Asymmetric Transfer Hydrogenation ATH

the activities and selectivities were observed to depend heavily on many variables, including KOH concentration, the presence of water, and the nature of 

A substrate screening was also carried out and reported [67]. For both penta- and tetracoordinate complexes the reaction rate and selectivity increased on going from methyl to t-butyl ketone, thus following the steric hindrance and electrophilicity of the substrate. In the comparison between PPEI and APPEI, the former were markedly more selective in both the neutral (Table 4.7) and cationic complexes. An increase in the iodide Ir ratio also had an improving effect on the asymmetric induction for 77a, reaching a maximum 84% ee at [ ] [Ir] = 3. 

Industrial applications of this type of Ir complex can be found in the patent Uterature. Optically active Ir complexes of 6-alkyl substituted pyridylimine Ir(I) 

Chirality was also achieved by using cyclic (chiral) substituents on the imino nitrogen. Complexes 79 and 80 (the latter obtained by reduction of the C=N double bond) were tested for the ATH of butyrophenone in isopropanol at 60 °C with NaOH. The activity (26% versus 68% conversion for 79a,b) and stereoselectivity (64% versus 3% for 79a,b) were sharply reduced when a methyl group was introduced into the 6-position of the pyridine ring. Tetracoordinated cationic complexes and pentacoordinated neutral species displayed similar efficiencies (64 versus 66% ee for 79a and 80a, respectively). 

The same authors further developed the catalyhc system described above, wherein the chiral Ir catalytic system generated in situ from the iridium hydride complex [IrH(cod)Cl2]2 and chiral diaminodiphosphine ligand 83 was employed in the ATH of aromahc ketones PhC(0)R (R = Me, Et, Pr, cy, Bu, etc.) to produce 

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

Another useful reduction process is asymmetric transfer hydrogenation (ATH) where the hydrogen is transferred from the solvent, often isopropanol, to the ketone or imine function to produce the enantiopure alcohol or amine. For example, Baratta et alP made ruthenium complexes containing the (/ ,S)-Xyliphos ligand to reduce a simple ketone to (5)-l-(3-trifluoromethylphenyl)ethanol, used in the synthesis of the fungicide (5)-MA20565 (Scheme 3). 

Asymmetric Transfer Hydrogenation of Ketones. The first reports on asymmetric transfer hydrogenation (ATH) reactions catalyzed by chiral metallic compounds were published at the end of the seventies. Prochiral ketones were reduced using alcohols as the hydrogen source, and Ru (274,275) or Ir (276) complexes were used as catalysts. Since then, many chiral catalytic systems for homogeneous ATH of ketones, imines, and olefins have been developed (37,38,256,257,277-289). The catalytic systems are usually based on ruthenium, rhodium, or iridium, and the ATH of aryl ketones is by far the most studied. Because of the reversibility of this reaction, at high conversions, a gradual erosion of the ee of the product has been frequently reported. An azeotropic 5 2 mixture of formic acid/triethylamine can be used to overcome this limitation. 

Asymmetric transfer hydrogenation (ATH) reactions of 2-substituted a-alko gr-p-ketophosphonates (602) driven by dynamic kinetic resolution, afforded the corresponding 2-substituted a-alko gr-p-hydroxyphos-phonates (603) with excellent levels of diastereo- and enantioselectivity (Scheme 175). The reactions have been promoted by using chiral ruthenium catalyst (604) and a 0.2 1 mixture of formic acid and triethylamine as the hydrogen source and solvent. ... 

Fig. 19 Amino acid-derived tridentate click chelators, 86, used as ligands in asymmetric transfer hydrogenation (ATH) reactions...

Asymmetric transfer hydrogenation (ATH), where an alternative source of hydrogen, e.g., hydrogen-donor (known also as the transfer hydrogenation reductant), is used, such as formic acid or iso-propopanol ... 

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. 

Asymmetric Transfer Hydrogenation of Imines. In spite of the great importance of optically active amines for pharmaceutical and agrochemical industries, the ATH of C=N imine bonds has been much less studied than that of ketone bonds (278,280,284,289,340). Cyclic imines are reduced with greater ee values than their acyclic counterparts. The existence of geometrical isomers for the latter is based on the encountered difference in selectivity. 

Asymmetric Transfer Hydrogenation of Imines in Water. The catalytic ATH of imines in aqueous solution has been, so far, much less studied than that of the ketones (289). The tried imines are shown in Figure 89. 

Ketones are among the most common unsaturated substrates containing a C=0 group. Homogeneous transition metal-catalyzed asymmetric hydrogenation (AH) and transfer hydrogenation (ATH) of prochiral ketones is one of the most powerful and efficient methods for... 

Application of ATH in Stereoselective Synthesis Murlcatacln can be isolated as a scalemic mixture from the seeds of Annona muricata Muricatacin and epi-muricata-cin showed anti-proliferative activity against certain cell Unes. The enantioselective total synthesis of a potent cytotoxic agent (- -)- p/-muricatacin was reported by Kumarasw-amy et employing Noyori catalytic asymmetric transfer hydrogenation of benzyl 128 to (15,25)-1,2-diphenylethane-1,2-diol, which subsequently reacted with 129 to produce a key chiral intermediate 130 (Scheme 30.26). 

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