Visible-Light-Mediated Multicomponent Strain-Release-Driven Synthesis of Highly Functionalized Spiroazetidines

Abstract Saturated spirocyclic N-heterocycles are privileged structural motifs in medicinal chemistry, yet access to these valuable motifs from simple and readily available building blocks under mild conditions remains a challenge. Herein, we describe a visible-light-mediated multicomponent coupling of azabicyclo[1.1.0]butanes (ABBs), alkenes, and N-activating electrophiles, which provides a general and modular strategy for the rapid assembly of pharmaceutically interesting yet synthetically challenging azetidine-containing spirocycles in a single step. This practical protocol features a broad substrate scope, high functional group compatibility, operational simplicity, scalability, and excellent chemoselectivity and regioselectivity. Its versatility is demonstrated by the late-stage modification of pharmaceutically relevant molecules, diverse downstream derivatizations, and the synthesis of bioisosteric analogues of bioactive molecules.