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

Abstract 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.