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 H 2 O 2 or O 2 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.