Aminyl Radical-Enabled Photoredox/Nickel-Catalyzed C(sp³)-C(sp³) Suzuki-Miyaura Cross-Coupling via Halogen-Atom...

Although Suzuki-Miyaura coupling has become a state-of-the-art method for constructing C(sp²)-C(sp²) bonds, the development of its C(sp³)-C(sp³) counterpart remains a long-standing challenge. The difficulty likely arises from the low propensity of alkyl pinacol boronic esters (APEs) to undergo radical generation, the low reactivity of alkyl electrophiles, and competitive β-hydride elimination. In this study, we employ an aminyl radical to activate APEs, enabling the generation of alkyl radicals under photoredox conditions, while a nickel catalyst activates alkyl electrophiles to achieve the challenging formation of C(sp³)-C(sp³) bonds. This strategy operates under mild conditions and exhibits a broad substrate scope with excellent functional group tolerance, particularly toward alkyl bromides bearing free hydroxyl and carboxylic acid groups. Moreover, this method enables site-selective alkylation, alkenylation, alkynylation, and arylation of 1,n-bis(boronic) esters. Mechanistic studies support a pathway in which N-centered radicals generate alkyl radicals, followed by radical capture by an alkylnickel(II) species formed via an intriguing halogen-atom transfer (XAT) between Ni(0)L and alkyl bromides. The robustness and synthetic utility of this methodology are demonstrated through scale-up and continuous-flow experiments, diverse downstream transformations, and the direct synthesis of a bioactive molecule without the need for a hydroxyl protecting group.