The conformation of the hydroxymethyl group

The conformation of the hydroxymethyl group in carbohydrates is best described as an equilibrium between three staggered rotamers. In hexopyranoses and pentofuranoses they are referred to as gt (gauche-trans), gg (gauche-gauche) and tg (trans-gauche). The corresponding torsion angles between the terminal oxygen and the ring oxygen (ω) are +65°, -65° and 180°.

Hydroxymethyl rotamers in hexopyranoses

gauche-trans rotamer	gauche-gauche rotamer	trans-gauche rotamer
ω=+65°	ω=-65°	ω=180°
No unfavourable 1,3-interactions	Unfavourable 1,3-interactions in galacto-compounds	Unfavourable 1,3-interactions in gluco-compounds
Favoured by the gauche-effect	Favoured by the gauche-effect

The common method for determining the relative rotamer populations is to use the proton-proton couplings between H5 and H6_proR and H6_proS in hexoses (or H4 and H5_proR and H5_proS in pentoses). This requires the resonances of the prochiral hydroxymethyl protons to be assigned. In general the H_proR resonance will appear upfield of the H_proS resonance. In derivatives that are acetylated or α-D-glycosylated at the hydroxymethyl group the order of the resonances is reversed.

Newman projection of the hydroxymethyl rotamers in D-hexopyranoses

gauche-trans rotamer	gauche-gauche rotamer	trans-gauche rotamer
³J_H5,H6proR large	³J_H5,H6proR small	³J_H5,H6proR small
³J_H5,H6proS small	³J_H5,H6proS small	³J_H5,H6proS large

In galactose derivatives the chemical shift difference between H6_proR and H6_proS is small which makes both the assignment and the measurement of the coupling constants difficult. Other methods that have been used with varying success include the optical rotation and other coupling constants such as ³J_CH. In general they confirm the results of the analyses based on ³J_HH but are more prone to errors.

The results from the conformational analysis can be summarized as follows:

The most important interaction is that between the O6 oxygen and the substituent at C4 (in hexopyranoses, C3 in pentofuranoses). 1,3-interactions between the terminal oxygen atom and ring substituents, i.e. parallell arrangements of the C6-O6 and C4-O4 bonds, are avoided. Thus, gluco-derivatives have very little tg rotamer and galacto-derivatives little gg-rotamer. This is refered to as the Hassel-Ottar effect (strictly this refers to 1,3 interactions in a six membered ring).
The gauche effect causes the population in the gg and gt rotamers, which have O6 gauche to O5, to be favoured compared to tg. The reason is the unfavourable interaction between the antibonding orbitals of the C5-O5 and C6-O6 bonds in the trans-gauche rotamer.
The anomeric configuration has some influence on the rotamer distribution (and vice versa) but the difference between α and β anomers approaches the accuracy of the conformational analyses. The effect appears to be larger in furanosed than in pyranoses.
The rotamer distribution of the C6-O6 bond can be estimated from the ²J_HH values. Small ²J_HH values suggest an anti arrangement of the C5-C6 and O6-X bonds. Most derivatives seem to have a roughly equal amount of all three rotamers but the trans rotamer becomes favoured if the substituent at O6 is very large, e.g. trityl. There seems to be little, if any correlation with the ω angle.
The reason that galacto-derivatives have smaller ²J_HH values than gluco-derivatives is the small effect of C5-C6 rotamer distribution on the magnitude of this coupling and not the presence of more trans rotamer.