Synthetic Strategies for the Construction of Cyclobutane‐Fused Heterocycles

Abstract

Cyclobutane‐fused heterocycles represent a distinctive class of structurally constrained scaffolds with significant relevance in natural products and medicinal chemistry. Recent advances in synthetic organic chemistry have enabled the development of diverse, increasingly efficient strategies for their construction. Among these, [2 + 2] cycloaddition‐based approaches have emerged as central tools, spanning photochemical dearomative transformations of heteroarenes, olefin [2 + 2] photocycloadditions, and Lewis acid‐ or transition‐metal‐catalyzed variants, including enantioselective and visible‐light‐mediated processes. Alongside these approaches, complementary ring‐closure strategies, including cascade processes and strain‐release annulations, have also been reported in recent years, providing efficient and elegant access to cyclobutane‐fused heterocycles through mechanistically distinct pathways. This review provides a critical overview of the principal synthetic strategies for constructing cyclobutane‐fused heterocycles, with an emphasis on reactivity patterns, selectivity control, and mechanistic features.