Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives
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nihms-1021427.pdf
Description
Accepted version
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807.31 KB
Format
Adobe PDF
Checksum (MD5)
988f50cb238763eb40ac1dc3d65e94b1
Author(s)
Myers, Eddie L.
Palte, Michael J.
Raines, Ronald T
Date Issued
January 2019
Journal
Journal of Organic Chemistry
Publisher
American Chemical Society (ACS)
Citation
Myers, Eddie L. et al. "Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives." Journal of Organic Chemistry 84, 3 (January 2019): 1247-1256 © 2019 American Chemical Society
Version
Author's final manuscript
Abstract
The identification and understanding of structure–activity relationships is vital for rational catalyst design. A kinetic study of the hydrogen–deuterium exchange reaction of cyclohexanone in aqueous solution, as catalyzed by proline derivatives, has revealed valuable structure–activity relationships. In phosphate-buffered solution, cis-4-fluoroproline is more active than the trans isomer, a distinction that appears to originate from a destabilizing interaction between the fluorine atom and phosphate anion during general acid-catalyzed dehydration of the carbinolamine intermediate. trans-4-Ammoniumprolines are exceptionally active catalysts owing to favorable Coulombic interactions involving the ammonium group and the alkoxide moiety formed upon 1,2-addition of the proline derivative to the ketone. These results could be used for the optimization of proline catalysts, especially in transformations where the formation of the putative iminium ion is rate-limiting.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/acs.joc.8b02644
