CYCLOADDITIONS OF CEPHALOSPORINS - A COMPREHENSIVE STUDY OF THE REACTION OF CEPHALOSPORIN TRIFLATES WITH OLEFINS, ACETYLENES, AND DIENES TOFORM [2-ADDUCTS AND [4+2]-ADDUCTS(2])

Novel polycyclic cephalosporins are formed by the reaction of cephalos porin triflates with various unsaturated compounds in the presence of Hunigs base. 2,3-Fused cyclobutane and cyclobutene cephems are obtaine d with olefins and acetylenes, respectively, whereas [4 + 2] cycloaddu cts are obtained with furan. The reaction has been rationalized by inv oking the intermediacy of a strained 6-membered cyclic allene. The all ene undergoes an orbital symmetry allowed concerted (pi)2(8), + (pi)2( a), cycloaddition with olefins and acetylenes and a (pi)4(s) + (pi)2(s ) cycloaddition with furan. The regiochemistry of the [2 + 2] cycloadd ucts is independent of the substitution of the unsaturated component a nd of the oxidation state of the cephalosporin sulfur atom. However in the case of the [4 + 2] adducts, the sulfur oxidation state determine s the regiochemistry of the addition. Carbacephalosporins also partici pate in this reaction with olefins but require a stronger base such as DBU. Thus the reaction described provides a facile, one-step procedur e for the production of a rich variety of novel polycyclic cephalospor ins.