Silver(I)-Catalyzed A3-Coupling for the Regioselective Synthesis of 2-Chloro-(Phenylvinyl)imidazo[1,2-a]pyridines and
Abhishek Saini1, Rishu Mehta2, Kamaldeep Kaur2
1School of Sciences, Baba Farid College, Bathinda151002, India.
Abstract:
We report a silver(I)-catalyzed three-component A3-coupling strategy for the synthesis of 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines from 2-aminopyridines, terminal alkynes, and β-chlorovinyl aldehydes. The transformation proceeds under mild conditions with high regioselectivity, broad substrate scope, and excellent functional-group tolerance. Notably, retention of the vinylic C-Cl bond in the products provides access to structurally important chlorovinyl-substituted imidazo[1,2-a]pyridines. The retained chlorovinyl motif may offer potential value for further diversification and for the development of medicinal chemistry-oriented scaffolds and pharmacophores. The protocol is operationally simple and scalable, as demonstrated by gram-scale synthesis. Its synthetic utility is further highlighted through the late-stage functionalization of complex molecules, including Naproxen and Gemfibrozil, as well as the synthesis of amino acid-derived 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines. These results underscore the versatility of the protocol and its potential applications in medicinal chemistry, molecular diversification, and drug discovery.
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