Carbon Insertion into Electron-Deficient (Aza)indoles via a Radical-Polar Crossover Strategy

Abstract Despite a surge of progress in both strategic approaches and reagent design, carbon insertion into indoles remains limited to electron-rich substrates, notwithstanding the prevalence of electron-poor (aza)indoles in medicinal chemistry. We report herein a radical-polar crossover strategy that overcomes this limitation through a photocatalytic, iodomethyl-radical-mediated cyclopropanation/autoxidation approach. The method enables access to a range of highly substituted, electron-poor quinolines, naphthyridines, and triazanaphthalenes, many of which are challenging to prepare by traditional syntheses. We demonstrate the modification of medicinally relevant (aza)indoles, and preliminary mechanistic observations support autoxidation via an anionic cyclopropane ring opening pathway.