Determination of 2H KIEs from Competition Experiments: Increased Accuracy via Isotopic Enrichment

Methods for the determination of 2H KIEs at natural abundance of deuterium have not been widely used due to the requirement for very long NMR times or large reaction scale. We previously reported a simple methodology for reducing these restrictions by the addition of a small amount of deuterated substrate. Herein, we evaluate the deuterium loadings that give the lowest errors in the determination of 2H KIEs. Our simulations indicate that our approach leads to a 4000-fold reduction in NMR time over natural abundance methods.