Prochiral compounds, asymmetric

If kinetic resolution is being studied, the ratio of pseudo-e nantiomers can be measured by MS, allowing for the determination of ee-values (and/or of selectivity factors E). The same applies to the reaction of pseudo prochiral compounds. This system has been used successfully in the directed evolution of enantioselective enzymes. However, it should work equally well in the case of asymmetric transition metal catalyzed reactions. In the original version about 1,000 ee-deter-minations were possible per day (Figure 6).94 The second-generation version based on an 8-channel multiplexed spray system enables about 10,000 samples to be handled per day, the sensitivity being 2% ee.96... 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

Asymmetric synthesis starts with a prochiral compound. This is a compound which is not chiral, but can be converted into a chiral compound by a chiral (bio) catalyst. Subsequently, two types of prochiral compounds can be distinguished The first one has a stereoheterotopic face (which usually is a double bond) to which an addition reaction takes place. An example is the conversion of the prochiral compound propene into 1,2-epoxypropane (which has two enantiomers, of which one may be preferentially formed using an enantioselective catalyst). The second type of prochiral compound has two so-called enantiotopic atoms or groups. If one of these is converted, the compound becomes chiral. Meso-compounds belong to this class. Figure 10.5 and 10.6 show some examples of the different types of asymmetric catalysis with prochiral compounds. 

Kinetics of Asymmetric Synthesis from Prochiral Compounds... 

Asymmetric Induction during Cathodic Reduction of Prochiral Compounds in the Presence of Chiral Cations... 

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

Numerous biotranformation processes for fhe synthesis of amino acids have been described and for fhe purpose of this chapter, we have restricted the discussion to fhe unnatural amino acids fhat are not accessible by fermentation. For this class of amino acids, commercialized biotranformations are either based on asymmetric synthesis starting from a prochiral compound or on (dynamic) kinetic resolutions of a racemate. As an illustration the published processes for (R)- and (S)-tert-leucine are outlined in Scheme 4.4. Both stereoisomers of tert-leucine have been used for fhe synfhesis of peptides that serve as protease inhibitors acting against viral infections (e.g. Hepatitis C, HIV), bacterial infections, autoimmune diseases and cancer [27]. This particular amino acid is versatile in fhese applications since fhe tert-butyl moiety provides resistance against endogenous proteases and can enhance the binding affinity of fhe peptide to fhe target protease. 

Asymmetric deprotonation of a prochiral compound having a sufficiently acidic C-H bond can be performed by a lithium amide generated from an enantio-pure secondary amine or by an organolithium reagent in the presence of a chiral tertiary amine [557, 559]. A chiral mixed aggregate is usually formed [77, 81, 974], and the reaction of this intermediate with electrophiles (including proton sources) can lead to a predominant enantiomer. 

An asymmetric synthesis at silicon was developed starting from tetragonal silicon compounds. Prochiral compounds of type R1R2SiX2 having two enantiotopic functional groups X are of particular interest. Owing to the many stereospecific substitution reactions that can be performed at a functional silicon atom, the preparation of optically... 

A similar mechanism of action was found in the case of a Pd catalyst supported on silk fibroin in the asymmetric hydrogenation of C=N bonds in prochiral compounds. The mechanism of action consists of the formation of the chiral complexes on the silk fibres of the Pd-fibroin which act as chiral catalysts. This principle was later developed for a number chirally modified catalysts that are very effective in the asymmetric hydrogenation of Acta-keto esters... 

Colloid catalysts with chiral stabilizing agents can be used as asymmetric catalysts in the reactions of prochiral compounds. One such catalyst is the well-known "Skita-catalyst"(colloidal Pt or Pd with gum-arabicum as an optical active polysaccharide as a protective colloid). These catalysts have been used very often in a number of hydrogenations of unsaturated compounds, including prochiral molecules, but never were their asymmetrizing action noted. Nevertheless, including chiral components as protective colloids in such catalysts allowed for the discovery of asymmetric effects in their action. Indeed, Balandin, Klabimovskii et al. found small... 

The first attempts to use the asymmetric hydrogenation of prochiral compounds with C=C and C=N bonds over chiral modified heterogeneous Pt and Pd catalysts were not effective. Lipkin and Stewart found that the (+)-... 

This book contains many publications which represent analyses of the steps of elaboration of effective heterogeneous enantioselective hydrogenation catalysts, of their significant role in the theory of catalysis, and of their role in the practice of asymmetric catalysis. In addition to reviewing the first works on catal Tic hydrogenation of C=C double bond in prochiral compounds on metal catalysts supported on chiral carriers, which admittedly have only historical interest, the Chapters 1-3 review data on asymmetric adsorption of enantiomers and separation of racemic mixtures on organic and inorganic adsorbents. 

Kagan reported on asymmetric hydrosilylation of prochiral compounds with carbon-nitrogen double bonds.TV-(a-methylbenzylidene)benzyl-... 

Synthesis of a chiral compormd from an achiral compound requires a prochiral substrate that is selectively transformed into one of the possible stereoisomers. Important prochiral substrates are, for example, alkenes with two different substituents at one of the two C-atoms forming the double bond. Electrophilic addition of a substitutent different from the three existing ones (the two different ones above and the double bond) creates a fourth different substituent and, thus, an asymmetric carbon atom. Another class of important prochiral substrates is carbonyl compounds, which form asymmetric compounds in nucleophilic addition reactions. As exemplified in Scheme 2.2.13, prochiral compounds are characterized by a plane of symmetry that divides the molecule into two enantiotopic halves that behave like mirror images. The side from which the fourth substituent is introduced determines which enantiomer is formed. In cases where the prochiral molecule already contains a center of chirality, the plane of symmetry in the prochiral molecules creates two diastereotopic halves. By introducing the additional substituent diasterom-ers are formed. 

In conclusion, several methods are now at the disposal of the chemist which permit him to prepare optically active polymers with a hydrocarbon backbone and a great deal of structure and properties. Future work in this area should be mainly devoted to the attainment of optically active catalytic systems able to select with high specificity one enantiomer from a racemic mixture or to give a high asymmetric induction in the polymerization of prochiral compounds. 

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