Magnesium Coordination-Directed <i>N</i>-Selective Stereospecific Alkylation of 2-Pyridones, Carbamates, and Amides Using α-Halocarboxylic Acids

A general inversion-stereospecific, N-selective alkylation of substituted 2-pyridones (and analogues), amides, and carbamates using chiral α-chloro- or bromocarboxylic acids in the presence of KOt-Bu (or KHMDS) and Mg(Ot-Bu)2 is reported. The resulting α-chiral carboxylic acid products were isolated by crystallization in good chemical yields and in high ee (>90% ee). Mechanistic evidence suggests that the reaction proceeds through 2-pyridone O-coordinated Mg carboxylate intermediates, which afford the product through an intramolecular SN2 alkylation.