β‑Alkenylation of Saturated N‑Heterocycles via a C(sp3)–O Bond Wittig-like Olefination

Although the C–Hα functionalization of N-heterocycles is, in fact, an easy chemical transformation, the C–Hβ functionalization is, on the contrary, a quite difficult chemical process. Here, we present a two-step protocol that allows the ready conversion of pyrrolidines, piperidines, and an azepane into their corresponding 3-exo-alkenyl lactams via the transient formation of 3-alkoxyamino lactams followed by a Wittig-like C­(sp3)–O bond olefination with stabilized ylides from phosphonium salts mediated by t-BuOK. Additionally, as a proof of the synthetic effectiveness of this novel methodology, the first synthesis of the natural product callylactam A was achieved through a TiCl4-catalyzed double bond isomerization of a 3-exo-alkenyl 2-piperidone to its endo-isomer.