Hydrogenation of quinoline derivatives

Having established the optimal condition, the scope ofthe Ir catalyzed asymmetric hydrogenation of quinoline derivatives was explored. A variety of 2 substituted and... 

After the initial work of Zhou s group on iridium catalyzed enantioselective hydrogenation of quinoline derivatives, some other groups, such as Fan, Chan, Xu, Reetz, Rueping, Du and Bolm et al. have reported their results on asymmetric hydrogenation of quinoline derivatives. 

In 2005, Fan and coworkers developed a highly effective and air stable catalyst system Ir/P Phos/l2 for the asymmetric hydrogenation of quinoline derivatives (Scheme 10.4) [6]. They found that THF was the best solvent that gave the highest enantioselectivity (92% ee). The reactions were carried out at room temperature, and a series of quinoline derivatives were examined with full conversions and excellent enantioselectivity. More important, the catalyst could be effectively immobilized in DMPEG with retained reactivity and enantioselectivity in eight catalytic runs. 

In the same year, Xu and coworkers showed the usefulness of Ir L14 catalyst in the asymmetric hydrogenation of quinoline derivatives [7]. They found that better enantioselectivities were obtained using DMPEG/hexane as reaction medium than THF. The highest enantioselectivity was 97% ee. However, the recycling of the catalyst proved to be difficult (Scheme 10.5). 

Scheme 11.14 Asymmetric transfer hydrogenation of quinoline derivatives.

More recently. Fan s group [47] applied the same kind dendritic ligands to iridium-catalyzed asymmetric hydrogenation of quinoline derivatives. In the model reaction of asymmetric hydrogenation of quinaldine (Figure 4.19), the dendritic... 

The asymmetric hydrogenation of quinoline continues to be of interest. Li et al. reported the asymmetric hydrogenation of a variety of 2-substituted-quinolines to the corresponding tetrahydroquinolines using an Ir-catalyst with a BINOL-derived diphosphonite ligand... 

Using Ir/MeO-Biphep/l2 catalyst system, a variety of substituted quinoline derivatives were hydrogenated in 95% yield and up to 96% ee. This method provided an efficient accesss to three naturally occurring alkaloids (Scheme 17).328 Ferrocene N, P ligand 108 is also effective for the asymmetric hydrogenation of quinolines with up to 92% ee.188a... 

Fig. 16 Summary of the best results obtained in the Ir-catalyzed hydrogenation of quinolines, quinoxalines, and Af-aryl imines using binol-derived phosphoroamidite PipPhos 19 ligand...

Quinoline homologs and derivatives, including those with double bonds in the side chains, were reduced selectively by catalytic hydrogenation over platinum oxide (side chain double bonds), and to dihydro- and tetrahydro-quinolines by sodium in butanol, by zinc and formic acid, and by triethylam-monium formate [319, 472]. Catalytic hydrogenation of quinoline and its derivatives has been thoroughly reviewed [439]. 

The enantioselective hydrogenation of olefins, ketones and imines still represents an important topic and various highly enantioselective processes based on chiral Rh, Ru or Ir complexes have been reported. However, most of these catalysts failed to give satisfactory results in the asymmetric hydrogenation of aromatic and heteroaromatic compounds and examples of efficient catalysts are rare. This is especially the case for the partial reduction of quinoline derivatives which provide 1,2,3,4-tetrahydroquinolines, important synthetic intermediates in the preparation of pharmaceutical and agrochemical products. Additionally, many alkaloid natural products consist of this stmctural key element. 

The Brpnsted acid catalyzed hydrogenation of quinolines with Hantzsch dihydropyridine as reducing agent provides a direct access to a variety of substituted tetrahydroquinolines (Table 4.2). The mild reaction conditions of this metal-free reduction of heteroaromatic compounds, high yields, operational simplicity and practicability, broad scope, functional group tolerance and remarkably low catalyst loading render this environment-friendly process an attractive approach to optically active tetrahydroquinolines and their derivatives (Table 4.3) (see page 176). ... 

A chiral diphosphonite, derived from BINOL (18) and with an achiral diphenyl ether backbone, is an excellent ligand for the iridium-catalysed asymmetric hydrogenation of quinolines. Enantioselectivities ranging from 90 to 94% were obtained.343... 

Selectivity to Tetrahydro Derivatives. As already described, the hydrogenation of quinoline and isoquinoline usually occurs at the nitrogen ring to give the corresponding 1,2,3,4-tetrahydro derivatives, unless bulky substituents in the 2,3,... 

Reetz MT, Li X (2006) Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of BINOL-derived diphosphonites. Chem Commun May 28 2159-2160... 

Reactions of 4-aryl-5(2f/)-isoxazolones with 1,2-dibromoethane in acetonitrile in the presence of 1 equiv of triethyl-amine gave 2-bromoalkyl-4-aryl-5(2/f)-isoxazolones as major products that were converted to heterocyclic ketene AjO-acetals by treatment with sodium methoxide in boiling methanol <1997T10433>. The preparation of quinoline derivatives was achieved by catalytic hydrogenation of 2-(2-formylaryl)-5(2//)-isoxazolones <2003T9887>. 

Chiral dendritic catalysts 194 derived from BINAP was prepared and used for the asymmetric hydrogenation of quinolines (Scheme 3.63) [126]. The corresponding cyclic amine products were obtained with high enantioselectivities up to 93% ee. The dendritic catalyst showed excellent catalytic activities (TOP up to 3450h" ) and productivities (TON up to 43 000). The dendritic catalyst was recovered by precipitation and filtration and reused at least six times, with similar enantioselectivity. 

Cascade Transfer Hydrogenation of Quinoline and Pyridine Derivatives... 

Scheme 10.3 Asymmetric hydrogenation of quinolines using ferrocene derived N,P and S,P ligands.

Reetz and Li studied asymmetric hydrogenation of quinolines using iridium complex with a chiral BINOL derived diphosphonite ligand with an achiral diphenyl ether backbone as catalyst, achiral P ligands serving as possible additives (Scheme 10.7) [9]. Under the optimized conditions, 2 substituted and... 

In 2008, Vries group reported asymmetric hydrogenation of quinolines catalyzed by iridium complexes based on monodentate BINOL derived phos phoramidites PipPhos. They used tri ortho tolylphosphine and/or chloride salts as additives, and enantioselectivities were strongly enhanced to 89% ee (Scheme 10.13) [17]. Toluene and DCM were the best solvents, and the reaction was carried out at 60°C for 24h in the pressure of 50 bar H2, and a series of 2 substituted and 2,6 disubstituted quinolines were examined with excellent... 

In 2008, Fan and Xu developed an air stable and phosphine free Ir catalyst for the asymmetric hydrogenation of quinolines [20]. They used chiral cationic Cp Ir(OTf) (CF3TSDPEN) complex as catalyst ]21]. The reaction proceeded smoothly in unde gassed methanol with no need for inert gas protection and afforded the 1,2,3,4 tetrahydroquinoline derivatives in up to 99% ee (Table 10.3). The counterion of iridium catalyst is very important, OTf gave high reactivity and enantioselectivity, and no reactivity was observed for chloride. It is noted that it is one ofthe best results of asymmetric hydrogenation of quinolines. 

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