Catalytic strain-release enabled cycloaddition of carbonyl activated bicyclo[1.1.0]butanes

Abstract

Bicyclo[1.1.0]butanes (BCBs), characterized by their compact and highly strained carbocyclic frameworks, have emerged as versatile building blocks in modern synthetic chemistry. Their distinctive geometry and low activation barriers enable diverse strain-release cycloadditions, granting efficient access to architecturally complex ring systems. In recent years, significant progress has been achieved in catalytic cycloaddition strategies that harness the reactivity of carbonyl activated BCBs due to the presence of a carbonyl group on the bridgehead, especially Lewis acid-mediated and photochemical radical transformations. This review summarizes these advances with a focus on mechanistic principles, catalyst design, and synthetic applications. By organizing reactions across two-electron, single-electron or carbene pathways, we highlight current trends, challenges, and opportunities in this rapidly evolving field. We anticipate this review will inspire further innovations in BCB chemistry and promote interdisciplinary applications in drug discovery and molecular design.