Light‐Enabled [2 <i>σ</i>  + 2 <i>π</i> ] Cycloadditions of Bicyclo[1.1.0]butanes and Alkenes by Ti‐Salen Photocatalysis

Bicyclo[2.1.1]hexanes (BCHs) have emerged as promising three‐dimensional bioisosteres of benzenoids, garnering considerable interest from both synthetic and medicinal chemistry communities. In this study, we disclose a photoinduced intermolecular [2 σ + 2 π ] cycloaddition reaction between bicyclo[1.1.0]butanes (BCBs) and alkenes, mediated by an unprecedented Ti(Salen) photocatalytic system. Under violet light irradiation (390 nm), the photoexcited Ti(Salen) complex promotes the cleavage of the central CC bond in BCBs, enabling subsequent alkene insertion to afford polysubstituted BCHs with high efficiency. This Ti‐catalyzed protocol features a broad substrate scope, good functional group compatibility, and mild reaction conditions. The operational simplicity and scalability of this transformation are further demonstrated by the concise synthesis of BCH‐Lumacaftor—a conformationally restricted analog of the FDA‐approved drug Lumacaftor—highlighting its potential for pharmaceutical applications.