Stereoelectronic model

To explain tlie stereodieniistiy of tlie allylic substitution reaction, a simple stereoelectronic model based on frontier molecular orbital considerations bas been proposed fl55. Fig. G.2). Organocopper reagents, unlike C-nudeopbiles, possess filled d-orbitals fd - configuration), wbidi can interact botli witli tlie 7t -fC=C) orbital at tlie y-carbon and to a minor extent witli tlie cr -fC X) orbital, as depicted... 

This work and related studies provided the basis for the stereoelectronic model for homobenzylic ether cleavage in Fig. 3.1. This model includes overlap of the benzylic carbon-carbon bond with the SOMO of the aromatic ring (structure 13), thereby stabilizing the benzylic radical upon cleavage. Additionally, overlap of a heteroatom lone pair and the benzylic o orbital was shown to be necessary for cleavage (structure 14). 

Woerpel et al. [65, 99-101] conducted studies of the reactions of the five-membered ring oxocarbenium ions and postulated a stereoelectronic model to... 

Woerpel and Smith [101] assumed that the sulfur substituents might not participate in the chelated transition structure but would instead influence the conformational preference of the oxocarbenium ion intermediate. According to that hypothesis and the stereoelectronic model [101, 102], contrasteric 1,4-c/s product 84 would arise from inside attack of the nucleophile to the lower energy diequatorial oxocarbenium ion 85 (Fig. 4.30). This reaction pathway would provide a lower energy transition structure relative to inside attack of the nucleophile on the diaxial conformer 86 (vide infra) [84, 107] (Figs. 4.30 and 4.31). 

Larsen CH, Ridgway BH, Shaw JT, Woerpel KA (1999) A stereoelectronic model to explain the highly stereoselective reactions of nucleophiles with five-membered-ring oxocarbenium ions. J Am Chem Soc 121 12208-12209... 

Formation and reactivity of o-benzynes o-benzynes serve as illustrative stereoelectronic models due to two features a) structural rigidity that restricts orbital interactions exclusively to syn-periplanar geometries and b) distortion of the in-plane x-system. These features are translated in the interplay of two related stabilizing effects controlling the structure of substituted benzynes and their reactivity towards nucleophiles 1) interaction of o-acceptors with bent bonds and 2) interaction of o-acceptors with anionic centers. 

Figure 11.63 Stereoelectronic model for the [Fe] hydrogenase-catalyzed reduction of H MPT to H MPT.

Although the effects of anti- lone pairs and x-systems seem to be consistent with stereoelectronic models, the trends with other geometries are not always clear cut. For example, the syn-vicinal lone pair of pyridine imposes an apparent increase in the magnitude of C-C coupling constant at the ortho carbon. It would be interesting to analyze stereoelectronic contributions of a the relative contributions of the syn-anomeric and homoanomeric n o trend (Figure 12.52). ... 

Scheme 1 Stereoelectronic model for tetrahydrofiiran synthesis from oxoearbenium ion addition by Woerpel et al. [6]...

The high regioselectivity ( stereoelectronic control ) in the ring cleavage by chlorination of sulfur was anticipated. It had been found before that in corresponding bicyclic systems such as in the scheme below oxidation of the sulfur atom always led to the undesired cleavage of the S—Cg bond. This was rationalized through the observation on molecular models that... 

Addition of trimethylaluminum to norcamphor (3), regardless of the stoichiometry of the reactants, leads to a mixture of the diastereomeric alcohols in a ratio of 95 5 also in favor of the erafo-alcohol6. Examination of the norcamphor model indicates that endo attack is sterical-ly more hindered than exo attack. However, steric interaction may not fully account for the exceptionally high exo selectivity. On the other hand, no severe torsional strain is involved if the nucleophile approaches the carbonyl group from the exo side, however, a nucleophile approaching from the endo side encounters torsional strain between the incipient bond and the C-l to C-6 carbon-carbon bond. Thus, in the case of norcamphor, steric and stereoelectronic factors reinforce each other, resulting in a strong directional influence for exo attack. 

It is gratifying that the same model holds for the conformationally more flexible cyclohep-tenones. Again, the 4-methyl-2-cycloheptenone led preferentially to the s-compound in the (2-propenyl)siIane addition, based on stereoelectronic grounds. 

Acyclic Ketones. The stereochemistry of the reduction of acyclic aldehydes and ketones is a function of the substitution on the adjacent carbon atom and can be predicted on the basis of the Felkin conformational model of the TS,63 which is based on a combination of steric and stereoelectronic effects. 

FIGURE 7.13 Molecular model of the pyrrolo [ 1,2-<2] i ndol e showing the site of nucleophile attack that provides a favorable stereoelectronic effect. The inset shows expected orbital interactions. 

Deeth RJ (2001) The ligand field molecular mechanics model and the stereoelectronic effects of d and s electrons. Coord Chem Rev 212 11... 

Quantitative Structure-Activity Relationship models are used increasingly in chemical data mining and combinatorial library design [5, 6]. For example, three-dimensional (3-D) stereoelectronic pharmacophore based on QSAR modeling was used recently to search the National Cancer Institute Repository of Small Molecules [7] to find new leads for inhibiting HIV type 1 reverse transcriptase at the nonnucleoside binding site [8]. A descriptor pharmacophore concept was introduced by us recently [9] on the basis of variable selection QSAR the descriptor pharmacophore is defined as a subset of... 

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