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

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-gamma-chloro-enamides from the union of acrolein with secondary amides under mildly dehydrative conditions. Subsequent S(N)2 displacement of the primary alkyl chloride with a variety of nucleophiles allowed access to a number of trans-gamma-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. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Enamides are a unique structural moiety found in natural products and synthetic derivatives. This report discloses a novel, metal-free method for the synthesis of trans-gamma-chloro-enamides from the union of acrolein with secondary amides, followed by S(N)2 displacement reactions to access various trans-gamma-functionalized-enamides. Further reactions of two derivatives led to the formation of novel triazole products and di-and trienamide-containing materials.