Photocatalytic Radical Umpolung for Strain‐Release Difunctionalization of (Aza)bicyclo[1.1.0]butanes

Abstract Azetidines and cyclobutanes are increasingly valued as potent bioisosteres of pyridines and benzenes in medicinal chemistry. Herein, we report a radical umpolung strategy for the regioselective difunctionalization of azabicyclo[1.1.0]butanes (ABBs) and bicyclo[1.1.0]butanes (BCBs) that exhibits complementary regioselectivity to conventional polar strain‐release methods. This approach uses photocatalytically generated electrophilic sulfonyl radicals from readily available sulfinates to selectively add to nitrogen in ABBs and electron‐rich sites of BCBs, triggering strain‐release ring‐opening. The resulting radical intermediates are subsequently captured through two pathways: N ‐heterocyclic carbene (NHC)‐catalyzed radical–radical cross‐coupling enables efficient acylation, while single‐electron reduction generates carbanions capable of nucleophilic addition to electrophiles such as CO 2 and aldehydes. The umpolung reactivity of this protocol enhances synthetic versatility by accommodating diverse azetidine functionalities under mild conditions to afford densely functionalized azetidines and cyclobutanes that are difficult to access through existing methods.