Penem 2-alkyl

Extension of the Phosphorane Route. Ample evidence of the versatihty of the phosphorane synthesis strategy is provided by the proliferation of penems that followed. Nucleophilic displacement of the acetate function of the acetoxy-azetidinone (51, R = OCOCH ) [28562-53-0] (86) provided azetidinones where R = SCOCH, SCSSC2H, and SCSOC2H, which on elaboration gave the penems (52, R = CH ) (87), (52, R = SC2H ) (88), (52, R = 0C2H ) (89). Similar treatment of 3-substituted (or disubstituted) acetoxyazetidinones allowed the synthesis of a number of 2-substituted- 6-alkyl-and 6,6-dialkylpenems (90). 

This has been nicely demonstrated and exploited by Woodward s syntheses of bicyclic systems of the penem type. They are typically formed in moderate to good yields upon refluxing the requisite substituted starting -lactams in toluene or xylene for extended periods. The key step is the introduction of the ylidic moiety into the 1-position of a 4-functionalized azetidin-2-one which itself can be obtained as a relay substance by degradation of natural penicillins or from easily available 4-acetoxyazetidin-2-one. The ester ylide function is built up by reaction first with alkyl hemiacetals of glyoxylates to give a hemiaminal and then successive replacement of the OH-group of the latter by Cl with thionyl chloride and finally of the chlorine atom by triphenylphosphane under basic conditions. 

A method has been established to synthesize 6-methylidene penem compounds, which involves an aldol-type condensation on 6-bromopenem with aldehydes <04JOC5850>. S-Alkyl dithioformates, generated by a cycloreversion process, react as 1,3-dipolarophiles with... 

A successful penem synthesis was accomplished by first alkylating 263 on nitrogen with bromoacetate ester to afford (315 Treatment of 315 with base followed by carbon dioxide yielded the malonic acid derivative... 

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