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Pure Appl. Chem., 2005, Vol. 77, No. 12, pp. 2033-2040

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

Timothy Gallagher1, Sylvie Sanchez1, John H. Bateson2 and Peter J. O'Hanlon2

1 School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
2 GlaxoSmithKline, New Frontiers Science Park, Harlow CM19 5AW, UK

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.