Synthesis of Benzopyridoindolone Derivatives via a One-Pot Copper Catalyzed Tandem Reaction of 2-Iodobenzamide Derivatives and 2-Iodobenzylcyanides

Abstract

An efficient approach for the synthesis of benzo-fused pyridoindolone derivatives via a one-pot copper catalyzed tandem reaction of 2-iodobenzamides with 2-iodobenzylcyanides has been developed. Using this protocol, benzo-fused pyridoindolone derivatives are obtained in high yields in a relatively short period of time under mild reaction conditions. To the best of our knowledge, this is the first approach where one can synthesize free indole N-H benzo-fused pyridoindolones. Also, both indole and pyridone cores are constructed during the course of the reaction. The methodology shows good functional group tolerance and allows synthesis of thiophene-fused pyridoindolones and fused indolobenzonaphthyridone derivatives.

Synthesis of 1,2,3‐Fused Indole Polyheterocycles by Copper‐Catalyzed Cascade Reaction

“…To initiate our study, we chose 2‐iodo‐ N ‐(2‐iodobenzyl)benzamide ( 1a ) and 2‐iodobenzyl cyanide ( 2a ) as the model substrates. Employing the details of our recent publication for the synthesis of benzopyridoindolones from 2‐iodo‐ N ‐substituted benzamide derivatives and 2‐iodobenzyl cyanide, we initiated our experiment by using 15 mol‐% of CuCl, 30 mol‐% of l ‐proline, and 3 equiv. of Cs 2 CO 3 in dimethyl sulfoxide (DMSO) as the solvent at 80 °C.…”

“…To date, direct access to 1,2,3‐polycyclic‐fused indole derivatives from non‐indole derivatives has yet to be reported. Our group has been interested in the development of strategies for the synthesis of variety of polycyclic‐fused indole derivatives, and recently designed an easy and efficient method for the synthesis of benzopyridoindole derivatives from 2‐iodobenzamide and 2‐iodobenzyl cyanide by using a copper‐catalyzed tandem cyclization reaction …”

Recent Advancement in the Copper Mediated Synthesis of Heterocyclic Amides as Important Pharmaceutical and Agrochemicals

“…The catalytic system effectivelytolerateda broad range of functional groups allowing the synthesis of thiophene‐fused pyridoindolones and fused indolobenzonaphthyridone derivatives (See Figure 81). [119] …”

The synthesis ofN‐containing heterocyclic compounds catalyzed by copper/L‐proline

“…[ 70 ] In 2017, the method for the construction of pyridoindolone derivatives 201 could be realized by copper‐catalyzed cascade reaction of 2‐iodobenzamides 199 and 2‐iodobenzylcyanides 200 (Scheme 32). [ 71 ] This methodology was wide substrate scope and excellent product yields, but only 2‐iodobenzamides were accommodative in this reaction. This method was the first approach for the free indole N‐H benzopyridoindolones synthesis, which involved the subsequent transformation of Ullmann‐type C‐C coupling reaction, amino addition to nitrile, and Ullmann‐type C‐C coupling reaction.…”