Catalysis chiral discrimination

Most of the work on chiral recognition in the ground state deals with salts having chiral, primary alkylammonium cations. Another approach is the chiral discrimination between two enantiomeric anions present as counterions in metal-cation complexes (Lehn et al., 1978). Discrimination between enantiomeric transition states will be dealt with in the next section together with non-chiral mimicry of enzymic catalysis. 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

We found that inorganic helical structures such as helical silica serve as chiral triggers for asymmetric autocatalysis (Scheme 23). In the presence of helical silica, the enantioselective addition of z-P Zn to 2-alkynylpyrimidine-5-carbaldehyde 11 was examined. In the presence of right-handed helical silica, (S)-5-pyrimidyl alkanol 12 was formed [123]. In contrast, in the presence of left-handed helical silica, (S)-5-pyrimidyl alkanol 12 with high ee was obtained. These results clearly show that asymmetric auto catalysis can discriminate the helical structure in artificially tuned inorganic silica. 

In order to fulfill the function of chiral discrimination and enantioselective catalysis as well as some others, the corresponding dimeric and ohgomeric... 

Hilker et al. [59] studied the Novozym 435-catalyzed copolymerization of racemic a,a -dimethyl-l,4-benzenedimethanol with secondary hydroxyl groups with dimethyl adipate. Due to CALB enantioselectivity, hydroxyl groups at (R) stereocenters preferably reacted to form ester bonds with liberation of methanol. The reactivity ratio was estimated as (R)/(S) = 1 x 106. In situ racemization of monomer stereocenters from (S) to (R) by ruthenium catalysis allowed the polymerization to proceed and reach high functional group conversations. Readers should also refer to Chapter 11 for more information on chiral discriminations by lipases. 

Yet another full paper from the Cram group details the catalysis of transacylation of the 4-nitrobenzoate esters of several a-amino-acid salts by the thiol-crown (100), and the extent of chiral discrimination shown by the (5)-catalyst in favour of L-amino-acid substrates. These results are rationalized in terms of a model for preferred transition-state complexation cf. 1, 422). 

Asymmetric autocatalysis with amplification of chirality is a very efficient method of asymmetric catalysis. One of the implications is that the existence of a chemical reaction has been shown in which very slight bias of chirality can be amplified significantly to reach almost enantiopure. The reaction has been employed for the study on the origins of homochirality and on the chiral discrimination. We describe how we find the reaction and the recent aspects of asymmetric autocatalysis. 

CILs are a subclass of ILs in which the cation or the anion (or both) may be chiral. The chirality can be either central, axial, or planar. It is well established that chirality plays an important role in chemistry. Over the last few years, research for new chiral selectors, solvents, and materials based on CILs has become a topic of increasing interest. A growing number of CILs have been designed, synthesized, and utilized for potential applications in chiral discrimination and separation [24], asymmetric catalysis and synthesis [25], as well as optical resolution of racemates [26]. Because of their high-resolution abilities and liquidus properties, CILs can be used as either chiral agents in regular solvent, or chiral solvents, or both simultaneously. With the rapid development of CILs, these new chiral solvents have the potential to play an important role in enantioselective organic chemistry, chiral separation chemistry, and chiral materials chemistry. Thus, their role in these fields is expected to expand tremendously. 

A chiral Ru hydride 23 is formed and it is assumed that the hydrogen transfer occurs via metal-ligand bifunctional catalysis. The N-H linkage may stabilize a transition state 24 by formation of a hydrogen bond to the nitrogen atom. Stereochemistry is determined by formal discrimination of the enantiofaces at the sp2 nitrogen atom of the cyclic imine. 

The key NMR observations (i) that the proportion of homo- and heterochiral dimers is near-equal, and (ii) that their interconversion by a dissociative process is rapid compared to catalytic turnover, preclude the possibility of a monomer autocatalyst. In Kagan s classification, monomer catalysis with a positive NLE may only arise when there is an unequal concentration of homo- and heterochiral oligomers, in favour of the heterochiral form, which acts as a reservoir for the deficient enantiomer. NMR results show that the resting state for Soai s autocatalysis is an equal mixture of homo-and heterochiral species, predominantly dimeric. The lack of ground-state stereo-discrimination requires that the number of chiral entities in the resting state must be less than or equal to the number in the enantioselectivity-determining transition state, else there is no possibility of the vital non-linear effect. Even after the publication of these results in late 2004, their consequences are not always applied. For recent discussions where a monomeric catalyst for Soai s system is permitted or promoted, see [91-93]. 

Enzymic resolutions involve acceptance by the enzyme, which is a very finely honed chiral system, of one enantiomer of a racemic compound, but not the other. The selective acceptance arises because interactions between the enzyme and the enantiomers are diastereomeric. In its natural environment, the ability of an enzyme to discriminate between enantiomers is virtually absolute. In addition to their stereoselectivity, some enzymes can react at very high rates. Each round of catalysis by the enzyme carbonic anhydrase with its physiological substrate occurs in about 1.7 jus at room temperature, although for a small number of other enzymes, best exemplified by the more lethargic lysozyme, the corresponding figure is about a million times slower. Accordingly, the enzyme-catalysed hydrolysis of, say, one enantiomer of an ester proceeds at a finite rate and hydrolysis of the other not at all. Resolutions such as those of 39, 42 and 45 therefore have a kinetic basis and are also known as kinetic resolutions. 

We reported the first examples of asymmetric catalysis of intramolecular carbonyl-ene reactions of types (3,4) and (2,4), using the BINOL-derived titanium complex (1) [54,57]. The catalytic 7-(2,4) carbonyl-ene cyclization gives the ox-epane with high ee, and gem-dimethyl groups are not required (Scheme 18). In a similar catalytic 6-(3,4) ene cyclization, the trans-tetrahydropyran is preferentially obtained with high ee (Scheme 19). The sense of asymmetric induction is exactly the same as observed for the glyoxylate-ene reaction the (i )-BINOL-Ti catalyst provides the (i )-cyclic alcohol. Therefore, the chiral BINOL-Ti catalyst works efficiently for both the chiral recognition of the enantioface of the aldehyde and the discrimination of the diastereotopic protons of the ene component in a truly catalytic fashion. 

The geometry of a chiral 6-membered chelate ring is not conducive to effective asymmetric catalysis. Consider square-planar complexes of d[, l-2,3-diphenyl-l,3 bis (diphenylphosphino) propane (24), which are presumed to exist in chair conformation (Scheme 6) with rapid ring inversion. The close approximation to a-symmetry in the environment of the metal suggests that there will be little discrimination between the diastereomeric modes of binding of a prochiral bidentate ligand, since substituents on the olefin experience similar steric interactions in both isomers. The expectation of low selectivity is borne out in practice, for in some cases enamide complexes derived from this phosphine exist in two diastereomeric forms (Figure 3). 

There are few examples of the reactions of alkenes with diazoesters of chiral alcohols which give high face discrimination in rhodium-catalyzed reactions [936, 1497). However, Davies and coworkers [192, 193, 1503] have performed the reactions of alkenes with vinyldiazoesters of chiral alcohols under Rh2(OAc)4 or better yet Rh2(OCOC7H j 5)4 catalysis. The ester of (K)-pantolactone 1.16 is the most efficient substrate, and ftum-cyclopropanecarboxylates are obtained highly selectively. Starting from 7.141 (R = Ph), the enantioenriched plant hormone l-amino-2-phenylcyclopropanecarboxylic acid has been prepared (Figure 7.88). 

If nucleophilic attack constitutes the stereoselective step, special substitution patterns of the intermediate rc-allylpalladium complex are suitable for enantioselective catalysis, Racemic substrates with identical substituents in positions 1 and 3 give rise to chiral complexes incorporating a meso-n- y ligand. In this case, enantioselectivity is determined by discrimination of the nucleophile for the diastereotopic termini of the allylic system. 

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