Electrochemical [3+2] Cycloaddition of Anilines and 1,3‐Dicarbonyl Compounds: Construction of Multisubstituted Indoles

Abstract

Indoles, especially multisubstituted ones, are privileged scaffolds found widely in natural products, bioactive molecules, fine chemicals, and organic functional materials. Although several intramolecular electrochemical cyclization reactions of vinyl anilines to construct indoles have been reported in recent years, the intermolecular process between simple anilines and other readily available synthons, even though dominant, remains relatively unexplored. Herein, we report the intermolecular electro-oxidative cycloaddition of anilines and commercially available 1,3-dicarbonyl compounds. This method provides an alternative route for the synthesis of a broad range of multisubstituted indoles without a transition-metal catalyst or external chemical oxidant.

Recent advances in electrochemically enabled construction of indoles from non-indole-based substrates

“…The electrochemical annulation of anilines with 1,3dicarbonyl for the construction of multisubstituted indoles was demonstrated by Sun's group in 2022 (Scheme 16). 36 This method has the advantage of using readily available and easily prepared substrates. The reaction is probably initiated by the oxidation of 91a and 92a to their corresponding radicals 94 and 96.…”

Recent advances in the electrochemical generation of 1,3-dicarbonyl radicals from C–H bonds

“…In 2022, Sun's group reported the electrochemical [3 + 2] cycloaddition of anilines and 1,3-dicarbonyl derivatives (Scheme 5). 23 The reaction is directly executed with 30 mol% TfOH in a solution of n Bu 4 NBF 4 in HFIP without the need for metal catalysts or external oxidants, providing a powerful method for the construction of a broad range of multi-substituted indoles. The success of the reaction depends on the anodic oxidation of 5-7 and 5-9 at the same time to form nitrogen-centered radical 5-8 and 1,3-dicarbonyl radical 5-10 , in which 5-8 resonates to give carbon-centered radical 5-11 .…”

Indole frameworks via transition-metal-free annulation: a current perspective

“…Electrochemical [3+2] cycloaddition of substituted anilines 25 and 1,3-dicarbonyl 139 compounds for the construction of functionalized indoles 140 was reported by Sun et al 101 The electrochemical reaction was designed in an undivided cell equipped with a carbon anode and a platinum cathode connected to a DC regulated power supply (1.5 mA). A wide range of N -protected anilines (PG = Ts, Bs, Bz, Boc, Me) with diverse substitution in the aromatic ring (R 1 = OMe, OEt, O n Pr, NO 2 , CN, Br, Cl, etc. )…”