Stereoselective Formation of Tetrahydrofuran Rings via Intramolecular Alkoxycarbonylation of Hydroxyalkenes

Starting from 5-hydroxy- 1-pentenes, palladium-catalyzed intramolecular alkoxycarbonylation produces 2,5-disubstituted tetrahydrofurans in good yield. In the simplest cases, mixtures of cis- and trans-2,5-substitution are obtained. With a methyl group at C-4, the mixture is 1:1 or 2:1 depending on the relative configuration of the Me. With a methyl or phenyl group at C-3, the selectivity is much higher, producing either cis-2,5- or trans-2,5-disubstituted furans in >9:1 selectivity. In the best case, with a 3-phenyl derivative, the selectivity is >99%. The formation of cis or trans isomers depends on the configuration at C-3 in a predictible way.