Multicomponent Approach to the Synthesis of 4-(1H-indol-3-yl)-5-(4-methoxyphenyl)furan-2(5H)-one

Abstract

A simple one-pot approach was developed for the synthesis of furan-2(5H)-one derivative containing indole fragments. This method includes the telescoped multicomponent reaction of indole, 4-methoxyphenylglyoxal, and Meldrum’s acid. The synthetic utility of the prepared furan-2(5H)-one was demonstrated by condensation with 4-methoxybenzaldehyde. The advantages of this method include the employment of readily accessible starting materials, atom economy, process simplicity, and the easy isolation of the target products. The structure of the synthesized furanones was confirmed by 1H and 13C-NMR spectroscopy and high-resolution mass spectrometry with electrospray ionization (ESI-HRMS).

Aryl glyoxal: a prime synthetic equivalent for multicomponent reactions in the designing of oxygen heterocycles

“…For the synthesis of the furan-2(5H)-one derivative 10 with indole as a structural fragment, Andrey's group established a facile and one-pot novel methodology, which was completed in two steps starting with the interaction of aryl glyoxal 1, indole 9, and Meldrum's acid 8 in acetonitrile with triethylamine at reux, followed by a further acidic reux using acetic acid (Scheme 5). 46 The formation of the new oxygen heterocycle was considered to go through the aryl glyoxal 1 condensation with Meldrum's acid (intermediate) ca followed by the Michael Scheme 1 Gold-catalyzed three-component synthesis of furan derivatives 4. 44 addition to indole cb and nally cyclization with the elimination of CO 2 to give 10 (Scheme 6).…”

“…The formation of a new oxygen heterocycle was considered to occur through the aryl glyoxal condensation with Meldrum's acid followed by Michael addition to give the indole and nally cyclization occurs with the elimination of CO 2 (Scheme 64). 46 Aer this, Boris et al replaced the indole with hydroxycoumarin derivative 95 to access the novel furylacetic acid moiety 96. The pronounced advantage offered by the use of the photosensitizer and the biologically important furo-coumarin derivative synthesis is that the formation was possible through a single-pot approach using easily available staring materials with no harsh reaction conditions (Scheme 65).…”

“…The formation of a new oxygen heterocycle was considered to occur through the aryl glyoxal condensation with Meldrum's acid followed by Michael addition to give the indole and finally cyclization occurs with the elimination of CO 2 (Scheme 64). 46…”

“…using Meldrum's acid 8 46. Scheme 6 Mechanism to explain the synthesis of furan-2(5H)-one 10 using indole 9, Meldrum's acid 8, and aryl glyoxal 1 as starting materials.© 2023 The Author(s).…”

Indole frameworks via transition-metal-free annulation: a current perspective

“…[28][29][30] Furthermore, functionalized indole moieties are capable of serving as useful building blocks for the synthesis of complex molecular architectures. [31][32][33][34][35][36] The chemistry of indoles has been studied for more than 150 years; however, research toward synthesis of functionalized indoles is still in demand because of their enormous applications in diverse fields. Therefore, a variety of synthetic strategies have been adopted for constructing this heterocyclic system.…”