Synthesis of 2,2,5-Trisubstituted Tetrahydrofurans by Ferrocenium-Catalyzed Dehydrative Diol Cyclization Reactions

Abstract

A ferrocenium-catalyzed synthesis of trisubstituted tetrahydrofurans by dehydrative cyclization of diols is reported. Treatment of γ-phenyl-γ-butyrolactone or valerolactone with 2–3 equivalents of MeLi, n-BuLi, or PhLi yielded the corresponding substituted 1,4-butanediols in 41–86% yields. Subsequent dehydrative cyclization of the diols under non-inert conditions using catalytic ferrocenium tetrafluoroborate (10 mol%) produced trisubstituted tetrahydrofurans in 72–83% yields after 48–72 h at 45–70 °C in CH2Cl2. This study demonstrates ferrocenium-catalyzed dehydrative cyclization for the first time, offering a convenient route to substituted tetrahydrofurans in two steps from commercial or easily accessible starting materials.

Keywords

• diol cyclizations
• trisubstituted tetrahydrofurans
• iron catalysis
• ferrocenium catalysis