C-2 and C-4 reactions of cephalosporanates and their (S)- and (R)-oxides with toluene-p-sulphonyl azide, acrylonitrile, and ethyl chloroformate

Comparative reactions of cephalosporanates and their (S)- and (R)-oxides were performed. Diazo-exchange leading to 2-diazoceph-3-ems was accomplished only with the (S)-oxide. The 2-diazoceph-3-ems reacted with halogens and pseudohalogens to give 2,2-disubstituted ceph-3-ems. Michael additions with acrylonitrile, were performed, the cephalosporanates giving mainly a 4ß-(2-cyanoethyl)ceph-2-em. The (S)-oxides gave 2a-(2-cyanoethyl)ceph-3-em adducts, whereas the (R)-oxides gave the 4ß-adducts. Ethyl chloroformate reacted in the presence of triethylamine only with the (S)-oxides, giving by a Pummerer rearrangement both 2ß- and 2ß-(ethyl carbonate)s.