The synthesis and use of γ-chloro-enamides for the subsequent construction of novel enamide-containing small molecules

Abstract Enamides are a unique structural moiety in organic chemistry, present in numerous natural products and countless synthetic derivatives. In this report, we wish to disclose our recent work on the development of a novel, metal-free method to access trans-γ-chloro-enamides from the union of acrolein with secondary amides under mildly dehydrative conditions. Subsequent SN2 displacement of the primary alkyl chloride with a variety of nucleophiles allowed access to a number of trans-γ-functionalized-enamides. In addition to a concise substrate study, two of these derivatives were further reacted to form novel triazole products, as well as di- and trienamide-containing materials.