metal precursor used are different. In this example, the rhodium metal precursor used is rhodium bis(1,5-cyclooctadiene)tetrafluoroborate (Rh(COD)2BF4), and the molar ratio of rhodium bis(1,5-cyclooctadiene)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] Example 26

[0098] Prepare 4-((2S,3S)-3-nitrochroman-2-yl)phenol and (R)-4-(3-nitro-2H-chromen-2-yl)phenol, with the following structural formulas:

[0099]

[0100] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 4-(3-nitro-2H-chromene-2-yl)phenol, ultimately yielding a white solid, namely 4-((2S,3S)-3-nitrochromene-2-yl)phenol; 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 a yellow solid, namely (R)-4-(3-nitro-2H-chromene-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] Example 27

[0103] The structures of (2S,3S)-3-nitro-2-(4-(trifluoromethyl)phenyl)benzodihydropyran and (R)-3-nitro-2-(4-(trifluoromethyl)phenyl)-2H-chromene are shown below:

[0104]

[0105] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 3-nitro-2-(4-(trifluoromethyl)phenyl)-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-3-nitro-2-(4-(trifluoromethyl)phenyl)benzodihydropyran; 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 a 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] Example 28

[0108] The structures of (2S,3S)-6,8-dibromo-2-(4-bromophenyl)-3-nitrochromene and (R)-6,8-dibromo-2-(4-bromophenyl)-3-nitro-2H-chromene are shown below:

[0109]

[0110] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 6,8-dibromo-2-(4-bromophenyl)-3-nitro-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-6,8-dibromo-2-(4-bromophenyl)-3-nitrochromene; 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 a 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] Example 29

[0113] The structures of (2S,3S)-6-methyl-3-nitro-2-phenylchromene and (R)-6-methyl-3-nitro-2-phenyl-2H-chromene are shown below:

[0114]

[0115] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 6-methyl-3-nitro-2-phenyl-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-6-methyl-3-nitro-2-phenylchromane; 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 a 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] Example 30

[0118] The structures of (2S,3S)-6-methoxy-3-nitro-2-phenylchromene and (R)-6-methoxy-3-nitro-2-phenyl-2H-chromene are shown below:

[0119]

[0120] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 6-methoxy-3-nitro-2-phenyl-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-6-methoxy-3-nitro-2-phenylchromane; 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 a 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] Example 31

[0123] The structures of (2S,3S)-3-nitro-2-(o-tolyl)benzodihydropyran and (R)-3-nitro-2-(o-tolyl)-2H-chromene are shown below:

[0124]

[0125] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 3-nitro-2-(o-tolyl)-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-3-nitro-2-(o-tolyl)benzodihydropyran; 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 a 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] Example 32

[0128] The structures of (2S,3S)-2-(2-methoxyphenyl)-3-nitrochromane and (R)-2-(2-methoxyphenyl)-3-nitro-2H-chromene are shown below:

[0129]

[0130] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 2-(2-methoxyphenyl)-3-nitro-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-2-(2-methoxyphenyl)-3-nitrochromane; 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 a 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] Example 33

[0133] The structures of (2S,3S)-2-isopropyl-3-nitrochromane and (R)-2-isopropyl-3-nitro-2H-chromene are shown below:

[0134]

[0135] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 2-isopropyl-3-nitro-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-2-isopropyl-3-nitrochromene; 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 a yellow solid, namely (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] Example 34

[0138] The structures of (2S,3S)-2-heptyl-3-nitrochromane and (R)-2-heptyl-3-nitro-2H-chromene are shown below:

[0139]

[0140] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 2-heptyl-3-nitro-2H-chromene, ultimately yielding a colorless oily liquid, namely (2S,3S)-2-heptyl-3-nitrochromene; 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 a yellow oily liquid, namely (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] Example 35

[0143] The structures of (2S,3S)-2-cyclopropyl-3-nitrochromene and (R)-2-cyclopropyl-3-nitro-2H-chromene are shown below:

[0144]

[0145] The experimental conditions were the same as in Example 17, except that 3-nitro-2-phenyl-2H-chromene in Example 17 was replaced with 2-cyclopropyl-3-nitro-2H-chromene, ultimately yielding a white solid, namely (2S,3S)-2-cyclopropyl-3-nitrochromane; 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 a 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] This invention is not limited to the specific embodiments described above. Any modifications made by those skilled in the art based on the above concept without creative effort are within the scope of protection of this invention.

Claims

1. A method for preparing a cyclic chiral nitro compound, characterized in that, Includes the following steps: S1. Under a protective gas atmosphere, a rhodium metal precursor and a chiral bisphosphine ligand are added to a solvent and stirred to react, thereby obtaining a chiral rhodium catalyst. The rhodium metal precursor is either cyclooctadiene rhodium chloride dimer or bis(1,5-cyclooctadiene)tetrafluoroborate rhodium; the chiral bisphosphine ligand is ( S,S )-f-spiroPhos; the solvent is toluene and dichloromethane; S2. Dissolve the cyclic nitro olefins with the structural formula shown in Formula III in an organic solvent, and carry out an asymmetric hydrogenation reaction under a hydrogen atmosphere and a chiral rhodium catalyst to obtain 2-substituted cyclic chiral nitro compounds with the structural formula shown in Formula IV and 2-substituted cyclic chiral nitro olefins with the structural formula shown in Formula V. In formulas III, IV, or V, R 1 Selected from any one of H, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl, and halogen; R 2 Selected from C1-C20 alkyl, substituted C1-C20 alkyl, phenyl, naphthyl or substituted phenyl; Wherein, the substituted C1-C20 alkyl is a C1-C20 alkyl in which one or more H atoms on the C1-C20 alkyl are replaced by substituent A; the substituted phenyl is a phenyl in which one or more H atoms on the phenyl are replaced by substituent A, wherein substituent A is selected from C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, hydroxyl, halogen or phenyl.

2. The method for preparing cyclic chiral nitro compounds according to claim 1, characterized in that, In step S1, the reaction temperature is 15~35℃ and the reaction time is 20~30min.

3. The method for preparing cyclic chiral nitro compounds according to claim 1, characterized in that, The molar ratio of the rhodium metal precursor to the cyclic nitro olefin is 1-2:

100.

4. The method for preparing cyclic chiral nitro compounds according to claim 1, characterized in that, In step S2, the hydrogen pressure during the reaction is 300~1200 psi, the reaction temperature is room temperature~60℃, and the reaction time is 4~24h.

5. The method for preparing cyclic chiral nitro compounds 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.

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