Method of synthesizing (1R,2R)-nitroalcohol compound

Abstract

Disclosed is a method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme, including: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), where R.sup.1 and R.sup.2 are defined in the same manner as that in the specification. The method involves mild reaction conditions, excellent diastereoselectivity and high chemical yield, and thus it is suitable for industrial applications. ##STR00001##

Claims

1. A method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), comprising: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme: ##STR00005## wherein: R.sup.1 is hydrogen, methylsulfonyl, bromo, cyano, fluoro, methoxy, methylthio, methyl, trifluoromethyl, phenyl, acetoxy, or chloro; and R.sup.2 is hydrogen or tert-butyl dim ethyl silyl; the chiral (1S,2R)-amino alcohol ligand is (1S,2R)-2-(diisopropylamino)-1,2-diphenyl ethan-1-ol; the cupric salt is cupric acetate monohydrate or cupric trifluoromethanesulfonate; and the condensation reaction is performed at −15-15° C. for 48-120 h.

2. The method of claim 1, wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S,2R)-amino alcohol ligand is 1:1.1-8:0.05-0.15:0.08-0.2.

3. The method of claim 2, wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S,2R)-amino alcohol ligand is 1: 2-6:0.05-0.15:0.08-0.2.

4. The method of claim 1, wherein the organic solvent is a polar aprotic solvent.

5. The method of claim 2, wherein the organic solvent is a polar aprotic solvent.

6. The method of claim 3, wherein the organic solvent is a polar aprotic solvent.

7. The method of claim 4, wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

8. The method of claim 5, wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

9. The method of claim 6, wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

Description

DETAILED DESCRIPTION OF EMBODIMENTS

(1) As used herein, the term “halogen” refers to fluorine, chlorine, bromine or iodine.

(2) The invention is described in detail below with reference to the embodiments, and these embodiments are not intended to limit the invention.

Example 1

(3) 2.0 g of cupric acetate monohydrate (10 mmol), 2.7 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (10 mmol) and 150 mL of tetrahydrofuran were added in a dry flask. The reaction mixture was stirred at room temperature for 1 h, and then sequentially added with 36.4 g of nitroethanol (400 mmol) and 18.4 g of 4-(methylsulfonyl)benzaldehyde (100 mmol) at −15° C. Then the reaction mixture was reacted at −15° C. under stirring for 48 h. After the reaction was completed, tetrahydrofuran was recovered under vacuum, and the reaction mixture was dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 27.0 g of a white crystalline powder (1R,2R)-1-(4-(methylsulfonyl)phenyl)-2-nitropropan-1,3-diol (98% yield, dr=32:1, 98% ee) with a melting point of 136-138° C. and [α].sup.25.sub.D of −32.6 (c=0.29, EtOH).

(4) .sup.1H NMR (400 MHz, DMSO): δ 7.93 (d, J=8.0 Hz, 2H), 7.71 (d, J=8.4 Hz, 2H), 6.35 (d, J=4.8 Hz, 1H), 5.28 (dd, J.sub.1=6.4 Hz, J.sub.2=4.4 Hz, 1H), 5.06 (dd, J.sub.1=8.8 Hz, J.sub.2=4.8 Hz, 1H), 4.80 (td, J.sub.1=9.2 Hz, J.sub.2=3.2 Hz, 1H), 3.84-3.77 (m, 1H), 3.25 (dt, J.sub.1=12.4 Hz, J.sub.2=4.0 Hz, 1H), 3.21 (s, 3H) ppm.

(5) .sup.13C NMR (100 MHz, DMSO): δ 146.5, 141.1, 128.4, 127.6, 95.4, 71.2, 60.5, 43.9 ppm.

(6) ESI HRMS: C.sub.10H.sub.13NO.sub.6S+Na (calculated: 298.0361; measured: 298.0362).

Example 2

(7) 2.0 g of cupric acetate monohydrate (10 mmol), 2.4 g of (1S,2R)-2-(dimethylamino)-1,2-diphenylethan-1-ol (10 mmol) and 200 mL of dioxane were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 27.4 g of nitroethanol (300 mmol) and 18.5 g of o-bromobenzaldehyde (100 mmol) at 0° C. and reacted at 0° C. under stirring for 72 h. After the reaction was completed, the dioxane was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 27.1 g of a white crystalline powder (1R,2R)-1-(2-bromophenyl)-2-nitropropan-1,3-diol (98% yield, dr=11:1, 97% ee) with a melting point of 70-73° C. and [α].sub.D.sup.25 of −3.3 (c=0.33, EtOH).

(8) .sup.1H NMR (400 MHz, CD.sub.3OD): 7.61 (dd, J.sub.1=8.0 Hz, J.sub.2=1.2 Hz, 1H), 7.57 (dd, J.sub.1=7.6 Hz, J.sub.2=2.0 Hz, 1H), 7.43 (td, J.sub.1=7.6 Hz, J.sub.2=1.2 Hz, 1H), 7.25 (td, J.sub.1=7.6 Hz, J.sub.2=2.0 Hz, 1H), 5.49 (d, J=8.4 Hz, 1H), 4.92-4.89 (m, 1H), 4.15-4.09 (m 1H), 3.43 (dd, J.sub.1=12 Hz, J.sub.2=3.2 Hz, 1H) ppm.

(9) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 139.0, 132.6, 129.9, 128.5, 127.9, 122.1, 95.3, 70.4, 60.2 ppm.

(10) ESI HRMS: C.sub.9H.sub.10BrNO.sub.4+Na (calculated: 297.9691; measured: 297.9689).

Example 3

(11) 1.6 g of cupric trifluoromethanesulfonate (4.5 mmol), 2.1 g of (1S,2R)-2-(diisopropylamino)-1,2-diphenylethan-1-ol (7.2 mmol) and 130 mL of dichloromethane were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 41 g of nitroethanol (450 mmol) and 11.8 g of 4-cyanobenzaldehyde (90 mmol) at −5° C. and reacted under stirring at −5° C. for 96 h. After the reaction was completed, the dichloromethane and nitroethanol were recovered under vacuum, and the reaction mixture was slowly dropwise added 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 80 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 19.6 g of a white crystalline powder 4-((1R,2R)-1,3-dihydroxy-2-nitropropyl)benzonitrile (98% yield, dr=20:1, 97% ee) with a melting point of 110-111° C. and [α].sub.D.sup.25 of −36.4 (c=0.45, EtOH).

(12) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.77-7.74 (m, 2H), 7.63-7.61 (m, 2H), 5.14 (d, J=8.8 Hz, 1H), 4.83-4.78 (m, 1H), 3.86 (dd, J.sub.1=12.4 Hz, J.sub.2=8.8 Hz, 1H), 3.48 (dd, J.sub.1=12.0 Hz, J.sub.2=3.2 Hz, 1H) ppm. .sup.13C NMR (100 MHz, CD.sub.3OD): δ 143.8, 130.7, 126.1, 116.5, 110.5, 92.9, 69.8, 58.7 ppm.

(13) ESI HRMS: C.sub.28H.sub.37N.sub.5O.sub.9+Na (calculated: 245.0538; measured: 245.0533).

Example 4

(14) 1.0 g of cupric acetate monohydrate (5 mmol), 1.9 g of (1S,2R)-2-(dimethylamino)-1,2-diphenylethan-1-ol (8 mmol) and 200 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 18.3 g of nitroethanol (200 mmol) and 12.4 g of 2-fluorobenzaldehyde (100 mmol) at 10° C. and reacted under stirring at 10° C. for 120 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 21.1 g of a colorless oil product (1R,2R)-1-(2-fluorophenyl)-2-nitropropan-1,3-diol (98% yield, dr=22.5:1, 99% ee) with [α].sup.25.sub.D of −12.0 (c=0.52, EtOH).

(15) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.55 (td, J.sub.1=7.6 Hz, J.sub.2=2.0 Hz, 1H), 7.43-7.37 (m, 1H), 7.26 (t, J=7.6 Hz, 1H), 7.17-7.13 (m, 1H), 5.36 (dd, J.sub.1=9.2 Hz, J.sub.2=3.2 Hz, 1H), 4.96-4.93 (m, 1H), 3.96 (td, J.sub.1=12 Hz, J.sub.2=2.8 Hz, 1H), 3.96 (dt, J.sub.1=12 Hz, J.sub.2=3.6 Hz, 1H) ppm.

(16) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 160.9 (d, J=244.0 Hz), 131.3 (d, J=8.5 Hz), 129.3 (d, J=3.9 Hz), 127.6 (d, J=13.2 Hz), 125.6 (d, J=3.4 Hz), 116.1 (d, J=21.4 Hz), 95.6 (d, J=2.5 Hz), 66.9, 61.2 ppm.

(17) ESI HRMS: C.sub.9H.sub.10FNO.sub.4+Na (calculated: 238.0492; measured: 238.0487).

Example 5

(18) 2.0 g of cupric acetate monohydrate (10 mmol), 4.1 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (15 mmol) and 140 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 36.4 g of nitroethanol (400 mmol) and 13.6 g of 4-methoxybenzaldehyde (100 mmol) at 15° C. and reacted under stirring at 15° C. for 120 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 21.6 g of a colorless oil product (1R,2R)-1-(4-(methoxy)phenyl)-2-nitropropan-1,3-diol (95% yield, dr=13.7:1, 96% ee) with [α].sup.25.sub.D of −6.9 (c=0.79, EtOH).

(19) .sup.1H NMR (400 MHz, CD.sub.3OD): δ7.34-7.32 (m, 2H), 6.97-6.95 (m, 2H), 4.94 (d, J=9.6 Hz, 1H), 4.84-4.78 (m, 1H), 3.83-3.79 (m, 4H), 3.36 (dd, J.sub.1=12.0 Hz, J.sub.2=3.2 Hz, 1H) ppm.

(20) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 161.3, 132.6, 129.0, 115.0, 96.6, 73.1, 61.7, 55.5 ppm.

(21) ESI HRMS: C.sub.10H.sub.13NO.sub.5+Na (calculated: 250.0691; and measured: 250.0683).

Example 6

(22) 2.0 g of cupric acetate monohydrate (10 mmol), 4.1 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (15 mmol) and 180 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 45.5 g of nitroethanol (500 mmol) and 15.2 g of 4-methylthiobenzaldehyde (100 mmol) at 5° C. and reacted under stirring at 5° C. for 120 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 23.1 g of a colorless oil product (1R,2R)-1-(4-(methylthio)phenyl)-2-nitropropan-1,3-diol (95% yield, dr=10.7:1, 98% ee) with [α].sup.25.sub.D of −22.8 (c=0.64, EtOH).

(23) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.35-7.23 (m, 4H), 4.96 (d, J=9.6 Hz, 1H), 4.84-4.78 (m, 1H), 3.83 (dd, J.sub.1=12.0 Hz, J.sub.2=9.2 Hz, 1H), 3.39 (dd, J.sub.1=12.4 Hz, J.sub.2=3.2 Hz, 1H), 2.48 (s, 3H) ppm.

(24) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 139.7, 136.1, 127.1, 126.1, 95.2, 71.9, 60.5, 14.0 ppm.

(25) ESI HRMS: C.sub.10H.sub.13NO.sub.4S+Na (calculated: 266.0463; measured: 266.0465).

Example 7

(26) 1.0 g of cupric acetate monohydrate (5 mmol), 2.7 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (10 mmol) and 180 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 45.5 g of nitroethanol (500 mmol) and 10.6 g of benzaldehyde (100 mmol) at 0° C. and reacted under stirring at 0° C. for 120 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 18.7 g of a colorless oil product (1R,2R)-2-nitro-1-phenylpropan-1,3-diol (95% yield, dr=23:1, 99% ee) with [α].sup.25.sub.D of 2.0 (c=0.79, EtOH).

(27) .sup.1H NMR (400 MHz, CDCl.sub.3): δ 7.41-7.36 (m, 5H), 5.24 (dd, J.sub.1=8.8 Hz, J.sub.2=3.2 Hz, 1H), 4.81-4.76 (m, 1H), 3.83-3.72 (m, 2H), 2.85 (d, J=4.0 Hz, 1H), 2.28 (d, J=6.0 Hz, 1H) ppm.

(28) .sup.13C NMR (100 MHz, CDCl.sub.3): δ138.0, 129.4, 129.2, 126.6, 93.8, 72.6, 61.3, ppm.

(29) ESI HRMS: C.sub.9H.sub.11NO.sub.4+Na (calculated: 220.0586; measured: 220.0582).

Example 8

(30) 2.0 g of cupric acetate monohydrate (10 mmol), 2.4 g of (1S,2R)-2-(dimethylamino)-1,2-diphenylethan-1-ol (10 mmol) and 200 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 27.4 g of nitroethanol (300 mmol) and 12.0 g of 3-methylbenzaldehyde (100 mmol) at 5° C. and reacted under stirring at 5° C. for 72 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 m. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 20.7 g of a colorless oil product (1R,2R)-2-nitro-1-(m-methylphenyl)propan-1,3-diol (98% yield, dr=19.7:1, 99% ee) with [α].sub.D.sup.25 of −7.4 (c=0.75, EtOH).

(31) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.26 (t, J=7.6 Hz, 1H), 7.22 (t, J=2.0 Hz, 1H), 7.20-7.11 (m, 2H), 4.92 (d, J=9.2 Hz, 1H), 4.82-4.76 (m, 1H), 3.81 (dd, J.sub.1=12.4 Hz, J.sub.2=9.6 Hz, 1H), 3.33 (dd, J.sub.1=12.0 Hz, J.sub.2=3.2 Hz, 1H), 2.35 (s, 3H) ppm.

(32) .sup.13C NMR (100 MHz, CD.sub.3OD): δ140.6, 139.5, 130.2, 129.4, 128.2, 124.7, 96.4, 73.5, 61.6, 21.1 ppm.

(33) ESI HRMS: C.sub.10H.sub.13NO.sub.4+Na (calculated: 234.0742; measured: 234.0733).

Example 9

(34) 1.0 g of cupric acetate monohydrate (5 mmol), 2.2 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (8 mmol) and 180 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 36.4 g of nitroethanol (400 mmol) and 17.4 g of 4-(trifluoromethyl)benzaldehyde (100 mmol) at 0° C. and reacted under stirring at 0° C. for 48 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 25.5 g of a colorless oil product (1R,2R)-2-nitro-1-(4-(trifluoromethyl)phenyl)propan-1,3-diol (96% yield, dr=10:1, 97% ee) with [α].sup.25.sub.D of −14.7 (c=1.0, EtOH).

(35) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.70 (d, J=8.0 Hz, 2H, syn), 7.62 (d, J=8.0 Hz, 2H, syn), 5.13 (d, J=9.2 Hz, 1H), 4.82 (td, J.sub.1=9.2 Hz, J.sub.2=3.2 Hz, 1H), 3.86 (dd, J.sub.1=12.0 Hz, J.sub.2=8.8 Hz, 1H, syn), 3.45 (dd, J.sub.1=12.4 Hz, J.sub.2=3.2 Hz, 1H, syn) ppm.

(36) .sup.13C NMR (100 MHz, CD.sub.3OD): δ142.6, 128.8 (q, J=32 Hz), 125.8, 123.7 (q, J=4 Hz), 122.6 (q, J=269 Hz), 93.2, 69.9, 58.7 ppm.

(37) ESI HRMS: C.sub.10H.sub.10F.sub.3NO.sub.4+Na (calculated: 288.0460; measured: 288.0465).

Example 10

(38) 2.0 g of cupric acetate monohydrate (10 mmol), 3.3 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (12 mmol) and 200 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 36.4 g of nitroethanol (400 mmol) and 18.2 g of 4-phenylbenzaldehyde (100 mmol) at 5° C. and reacted under stirring at 5° C. for 72 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 26.5 g of a white crystalline powder (1R,2R)-1-([1,1′-biphenyl]-4-yl)-2-nitropropan-1,3-diol (97% yield, dr=12.8:1, 99% ee) with a melting point of 122-126° C. and [α].sup.25.sub.D of −24.3 (c=1.0, EtOH).

(39) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.58-7.49 (m, 4H), 7.38 (d, J=8.0 Hz, 2H), 7.32 (t, J=8.0 Hz, 2H), 7.26-7.21 (m, 1H), 4.95 (d, J=9.2 Hz, 1H), 4.80-4.75 (m, 1H), 3.78 (dd, J.sub.1=12.0 Hz, J.sub.2=9.2 Hz, 1H), 3.34 (dd, J.sub.1=12.0 Hz, J.sub.2=3.2 Hz, 1H) ppm.

(40) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 141.5, 140.3, 138.6, 128.5, 127.2, 127.1, 127.0, 126.6, 95.2, 72.1, 60.5 ppm.

(41) ESI HRMS: C.sub.15H.sub.15NO.sub.4+Na (calculated: 296.0899; measured: 296.0894).

Example 11

(42) 2.0 g of cupric acetate monohydrate (10 mmol), 2.7 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (10 mmol) and 180 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 36.4 g of nitroethanol (400 mmol) and 16.4 g of 4-acetoxybenzaldehyde (100 mmol) at 0° C. and reacted under stirring at 0° C. for 60 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 24.5 g of a colorless oil product 4-((1R,2R)-1,3-dihydroxy-2-nitropropyl)phenyl acetate (96% yield, dr=16:1, 99% ee) with [α].sup.25.sub.D of −17.6 (c=1.0, EtOH).

(43) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.46-7.44 (m, 2H), 7.15-7.13 (m, 2H), 5.04 (d, J=9.2 Hz, 1H), 4.84 (td, J.sub.1=9.2 Hz, J.sub.2=3.2 Hz, 1H), 3.85 (dd, J.sub.1=12.4 Hz, J.sub.2=9.6 Hz, 1H), 3.42 (dd, J.sub.1=12.4 Hz, J.sub.2=3.2 Hz, 1H), 2.27 (s, 3H) ppm.

(44) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 171.0, 152.1, 138.2, 128.8, 122.9, 96.2, 72.7, 61.5, 20.7 ppm.

(45) ESI HRMS: C.sub.11H.sub.13NO.sub.6+Na (calculated: 278.0641; measured: 278.0640).

Example 12

(46) 2.0 g of cupric acetate monohydrate (10 mmol), 2.7 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (10 mmol) and 180 mL of tetrahydrofuran were added to a dry flask. The reaction mixture was stirred at room temperature for 1 h, sequentially added with 36.4 g of nitroethanol (400 mmol) and 14.1 g of 2-chlorobenzaldehyde (100 mmol) at 0° C. and reacted under stirring at 0° C. for 84 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 22.7 g of a colorless oil product (1R,2R)-1-(2-chlorophenyl)-2-nitropropan-1,3-diol (98% yield, dr=11.1:1, 97% ee) with [α].sup.25.sub.D of −11.4 (c=1.0, EtOH).

(47) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.63 (dd, J.sub.1=7.6 Hz, J.sub.2=2.0 Hz, 1H), 7.47-7.34 (m, 3H), 5.57 (d, J=8.4 Hz, 1H), 4.99-4.94 (m, 1H), 4.14 (dd, J.sub.1=12.0 Hz, J.sub.2=9.6 Hz, 1H), 3.51 (dd, J.sub.1=12.0 Hz, J.sub.2=3.2 Hz, 1H) ppm.

(48) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 138.2, 133.1, 130.6, 130.2, 129.2, 128.4, 96.0, 69.0, 61.1 ppm.

(49) ESI HRMS: C.sub.9H.sub.10ClNO.sub.4+Na (calculated: 254.0196; measured: 254.0193).

Example 13

(50) 2.0 g of cupric acetate monohydrate (10 mmol), 2.7 g of (1S,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol (10 mmol) and 200 mL of tetrahydrofuran were added to a dry flask, The reaction mixture was stirred at room temperature for 1 h, sequentially added with 61.6 g of tert-butyldimethyl(2-nitroethoxy)silane (300 mmol) and 18.4 g of 4-methylsulfonylbenzaldehyde (100 mmol) at 0° C. and reacted under stirring at 0° C. for 84 h. After the reaction was completed, the tetrahydrofuran was recovered under vacuum, and the reaction mixture was slowly dropwise added with 100 mL of 5% hydrochloric acid, stirred at room temperature for 20 min and extracted with ethyl acetate three times each for 100 mL. The organic phases were collected, combined, concentrated under vacuum and cooled to room temperature to give 38.2 g of a white crystalline powder (1R,2R)-3-((tert-butyldimethylsilyl)oxy)-1-(4-(methanesulfonyl)phenyl)-2-nitropropan-1-ol (98% yield, dr=20:1, 97% ee) with a melting point of 98-100° C. and [α].sup.25.sub.D of −2.4 (c=1.0, EtOH).

(51) .sup.1H NMR (400 MHz, CD.sub.3OD): δ 7.98 (d, J=8.4 Hz, 2H), 7.71 (d, J=8.0 Hz, 2H), 5.22 (d, J=8.8 Hz, 1H), 4.86-4.81 (m, 1H), 3.95 (dd, J.sub.1=11.6 Hz, J.sub.2=8.4 Hz, 1H), 3.61 (dd, J.sub.1=11.6 Hz, J.sub.2=2.8 Hz, 1H), 3.13 (s, 3H), 0.83 (s, 9H), 0.02 (s, 6H) ppm.

(52) .sup.13C NMR (100 MHz, CD.sub.3OD): δ 146.0, 140.8, 127.7, 127.4, 94.2, 71.0, 61.7, 42.9, 24.7, 17.5, −6.9, −7.0 ppm.

(53) ESI HRMS: C.sub.16H.sub.27NO.sub.6SSi+Na (calculated: 412.1226; measured: 412.1223).

(54) Described above are merely some preferred embodiments of the invention, and it should be understood that the invention is not limited thereto. Any combinations, modifications and changes made without departing from the spirit of the invention, shall fall within the scope of the invention defined by the appended claims.