Electrochemical Cascade Cyclization of N-Centered Radicals with Electro-Deficient Alkynes

Indoline-fused polycyclic scaffolds are virtually universal in biological and pharmaceutical. Here we demonstrate a facile electrooxidative cascade cyclization for indoline-based derivatives, employing amidyl radicals with ynones under mild conditions. The efficient method enables the formation of two new C-N and C-C bonds in a single step with high regioselectivity. Various indoline-based tetracyclic 6/5/6/6 skeletons can be achieved through a biscyclization/dehydrogenation cascade process. Additionally, this electrochemical strategy proceeds in a sustainable metal- and oxidant-free condition, with H2 being the solely byproduct. An electrochemcial synthesis of indoline-fused polycycles by constructing both the five- and six-membered heterocyclic rings in a single step from arylamide-tethered ynones has been developed, which provides facile access to various indoline-based tetracyclic 6/5/6/6 skeletons with highly regioselective control in a sustainable, metal- and oxidant-free condition.+ image