Asymmetric Hydrogenation of Heteroaromatics

Use of a BINAP/chiral diamine Ru complex trans- RuCl2[(R)-xylbinap][(R)-daipen] or the S,S complex efficiently catalyzes asymmetric hydrogenation of heteroaromatic ketones, with little influence of the ring properties on the enantioselectivity. Duloxetine, an inhibitor of serotonin and norepinephrine uptake carriers, has been synthesized in this way (Ohkuma, 2000b). 

Recent advances in asymmetric hydrogenation of heteroaromatic compounds (quinoxaline, pyridine, and furan derivatives) 05CJO634. 

Zhou YG (2007) Asymmetric hydrogenation of heteroaromatic compounds. Ace Chem Res 40 1357-1366. doi 10.1021/ar700094b... 

Asymmetric hydrogenation of heteroaromatic compounds provides a straightforward synthetic pathway to access enantioenriched heterocycles, which are of great importance in the synthesis of pharmaceuticals and natural products. Rueping et al. reported several examples of enantioselective cascade transfer hydrogenation reaction of heteroaromatic substrates under metal-free conditions [19,20]. The same group also developed a cascade reaction between enamines 42 and oc,P-unsaturated... 

Kuwano R, Sato K, Kurokawa T, Karube D, Ito Y (2000) Catalytic asymmetric hydrogenation of heteroaromatic compounds, indoles. J Am Chem Soc 122 7614-7615... 

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. 

PhanePhos-ruthenium-diamine complexes catalyze the asymmetric hydrogenation of a wide range of aromatic, heteroaromatic, and cx,P-unsaturated ketones with high activity and excellent enantioselectivity (Burk, 2000). 

Because a comprehensive review on the catalytic performance of Josiphos ligands has been published,20 we restrict ourselves to a short overview on the most important fields of applications. Up to now, only the (7 )-(S)-family (and its enantiomers) but not the (R)-(R) diastereoisomers have led to high enantioselectivities (the first descriptor stands for the stereogenic center, and the second stands for the planar chirality). The most important application is undoubtedly the hydrogenation of C = N functions, where the effects of varying R and R1 have been extensively studied (for the most pertinent results see Table 15.5, Entries I—4). Outstanding performances are also observed for tetrasubstituted C = C bonds (Entry 5) and itaconic and dehydroamino acid derivatives (Entries 6 and 7). A rare example of an asymmetric hydrogenation of a heteroaromatic compound 36 with a respectable ee is depicted in Scheme 15.6.10b... 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

TO Enantioselective Reduction of Nitrogen Based Heteroaromatic Compounds Table 10.3 Asymmetric hydrogenation of quinolines by Lam, Fan, and Chan. (S,S)-Cp lr(OTf)(CF3TsDPEN)... 

W Enantioselective Reduction of Nitrogen Based Heteroaromatic Compounds Table 10.15 Asymmetric hydrogenation of 2 methylquinoxaline. 

Asymmetric hydrogenation. A prec from asymmetric hydrogenation of 2.3-h l,l,l-trifluoroalkan-2-ols can be synthesi ketones. A general method for access heteroaromatic ketones is by asymmetric I... 

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). 

As the asymmetric hydrogenations of amino acid with various kinds of chiral phosphinerhodium complexes as catalysts [68-70], the selective hydrogenations of heteroaromatic compounds [71 ] have been also reported. 

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