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Mechanism of the Acid-Promoted Intramolecular Schmidt Reaction: Theoretical Assessment of the Importance of Lone Pair–Cation, Cation−π, and Steric Effects in Controlling Regioselectivity

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    Mechanism of the Acid-Promoted Intramolecular Schmidt Reaction: Theoretical Assessment of the Importance of Lone Pair–Cation, Cation−π, and Steric Effects in Controlling Regioselectivity
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    † Department of Chemistry, University of California at Davis, Davis, California 95616, United States
    ‡ Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, United States
    *E-mail: [email protected]
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    The Journal of Organic Chemistry

    Cite this: J. Org. Chem. 2012, 77, 1, 640–647
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    https://doi.org/10.1021/jo202338m
    Published November 29, 2011
    Copyright © 2011 American Chemical Society
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    Abstract

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    The mechanism of the acid-catalyzed intramolecular Schmidt reaction of 2-azidopropylcyclohexanones was studied using density functional theory (primarily M06-2X). The reaction was found to proceed through rapid formation of azidohydrin intermediates followed by rate-determining concerted N2-loss/shift of the alkyl group antiperiplanar to the N2 leaving group. For cases where steric, lone pair–cation, and cation−π effects have been invoked previously as regiocontrol elements, the origins and magnitudes of these effects have been examined theoretically.

    Copyright © 2011 American Chemical Society

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    Additional details on computations, including energies and coordinates for all minima and transition state structures, IRC plots, and full GAUSSIAN reference. This material is available free of charge via the Internet at http://pubs.acs.org.

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    33. J. Aubé, C. Fehl, R. Liu, M.C. McLeod, H.F. Motiwala. 6.15 Hofmann, Curtius, Schmidt, Lossen, and Related Reactions. 2014, 598-635. https://doi.org/10.1016/B978-0-08-097742-3.00623-6
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    The Journal of Organic Chemistry

    Cite this: J. Org. Chem. 2012, 77, 1, 640–647
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jo202338m
    Published November 29, 2011
    Copyright © 2011 American Chemical Society
    Request reuse permissions

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