Expeditious Synthesis of Spiroindoline Derivatives via Tandem C(sp²)–H and C(sp³)–H Bond Functionalization of <i>N</i>-Methyl-<i>N</i>-nitrosoanilines

Abstract

Presented herein is a novel synthesis of pharmaceutically privileged spiroindoline derivatives via cascade reactions of <i>N</i>-methyl-<i>N</i>-nitrosoanilines with diazo homophthalimides. A group of mechanistic studies disclosed that the formation of product involves an unusual reaction mode of <i>N</i>-methyl-<i>N</i>-nitrosoaniline featuring an initial C(sp²)-H bond activation/alkylation followed by a C(sp³)-H bond activation/spiroannulation. To our knowledge, this is the first example in which <i>N</i>-methyl-<i>N</i>-nitrosoaniline acts as a C3N1 synthon to accomplish formal [4+1] spiroannulation with the participation of the <i>N</i>-methyl unit rather than the previously reported C2N1 synthon to undergo formal [3+2] annulation without the participation of the <i>N</i>-methyl unit. In general, this newly developed synthetic protocol features simple and readily accessible starting materials, valuable products, unique reaction mechanism, high efficiency and atom-economy, excellent compatibility with diverse functional groups, and ready scalability.