Modular Platform for Directing-Group-Free Radical Dicarbofunctionalization of Unactivated Alkenes via Dual Nickel/Energy-Transfer Catalysis.

Multicomponent cross-coupling reactions of alkenes offer a powerful strategy for constructing three-dimensional, sp3 -rich molecular architectures, a key objective in modern medicinal chemistry. However, the regioselective dicarbofunctionalization of unactivated alkenes without the use of directing groups remains a significant challenge. Herein, we report a visible-light-induced, Ni-catalyzed platform that enables the radical 1,2-dicarbofunctionalization of unactivated alkenes using diverse alkyl radical precursors and aryl, vinyl, acyl, alkynyl, and alkyl coupling partners. Mechanistic studies support a catalytic cycle in which multiple electron donor-acceptor (EDA) complexes mediate radical generation, atom-transfer radical addition (ATRA), and cross-electrophile coupling (XEC) or bimolecular homolytic substitution (SH2) processes. Additionally, preferential formation of a complex between the Ni catalyst and the radical precursor suppresses undesired homocoupling of the electrophilic partner. Notably, delivery of gaseous radical precursors such as trifluoromethyl iodide (TFMI) from the robust metal-organic framework (MOF) Al(OH)fum (fum- = fumarate) or Al-fum offers advantages in terms of both operational safety and reaction efficiency, and the MOF further boosts the yields of reactions by decreasing the concentration of free amine (employed for radical generation) in solution. Collectively, this flexible, directing-group-free approach establishes a general platform for the rapid construction of structurally complex and pharmaceutically relevant molecules from readily available precursors.