Mn-Catalyzed Electrochemical Radical Cascade Cyclization toward the Synthesis of Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one Derivatives

Abstract

Benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives are prevalent in many synthetic intermediates, pharmaceuticals, and organic materials. Herein, we develop a Mn-catalyzed electrochemical radical cascade cyclization reaction that uses electricity as the primary energy input to promote the reaction, leading to a series of benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives under exogenous-oxidant-free conditions. It is worth noting that this electrochemical method can not only realize the synthesis of benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives but also provides a new strategy for generating alkyl radicals from alkylboronic acids.

Electrochemical Tri‐ and Difluoromethylation‐Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives

“…For example, the challenging task of constructing functionalized oxindoles has been accomplished by the groups of Lei, [7d] Zeng, [7e] Mo, [7g] and other groups (Scheme 1 a). Also, addition of various carbon or phosphorous [8] radicals, including fluorinated ones, [8c] to the same 2‐Ph indoles N‐substituted by an acryloyl group is known to be promoted by electrochemistry, [8a] visible light, [8b,c] or stoichiometric oxidants [8d, e] . The difference with the present work is that the oxidative cleavage of the indole does not occurs in these previous reports.…”

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

“…In their developed system, acyl radicals were generated from benzoyl chlorides and added to 2‐aryl‐ N ‐acryloyl indoles, which triggered the radical cascade cyclization process (Scheme 1a). In 2020, Lei and co‐ workers reported a Mn‐catalyzed electrochemical radical cascade cyclization reaction that utilized alkylboronic acids as alkyl radical precursors, leading to a series of alkylated indolo[2,1‐α]isoquinolines as products [9] . In addition, the synthesis of perfluoroalkyl‐, phosphoryl‐, and selenyl‐substituted indolo[2,1‐α]isoquinoline derivatives from 2‐aryl‐ N ‐acryloyl indoles was further developed through visible light‐, manganese‐, and iron‐promoted synthetic pathways, respectively [10–12] …”

“…All the starting materials are known compounds. They can be synthesized according to the published methods [8,9] …”

“…Replacing the Pt anode with a graphite rod led to a dramatic drop in the yield of 3 a (entry 6). Moreover, other solvent systems were explored but provided no improvement over THF/H 2 O (entries [7][8][9][10][11]. Notably, the yield of 3 a was slightly reduced when 2.0 equiv.…”

Synthesis of Indolo[2,1‐a]isoquinolin‐6(5H)‐Ones Derivatives via Fe(OTf)3‐Promoted Tandem Selenylation/Cyclization of 2‐Arylindoles

“…Yu's group reported a metal‐free visible‐light‐induced radical cyclization procedure for the synthesis of perfluoroalkyl‐substituted indolo[2,1‐ a ]isoquinolin‐6(5 H )‐ones [8] . Lei's group reported a Mn‐catalyzed electrochemical radical cascade cyclization reaction to indolo[2,1‐a]isoquinoline derivatives from 2‐arylindoles and boronic acids [9] . Very recently, Li's group reported Mn‐promoted tandem phosphinoylation /cyclization of 2‐arylindoles to phosphoryl‐substituted indolo[2,1‐ a ]isoquinolin‐6(5 H )‐ones [10] .…”