Copper‐Catalyzed Decarboxylative Three‐Component Reactions for the Synthesis of Imidazo[1,2‐a]pyridines

Abstract

Imidazo[1,2‐a]pyridine derivatives were synthesized through multicomponent coupling reactions of 2‐aminopyridines, aldehydes, and alkynecarboxylic acids in the presence of 10 mol‐% CuI/Cu(OTf)2. Both aryl‐ and alkyl‐substituted alkynecarboxylic acids, including propiolic acid, were good alkyne sources and afforded the desired imidazo[1,2‐a]pyridines in good yields through the decarboxylative coupling reactions. Arylalkynecarboxylic acids were synthesized through palladium‐catalyzed coupling reactions between aryl iodides and propiolic acid and reacted with 2‐aminopyridine and aldehydes, with or without a purification step. In both cases the desired imidazo[1,2‐a]pyridines were obtained in good yields. Mechanistic studies suggested that in the case of propiolic acid the decarboxylative addition predominates over terminal alkyne addition.

Copper‐Catalyzed Double Decarboxylative Coupling Reactions of Alkynyl Carboxylic Acid and Glyoxylic Acid: Synthesis of Propargyl Amines and Imidazopyridines

“…Recently, we reported the synthesis of imidazo[1,2‐ a ]pyridines from the three‐component copper‐catalyzed decarboxylation reaction of an alkynyl carboxylic acid, an aldehyde, and 2‐aminopyridine . Instead of the aldehyde, phenylglyoxylic acid was combined in the reaction with the alkynyl carboxylic acid and 2‐aminopyridine.…”

“…3‐(Naphthalen‐1‐ylmethyl)‐2‐phenylimidazo[1,2‐ a ]pyridine (6 h) : 2‐Aminopyridine (94 mg, 1.0 mmol), phenylglyoxylic acid (180 mg, 1.2 mmol), and 3‐(naphthalen‐1‐yl)propiolic acid (235 mg, 1.2 mmol) afforded product 6 h (183.9 mg, 0.55 mmol, 55 % yield) as a yellow solid. M.p.…”

Recent synthetic scenario on imidazo[1,2-a]pyridines chemical intermediate

“…These aldehydes then underwent a MCR with 2-aminopyridines and isocyanides to afford imidazo[1,2-a]pyridines 1.92a-b (Scheme 21) [58,59]. In addition, they further developed a one-pot synthesis of imidazo[1,2-a]pyridines 1.97b through multicomponent couplings of 2-aminopyridines, aldehydes and arylalkynecarboxylic acids 1.96b, which were generated in situ through palladium-catalyzed coupling of aryl iodides and propiolic acid (Scheme 25) [65]. Pericherla et al [73] have developed a simple and convenient strategy for the synthesis of imidazo[1,2-a]pyridines via inexpensive copper catalyzed tandem imine formation and intramolecular aerobic oxidative C-H bond amination/cyclizations (Scheme 33).…”

Copper‐Catalysed Multicomponent Syntheses of Heterocycles

“…The use of alkynecarboxylic acids as alkyne sources was investigated for the first time in the synthesis of imidazo[1,2‐ a ]pyridines . Thus a three‐component reaction for the synthesis of imidazo[1,2‐ a ]pyridines involving 2‐aminopyridines, aldehydes and alkynecarboxylic acids in presence of CuI and Cu(OTf) 2 as catalyst via a decarboxylative coupling reaction was performed (Scheme ).…”