Relaxation Dispersion NMR to Reveal Fast Dynamics in Brønsted Acid Catalysis: Influence of Sterics and H-Bond Strength on Conformations and Substrate Hopping
Open Access
- 23 September 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 141 (41), 16398-16407
- https://doi.org/10.1021/jacs.9b07841
Abstract
NMR provides both structural and dynamic information, which are key to connect intermediates and to understand reaction pathways. However, fast exchanging catalytic intermediates are often inaccessible by conventional NMR due its limited time resolution. Here we show the combined application of 1H off-resonance R1ρ NMR method and low tem-perature (185-175 K) to resolve intermediates exchanging on a μs time scale (ns at room temperature). The potential of the approach is demonstrated on chiral phosphoric acid (CPA) catalysts in their complexes with imines. The otherwise inaccessible exchange kinetics of the E-I⇌E-II imine conformations and thermodynamic E-I:E-II imine ratios inside the catalyst pocket are experimentally determined and corroborated by calculations. The E-I⇌E-II exchange rate constants (kex185K) for different catalyst-substrate binary complexes varied between 2500-19000 s-1 (kex = 500-50 µs). Theoretical analysis of these exchange rate constants revealed the involvement of an intermediary tilted conformation E-III, which structurally resembles the hydride transfer transition state. The main E-I and E-II exchange pathway is a hydrogen bond strength dependent tilting-switching-tilting mechanism via a bifurcated hydrogen bond as transition state. The reduction in the sterics of the catalyst showed an accelerated switching process by at least an order of magnitude and enabled an additional rotational pathway. Hence, the exchange process is mainly a function of the intrinsic properties of the 3,3´-substituents of the catalyst. Overall, we believe that the present study opens a new dimension in catalysis via experimental access to structures, populations and kinetics of catalyst-substrate complexes on the μs time scale by 1H off-resonance R1ρ method.Funding Information
- Deutsche Forschungsgemeinschaft (SPP 1807)
- FP7 Ideas: European Research Council (ERC-CoG 614182)
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