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

• Intramolecular conjugate displacements are stepwise: Computational evaluations of the mechanism

• Author(s) / Creator(s)

  • Noey, Elizabeth L.
  • Jiménez-Osés, Gonzalo
  • Clive, Derrick J. L.
  • Houk, K. N.

• Intramolecular conjugate displacement (ICD) reactions, developed by the Clive
  group, form carbocycles and cyclic 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.

• Date created

  2016-01-01

• Subjects / Keywords

  • Activation Energy
  • Amines
  • Carbon
  • Chemical Activation
  • Density Functional Theory
  • Quantum Theory
  • Substitution Reactions
  • Carbon Nucleophiles
  • Displacement Reactions
  • Electron Withdrawing Group
  • Intramolecular Nucleophilic Attack

• Type of Item

  Article (Draft / Submitted)

• DOI

  https://doi.org/10.7939/r3-zzsj-9z16

• License

  This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Organic Chemistry, copyright © 2016 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.joc.6b00691.