Electrooxidation Enables Selective Dehydrogenative [4+2] Annulation between Indole Derivatives

TLDR: Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between in situ generated indole radical cation and N-centered radical.

Abstract: Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.