Site-selective coupling of remote C(sp(3))–H/meta-C(sp(2))–H bonds enabled by Ru/photoredox dual catalysis and mechanistic studies

Construction of C(sp(2))–C(sp(3)) bonds via regioselective coupling of C(sp(2))–H/C(sp(3))–H bonds is challenging due to the low reactivity and regioselectivity of C–H bonds. Here, a novel photoinduced Ru/photocatalyst-cocatalyzed regioselective cross-dehydrogenative coupling of dual remote C–H bonds, including inert γ-C(sp(3))–H bonds in amides and meta-C(sp(2))–H bonds in arenes, to construct meta-alkylated arenes has been accomplished. This metallaphotoredox-enabled site-selective coupling between remote inert C(sp(3))–H bonds and meta-C(sp(2))–H bonds is characterized by its unique site-selectivity, redox-neutral conditions, broad substrate scope and wide use of late-stage functionalization of bioactive molecules. Moreover, this reaction represents a novel case of regioselective cross-dehydrogenative coupling of unactivated alkanes and arenes via a new catalytic process and provides a new strategy for meta-functionalized arenes under mild reaction conditions. Density functional theory (DFT) calculations and control experiments explained the site-selectivity and the detailed mechanism of this reaction.