posted on 2021-12-06, 19:11authored byHarvey
J. A. Dale, Andrew G. Leach, Guy C. Lloyd-Jones
Chemists have many options for elucidating
reaction mechanisms.
Global kinetic analysis and classic transition-state probes (e.g.,
LFERs, Eyring) inevitably form the cornerstone of any strategy, yet
their application to increasingly sophisticated synthetic methodologies
often leads to a wide range of indistinguishable mechanistic proposals.
Computational chemistry provides powerful tools for narrowing the
field in such cases, yet wholly simulated mechanisms must be interpreted
with great caution. Heavy-atom kinetic isotope effects (KIEs) offer
an exquisite but underutilized method for reconciling the two approaches,
anchoring the theoretician in the world of calculable observables
and providing the experimentalist with atomistic insights. This Perspective
provides a personal outlook on this synergy. It surveys the computation
of heavy-atom KIEs and their measurement by NMR spectroscopy, discusses
recent case studies, highlights the intellectual reward that lies
in alignment of experiment and theory, and reflects on the changes
required in chemical education in the area.