Orito reaction

One notable property of the Orito reaction is that two chiral modifiers, CD and CN, are diastereomers of each other. The configurations of the functional groups which are expected to create the molecular recognition are antipodes, and only the... 

Scheme 10.2 The Orito reaction enantioselective hydrogenation of ketone over CD- or CN-modified Pd/C...

A transition-state model of the Orito reaction is presented at the end of the section although various models have been proposed on many occasions, the structure shown in Figure 10.2 is currently the most reliable. The CD is adsorbed onto the catalyst surface with the quinoline ring facing against the surface, while the hydroxy group stays near the surface. In this conformation (the so-called Open-3 ), the ammonium proton at the quinuclidine interacts with the carbonyl and is reduced. 

For example, the Pt-alumina-alkaloid catalytic systems proved to be the best for enantioselective hydrogenations of 2-oxocarboxylic acids and their esters, especially the pyruvates (Blaser Baiker ), and the formates (Orito et al. ), originally studied in the "Orito Reaction" (see Bartok et... 

Owing to the last experimental and theoretical works in the study of the Orito reaction some insight in the mechanism of the reaction has been gained but full understanding has not yet been achieved. Therefore much more effort is needed in the future, especially in studying the role of the nature of the metal catalysts and the effects of triple intermediate complexes, [Metal-Modifier-Reactant], in enantioselectivity as shown in the case of the enantioselective hydrogenation of alpha-keio esters on tartaric acid modified Ni, Cu, and Co eatalysts... 

Bartok, M., Felfoldi, K., Szollosi, G., Bartok, T. (1999) Rigid cinchona conformers in enantioselective catalytic reactions new cinchona-modified Pt catalysts in the Orito reaction, Catal. Lett. 61, 1-5. 

Lavoie, S., Laliberte, M.A., McBreen, P.H. (2003) Adsorption states and modifier-HSubstrate interactions on Pt (111) relevant to the enantioselective hydrogenation of alkyl p Tuvates in the Orito reaction, J. Amer. Chem. Soc. 125, 15756-15757. 

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 alkaloid-modified catalyst can be easily prepared either by stirring the metal catalyst with a solution of the alkaloid in air and subsequent separation by decantation, as described by Orito and coworkers [103], or by in situ addition of alkaloid to the reactant mixture [226], Good OYs are achieved with both methods. Reactions are generally carried out at room temperature, or slightly above, and at hydrogen pressures in the range 1 to 10 MPa. The best solvent is AcOH. Under optimal reaction conditions the decrease in e.e. can be ascribed to the hydrogenation of the modifier. 

Another useful method is the modification of Pt black by cinchona alkaloids, initially developed by Orito, which permits the asymmetric hydrogenation of a-keto esters in up to 90% optical yield (Scheme 17) (43). The reaction with Pt-Al203 modified by cinchonidine can be carried out on 10-200-kg scale in greater than 98% chemical yield and in... 

Systematic investigation of the Pt - cinchona alkaloid system, discovered by Orito et al. in 19797, has led to a better understanding of the a-ketoester-modifier-Pt interaction. It has been therefore possible to increase the enantioselectivities of the original reaction and, more importantly, to broaden the application range of cinchona-modified platinum. 

In 1989, a different approach was published by Orito [60], in which elaidinization ((Z) —> ( ) double bond isomerization) is used to obtain ( )-MNA from a (Z, )-mixture ofdiastereomers (Scheme 4.6). Gannet had observed that the iodine-induced photoisomerization of the methyl ester of MNA (48) gave only a 7 3 ( /Z) mixture [59], but Orito obtained a better diastereomeric ratio (8 1) using nitrous acid. Remarkably, no double-bond migration to form the more stable trisubstituted olefin was observed. This discovery paved the way to a very simple and general synthesis of the acidic component of capsaicinoids. Thus, a Wittig reaction of the phosphonium salt of a 6-bromohexanoic acid (49) with isobutyraldehyde (SO) afforded a 1 11... 

Orito also developed a variation of this synthesis, based on the Wittig reaction of the phosphonium salt from isobutylbromide with a series of lactols. After alcohol-to-acid oxidation, a mixture of MNA isomers is obtained, then isomerized with nitrous acid [61,62]. 

The group of Baiker also conhibuted significanhy to the Orito reachon. For the classic combinahon of the Pt/CD/pyruvate ester, these authors found that a side (aldol) reaction affected the product ee-value, and that some improvement was observed following its removal [11]. Conhnuous hydrogenahon in a fixed-bed reactor was also demonstrated in supercritical ethane [12] and in acehc acid [13]. The range of applicable substrates was also expanded to P-trifluoromethyl-P-ketoester [14], cyclohexane-1,2-dione [15], aromahc methyl ketones [16], -hydroxyketones [17] and isahn derivatives [18]. Some selected results are shown in Scheme 10.3. 

The use of Kieselguhr did not increase but actually somewhat decreased ee s even when modification was carried out by the method of Orito at pH 4.1. The reaction rate on all samples of Ni-Si02-TA catalysts were similar and amounted to 1.4 - 0.8 mmol/min/g Ni. The introduction of Pd decreased somewhat the average size of the crystallites, which increased the rate of reaction, but did not increase ee s. However, according to Orito the catalysts on Kieselguhr with added Pd are more active (the rates of the reactions were 2.5-8.7 nunol/min/g Ni ) and more enantioselective, with ee s 63.8 - 89.1%. Thus, contrary to Orito s data the introduction of Pd and the use of Kieselguhr as a support does not lead to the formation of especially effective catalysts... 

The Sj reaction has been featured in other indole syntheses, such as Molina and Fresneda s route to crypto-tackieine (Scheme 2, equation 1 [8]) and Orito s approach to indolo[2,l-fl]isoquinoline alkaloids (equations 2 and 3 [9]), even though neither substrate seems suitable for an Sj reaction. The successful indolization in equation 3 precludes a thermal electrocyclization mechanism because the gem-dimethyls block the required imine tautomerism. 

Each catalyst has been modified by the deposition on its surface of cinchonidine(I) and used for the high pressure hydrogenation of methyl pyruvate, MeCOCOOHe, to HeCH(0H)C00Me according to our variation of Orito s method (refs. 7, 17). The reaction provides an excess of R-(+)-lactate. Typical optical yields (%R - %S) at 290 K and 25 to 50% conversion were 87% over... 

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