Computations Reveal That Electron-Withdrawing Leaving Groups Facilitate Intramolecular Conjugate Displacement Reactions by Negative Hyperconjugation

  1. Noey, E.L. 2
  2. Jiménez-Osés, G. 2
  3. Clive, D.J.L. 1
  4. Houk, K.N. 2
  1. 1 University of Alberta
    info

    University of Alberta

    Edmonton, Canadá

    ROR https://ror.org/0160cpw27

  2. 2 University of California Los Angeles
    info

    University of California Los Angeles

    Los Ángeles, Estados Unidos

    ROR https://ror.org/046rm7j60

Revista:
Journal of Organic Chemistry

ISSN: 0022-3263

Año de publicación: 2016

Volumen: 81

Número: 10

Páginas: 4290-4294

Tipo: Artículo

DOI: 10.1021/ACS.JOC.6B00691 SCOPUS: 2-s2.0-84971232269 GOOGLE SCHOLAR

Otras publicaciones en: Journal of Organic Chemistry

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Resumen

Intramolecular conjugate displacement (ICD) reactions, developed by the Clive group, form carbocycles and polycyclic amines by intramolecular nucleophilic attack on a Michael acceptor with an allylic leaving group. Quantum mechanical investigations with density functional theory show that ICDs involve a stepwise addition, forming an intermediate stabilized carbanion, followed by elimination. The electron-withdrawing nature of the allylic leaving group facilitates the addition by negative hyperconjugation; the twist-boat conformation of the addition and intermediate is stabilized by this interaction. In the absence of an activating electron-withdrawing group as part of the Michael acceptor, a high energy concerted SN2′ reaction occurs. The reactions of carbon nucleophiles have lower activation energies than those of amines. © 2016 American Chemical Society.