Propargylamines in Pd/Cu-catalyzed tandem coupling-cyclization-N-deprotection in a single pot: Construction of N-unsubstituted vs N-sulfonyl indole ring

Abstract

The Pd/Cu-catalyzed tandem coupling–cyclization-N-deprotection in a single pot (Method a) vs sequential coupling–cyclization under similar conditions (Method b) has been studied using propargylamine as a terminal alkyne under environmentally friendly conditions. The first sequence (Method a) was followed to afford the N-unsubstituted indoles when 2,2,2-trifluoro-N-(2-iodophenyl)acetamides were employed as halides whereas N-sulfonyl indoles were obtained following the second path (Method b) when 2-iodo sulfanilides were used as halides. A number of compounds based on either the framework indolo[2,3–b]quinoxaline-indole or a similar framework possessing a sulfonyl group at the indole nitrogen were obtained in good yield employing the Method a or b, respectively. While the study was carried out with the goal of accessing a library of indolo[2,3–b]quinoxaline-indole based small molecules of potential biological interest (especially as anti-tubercular agents) the generality/scope of Method a was expanded further via the synthesis of simpler indole derivatives using various other propargylamines as terminal alkynes.