Lithium Iodide Enables Bis‐electrophilic Ring‐Opening of Azabicyclo[1.1.0]butanes

Azetidines are privileged nitrogen heterocycles in medicinal chemistry; however, current synthetic methodologies utilizing azabicyclo[1.1.0]butanes (ABBs) predominantly rely on classical nucleophile-electrophile or radical-based approaches. Here, we report an unprecedented electrophile-electrophile ring-opening strategy enabled by lithium iodide-mediated activation of ABBs, offering direct and versatile access to densely substituted azetidines through sequential electrophilic incorporation. This new reactivity exploits the inherent ring strain of ABBs under mild, base-free, room-temperature conditions, thereby eliminating the necessity for harsh reaction environments. Mechanistic studies and control experiments unequivocally establish the pivotal role of lithium iodide in ring-opening and generating an in situ enolate intermediate, facilitating efficient bisfunctionalization via electrophilic trapping. The operational simplicity, extensive substrate scope, and remarkable compatibility with late-stage functionalization significantly enhance the synthetic versatility and modularity of ABB-derived azetidines, presenting a powerful approach for rapidly assembling complex molecules containing azetidines.