Synthesis of 1,2,3‐Fused Indole Polyheterocycles by Copper‐Catalyzed Cascade Reaction

Abstract

A one‐pot reaction has been devloped for the preparation of 1,2,3‐fused indole polyheterocycles by starting from 2‐iodobenzamide and 2‐iodobenzyl cyanide in the presence of a copper catalyst. The cascade process involves the efficient formation of one C–C and three C–N bonds. A broad substrate scope, good yields, and short reactions times are key features of this strategy.

One‐Pot Regio‐ and Diastereoselective Synthesis of Tetrahydro‐α‐carbolines via Cascade Reactions of Iminoindolines with Morita‐Baylis‐Hillman Bromides of Nitroalkenes

“…[2] However, methods for the synthesis of tetrahydrocarbolines, particularly, tetrahydro-α-carbolines are rare. [8][9][10][11][12][13][14][15][16] Substrates for the synthesis of tetrahydro-α-carbolines via various intra-and intermolecular cyclizations include 3-substituted indoles, [8] 2-substituted indoles, [9] tosyliminoindolines [10][11][12][13][14] and others such as nitropyridine [15] and o-iodobenzamide. [16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a).…”

“…[8][9][10][11][12][13][14][15][16] Substrates for the synthesis of tetrahydro-α-carbolines via various intra-and intermolecular cyclizations include 3-substituted indoles, [8] 2-substituted indoles, [9] tosyliminoindolines [10][11][12][13][14] and others such as nitropyridine [15] and o-iodobenzamide. [16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a). Although α,β-unsaturated carbonyl compounds participate in the [3 + 3] annulation of tetrahydro-α-carbolines, [12][13][14] nitroalkene derivatives have not been employed in such capacity as 3-carbon components.…”

“…Several methods have been developed for the efficient construction of carboline moieties [2] . However, methods for the synthesis of tetrahydrocarbolines, particularly, tetrahydro‐ α ‐carbolines are rare [8–16] . Substrates for the synthesis of tetrahydro‐ α ‐carbolines via various intra‐ and intermolecular cyclizations include 3‐substituted indoles, [8] 2‐substituted indoles, [9] tosyliminoindolines [10–14] and others such as nitropyridine [15] and o ‐iodobenzamide [16] .…”

Copper‐Catalyzed Oxidative Cascade Inter‐Molecular Double Cyclization of 2‐Iodobenzamide Derivatives and Propargyl Dicarbonyl Compounds for Accessing 3‐Hydroxy‐3‐Furylisoindolinone Derivatives

“…[13] Although several methods have been reported for generating 3hydroxyisoindolinone, [14] To the best of our knowledge, the use of 2-halobenzamide and propargyldicarbonyl compounds for the synthesis of 3-hydroxy-3-isolinolinone derivatives has not been extensively explored. Hence, in a continuation of our interest in exploring the generation of various heterocycles from 2halobenzamide, [15] we investigated the reaction of 2halobenzamide and propargyldicarbonyl compounds under conditions of copper catalysis.…”

Hexafluoroisopropanol-Mediated Intramolecular Ring-Opening Cyclization of Indolyl-N-Tethered Epoxides: Tether-Length-Controlled Synthesis of 1,7- and 1,2-Fused Indoles

“…Annulated indole compounds are very structurally diverse and are prevalent across a variety of compounds, starting from bioactive natural products to synthetic intermediates, pharmaceuticals, agrochemicals, and functional materials . Hence, numerous methods have been developed to synthesize such compounds, including Friedel–Crafts alkylation, transition-metal-catalyzed reactions, radical cyclization reactions, cascade reactions, and many others . The pyrrolo­[3,2,1- ij ]­quinoline and tetrahydropyrido­[1,2- a ]­indole scaffolds represent two important members of annulated indole skeletons (Figure ).…”