Enantioselective catalysts creation

For a review see Reetz, M.T. (2001) Kombinatorische und evolutions-gesteuerte Methoden zur Bildung enantioselektiver Katalysatoren. Angeiv. Cbem., 113, 292-310 (2001) Combinatorial and evolution-based methods in the creation of enantioselective catalysts. Angew. Chem., Int. Ed., 40. 284-310. 

One of the outstanding characteristics of enzymes is that they are able to function as enantioselective catalysts and carry out chemical reactions with absolute stereospecificity. As a result, most natural compounds are produced as optically pure enantiomers. The enantioselectivity of enzymatic catalysis is ascribed to the formation of a multibonded complex of substrate and reagent within the active center of the chiral enzyme molecule. The creation of chemical systems capable of serving as enantioselective catalysts represents one of the central and most challenging problems of modern chemistry. In the last decades. 

Reetz M. Combinatorial and evolution-based methods in the creation of enantioselective catalysts. Angew. Chem. Int. Ed. 2001 40 284-310. 

Reetz MT, Zonta A, Simpelkamp J (1996) Efficient immobUzation of lipases by entrapment in hydrophobic sol-gel materials. Biotechnol Bioeng 49 527—534 Reetz MT (2001) Combinatorial and evolution-based methods in the creation of enantioselective catalyst. Angew Chem Int Ed 40 284-310... 

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] ... 

In the last 20 years a great deal of effort has been focused towards the immobilization of chiral catalysts [2] and disparate results have been obtained. In order to ensure the retention of the valuable chiral hgand, the most commonly used immobihzation method has been the creation of a covalent bond between the ligand and the support, which is usually a solid, hi many cases this strategy requires additional functionalization of the chiral hgand, and this change - together with the presence of the very bulky support - may produce unpredictable effects on the conformational preferences of the catalytic complex. This in turn affects the transition-state structures and thus the enantioselectivity of the process. 

Future challenges of major interest will be the creation of new catalysts and ligand types, and the identification of new catalytic reactions. While HTE can clearly be used to speed up this research, the large number of experiments associated with HTE has led in the past - and will continue to lead in the future -to totally unexpected findings. Ultimately, further applications outside the area of enantioselective catalysis are also expected. 

It is worthwhile emphasising that the abovementioned syntheses using chiral auxiliaries covalently bound to the substrate bearing the prochiral center prior to the creation of the new asymmetric centre mean converting the problem of enantiofacial recognition into a problem of diastereofacial selectivity i.e. the pair of enantiomers 41 and 42 are actually obtained from hydrolysis of two different diastereomers 39 and 40. In fact, "direct enantioselectivity" can only be attained by using an external chiral catalyst,23 as shown in Figure 9.1 [26]. 

Abstract 1,3-Dipolar cycloaddition reactions (DCR) are atom-economic processes that permit the construction of heterocycles. Their enantioselective versions allow for the creation of up to four adjacent chiral centers in a concerted fashion. In particular, well-defined half-sandwich iridium (111) catalysts have been applied to the DCR between enals or methacrylonitrile with nitrones. Excellent yield and stereoselectivities have been achieved. Support for mechanistic proposals stems from the isolation and characterization of the tme catalysts. 

Mikami et al. studied the Diels-Alder reaction between a-methylstyrene and n-butyl glyoxylate catalyzed by a titanium binolate catalyst.76-78 Addition of 0.5 equivalents of (Zf)-BINOL to 1 equivalent of the racemic catalyst accelerated the reaction and gave the product with 89.8% ee (Scheme 20). Enantiopure catalyst derived solely from (/ )-BINOL gave the product with 94.5% ee. Here the amplification originates from the creation of a new chiral complex 9 of higher efficiency (rate and enantioselectivity) with respect to each enantiomer of the original racemic catalyst. 

The catalytic activation of allylic carbonates for the alkylation of soft car-bonucleophiles was first carried out with ruthenium hydride catalysts such as RuH2(PPh3)4 [108] and Ru(COD)(COT) [109]. The efficiency of the cyclopen-tadienyl ruthenium complexes CpRu(COD)Cl [110] and Cp Ru(amidinate) [111] was recently shown. An important catalyst, [Ru(MeCN)3Cp ]PF6, was revealed to favor the nucleophilic substitution of optically active allycarbonates at the most substituted allyl carbon atom and the reaction took place with retention of configuration [112] (Eq. 85). The introduction of an optically pure chelating cyclopentadienylphosphine ligand with planar chirality leads to the creation of the new C-C bond with very high enantioselectivity from symmetrical carbonates and sodiomalonates [113]. 

Therefore, catalytic activity and enantioselectivity essentially depend on the specific Pt surface area of the catalyst. This means that Pt particles of appropriate geometry and size are necessary to generate high enantioselectivity and catalytic activity. Zeolites Y, mordenite and erionite turned out to be appropriate templates for the creation of such Pt particles during catalyst preparation. This was confirmed by temperature-programmed CO desorption measurements. 

Ma F, Hanna MA (1999) Biodiesel production a review. Biores Technol 70 1-15 Magnusson A, Hull K, Holmquists M (2001) Creation of an enantioselective hydrolase by engineered substrate-assisted catalysis. J Am Chem Soc 123 4354 355 Manjon A, Iborra JL, Arocas A (1991) Short-chain flavour ester synthesis by immobilized lipase in organic media. Biotechnol Lett 13 339-345 Margolin A (1996) Novel crystalline catalysts. TIBTECH 14 223-230... 

Another approach involves the stereoselective creation of the sulfinyl moiety by oxidative processes. One possibility is the use of a sulfide (4) bound to a chiral auxiliary R, with a structure or a functional group (usually a hydroxy) able to control the course of the transformation of sulfide (4) into sulfoxide (2). A second approach is the enantioselective oxidation of an achiral sulfide. In this case, the chiral auxiliary is connected to the oxidant, and the process is stoichiometric with respect to the chiral auxiliary. The most efficient production of chiral sulfoxides results where the chiral auxiliary is part of m oxidation catalyst, when, in principle, a large amount of enantiopure sulfoxide (2) is produced from a small amount of the chiral auxiliary. 

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