Oxidation of Nonactivated Anilines to Generate N-Aryl Nitrenoids

J Am Chem Soc. 2020 Mar 4;142(9):4456-4463. doi: 10.1021/jacs.9b13599. Epub 2020 Feb 25.

Abstract

A low-temperature, protecting-group-free oxidation of 2-substituted anilines has been developed to generate an electrophilic N-aryl nitrenoid intermediate that can engage in C-NAr bond formation to construct functionalized N-heterocycles. The exposure of 2-substituted anilines to PIFA and trifluoroacetic acid or 10 mol % Sc(OTf)3 triggers nitrenoid formation, followed by productive and selective C-NAr and C-C bond formation to yield spirocyclic- or bicyclic 3H-indoles or benzazepinones. Our experiments demonstrate the breadth of these oxidative processes, uncover underlying fundamental elements that control selectivity, and demonstrate how the distinct reactivity patterns embedded in N-aryl nitrenoid reactive intermediates can enable access to functionalized 3H-indoles or benzazepinones.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.