Hydrogenation of functionalized ketones

Catalyst R XR S/C ratio Reaction conditions Percent ee of product (confign.) References 

Although Ru(OCOCH3)2(binap) exhibits excellent catalytic performance on asymmetric hydrogenation of functionalized olefins, it is feebly active for reaction of ketones. This failure is due to the property of the anionic ligands. Simple replacement of the carboxylate ligand by halides achieves high catalytic activity for reaction of functionalized ketones. 

chiral precatalysts includ-RuCl2[(R)-binap](dmf) (oligomeric [NH2(C2H5)2][ RuCl[(R)-binap] 2- 

When Ru(OCOCH3)2(binap) is used, acetic acid is produced instead 

An axially chiral SEGPHOS efficiently discriminates two enantiofaces of a- and p-keto esters in the Ru-catalyzed hydrogenation.The small angle, 65°, between 

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BPPM Scheme 1.17) was used as catalyst [60]. The enantioselective hydrogenation of functionalized ketones was also efficiently achieved by a series of rhodium(I) aminophosphine- and amidophosphine-phosphinite complexes [61]. 

Rhodium-Catalyzed Enantioselective Hydrogenation of Functionalized Ketones... 

In this chapter, we will focus on the rhodium-catalyzed hydrogenation of functionalized ketones and the development of chiral phosphorous ligands for this process. Although there are other chiral phosphorous ligands which are effective for ruthenium-, iridium-, platinum-, titanium-, zirconium-, and palladium-catalyzed hydrogenation, they will not be discussed here. For details of these chemistries, the reader should refer to other chapters of this book. 

Rhodium-Catalyzed Enantioselective Hydrogenation of Functionalized Ketones 33.3.2.2 a,y-Diketoesters... 

Asymmetric hydrogenation of ketones is one of the most efficient methods for making chiral alcohols. Ru-BINAP catalysts are highly effective in the asymmetric hydrogenation of functionalized ketones,54,55 and this may be used in the industrial production of synthetic intermediates for some important antibiotics. The preparation of statine 65 (from 63b R = i-Bu) and its analog is one example (Scheme 6-28).56 Table 6-6 shows the results when asymmetric hydrogenation of 63 catalyzed by RuBr2[(R)-BINAP] yields threo-64 as the major product. 

In contrast to their success in the asymmetric hydrogenation of functionalized ketones, BINAP-Ru catalysts fail to give good results with simple ketone because such substrates lack heteroatoms that enable the substrate to anchor strongly to the Ru metal. 

The best studied systems are the Raney Ni/tartaric acid/NaBr combination, for the hydrogenation of / -functionalized ketones, and the Pt- and Pd-on-support/cinchona alkaloid systems for the enantioselective hydrogenation of a-functionalized ketones. 

Figure 1.13. Asymmetric hydrogenation of functionalized ketones catalyzed by BINAP-Ru complexes.

BINAP and MeO-BIPHEP/Ru-catalyzed hydrogenation of functionalized ketones has been applied to the synthesis of more than ten important compounds, for example, antibiotics, anti-inflammatory compounds, and anticancer agents, since 1999 [59],... 

Highly enantioselective hydrogenation of functionalized ketones has been achieved with chiral phosphine-Rh(I) and -Ru(II) complexes [1,162], The presence of a functional group close to the carbonyl moiety efficiently accelerates the reaction and also controls the stereochemical outcome. The heteroatom-metal interaction is supposed to effectively stabilize one of the diastereomeric-transition states and/or key intermediates in the hydrogenation. 

Despite fruitful results of asymmetric hydrogenation of functionalized ketones, only limited examples have been reported for reaction of ketonic substrates with no functionality near the carbonyl group [1,162,254]. Transition-metal catalysts with a bidentate chiral phosphine, successfully used for functionalized ketones, are often ineffective for reduction of simple ketones in terms of reactivity and enantioselectivity [162b,c]. However, a breakthrough in this subject has been provided by the invention of a new chiral Ru catalyst system. 

Keto Esters Asymmetric transfer hydrogenation of functionalized ketones is rare. However, an excellent optical yield is obtainable inreduction of methyl benzoylformate by using 2-propanol and with a catalyst system consisting of [RhCl(C6H]0)]2, (S,S)-DMDPEN, and KOH (Scheme 1.89) [313],... 

K. Evetraere, J.-F. Carpentier, A. Morteux, and M. Bulliard, N-Benzoyl-norephedrine derivatives as new, effident ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones, Tetrahedron Asymm. 1999, 10, 4083 4086. 

Asymmetric reduction The ruthenium(II)-BINAP catalysts developed by Noyori s group in 1980s were the most successful for the asymmetric hydrogenation of functionalized ketones such as a-ketoesters, a-hydroxyketones and a-aminoketones because the second... 

The reactivity of achiral Ru compounds for the hydrogenation of functionalized ketones has not been extensively studied. RuCl2 P(C6H5)3 3 reduces y-keto carboxylic acid at 180 °C to the corresponding y-lactone (Eq. 2.15) [115]. Heterogeneous Ru/C catalyzes the atmospheric pressure hydrogenation of furfural in water at 25 °C [86]. Under such mild conditions, glucose is industrially converted to sorbitol (Eq. 2.16) [116]. At elevated temperature and pressure, tetramethyl-l,3-cyclobutanedione can be converted to a 98 2 diastereomer mixture of the diol (Eq. 2.17) [117]. 

Kitamura, M., Tokunaga, M., Ohkuma, T., Noyori, R. Convenient preparation of BINAP-ruthenium(ll) complexes for catalyzing the asymmetric hydrogenation of functionalized ketones. Tetrahedron Lett. 1991, 32, 4163-4166. 

Blanc, D., Henry, J.-C., Ratovelomanana-Vidal, V., and Genet, J.-P, Skewphos-RufB). An efficient catalyst for asymmetric hydrogenation of functionalized ketones. Tetrahedron Lett., 38, 6603, 1997. 

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