Direct Synthesis of Substituted Vinyl Aziridines

Abstract

Synthesis of a range of vinyl aziridines with varying substitution on the alkene has been achieved by the reaction of N-(di­methylsulfamoyl)phenylimine with a range ylides derived by deprotonation of substituted allyltetrahydrothiphenium salts. Yields of the substituted vinyl aziridines range from 57% to 77%.

aziridine - imine - ylide - sulfonium - vinyl

References and Notes

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12 Trimethylsulfoxoniummethylide has been reported to form an aziridine from a N-(dimethylsulfamoyl)ketimine: Hannam J. Harrison T. Heath F. Madin A. Merchant K. Synlett  2006,  833 

13

Typical Procedure for 1-(2′-Dimethylamine-2′-sulfonyl)-2-phenyl-3-vinylaziridine (2a) Vacuum-dried sulfonium salt 1a (0.61 g, 2 equiv, 4.73 mmol) in DMSO, (15 mL) was stirred under argon.
N-(Dimethylsulfamoyl)phenylimine (0.48 g, 1 equiv, 2.26 mmol) in DMSO (8 mL) was added to the solution followed by LiOt-Bu, (0.38 g, 2 equiv, 4.45 mmol), and the progress of the reaction was monitored by TLC (25% EtOAc-PE). After 10 min the reaction was judged to be complete and was quenched with ice-cold brine, filtered through a pad of Celite and washed with Et₂O. The resultant bilayer was separated and the aqueous layer was extracted with Et₂O, the combined organic extracts were dried over anhyd Na₂SO₄, filtered, and concentrated under vacuum. Purification by flash column chromatography on neutral alumina, eluting with 5% EtOAc-PE, furnished (0.39 g, 66%) as a 2:1 mixture of trans/cis diastereomers. The separated aziridines were formed as a clear oil. Assignments are of the major trans isomer. IR (thin film): ν_max = 1170, 1450, 2900 cm^-1. MS (EI/Cl): m/z (%) = 253 (100) [M + H]. HRMS: m/z calcd for C₁₂H₁₆S₁O₂N₂ [M + H]⁺: 253.1005; found: 253.1006. ¹H NMR (400 MHz, CDCl₃): δ = 7.40-7.20 (5 H, m), 6.2 (1 H, ddd, J = 9.6, 10.4, 16.8 Hz), 5.57 (1 H, dd, J = 0.8, 16.8 Hz), 5.45 (1 H, dd, J = 0.8, 10.4 Hz), 3.78 (1 H, d, J = 3.6 Hz), 3.18 (1 H, dd, J = 3.6, 9.6 Hz), 2.79 (6 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 136.0, 131.9, 129.0, 128.6, 126.4, 122.8, 53.8, 49.6, 39.0.
1-(2′-Dimethylamine-2′-sulfonyl)-2-phenyl-3-propenyl­-aziridine (2b)
Assignments are of the major diastereomer. IR (thin film): ν_max = 1180, 1260, 1343, 1454 cm^-1. MS (EI/Cl): m/z (%) 267 (47) [M + H], 145 (86), 60 (100). HRMS: m/z calcd for C₁₃H₁₈S₁O₂N₂ [M + H]⁺: 267.1162; found: 267.1163. ¹H NMR (300 MHz, CDCl₃): δ = 7.29 (5 H, m), 5.97 (1 H, m), 5.72 (1 H, m), 3.67 (1 H, d, J = 4.2 Hz), 3.99 (1 H, dd, J = 4.2, 9.6 Hz), 2.73 (6 H, s), 1.56 (3 H, d, J = 6.6 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 133.9, 128.9, 127.7, 127.2, 126.1, 122.8, 53.04, 48.96, 38.48, 17.96.
1-(2′-Dimethylamine-2′-sulfonyl)-2-isopropenyl-3-phenylaziridine (2c) Assignments are of the trans diastereomer. IR (thin film): ν_max = 1180, 1342, 1453 cm^-1. MS (EI/Cl): m/z (%) = 267 (100) [M + H]. HRMS: m/z calcd for C₁₃H₁₈S₁O₂N₂ [M + H]⁺: 267.1162; found: 267.1163. ¹H NMR (400 MHz, CDCl₃): δ = 7.37 (5 H, m), 5.29 (1 H, s), 5.20 (1 H, s), 3.87 (1 H, d, J = 4.8 Hz), 3.51 (1 H, d, J = 4.8 Hz), 2.79 (6 H, s), 1.97 (3 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 138.0, 136.2, 129.7, 128.4, 127.8, 117.2, 52.3, 48.0, 38.2, 20.4.
1-(2′-Dimethylamine-2′-sulfonyl)-2-(2′′-methyl-propenyl)-3-phenylaziridine (2d) Assignments are of the trans diastereomer. IR (thin film): ν_max = 1180, 1343, 1453 cm^-1. MS (EI/Cl): m/z (%) = 281 (100) [M + H]. HRMS: m/z calcd for C₁₄H₂₀S₁O₂N₂ [M + H]⁺: 281.1318; found: 281.1320. ¹H NMR (300 MHz, CDCl₃): δ = 7.30-7.19 (5 H, m), 4.62 (1 H, d, J = 8.6 Hz), 3.62 (1 H, d, J = 7.2 Hz), 3.57 (1 H, dd, J = 7.2, 8.6 Hz), 2.84 (6 H, s), 1.72 (3 H, s), 1.57 (3 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 127.6, 127.3, 127.1, 126.8, 115, 45.4, 42.8, 37.7, 24.9, 17.59.
1-(2′-Dimethylamine-2′-sulfonyl)-2-phenyl-3-styryl­-aziridine (2e) Assignments are of the trans diastereomer. IR (thin film): ν_max = 1153, 1344, 1452 cm^-1. MS (EI/Cl): m/z (%) = 329 (100) [M + H]. HRMS: m/z calcd for C₁₈H₂₀S₁O₂N₂ [M + H]⁺: 329.1318; found: 329.1320. ¹H NMR (400 MHz, CDCl₃): δ = 7.40-7.10 (10 H, m), 6.78 (1 H, d, J = 15.6 Hz), 6.40 (1 H, dd, J = 9.2, 15.6 Hz), 3.8 (1 H, d, J = 3.6 Hz), 3.28 (1 H, dd, J = 3.6, 9.2 Hz), 2.79 (6 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 137.1, 136.0, 133.8, 129.1, 128.9, 128.4, 128.2, 127.6, 127.1, 121.9, 48.0, 46.2, 39.0.