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

Abstract

ABSTRACT 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.