Penem 2-thio

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the >S-lactam given below using polymeric Hflnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wlttig reaction with an acetyl-thio group to yield the extremely acid-sensitive penicillin analogue (a penem I. Ernest, 1979). 

The cyclization of 1,5-dicarbonyl chains by means of the deoxygenating reagent triethyl phosphite provides an alternate strategy for building the fused hve-membered penem ring. The first example in fact actually comprises a 1,5-oxa-thio array. Reaction of the perhydrothiophene oxide (16-1) with the anion from carbon disulhde... 

In such desulfurizing 2,3-rearrangements, the alcohol is usually sought and the thiophile-SR molecule undesired. One of the few instances where the thio compound was desired, is the conversion of sulfoxide (184) into a penem (equation 57). ... 

Finally, thioethylidene 445 was prepared by 1,4-addition of thio-acetic acid on the vinylpenem 444, itself obtained from clavulanic acid via mesylation of 443a. Exposure of 445 to TEA promoted isomerization to penem 443b [227]. 

New syntheses of ( )-clavulanic acid and its thio-analogue have appeared. The synthesis of the latter compound makes use of yet another internal Wittig reaction (Scheme 136), and it is readily converted into a penem. 

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