THE DEVELOPMENT OF ORGANOMETALLIC METHODOLOGIES FOR THE STEREOSPECIFIC INTRODUCTION OF CEPHALOSPORIN SIDE-CHAINS

A variety of 3-substituted cephems has become available via the coupli ng of 3-trifloxycephems with organostannanes, by a modified Stille cou pling procedure that includes a new palladium ligand, tri(2-furyl)phos phine. A complementary cuprate coupling via the same intermediates is also described. A cheaper alternative to the triflates are the enol fl uorosulfonates, which also undergo Stille and organocuprate couplings. A radically, different approach to cephalosporins from penicillins in volves a modification of the Morin rearrangement that involves the int ermediacy of allenylazetidinones; these undergo chemoselective additio n of cuprates to the allene central carbon, followed by rapid cyclizat ion by intramolecular sulfenylation. The process was applied, i.a., to the efficient synthesis of the new oral antibiotic Cefprozil.