DOI: 10.1002/adsc.200900763 Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines Maja Heitbaum, a Roland Frçhlich, a and Frank Glorius a, * a Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany Fax: (+ 49)-251-83-39-772; e-mail: glorius@uni-muenster.de Received: November 30, 2009; Revised: December 31, 2009; Published online: February 9, 2010 Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/adsc.200900763. Abstract: The stereoselective hydrogenation of aux- iliary-substituted quinolines was used to build up saturated and partially saturated heterocycles. In a first step, the formation and diastereoselective hy- drogenation of 2-oxazolidinone-substituted quino- lines to 5,6,7,8-tetrahydroquinolines is reported. In this unprecedented process, stereocenters on the carbocyclic quinoline ring were formed with a dr of up to 89:11. Platinum oxide as a catalyst and tri- fluoroacetic acid as a solvent were found to be opti- mal for high levels of chemo- and stereoselectivity in this step. In a second hydrogenation step, the completely saturated decahydroquinolines with 4 newly formed stereocenters were obtained with enantioselectivities of up to 99%. Rhodium on carbon as a catalyst and acetic acid as a solvent gave the best results for this hydrogenation and al- lowed a traceless cleavage of the chiral auxiliary. Thus, this new method allows an efficient stereose- lective synthesis of valuable 5,6,7,8-tetrahydro- and decahydroquinoline products. Keywords: asymmetric synthesis; chiral auxiliaries; decahydroquinolines; heterocycles; hydrogenation Enantiomerically pure saturated or partially saturated heterocyclic compounds are important building blocks and fragments of many biologically active compounds like coniine, the poisonous alkaloid of hemlock, or the multiply substituted Lycopodium alkaloids . [1] The asymmetric hydrogenation of heteroaromatic sub- strates presents an attractive strategy for their prepa- ration and the last years have seen many significant contributions to this field. [2] For example, several dif- ferent approaches have been reported for the asym- metric hydrogenation of pyridines: e.g., Charette et al. developed a highly selective Ir-catalyzed homo- geneous hydrogenation of pyridine ylides, [3d] Zhang and Lei used a sequential combination of heterogene- ous and homogeneous hydrogenation, [3c] Rueping et al. reported an organocatalytic approach employing chiral Brønsted acids, using a Hantzsch ester as the reducing agent. [3b] Whereas all these methods employ chiral, enantiomerically pure catalysts, Glorius et al. developed an efficient hydrogenation of chiral oxazo- lidinone-substituted pyridines using achiral heteroge- nous hydrogenation catalysts like Pd(OH) 2 /C. [3e,f] In this latter reaction, the auxiliary was cleaved under the reaction conditions and fully saturated piperidines with up to 4 newly formed stereocenters and high ees (85–98%) were obtained. Significantly more methods have been reported for the asymmetric (partial) hy- drogenation of quinolines. Since the aromatic stabili- zation of the second aromatic ring in bicyclic aromat- ics is somewhat lower, hydrogenation of the annulat- ed ring is significantly facilitated. Most of these meth- ods employ homogeneous iridium, rhodium or ruthe- nium complexes of chiral ligands [4a–n] together with molecular hydrogen or, alternatively, chiral Brønsted acids as organocatalysts [4o,p] in transfer hydrogenations (Scheme 1). [2] However, despite these advances in the area of asymmetric hydrogenation of (hetero)aromatics, many challenges remain. For example, the asymmetric hydrogenation of benzene rings is still an unsolved, though important task. Consequently, whereas the asymmetric hydrogenation of substituted quinolines to 1,2,3,4-tetrahydroquinolines with a newly formed Adv. Synth. Catal. 2010, 352, 357 – 362 # 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 357 COMMUNICATIONS