Catalytic approaches to the synthesis of beta-lactamase inhibitors

Catalytic couplings were utilized to stereospecifically synthesize several 7E- and 7Z-alkylidenecephalosporins. Members of this class are known inhibi tors of beta-lactamase. Zinc/NH4Cl reduction of dibromide 14 stereospecific ally produced E-monobromide, 15. In contrast, treatment of 14 with isopropy lmagnesium bromide, followed by mild acid, stereospecifically produced Z-mo nobromide 27. These reactions involves table, intermediate alpha-(metalloal kylidene)-beta-lactams. Monobromides 15 and 27 were stereo specific ally co upled to organostannanes, or were converted to the corresponding organostan nanes, 22 and 32, which coupled with organohalides. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.