Radical Rearrangement: A Strategy for Conversion of Cephalosporin to 1-Carba(dethia)cephalosporin

A radical rearrangement approach to semisynthesis of the carbacephem class of β-lactam antibiotics is reported. The crucial bond construction in assembly of the carbacephem framework was accomplished by intramolecular C–C bond formation between an azetidin-2-one-4-yl and a pendant diene ester. This reactive intermediate was generated by fragmentation of a cephem derived radical followed by loss of sulfur dioxide. The radical precursor was prepared in 63% yield over four steps and the subsequent rearrangement reaction provided carbacephem products in a single step at 23% yield.