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

• DOI: 10.1021/acs.orglett.4c00703
• Publication Date: 2024-04-03T11:51:50Z
• Authors: Kelin Wang; Yuqian Sun; Bin Li; Xinying Zhang; Xuesen Fan
• Keywords: Synthon; Annulation; Tandem; Methyl group; Surface Modification; Cascade reaction

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