Cinchonidine enantioselective sites

Fig. 9.12 Methyl pyruvate adsorbed by each of its enantiofaces at the enantioselective site adjacent to cinchonidine adsorbed in the open-3 conformation. On hydrogenation (a) gives R-lactate and (b) gives S-lactate.

Cinchonidine, being a bulky molecule, reduces the accessible active platinum surface as it adsorbs and should causes some deactivation with respect to racemic hydrogenation. The decrease in formation rate of the main product after the maximum can be a result of poisoning by adsorbed spectator species, which inhibit enantiodifferentiating substrate-modifier interaction. Adsorbed cinchonidine in parallel mode (active form) provides an enantioselective site (Figure 7.8) and when the reactant is adsorbed in the vicinity, interaction between reactant and modifier leads to such orientation that hydrogenation towards the main product (e.g. B or 1-R enantiomer) is preferred. However, when the tilted form (Figure 7.8) of... 

In addition to the enantioselective effect, cinchona alkaloids also produce a rate acceleration, i.e. this is an example of ligand accelerated catalysis [14]. The model of a non-closepacked ordered array of cinchonidine molecules adsorbed on platinum, proposed by Wells and co-workers, was abandoned in their later study [15]. Augustine [16] deduced from the behaviour of this system at low modifier concentrations that the chiral sites are formed at the edge and comer platinum atoms, which involve the adsorbed cinchonidine and a metal adatom. The different authors agreed that the quinoline ring of the modifier is responsible for the adsorption on platinum, the quinuclidine part, through the nitrogen atom, interacts with... 

Only the Pt particles sited at the external surface of the zeolites can participate in the enantioselective hydrogenation, because the cinchonidine used as chiral auxiliary is too large to penetrate the zeolitic pore systems. 

Bi adsorbed at steps in the polycrystalline Pt surface and lowered enantioselectivity. Thus cinchonidine adsorbed at or near a step was more effective as a modifier than cinchonidine adsorbed elsewhere on the terrace away from the step. On this basis S, which adsorbed preferentially on the terraces away from the steps, raised enantioselectivity because it blocked away-from-step sites of lower enantioselectivity leaving a larger proportion of reaction to occur at the near-step sites. 

This study has shown (a) that sites at the polycrystalline Pt surface adjacent to steps give higher enantioselectivities than sites on terraces when both are available for cinchonidine and pyruvate ester adsorption (b) that the rate enhancement in the presence of alkaloid is due at least in part to the ability of organic N-bases to inhibit pyruvate ester conversion to... 

The simplest cinchona alkaloids, cinchonidine and its 10,11-dihydro-derivative, have been shown by D-tracer studies and by NEXAFS and ATR-IR spectroscopy to adsorb by interaction of the quinoline moiety with the platinum surface. Mechanistic studies have established that a site exists adjacent to the open-3 conformation of adsorbed cinchonidine at which pyruvate ester can undergo selective enantioface adsorption. Hydrogenation of the preferred enantioface results in preferential formation of one enantiomer of the product, methyl lactate, MeC H(OH)COOMe. Pt modified by cinchonidine provides R-lactate preferentially, whereas the near enantiomer cinchonine provides 5-lactate in excess. Values of the enantiomeric excess of 75% can be obtained without optimisation, and of 98% under special conditions. In solution, conditions that achieve enantioselectivity normally promote the reaction rate by a factor of 2 to 100 depending on conditions. ... 

The differences between the two systems are (i) the reaction on modified sites is faster then on unmodified ones (Pt-cinchonidine) (ii) the hydrogenation of pyruvic acid ester is enantioselective even if the cinchonidine is only solved in the reaction mixture without premodification of the catalyst. 

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