One-pot synthesis of novel 5-(azidomethyl)-2-aryloxazole derivatives from propargylamide through Cu-catalyzed C–N bond formation

Abstract

A series of N-propargylarylamide derivatives were successfully transformed into novel 5-(azidomethyl)-2-aryloxazole systems bearing a single azide group. The transformation involved a two-step process: (1) synthesis of 5-(iodomethylene)-2-aryl-4,5-dihydrooxazoles, followed by (2) azide coupling with sodium azide (NaN₃). Additionally, a one-pot protocol was developed for the synthesis of triazole-methylene-oxazole derivatives, integrating N-iodosuccinimide (NIS)-mediated oxazole formation, azide coupling, and a subsequent click reaction. This streamlined approach demonstrated excellent overall efficiency, yielding products in 68–82% yield across a broad substrate scope. Notably, the entire reaction sequence could be conducted using a single precatalyst, significantly reducing reaction waste and enhancing both economic and environmental sustainability.

Graphical abstract

A series of N-propargylarylamide derivatives were transformed into the corresponding novel 5-(azidomethyl)-2-aryloxazole systems that bear one azide group. The two-step procedure consisted of a 5-(iodomethylene)-2-aryl-4,5-dihydrooxazole synthesis and a subsequent azide coupling with NaN₃.