Asymmetric 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). 

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... 

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... 

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

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. 

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. 

Scheme 11.14 Asymmetric transfer hydrogenation of quinoline derivatives.

Binol-derived phosphoroamidite PipPhos (19) has been successfully used as a ligand for the Ir-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines [39], 2- and 2,6-substituted quinoxalines [40], and IV-aryl imines [41] (Fig. 16). 

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. 

Examples of efficient catalysts for the asymmetric hydrogenation of aromatic and heteroaromatic compounds are quite rare, even with hydrogenation procedures catalyzed by chiral Rh, Ru, and Ir complexes. Therefore an important breakthrough was by Rueping s group in 2006 the development of an enantioselective phosphoric acid-catalyzed partial reduction of quinoline derivatives [62]. This represents the first example of a metal-free reduction of heteroaromatic compounds. (/ )-(—)-9-phe-nanthryl-l,l -binaphthyl-2,2 -diyl hydrogenphosphate was selected as chiral element of choice to perform stereocontrol (97% ee. Scheme 15.29). 

Iridium(I)-diphosphane complexes are known as effective hydrogenation catalysts for a long time. Lately, BINAP, BCPM, and dihydrooxazol derivatives were used as ligands for enantioselective hydrogenation of imines (244). Iridium-(P-Phos) catalysts have been used for the asymmetric hydrogenation of the C=N bond of quinolines (245). 

The pyrrolobenzodiazepine-5,11 -diones II have been utilized in asymmetric syntheses of both the cis- and tra i-decahydro-quinoline alkaloids (Schemes 21 and 22). For example, reduction of 100 with 4.4 equiv. of potassium in the presence of 2 equiv. of t-BuOH, followed by protonation of the resulting enolate with NH4CI at —78 °C gave the cA-fused tetra-hydrobenzene derivative 101.Amide-directed hydrogenation of 101 gave the hexahydrobenzene derivative with diastereo-selectivity greater than 99 1. Removal of the chiral auxiliary and adjustment of the oxidation state provided aldehyde 103 which was efficiently converted to the poison frog alkaloid (+)-pumiliotoxin C. 

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