Regiodivergent Rhodium Catalysis: Enantioselective Hydroacylation of 2-Azetines.

In this article, we report a regio- and enantioselective Rh-catalyzed hydroacylation of 2-azetines, enabled by strategic ligand control. The choice of the bisphosphine ligand dictates whether the reaction yields chiral 2-acylazetidines or achiral 3-acylazetidines. Electron-rich Josiphos ligands promote selective formation of 2-acylazetidines with high enantioselectivity, while biaryl bisphosphines such as dppe favor the formation of the 3-acylazetidine isomer. This study pioneers the use of enecarbamates as viable coupling partners in hydroacylation, expanding the scope of strained heterocyclic functionalization. Mechanistic analysis using distortion-interaction models reveals that regiodivergence arises from distinct transition-state stabilization modes: dppe ligands allow regioselectivity to follow substrate electronics, while bulkier Josiphos ligands enforce steric and non-covalent interactions that override inherent reactivity.