Conformational Free Energies in Pyranoses

The length of the C-O bond in ethers is generally taken as 1.43 whereas the length of an unstrained C C bond is around 1.53 This makes tetrahydro-pyran slightly less puekered than eyelohexane. In eyelohexane chemistry, conformational preferences are discussed in terms of A values for substituents (the free energy dilference between the axial and equatorial chair conformers of a monosubstituted cyclohexane). These A values for cyclohexane carmot be applied directly to tetrahydropyran, even in the absence of an anomeric elfect, not least because they vary with the position of substitution, even with non-polar substituents which do not exert an anomeric elfect (Table 2.1). 

For 2-aryloxysubstituents, which do exert an anomeric elfect, Kirby and Williams combined their own data for cyclohexane with that of Ouedrago and Lessard for aryloxytetrahydropyrans to derive eqn (2.9) for the strength of the anomeric elfect of a 2-phenoxysubstituent  

The existence of a destabilising interaction between gauche vicinal oxygen substituents seems at variance with the results from studies of acyclic sugars, but may be a solvation elfect. 

An example of the power of these instability factors is their prediction that epimerisation of p-o-mannopyranose at C5 to give a-L-gulose will change the conformational preference of the ring from Ci to 4. A closely analogous epimerisation occurs during biosynthesis of alginate (Chapter 4), whose 

Vicinal O-vicinal O (e-e or a-e only, not a-a) Vicinal O-vicinal C (e-a or e-e only, not a-a) Anomeric effect, 01 and 02 equatorial Anomeric effect, 01 equatorial, 02 axial 

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