Keele Research Repository

A number of stereoselective syntheses have been investigated employing the ability of a furanyl ether chiral centre to epimerise under acidic conditions, therefore allowing the more stable diastereoisomer to preferentially form under thermodynamic control. As the furanyl group is able to undergo a number of synthetically useful transformations (e.g. Diels-Alder reactions, hydrogenations, oxidative cleavage, Achmatowicz oxidation, etc.) these syntheses represent a highly useful pathway to important moieties in a number of biologically active and pharmaceutically interesting molecules.

Previous work within the group has investigated utilising the acid-catalysed epimerisation of furanyl ether chiral centres on conformationally well-defined scaffolds. This has been demonstrated in the synthesis of 2,6-disubstituted tetrahydropyrans, 2,6-disubstituted piperidines and also in spiroketals. In all cases high levels of stereocontrol were observed.

Attention was focused on the stereoselective synthesis of 2,4-disubstituted and 2,4,5-trisubstituted tetrahydropyrans starting from ‘stereorandom’ precursors. In all cases high levels of stereocontrol were observed, going from an approximately 1:1 diastereomeric mixture of the corresponding diol or triol to ratios exceeding 10:1 in the case of the disubstituted tetrahydropyrans and to ratios exceeding 15:1:0.9:0 in the case of the trisubstituted tetrahydropyrans. This is due to the rapid
epimerisation of the furanyl chiral centre allowing the substituents to adopt the thermodynamically favoured equatorial position on a chair conformation.