Lokesh, N. and Seegerer, Andreas and Hioe, Johnny and Gschwind, Ruth M. (2018) Chemical Exchange Saturation Transfer in Chemical Reactions: A Mechanistic Tool for NMR Detection and Characterization of Transient Intermediates. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 140 (5). pp. 1855-1862. ISSN 0002-7863,
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The low sensitivity of NMR and transient key intermediates below detection limit are the central problems studying reaction mechanisms by NMR. Sensitivity can be enhanced by hyperpolarization techniques such as dynamic nuclear polarization or the incorporation/interaction of special hyperpolarized molecules. However, all of these techniques require special equipment, are restricted to selective reactions, or undesirably influence the reaction pathways. Here, we apply the chemical exchange saturation transfer (CEST) technique for the first time to NMR detect and characterize previously unobserved transient reaction intermediates in organocatalysis. The higher sensitivity of CEST and chemical equilibria present in the reaction pathway are exploited to access population and kinetics information on low populated intermediates. The potential of the method is demonstrated on the proline-catalyzed enamine formation for unprecedented in situ detection of a DPU stabilized zwitterionic iminium species, the elusive key intermediate between enamine and oxazolidinones. The quantitative analysis of CEST data at 250 K revealed the population ratio of [Z-iminium]/[exo-oxazolidinone] 0.02, relative free energy +8.1 kJ/mol (calculated +7.3 kJ/mol), and free energy barrier of +45.9 kJ/mol (Delta G(calc.)(double dagger)(268 K) = +42.2 kJ/mol) for Z-iminium -> exo-oxazolidinone. The findings underpin the iminium ion participation in enamine formation pathway corroborating our earlier theoretical prediction and help in better understanding. The reliability of CEST is validated using 1D EXSY-build-up techniques at low temperature (213 K). The CEST method thus serves as a new tool for mechanistic investigations in organocatalysis to access key information, such as chemical shifts, populations, and reaction kinetics of intermediates below the standard NMR detection limit.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DYNAMIC NUCLEAR-POLARIZATION; ASYMMETRIC ALDOL REACTIONS; PROLINOL ETHER ENAMINES; BRONSTED ACID CATALYSIS; EXCITED PROTEIN STATES; MAGNETIZATION-TRANSFER; CEST SPECTROSCOPY; FORMATION PATHWAY; IN-VIVO; MRI; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Prof. Dr. Ruth Gschwind |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2020 12:30 |
| Last Modified: | 19 Mar 2020 12:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15054 |
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