Cycloadditions of Cephalosporins. A Comprehensive Study of the Reaction of Cephalosporin Triflates with Olefins, Acetylenes, and Dienes To Form [2 + 2] and [4 + 2] Adducts

• Published in: Journal of organic chemistry Vol. 62; no. 15; pp. 4998 - 5016
• Main Authors: Elliott, Richard L, Nicholson, Neville H, Peaker, Fiona E, Takle, Andrew K, Richardson, Christine M, Tyler, John W, White, Janet, Pearson, Michael J, Eggleston, Drake S, Haltiwanger, R. Curtis
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.07.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; CONSTANTS; 1,2-CYCLOHEXADIENE; CEPHEM; CHEMISTRY; BETA-LACTAM ANTIBIOTICS; 3-SUBSTITUTED CEPHALOSPORINS; GENERATION; STYRENE; SYNTHETIC APPROACH; HECK REACTION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo970176s

Novel polycyclic cephalosporins are formed by the reaction of cephalosporin triflates with various unsaturated compounds in the presence of Hunigs base. 2,3-Fused cyclobutane and cyclobutene cephems are obtained with olefins and acetylenes, respectively, whereas [4 + 2] cycloadducts are obtained with furan. The reaction has been rationalized by invoking the intermediacy of a strained 6-membered cyclic allene. The allene undergoes an orbital symmetry allowed concerted π2s + π2a cycloaddition with olefins and acetylenes and a π4s + π2s cycloaddition with furan. The regiochemistry of the [2 + 2] cycloadducts is independent of the substitution of the unsaturated component and of the oxidation state of the cephalosporin sulfur atom. However in the case of the [4 + 2] adducts, the sulfur oxidation state determines the regiochemistry of the addition. Carbacephalosporins also participate in this reaction with olefins but require a stronger base such as DBU. Thus the reaction described provides a facile, one-step procedure for the production of a rich variety of novel polycyclic cephalosporins.