Enantioselective Reactions in Organic Solvents

The exploitation of hydrolases as catalysts in organic solvents is described in the following sections. The overview is by no means comprehensive, and the selection of examples is subjective. The names of the hydrolases will be those used by the authors, despite the fact that some of the names have been changed since the cited work was published. 

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Cyclopropanation reactions involving ethyl diazoacetate and olefins proceed with high efficiency in aqueous media using Rh(II) carboxy-lates. Nishiyama s Ru(II) Py-box and Katsuki s Co(II) salen complexes that allow for highly enantioselective cyclopropanations in organic solvents can also be applied to aqueous cyclopropanations with similar results. In-situ generation of ethyl diazoacetate and cyclopropanation also proceeds efficiently (Eq. 3.33).135... 

C. S. Chen and C. J. Sih, Enantioselective biocatalysis in organic solvents. Lipase catalyzed reactions, Angew. Chem. 1989,... 

Lipases are the most frequently used enzymes in organic chemistry, catalyzing the hydrolysis of carboxylic acid esters or the reverse reaction in organic solvents [3,5,34,70]. The first example of directed evolution of an enantioselective enzyme according to the principle outlined in Fig. 11.2 concerns the hydrolytic kinetic resolution of the chiral ester 9 catalyzed by the bacterial lipase from Pseudomonas aeruginosa [8], This enzyme is composed of 285 amino acids [32]. It is an active catalyst for the model reaction, but enantioselectivity is poor (ee 5 % in favor of the (S)-acid 10 at about 50 % conversion) (Fig. 11.10) [71]. The selectivity factor E, which reflects the relative rate of the reactions of the (S)- and (R)-substrates, is only 1.1. 

MTO [methyltrioxorhenium(VII), cf. Chapter 3.3.13] can be used as a catalyst for the epoxidation of olefins with urea hydroperoxide in [EMIMJBF4 [19]. The activity is reported to be comparable with the reaction in organic solvents but side reactions are suppressed. The use of an ionic liquid as a co-solvent in CH2CI2 for the enantioselective Mn-salen complex-catalyzed epoxidation of olefins with Na(OCl) was reported to result in enhanced reaction rates at no loss of enantioselectivity [20]. Cr-salen complexes can further be used for the asymmetric kinetic resolution of epoxides by ring-opening with azide [21]. 

Compared to studies of enantioselective Diels-Alder reactions in organic solvents, there are few reports in water. The first reported enantioselective Diels-Alder reaction in water used... 

In recent years a lot of information related to the use of ionic Uquids as media for organocatalytic reactions catalyzed by chiral amine derivatives has been reported [11,13, 24]. ILs specifically solvate polar enamine or iminium intermediates generated from a carbonyl substrate and a catalyst and significantly polarize nucleophilic or electrophilic compounds that enantioselectively interact with these intermediates (Figure 22.1), leading to a rise in reaction rates, sometimes at the expense of a slight drop in the enantiomeric enrichment of products as compared with similar reactions in organic solvents [12]. 

The enantioselectivity of an enzymatic reaction is usually expressed by the enantiomeric excess (e.e.) and several group studies focus on die experimental conditions that are finalized to reach the maximum e.e. In these cases, we will select the results that show the highest enantioselectivity of the process. The enantiomeric ratio is a parameter introduced to express quantitatively the enantiopreference of an enzyme by the analysis of the kinetic data [40-42], and recent refinements of the calculation of E are based on new computer programs [43,44]. The enantioselectivity of an enzymatic reaction in organic solvents can be improved in different ways. The enzyme can be biologically modified via... 

Similar reactions can be realized in the presence of acetone powder from germinating rapeseed [69] or with immobilized lipase in supercritical carbon dioxide [70]. The application of interesterification reactions to enantioselective resolutions has found scarce examples. For instance, it has been reported that when racemic 2-(p-chlorophenoxy)propionic acid is used to exchange with acetic acid of the racemic acetates of a bicycloheptanol and 2-methoxycyclohexanol, optically active p-chlorophenoxy esters are obtained (Scheme 4). The enzymatic process is diastereoselective and doubly enantioselective for the acid and alcohols [71]. Another example of enantioselective interesterification in organic solvents leading to a nearly optically pure octanoate (Scheme 5) proceeds via acid exchange of the formate of a pyranyl alcohol with methyl octanoate [72]. 

Cemia et al. [90] found an increase in enantioselectivity, conversion, and remaining activity of the lipase for acylation of different secondary alcohols in SCCO2 compared to reactions in organic solvents. 

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