Heterogeneous enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona-modified Pt catalysts: Effect of modifier structure

The effect of the structure of chiral modifiers derived from natural cincho na alkaloids on the enantioselectivity and rate of the Pt/Al2O3-catalyzed h ydrogenation of ethyl pyruvate was investigated. The influence of the follo wing structural elements was studied: the cinchonidine versus the cinchonin e backbone; effect of the nature and the size of substituents attached to C -9; effect of partial hydrogenation of the quinoline ring; effects of chang es of the substituent at the quinuclidine moiety. The strongest effects on ee and somewhat less on rate were observed for changes in the O-C-9-C-8-N p art of the cinchona alkaloid and for partial or total hydrogenation of the quinoline rings. The nature of the substituents in the quinuclidine part ha d a comparably minor influence. The solvent was found to have a significant effect on enantioselectivity and rate. In acetic acid, the best results we re obtained with O-methyl-10,11-diydroeinchonidine tee's up to 93%), wherea s dihydrocinchonidine was the most effective modifier in toluene. In agreem ent with a basic model proposed by Pfaltz, it was concluded that the minima l requirements for an efficient modifier for the hydrogenation of a-keto es ters is the presence of a basic nitrogen:center close to one or more stereo genic centers and connected to an aromatic system. The results are in quali tative agreement with mechanistic models based on hydrogen-bonding interact ions between an adsorbed modifier molecule and adsorbed ethyl pyruvate or i ts half-hydrogenated intermediate.