A novel efficient and stereoselective synthesis of cis- or trans-2,5-disubstituted tetrahydrofurans

A general route to either cis- or trans-2,5-alkyl or aryl disubstituted tetrahydrofurans is described, using the nucleophilic addition of organolithium derivatives to tricyclic lactones, followed by a highly stereocontrolled acid-assisted reduction with sodium cyanoborohydride of the hemiketals formed. The stereoselectivity observed can be rationalized by the preferential approach of the hydride on the less hindered face of an oxonium ion intermediate.