Biomimetic Dynamic Kinetic Asymmetric N-Oxidation with H2O2 and O2

Optically active chiral sulfoxides, phosphine oxides, and amine oxides are ubiquitous in pharmaceutical and asymmetric synthesis. However, unlike the well-developed synthetic method for chiral sulfoxides and phosphine oxides, routes to N-chiral amine oxides have garnered less attention due to the instability of the N-centers in tertiary amines. So far, resolution and asymmetric induction are still the main strategies for N-chiral amine oxides, while asymmetric N-oxidation is only limited to several underdeveloped enzymatic and metal-catalyzed processes. Here, we develop an efficient biomimetic asymmetric N-oxidation method by designing various chiral alloxan catalysts to mimic the flavin-containing monooxygenases in vivo, which presents an entry into N-chirality control. With H2O2 or O2 as an eco-friendly oxidant, a range of N-chiral acyclic tertiary amine oxides were obtained in high yields (up to 98%) and with ee values (up to 93%). Control experiments and density functional theory (DFT) calculations revealed this successful stereocontrol might rely on hydrogen-bond-mediated dynamic kinetic resolution.