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

• Published in: Tetrahedron Vol. 102; pp. 132536 - 132545
• Main Authors: Golliher, Alexandra E., Tenorio, Antonio J., Cornali, Brandon M., Monroy, Erika Y., Tello-Aburto, Rodolfo, Holguin, F. Omar, Maio, William A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 03.12.2021; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Click chemistry; Diels-Alder reaction; Enamides; Natural products; Physical Sciences; Science & Technology; Wittig olefination; Enamides; Click chemistry; Diels-Alder reaction; Wittig olefination; Natural products; ASYMMETRIC-SYNTHESIS; ACID; HYDROGENATION; LYNGBYA-BOUILLONII; ISOMERIZATION; MACROLIDES; FUNCTIONALIZATION; STEREOSELECTIVE-SYNTHESIS; AMIDES; PALMYROLIDE
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2021.132536

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. [Display omitted]