Lewis acid-catalyzed rearrangements and cycloadditions of N-sulfonyl oxaziridines.

摘要

One focus in the Yoon laboratory is the development of novel reaction of oxaziridines. We report herein that N-(4-nitrobenzene)sulfonyl (nosyl) oxaziridines rearrange in the presence of a Lewis acid to form unstable 1,3-dipoles, which can then cyclize with olefins in situ to afford isoxazolidines. Notably, the identity of the Lewis acid directs the pathway of the oxaziridine rearrangement. TiCl4 selectively catalyzes the isomerization of oxaziridines to N-sulfonyl nitrones and generates cis-substituted-N-nosyl-isoxazolidines. N-Sulfonyl nitrones are one of a limited number of nitrones bearing electron-deficient substrates on the nitrogen. In a complementary methodology, Sc(III)bis(oxazoline) complexes catalyze the formation of trans-substituted- N-nosyl-isoxazolidines, via carbonyl imines cycloadditions. Carbonyl imines have not been previously identified or utilized in organic synthesis, despite the depth and breadth of 1,3-dipolar cycloadditions.;Both N-sulfonyl nitrone and carbonyl imine cycloadditions proceed smoothly with a diverse range of olefins and oxaziridines producing structurally varied N-nosyl isoxazolidines in good yields and with excellent diastereoselectivity. The nosyl protecting group can be easily removed under mild conditions without concomitant cleavage of the sensitive isoxazolidine nitrogen-oxygen bond, allowing efficient access to N-unsubstituted isoxazolidines for further synthetic manipulation and biological evaluation. Alternatively, reduction of the N--O bond provides complementary access to stereochemically well-defined 1,3-aminoalcohols.