Stereocontrolled synthesis of 2,5-disubstitutedtetrahydrofurans

Abstract

Structurally complex tetrahydrofuranyl derivatives are often found in nature, some of which show a variety of biological activities. One of the most effective approaches to tetrahydrofurans is electrophile-mediated cyclization of $\gamma$-hydroxyalkenes. One of the concerned issues for these reactions is the stereochemistry of newly formed stereogenic centers. Since they are formally a 5-Exo-Trig favored process, a stereogenic center can be introduced to the exocyclic side chain. If the 5-Endo disfavored process of $\beta$-hydroxyalkenes is achieved in a stereocontrolled manner, it can be complementary to the above 5-Exo favored process due to feasible creation of endocyclic stereogenic centers to tetrahydrofurans. In this context we performed iodoetherification of 4-(3 $^\prime$ furanyl)-3-butenol derivatives. The best reaction conditions for anti-2,5-disubstituted tetrahydrofuran were achieved by using iodine(5eq.) with potassium carbonate(2eq.) in diethyl ether at -78$^\circ$C, and the corresponding syn-isomer was obtained when substrate and triethylamine(0.5eq.) in acetonitrile were added dropwise to the solution of iodine(10eq.), potassium carbonate(2eq.) and tbutanol(4eq.) in acetonitrile at 0$^\circ$C.