Asymmetric transfer hydrogenation of ketones

New Cp lr and Cp Rh complexes having a chiral diamine Hgand, which are isoelectric with Noyori s chiral (arene)Ru complex [38], have been synthesized by 

Mashima and Tani et al., and employed in the asymmetric transfer hydrogenation of aromatic ketones [39, 40], 

12b under the same reaction conditions, whereas the catalyhc activity and enantioselectivity of 12 were less than those of the chiral mthenium catalyst 

4 Asymmetric Synthesis Based on Hydrogen Transfer 117 HaN NHSOaC6H4S03Na-p 15b 

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On the other hand, one of the first chiral sulfur-containing ligands employed in the asymmetric transfer hydrogenation of ketones was introduced by Noyori el al Thus, the use of A-tosyl-l,2-diphenylethylenediamine (TsDPEN) in combination with ruthenium for the reduction of various aromatic ketones in the presence of i-PrOH as the hydrogen donor, allowed the corresponding alcohols to be obtained in both excellent yields and enantioselectivities, as... 

The use of chiral ruthenium catalysts can hydrogenate ketones asymmetrically in water. The introduction of surfactants into a water-soluble Ru(II)-catalyzed asymmetric transfer hydrogenation of ketones led to an increase of the catalytic activity and reusability compared to the catalytic systems without surfactants.8 Water-soluble chiral ruthenium complexes with a (i-cyclodextrin unit can catalyze the reduction of aliphatic ketones with high enantiomeric excess and in good-to-excellent yields in the presence of sodium formate (Eq. 8.3).9 The high level of enantioselectivity observed was attributed to the preorganization of the substrates in the hydrophobic cavity of (t-cyclodextrin. 

Noyori and coworkers reported well-defined ruthenium(II) catalyst systems of the type RuH( 76-arene)(NH2CHPhCHPhNTs) for the asymmetric transfer hydrogenation of ketones and imines [94]. These also act via an outer-sphere hydride transfer mechanism shown in Scheme 3.12. The hydride transfer from ruthenium and proton transfer from the amino group to the C=0 bond of a ketone or C=N bond of an imine produces the alcohol or amine product, respectively. The amido complex that is produced is unreactive to H2 (except at high pressures), but readily reacts with iPrOH or formate to regenerate the hydride catalyst. 

Palmer and Wills in 1999 reviewed other ruthenium catalysts for the asymmetric transfer hydrogenation of ketones and imines [101]. Gladiali and Mestro-ni reviewed the use of such catalysts in organic synthesis up to 1998 [102]. Review articles that include the use of ruthenium asymmetric hydrogenation catalysts cover the literature from 1981 to 1994 [103, 104], the major contributions... 

Evans et al.106 report an asymmetric transfer hydrogenation of ketones using samarium(III) complex (108) as the catalyst at ambient temperature in 2-propanol. The products showed ee comparable with those obtained through enantioselective borane reduction (Scheme 6-48). 

The asymmetric transfer hydrogenation of ketones is further described elsewhere.117... 

Palmer, M.J., Kenny, J.A., Walsgrove, T., Kawamoto, A.M. and Wills, M., Asymmetric transfer hydrogenation of ketones using amino alcohol and monotosylated diamine derivatives of indane. 

Figure 1.23. Asymmetric transfer hydrogenation of ketones catalyzed by chiral arene-Ru...

Figure 1.25 exemplifies the strucmres of certain efficient precatalysts for asymmetric transfer hydrogenation of ketones. Precatalysts C1-C3 use the NH effect described above. A turnover frequency, defined as moles of product per mol of catalyst per hour, of 30,000 h is achieved by using of C2 and an alkaline base in 2-propanol. A Rh complex C3 is an isolobal to the corresponding arene-Ru complex (see Figure 1.23). The Ru complexes C4 " and C5 without NH group in ligand catalyze the reaction by different mechanisms. A higher than 90% optical yield is achieved by using C5 in reduction of certain aliphatic ketones.

Figure 1.25. Examples of chiral precatalyst for asymmetric transfer hydrogenation of ketones.

An Rh(III)-tetramethylcyclopentadienyl complex containing a tethered functionality is found to give excellent results in the asymmetric transfer hydrogenation of ketones in both aqueous, using sodium formate, and formic acid-triethylamine media. Quantitative yields and almost 100% ees are obtained.374... 

Chan et al. synthesized first- and second-generation dendrimers containing up to 12 chiral diamines at the periphery (Fig. 8) [29]. Their ruthe-nium(II) complexes displayed high catalytic activity and enantioselectivity in the asymmetric transfer hydrogenation of ketones and imines. Quantitative yields, and in some cases a slightly higher enantioselectivity compared to those of the monomeric systems (up to 98.7% ee), were obtained. 

One place to look for good alcohol racemization catalysts is in the pool of catalysts that are used for hydrogen transfer reduction of ketones. One class of complexes that are excellent catalysts for the asymmetric transfer hydrogenation comprises the ruthenium complexes of mono sulfonamides of chiral diamines developed by Noyori and coworkers [20, 21]. These catalysts have been used for the asymmetric transfer hydrogenation of ketones [20] and imines [21] (Fig. 9.9). 

Shingote, S.K., Kelkar, A.A., Borole, Y.L., Joshi, P.D., and Chaudhari, R.V. 2008. Ultrasound promoted asymmetric transfer hydrogenation of ketones using Ru(ll)arene/amino alcohol catalyst system. Ultrasonics Sonochemistry, 15 289-93. 

Ru catalysts with a P-Phos and a 1,2 - or 1,4-diamine ancillary ligand The catalyst (sulfonyl-diamine)RuCl(arene) 6.76, without the expensive phosphine ligand, and the hydrogen donor such as 2-propanol or formic acid in the presence of a base are used for the asymmetric transfer hydrogenation of ketones ". ... 

Diselenides as Chiral Ligands for Asymmetric Transfer Hydrogenation of Ketones... 

Although simple phosphine-Ru catalysts are not very effective for asymmetric transfer hydrogenation of ketones, Ru complexes with chiral phosphine ligands combined with oxazoline or secondary amine realize high reactivity and enantio-... 

Other aminophosphines have also been sought and applied in different enantio-selective transformations, e. g., allylic substitution [56] (up to 95 % ee), and Ir-based imine hydrogenation (88% ee) [57]. Chiral aminophosphines have also been investigated in the asymmetric transfer hydrogenation of ketones (up to 84 % ee for the reduction of aryl ketones) [58],... 

Bianchini, C., Glendenning, L. Ruthenium(ll)-catalyzed asymmetric transfer hydrogenation of ketones using a formic acid-triethylamine mixture. Asymmetric transfer hydrogenation of imines. Chemtracts 1997, 10, 333-338. 

In order to facilitate recycling of the multiple TsDPEN-functionalized dendrimer catalysts, the same group recently reported the synthesis of a novel form of hybrid dendrimer ligands by coupling polyether dendrons with peripherally TsDPEN-functionahzed Newkome-type poly(ether-amide) dendrimer (Figure 4.28) [90]. The solubility of these hybrid dendrimers was found to be affected by the generation of the polyether dendron. The ruthenium complexes produced were applied in the asymmetric transfer hydrogenation of ketones, enones, imines and activated... 

Asymmetric transfer hydrogenation of ketones in the presence of soluble transition metal catalysts has been developed [8-10], enantioselectivities up to 99% ee being obtained using a ruthenium catalyst bearing mono-N-tosylated diphenyl-ethylenediamine as a ligand. Iridium complexes associated with fluorous chiral diimines 3a-3c or diamines 4a—4b have also been shown to be effective catalysts in hydrogen-transfer reduction of ketones [11,12]. 

The reduction of the carbonyl group (and related functionalities) by catalytic methods has been successfully achieved by a number of methods. Rhodium and ruthenium complexes are the most popular catalysts used in the hydrogenation of ketones. While most catalyst systems of this type require the presence of additional chelating functionality on the substrate the recent development of highly active ruthenium(diamine) complexes allows the reduction of simple unfunctionalised ketones. Ruthenium catalysts have also been applied, with much success, to the catalytic asymmetric transfer hydrogenation of ketones in the presence of alcohols or formate. 

The asymmetric transfer hydrogenation of ketones is an effective way to prepare enan-tiopure alcohols." " We were attracted to this reaction as we anticipated that one could exploit the reversibility of the reaction to perform either for the enantioselective reduction or for the kinetic resolution of racemic alcohols via oxidation. This behaviour is reminiscent of alcohol dehydrogenases which can operate either as oxidases or reductases. ... 

Polar bis(phosphonic acid)-derived Ru pre-catalysts (Figure 9) immobilized in room-temperature ILs were also successful for asymmetric transfer hydrogenation of ketones with ee values of up to 98%. Excellent catalytic performance and catalyst recycle were observed with 2-methyl-imidazolium-based ILs such as [G4G1-4-... 

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