Conformational control, medium-sized

Scheme 10.3 Free radical retrosynthetic disassembly of bond d in 7. Advantages it does not necessitate the construction of a functionalised medium-sized ring. It forms the bicyclooctane ring system by a favourable 5-exo-trig pathway. Conformational and steric bias will allow the stereochemistry of the methyl a to the ketone to be controlled.

It has also been found that in medium-sized (8- to 12-membered) lactones containing a single chiral center at a remote position, highly stereoselective formation of a new chiral center adjacent to the carbonyl group occur (equation 79). This effect falls off as the distance between the enolate and the controlling asymmetric center increases561. Such stereocontrol is caused by the conformational properties of the particular lactone being alkylated. 

Also, it was demonstrated that acyclic radicals can react with high stereoselectivity [45]. In order for the reactions to be stereoselective, the radicals have to adopt preferred conformations where the two faces of the prochiral radical centers are shielded to different extents by the stereogenic centers. Giese and coworkers [49] demonstrated with the help of Electron Spin Resonance studies that ester-substituted radicals with stereogenic centers in (3-positions adopt preferred conformations that minimize allylic strain [49] (shown below). In these conformations, large (L) and medium sized substituents (M) shield the two faces. The attacks come preferentially from the less shielded sides of the radicals. Stereoselectivity, because of A-strain conformation, is not limited to ester-substituted radicals [50]. The strains and steric control in reactions of radicals with alkenes can be illustrated as follows [50] ... 

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