Charge transfer and electron localization as the origin of the anomeric effect in theO─C─Osegment of dimethoxymethane and spiroketals

Abstract

Every day, more evidence accumulates, leading to the conclusion that the stereoelectronic model through the nO → σ*C─O interaction is of minor relevance or even inoperative to explain conformational preference in the specific O─C─O segment. In the present study, dimethoxymethane (DMM) and some model spiroketals were chosen to develop a reliable and easy to apply methodology that is simple to interpret by experimental chemists. The general conformation observed in these molecules, present in many biologically active natural products, is the gauche‐gauche (g,g) in DMM and bis‐diaxial in spiroketals. To study this conformational preference, this paper presents a new approach, where general trends for the atomic and molecular energetic components, as well as localization and delocalization indices, and their bonded (Δb) and nonbonded (Δnb) electronic contributions are analyzed. In addition, group contributions to the electron localization and polarization are also defined, agreeing with the conformational preference. It is clear that electronic localization/delocalization is capable of reproducing experimental observations, showing an adequate correlation of this property to the cos θ term in the context of Pople's analysis. It is proposed that electron delocalization between electronegative atoms or total delocalization between nonbonded atoms is not the major contributors to the axial conformational preference observed in spiroketals. Conformational preference shows defined trends in terms of group delocalization in DMM and ring localization and charge transfer between groups in spiroketals. This way, electronic delocalization can be used to evaluate the anomeric effect, using just a few parameters, which makes the method broadly functional.

The contribution of non-classical CHax⋯OC hydrogen bonds to the anomeric effect in fluoro and oxa-methoxycyclohexanes

“…6 Then there is greater nO/nO steric hindrance in the equatorial conformer, which has parallel 2p-type nO filled orbitals again favouring the axial conformer (Figure 1c). 7,8,9,10 Finally and most recently, non-classical hydrogen bonds (NCHBs) such as transannular CHax•••OC interactions have been proposed by Nishio 11 and supported by Wiberg 12 and Cuevas 13 which introduce a further electrostatic factor. NCHBs occur when an electronegative atom (in this case O) interacts with a covalently bound X-H hydrogen but where the X atom is of moderate to low electronegativity (in this case C).…”

“…NCHBs occur when an electronegative atom (in this case O) interacts with a covalently bound X-H hydrogen but where the X atom is of moderate to low electronegativity (in this case C). 14,15 These authors [11][12][13] and particularly Wiberg 12 have argued an increasing significance for electrostatic interactions in determining the anomeric effect with a decreasing emphasis on the more widely propagated hyperconjugation model. It is the NCHB interactions which form the focus of this work, where we deconvolute [using Natural Bond Orbital (NBO) analysis, 16 Quantum Theory of Atoms in Molecules (QTAIM) 17 and Non Covalent Interactions (NCI) 18 ] their contributions relative to hyperconjugation, and provide quantitative support to this revision, in an approach which extends from a deeper analysis of our recent observations of 'pseudo' anomeric effects in cyclohexanes 2, 4, 5 and 8.…”

Latin American contributions to quantum chemical topology

“…Recently, the same authors used the ED index to explain the conformational preference of dimethoxy‐methane and spiroketals . In these cases, they analyzed the atomic and molecular energetic components, as well as localization (Equation ) and delocalization indexes (Equation ), and their bonded ( Δ b ) and nonbonded ( Δ nb ) electronic contributions .…”

“…Adapted from New J Chem 2014;38:58925904 with permission of the Royal Society of Chemistry [46] Recently, the same authors used the ED index to explain the conformational preference of dimethoxy-methane and spiroketals. [50] In these cases, they analyzed the atomic and molecular energetic components, as well as localization (Equation (10)) and delocalization indexes (Equation (11)), and their bonded (Δ b ) and nonbonded (Δ nb ) electronic contributions. 1 It was observed that ED between electronegative atoms or total delocalization between nonbonded atoms is not the major contributor to the axial conformational preference observed in spiroketals that could be expected from hyperconjugative models.…”

Eco-Friendly Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones Catalyzed by FeCl3/Al2O3 and Analysis of Large 1 H NMR Diastereotopic Effect

“…Electronic delocalization index DI(A,B), an average number of electrons delocalized between atoms A and B, is an additional information that can be extracted from AIM calculations. 43 Table 5 shows the delocalization index between the oxygen and the analyzed hydrogens. These values are higher when the hydrogen is closer to the carbonyl group, showing that the difference in chemical shifts of protons proR and proS may be attributed to this interaction.…”