Mechanisms and Beyond: Elucidation of Fluxional Dynamics by Exchange NMR Spectroscopy

Detailed mechanistic information is crucial to our understanding of reaction pathways and selectivity. Dynamic exchange NMR techniques, in particular 2D exchange spectroscopy (EXSY) and its modifications, provide indispensable intricate information on the mechanisms of organic and inorganic reactions and other phenomena, for example, the dynamics of interfacial processes. In this Review, key results from exchange NMR studies of small molecules over the last few decades are systemised and discussed. After a brief introduction to the theory, the key types of dynamic processes are identified and fundamental examples given of intra- and intermolecular reactions, which, in turn, could involve, or not, bond-making and bond-breaking events. Following that logic, internal molecular rotation, intramolecular stereomutation and molecular recognition will first be considered because they do not typically involve bond breaking. Then, rearrangements, substitution-type reactions, cyclisations, additions and other processes affecting chemical bonds will be discussed. Finally, interfacial molecular dynamics and unexpected combinations of different types of fluxional processes will also be highlighted. How exchange NMR spectroscopy helps to identify conformational changes, coordination and molecular recognition processes as well as quantify reaction energy barriers and extract detailed mechanistic information by using reaction rate theory in conjunction with computational techniques will be shown.