Stereochemistry lactol formation

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

Fig. 9.5. Stereochemistry of the formation of d-valerolactol (neat, at 38°C < 5% of the free hydroxyaldehyde is present). The top formulas represent the 78 22 mixture of the two chair conformers of one lactol enantiomer, whereas the bottom formulas represent the 78 22 mixture of the two chair conformers of the other lactol enantiomer.

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