Divergent synthesis of γ-lactones and cyclopropanes via efficient [1 + 4] and [1 + 2] annulations of amide-sulfoxonium ylides.

Functionalized γ-lactones and cyclopropanes, especially those bearing amide substituents, play important roles in diverse chemical and pharmacological processes, but their synthesis remains challenging. Here, we report a high-throughput protocol that employs amide-sulfoxonium ylides as versatile C1 synthons in efficient [1 + 4] and [1 + 2] annulation reactions with readily available alkene derivatives, delivering a variety of (hetero)amide-substituted γ-lactones and cyclopropanes in good yields. This simple approach demonstrates a broad substrate scope, high functional group compatibility, and excellent chemo- and diastereoselectivity, and can even be utilized for the late-stage diversification of complex bioactive molecules. Combined with machine learning, a yield predictive model for cyclopropane formation is established. Mechanistically, both [1 + 4] and [1 + 2] annulations are initiated by intermolecular Michael addition, diverging into selective 5-exo-trig and 3-exo-trig cyclization, respectively. Moreover, these synthetic transformations provide a reliable and efficient route to complex γ-lactones and cyclopropanes that are otherwise difficult to access.