Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines

Abstract

Abstract:The stereoselective hydrogenation of auxiliary-substituted quinolines was used to build up saturated and partially saturated heterocycles. In a first step, the formation and diastereoselective hydrogenation of 2-oxazolidinone-substituted quinolines 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 trifluoroacetic acid as a solvent were found to be optimal 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 allowed a traceless cleavage of the chiral auxiliary. Thus, this new method allows an efficient stereoselective 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 substrates presents an attractive strategy for their preparation and the last years have seen many significant contributions to this field.[2] For example, several different approaches have been reported for the asymmetric hydrogenation of pyridines: e.g., Charette et al. developed a highly selective Ir-catalyzed homogeneous hydrogenation of pyridine ylides, [3d] Zhang and Lei used a sequential combination of heterogeneous 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 oxazolidinone-substituted pyridines using achiral heterogenous 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) hydrogenation of quinolines. Since the aromatic stabilization of the second aromatic ring in bicyclic aromatics is somewhat lower, hydrogenation of the annulated ring is significantly facilitated. Most of these methods employ homogeneous iridium, rhodium or ruthenium 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 hydrogena...

Metal-free intermolecular formal cycloadditions enable an orthogonal access to nitrogen heterocycles

“…7a ). Removal of the oxazolidinone takes place under these conditions analogously to previous work by Glorius et al 56 on related pyridines and quinolones 57 . It is noteworthy that the use of a chiral 2-oxazolidone analogue, as in 3hi , enabled the hydrogenation to proceed with some level of asymmetric induction (55% e.e.…”

Brønsted‐Säure‐Aktivierung bei der übergangsmetallkatalysierten asymmetrischen Hydrierung N‐ungeschützter Imine, Enamine und N‐Heteroarene

“…118 Ähnlich wie bei der asymmetrischen Hydrierung von Pyridinen mit einem Auxiliar ( 62 )10 wurde die stereoselektive Hydrierung der substituierten Chinoline 81 zur Herstellung partiell und vollständig gesättigter N‐Heterocyclen mit bis zu 99 % ee verwendet [Gl. (21); TFA=Trifluoressigsäure] 119 …”

P37.06: Prenatal diagnosis of conjoined twins: Our experience

“…118 In a fashion similar to the asymmetric hydrogenation of pyridines bearing an auxiliary ( 62 ),10 the stereoselective hydrogenation of the substituted quinolines 81 was used to access partially saturated and saturated N‐heterocycles in up to 99 % ee [Eq. (21); TFA=trifluoroaceteic acid] 119 …”