Intramolecular hydroalkoxylation of syn- and anti-1-R-2-arylhex-4-en-1-ols. Efficient stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans

Abstract

Reactions of syn- and anti-4-(4-bromophenyl)-2-methylnon-1-en-5-ols and 3-(4-bromophenyl)-5- methyl-1-phenylhex-5-en-2-ols with trifluoromethanesulfonic acid and salicylaldehyde derivatives in the presence of Et₂O · BF₃ (Prins reaction) or with salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid stereoselectively afforded tri- and tetrasubstituted tetrahydrofurans with one or two fused heterocycles and various functional groups (COOEt, Br, MeC=CH₂). The reactivity of the synthesized compounds toward thiophen-2-ylboronic acid in the Suzuki reaction was studied, and hydrolysis and reduction (LiAlH₄) of the ester group therein gave the corresponding carboxylic acids and alcohols. One of the obtained tetrahydrofuran derivatives was converted into amide, aldehyde, and aldehyde oxime. Stereochemical configuration of substituents was retained in all chemical transformations.