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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


Félix León, Pedro J. González-Liste, Sergio E. García-Garrido, Inmaculada Arribas, Miguel Rubio, Victorio Cadierno, and Antonio Pizzano. The Journal of Organic Chemistry 2017, Vol. 82, 5852-5867

The catalytic asymmetric hydrogenation of trisubstituted enol esters using Rh catalysts bearing chiral phosphinephosphite ligands (P-OP) has been studied. Substrates covered comprise α,β-dialkyl, α-alkyl-β-aryl, and α,β-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: α,β-dialkyl > α-alkyl-β-aryl > α,β-diaryl. Based on the highly modular structure of P-OP ligands employed, catalyst screening identified highly enantioselective catalysts for α,β-dialkyl (95−99% ee) and nearly all of α-alkyl-β-aryl substrates (92−98% ee), with the exception of α- cyclohexyl-β-phenylvinyl acetate which exhibited a low enantioselectivity (47% ee). Finally, α,β-diarylvinyl substrates showed somewhat lower enantioselectivities (79−92% ee). In addition, some of the catalysts provided a high enantioselectivity in the hydrogenation of E/Z mixtures (ca. Z/E= 75:25) of α,β-dialkylvinyl substrates, while a dramatic decrease on enantioselectivity was observed in the case of α-methyl-β-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 α,β-dialkylvinyl esters. In contrast, deuteration shows a complex behavior for α-methyl-β-anisylvinyl acetate derived from the participation of the E isomer in the reaction.