Iron-Catalyzed Asymmetric α-Alkylation of 2-Acylimidazoles via Dehydrogenative Radical Cross-Coupling with Alkanes

The direct alpha-alkylation of acyclic carbonyls with nonactivated hydrocarbons through C(sp3)-H functionalization is both extremely promising and notably challenging, especially when attempting to achieve enantioselectivity using iron-based catalysts. We have identified a robust chiral iron complex for the oxidative cross-coupling of 2-acylimidazoles with benzylic and allylic hydrocarbons, as well as nonactivated alkanes. The readily available and tunable N,N '-dioxide catalysts of iron in connection with oxidants exhibit precise asymmetric induction (up to 99 % ee) with good compatibility in moderate to good yields (up to 88 % yield). This protocol provides an elegant and straightforward access to optically active acyclic carbonyl derivatives starting from simple alkanes without prefunctionalization. Density functional theory (DFT) calculations and control experiments were made to gain insight into the nature of C-C bond formation and the origin of enantioselectivity. We propose a radical-radical cross-coupling process enabled by the immediate interconversion between chiral ferric species and ferrous species. The asymmetric alpha-alkylation of acyclic carbonyls with hydrocarbons is of substantial interest and challenge. Herein, we achieved the enantioselective oxidative cross-coupling of 2-acylimidazoles with up to 99 % ee in moderate to good yields, thus providing an elegant access to optically active carbonyl compounds. Density functional theory calculations suggest a radical-radical cross-coupling pathway.+image