Chemo- and Enantioselective Oxidative α-Azidation of Carbonyl Compounds

We report high-performance I⁺ /H₂ O₂ catalysis for the oxidative or decarboxylative oxidative α-azidation of carbonyl compounds by using sodium azide under biphasic neutral phase-transfer conditions. To induce higher reactivity especially for the α-azidation of 1,3-dicarbonyl compounds, we designed a structurally compact isoindoline-derived quaternary ammonium iodide catalyst bearing electron-withdrawing groups. The nonproductive decomposition pathways of I⁺ /H₂ O₂ catalysis could be suppressed by the use of a catalytic amount of a radical-trapping agent. This oxidative coupling tolerates a variety of functional groups and could be readily applied to the late-stage α-azidation of structurally diverse complex molecules. Moreover, we achieved the enantioselective α-azidation of 1,3-dicarbonyl compounds as the first successful example of enantioselective intermolecular oxidative coupling with a chiral hypoiodite catalyst.