Heterogeneous Enantioselective Hydrogenation of Vicinal Diketones

Abstract

Hydrogenation of seven prochiral vicinal diketones over heterogeneous cinchona alkaloid modified Pt catalyst is reviewed. Cinchona alkaloids induce enantioselectivity among product hydroxyketones and diols. Effect of modifier structure, reaction parameters (concentration, solvent, hydrogen pressure, temperature) and transient operation is reported. Presence of two reactive carbonyl groups complicate reaction scheme and increase number of possible reactant-modifier diastereomeric complexes. Both regio- and diastereoselctivity aspects are involved. For maximum enantiomeric excess (ee) relatively high molar modifier-to-surface Pt ratios (2–3:1) are required. Non-polar solvents give high ee while acetic acid has a negative effect on the ee. Modifier structure-selectivity correlations are quite specific. Presence of C9–OH group is important to achieve high ee. The highest ee has been obtained with 11-(triethylsilyl)-10,11-dihydrocinchonidine modifier giving 70 % ee at 50 % 1-phenyl-1,2-propanedione (A) conversion. Parameters and structural aspects that result in optimal enantioselectivity are reviewed. The highest ever reported ee = 77 % (at maximum yield of 66 %) in the hydrogenation of A was obtained applying transient operation in continuous fixed bed reactor.