Modular Synthesis of Tetrasubstituted Pyrroles through a Four-Component Cyclization Strategy Using Ammonium Salt as the Nitrogen Source

Abstract

A four-component synthesis of tetrasubstituted pyrroles was developed under metal-free conditions. The pyrrole ring was formed in one pot through [2 + 1 + 1 + 1] condensation using ammonium salt as the nitrogen source. In this strategy, 1,4-naphthoquinones and maleimides were used as the versatile C2 fragments to provide substituted benzo[f]isoindole-4,9-diones and pyrrolo[3,4-c]pyrrole-1,3-diones, respectively. This work is highlighted by using ammonium salt as the nitrogen source, readily available starting materials and multibond formation (two C–C and two C–N bonds) in a single operation.

Base-promoted fused β-carboline formation from 2-(1H-indol-3-yl)cyclohexan-1-ones, aldehydes and ammonium salts

“…In this context, using ammonium salts as a nitrogen source, simple and effective approaches for constructing structurally diverse N-heterocycles have been reported. 12 In recent years, our group also successfully utilized ammonium salts as a nitrogen source for a facile construction of thiazoles, 13 quinazolines, 14 pyridines, 15 pyrimidines, 16 pyrroles, 17 benzimidazo[1,2- a ]-1,3,5-triazine, 18 phenothiazines, 19 and heteroaromatic-fused indoles. 20 In continuation of our interest in utilizing ammonium salts to synthesize N-heterocycles under metal-free conditions, herein we report a novel strategy for the formation of β-carbolines from 2-(indol-3-yl)cyclohexanones, aldehydes, and ammonium salts (Fig.…”

Water as an oxygen source in I2-mediated construction of highly functionalized maleimide-fused phenols

“…16 To the best of our knowledge, the assembly of multi-substituted 4-hydroxyisoindoline-1,3-diones with unsymmetric structures is still unexplored. In this context and with our continuing efforts in developing novel protocols to synthesize fused heterocyclic skeletons under transition-metal free conditions, 17 we became interested in the construction of highly functionalized maleimide-fused phenols. Herein, we disclose an iodine-mediated generation of diverse 4-hydroxyisoindoline-1,3-diones from readily available maleimides and acetophenones in the presence of water as an oxygen source (Scheme 1c).…”

Metal-Controlled Switchable Regioselective Synthesis of Substituted Imidazoles and Pyrroles via Ring Opening/Cyclocondensation with 2H-Azirines

“…Moreover, [3 + 2] cycloaddition of ynamides with 4,5-dihydro-1,2,4-oxadiazoles and visible-light-induced photocatalytic aerobic oxidation/[3 + 2] cycloaddition/aromatization cascade have been recognized as reliable methods to synthesize imidazoles . For pyrroles, striking progress has been achieved on a four-component cyclization strategy, three-component coupling reaction of ketones, amines, and vicinal diols, dehydrogenative coupling of β-aminoalcohols with alcohols, trans-annulation of 1-sulfonyl-1,2,3-triazoles with β-diketones, and the reaction of α-imino rhodium carbene with enol ether or β-diketone . Despite these advances, most of the reported methodologies have one or more major drawbacks, such as the use of unavailable starting materials, limited substrate scope, poor atom economy, and relatively low regioselectivity.…”