Facile access to 3-allyl- and 3-benzyl-Δ3-cephems through reductive addition/cyclization of allenecarboxylate with allylic and benzylic halides in an [NiCl2(bipy)]/PbBr2/Al redox system

Abstract

Sequential reductive addition/cyclization of the allenecarboxylate 1, derived from penicillin G, with allylic and benzylic halides is successfully achieved by the aid of a three-metal redox system consisting of aluminium metal (2.5 molar equiv.) and catalytic amounts of [NiCl₂(bipy)] (0.1 molar equiv.) and PbBr₂ (0.05 molar equiv.) in N-methyl-2-pyrrolidone (NMP) to afford the corresponding 3-allyl- and 3-benzyl-Δ³-cephems 3a–i in 20–85% yields. The reactions of 1 with vinyl, prop-2-ynyl and phenyl halides in the same three-metal redox system result in the recovery of 1 and/or partial formation of 2-exo-methylenepenam 4. A similar electroreductive addition/cyclization of 1 with allyl bromide is performed by passage of an electrical current (3.2 F mol^-1) in an [NiCl₂(bipy)]/PbBr₂/NMP/(Pt cathode)–(Al anode) system.