Electro‐Oxidative Coupling of Azoles with 2‐ and 3‐Haloindoles/Thiophenes Providing Access to 2/3‐Halo(Azol‐1‐Yl)Indoles/Thiophenes

Abstract

This report discloses an electrochemical oxidative CÀ H/NÀ H cross coupling method for the synthesis of C-2/C-3 azolated halo-indoles/thiophenes under metal catalyst-free and external chemical oxidant free condition. Hydrogen gas was the only byproduct of this CÀ H/NÀ H cross-coupling reaction. The synthetic utility of this electrochemical approach is highlighted by its easy scalabity and compatibility with highly functional indoles and azoles. The retention of halogen on the heterocycles could serve as a useful functional group for future late-stage modifications.

Recent advances in metal catalyst- and oxidant-free electrochemical C-H bond functionalization of nitrogen-containing heterocycles

“…Control experiments suggested that a radicalradical cross-coupling process between the N-centered radical and cationic indole radical may be involved for this amination reaction. Very recently, the same group (Zhou et al, 2022) further developed an electrochemical oxidative coupling of azoles 38 with 2-and 3-Haloindoles/Thiophenes 39 under metal catalyst-and oxidant-free conditions. A series of C-2/C-3 aminated halo-indoles/thiophenes 40 were obtained in a simple undivided cell equipped with two platinum electrodes at a constant current of 10 mA, using n-Bu 4 NBF 4 as an electrolyte (Scheme 9b).…”

NaClO‐Mediated Cross Installation of Indoles and Azoles Benefits Anticancer Hit Discovery

“…[9] More recently, radical-mediated C-2 azolation of indoles with electrochemical strategy or copper catalysis were developed, yet with limited substrate scope. [10] Besides, by switching the oxidant from iodine to sodium hypochlorite, Yu et al discovered an efficient and rapid protocol for chloroamidation of indoles with sulfonamides and sodium hypochlorite. [11] Inspired by these elegant research and driven by our continuing interests in searching for innovative installation approaches towards indoles [12] and peptides, [13] we anticipated to develop an approach of sodium hypochlorite (NaClO) mediated cross installation of two medicinal modules indoles and azoles, and further Trp and His in peptides, for quick access to original N-linked 2-(azol-1-yl) indole derivatives and peptide late-stage modification.…”

Consecutive cross-dehydrogenative C–O and C–N construction for the synthesis of polyarene with AIE properties under electrochemical condition involving oxygen radical species

“…8 Moreover, this protocol shows great advantages in CDC reactions with the evolution of H 2 as the sole byproduct. 9 In our ongoing interest in developing electrochemically synthetic methodologies featuring atom-economy and step-economy, 10 we propose a consecutively cross-dehydrogenative C–O and C–N process to construct polyarene (Scheme 1c): (1) phenol derivatives could be oxidized on the surface of an electrode to generate a mixture of C/O radical species, which can be readily coupled to give a C–O coupling intermediate; 11 (2) the in situ formed intermediate would be further oxidized, and then react with azoles via S N Ar process to form a C–N bond. 12 From a synthetic perspective, very few one-pot transformations could achieve multi-CDC steps to establish C–N and C–O bonds, and the method described herein thus provides a new strategy for selectively constructing multiple C–X bonds in a green manner.…”