Computations Reveal That Electron-Withdrawing Leaving Groups Facilitate Intramolecular Conjugate Displacement Reactions by Negative Hyperconjugation.
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.
Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United, States.
Elizabeth L
EL
Noey
Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United, States.
Gonzalo
G
Jiménez-Osés
Department of Chemistry, University of Alberta , Edmonton, Alberta T6G 2G2, Canada.
Derrick J L
DJ
Clive
Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United, States.
K N
KN
Houk