Dyotropic Rearrangement of β‐Lactams: Reaction Development, Mechanistic Study, and Application to the Total Syntheses of Tricyclic Marine Alkaloids

Abstract

An unprecedented dyotropic rearrangement of β‐lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ‐butyrolactams. Unlike the well‐established dyotropic rearrangements of β‐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 β‐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 β‐lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (–)‐lepadiformine A, (+)‐cylindricine C, and (–)‐fasicularin within 11‐12 longest linear steps.