Non-linear effect of modifier composition on enantioselectivity in asymmetric hydrogenation over platinum metals

Prominent non-linear behavior was observed when mixtures of cinchona alkaloids were applied as chiral modifiers in enantioselective hydrogenations over Pt/Al2O3 and Pd/TiO2. The phenomenon is traced to differences in the strength and geometry of alkaloid adsorption on the metal surface. In ethyl pyruvate hydrogenation under close to ambient conditions the weaker adsorbing quinidine (OD) outperformed the generally preferred modifier cinchonidine (CD) and afforded the highest ee (96-98%) at 1 - 5 bar. In the partial hydrogenation of 4-methoxy-6-methyl-2-pyrone to the dihydro derivative 4 CD gave 73% ee to (S)-4 and QD provided 72% cc to (R)-4, and still the alkaloid mixture containing less than 5 mol % CID afforded 15% ee to (S)-4. This nonlinear behavior may be advantageous in asymmetric synthesis as low purity chiral compounds can be applied as efficient modifiers for Pt or Pd.