DOI: 10.1002/adsc.200800531 Kinetic Study of the Asymmetric Hydrogenation of Methyl Acetoacetate in the Presence of a Ruthenium Binaphthophosphepine Complex Eva Öchsner, a Bastian Etzold, a Kathrin Junge, b Matthias Beller, b, * and Peter Wasserscheid a, * a Lehrstuhl für Chemische Reaktionstechnik, Universität Erlangen-Nürnberg, Egerlandstr. 3, 91058 Erlangen, Germany Fax: (+ 49)-9131-852-7421; e-mail: Peter.Wasserscheid@crt.cbi.uni-erlangen.de b Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str.29a, 18059 Rostock, Germany Fax: (+ 49) 381-1281-5000; e-mail: Matthias.Beller@catalysis.de Received: August 25, 2008; Revised: October 31, 2008; Published online: December 19, 2008 Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/adsc.200800531. Abstract: The asymmetric hydrogenation of methyl acetoacetate (MAA) in methanol using dibromo- bis{(S)-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c : 1’,2’-e]phosphepine}-ruthenium was studied in detail. For the determination of the reaction network, data from kinetic experiments were compared to different possible reaction networks using the kinetic software Presto Kinetics. The simulation was optimised to de- scribe the reaction accurately with a minimal set of process parameters and reaction equations. For the best model the reaction orders, collision factors and activation energy of all reaction steps were deter- mined. Additionally, the influence of reaction tem- perature and hydrogen pressure on the enantiomeric excess (ee) of the reaction was studied. It was found that high reaction temperatures and high hydrogen pressures result in increasing enantioselectivities. Keywords: asymmetric catalysis; asymmetric hydro- genation; hydrogenation; keto esters; ketones; kinet- ic study Introduction Today, asymmetric hydrogenation plays an important role in the production of chiral compounds and inter- mediates. In particular, asymmetric hydrogenations are applied for the commercial manufacture of phar- maceuticals, for example, naproxen, vitamin E, b- lactam antibiotics and adrenaline. [1,2] Moreover, asym- metric hydrogenation processes are also used in the synthesis of perfumery ingredients, intermediates of fine chemicals and for the development of new mate- rials like ferro-electric liquid crystals and biodegrad- able polymers. [1,3] In the past the development of asymmetric hydro- genation was significantly based on the synthesis of novel catalysts and suitable chiral ligands. [4,5,6,7] A par- ticularly successful type of chiral ligand is the axially dissymmetric bisphosphine ligand BINAP which has been developed in the early 1980s. [8] Using this new ruthenium/BINAP complexes a wide range of func- tionalised olefins ranging from a-arylacrylic acids through a,b- and b,g-unsaturated carboxylic acid to allylic alcohols as well as ketones could be hydrogen- ated with high selectivity and yield. In 2000, several monodentate phosphorus ligands with a 2,2’-binaph- thol core were introduced. [9,10,11] The easier prepara- tion of these monodentate ligands proved to be an es- sential advantage compared to most known bidentate ligands. [12] Surprisingly, for asymmetric hydrogenation reac- tions detailed kinetic and thermodynamic studies are rarely found in literature. However, for a deeper un- derstanding of the respective reaction it is essential to describe its properties with kinetic and thermodynam- ic parameters, in particular if more than one reaction mechanism is principally possible. In such case a de- tailed kinetic analysis can help to identify the most appropriate mechanistic model as the latter describes the experimental results with the smallest set of inde- pendent parameters and in the most accurate way. In this study kinetics models are used to deduce possible reaction pathways for the asymmetric hydro- genation of methyl acetoacetate (MAA). Therefore, a large number of hydrogenation experiments have Adv. Synth. Catal. 2009, 351, 235 – 245  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 235 FULL PAPERS