Highly regioselective C–H bond functionalization: palladium-catalyzed arylation of substituted imidazo[1,2-a]pyridine with aryl chlorides

Abstract

We have developed an efficient Pd-catalyzed regioselective arylation of substituted imidazo[1,2-a]pyridines with aryl chlorides, which is rarely reported. This methodology has been successfully applied to the synthesis of a variety of substituted imidazo[1,2-a]pyridine core p systems which exhibit a wide range of biological activities in many drugs.

Dimetallic Palladium‐NHC Complexes: Synthesis, Characterization, and Catalytic Application for Direct C−H Arylation Reaction of Heteroaromatics with Aryl Chlorides

“…In a literature example, 2-bromotoluene was 1). [23] For palladium-catalyzed direct arylation reactions of heteroaromatics with aryl halides, electrophilic aromatic substitution (S E Ar), [4a,24] and concerted metalation-deprotonation (CMD) [15b,25] pathways have the most experimental and theoretical support. [23] For palladium-catalyzed direct arylation reactions of heteroaromatics with aryl halides, electrophilic aromatic substitution (S E Ar), [4a,24] and concerted metalation-deprotonation (CMD) [15b,25] pathways have the most experimental and theoretical support.…”

Environmentally Benign Arylations of 5‐Membered Ring Heteroarenes by Pd‐Catalyzed C−H Bonds Activations

“…A similar procedure, using Cs 2 CO 3 as base was reported by Cao et al. for the C3‐arylation of imidazo[1,2‐ a ]pyridines with aryl chlorides …”

“…With a few exception, aryl chlorides are generally unreactive under the conditions employed to couple other starting materials such as aryl bromides or iodides. However, monodentate electron‐rich phosphine‐ligands associated to palladium, catalytic systems based on a chelating di‐ or poly‐phosphines or the use of carbenes as ligands were found to promote a limited number of coupling reactions based on mostly electron‐deficient aryl chlorides, chlorotoluenes, chloroanisoles and chloro‐substituted heteroaromatics …”

“…Our group in association with Hierso's group also described the efficiency of an air-stable ferrocenyl triphosphane ligand in the direct arylation of heteroarenes with aryl chlorides (Scheme 34). [57] A variety of heteroaromatic compounds such as furans, thiophenes, pyrroles, and thiazoles were tolerated by this procedure. Moreover, catalyst loadings ranging between 0.1 and 0.5 mol% could be employed.…”

Functionalization of Imidazo[1,2‐a]pyridines by Means of Metal‐Catalyzed Cross‐Coupling Reactions

“…Cao et al78 developed an efficient Pd‐catalyzed procedure for regioselective arylation (at the C‐3 position) of substituted imidazo[1,2‐ a ]pyridines 129 with aryl chlorides 130 . This methodology was successfully applied to the synthesis of a variety of substituted imidazo[1,2‐ a ]pyridines 131 in good yields (Scheme ).…”