Many enzymes contain an essential arginyl residue at the active site. Butanedione and other simple α-diketones characteristically inactivate these enzymes by bonding covalently to arginine. In an effort to confer specificity to this interaction, we have sought methods for incorporating an -diketone moiety into polyfunctional inhibitors of such enzymes. The ideal synthetic method for our purpose would involve the conversion of an existing carboxylic acid function into an α-diketone under mild conditions. Here we report on studies directed to developing such a route.