Tunable synthesis of quinolinone-fused isoquinolines through sequential one-pot nucleophilic addition and palladium-catalyzed intramolecular C–H alkenylation

Abstract

An efficient sequential one-pot synthesis of N-fused heterocycles based on 4-quinolinone and isoquinoline scaffolds of biological interest has been developed.

Palladium-Catalyzed Synthesis of Fluorescent Benzo[4,5]imidazo[1,2-a]pyridines through Annulation Reaction of Benzimidazoles and Alkynyl Bromides with Internal Alkynes

“…Based on the above results and our previous work ,,,, and others, a plausible reaction pathway for the synthesis of benzo­[4,5]­imidazo­[1,2- a ]­pyridines was outlined in Scheme . In the nucleophilic addition step, benzimidazole 1 might form a hydrogen bond with the solvent ( tert -pentyl alcohol) to give hydrogen-bond structure 1′ .…”

“…For the initial experiments, benzimidazole ( 1a ), bromoethynylbenzene ( 2a ), and diphenylacetylene ( 4a ) as model substrates were selected for sequential nucleophilic addition/Pd-catalyzed intermolecular C–H annulation reaction to construct π-extended (benz)­imidazole 5aaa (Scheme and Table ). Our recent study reveals that alkynyl bromides can undergo addition by the nitrogen nucleophilic reagent (quinolin-4-ones) to give ( Z )-alkenyl bromides regio- and stereoselectively with good yields in the presence of a base using tert -pentyl alcohol as the solvent at 110 °C . On the basis of this reaction condition, some new investigations are summarized in Scheme using benzimidazole ( 1a ) as the nucleophilic reagent.…”

“…Purification of reaction products was done by flash chromatography with 230–400 mesh silica gel. Benzimidazoles ( 1c and 1d ), alkynyl bromides ( 2a–2k ), and internal alkynes ( 4a–4j ) were prepared according to the literature methods. All these substrates are known compounds, and the spectroscopic and physical data are matched with those from the literature.…”

“…Our recent study reveals that alkynyl bromides can undergo addition by the nitrogen nucleophilic reagent (quinolin-4-ones) to give (Z)-alkenyl bromides regio-and stereoselectively with good yields in the presence of a base using tert-pentyl alcohol as the solvent at 110 °C. 22 On the basis of this reaction condition, some new investigations are summarized in Scheme 2 using benzimidazole (1a) as the nucleophilic reagent. Using K 2 CO 3 as the base, protonic solvents (methanol and n-butanol) provided better yields than nonprotonic solvents such as dimethylformamide (DMF), 20a dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), toluene, tetrahydrofuran (THF), dichloromethane, DCE, and acetonitrile (left column, Scheme 2).…”

Synthesis and Functionalization of 4‐Quinolones – A Progressing Story

“…Very recently, Peng et al described an elegant and efficient one‐pot synthesis of fused heterocycles by a regiocontrolled nucleophilic addition of 4‐quinolinones to alkynyl bromides with a subsequent Pd‐catalyzed intramolecular C–H alkenylation reaction (Scheme ) . The scope and generality of both substrates were well explored.…”