Kinetic isotope effects in the deprotonation of chiral formamidines

Abstract

Metallation of 6,7-dimethoxy isoquinoline formamidines show a kinetic isotope effect, in contrast to the metallation of the 6,7-dihydro system; the isotope effect for the secondary proton in the dimethoxy system is smaller than usual (2.0) while the isotope effect for tertiary proton removal is somewhat larger (∼4.0), this is explained by the magnitude of pK_a on isotope effect as well as competition between the pre-complexation step and the deprotonation step.