General Synthesis of N -Alkylindoles from N , N -Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.

Strategies enabling the construction of indoles and novel polycyclic heterocycles from simple building blocks streamline syntheses in synthetic and medicinal chemistry. Herein, we report a C-H functionalization approach to N -alkylindoles proceeding via a double, site-selective C(sp 3 )-H/C(sp 2 )-H [4 + 1] annulation of readily accessed N,N -dialkylanilines. This protocol features a site-selective hydrogen atom transfer by a tuned N - t Bu amidyl radical and addition of a sulfonyl diazo coupling partner, which promotes highly site-selective homolytic aromatic substitution of the (hetero)aromatic core. Mild decarboxylation of the annulation product enables the overall introduction of a carbyne equivalent into the N,N -dialkylaniline scaffold. Furthermore, the site-selectivity and mild conditions of the indolization facilitate direct access to N -alkyl indole scaffolds in late-stage functionalization (LSF) settings.