Broadly Applicable Directed Catalytic Reductive Difunctionalization of Alkenyl Carbonyl Compounds

Summary Catalytic alkene difuntionalization is a convenient platform for introducing complexity in molecules and has wide applications in organic synthesis. Yet a compelling challenge that remains to be solved is the regioselective insertion of two highly functionalized carbon-based moieties, derived from stable and readily available organohalide electrophiles without the need for pre-synthesized organometallic reagents, across C=C bonds in unactivated alkyl-substituted alkenes. Here, we show that catalytic amounts of an inexpensive Ni-based catalyst, in combination with a readily recyclable 8-aminoquinoline directing group, promotes efficient and site-selective addition of two different organohalides (iodides and bromides) across aliphatic alkenes under mild reductive conditions. Compared to previous studies, this protocol exhibits broad and complementary functional group tolerance that extends to aryl-alkylation, alkenyl-alkylation, and dialkylation transformations. The utility of the strategy is demonstrated through concise synthesis of biologically active molecules. Kinetic studies and other control experiments shed further light on the mechanistic underpinnings of the multicomponent reaction.