Simple designs for the construction of complex trans-fused polyether toxin frameworks. A convergent strategy based on hydroxy ketone cyclization of C-linked oxacycles

Abstract

A single, unified convergent strategy for the stereocontrolled synthesis of trans-fused polyethers was developed. It was demonstrated that the epimerization and reductive intramolecular coupling of hydroxy ketones in reactions with silane−Lewis acids (SI−LA) to generate ethers in C-linked oxacycles is affected by its conformational preference in a predictable manner. The obtained results make evident that the influence of hydrogen bonding between a hemiketal hydroxyl and a 1,3-diaxial C−O bond is regular and predictable and that convergent synthesis of trans-fused polyethers may confidently be conducted on driving ring closure to oxane rings under thermodynamic conditions