Stereoselective synthesis of tri- and tetrasubstituted tetrahydropyrans from syn- and anti-1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols and some chemical transformations of the products

Abstract

Tri- and tetrasubstituted tetrahydropyranes fused to one and two heterocycles with various functional groups (COOEt, Br, MeC=CH2) were synthesized in stereoselective fashion by reactions of syn- and anti-1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols (R = Bu, PhCH2) with trifluoromethanesulfonic acid, aldehydes in the presence of boron trifluoride–diethyl ether complex (Prins reaction), and salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid. The obtained compounds were brought into Suzuki coupling with thiofen-2-ylboronic acid, hydrolysis, and reduction of the ester group with lithium tetrahydridoaluminate. The resulting carboxylic acid was converted to carboxamide, and the alcohol was oxidized to aldehyde which was converted to oxime. The steric configuration of substituents remained unchanged in all chemical transformations.