Stereoselective formation of trans-2,5-disubstituted tetrahydropyrans by intramolecular nucleophilic substitution and a computational study at the AM1 level

The synthesis of 2,5-disubstituted tetrahydropyrans bearing a hydrophobic m oiety at the C5 position from (E)- and (Z)-7-hydroxy-6-substituted 2,3-unsa turated esters by way of intramolecular nucleophilic substitution proceeded with high stereoselectivity. A theoretical study at the AM I level of the cyclization reaction suggested that the reaction is kinetically controlled and that the preferred path for the cyclization reaction proceeds via a tra nsition state in which 1,3-diaxial-like repulsions are minimized to give th e trans product in accordance with experimental results.