Palladium‐Catalyzed Three‐Component Coupling Through Carbene Migratory Insertion: Access to Allenes and 1,5‐Enynes

Palladium-catalyzed cross-coupling reactions of propargylic electrophiles with carbon nucleophiles have been established as straightforward and reliable methods for the synthesis of allenes and 1,5-enynes. However, such transformations have so far been limited to two-component systems. Herein, we report a palladium-catalyzed three-component coupling reaction involving bromoalkynes, diazoesters, and boronates. The reaction proceeds via allenylpalladium or propargylpalladium intermediates, generated through a sequence of oxidative addition, carbene formation, and migratory insertion upon interaction of haloalkynes with diazo compounds under palladium catalysis. Depending on the structure of the boronate substrate, the three-component coupling selectively delivers either allenes or 1,5-enynes. DFT calculations provide insight into this substrate-dependent chemoselectivity. The method exhibits broad substrate scope and has been successfully applied to the concise synthesis of two pharmaceutical agents-aminoglutethimide and anileridine.