Bromine oxidation accelerator

A rapid synthesis of carbon-14 labeled [l-14C]levulinic acid from simple building blocks has been demonstrated by Johansen and coworkers (Scheme 6.172) [324], In all three of the synthetic steps, starting from bromo[l-14C]acetic acid, microwave heating was used to accelerate the reactions, allowing a total preparation time of less than 1 h. The labeled levulinic acid was subsequently transformed into (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone in a bromination/oxidation sequence (not shown), a potent quorum sensing inhibitor. 

For example, a 6-rlng TS is favored for proton transfer to the carboxylate center in CH3CHN02CH2CH2C02 to form the nitrocarbanion. Hydride transfer is Intramolecularly base-catalyzed in the bromine oxidation of o-for-myl benzoate ion to produce a 70x acceleration (other substituents affect the benzaldehyde rate only within 3x). Nucleophilic addition of -OO2 to the formyl group Is excluded because phthallc anhydride hydrolyzes too... 

Several trends emerge in these data (1) The reductive elimination of bromine is 6-13kJmol more facile than reductive elimination of chlorine in similar structures, which is consistent with weaker chalcogen-bromine bonds relative to chalcogen-chlorine bonds.(2) The reductive elimination of chlorine is accelerated by the presence of a chloride counterion as opposed to a less nucleophilic counterion such as hexafluorophosphate. (3) The rate of reductive elimination is accelerated by the presence of a more polar solvent (acetonitrile) relative to tetrachloroethane, which is consistent with development of charge in the rate-determining step. These observations suggest mechanisms for oxidative... 

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