Strain Release of 1‐Azabicyclo[1.1.0]butanes as a Gateway to Highly Functionalized Azetidines: New Strategies and Structural Motifs

Over the past decade, the interest of synthetic and medicinal chemists in the azetidine ring has continuously risen, given its impact on (positive) modulation of various physicochemical properties. In fact, the exploration of new azetidine-based monocyclic, spirocyclic, and bridged scaffolds has led to the discovery of new potential 3D bioisosteres for 2D or nonstrained 3D rings frequently employed in drug discovery programs. A popular and recently revived strategy en route to azetidines relies on the use of 1-azabicyclo[1.1.0]butanes as precursors, leveraging the inherent reactivity of the "spring-loaded" transannular bond, connecting the bridgehead carbon to the nitrogen. This review provides an overview of synthetic advances since 2021, emphasizing newly accessed structural motifs, patterns in activation tactics, and use of enabling technologies such as photocatalysis and flow chemistry.