Strain-Release Cycloadditions: Bicyclobutanes and Beyond

Abstract Strain-release cycloadditions have emerged as powerful reactions for converting distorted ring systems into complex and otherwise hardly attainable organic molecular architectures. This Review encompasses the fundamentals of strain, its role in governing cycloaddition pathways, and offers a systematic examination of strained carbocycles and heterocycles, from bicyclo[1.1.1]butanes and 1-azabicyclo[1.1.1]butanes, housanes and aza-housanes, 2H-azirines and aziridines, azetidines, cyclopropanes, cyclobutanes, oxiranes, oxetanes, and strained alkynes and alkenes. Across these motifs, the general principles that dictate reactivity, the breadth of known cycloadditions and activation strategies, from Brønsted and Lewis acid catalysis to transition-metal activation, photocatalysis, and double strain-release mechanisms, are highlighted. Key opportunities, current limitations, and future directions are outlined.