Enantioselective Hydrogenation with Solid Catalysts

Chitin (Fig. 27) was supported on silica by grinding the two solids together. The Pt complex was tested as a catalyst in the enantioselective hydrogenation of racemic 1-phenylethanol to obtain (i )-l-cyclohexylethanol [82]. Up to 65% yield with 100% ee was obtained and the catalyst was reused five times with almost the same results. 

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

We have identified reaction conditions where intrinsic kinetics can be obtained for the very fast enantioselective hydrogenation of ethyl pyruvate using a commercially available Pt/Al203 powder catalyst, modified with dihydrocinchonidine. We conclude that this is in pan due to i) the egg-shell structure of the catalyst, ii) the high turbulence achieved in the reactor and iii) the density and/or the viscosity of the solvent used. In solvents like ethyl pyruvate, liquid-solid transpon problems can arise. 

The topic of this chapter is enantioselective hydrogenation over chiral or chirally modified solid catalysts. Diastereoselective hydrogenation of chiral compounds and asymmetric hydrogenation with heterogenized (supported, embedded) homogeneous transition metal complexes will not be discussed. 

Despite the importance of this reaction for the synthesis of chiral amines and amino acids, no effective solid catalyst is yet available [3]. There are two instances where 26 % ee was achieved (Fig. 9), but results with silk-supported Pd are difficult to reproduce, and in the hydrogenation of acetophenone oxime and pyruvic acid oxime stoichiometric amounts of chiral auxiliary were used [21,49]. The latter reaction was also extremely slow - only 15 % yield of alanine was obtained in 45 h. Efficient enantioselective hydrogenation of imines and oximes apparently remains a challenge for future development. 

As described later in Chapter 9, it is necessary to sulfonate an asymmetric catalyst to produce a water-soluble version. In supporting this on a solid as described, the water is first evacuated. However, an exact amount is reintroduced by contact with water vapor because the presence of water is necessary and the extent of enantioselectivity depends on the amount of water. A useful application of SAP catalysis is the use of SAP-Ru-BINAP-4SOjNa supported on controlled pore glass GPG-240 (supplied by CPG Inc.) in the enantioselective hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid to naproxen (Wan and Davis,... 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

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