Ketones asymmetric transfer hydrogenation

Keywords Ketones Asymmetric transfer hydrogenation Chiral metal catalysts Recyclable catalysts Transfer hydrogenation in water... 

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. 

Among the most active catalysts for the asymmetric transfer hydrogenation of prochiral ketones and imines to chiral alcohols and amines are arene-ruthenium(II) amino-alcohol (or primary/ secondary 1,2-diamine)-based systems, with an inorganic base as co-catalyst, developed by Noyori139-141 and further explored by others (Scheme 27).142-145... 

Asymmetric transfer hydrogenation can be employed in the asymmetric hydrogenation of prochiral ketones with a ruthenium complex of bis(oxazolinylmethyl) amine ligand 110. Enantioselectivities are greater than 95%.643... 

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... 

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

The synthesis of amines by the in-situ reductive amination of ketones is termed the Leuckart-Wallach reaction. Recently, an asymmetric transfer hydrogenation version of this reaction has been realized [85]. Whilst many catalysts tested give significant amounts of the alcohol, a few produced almost quantitative levels of the chiral amine, in high enantiomeric excess. 

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). 

Increasing effort has been applied to develope asymmetric transfer hydrogenations for reducing ketones to alcohols because the reaction is simple to perform and does not require the use of reactive metal hydrides or hydrogen. Ruthenium-catalyzed hydrogen transfer from 2-propanol to ketones is an efficient method for the preparation of secondary alcohols. 

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

I. S. 3/ >.4/ >j-2-AZANORBORNYLMETIIANOL, AN EFFICIENT LIGAND FORRUTHENIUM-CATALYSED ASYMMETRIC TRANSFER HYDROGENATION OF AROMATIC KETONES... 

The procedure is very easy to reproduce and the asymmetric transfer hydrogenation may be applied to a wide range of aromatic ketones. Table 9.3 gives different substrates that can be reduced with the Ru(II)-(2-azanorbornylmetha-nol) complex in Ao-propanol... 

A. Ruthenium Catalyzed Asymmetric Transfer Hydrogenation (ATH) TO Ketones... 

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. 

Keywords Alcohols Alkenes Asymmetric transfer hydrogenation C-alkylation Imines Ketones W-aUcylation Oxidation Reduction Transfer hydrogenation... 

Table 4.8 Asymmetric transfer hydrogenation of aromatic ketones, catalyzed by [lrH(CO)(PPh3)3]/83 under base-free conditions.

Table 4.9 Asymmetric transfer hydrogenation of aryl alkyl ketones in Pr0H/H20, catalyzed by 93a,b and 94a,b. ...

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

The treatment of [Cp MCl2]2 (M = Rh and Ir) with (S,S)-TsDPEN gave chiral Cp Rh and Cp Ir complexes (12a and 12b Scheme 5.9). An asymmetric transfer hydrogenation of aromatic ketones using complex 12 was carried out in 2-propanol in the presence of aqueous KOH (1 equiv.) the results obtained are summarized in Table 5.4. In all of the reactions, the (S)-alcohols were obtained with more than 80% enantiomeric excess (ee) and in moderate to excellent yields. The rhodium catalyst 12a was shown to be considerably more active than the iridium catalyst... 

Table 5.4 Asymmetric transfer hydrogenation of prochiral ketones catalyzed by 12 giving (S)-alcohols. ...

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