Bicyclobutanes as unusual building blocks for complexity generation in organic synthesis

Abstract Bicyclobutanes are among the most highly strained isolable organic compounds and their associated low activation barriers to reactivity make them intriguing building-blocks in organic chemistry. In recent years, numerous creative synthetic strategies exploiting their heightened reactivity have been presented and these discoveries have often gone hand-in-hand with the development of more practical routes for their synthesis. Their proclivity as strain-release reagents through their weak central C–C bond has been harnessed in a variety of addition, rearrangement and insertion reactions, providing rapid access to a rich tapestry of complex molecular scaffolds. This review will provide an overview of the different options available for bicyclobutane synthesis, the main classes of compounds that can be prepared from bicyclobutanes, and the associated modes of reactivity used.