New route to 3-(substituted) methyl 1-oxa- and (1-thia)cephems from 3-exomethylene intermediates via sulfenyl chloride adducts

Article abstract of DOI:10.1016/S0040-4020(01)92145-3

Addition of methane- and benzenesulfenyl chlorides to 3-exomethylene-1-oxacephams 10 and 14 gave 3β-sulfenyl-3α-chloromethyl adducts 11 and 15. Nucleophilic substitution of the adducts proceeded facilely to afford compounds 18-23, which were converted into Δ³-dervatives 26 and 27 by oxidative elimination. This new route, as illustrated by the sequence 6 → 7 → 8 → 3, has an essential advantage in using the saturated intermediated 7 and 8 with a stabler β-lactam ring which is compatible in nucleophilic substitution, alkaline ester hydrolysis and further manipulations. These synthetic features are well demonstrated by successful synthesis of 1-oxacefamandol 35 and 7β-(2-thienylacetyl-amino)-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-ceph em-4-carboxylic acid (45).