Exterior Frontier Orbital Extension Model Research Articles

The Danishefsky pyranone puzzle: an explanation based on the exterior frontier orbital extension model

The unusual facial stereoselection in the hydride reduction of the Danishefsky pyranones (2,3,5,6-tetrahydro-4-pyranones) with L-Selectride (Li- sec-Bu 3BH) has been explained based on the exterior frontier orbital extension model (the EFOE model).

Theoretical study of solvent effect on diastereoselectivity in protonation of methyl 3-fluorobutanoate anion by ethanol: Application of the 3D-RISM theory

The H/D exchange reaction of carbonyl compounds is one of the most important reactions in synthetic organic chemistry as well as in biochemistry. In the present study, 3D-RISM theoretical model has been used to examine the high diastereoselectivity and the solvent effects in the protonation of methyl 3-fluorobutanoate anion by ethanol. The 3D-RISM analysis along the IRC coordinates clearly suggested that not only solvent molecules stabilize the reaction system throughout the entire reaction process, but also the stabilization mechanism operates so as to minimize the energy difference between the two diastereofacial processes. The energy difference between the two diastereofacial processes in the ground state carries directly through the transition state. This strongly suggested that diastereoselectivity of the protonation reaction should be determined essentially in the ground state. Confirmative evidence for this conclusion was obtained by the EFOE (exterior frontier orbital extension model) model.

Stereoelectronic and conformational effects on the stereochemical course of reduction of bicyclo[3.3.1]nonane 1,3-diketones

The stereoselectivity of the reduction of bicyclo[3.3.1]nonane 1,3-diketones was studied. The experimental data of π-facial stereoselection of the reduction of the carbonyl group were successfully rationalized by the application of the exterior frontier orbital extension (EFOE) model. The observed facial diastereoselectivity of the carbonyl reduction of bicyclo[3.3.1]nonane diketones could be reasonably explained by the ground-state facial anisotropy of the frontier orbital extension, steric effects, and the intrinsic reactivity of carbonyl groups. Although the EFOE density and PDAS values predicted the enhanced reactivity at the C-2 carbonyl compared to C-9 carbonyl, transition-state calculations at the B3LYP/6-31+G(d,p) level showed that the reactivity of C-9 and C-2 in a hydride addition to both carbonyl groups should be nearly the same. The EFOE analysis also strongly indicated that in the second hydride reduction step the corresponding oxobicyclononanolates are most likely to be involved in the reduction as the major species rather than the free hydroxyketones. The antiperiplanar effects in the transition states of the LiAlH4 reduction as measured by both the elongation and the natural bond population of the antiperiplanar bonds clearly indicated they should not be an essential factor of the facial diastereoselection of studied diketones.Key words: bicyclo[3.3.1]nonanedione, EFOE model, reduction, stereoselectivity, transition state.

π‐facial diastereoselection of hydride reduction of 1,3‐diheteran‐5‐ones: application of the exterior frontier orbital extension model

AbstractTo obtain further evidence for the importance of the ground state conformational and orbital properties in π‐facial diastereoselection of 1,3‐diheteran‐5‐ones (heteroatom = O, S, Se), 2‐phenyl‐1,3‐diselenan‐5‐one (3a) has been synthesized, and its π‐facial diastereoselection upon hydride reduction has been examined. The experimental data of π‐facial stereoselection of 3a has been successfully rationalized by the exterior frontier orbital extension model (the EFOE model). Intrinsic reaction coordinate (IRC) and natural bond orbital (NBO) analyses of transition states of LiAlH4 reduction of this ketone have strongly indicated that the transition state effects (the torsional strain of the carbonyl moieties and the antiperiplanar effects involving the incipient bond proposed by the conventional theoretical models for π‐facial diastereoselection; the Felkin‐Anh model and the Cieplak model) are not responsible for facial selection. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:358–368, 2001

Reversal of π-facial diastereoselection in the hydride reduction of selenanones. Further application of the exterior frontier orbital extension model

Reversal of π-facial diastereoselection in the hydride reduction of 2-phenyl-4-selenanone ( 1b) and 6-phenyl-3-selenanone ( 2b) has been rationalized by the exterior frontier orbital extension model (EFOE model).

Origin of p-Facial Diastereoselection in Carbonyl Addition. Application of the Exterior Frontier Orbital Extension Model to 1,3-Diheteran-5-ones (Heteroatom = O, S)

Origin of p-Facial Diastereoselection in Carbonyl Addition. Application of the Exterior Frontier Orbital Extension Model to 1,3-Diheteran-5-ones (Heteroatom = O, S)

Origin of π-Facial Diastereoselection in Nucleophilic Addition to 1,3-Diheteran-5-ones (Heteroatom = O, S). Theoretical Evidence for the Importance of Ground-State Effects

Abstract The exterior frontier orbital extension model (the EFOE Model) strongly suggested that reversal of π-facial diastereoselection in nucleophilic additions of 1,3-diheteran-5-ones (heteroatom = O or S) may originate from the unique ground-state conformation and the π-facial difference in the LUMO extension around the carbonyl carbon rather than from transition state effects.

Origin of π-Facial Diastereoselection in Hydride Reduction of Piperidones. The Importance of Ground-State Effects

Abstract The exterior frontier orbital extension model (the EFOE Model) strongly suggested that the ground-state conformation (steric effects) and the anisotropic frontier orbital (LUMO) extension over π-faces may be the origin of the π-facial diastereoselection in hydride reductions of substituted piperidones.

Origin of pi-Facial Stereoselectivity in Nucleophilic Additions. Application of the Exterior Frontier Orbital Extension Model to Imines and Iminium Ions.

The experimental data of pi-facial stereoselection of the imines and the iminium ions of cyclohexanone, tropinone, and adamantan-2-ones have been explained by the exterior frontier orbital extension model (EFOE model) previously proposed. In all cases, facial difference in the pi-plane-divided accessible space (PDAS), which represents simple summation of the pi-plane-divided exterior three-dimensional space nearest to the reaction center outside the van der Waals surface, significantly depends on the structure of the imino moieties. In particular the formation of iminium salt significantly affects the magnitude of both the EFOE density and the PDAS values.

Origin of π-Facial Stereoselectivity in Nucleophilic Addition. Application of the Exterior Frontier Orbital Extension Model to Substituted Bicyclo[2.2.1]heptan-7-ones

Abstract The exterior frontier orbital extension model (EFOE model) has shown that π-facial stereoselection in nucleophilic additions of 2,3-endo,endo-disubstituted bicyclo[2.2.1]heptan-7-ones (1) is dictated by the three terms of the Salem-Klopman equation – steric effect, electrostatic interaction and orbital interaction.

Origin of π-facial stereoselection in nucleophilic additions of adamantanones. A new interpretation based on the exterior frontier orbital extension model

The experimental data of π-facial stereoselection of 5-substituted adamantan-2-ones, 5-aza-adamantan-2-ones, and nor- and homo-adamantanones have been successfully rationalized by the exterior frontier orbital extension model (EFOE model). The values of π-plane-divided accessible space (PDAS), which represents simple summation of the π-plane-divided exterior three-dimensional space nearest to the reaction center outside the van der Waals surface, showed that the adamantanone system is sterically biased and sterically much more demanding than cyclohexanone. The PDAS values indicated that in most cases steric effects are responsible for π-facial stereoselection except for a series of 5-aryladamantan-2-ones, the facial stereoselection of which was found to be orbital-controlled. In most cases, the facial differences in the frontier orbital (LUMO) extension as quantified by the EFOE density were marginal, but were consistent with experimental stereoselectivity except for a few cases with electron-withdrawing substituents. The structures of the transition states of a few 5-substituted adamantan-2-ones with LiAlH4 (B3LYP/6−31+G(d)) have shown that (1) hyperconjugative anti-periplanar stabilization effects involving an incipient bond (AP effects) are much larger in adamantan-2-one than in cyclohexanone, in spite of enhanced reactivity with hydride of the latter, (2) the facial differences of AP effects are marginal and (3) they often operate against observed stereoselectivity.

Origin of π-facial stereoselectivity of nucleophilic addition to carbonyl compounds. Application of the exterior frontier orbital extension model to cyclohexanones with polar substituent

The application of the exterior frontier orbital extension model (EFOE model) to π-facial stereoselection of cyclohexanones with a polar substituent at C3 or C4 have been described. The theoretical prediction that a linear correlation should exist between the π-facial ( axial and equatorial) difference in the square of the EFOE densities ( λ = EFOE( ax) 2 − EFOE( eq) 2) and experimentally obtained facial selectivity (ln( ax/eq)) has been demonstrated for 5-substituted 2-decalones ( 1), 4-substituted cyclohexanones ( 2) and 3-substituted cyclohexanones ( 3). In addition, facial stereoselection of 3, where the substituent is located closer to the reaction center compared with those of 1 or 2, showed remarkable dependence on steric effects evaluated by the π-plane-divided accessible space (PDAS), another important quantity of the EFOE model, which represents simple summation of the π-plane-divided exterior three-dimensional space nearest to the reaction center outside the van der Waals surface of the substrate.