Phosphine‐Catalyzed Strain‐Release Alkynylation of Bicyclo [1.1.0] Butanes

Nucleophilic addition to bicyclo [1.1.0] butanes offers a straightforward and efficient approach for constructing 1,3‐disubstituted cyclobutanes, which play an important role in medicinal chemistry. However, due to the limited nucleophilicity of many common nucleophiles, such transformations typically require stoichiometric bases or additives or the use of highly reactive organometallic reagents. Herein, we present a phosphine‐catalyzed strategy that enables the direct addition of a broad range of terminal alkynes to bicyclo[1.1.0]butanes (BCBs) under mild and solvent‐free conditions. This catalytic method eliminates the need for external bases or additives and provides an efficient and practical route to cyclobutylated alkynes, featuring broad substrate scope, good functional group tolerance, and high applicability in late‐stage derivatization, product downstream transformation, and scale‐up synthesis. Mechanistic studies, including intermediate probing and isotope labeling experiments, support the involvement of a covalent intermediate generated by the reaction of the BCB substrate with the catalyst.