Cu(I)-Catalyzed and Base-Promoted [5 + 2 + 1] Cascade Cyclization of 2-Nitrochalcones with Aliphatic Primary Amines to 5H-Pyrimido[5,4-b]indole Frameworks

Abstract

An unprecedented [5 + 2 + 1] cascade cyclization to the preparation of 5H-pyrimido­[5,4-b]­indole derivatives has been disclosed. The novel protocol of 2-nitrochalcones reacted with aliphatic primary amines catalyzed by CuI and promoted by Cs2CO3, which underwent a critical intermediate 2,3-disubstituted indole, providing structurally diverse 5H-pyrimido­[5,4-b]­indoles in generally high yields (77–90%) and broad substrate scopes (34 examples).

Nitroarenes and nitroalkenes as potential amino sources for the synthesis of N-heterocycles

“…In 2022, Huang et al described an unprecedented copper-catalyzed [5 + 2 + 1] cascade cyclization of 2-nitrochalcones with aliphatic primary amines for the construction of 5 H -pyrimido[5,4- b ]indole derivatives (Scheme 12). 35 The optimization studies showed that CuI was the most effective catalyst in the presence of Cs 2 CO 3 as a base. Various 2-nitrochalcone derivatives with different electron-donating /withdrawing substituents are all compatible with the reaction (34 examples), giving products in generally high yields (77–90%).…”

Annulation strategies for diverse heterocycles via the reductive transformation of 2-nitrostyrenes

“…Recently, Huang et al explored the synthesis of 5 H -pyrimido[5,4- b ]indoles 30 via the [5 + 2 + 1] cascade cyclization of 2-nitrochalcones 1 with two equivalents of primary amine 22 in the presence of copper iodide and cesium carbonate (Scheme 9). 8 2-Nitrochalcones bearing different substitution patterns on the aromatic ring readily reacted with primary amines to give pyrimidoindole derivatives 30 in high yields. Importantly, 2-nitrochalcones bearing heterocycles were well-tolerated in this transformation.…”

“…Thus, molecules bearing the 2-nitrostyrene motifs have gained considerable attention because they contain a versatile nitro group; and their chemistry has been explored in a variety of organic reactions, including transition metal-catalyzed couplings, 6 Michael addition reactions, 7 domino [ k + l + m ] annulations, 8 intramolecular Baeyer–Villiger oxidation and 6π-electrocyclization processes, 9 among others. Recently, significant effort has been devoted to the development of novel methods to construct diverse heteroaromatics using 2-nitrostyrenes, and the volume of work using these substrates is increasing.…”

Cu(II)-Catalyzed Cascade of N-Phenyl-o-phenylenediamine with Benzaldehyde: One-Step Direct Construction of 2-(1-Phenyl-1H-benzo[d]imidazol-2-yl)phenols

“…Based on our research group's interest in Cu-catalyzed multicomponent participation in the construction of nitrogen heterocycles, 10 we report a practical cascade annulation C−H hydroxylation of N-phenyl-o-phenylenediamine with benzaldehydes to directly construct a series of PBIs whose skeletons comprise both benzimidazoles and phenols (Scheme 1c). We hope that the new synthetic strategy and product PBI can provide ideas and new modification sites for the development of new drug molecules in the future.…”