Ligand‐Enabled Cu‐Catalyzed Deoxyalkynylation of α‐Unfunctionalized Alcohols with Terminal Alkynes

Despite the widespread utility of transition metal‐catalyzed cross‐couplings in organic synthesis, the coupling of unactivated alkyl electrophiles remains challenging due to sluggish oxidative addition and competing side reactions. Here, we describe a general and practical copper‐catalyzed radical deoxyalkynylation of α‐unfunctionalized alcohols through a synergistic combination of Barton‐McCombie deoxygenation and copper‐catalyzed radical cross‐coupling. Key to the success of this method lies in not only the development of rigid anionic multiple N , N , N ‐ligand to exert remarkable selectivity of highly reactive unactivated alkyl radicals, but also the selection of one suitable oxidant to suppress Glaser homocoupling and other side products. This method provides a complementary approach for the cross‐coupling of unactivated alkyl halides, which face notable difficulties in reaction initiation and bond formation under mild thermal conditions, especially the tertiary variants. This protocol not only exhibits a broad scope with respect to both coupling partners, covering alkyl‐ and (hetero)aryl alkynes, as well as α‐unfunctionalized primary‐, secondary‐, and tertiary‐ alcohols with good functional group compatibility, but also facilitates the late‐stage functionalization of a series of important natural and bioactive complex molecules.