α,β-Epoxy Esters in Multiple C–O/C–N Bond-Breaking/Formation with 2-Aminopyridines; Synthesis of Biologically Relevant (Z)-2-Methyleneimidazo[1,2-a]pyridin-3-ones.

A new reaction of aryl 2,3-epoxy esters with 2-aminopyridines has been developed that involves multiple C-O/C-N bond-breaking/formation reactions in one chemical step. Compared with known reactions of α,β-epoxy esters, which take place through oxiranyl C-O or C-C bond cleavage, the present reaction exploits the tendency of the oxirane ring to act as a bi-electrophile. Thus, the reaction follows a unique cascade pathway of epoxide C-O bond cleavage, formation of an α-enamine ester, and intramolecular transamidation with chemo-, regio- and diastereoselectivity. The reaction allows access to biologically relevant (Z)-2-methyleneimidazo[ 1,2-α]pyridin-3-ones. Water and ethanol are the only by-products. The reaction is flexible, and aryl 2,3-epoxy esters as well as 2-aminopyridines possessing either electron-donating or -withdrawing functionalities, can be used. In contrast to various Brønsted and Lewis acid catalysts, polyphosphoric acid plays a multifunctional role in this intermolecular cascade reaction. [ABSTRACT FROM AUTHOR]