Enantioselective heterogeneous hydrogenations

Enantioselective heterogeneous hydrogenations on platinum-alumina catalysts modified with cinchonidine (Cnd) is an asymmetric organic reaction... 

The first enantioselective heterogeneous hydrogenation of KPL was reported in a Japanese patent (Niwa ). Over a 5% Pt/C catalyst previously modified with Cnd in ethanolic solution at reflux, KPL was hydrogenated in benzene at 60 bar to (R)-PL with an ee of 36%. Later, a Pd/C catalyst modified with Cnd proved to be more effective and gave (R)-PL with an ee of 52% (see Baiker "). Even more effective proved to be a Pt-alumina-DHCnd catalysts that produced (R)-(-)-PL with an ee of 79% under optimal conditions (22°C and 70 bar) in toluene at low concentrations of alkaloid (Schuerch et al. ). 

Baiker, A. (2000) Transition state analogues-a guide for the rational design of enantioselective heterogeneous hydrogenation catalysts, J. Mol. Catal. A. Chem. 163, 203-220. 

Among the various strategies [34] used for designing enantioselective heterogeneous catalysts, the modification of metal surfaces by chiral auxiliaries (modifiers) is an attractive concept. However, only two efficient and technically relevant enantioselective processes based on this principle have been reported so far the hydrogenation of functionalized p-ketoesters and 2-alkanons with nickel catalysts modified by tartaric acid [35], and the hydrogenation of a-ketoesters on platinum using cinchona alk oids [36] as chiral modifiers (scheme 1). 

Chiral amines were always considered important targets for synthetic chemists, and attempts to prepare such compounds enantioselectively date back to quite early times. Selected milestones for the development of enantioselective catalysts for the reduction of C = N functions are listed in Table 34.1. At first, only heterogeneous hydrogenation catalysts such as Pt black, Pd/C or Raney nickel were applied. These were modified with chiral auxiliaries in the hope that some induction - that is, transfer of chirality from the auxiliary to the reactant -might occur. These efforts were undertaken on a purely empirical basis, without any understanding of what might influence the desired selectivity. Only very few substrate types were studied and, not surprisingly, enantioselectivities were... 

Enantioselective heterogeneous catalytic hydrogenation of acetophenone469 -471 to (R)-(-l-)-l-phenylethanol (ee 20%) in the presence of (S )-proline (the chiral auxiliary) was investigated. The effect of various catalytically active metals (Pt, Rh, Raney Ni, Pd), the reaction temperature and the amount of catalyst on the optical purity was studied. The correlation between the optical yield and the conversion, the concentration of the reactants, different pretreatment methods and additives was also investigated469 (equation 49). 

Enantioselective heterogeneous catalytic hydrogenation using a chiral catalyst was pioneered by Aka-bori and Izumi, who prepared a palladium catalyst supported on silk fibroin. The oxime acetates of diethyl a-ketoglutarate or of ethyl phenylpyruvate were hydrogenated to form glutamic acid (7-15% ee) and phenylalanine (30% Similarly, a palladium-poly-L-leucine catalyst was used for the asym-... 

Systematic studies on the enantioselective heterogeneous catalytic hydrogenation of carbonyl compounds were carried out by Izumi using Raney nickel modified with various chiral reagents. Hydroxy acids or amino acids were used for the modification of the nickel catalyst, and (-i-)-tartaric acid (2R,3R)... 

The presence of the quinuclidine base functionality makes them effective ligands for a variety of metal-catalyzed processes (Chapters 2-4). The most representative example is the osmium-catalyzed asymmetric dihydroxylation of olefins [9]. The metal binding properties of the quinuclidine nitrogen also allow to use cinchona alkaloids as metal surface modifiers, for example, in the highly enantioselective heterogeneous asymmetric hydrogenation of a-keto esters (Chapter 2). Both... 

Historically, the chiral modification of classical heterogeneous hydrogenation catalysts was the first successful approach to practically useful enantioselective catalysts [7]. (For a detailed update, see Chapter 11.) However, despite considerable efforts only two types of catalytic system are of practical importance for preparative purposes, namely Ni catalysts modified with tartaric acid, and cinchona-modified Pt (and to some extent Pd) catalysts. 

In contrast to Raney nickel catalysts ( 3.4.1), heterogeneous hydrogenation catalysts based on Pt, Rh or Pd do not induce asymmetry in the presence of tartaric acid [113, 578], Platinum catalysts modified by cinchona alkaloids 3.1 and 3.2 cause asymmetric hydrogenation of the carbonyl group of a-ketoesters with a high enantiomeric excess (> 90%). From other types of ketones, the enantioselectivities are lower. 

Until recently, access to optically active 3-hydroxyalkanoates by enantioselective transition metal catalysis was based primarily on the heterogeneous hydrogenation of 3-oxo esters by Raney nickel modified with tartaric acid and sodium bromide (see Section 2.3.1.1.). As far as homogeneous catalysis is concerned, the best optical induction (71 % ee) in the hydrogena-... 

New Chiral Modifier for Enantioselective Heterogeneous Catalytic Hydrogenation... 

The assun5>tion was correct that the 5 -a.a-diphenyl-2-pyrrolidimnethanol (DPPM) could be applicable as chiral modifier in heterogeneous hydrogenation. Although the afforded enantioselectivities are moderate (for ethyl pyravate 25%, for isophorone 40%), this cotr5>ound increases the narrow choice of chiral molecules that could be used as modifiers. 

Sipos, E., Tungler, A., Bitter, 1. (2002) New chiral modifier for enantioselective heterogeneous catalytic hydrogenation. Chemical Industries Series (Dekker), Catalysis of Organic Reactions, Morrell D.G., ed.) 89, 653-658. 

Smith, G.V., Notheisz, F. (1999) Enantioselective hydrogenations, in Heterogeneous Catalysis in Organic Chemistry, Acad. Press, pp. 97-117. Augustine, R.E., Tanielyan, S.K., Doyle, L.K. (1993) Enantioselective heterogeneous catalysts 1. A working model for the catalyst modifier sub-strate interactions in chiral pyruvate hydrogenations. Tetrahedron Asymm. 4, 1803-1827. 

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