Cinchonidine catalyst

The (R) enantiomer was prepared with 40% ee using the cinchonidine catalyst (2). When the vinyl group of... 

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). ... 

Investigation of the Michael addition reaction of phosphonate carba-nions to a-nitroalkenes revealed that diethyl ether, used either as an achiral additive for the cinchonine or a mixture of cinchonine/cinchonidine catalysts or as a solvent, delivered different stereoisomers of y-nitroalkylpho-sphonates (203) than in THF, often with a reversal of enantioselectivity (Scheme 71). ... 

The hydrogenation of the esters methyl tiglate, methyl trifluorotiglate, and methyl angelate occurred slowly over 1% Pd/SiOa at room temperature and 10 bar pressure. Modification of the catalyst by cinchonidine or cinchonine induced no enantioselectivity under any conditions Typical results are given in Table 2. 

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 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 reduction of this ester over Pd differed from the corresponding reaction over Pi in every important particular. Enantiomeric excess was low (high over Pt) and in the reverse sense (e g cinchonidine modification provided an S-excess in the product over Pd but an R-excess over Pt) Enantioselective reactions underwent self-poisoning over Pd (proceeded to completion over Pt), were of non-integral order (integral over Pt) and proceeded more slowly than reaction over unmodified catalyst (enhanced rate over Pt) Enantioselective reaction was solvent-specific over Pd (not over Pt) and was favoured by low catalyst reduction temperature (high reduction temperature for Pt)... 

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). 

Influence of Achiral Tertiary Amines on the Enantioselective Hydrogenation of a,p-diketones Over Cinchonidine-Pt/Al203 Catalyst... 

Enantioselective hydrogenation of 2,3-butanedione and 3,4-hexanedione has been studied over cinchonidine - Pt/Al203 catalyst system in the presence or absence of achiral tertiary amines (quinuclidine, DABCO) using solvents such as toluene and ethanol. Kinetic results confirmed that (i) added achiral tertiary amines increase both the reaction rate and the enantioselectivity, (ii) both substrates have a strong poisoning effect, (iii) an accurate purification of the substrates is needed to get adequate kinetic data. The observed poisoning effect is attributed to the oligomers formed from diketones. 

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],... 

Further amount of cinchonidine (4.8xlCr M) injected at 60 min, bdouble amount of Pt/Al203 CD injection technique, Tr 20 °C pH2 50 bar, catalyst 0.125g 5% Pt/Al203 (E4759), in all experiments after 240 min the yield of hexanediols is less than 5 %. 

CD cinchonidine S substrate 3,4-HD 3,4-hexanedione premixing technique Tr 20 °C pm 50 bar amount of catalysts used was calculated to have equal amount of surface platinum (Pts) in each reaction. 

The enantioselective hydrogenation of a,p-unsaturated acids or esters, using 5wt% Pt/Al203 or Pd/Al203 commercial catalysts doped with cinchonidine (CD), was deeply investigated to evidence the specific activity of Pd or Pt and the role of the reaction parameters and solvent polarity. Finally, the steric and electronic effects of different substituent groups were also studied. 

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 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],... 

Another interesting observation using molecular sieves supported by Ru catalysts is the one related to the effect of the modifier. The use of an alkaloid-type modifier, like cinchonidine, enhances the d.e. to the same (1 IS, 15R) form. But the use of TA leads to a decrease in the d.e., and the addition of pivalic acid in mixture with TA leads to a spectacular inversion in diasteieoselectivity, resulting in the isomer with natural-like configuration, namely (1 IS, 15S). 

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