Recent advances in the strain-release driven reactions of bicyclobutanes: an emerging landscape in organic synthesis.

Bicyclo[1.1.0]butanes (BCBs) are among the smallest and most strained carbocycles and have emerged as powerful synthetic building blocks in modern organic chemistry. Recent years have witnessed a surge of interest in understanding and exploiting their unique reactivity. The high strain energy associated with the central C-C bond enables a variety of transformations, including insertions, additions, cycloadditions, and molecular rearrangements, often proceeding under mild conditions. This inherent strain facilitates the rapid and efficient construction of diverse and complex molecular architectures. Moreover, the incorporation of BCB motifs as bioisosteres of benzene derivatives has drawn significant attention in medicinal chemistry, owing to their high sp3 character and three-dimensionality. In this review, we summarize the important structural features and the recent advances in the reactivity of BCBs, highlighting key developments, mechanistic insights and the associated modes of reactivity explored.