Ketone hydrogenation chiral alcohols

Surface modification of skeletal nickel with tartaric acid produced catalysts capable of enantiose-lective hydrogenation [85-89], The modification was carried out after the formation of the skeletal nickel catalyst and involved adsorption of tartaric acid on the surface of the nickel. Reaction conditions strongly influenced the enantioselectivity of the catalyst. Both Ni° and Ni2+ have been detected on the modified surface [89]. This technique has already been expanded to other modified skeletal catalysts for example, modification with oxazaborolidine compounds for reduction of ketones to chiral alcohols [90],... 

Hydrogenation The enantioselective reduction of prochiral ketones to chiral alcohols has been intensely investigated. The highest enantioselectivity has been found for 2-acetylpyridine, which was reduced in buffered EtOH (pH 4.5), in the presence of strychnine to l-(2-pyridyl[-ethanol with 48% ee. The selectivity was... 

Abdur-Rashid, K. Faatz, M. Lough, A. J. Morris, R. H. Catalytic cycle for the asymmetric hydrogenation of prochiral ketones to chiral alcohols Direct hydride and proton transfer from chiral catalysts trans-Ru(H)2(diphosphine) (diamine) to ketones and direct addition of dihydrogen to the resulting hydridoamido complexes. ]. Am. Chem. Soc. 2001,123, 7473-7474. 

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.). 

Closely related to the concept of chirality, and particularly important in biological chemistry, is the notion of prochirality. A molecule is said to be prochiral if can be converted from achiral to chiral in a single chemical step. For instance, an unsymmetrical ketone like 2-butanone is prochiral because it can be converted to the chiral alcohol 2-butanol by addition of hydrogen, as we ll see in Section 17.4. 

In another context, chiral thioimidazolidine ligands have been successfully applied to the ruthenium-catalysed asymmetric hydrogen transfer of several aryl ketones by Kim et al., furnishing the corresponding chiral alcohols with high yields and enantioselectivities of up to 77% ee (Scheme 9.12). ... 

Manufacture of ruthenium precatalysts for asymmetric hydrogenation. The technology in-licensed from the JST for the asymmetric reduction of ketones originally employed BINAP as the diphosphine and an expensive diamine, DAIPEN." Owing to the presence of several patents surrounding ruthenium complexes of BINAP and Xylyl-BINAP, [HexaPHEMP-RuCl2-diamine] and [PhanePHOS-RuCl2-diamine] were introduced as alternative catalyst systems in which a cheaper diamine is used. Compared to the BINAP-based systems both of these can offer superior performance in terms of activity and selectivity and have been used in commercial manufacture of chiral alcohols on multi-100 Kg scales. 

A number of ketones, pharmaceutical compounds, alcohols and hydroxy acids have also been resolved on this phase [724,765-767]. A chiral polysiloxane phase with tartramide substituents has been used for the separation of enantiomers capable of hydrogen bonding interactions with the stationary phase, such as enantiomers containing carboxylic, hydroxyl and amine functional groups [768]. 

On the other hand a direct hydrogen transfer through a Meerwein-Ponndorf mechanism, involving coordination of both the donor alcohol and the ketone to the copper site may also be considered. In this case, by using alcohols other than 2-propanol, we could expect some difference in stereochemistry. This would also imply the possibility of carrying out the enantioselective reduction of a prochiral ketone with a chiral alcohol as donor. 

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... 

Equation (81)), while the other two C=C double bonds in the structure are intact. Under the same reaction conditions, the racemic carvone is also resolved kinetically with a KR/KS ratio of 33 1. Asymmetric hydrogenation of a,/Tacetylenic ketones to chiral propargylic alcohols is still unavailable. 

Asymmetric Hydrogenation of Enol Esters. Prochiral ketones represent an important class of substrates. A broadly effective and highly enantioselective method for the asymmetric hydrogenation of ketones can produce many useful chiral alcohols. Alternatively, the asymmetric hydrogenation of enol esters to yield a-hydroxyl compounds provides another route to these important compounds. 

Asymmetric hydrogenation of ketones is one of the most efficient methods for making chiral alcohols. Ru-BINAP catalysts are highly effective in the asymmetric hydrogenation of functionalized ketones,54,55 and this may be used in the industrial production of synthetic intermediates for some important antibiotics. The preparation of statine 65 (from 63b R = i-Bu) and its analog is one example (Scheme 6-28).56 Table 6-6 shows the results when asymmetric hydrogenation of 63 catalyzed by RuBr2[(R)-BINAP] yields threo-64 as the major product. 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

Hydrosilylation can be applied to alkenes, alkynes, and aldehydes or ketones. A wide range of metal compounds can be used as a catalyst. The most common and active ones for alkenes and alkynes are undoubtedly based on platinum. Hydrosilylation of C-0 double bonds gives silyl ethers, which are subsequently hydrolysed to their alcohols. The reaction is of interest in its enantioselective version in organic synthesis for making chiral alcohols, as the achiral hydrogenation of aldehydes or ketones does not justify the use of expensive silanes as a reagent. 

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