Synthesis of Polysubstituted Tetrahydropyrans by Stereoselective Hydroalkoxylation of Silyl Alkenols: En Route to Tetrahydropyranyl Marine Analogues

Tetrahydropyrans are abundantly found in marine natural products. The interesting biological properties of these compounds and their analogues make necessary the development of convenient procedures for their synthesis. In this paper, an atom economy access to tetrahydropyrans by intramolecular acid-mediated cyclization of silylated alkenols is described. p-TsOH has shown to be an efficient reagent to yield highly substituted tetrahydropyrans. Moreover, excellent diastereoselectivities are obtained both for unsubstituted and alkylsubstituted vinylsilyl alcohols. The methodology herein developed may potentially be applied to the synthesis of marine drugs derivatives.