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.