Rhodium(III)-Catalyzed Indole Synthesis Using N–N Bond as an Internal Oxidant

by Baoqing Liu, Chao Song, Chao Sun, Shuguang Zhou and Jin Zhu*

We report herein a Rh(III)-catalyzed cyclization of N-nitrosoanilines with alkynes for streamlined synthesis of indoles. The synthetic protocol features a distinct internal oxidant, N–N bond, as a reactive handle for catalyst turnover, as well as a hitherto tantalizingly elusive intermolecular redox-neutral manifold, predicated upon C–H activation, for the formation of a five-membered azaheterocycle. The compatibility of seemingly dichotomous acidic and basic conditions ensures reaction versatility for multifarious synthetic contexts. The tolerance of an array of auxiliary functional groups potentially permits predefined, programmable substitution patterns to be incorporated into the indole scaffold. Comprehensive mechanistic studies, under acidic condition, support [RhCp*]²⁺ as generally the catalyst resting state (switchable to [RhCp*(OOC^tBu)]⁺ under certain circumstance) and C–H activation as the turnover-limiting step. Given the variety of covalent linkages available for the nitroso group, this labile functionality is likely to be harnessed as a generic handle for strikingly diverse coupling reactions.

Journal of the American Chemical Society

Publication Date (Web): October 7, 2013

DOI: 10.1021/ja408541c