SWERN Oxidation. Transition State Theory is OK

We investigate the model originally used to compare deuterium kinetic isotope effects (KIE) computed for the intramolecular hydrogen transfer step in the mechanism of the Swern oxidation of alcohols to aldehydes with those measured. Whereas the replication of the original computed values reported in 2010 for the gas-phase proved entirely successful, several issues were discovered when a continuum solvent model was used. These included uncertainty regarding the parameters and methods used for the calculations and coordinates for the original reactant and transition states, via their provision as data in the electronic supporting information (ESI). The original conclusions, in which a numerical mis-match between the magnitude of the computed and experimentally measured KIE was attributed to significant deviations from transition state theory, are here instead rationalised as a manifestation of basis-set effects in the computation. Transition state theory appears to be operating successfully. We now recommend the use of basis sets of triple- or quadruple-ζ quality, rather than the split-valence level previously employed, that dispersion energy corrections be included and that a continuum solvent model using smoothed reaction cavities is essential for effective geometry optimisation and hence accurate normal coordinate analysis. An outlying experimental KIE obtained for chloroform as solvent is attributed to a small level of an explicit hydrogen bonded interaction with the substrate. A temperature outlier for the measured KIE at 195K is suggested for further experimental investigation, although it may also be an indication of an unusually abrupt incursion of hydrogen tunnelling, which would need non-Born-Oppenheimer methods in which nuclear quantum effects are included to be more accurately modelled. We predict KIE for new substituents, of which those for R=NMe2 are significantly larger than for R=H. This approach could be useful in designing variations of the Swern reagent that could lead to synthesis of aldehydes incorporating much higher levels of deuterium. The use of FAIR data rather than the traditional model of its inclusion in electronic supporting information (ESI) is discussed.