Catalytic Approaches to the Synthesis of β-Lactamase Inhibitors

Abstract

Catalytic couplings were utilized to stereospecifically synthesize several 7 E- and 7 Z-alkylidenecephalosporins. Members of this class are known inhibitors of β-lactamase. Zinc/NH 4Cl reduction of dibromide 14 stereospecifically produced E-monobromide, 15. In contrast, treatment of 14 with isopropylmagnesium bromide, followed by mild acid, stereospecifically produced Z-monobromide 27. These reactions involve stable, intermediate α-(metalloalkylidene)-β-lactams. Monobromides 15 and 27 were stereospecifically coupled to organostannanes, or were converted to the corresponding organostannanes, 22 and 32, which coupled with organohalides.