title: Controlling the Conformational Energy of a Phenyl Group by Tuning the Strength of a Nonclassical CH···O Hydrogen Bond: The Case of 5-Phenyl-1,3-dioxane.
abstract: Anancomeric 5-phenyl-1,3-dioxanes provide a unique opportunity to study factors that control conformation. Whereas one might expect an axial phenyl group at C(5) of 1,3-dioxane to adopt a conformation similar to that in axial phenylcyclohexane, a series of studies including X-ray crystallography, NOE measurements, and DFT calculations demonstrate that the phenyl prefers to lie over the dioxane ring in order to position an ortho-hydrogen to participate in a stabilizing, nonclassical CH···O hydrogen bond with a ring oxygen of the dioxane. Acid-catalyzed equilibration of a series of anancomeric 2-tert-butyl-5-aryl-1,3-dioxane isomers demonstrates that remote substituents on the phenyl ring affect the conformational energy of a 5-aryl-1,3-dioxane: electron-withdrawing substituents decrease the conformational energy of the aryl group, while electron-donating substituents increase the conformational energy of the group. This effect is correlated in a very linear way to Hammett substituent parameters. In short, the strength of the CH···O hydrogen bond may be tuned in a predictable way in response to the electron-withdrawing or electron-donating ability of substituents positioned remotely on the aryl ring. This effect may be profound: a 3,5-bis-CF3phenyl group at C(5) in 1,3-dioxane displays a pronounced preference for the axial orientation. The results are relevant to broader conformational issues involving heterocyclic systems bearing aryl substituents.
authors.affiliation: Department of Chemistry, University of Connecticut , Storrs, Connecticut 06269-3060, United States.
authors.forename: William F
authors.identifier: 0000-0001-9159-0218
authors.initials: WF
authors.lastname: Bailey
authors.affiliation: Department of Chemistry, University of Connecticut , Storrs, Connecticut 06269-3060, United States.
authors.forename: Kyle M
authors.identifier: 0000-0002-8230-2840
authors.initials: KM
authors.lastname: Lambert
authors.affiliation: Department of Chemistry, University of Connecticut , Storrs, Connecticut 06269-3060, United States.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Stempel
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Wiberg
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Brandon Q
authors.initials: BQ
authors.lastname: Mercado