Three-Component Synthesis of Pyrrolo/indolo[1,2-a]quinoxalines Substituted with o-Biphenylester/N-arylcarbamate/N-arylurea: A Domino Approach Involving Spirocyclic Ring Opening

Abstract

A p-TsOH-mediated one-pot, three-component methodology has been developed for the synthesis of pyrrolo/indolo­[1,2-a]­quinoxalines substituted with o-biphenylester/N-arylcarbamate/N-arylurea at the C-4 position under open-air heating conditions. The protocol offers a transition-metal-free and external oxidant-free solvent-mediated pathway to afford a library of diversely substituted quinoxalines in moderate to good yields. Various water-miscible aliphatic alcohols and amines participate in the reactions both as solvent as well as reactant. X-ray crystal structure analysis suggests that some of the suitably substituted quinoxalines may exhibit atropisomerism at room temperature.

Recent Examples in the Synthesis and Functionalization of C−H Bonds in Pyrrolo/Indolo [1,2‐a]Quinoxalines

“…Multicomponent assemblies have been underdeveloped toward synthesis of substituted pyrrolo[1,2‐ a ]quinoxalines. In 2021, Pramanik and Mandal reported a rare method for coupling of 2‐( N ‐indolyl)anilines with isatins and nucleophiles [16] . During the optimization study, the mixture of a spirooxindole‐fused quinoxaline and an indolo[1,2‐ a ]quinoxaline substituted N ‐phenylcarbamate was observed.…”

“…In 2021, Pramanik and Mandal reported a rare method for coupling of 2-(N-indolyl)anilines with isatins and nucleophiles. [16] During the optimization study, the mixture of a spirooxindole-fused quinoxaline and an indolo[1,2a]quinoxaline substituted N-phenylcarbamate was observed. The latter product was presumably obtained via a ring opening of the spirooxindole-fused quinoxaline product by the nucleophile ethanol, used as the solvent.…”

Recent advances in the transition-metal-free synthesis of quinoxalines

“…132 Recently, a transition-metal-free one-pot domino process for the synthesis of diverse pyrrolo/indolo[1,2-a]quinoxaline derivatives has been realized by Mandal and Pramanik (Scheme 46). 133 By using 50 mol% of p-TsOH as the catalyst, a threecomponent reaction of N-(2-aminophenyl)pyrroles/indoles 159, with various cyclic 1,2-dicarbonyl compounds 160 or 163 and alcohols 161 or aliphatic amines 166 were performed in open-air heating condition. The reactions provide a variety of different fused quinoxaline derivatives 162, 164, and 167 in moderate to good yields.…”

Efficient synthesis of pyrrolo[1,2-α]quinoxalines mediated by ethyl 2-(4-nitrophenyl)azocarboxylate

“…14 The most common methods are Pictet–Spengler type reactions between 2-(1 H -pyrrol-1-yl)anilines and cyclization partners such as aldehydes, 15 alcohols, 16 amines, 17 alkyl halides, 18 ketones, 19 1,3-diketones, 20 α-keto acids, 21 α-hydroxyl acids, 22 α-amino acids, 23 aryl acetic acids, 24 cyclic ethers, 25 and methyl arenes 26 in the presence of various oxidants (Scheme 1B). 27,28 Although these oxidants facilitated Pictet–Spengler type pyrrolo[1,2-α]quinoxaline synthesis, a high reaction temperature was usually required and the substrate scope was mostly limited to 4-aryl substituted pyrrolo[1,2-α]quinoxalines. Herein, we report a mild and efficient synthesis of various 4-substituted pyrrolo[1,2-α]quinoxalines using ethyl 2-(4-nitrophenyl)azocarboxylate 1d as a recyclable oxidant for the first time (Scheme 1C).…”