A new strategy for the elaboration of pyrrolidine N-oxides using the reverse-Cope elimination

Abstract

Condensations of the unsaturated nitrones 13 with lithiated methyl phenyl sulfone provide excellent yields of the unsaturated hydroxylamines 14 as single stereoisomers, which undergo rapid reverse-Cope elimination at ambient temperature, assisted by the constraint of the acetonide ring, leading to the pyrrolidine N-oxides 15 as single enantiomers.

References

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10. Selected data for 15a: [α]_D²⁰+16.1 (c 0.51, CH₂Cl₂), δ_H(CDCl₃) 1.18 (3H, s, CH₃), 1.41 (3H, s, CH₃), 1.48, (3H, d, J 6.5, 5-CH₃), 2.95 (3H, s, N-CH₃), 3.25 (1H, dq, J 6.5 and 6.5, 5-H), 3.52 (1H, dd, J 15.0 and 6.5, CH_aH_bSO₂), 3.85 (1H, ddd, J 9.0, 6.5 and 4.0, 2-H), 4.05 (1H, dd, J 15.0 and 4.0, CH_aH_bSO₂), 4.50 (2H, m, 3- and 4-H), 7.35–7.50 (3H, m, ArH) and 7.80 (2H, m, ArH)δ_C(CDCl₃) 11.4 (5-CH₃), 25.1 (CH₃), 27.4 (CH₃), 53.1 (N-CH₃), 55.0 (CH₂SO₂), 77.0 (2-CH), 78.4 (5-CH), 83.1 [3(4)-CH], 83.4 [4(3)-CH], 115.5 (OCO), 128.6 and 129.8 (both 2 × ArCH), 134.7 (ArCH) and 139.5 (ArC); m/z[ES] 342 (M⁺+ H, 100%)[Found: M⁺+ H, 342.1375. C₁₆H₂₃NO₅S requires M, 342.1375]. Selected NOE data: 2-H/5-H (5.9%) 2-H/N-Me (2.6%) 5-H/N-Me (2.3%); 5- Me/N-Me (< 1%); N-Me/CH₂SO₂(< 1%).