Oxidative decarboxylation of clavulanic acid and its 9-methyl ether

Abstract

The carboxy group of clavulanic acid has been replaced by a methoxy group, an acetoxy group, and a m-chlorobenzoyloxy group using standard methods for oxidative decarboxylation (electrolysis, reaction with lead tetra-acetate, and decarboxylative rearrangement of a diacyl peroxide, respectively). In an unexpected reaction, 9-O-methylclavulanic acid (20) reacted with p-chlorophenylselenenyl bromide and base to give 3-(p-chlorophenylseleno)-2-(2-methoxyethylidene)clavam (21). Refluxing a solution of compound (21) in toluene gave 3-hydroxy-2-(2-methoxyethylidene)clavam and bis(p-chlorophenyl)diselenide, the overall result being the replacement of the carboxy group in the acid (20) by a hydroxy group. In chloroform, this 3-hydroxyclavam exists predominantly as the ring-opened aldehyde. Possible mechanisms for the formation of the seleno derivative (21) and its decomposition in refluxing toluene are discussed.