Diels−Alder Reactions of N-Acyl-2-alkyl(aryl)-5-vinyl-2,3-dihydro-4-pyridones

• Published in: Journal of organic chemistry Vol. 70; no. 13; pp. 5221 - 5234
• Main Authors: Comins, Daniel L, Kuethe, Jeffrey T, Miller, Teresa M, Février, Florence C, Brooks, Clinton A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.06.2005; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Amino Acids - chemical synthesis; Chemistry; Chemistry, Organic; Combinatorial Chemistry Techniques; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Ketones - chemical synthesis; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Pyridones - chemistry; Science & Technology; Stereoisomerism; ASYMMETRIC-SYNTHESIS; CHIRAL 1-ACYLPYRIDINIUM SALTS; GEPHYROTOXIN; MONOMERIC VINCA ALKALOIDS; SYNTHETIC APPLICATIONS; REACTIVITY; LYCOPODIUM ALKALOIDS; DL-VINCADIFFORMINE; MINOVINE; GRIGNARD-REAGENTS; Pyridone derivatives; Nitrogen heterocycle; Vinylic compound; Quinoline derivatives; Diels Alder addition; Aromatic compound; Ketone; Ethylenic compound; Ring cleavage; Pyridine derivatives
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo050559n

Readily available N-acyl-5-vinyl-2,3-dihydro-4-pyridones undergo Diels−Alder cyclization with various dienophiles to afford novel octahydroquinolines containing synthetically useful functionality. With dihydropyridone 5 and cis-disubstituted dienophiles, the resulting cycloadducts were obtained as single diastereomers in good to excellent yield. The corresponding reaction of 5 with methyl acrylate, acrylonitrile, and phenyl vinyl sulfone showed modest preference for the endo adducts. The effect of the dihydropyridone C-2 and C-4 substituents on the degree of diastereofacial control was examined. By using this methodology, the core decahydroquinoline skeleton of gephyrotoxin was prepared in a stereocontrolled fashion. Interesting reactivity was observed with certain dienophiles leading to ring-opening of the initially formed cycloadducts. This tandem reaction provides a route to uniquely substituted β-aminoketones, alcohols, and unnatural amino acids.