Pt-cinchona system

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

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],... 

Ni/tartrate and the Pt/cinchona systems and describe the proposed conclusions concerning their mode of action. As usual the first hypotheses were based on qualitative and unsystematic observations as described in Section in. These were then refined or rejected in the course of further investigations. 

FIGURE 18.2 Alcohols prepared with the Pt-cinchona system and best ee s reported. 

Significant progress in the substrate scope of the Pt-cinchona systems has been made in the last 5 years. Besides a-keto acids and esters, a-keto acetals, a-keto ethers, and some trifluoromethyl ketones have been shown to give high ee s. It is now possible to classify ketones concerning their suitability as substrates for the Pt-cinchona catalyst system, as depicted in Figure 18.6. Nevertheless, for the synthetic chemist, the substrate scope is still relatively narrow, and it is not expected that new important substrate classes will be found in the near future. However, the chemoselectivity of this system has not yet been exploited to its full value, and this might be a potential for future synthetically useful applications. 

There are two views on the origin of enantiodifferentiation (ED) using Pt-cinchona catalyst system. In the classical approach it has been proposed that the ED takes place on the metal crystallite of sufficient size required for the adsorption of the chiral modifier, the reactant and hydrogen [8], Contrary to that the shielding effect model suggest the formation of substrate-modifier complex in the liquid phase and its hydrogenation over Pt sites [9],... 

Starting from the Pt-cinchona modified system, more recently an interesting concept has been developed by Feast and coworkers [144], A chiral acidic zeolite was created by loading one molecule of iM,3-dithianc-l-oxide per supercage of zeolite Y, either during or after the zeolite synthesis. Other chiral zeolites were formed by adsorbing ephedrine as a modifier on zeolites X and Y for the Norrish-Yang reaction [145],... 

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. 

Scheme 1 The best enantiomeric excesses in the hydrogenation of activated ketones with the Pt - cinchona alkaloid system...

Fig. 3.16 The Pt/cinchona alkaloid system for the enantio-selective hydrogenation of a-functionalized ketones.

Here, the key step was the enantioselective hydrogenation of methoxyacetone (Fig. 4), in analogy with the Pt-cinchona-catalyzed hydrogenation of a-ketoesters [5] (the Ru-binap system was not known at that time). It was anticipated that the nucleophilic substitution with a clean inversion would be difficult. 

The CV for dihydrocinchonidine adsorption on Pt(976) is identical to that for its adsorption on Pt(976) (Figure 2). The absence of an adsorption rate differentiation in this system, viewed alongside the presence of a reaction differentiation in the Pt/sugar system, suggests that molecular recognition in these chiral systems may require relatively weak interactions, and that perhaps the cinchona alkaloids are too strongly adsorbed to show delicate chiral-chiral interactions under these conditions. 

The repeated use of Pt-alumina modified by dihydrocinchonidine was studied by Balazsik and Bartok for the enantioselective hydrogenation of ethyl pyruvate under mild experimental conditions in toluene and AcOH. In toluene, depending on the reaction conditions, an increase of ee by 10-20% was observed on the reused catalysts. The same effect, however, was not found in AcOH. The phenomenon was attributed to an intrinsic feature of the Pt-alumina-cinchona system, in which the restructuring of the Pt surface may play an important role. 

One of the simplest approaches to the creation of an enantioselective catalyst is the adsorption of a chiral molecule (often referred to as a modifier) onto the surface of a metal catalyst. The metals most commonly employed for this type of catalysis have been the Pt group metals and Ni [29]. The most successful chiral modifiers have been naturally occurring alkaloids (Pt) and tartaric acid (Ni) (Scheme 5.2). Each system has primarily been used for hydrogenation reactions with Pt/cinchona producing ee values of greater than 90% for the hydrogenation of a-ketoesters [42, 43] ... 

The principles of the SE were applied for two enantioselective hydrogenation reactions (i) hydrogenation of P-keto esters over Ni-tartrate and (ii) hydrogenation of a-keto esters over cinchona-Pt/Al203 catalysts. In this respect the tartaric acid - P-keto ester system gave a negative result. Neither the substrate nor the modifier have bulky substituents required for SE. 

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],... 

In order to evaluate the catalytic characteristics of colloidal platinum, a comparison of the efficiency of Pt nanoparticles in the quasi-homogeneous reaction shown in Equation 3.7, with that of supported colloids of the same charge and of a conventional heterogeneous platinum catalyst was performed. The quasi-homogeneous colloidal system surpassed the conventional catalyst in turnover frequency by a factor of 3 [157], Enantioselectivity of the reaction (Equation 3.7) in the presence of polyvinyl-pyrrolidone as stabilizer has been studied by Bradley et al. [158,159], who observed that the presence of HC1 in as-prepared cinchona alkaloids modified Pt sols had a marked effect on the rate and reproducibility [158], Removal of HC1 by dialysis improved the performance of the catalysts in both rate and reproducibility. These purified colloidal catalysts can serve as reliable... 

Cinchona-modified platinum catalysts received special interest mainly because of to the results obtained for the hydrogenation of methyl pyruvate (MP) or ethyl pyruvate. E.e. s up to 80% or even higher (98% for ethyl pyruvate) made this system one of the most interesting ones from the application point of view. At present, 5% Pt/alumina with low dispersion (metal particles > 2 nm) and a rather large pore volume constitutes one of the best catalysts commercially available. 

The best studied systems are the Raney Ni/tartaric acid/NaBr combination, for the hydrogenation of / -functionalized ketones, and the Pt- and Pd-on-support/cinchona alkaloid systems for the enantioselective hydrogenation of a-functionalized ketones. 

Enantioselective hydrogenation of a-ketoesters on cinchona alkaloid-modified Pt/Al203 is an interesting system in heterogeneous catalysis [143-146], The key feature is that on cinchonidine-modified platinum, ethyl pyruvate is selectively hydrogenated to R-ethyl lactate, whereas on einchonine-modified platinum, S-ethyl pyruvate is the dominant product (Figure 16) [143]. 

Recently, the enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona modified Pt/Al203 (ref. 1) was shown to be a ligand accelerated reaction (ref. 2). The rate of reaction for the fully modified system is more than 10 times faster than the racemic hydrogenation using unmodified catalyst. Under certain reaction conditions, this liquid phase hydrogenation exhibits a turn-over frequency of up to 50 s 1 (3.4 mol/kg-cat s). Emphasis until now has been directed at empirically increasing optical yields (ref. 3,4). 

Sutherland, Ibbotson, Moyes and Wells have published a detailed account of the heterogeneous enantioseleetive hydrogenation of methyl pyruvate (CH3COCOOCH3) to R-(+)-methyl lactate over Pt/siliea surfaces modified by sorbed cinchona alkaloids.16 Kinetic, isotherm and molecular modeling calculations were used to develop an idea of the role of the cinchonidine modifier. This system is quite unusual high enantioselectivity is achieved only with Pt, only in the presence of cinchonidine modifiers and only for the hydrogenation of a-ketoesters. 

In this chapter, we do not attempt to give a comprehensive overview of the field, but we would rather concentrate on results where both enantioselectivity and catalyst activity are relevant to preparative application. In the first section, results obtained with cinchona-mediated homogeneous systems for the reduction of ketones are briefly reviewed. Then, heterogeneous cinchona-modified Pt catalysts applied to the hydrogenation of a-functionalized ketones and cinchona-modified Pd catalysts for the hydrogenation of activated C=C bonds are discussed from a synthetic point... 

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