Stereodifferentiation in heterogeneous catalytic hydrogenation. Kinetic resolution and asymmetric hydrogenation in the presence of (S)-proline: Catalyst-dependent processes Nóra Gy } orffy a, * , Antal Tungler a , Mátyás Fodor b a Institute of Isotopes, Hungarian Academy of Sciences, P.O. Box 77, Budapest H-1525, Hungary b Budapest University of Technology and Economics, Department of Chemical and Environmental Process Engineering, Hungary article info Article history: Received 28 August 2009 Revised 5 October 2009 Accepted 22 October 2009 Available online 22 January 2010 Keywords: Kinetic resolution 3,5,5-Trimethyl cyclohexanone Asymmetric C@C hydrogenation Isophorone (S)-Proline Palladium catalysts abstract The kinetic resolution of 3,5,5-trimethyl cyclohexanone (TMCH) and asymmetric hydrogenation of isoph- orone (3,5,5-trimethyl cyclohex-2-enone, IP) were investigated on different Pd catalysts in the presence of (S)-proline (Pr). It could be proven that in isophorone hydrogenation the optically active TMCH was formed not only by kinetic resolution but also through asymmetric C@C hydrogenation. The activity and stereoselectivity of different Pd catalysts depended on the support material, preparation method, and reaction conditions as well, confirming our assumption that enantiodifferentiation takes also place on the catalyst surface and not only in the homogeneous liquid phase condensation reaction. Ó 2010 Published by Elsevier Inc. 1. Introduction Heterogeneous catalytic asymmetric hydrogenation of isopho- rone (3,5,5-trimethyl cyclohex-2-enone, IP, 2) in the presence of (S)-proline (Pr, 1) was first reported more than 20 years ago [1–3]. IP was the only substrate among several a,b-unsaturated ke- tones which afforded significant ee (60% at 55% chemical yield of trimethyl cyclohexanone, TMCH, 3) in this reaction [4]. Continuing this work, asymmetric hydrogenation of acetophenone [5,6], dia- stereoselective reductive alkylation of Pr with ethyl pyruvate [7,8], asymmetric hydrogenation of benzylidene benzosuberone [9], synthesis of chiral modifiers based on (S)-proline, and their use in the enantioselective hydrogenation of IP [10–14] were also investigated. Detailed circular dichroism, NMR and IR spectroscopy mea- surements, and preparative experiments resulted in the conclu- sion that asymmetric hydrogenation of IP can proceed through carbonylamine (4) and oxazolidinone-type intermediate (5), which was verified on the basis of the work of Joucla and Mortier [15]. Recently, Seebach et al. [16] studied these compounds and their reactivity in detail, stressing their role in proline catalysis. List et al. [17] tried to find out which intermediate compounds play significant role in the proline-catalyzed aldol reaction of different ketones, using O 18 -labeled water. Based on these results they suggest a covalent, enamine intermediate (8). In IP hydrogenation [4], the optical purity of TMCH depended on the catalytic metal. Pd and Rh gave higher ee, but only alkylated proline was formed with Pt. The product ee changed also with the solvent, methanol proved to be the best one. The effect of IP/ Pr molar ratio on ee was tested too, 1:1 ratio gave the best result. Török and co-workers [18] initiated the revival of the Pd-med- iated asymmetric hydrogenation of IP with Pr, they regarded Pr as a catalyst modifier, not as a chiral auxiliary. Two years later Török and co-workers [19] proposed another mechanism for IP/Pr hydro- genation on different Pd catalysts. The participation of kinetic res- olution in the formation of optically active TMCH was stressed. They emphasized the role of Pr-modified catalyst surface in IP hydrogenation, contradicting Lambert and co-workers [20], who claimed that enantiodifferentiation takes place only in solution. Lambert and co-workers tested the IP hydrogenation exten- sively [20,21]. They claimed on the basis of spectroscopic and ki- netic measurements that optically active TMCH was formed solely in the kinetic resolution of this compound, namely with reductive alkylation of Pr and in complete contrast to the case of ketoester asymmetric hydrogenation, the metal surface was not in- volved in the crucial enantiodifferentiation step. Li et al. [22] tested Pd supported on Al 2 O 3 –K 2 CO 3 and concluded that the main source of optically active TMCH was kinetic resolution. 0021-9517/$ - see front matter Ó 2010 Published by Elsevier Inc. doi:10.1016/j.jcat.2009.10.018 * Corresponding author. Fax: +36 1 392 2533. E-mail address: gyorffy@iki.kfki.hu (N. Gy} orffy). Journal of Catalysis 270 (2010) 2–8 Contents lists available at ScienceDirect Journal of Catalysis journal homepage: www.elsevier.com/locate/jcat