Electrochemical and stereochemical investigation on the mechanism of the decay of 2-halo amide anions. The intermediacy of aziridinones

Article abstract of DOI:10.1021/ja00068a012

2-Halo amide anions can be generated by electroreduction of the corresponding NH-protic 2-halo amides through the self-protonation mechanism. Such anions are labile species whose decay, in the case of 2-bromo amide anions, competes with their electroreduction in the voltammetric time scale. Using the appropriate voltammetric treatment, the first-order rate constant of the decay has been determined for a series of representative 2-bromo amides. The lability orders point to an S_N2-type intramolecular substitution of bromine and thus to the formation of a three-membered ring. Stereochemical information on the decay has been gained using a chiral nonracemic 2-bromopropanamide, an amine nucleophile, and DMF as the solvent. The direct substitution by the amine proceeds by an S_N2 reaction, as witnessed by inversion of configuration at the α-carbon and voltammetric analysis. Conversely, when the reaction is triggered by electroreduction, the decay of the 2-bromo amide anion eventually leads to the formation of the retention product 2-amino amide together with other optically active products, namely two diastereomeric oxazolidin-4-ones, arising by cyclocondensation with DMF, and cis-2,5-dioxopiperazine. Analysis of the electrochemical and Stereochemical results indicates that the mechanism of the base-promoted reactions of 2-halo amides proceeds through the transient formation of the corresponding aziridinone, independently of the fact that the latter is isolable or not. The formation of the aziridinone takes place by concerted intramolecular nucleophilic substitution of bromide ion within the 2-halo amide anion. The transient aziridinone behaves not only as the product-determining intermediate but also as a species capable of reacting with suitable partners under remarkable enantioselectivity control.