2-azetidinone, fluorinated

For a given set of substituents at position C3, the efficiency of the inhibition depends on the nature of the benzylic leaving group X (Table 11.4). No significant inactivation is found with a fluorine atom at this position. The brominated azetidinone (24b) is a better inactivator than its chlorinated counterpart (24a). 

A fluorinated 2-oxo derivative of 3,4-dihydro-2//-1,3-oxazine (58) was obtained, along with a 2,3-dihydro derivative (59) and an azetidinone, from perfluoromethacryloyl fluoride and cyclohexyl isocyanate190 [Eq. (44)]. 

It is important to note that Bu4NBF4 leads to tar and that, if 8 Fmol-1 are consumed in the case of A -benzyl derivatives, 20 Fmol-1 are needed for A -butyl derivatives.358 Diverse 4 -1 r i m e t h y I s i I y I - A - b e n z y I azetidinones have been successfully fluorinated using this technique.358... 

Other compound classes in the synthesis of which chiral 3-carbon synthons were used include sphingosine chains (32), 3-amino-2-azetidinones (33), (3,y-unsaturated-a-amino acids 34), fluorinated macrocyclic bis(indolyl) maleimides35, fluorocyclopropyl alcohols (36), l-O-phosphocholine-2-O-acyl-octadecanes and l-Ophosphocholine-2-N-acyl-octadecane (37) diacyl glycerols 38-42) and analogs of fragments of leukotriene-B4 43). 

Monofluorinated S-lactams are of considerable interest as intermediates for syntheses of fluorine-containing antibiotics and as building units for syntheses of amino acids and sugars. Thus, regioselective anodic monofluorination of 3-phenyl-thio-2-azetidinones and 4-phenylthio-2-azetidinones leads to 3- and 4-substituted... 

The Staudinger reaction of ketenes to aldimines is well known to provide cw-p-lactams. However, it had never been studied in the case of fluoroalkyl imines. The trifluoroacetaldimine 17a has been prepared by the usual route from the corresponding ethyl trifluoromethyl hemiketal and p-methoxyaniline. " Reaction of the benzyloxyketene, generated from a-benzyloxyacetyl chloride, with imine 17a, performed at 45 °C in CHjClj, provided the expected cis azetidinone 16a in 65 % yield (Scheme 8). In azetidinone 16a, the Vh.3,h-4 coupling constant of 5 Hz indicates the cis relative configuration. Coupling constants in parent non-fluorinated P-lactams have been reported to be 2 Hz for the trans isomer and 5-6 Hz for the cis one. Condensation of the aldimine 17b with the same ketene led to the cis P-lactam 16b in 72 % yield. The cis P-lactam 16c was obtained in a satisfatory yield (55 %) from the aldimine 17c (Scheme 8). 

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