Kagan catalyst

In terms of catalyst development, studies by Otsuka and Tani led the way with a (+)-D10P-modified cobalt catalyst (Kagan, 1972). [126] Diethylneryl-amine could be converted, in 23 % yield and with an enantiomeric excess of 32 %, to the corresponding enamine of citronellal. However, concomitantly a dien-amine was produced in quantities which were not insignificant. 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

HORNER - KNOWLES - KAGAN Asymmetric Hydrogenation Enantnselective hydrogenation of prochirai olefins with chiral Rh catalysts... 

Until now, only a few effective ligands of this type have been identified (Fig. 25.4). Kagan and co-workers [5] prepared one of the few chiral diphosphines with only planar chirality and obtained 95% ee for the hydrogenation of DM IT with LI (Table 25.1, entry 1.1.), but enantioselectivities for several enamide derivatives were below 82% ee (the best results were with the cyclohexyl analogue of LI). For the reactions with DM IT or MAC, the cationic Rh-kephos complex showed comparable or better performance than corresponding duphos catalysts. 

Of several procedures for the stereoselective oxidation of sulfides using organometallic complexes, two adaptations of Kagan s original process have gained prominence. In the first method the diol (36) is reacted with Ti(0 Pr)4 to form the catalyst. With cumyl hydroperoxide as the stoichiometric oxidant, methyl para-tolyl sulfide was converted into the optically active sulfoxide in 42 % yield (98 % ee)[109]. 

In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

Kagan and coworkers studied the reaction between cyclopentadiene and 310 in the presence of aluminum alcoholates of chiral diols and their chiral mono ethers208. Among the various diols studied, only 1,1-diphenyl-1,2-propanediol (325) gave satisfactory results. Optimization by variation of the dienophile/catalyst ratio, aging of the catalyst and variation of the temperature ultimately resulted in a maximum of 86% ee at —100 °C. 

The development of a large scale manufacturing route to Esomeprazole is described by Federsel and Larsson ° using the titanium catalyst originally described by Kagan and Luukas. Employment of a tartaric acid derived chiral auxiliary, with the addition of a base such as diisopropylethylamine to the reaction mixture, resulted in a full-scale catalytic process capable of delivering multi-ton quantities of product with optical yields well above 90 %, a figure which could be raised to 99.5 % ee by recrystallization from methyl isobutyl ketone. 

Much attention has been paid to asymmetric amplification where the enantiomeric excess ( ) of the product is higher than that of the chiral catalyst (equation 35)136. The first experiment on asymmetric amplification was reported by Kagan and coworkers in the Katsuki-Sharpless asymmetric epoxidation of allyl alcohols137. Asymmetric amplification has also been studied in the asymmetric addition of dialkylzincs to carbonyl compounds. 

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