Inversion of enantioselectivity in the 2,2,2-trifluoroacetophenone hydrogenation over Pt-alumina catalyst modified by cinchona alkaloids

The enantioselective hydrogenation of 2,2,2-trifluoroacetophenone (TFAP) was investigated over Pt-cinchonidine (CD) and Pt-cinchona alkaloid derivatives chiral catalysts not yet studied in this reaction, such as Pt-cinchonine (CN), Pt-quinine (QN), Pt-quinidine (QD), Pt-β-isocinchonine (β-ICN), Pt-cinchona-C9-methyl ethers, Pt-hydroquinine- and -hydroquinidine-4-chlorobenzoate. As a result of the studies in toluene, toluene + trifluoroacetic acid, 2-propanol, acetic acid and dichloromethane, relationships were established between the structure and concentrations of the chiral modifiers in different solvents and the reaction rates and enantioselectivities (ee). As compared with the enantioselective hydrogenation of other activated ketones low to medium ee values and low rate enhancements were obtained which is probably due to the structure of the adsorbed intermediate complexes responsible for enantioselection. It has been confirmed by NMR measurements that, under the conditions of the hydrogenations, TFAP is present in the form of H-bonded dimers and oligomers in the liquid phase, which accounts for the low hydrogenation rate. When CN, QD and their C9-ether and ester derivatives were used as modifiers inversion of the sense of the enantioselection was observed, which amounted up to ee 30% over the cinchonine methyl ether and β-ICN modified catalysts. The present study is the first to report inversion of the enantioselectivity over Pt-CN chiral catalyst in the hydrogenation of an activated ketone.

Inversion in the sense of the enantioselectivity was observed in the hydrogenation of 2,2,2-trifluoroacetophenone, when the C8(R)-C9(S) cinchonas (CN, QD, MeOCN, β-ICN) were used in neutral solvents as compared with the reactions in acidic media.Figure optionsDownload as PowerPoint slide