Nickel‐Catalyzed Cross‐Electrophile Coupling of Alkynyl Halides With Allylic Acetates

We have developed a Ni‐catalyzed cross‐electrophile coupling (XEC) strategy that enables the efficient synthesis of diverse skipped enynes from readily accessible alkynyl halides and allylic acetates. This method exhibits broad substrate scope, accommodating a wide range of aliphatic and aromatic electrophiles, as well as complex natural product‐ and pharmaceutical‐derived motifs, which remains a challenge using the current methods. Mechanistic experiments and DFT studies support a double oxidative addition pathway, wherein Ni 0 preferentially undergoes oxidative addition with the alkynyl halide. To our knowledge, this work represents the first example of a TM‐catalyzed reductive cross‐coupling between two electrophiles for the preparation of skipped enynes. The process proceeds with excellent stereoselectivity and notable regioselectivity, offering a promising platform for future development of asymmetric skipped enynes synthesis.