Thiocarbonyl-based 1,3-dipolarophiles for the synthesis of C(2)-unsubstituted penems

Abstract

The azomethine ylid strategy for β-lactam synthesis, which involves the fragmentation of a β-lactam-based oxazolidinone to give a carboxylated azomethine ylid, has been extended to the C(2)-unsubstituted penem scaffold associated with C(6)-exoalkylidene penems. This involved the use of S-methyl dithioformate as a reactive 1,3-dipolarophile, which was most effectively employed by initial trapping with cyclopentadiene and subsequent regeneration of S-methyl dithioformate via a retro Diels-Alder reaction in the presence of the requisite oxazolidinone. This provided access to the penam scaffold, and this overall sequence was very effectively accelerated by microwave irradiation. The synthesis of C(2)-unsubstituted penems was then accomplished by application of an oxidative elimination sequence.