Novel 2-Methyl-1-oxacephalosporins 1. Synthesis of 2-Methyl-3-nor-1-oxacephem Nucleus

The Zo-and 20-methyl-1-oxacephems were synthesized stereoselectively starting from (3R.4S)-oxazolinoazetidinone by reaction with chiral alcohols followed by intramolecular carbene insertion of a-diazo-6-keto intermediates.1-Oxacephem compounds have received considerable attention since antibacterial activity was~found to be enhanced by the nuclear exchange of the sulfur atom of cephems to 0 ~y ~e n .l -5 We assumed that an introduction of a-or @-methyl substituent on C-2 to the 1-oxacephem ring might confer ring constraint and hence might influence the antibacterial activity including 6-lactamase stability.Herein we report the stereoselective syntheses of novel 2a-methyl-(la and a) and 20methyl-3-nor-1-oxacephems (s and &)6 having a 7u-acylamino group.A chiral building block, (3~.4~)-oxazolinoazetidinone7~10 2 was reacted with neat chiral alcohol (a or B; 300 mglml) in the presence of CF3S03H at room temperature for 1.5 h to give crystalline u-4-alkoxyazetidinone fi (49%; mp 133-135°C) or (53%; mp 104-105'C) in a stereoselective manner,ll respectively.In these cases the yield of 5 was not improved either with solvent (CHC13,