Synthesis of gem-dibromo 1,3-oxazines by NBS-mediated electrophilic cyclization of propargylic amides

Abstract

We present a highly efficient and practical method for synthesizing gem-dibromo 1,3-oxazines through 6-endo-dig cyclization of propargylic amides, using N-bromosuccinimide (NBS) as an electrophilic source. The metal-free reaction can be conducted under mild conditions with good functional group compatibility, delivering excellent yields of the desired products. Mechanistic studies suggest that the reaction proceeds via a double electrophilic attack by NBS on the propargylic amide substrate.