A simple method for the precise and simultaneous determination of primary and multiple secondary kinetic deuterium isotope effects in organic reactions at natural abundance

A method for the determination of kinetic isotope effects (KIEs) in organic reactions using natural abundance deuterium NMR is proposed. The method consists of the determination of the site-specific H/D isotopic ratios of the starting reactant and the product in a reaction run under pseudo-first-order kinetic conditions. Using simple and easy experimental procedures, primary and/or multiple secondary KIEs can be measured simultaneously with high precision. The application of this approach to different types of reaction is described. The primary and a-secondary KIEs for C-H(D) bond breaking of -CDH- can be measured separately. The uncertainty in the determination of small secondary KIEs can reach less than 1%. The results show that some remote secondary KIEs are not negligible. The advantages and limitations of the method are discussed. One of its merits is that the method can even be used in complex situations when there are branch reactions and when the reaction is reversible. The performance depends essentially on the signal separation in the NMR spectra. Copyright (C) 2001 John Wiley & Sons, Ltd.