posted on 2023-11-29, 20:37authored byBowen Zhang, Frederik R. Erb, Aristidis Vasilopoulos, Eric A. Voight, Erik J. Alexanian
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(sp3)–H/C(sp2)–H
[4 + 1] annulation of readily accessed N,N-dialkylanilines.
This protocol features a site-selective hydrogen atom transfer by
a tuned N-tBu 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.