Factors Influencing the Regioselectivity of the Oxidation of Asymmetric Secondary Amines with Singlet Oxygen

Aerobic amine oxidation is an attractive and elegant process for the α functionalization of amines. However, there are still several mechanistic uncertainties, particularly the factors governing the regioselectivity of the oxidation of asymmetric secondary amines and the oxidation rates of mixed primary amines. Herein, it is reported that singlet‐oxygen‐mediated oxidation of 1° and 2° amines is sensitive to the strength of the α‐C?H bond and steric factors. Estimation of the relative bond dissociation energy by natural bond order analysis or by means of one‐bond C?H coupling constants allowed the regioselectivity of secondary amine oxidations to be explained and predicted. In addition, the findings were utilized to synthesize highly regioselective substrates and perform selective amine cross‐couplings to produce imines.