syn-Oxidative polycyclizations of hydroxypolyenes: Highly stereoselective and potentially biomimetic syntheses of all-trans-polytetrahydrofurans

Acylperrhenate reagents promote hydroxyl-directed syn-oxidative polycyclizations of primary and secondary hydroxypolyenes, forming bis- and tristetrahydrofuranyl alcohols with excellent trans-stereoselectivity for each tetrahydrofuran ring. The combination of dichloroacetylperrhenate/dichloroacetic anhydride affords stereoselective syn-oxidative bicyclization to bistetrahydrofuranyl alcohol products, whereas trifluoroacetylperrhenate/trifluoroacetic anhydride or trichloroacetylperrhenate/trichloroacetic anhydride are more suitable for stereoselective formation of tristetrahydrofuranyl alcohols from acyclic hydroxytrienes. In the tricyclization reaction chirality induction from a single stereogenic hydroxyl group affords diastereoselective formation of six additional stereocenters in a single step. However, we have found that the growing polytetrahydrofuran chain can exert chelation effects upon the alkoxyrhenium intermediate, thus diminishing the degree of product diastereoselectivity. These syn-oxidative cyclization synthesis strategies mimic a possible pathway for the biosynthesis of many polycyclic ether natural products, including the tristetrahydrofuran acetogenin goniocin (1).