Asymmetric Catalysis on Cinchonidine-Modified Pt/Al₂O₃: Kinetics and Isotope Effect in the Hydrogenation of Trifluoroacetophenone

Abstract

Kinetics and parametric sensitivity of the asymmetric hydrogenation and deuteration of the trifluoro-activated ketone, 2,2,2-trifluoroacetophenone (TFAP), to (R)-1-phenyl-2,2,2-trifluoroethanol have been studied on an alumina supported Pt catalyst modified by cinchonidine (CD). The observed catalytic behavior is explained by a reaction network consisting of three catalytic cycles which are mutually interconnected: asymmetric hydrogenation of TFAP on CD-modified sites (Pt-CD), asymmetric hydrogenation on Pt-CD sites interfering with the acidic product alcohol Pt-CD-P, and the racemic hydrogenation occurring on unmodified Pt sites. The contributions of these reaction cycles change with progress of TFAP conversion. The catalytic performance is shown to depend strongly on various factors such as the concentrations of ketone and modifier, catalyst amount, solvent, and hydrogen pressure. Depending on reaction conditions, addition of CD can induce considerable rate enhancement (rmodified > runmodifed). Particularly striking is the influence of hydrogen pressure (coverage) on enantioselection, as higher coverage diminishes the ee, which contrasts the corresponding behavior of α-ketoesters. The special role of hydrogen is investigated by substituting H2 by its heavier isotope D2. With the aid of time-resolved attenuated total reflection infrared spectroscopy the kinetic effects of the isotopic substitution along with other reaction parameters are studied and a kinetic isotope effect for unmodified and modified reactions is determined, which suggests that hydrogen is involved in the rate-determining step.