Medium ring stereocontrol in the functionalisation of eight-membered lactones

Medium ring lactones with up to three substituents have been prepared as single diastereoisomers via Claisen rearrangement. Application of medium ring stereocontrol to a γ,δ-unsaturated eight-membered ring lactone prepared by this route enabled the overall diastereoselective functionalisation of all but one of the ring positions. A comparison of the ring-induced selectivity was made with that of the corresponding acyclic hydroxy ester which exhibited an overall reversal of stereoselectivity. This methodology provides access to highly substituted polyketide fragments.