Asymmetric transfer hydrogenation activity

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. 

Apart from the Meerwin-Ponndorf-Verley (MPV) reaction,16 18catalytic asymmetric transfer hydrogenation has remained quite primitive,111,112 with successful examples of reduction of activated olefins, using alcohols or formic acid as hydrogen source, being reported only recently.113,114... 

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... 

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 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... 

A wide range of metals and ligand combinations have been demonstrated to effect the ATH reaction and in this book we concentrate on the systems that have demonstrated high activities and ees that would be the requirement of an industrial application. The initial breakthrough in this area came in 1995 with the report from Ohkuma et alP on the use of chiral monotosylated diamine complexes for asymmetric transfer hydrogenation. 

A -ARENESULFONYL- AND A-ALKYLSULFAMOYL-1,2-DIPHENYLETHYLENEDIAMINE LIGANDS FOR RUTHENIUM-CATALYZED ASYMMETRIC TRANSFER HYDROGENATION OF ACTIVATED KETONES... 

Table 3.4 [RuCl2(p-cymene)]2-RS02-DPEN catalyzed asymmetric transfer hydrogenation of activated ketones R COR. ...

These ligands and their ruthenium complexes are easy to prepare and are useful in asymmetric transfer hydrogenation of a variety of activated ketones. Table 3.4 shows a selection of substrates that can be reduced with the Ru(II)-RS02-DPEN complexes using HC02H-Et3N 5 2. 

The catalytic, asymmetric hydrogenations of alkenes, ketones and imines are important transformations for the synthesis of chiral substrates. Organic dihydropyridine cofactors such as dihydronicotinamide adenine dinucleotide (NADH) are responsible for the enzyme-mediated asymmetric reductions of imines in living systems [86]. A biomimetic alternative to NADH is the Hantzsch dihydropyridine, 97. This simple compound has been an effective hydrogen source for the reductions of ketones and alkenes. A suitable catalyst is required to activate the substrate to hydride addition [87-89]. Recently, two groups have reported, independently, the use of 97 in the presence of a chiral phosphoric acid (68 or 98) catalyst for the asymmetric transfer hydrogenation of imines. 

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. 

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... 

E., King, F. and Xiao, J. (2004) Organic Letters, 5, 3321. The asymmetric transfer hydrogenation of various acetophenones was catalyzed in water by a ruthenium complex of PEG-TsDPEN (0.1-1.0mol%) with sodium formate, and the polymeric catalyst was readily recovered via precipitation, and reused 14 times without significant loss of either catalytic activity or stereoselectivity. 

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