Rh−DuPHOS-Catalyzed Enantioselective Hydrogenation of Enol Esters. Application to the Synthesis of Highly Enantioenriched α-Hydroxy Esters and 1,2-Diols

Abstract

The asymmetric hydrogenation of α-(acetyloxy)- and α-(benzoyloxy)acrylates 4 catalyzed by cationic rhodium−DuPHOS complexes has been examined. A wide range of substrates ( 4 ) were prepared via a convenient Horner−Emmons condensation protocol, and subsequently hydrogenated under 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 cationic Et−DuPHOS−Rh catalysts with very high levels of enantioselectivity (93−99% ee). Importantly, substrates 4 bearing β-substituents could be employed as E/Z isomeric mixtures with no detrimental effect on the selectivity. Labeling studies indicated that no significant E/Z isomerization of the substrates occurs during the course of these reactions. Details concerning optimization of the reaction, interesting solvent effects, and deprotection procedures for the synthesis of highly enantioenriched α-hydroxy esters and 1,2-diols also are provided.