Heterogeneous Enantioselective Hydrogenation in a Continuous-flow Fixed-bed Reactor System: Hydrogenation of Activated Ketones and Their Binary Mixtures on Pt–Alumina–Cinchona Alkaloid Catalysts

Abstract

Under the experimental conditions of the Orito reaction the individual hydrogenation and the competitive hydrogenations of three binary mixtures of methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on platinum–alumina catalysts modified by cinchonidine, cinchonine, quinine and quinidine (Pt–CD, Pt–CN, Pt–QN, Pt–QD) were studied for the first time using continuous-flow fixed-bed reactor system. Conversions of chiral (C_c) and racemic (C_r) hydrogenations of all three compounds and enantioselectivities (ee) were determined under the same experimental conditions (under 4 MPa H₂ pressure, at room temperature using toluene/AcOH 9/1 as solvent).The order of the rates of the enantioselective hydrogenations of the three substrates studied is MBF > PA > DAP, and the order of their ee values is MBF ~ PA > DAP. The hydrogenation rate and the effect of rate on ee depend on the structure of the cinchona used: hydrogenation of MBF and PA may produce ee values over 90 %, however, the ee values were conspicuously low in the presence of Pt–QN and especially of Pt–QD catalysts. In the chiral hydrogenation of DAP considering racemic hydrogenation rate decrease (C_c/C_r < 1) takes place instead of rate enhancement over all four catalysts. The new experimental data supported the so far known fundamental rules of the Orito reaction based on batch studies.

Graphical Abstract