Dynamic stereoelectronics

Anomeric effects increase as interacting antibending orbitais are transformed into nonbonding orbitais 

State structural distortion and the dominant force of TS stereoelectronic stabilization coincide, trends in the ground state geometry correctly predict the observed reaction product. 

The ground state distortion effects can be subtle and often require a computational analysis to reveal themselves. Although such effects are useful for a posteriori analysis and rationalization of results, their predictive power can be limited. 

Deactivate an electronic effect that stabilizes an unproductive conformation = remove stereoelectronic penalty for reaching the productive TS 

The following sections will discuss examples of such effects. They can involve either appearance/straigthening or disappearance/weakening of a stereoelectronic interaction in the course of a reaction. Both approaches can be useful for the control of reactivity and selectivity. A particularly elegant implementadon of this strategy involves deactivation or activation of precisely chosen electronic interactions that are directly associated with the taigeted reaction. 

---

Summary The collection of examples and concepts provided in this chapter illustrates that timing of stereo-electronic interaction determines their effects on reactivity. Delocalizing interactions can be counterproductive when they fade out of existence along the reaction path or productive/accelerating when they are amplified in the transition state. In the following sections, we will provide further examples of dynamic stereoelectronic interplay between structure and reactivity in a variety of chemical areas. 

Stereoelectronic factors are also important in the conformational dynamics of acyclic acetals [6] (Cosse-Barbi and Dubois, 1986). Here the usual preference for staggered conformations is supplemented by the anomeric effect (Kirby, 1983), which favours the gauche stereochemistry ( = 60°) about both central C-O bonds, mainly because this allows optimal n-rr overlap between an oxygen lone pair and the antibonding (cr ) orbital of the C-0 bond. Thus the pathway for conformational isomerization suggested by... 

C. B. Post and M. Karplus, Does lysozyme follow die lysozyme pathway An alternative based on dynamics, structural, and stereoelectronic considerations, J. Am. Chem. Soc., 108 (1986) 1317—1319. 

Stability and reactivity of crown-ether complexes, 17, 279 Stereochemistry, static and dynamic, of alkyl and analogous groups, 25, 1 Stereoelectronic control, the principle of least nuclear motion and the theory of, 24, 113 Stereoselection in elementary steps of organic reactions, 6, 185 Steric isotope effects, experiments on the nature of, 10, 1... 

Mekenyan, O.G., Ivanov, J.M., Veith, G.D., and Bradbury, S.P., DYNAMIC QSAR a search for active conformations and significant stereoelectronic indices, Quant. Struct.-Act. Relat., 13, 302-307, 1994. 

Furthermore, the availability of effective discrete/continuum solvent models and of different dynamical approaches, together with the N07D basis set, allow to perform comprehensive analyses aimed at evaluating the roles of stereoelectronic, vibrational,... 

Post, C. B. and Karplus, M. (1986) Does Lysozyme Follow the Lysozyme Pathway An Alternative Based on Dynamic, Structural, and Stereoelectronic Considerations, J. Am. Chem. Soc. 108, 1317-1319. 

The fluorescence quenching dynamics of excited state electron donors by various pyrimidine and 5,6-dihydropyrimidine substrates have been examined and found to obey the Rehm-Weller relationship." In addition, an unexpected difference was observed between the reduction potentials for the trans-syn and cis-syn diastereoisomers of dimethylthymine cyclobutane dimers, and this has been ascribed to a stereoelectronic effect in the cis-syn dimer anion radical resulting from an unfavourable charge-dipole interaction between the added electron and the O carbonyl group of the pyrimidine ring... 

The reactivity of six-membered systems is problematical, since ring strain is no longer a dominant feature. A complex balance of forces may pertain in addition to those considered by Westheimer s guidelines. Steric, stereoelectronic, electrostatic, solvation and other effects may dominate the dynamics of six-membered TBP intermediates. However, it is probable that the conformation of the six-membered ring itself plays a major role in determining the balance of these effects and hence reactivity. 

Stereochemistry, static and dynamic, of alkyl and analogous groups, 25, 1 Stereoelectronic control, the principle of... 

It has been argued above that a threefold symmetrical chiral podand may simplify the stereochemistry of key catalytic intermediates for cases in which it only acts as bidentate ligand in the stereoselectivity-determining step in other words, for metal complexes with a stereoelectronic preference for non-deltahedral coordination geometries. Palladium(ll)-catalyzed allylic substitutions provide appropriate test reactions alongthese lines [27], and it was possible to study the dynamic exchange in model systems for both the Pd" and Pd intermediates of this catalytic reaction. 

E. Juaristi, in Conformational Behavior of Six-membered Rings Analysis, Dynamics, and Stereoelectronic Effects", VCH Publishers, New York, 1995. 

---