Cinchonidine-modified catalyst

Cinchonidine modified catalysts, though, have been effectively used for several other enantioselective hydrogenations. Platinum-cinchonidine catalysts have been used for the hydrogenation of the a ketolactone, 36, to D-pantolactone (37) in 35% ee at complete conversion (Eqn. 14.26) while palladium-cinchonidine catalysts have been used for the enantioselective dehydrohalogenation of a,a-dichloro-2-benazapinone (38) (Eqn. 14.27) and the hydrogenation of (E) a phenylcinnamic acid (39) to (S) 2, 3-diphenylpropionic acid (40) in a 44% ee (Eqn. 14.28). ... 

Hydrogenation of the free acids over unmodified catalyst occurred slowly, proceeded to completion in 20 h and gave racemic product as expected Enantioselective hydrogenation occurred at a slower rate over alkaloid-modified catalyst, cinchonidine modification providing an excess of S-product and cinchonine an excess ofR-product... 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

In catalysis, adsorbed CO may retard some reactions such as olefin hydrogenation, fuel cell conversion, and enantioselective hydrogenation. For instance, Lercher and coworkers observed the deactivation of Pt/Si02 in the liquid-phase hydrogenation of crotonaldehyde, and ascribed this deactivation to the decomposition of crotonaldehyde on platinum surface to adsorbed CO [138]. Blaser and coworkers found that the addition of a small amount of formic acid decreases the rate of liquid-phase hydrogenation of ethyl pyruvate on cinchonidine-modified Pt/Al203 catalyst, which they explained as the decomposition of formic acid on the catalyst to adsorbed CO. Interestingly, the addition of acetic acid does not decrease the reaction rate, but whether acetic acid decomposes on the catalyst as formic acid does was not mentioned [139]. 

Theoretical calculations proved that the reaction intermediate leading to R-ethyl lactate on cinchonidine-modified Pt(lll) is energetically more stable than the intermediate leading to the S-ethyl lactate [147], However, the catalytic system is complex and the formation and breaking of intermediates are transient, so it is certainly difficult to obtain direct information spectroscopically. It is therefore advisable to use simplified model systems and investigate each possible pairwise interaction among reactants, products, catalyst, chiral modifier, and solvent separately [147, 148]. In order to constitute these model systems, it is important to get initial inputs from specific catalytic phenomena. 

Catalyst preparation. Activity and selectivity of the cinchonidine modified Pt catalysts have been shown to depend primarily on the platinum salt used for impregnation and the reduction method. Support material and platinum content also influence the catalyst performance [31, 59]. The best results (optical yields >80%) are obtained when catalyst precursors, made by impregnation of the alumina with 5% H2PtCl6, are reduced in aqueous solutions of Na(HCOO), K(HCOO) or CH20 [59], Commercial catalysts can be used [30, 31]. 

Heterogeneous catalytic hydrogenation of the methyl esters of a-keto acids over modified metal catalysts other than nickel have been studied using a cinchonidine-modified platinum catalyst. " Methyl pyruvate and methyl benzoylformate were hydrogenated to form methyl (R)-lactate and (R)-mandelate with high ee (81-84%). 

This paper deals with the asymmetric hydrogenation of ethyl pyruvate to ethyl lactate showing a high enantiomeric excess in favour of the R-enantiomer over (-)cinchonidine modified Pt/carrier catalysts. Due to their regular structures, zeolites in particular have been used as carrier materials. 

Enantiomeric excess and catalytic activity of the asymmetric hydrogenation of ethyl pyruvate over (-)cinchonidine modified Pt/carrier catalysts depend significantly on the specific Pt surface area This is due to the morphology of the Pt particles and to surface chemical Pt/support interaction. Thus, reaction pathway control is possible by varying these parameters. 

Enantioselective hydrogenation of ( )-a-phenylcinnamic acid on cinchonidine-modified palladium catalysts influence of support... 

In the course of the studies to improve the enantioselectivity of cinchonidine-modified Pd catalysts for the hydrogenation of 1, we found that the support materials used in the catalyst preparation, as well as the preparation method, had significant influence on the activity and selectivity of the resulting catalysts [12-14], The highest optical yield (72%ee) of 2 was obtained with a Pd/TiOi catalyst under optimal reaction conditions [15], In the present study,... 

Catalysts were pre-modified by immersion in solutions of cinchonidine in dichloromethane. 200 mg samples of catalyst were stirred for 10 min in 25 ml of 0.34 or 3.4mM solutions of alkaloid. Modified catalyst was filtered and dried under vacuum before use. 25 mg (Pt/silica) or 50 mg (Pt/a-alumina) samples were used in the reactor. 

Pt/a-alumina was active in the unmodified state for racemic hydrogenation of methyl pyruvate and in the cinchonidine-modified state for enantioselective hydrogenation of the ester. Conversions observed in reactions over unmodified and modified catalysts over the first hour of time on line are shown in Figure 1. Activity decayed with time in each case and modification by alkaloid reduced catalytic activity. 

Gas phase enantioselective hydrogenation of methyl pyruvate over cinchonidine modified Pt has been achieved. Enantioselectivity was accompanied by a reduction in reaction rate. Modifier concentration during catalyst preparation determined catalyst performance. 

Table 4 - Enantioselective Hydrogenation of Methyl Pyruvate Catalysed by Cinchonidine Modified Ir/silica catalyst in Ethanol Solution at 293 K and 10 bar pressure.

The PtySi02 catalyst EUROPT-l/cinchonidine modifier system has also been evaluated Tor substrates similar but different to [Pg.12]

The enantioselective hydrogenation of fluoroketones on cinchonidine modified Pt-alirmina in toluene with and without trifluoroacetic acid was also studied, and it was proposed that the compounds responsible for the chiral induction were the intermediate complexes, the structures of which depended on whether hydrogenation was performed with or without TFA An unexpected change in the sense of enanatioselectivity was observed in the hydrogenation of ethyl pyruvate (EtPy) over Zreto-isocinchonine modified Pt-alumina catalysts, where (A)-(-)-ethyl lactate was the major product in toluene, while (5)-(+)-EtLt was formed in AcOH... 

Minder, R, Mallat, T., Srabal, P., Baiker, A. (1994) Enantioselective hydrogenation of ethyl pyruvate-influence of oxidative treatment of cinchonidine-modified platinum catalyst and hemiketal formation in alcoholic... 

Nitta, Y., Kobiro, K. (1995) Solvent effect on enantioselective hydrogenation of ( )-fl//7/ja-phenylcinnamic acid with cinchonidine-modified Palladium catalysts, Zeft 165-165. 

Nitta, Y., Kubota, T., Okamoto, Y. (2000) Preparation of cinchonidine-modified Palladium catalysts for the enantioselective hydrogenation of ( )-fl// /ifl-Phenylcinnamic acid. Bull. Chem. Soc. Jpn., 73,2635-2641. Tungler, A., Nitta, Y., Fodor, K., Farkas, G., Mathe, T. (1999) Comparison of chiral modifiers in the Pd catalysed hydrogenation of phenylcinnamic acid and isophorone, J. Mol. Catal. A. Chem. 149, 135-MO. 

Taskinen, A., Paivarinta, J., Hotokka, M., and Murzin, D.Y. (2004) A combined experimental and theoretical study of l-phenylpropane-l,2-dione hydrogenation over heterogeneous cinchonidine-modified Pt catalyst. J. Catal, 224, 326-339. doi 10.1016/j.jcat.2004.03.022... 

Deuterium exchange into starting material recovered from asymmetric reductions of fraui-2-methyl-2-pentenoic acid with cinchonidine-modified Pd/Al203 catalysts has been observed ... 

The hydrogenation of methyl pyruvate proceeded over 4% Pd/Fe20 at 293 K and 10 bar when the catalyst was prepared by reduction at room temperature Racemic product was obtained over utunodified catalyst, modification of the catalyst with a cinchona alkaloid reduced reaction rate and rendered the reaction enantioselective. S-lactate was formed in excess when the modifier was cinchonidine, and R-lactate when the modifier was cinchonine... 

The hydrogenation of ehtyl pyurvate (EtPy) was carried out at 23 °C in a SS autoclave equipped with an injection chamber for separate introduction of the modifier Cinchonidine (CD) and Troger s base (TB) was used as modifiers. Different batches of EtPy, (Fluka) and Pt/Al203 catalysts (Engelhard E 4759, 5 %w Pt, Dpt = 25 %) were used. Experimental details incliding GC analysis can be found elsewhere [3,12]. The optical yield was calculated as e.e. = ([R]-[S])/([R]+[S]). The e.e. values were corrected for the amount of racemic product formed in minor amount in the reactor prior to the injection of CD. 

In the most effective, chirally modified catalytic systems, Pt/cinchonidine and Raney-Ni/tartaric acid, the enantioselectivity was also sensitive to the method of catalyst preparation and on support properties (5, 6). 

Pt/Al2C>3-cinchona alkaloid catalyst system is widely used for enantioselective hydrogenation of different prochiral substrates, such as a-ketoesters [1-2], a,p-diketones, etc. [3-5], It has been shown that in the enantioselective hydrogenation of ethyl pyruvate (Etpy) under certain reaction conditions (low cinchonidine concentration, using toluene as a solvent) achiral tertiary amines (ATAs triethylamine, quinuclidine (Q) and DABCO) as additives increase not only the reaction rate, but the enantioselectivity [6], This observation has been explained by a virtual increase of chiral modifier concentration as a result of the shift in cinchonidine monomer - dimer equilibrium by ATAs [7],... 

---