Broad Scope Synthesis of Ester Precursors of Nonfunctionalized Chiral Alcohols Based on the Asymmetric Hydrogenation of α,β-Dialkyl-, α,β-Diaryl-, and α-Alkyl-β-aryl-vinyl Esters

The catalytic asymmetric hydrogenation of trisubstituted enol esters using Rh catalysts bearing chiral phosphine-phosphite ligands (P-OP) has been studied. Substrates covered comprise alpha,beta-dialkyl, alpha-alkyl-beta-aryl, and alpha,beta-diarylvinyl esters, the corresponding hydrogenation products being suitable precursors to prepare synthetically relevant chiral nonfunctionalized alcohols. A comparison of reactivity indicates that it decreases in the order: alpha,beta-dialkyl > alpha-alkyl-beta-aryl > alpha,beta-diaryl. Based on the highly modular structure of P-OP ligands employed, catalyst screening identified highly enantioselective catalysts for alpha,beta-dialkyl (9599% ee) and nearly all of alpha-alkyl-beta-aryl substrates (9298% ee), with the exception of alpha-cyclohexyl-beta-phenylvinyl acetate which exhibited a low enantioselectivity (47% ee). Finally, alpha,beta-diarylvinyl substrates showed somewhat lower enantioselectivities (7992% ee). In addition, some of the catalysts provided a high enantioselectivity in the hydrogenation of E/Z mixtures (ca. Z/E = 75:25) of alpha,beta-dialkylvinyl substrates, while a dramatic decrease on enantioselectivity was observed in the case of alpha-methyl-beta-anisylvinyl acetate (Z/E = 58:42). Complementary deuteration reactions are in accord with a highly enantioselective hydrogenation for both olefin isomers in the case of alpha,beta-dialkylvinyl esters. In contrast, deuteration shows a complex behavior for alpha-methyl-beta-anisylvinyl acetate derived from the participation of the E isomer in the reaction.