Pd-Silk Catalyst

In 1956 Akabori et al. reported an entirely new type of asymmetrie catalysts, Pd deposited on natural silk, which was active in the hydrogenation of C=C and C=N bonds. Silk fibroin has a rigid structure, and can coordinate metal cations. So, if silk fibroin is boiled with aqueous Pd-chloride and after the formation of the chelate complex, it is reduced, one obtains a Pd catalyst in which Pd atoms are embedded in an asymmetric environment. 

More effective, with an ee of 35%, was the hydrogenation of the azlactone of the 2-acetamidocinnamic acid, into D-(+)-A-acetylphenyl-alanine, 6.  

These Pd-silk catalysts are of interest but after their publications there was no confirmation in the literature on the enantioselectivity of these catalysts, and moreover, the same authors noted bad reproducibility of these data. The results varied with the type of silk. 

Moreover, if the silk-fibroin was dissolved in copper-ammonia solution and reprecipitated, its chiral properties were lost. It seems therefore, that the asymmetric properties depends not only on the asymmetric structures of the fibroin but also on the asymmetric structure of the whole molecule 

Although these catalysts were not very promising as asymmetric catalysts, they proved to be very perspective liquid phase hydrogenation catalysts. They have very low densities, may be spun or woven into sheets or cloth, and can be readily separated from reactants. 

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For the Pd-silk catalyst,2 PdCl2 was deposited on silk and reduced to Pd° moderate enantioselectivities were obtained for the hydrogenation of a C=C bond (66% enantiomeric excess, ee, which is the difference between enantiomers divided by the sum of enantiomers), but the silk support presented two problems it tended to deteriorate with time on stream and it varied from source to source, so enantioselectivities were not reproducible (Scheme 3.2). On the other hand, deterioration was not a problem with the metal-quartz catalysts. 

This is the earliest strategy for preparing a chiral solid hydrogenation-dehydrogenation catalyst (for reviews see [l-3,5,7,8]). Quartz, silk fibroin, cyclodextrin, and cellulose were applied as chiral supports of natural origin. With a Pd/silk catalyst up to 66 % optical yield was obtained in C=C bond hydrogenation, but subsequently the results proved irreproducible. 

The first successful experiments were reported by Schwab [16] Cu, Ni and Pt on quartz HI were used to dehydrogenate racemic 2-butanol 23. At low conversions, a measurable optical rotation of the reaction solution indicated that one enantiomer of 23 had reacted preferentially (eeright-handed quartz gave the opposite optical rotation it was deduced that the chiral arrangement of the crystal was indeed responsible for this kinetic resolution (for a review see [8]). Later, natural fibres like silk fibroin H5 (Akabori [21]), polysaccharides H8 (Balandin [23]) and cellulose H12 (Harada [29]) were employed as chiral carriers or as protective polymer for several metals. With the exception of Pd/silk fibroin HS, where ee s up to 66% were reported, the optical yields observed for catalysts from natural or synthetic (H8, Hll. H13) chiral supports were very low and it was later found that the results observed with HS were not reproducible [4],... 

The stereoselectivity of the silk-catalysts was demonstrated by the production with almost 100% ee ofZ-proline on Pd-silk orZ-omithine on Pt-silk A catalyst of 6% Pd-silk was used also in the pilot scale for hydrogenation of nitrotoluenes into amines with 80% yield. ... 

Mesityl oxide hydrogenated 1 hr. with Pd-silk at 30 /90 atm. methyl isobutyl ketone. Y 86%.—The catalyst is particularly suitable for the prepn. of satd. aliphatic aldehydes and ketones from the corresponding unsatd. compounds. F. e. and reductions s. Y. Izumi, Bull. Ghem. Soc. Japan 32, 936 (1959). 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

SCHEME 14. Asymmetric hydrogenation with silk fibroin-Pd catalyst. 

The first report of enantioselective catalysis over metal catalysts was made in 1939 by Lipkin and Stewart who showed that hydrocinchonine / -methylcinnamate could be hydrogenated in ethanol over an Adams Pt catalyst to yield / -phenylbutyric acid which exhibited an optical rotation of 8%.89 Some 20 years later, Akabori and co-workers reported that Pd supported on silk-fibroin was enantioselective for compounds containing both C=N and C=C functionalities, yielding optical yields as high as 66%, although the origin of the enantioselectivity in these systems has never been clear.90 A further 20 years later, Orito and co-workers reported... 

An asymmetric synthesis involving the hydrogenation of a prochiral olefin can be accomplished over an asymmetric heterogeneous catalyst such as Ni or Pd on d- or /-quartz. This asymmetric environment gives low optical yields. Better results are obtained over finely divided Ni in alkaline glucose solution or Pd deposited on silk fibroins which gives optical yields up to 70%. 

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. 

A similar mechanism of action was found in the case of a Pd catalyst supported on silk fibroin in the asymmetric hydrogenation of C=N bonds in prochiral compounds. The mechanism of action consists of the formation of the chiral complexes on the silk fibres of the Pd-fibroin which act as chiral catalysts. This principle was later developed for a number chirally modified catalysts that are very effective in the asymmetric hydrogenation of Acta-keto esters... 

Polymers can find use in heterogeneous catalysis as support for metallic catalysts (as we have seen in the example of Pd dispersed on silk or resins [78, 80, 82]). A third class should be added, that of insoluble polymers containing catalytic pendant groups (e.g. a polyvinylimidazole in a system in which only substrate and products are soluble, and not the polymer). However, this kind of catalysis has not yet been investigated in detail. 

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