Chemo‐ and Enantioselective Oxidative α‐Azidation of Carbonyl Compounds

• Published in: Angewandte Chemie International Edition 2020-09, Vol.59 (39), p.17110-17117
• Main Authors: Uyanik, Muhammet, Sahara, Naoto, Tsukahara, Mayuko, Hattori, Yuhei, Ishihara, Kazuaki
• Format: Article
• Language: English
• Subjects: Ammonium; azides; Carbonyl compounds; Carbonyls; Catalysis; Catalysts; chemoselectivity; Coupling (molecular); Coupling agents; Enantiomers; enantioselectivity; Functional groups; Hydrogen peroxide; hypoiodite catalysis; Iodides; oxidative coupling; Sodium azide; Sodium azides
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202007552

We report high‐performance I+/H2O2 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+/H2O2 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. High‐performance hypoiodite catalysis was developed for the chemoselective oxidative or decarboxylative oxidative α‐azidation of 1,3‐dicarbonyl compounds (see scheme). By this method, the late‐stage azidation of complex molecules with NaN3 and hydrogen peroxide as the azide source and oxidant, respectively, was possible under extremely mild conditions.