The Multiple Reactions in the Monochlorodimedone Assay: Discovery of Unique Dehalolactonizations under Mild Conditions

The monochlorodimedone assay has been widely used as an assay of the brominating activity of halogenating enzymes; however, the assumed product was found to spontaneously decompose during the measurement. The decomposition mechanism and systematic error in the assay were explained by five reactions in their multiple reactions. We discovered unique dehalolactonizations of halogenated δ‐keto acids in aqueous solution among many reactions in the assay. Its reaction mechanism was suggested as the cyclization via a cyclopropanone intermediate produced by the intramolecular catalysis of the carboxylate anion. Lose the halo: It was clarified that spontaneous decomposition of the assumed product in the monochlorodimedone assay for halogenating enzymes occurs. The unique dehalolactonization of halogenated δ‐keto acids, which was discovered from among many reactions in the assay, are selective cyclizations without any sacrificial reagent and external catalyst in aqueous solution.