A Homolytic Substitution Approach for Directing Group-Free Nickel-Catalyzed Dialkylation of Unactivated Alkenes

The selective construction of two C(sp3)–C(sp3) bonds via trimolecular cross-coupling of unactivated alkenes remains one of the most difficult challenges in organic synthesis. Despite previous advances on metal-catalyzed coupling for the dicarbofunctionalization of alkenes, dialkylation is still problematic due to the requisite metal-alkyl intermediates' instability (undergoes facile β-hydride elimination or protodemetalation). Recently, our group was successful in developing a bimolecular homolytic substitution (SH2) strategy that circumvents metal-alkyl side reactions and accomplishes the challenging cross-coupling of metal-alkyl intermediates with alkyl radicals in the absence of a directing auxiliary, enabling highly regioselective dialkylation of unactivated alkenes.