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

Lambert, Kyle M.; Stempel, Zachary D.; Wiberg, Kenneth B.; Bailey, William F.

doi:10.1021/acs.orglett.7b03287

Cited by 6 publications

(8 citation statements)

References 14 publications

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“…We recently presented evidence for an attractive, nonbonded Coulombic interaction of the type CH•••G in a simple cyclohexane derivative that serves to stabilize an axial CN group. 17 As illustrated in Figure 2, replacement of cis-3,5dimethyl holding groups in anancomeric models with electronwithdrawing CF 3 groups dramatically increases the proportion of the axial cyano isomer present at equilibrium in cyclohexane solvent. The CF 3 groups render both the C(3,5) carbons as well as the attached syn-axial hydrogens more positive vis-a-vis the 3,5-dimethyl cyclohexane.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Moreover, it is known from experimental studies that the hydrogen of C−H bonds in alkanes has a small positive charge 18 and a more modest CH•••CN hydrogen bond may also be involved in the di-CH 3 system. 17 In an effort to explore the extent to which Coulombic interactions of this kind contribute to an anomeric effect in heterocyclic systems, we have investigated the axial−equatorial energy difference in 1,3-dioxanes bearing 2-OCH 3 or 2-CN substituents. Conformational equilibria of this sort are investigated most conveniently by equilibration of configurationally isomeric models for the conformational isomers and, as Eliel has demonstrated, 19 a cis-4,6-dimethyl-1,3-dioxane is a good surrogate for the unbiased system.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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The Anomeric Effect: It’s Complicated

et al. 2018

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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. A CH···G nonbonded attraction between a polar axial substituent (G) and the syn-axial hydrogen(s) in the heterocycle has been demonstrated experimentally. The hyperconjugation model involving electron transfer from a ring heteroatom to an excited state of an axial C-G bond was shown to be, at most, a minor contributor because of the very small changes in charge density at the ring heteroatom(s): the main charge transfer is from hydrogen to G in the H-C-G unit. This appears to result from lengthening the C-G bond to minimize repulsion with the ring atom lone pair(s) and the advantage of having a more positive hydrogen that leads to a stabilizing Coulombic interaction with the ring heteroatom(s). In short, the anomeric effect arises mainly from two separate CH···G nonbonded Coulombic attractions.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

The Anomeric Effect: It’s Complicated

et al. 2018

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“…The enynamide might be stabilized by the regulation of its molecular conformation and increased the barrier to rotation of the C–C bond a , so that the nucleophilic attack of the oxygen atom was unfavored. Based on our previous research about the N -quinolone amide, this hypothesis might be achieved with N -quinolone enynamides as the substrate due to the interaction of its intramolecular H-bonds (Scheme , eq 3) . This assumption was indeed supported by the H-bonds (N–H···N and C–H···O) and approximately plane conformation of enyamide 1m observed in the X-ray crystal structure (see SI), in which the oxygen and alkynyl group were on the opposite side of the C–C single bond a .…”

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confidence: 77%

Asymmetric Organocatalytic Synthesis of 2,3-Allenamides from Hydrogen-Bond-Stabilized Enynamides

Wei

Lin

et al. 2019

Org. Lett.

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Asymmetric catalytic synthesis of 2,3-allenamides from hydrogen-bond-stabilized enynamides in the presence of quinine-based bifunctional squaramide organocatalysts is described. This protocol forms a variety of 2,3-allenamides in high yields and excellent stereoselectivities, in which the elaborated introduction of intramolecular H-bonds within the N,N-bidentate amide group constitutes one of the keys to this highly enantioselective transformation. The synthetic practicality of this reaction has been demonstrated by the axis-to-center chirality transfer of allenamides to furnish enantiomerically enriched building blocks.

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“…The increased charge could also be seen in calculations. 12 It has also been found that hydrogens are quite sensitive to electronic effects at the atom to which they have been attached. With only a small nuclear charge, it is readily possible to shift some charge either to or from a hydrogen atom.…”

Section: Hydrogen Atom Problemmentioning

confidence: 96%

“…This led to an increased Coulombic attraction with the axial F that could be observed via equilibrium constant measurements. The increased charge could also be seen in calculations …”

Section: Hydrogen Atom Problemmentioning

confidence: 99%

Atomic Charges

Wiberg

Rablen

2018

J. Org. Chem.

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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. The Hirshfeld, CM5, and MBS methods, but not the others, provided an excellent correlation for H atomic charge with the H–C–H bond angle, and with calculated gas-phase acidity. The two methods that were linearly related and gave hydrogen charges in agreement with an experimental study of partially deuterated methanes are MBS and Hirshfeld. In order to see which of the two methods is the more satisfactory, the methanol dimer was examined. The calculated H bond energy was 6.2 kcal/mol, which was in good agreement with studies of hydrogen bonds. The Coulombic interaction for the O···H bond was estimated using the MBS and Hirshfeld charges. The latter gave a calculated energy of 3–6 kcal/mol, whereas MBS gave an energy of ∼35 kcal/mol. Clearly, the Hirshfeld method is more satisfactory and should be the method of choice.

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

Cited by 6 publications

References 14 publications

The Anomeric Effect: It’s Complicated

The Anomeric Effect: It’s Complicated

Asymmetric Organocatalytic Synthesis of 2,3-Allenamides from Hydrogen-Bond-Stabilized Enynamides

Atomic Charges

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