Photoinduced Bartoli Indole Synthesis by the Oxidative Cleavage of Alkenes with Nitro(hetero)arenes

Abstract

Given the unique charm of dipole chemistry, intercepting N-O=C dipoles precisely generated by designed processes to develop novel reactivity has become a seminal challenge. The polar fragmentation of 1,3,2-dioxazolidine species generated through the radical addition of excited nitro(hetero)arenes to alkenes represents a significantly underappreciated mechanism for generating N-O=C dipoles. Herein, we present a photoinduced Bartoli indole synthesis by the oxidative cleavage of alkenes with nitro(hetero)arenes. Various indoles and azaindoles are constructed through the multi-step spontaneous rearrangement of carbonyl imine intermediates generated by the polar fragmentation of 1,3,2-dioxazolidine species. Mechanism studies and DFT calculations support that the reaction involves radical cycloaddition, ozonolysis-type cycloreversion, intramolecular H-shift of carbonyl imines, and 3,3-sigmatropic shift of O-Alkenyl hydroxylamines, etc. The implementation of continuous- flow photochemistry, in particular, significantly enhances efficiency, thereby overcoming obstacles to the commercialization process.

Keywords: Bartoli indole synthesis; Continuous-flow Chemistry; N−O=C dipoles; Photochemistry; nitro(hetero)arenes.