Stereoelectronic effects

As mentioned previously, radicals with electron-withdrawing or electron-donating substituents can be stabilized by interaction of the singly occupied orbital with an n-, n- or a-orbital. For effective stabilization, the interacting orbitals must overlay efficiently and this will depend on their geometry or position in space. Similarly, for a radical to react, the singly occupied orbital must be able to overlap with either another of its own orbitals (for intramolecular reactions) or another radical or non-radical orbital in a different molecule. For reaction of a radical with the different molecule, there is often no restriction on the orbital geometries and they can rotate freely so as to combine with the maximum overlap. 

Intermolecular linear interaction Intermolecular approximately linear interaction 

Intramolecular addition to an alkene, through a chair like transition state 

Radical fragmentation reactions are also stereoelectronically controlled. For the (3-elimination or fragmentation of carbon-carbon centred radicals, the 

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Figure 3-6. a) The charge distribution, b) the inductive effect, and c) the resonance effect, d) the polarizability effect, e) the steric effect, and f) the stereoelectronic effect,... 

Some reactions require the bonds being broken or made in a reaction to be aligned with other parts ti- or free electrons) of a molecule. These requirements are called stereoelectronic effects. Figure 3-6f shows that the bromide ion has to open a bro-monium ion by an anti attack in order that the new bond is formed concomitantly with the breaking of one bond of the three-membered ring. 

Effects that arise because one spatial arrangement of electrons (or orbitals or bonds) IS more stable than another are called stereoelectronic effects There is a stereoelec tromc preference for the anti coplanar arrangement of proton and leaving group in E2 reactions Although coplanarity of the p orbitals is the best geometry for the E2 process modest deviations from this ideal can be tolerated In such cases the terms used are syn periplanar and anti periplanar... 

A spectacular example of selective deliydiogenation in the steroid ring system (42) has been attributed to stereoelectronic effects (31) the yield is 80%. Several related steroids also show this chemistry. An extensive review containing many additional examples and a mechanistic discussion is available (23). 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

Another example of a stereoelectronic effect is observed in amines. Amines in which a C—H bond is oriented antiperiplanar to the nitrogen lone pair show a shift in the C—H bond stretching frequency that corresponds to a weakening of the bond by about... 

The more stable the LUMO, the stronger is the interaction with the HOMO of the approaching nucleophile. The observed (Cram s rule) stereoselectivity is then a combination of stereoelectronic effects ftiat establish a preference for a perpendicular substituent and a steric effect that establishes a preference for the nucleophile to approach from the direction occupied by the smallest substituent. 

A. J. Kirby, Stereoelectronic Effects, Oxford University Press, Oxford, U.K., 1996. 

A. J. Kirby, The Anomeric Effect and Related Stereoelectronic Effects at Oxygen, Springer-Verlag, New %rk, 1983. 

The substituent effects in aromatic electrophilic substitution are dominated by resonance effects. In other systems, stereoelectronic effects or steric effects might be more important. Whatever the nature of the substituent effects, the Hammond postulate insists diat structural discussion of transition states in terms of reactants, intermediates, or products is valid only when their structures and energies are similar. 

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