Transition Metal‐Free Synthesis of Sulfonyl‐ and Bromo‐Substituted Indolo[2,1‐α]isoquinoline Derivatives through Electrochemical Radical Cascade Cyclization

Abstract

A tunable electrosynthesis of sulfonyland bromo-substituted indolo[2,1-α]isoquinoline derivatives has been disclosed. In this reaction, a variety of easily available 2-aryl-N-acryloyl indoles can readily react with sulfonyl and/or bromine radicals, which are generated from arylsulfonyl hydrazides and potassium bromide respectively, to furnish the valuable sulfonyl-and bromo-substituted benzindolo-fused polycyclic compounds in moderate to good yields. Control experiment indicated that the reaction proceeds via a radical cascade cyclization pathway. This protocol features broad substrate scope and good functional group tolerance under transition metal-free and oxidant-free conditions.

Molecular Oxygen‐Mediated Radical Cyclization of Acrylamides with Boronic Acids

“…Undoubtedly, synthesis of indolo[2,1‐ a ]isoquinlinone derivatives through radical cyclization process is a simple and convenient approach [6] . For example, acyl‐, [7] polyfluoroalkyl‐, [8] phosphoryl‐, [9] thiocyanyl‐, [10] sulfonyl‐ and bromo‐substituted [11] indolo[2,1‐ a ]isoquinolinones were constructed from 2‐arylindoles via tandem radical addition/cyclization. On the other hand, organoboronic acid was demonstrated as an efficient radical precursor to construct C−C bonds in the past few years [2i–k,12–14] .…”

“…Initially, the reaction of boronic acid with molecular oxygen affords radical A and cyclohexyl radical B. Subsequently, the addition of cyclohexyl radical B to 2-phenyl-3-methyl-N-methacryloyl-indole 1 a forms the radical intermediate C, which followed by intramolecular radical cyclization to give radical D. [8][9][10][11] Finally, hydrogen-atom transfer from D to A affords the desired product 3 aa.…”

Progress in the Electrochemical Reactions of Sulfonyl Compounds

“…Another synthesis of functionalized indolo[2,1‐α]isoquinoline derivatives ( 84 ) was published by Shen et al. recently (Scheme 13b) [71] . This transition metal‐free and oxidant‐free reaction underwent a radical cascade cyclization, generating sulfonyl‐ and bromo‐ substituted indolo[2,1‐α]isoquinoline derivatives.…”

Synthesis of ester-functionalized indolo[2,1-a]isoquinolinesviairon-catalyzed radical cascade cyclization of 2-aryl-N-acryloyl indoles with carbazates

“…Indolo[2,1- a ]isoquinoline derivatives are important nitrogen-containing heterocycles and are commonly found in many organic synthetic intermediates, biologically active natural products, pharmaceuticals, and functional materials. 12 Recently, considerable effort has been devoted to the construction of structurally diverse indolo[2,1- a ]isoquinolines via a radical addition/cyclization process, including arylation, 13 alkylation, 14 sulfonylation, 15 acylation, 16 thiolation, 17 germylation, 18 selenylation 19 and phosphonation 20 (Scheme 1a). However, the application of this strategy for the synthesis of ester-functionalized indolo[2,1- a ]isoquinolines utilizing easily accessible and safe carbazates as the alkoxycarbonyl radical precursor has not been achieved.…”