Halogen-Halogen Nonbonded Interactions.

Halogen-halogen nonbonded interactions were studied for methyl halides and phenyl halides using both B3LYP and MP2 along with 6-311+G* and aug-cc-pVTZ. With the methyl halides, the linear approach was found to lead to little stabilization, whereas the "90°" approach gave 1-2 kcal/mol. This modest stabilization was due to long-range electron correlation effects.

Re-Examination of Some Carbocations. Structures, Energies, and Charge Distributions.

Chemists have had a long-standing interest in reactive intermediates such as carbenes, carbon radicals, carbanions, and carbocations. Carbocations are an interesting part of this group because of their tendency to undergo rearrangement, sometimes forming bridged ions, as well as their ability in many cases of spreading out the positive charge over several atoms. We have re-examined some of these cases using high-level compound procedures, W1BD and G4, as well as by considering the charge distributions making use of the Hirshfeld method that has been shown to uniquely correlate with several types of experimental data.

Total Synthesis of (±)-Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen-Oxygen Bonds.

The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described.

Increase in Strain Energy during Conversion of [4.4.4.5]Fenestrane to [4.4.4.4]Fenestrane: a Method for Estimating the Heats of Formation of Hydrocarbons and Their Derivatives from Ab Initio Energies.

Our interest in fenestranes led us to wonder how large the change in strain energy with changes in the ring size might be. This led us to consider if satisfactory estimates of heat of formation could be easily derived from ab initio calculated energies. We started by examining 21 hydrocarbons having well-determined heats of formation via calculations of their enthalpies using W1BD, G4, CBS-APNO, CBS-QB3, and M062X.

Relationship between Rotational Barriers and Charge Shifts.

Conjugation and hyperconjugation are closely related stereoelectronic effects that are usually discussed in a qualitative fashion. It is possible to make it more quantitative. The natural bond orbital method provides a means of estimating the energetic consequence.

Unrecognized Intramolecular and Intermolecular Attractive Interactions between Fluorine-Containing Motifs and Ether, Carbonyl, and Amino Moieties.

In order to elucidate to what extent Coulombic and other interactions contribute to the origins of contrasteric phenomena, we have identified a significant, previously unrecognized interaction between fluorine-containing motifs and groups or molecules containing main-group heteroatoms. The axial conformers of both 2-methoxy- and 2-trifluoromethoxytetrahydropyrans preferentially adopt a rotameric arrangement in which the OCH and the OCF groups are gauche to the ring oxygen. Given that one would expect a repulsive Columbic interaction to exist between the electronegative fluorines of the CF group and the ring oxygen in this rotomeric orientation, this surprising result suggests that an attractive interaction exists between the CF group and the oxygen of the ring.

Atomic Charges.

The problem of deriving atomic charges from the results of ab Initio MO calculations has been studied by the use of several reported methods: Mulliken population analysis, the minimal basis set (MBS) procedure, the natural population analysis (NPA), two electrostatic potential fitting methods, M-K and ChelpG, the Hirshfeld population analysis, and CM5 (charge model 5), which is related to the Hirshfeld method. The first set of studies were concerned with hydrogen charges. It was found that the MBS charges were linearly related to the Hirshfeld charges.

Role of Intramolecular Electron Delocalization in the C-X Bond Strength in CHX ( n = 0-4, X = F, Cl, CN, OCH).

Most recently, Wiberg and Rablen examined a few substituted methanes and identified the polar effect, which is associated with the atomic charge at the central carbon, as a possible factor for bond energy changes while the exact role of the hyperconjugation effect is unsettled. In this work, we revisited a series of substituted methanes CHX ( n = 0-4, X= F, Cl, CN, OCH) by explicitly computing the intramolecular electron delocalization energies using the simplest variant of ab initio valence bond (VB) theory, namely the block-localized wave function (BLW) method. This BLW method is designated to derive electron-localized states where intramolecular electron delocalization is "turned off".

Methoxymethane C-O Bond Strengths: Do Their Changes Result from Hyperconjugation or Polar Effects?

The methoxymethanes have been studied and compared with the fluoromethanes. The energies and atomic charges were calculated using MP2/aug-cc-pVTZ, and the group separation energies and bond dissociation enthalpies were calculated using CBS-QB3. The group separation energies are endothermic and the BDE increases with additional substitution as a result of the increase in charge at the central carbon.

Butadiene and Heterodienes Revisited.

Surprising features in a recently published high-level calculation of the rotational profile of butadiene led us to compare butadiene with a set of 17 heterodienes. The rotational profiles for this large group of compounds varied widely, thereby possessing a high information content. These data were subjected to a Fourier analysis yielding 1- through 6-fold terms: the one-fold terms represent the change in steric energy on going from 180° to 0°, while the changes in the 2-fold terms correspond to the expected change in π-delocalization energy with structure; the 3-fold terms were significant and found to be linearly correlated to the average of the atomic charges of the atoms at the central single bond of the cis-forms, but their origins are still not clear; we propose a novel 1,4 π-interactions that may account for this phenomenon.

The Anomeric Effect: It's Complicated.

The origin of the anomeric effect has been reexamined in a coordinated experimental and computational investigation. The results of these studies implicate a number of different, but correlated, interactions that in the aggregate are responsible for the anomeric effect. No single factor is uniquely responsible for the axial preference of a substituent that is the hallmark of the anomeric effect.

Experimental Demonstration of a Sizeable Nonclassical CH···G Hydrogen Bond in Cyclohexane Derivatives: Stabilization of an Axial Cyano Group.

Base-catalyzed equilibration of anancomeric cyanocyclohexanes demonstrates that replacement of cis-3,5-dimethyl holding groups with electron-withdrawing CF groups dramatically increases the proportion of the axial cyano isomer present at equilibrium. The CF groups exert an effect on the conformational energy of the cyano group worth about 0.6 kcal/mol.

Chiroptical Properties of Imines Derived from R-(+)-Norbornenone: The Role of Electronegativity Differences.

To allow a comparison with the specific rotations of R-(+)-5-methylenenorbornene (1) and R-(+)-norbornenone (2) we performed calculations at the LC-wPBE/aug-cc-pVTZ level for the imines (5a and 5b) derived from norbornenone and also for their protonated derivative (6). In accord with our results for simpler systems, the specific rotations increase in the order of 1 < 5 < 2 ≈ 6. In addition, the specific rotation of the protonated ketone was calculated and found to be considerably larger than that for 2 or 6.

Dispersive Optical Activity of (R)-Methylene Norbornene: Intrinsic Response and Solvation Effects.

The dispersive optical activity of a homoconjugated bicyclic diene, (R)-methylene norbornene (R-MNB), was interrogated under complementary vapor-phase and solution-phase conditions to elucidate the structural/electronic provenance of its unusual chiroptical signatures and to explore the marked influence of environmental perturbations. The intrinsic (isolated-molecule) values of specific rotation measured at 355 and 633 nm (1623.5 ± 5.

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.

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.

Chirality Induced by the Interaction of C═C and C═X Bonds (X═CH, NH, NH, O, and S) Separated by a Methylene Group.

The chirality derived from the interaction between two double bonds (C═C and C═X where X ═ CH, NH, NH, O and S) across a methylene group has been examined in some detail at the B3LYP/aug-cc-pVTZ level. The rotamers of these formally achiral molecules that lead to large calculated specific rotations are those that allow overlap between the pair of double bonds, and the rotation is increased when the distance between them is decreased. Although the large specific rotation of unconjugated enones such as norbornenone is usually attributed to a magnetic transition dipole arising from an n-π* interaction of the carbonyl group, it has been found that large rotations may also be found with some conformations of unconjugated dienes such as 1,4-pentadiene.

Electron Delocalization Range in Atoms and on Molecular Surfaces.

The electron delocalization range function EDR(r⃗; d) (J. Chem. Phys.

Effect of Conjugation on Electron Distributions. Separation of σ and π Terms.

The ground states of unsaturated molecules with C(s) symmetry have separate σ and π molecular orbitals. This makes it possible to separately calculate the σ and π Hirshfeld populations and to analyze the effect of structural changes in more detail. A number of types of compounds have been studied: vinyl derivatives, 1-substituted hexatrienes, phenyl derivatives, and six-membered ring heterocycles.

The Role of CH···O Coulombic Interactions in Determining Rotameric Conformations of Phenyl Substituted 1,3-Dioxanes and Tetrahydropyrans.

The rotameric conformations of the phenyl ring in both the axial and the equatorial conformers of phenyl substituted 1,3-dioxanes and tetrahydropyrans are compared with those of the corresponding phenylcyclohexanes at the MP2/6-311+G* level. The compounds with an axial phenyl commonly adopt a conformation in which the plane of the aromatic ring is perpendicular to the benzylic C-H bond. However, axial 5-phenyl-1,3-dioxane adopts a "parallel" conformation that allows an ortho hydrogen to be proximate to the two ring oxygens, leading to attractive CH···O interactions.

Intrinsic Optical Activity and Large-Amplitude Displacement: Conformational Flexibility in (R)-Glycidyl Methyl Ether.

The dispersive optical activity of (R)-(-)-glycidyl methyl ether (R-GME) has been interrogated under ambient vapor-phase and solution-phase conditions, with quantum-chemical analyses built on density functional (B3LYP and CAM-B3LYP) and coupled-cluster (CCSD) implementations of linear-response theory exploited to interpret experimental findings. Inherent flexibility of the heavy atom skeleton leads to nine low-lying structural isomers that possess distinct chiroptical and physicochemical properties, as evinced by marked changes in the magnitude and the sign of rotatory powers observed in various media. These species are interconverted by independent motion along two large-amplitude torsional coordinates and are stabilized differentially by interaction with the surroundings, thereby reapportioning their relative contributions to the collective response evoked from a thermally equilibrated ensemble.

Effect of remote aryl substituents on the conformational equilibria of 2,2-diaryl-1,3-dioxanes: importance of electrostatic interactions.

The conformational preference of a variety of 2,2-diaryl-1,3-dioxanes bearing remote substituents on the phenyl rings has been studied via equilibration of configurationally isomeric 2,2-diaryl-cis-4,6-dimethyl-1,3-dioxane epimers, X-ray crystallography, (1)H NOESY analysis, and B3LYP/6-311+G* calculations. When the aryl ring bears a remote electron-withdrawing substituent, the isomer having both the higher dipole moment and the electron-withdrawing group in the equatorial phenyl ring and/or an electron-donating group in the axial ring has the lower energy. These results differ from the conclusions reported in a previous study of similar systems.

Facile oxidation of primary amines to nitriles using an oxoammonium salt.

The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH2Cl2-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.

Calculations for the properties and reactions of the NH, PH, and AsH counterparts of dimethyl ether and acetone.

The properties and reactions of compounds in which the O of dimethyl ether or acetone has been replaced by NH, PH, or AsH have been studied computationally using CBS-QB3, CBS-APNO, G4, and W1BD. The properties include the bond dissociation energies and ionization potentials, and the reactions include those with with protons, methyl cations, and lithium cations. The effect on keto-enol equilibria also was examined.

Insights on the origin of the unusually large specific rotation of (1S,4S)-norbornenone.

Measurements and calculations of specific rotation are indispensable for the characterization of chiral molecules and are now performed routinely. However, the factors that determine the magnitude of this property are still not well-understood. The anomalously large specific rotation of (1S,4S)-norbornenone, an outstanding puzzle for over three decades, offers the chance to examine these factors in detail.

A computational study of RXHn X-H bond dissociation enthalpies.

Bond dissociation enthalpies can exhibit dramatic variations resulting from substituent effects. These variations result from changes in electronic structure that accompany bond dissociation. We have studied bond dissociation enthalpies (BDEs) at the W1BD level of theory for a series of RX-H compounds where X = CH2, NH, O, PH, and S.