Heteroaromatic compounds asymmetric hydrogenation

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. 

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... 

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. 

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

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). 

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

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. 

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... 

As heteroaromatic compounds are more stable, their asymmetric hydrogenation requires, usually, harsher reaction conditions this can lead to easy deactivation of the catalysts through the poisoning. Moreover, to achieve high enantioselectivities, the presence of additional functional groups that are able to coordinate to the metal catalyst is necessary and extremely important. 

Applications of asymmetric hydrogenation of several heteroaromatic nitrogen-containing substrates for the installation of chirogenic centers, and therefore enantioselective preparation of important precm ors and intermediates, as well as their use in the total syntheses of some bioactive natural compounds, are discussed below. 

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... 

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