RH-DUPHOS-CATALYZED ENANTIOSELECTIVE HYDROGENATION OF ENOL ESTERS - APPLICATION TO THE SYNTHESIS OF HIGHLY ENANTIOENRICHED ALPHA-HYDROXY ESTERS AND 1,2-DIOLS

The asymmetric hydrogenation of alpha-(acetyloxy)-and alpha-(benzoylox y)acrylates 4 catalyzed by cationic rhodium-DuPHOS complexes has been examined. A wide range of substrates (4) were prepared via a convenien t Horner-Emmons condensation protocol, and subsequently hydrogenated u nder mild conditions (60 psi of H-2) at substrate-to-catalyst ratios ( S/C) of 500. Overall, enol ester substrates 4 were reduced by the cati onic Et-DuPHOS-Rh catalysts with very high levels of enantioselectivit y (93-99% ee). Importantly, substrates 4 bearing beta-substituents cou ld be employed as E/Z isomeric mixtures with no detrimental effect on the selectivity. Labeling studies indicated that no significant E/Z is omerization of the substrates occurs during; the course of these react ions. Details concerning optimization of the reaction, interesting sol vent effects, and deprotection procedures for the synthesis of highly enantioenriched alpha-hydroxy esters and 1,2-diols also are provided.