On the Ability of the N-O Bond to Support a Stable Stereogenic Axis: Peptide-Catalyzed Atroposelective N -Oxidation.

During studies of atroposelective, peptide-catalyzed N -oxidations of pyridines, we observed lower-than-expected barriers to atropisomerization for these stereodynamic processes under the reaction conditions. Mechanistic studies indicate a hydrogen bond-assisted racemization mechanism intrinsic to both the starting materials and products. We also identified a protonation-dependent barrier to rotation that operates for the starting materials alone. Nonetheless, several substrates were amenable to atroposelective N -oxidations via kinetic resolution, yielding k rel values of up to 12.6 and the isolation of one N -oxide with >99:1 er after recrystallization.