(165c) Hydrogenation Kinetics and Deactivation of Chiral Catalysts

Chiral synthesis catalyzed by organometallic complexes is an important area of development for the production of pharmaceuticals, agrochemicals, fragrances and other fine chemicals.  Most of the studies have concentrated in the development of novel ligands and complexes, but there is hardly any study of chiral catalyst deactivation, in spite of the need for optimizing the catalyst/substrate ratio and reaction time.

In this work, we present a study of deactivation kinetics and possible mechanisms during the asymmetric hydrogenation of C=O and C=C double bonds. The pro-chiral substrates used were itaconic acid, α-acetamidocinnamic acid and acetophenone. The complexes studied were composed of either Pd or Ru as the central metal and ligands with axial chirality, namely (R)- and (S)-6,6’-dimethyl-2,2’-diaminobiphenyl, (R)-(+)-1-1´-Bi(2-naphtylamine), (R)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene and (R)-2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthyl. Complete details are given elsewhere (1).

Reaction results at room temperature and in the presence of 100 psi H₂showed practically 100% chemoselectivity, good yields and moderate enantioselectivities to either the (R) or (S) enantiomer. There was sensitivity of the global kinetics to the complex used as a catalyst as well as to the solvent and base present. They affect reactivity, enantioselectivity and deactivation. The substrate/catalyst ratio was adjusted in order to allow enough data acquisition as a function of reaction time and hence observe  the effect of deactivation.

The yield –time data clearly suggest the presence of deactivation, but in some cases, a non-zero limiting activity is apparent.  A generalized power-law model for deactivation was used (2), coupled with a first order dependence upon the substrate concentration. The fit of the data was excellent in all cases.  The possible mechanisms involved in chiral catalyst deactivation are also discussed.

1- V.M. Rivera, J.P. Ruelas-Leyva , G.A. Fuentes, Catalysis Today, in press (2013).

2- G.A. Fuentes, Applied Catal. 15 (1985) 33.