Dyotropic Rearrangement of ß-Lactams: Reaction Development, Mechanistic Study, and Application to the Total Syntheses of Tricyclic Marine Alkaloids.

ABSTRACT

An unprecedented dyotropic rearrangement of ß-lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ-butyrolactams. Unlike the well-established dyotropic rearrangements of ß-lactones, the present reaction probably proceeds through a dual-activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of ß-lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H-migration dyotropic rearrangement of ß-lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (-)-lepadiformine A, (+)-cylindricine C, and (-)-fasicularin within 11-12 longest linear steps.