Stereodivergent synthesis of highly substituted tetrahydropyrans

Intramolecular oxa-conjugate addition has been employed in a stereoselectiv e synthesis of enantiopure polyalkyl-substituted tetrahydropyrans, which ar e frequently found as substructures in many natural products. The requisite cyclization precursors, 7-hydroxy-2-enimides 3 and 7-hydroxy-2-enoates 6 w ere easily accessible by silyloxy Cope rearrangements of the appropriate ch iral syn-aldols. It was found that the stereoselectivity of the cyclization could be controlled by judicious choice of the carboxylic acid derivative, resulting in a kinetically controlled reaction for the imides and a thermo dynamically controlled process for the esters. Mechanistic considerations t hat could account for the stereocontrol of the process are outlined.