Lewis Acid‐Catalyzed Selective Synthesis of Diversely Substituted Indolo‐ and Pyrrolo[1,2‐a]quinoxalines and Quinoxalinones by Modified Pictet–Spengler Reaction

Abstract

An efficient tandem process for the selective synthesis of 1,2‐annulated α‐fused quinoxalines using benzotriazole methodology by a modified Pictet–Spengler reaction is described. The approach involves the reaction of arylamines 4 with aromatic aldehydes 5 to furnish 6‐endo‐dig‐cyclized products. Dihydroquinoxalines 6 were selectively obtained by using AlCl3 in tetrahydrofuran (THF) at room temperature for two hours. However, after ten hours, quinoxalines 7 were obtained exclusively in excellent yields. A series of biologically important fluoro‐ and piperazenyl‐substituted quinoxalines were also synthesized. This developed methodology also provides access to a novel tandem synthesis of quinoxalinones 9.

Domino Oxidative Cyclization for the One‐Pot Synthesis of Pyrrolo[1, 2‐a]quinoxaline Derivatives

“…Therefore, the synthesis of pyrrolo[1, 2‐ a ]quinoxaline moiety is of prime importance. Consequently, numerous methods to access structurally diverse pyrrolo[1, 2‐ a ]quinoxaline derivatives have been developed employing different catalysts such as Brønsted acid, Lewis acid and iodine . The Pictet–Spengler reaction of 1‐(2‐aminophenyl)pyrroles with aldehydes or ketones is one of the direct and most popular approaches for the synthesis of pyrrolo[1, 2‐ a ]quinoxalines .…”

“…Consequently, numerous methods to access structurally diverse pyrrolo[1, 2‐ a ]quinoxaline derivatives have been developed employing different catalysts such as Brønsted acid, Lewis acid and iodine . The Pictet–Spengler reaction of 1‐(2‐aminophenyl)pyrroles with aldehydes or ketones is one of the direct and most popular approaches for the synthesis of pyrrolo[1, 2‐ a ]quinoxalines . Other methods include gold‐catalyzed direct hydroamination/ hydroarylation of 2‐(1 H ‐pyrrol‐1‐yl)anilines with terminal alkynes and intramolecular reductive amination of 1‐(2‐nitrophenyl)pyrrole‐2‐carbaldehyde .…”

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

“…(b) AlCl 3 -catalyzed Pictet–Spengler reactions between 2-(1 H -indol-1-yl)anilines and aromatic aldehydes [38]. (c) Pd-catalyzed regioselective C–H olefination/cyclization sequences from indole-substituted anilines and electron-deficient terminal alkenes [37].…”

Synthesis of Highly Functionalized Polycyclic Quinoxaline Derivatives Using Visible‐Light Photoredox Catalysis

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A mild and facile method for preparing highly functionalized pyrrolo[1,2-a]quinoxalines and other nitrogenrich heterocycles, each containing a quinoxaline core or an analogue thereof, has been developed. [2] For instance, Kobayashi and coworkers recently reported the preparation of aminoalkyl or hydroxyalkyl pyrrolo[1,2-a]quinoxalines from iminium salts and aldehydes or ketones. A wide range of quinoxaline heterocycles have been prepared.

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