Chemoselectivity Control in the Asymmetric Hydrogenation of γ- and δ-Keto Esters into Hydroxy Esters or Diols.

Abstract

The asymmetric hydrogenation of aromatic γ- and δ-keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3-AMIQ-RuII complex was studied. Under the optimized conditions (8 atm H2 , Ru complex/t-C4 H9 OK=1:3.5, 25 °C) the γ- and δ-hydroxy esters (including γ-lactones) were obtained quantitatively with 97-99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2 , [t-C4 H9 OK]=50 mm, 40 °C), the 1,4- and 1,5-diols were obtained predominantly with 95-99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of β- and ϵ-keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ-ϵ-diketo diester into a trihydroxy ester.