Homochiral dimers enantiomers

In a related study involving structurally similar chiral methylzinc anisyl fencholates, both chiral amplification and depletion were observed in the catalytic alkylations of benzaldehyde.209 Thus, methylzinc anisyl fencholates, bearing sterically small substituents in the ortho-position of the anisyl group, crystallized preferentially as homochiral dimers, as shown for the methyl-substituted anisyl group in Scheme 91. Because of the greater stability of the homochiral dimers, scalemic mixtures of both enantiomers of the ligand showed a chiral depletion of the benzyl alcohol. 

Enantiomer recognition is a general principle in chemistry. Molecular recognition is achieved by numerous electronic and steric factors including chirality. This is also the case among molecules with the same atomic composition and connectivity. As illustrated in Scheme 27, chiral (/ ,/ )- or (5,5)-tartaric acid may be seen as a homochiral dimer of the / - or 5-pyramidal radicals, respectively meso tartaric acid is a result... 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

In addition to the chiral interactions of enantiomers, interactions of dissimilar chiral species are fundamentally important. As described above, adenine becomes chiral upon adsorption and forms homochiral dimer chains on Cu(110). These chains are tilted 19.5° with respect to the [001] surface direction. This tilt makes the sites right next to an enantiomorphous supramolecular chain chiral Consequently, the interactions of inherently chiral molecules with both chain types are energetically nonequivalent. This... 

Dimers RR and SS are termed homochiral dimers, whereas the mixed dimer RS is termed a heterochiral dimer. A fraction of pure enantiomer is always a mixture of the monomer and the corresponding homochiral dimer, but it does not contain any heterochiral dimer. It was shown, that the separation of the excess enantiomer of a non-racemic feed mixture is the combination of two effects [31], the difference in reaction equilibrium constants of the homo- and heterochiral dimerization reaction and the difference in the adsorptivity of the homo- and heterochiral dimers. 

Non-linear relationships between ee of catalyst and ee of product require some dimeric species. Suppose the true catalyst, the zinc derivative of the product, forms dimers. There are two diastereoisomers of these, a meso dimer 229 and a homochiral dimer 230. If the me so dimer is more stable than 230 it will absorb all the minor enantiomer 227 leaving only the major enantiomer 228 to catalyse the reaction. Of course, it could be the homochiral dimer 230 that is the active catalyst as the dimers have spare coordination sites on zinc. This phenomenon is described in more detail in an excellent paper.52... 

With the Noyori catalyst, the heterochiral dimer is considerably more stable than the homochiral dimer. The latter decomposes to the active, monomeric catalyst immediately upon exposure to a dialkylzinc or an aldehyde, whereas the heterochiral dimer does not. Thus, the minor enantiomer of the catalyst is tied up by the major enantiomer. ... 

The product alcohol catalyses its own formation and the reaction shows spectacular asynunetric amplification. If small amounts of product with 5% ee are added at the beginning of the reaction, new product is formed with 55% ee. If this product is used as a catalyst in consecutive reactions, nearly enantiopure product is achieved after a few runs. Even starting with completely racemic material, the reaction product is generally produced non-racemic, with stochastically either one or the other enantiomer in excess (23). Other chiral compoimds can direct the reaction towards the selective production of one particular enantiomer as well. About any form of chiral template has been shown to induce this effect, from helical hydrocarbons to chiral quartz crystals. The mechanism of this remarkable reaction was deduced with the help of kinetic studies and involves catalytically active homochiral dimers and inactive heterochiral ones (24, 25). 

The relative stability of the homochiral and the heterochiral dimers arising from self-CI of an equimolar mixture of the L and the D enantiomers of dimethyl- and di-isopropyltartrate has been evaluated by Nikolaev et al. using the FT-ICR... 

The chiral discrimination in the self-association of chiral l,3a,4,6a-tetrahydroi-midazo[4,5-d]imidazoles 3 has been studied using density functional theory methods [37], (Scheme 3.20). Clusters from dimers to heptamers have been considered. The heterochiral dimers (RR SS or SS RR) are more stable than the homochiral ones (RR RR or SS SS) with energy differences up to 17.5 kJ mol-1. Besides, in larger clusters, the presence of two adjacent homochiral molecules imposes an energetic penalty when compared to alternated chiral systems (RR SS RR SS...). The differences in interaction energy within the dimers of the different derivatives have been analyzed based on the atomic energy partition carried out within the AIM framework. The mechanism of proton transfer in the homo- and heterochiral dimers shows large transition-state barriers, except in those cases where a third additional molecule is involved in the transfer. The optical rotatory power of several clusters of the parent compound has been calculated and rationalized based on the number of homochiral interactions and the number of monomers of each enantiomer within the complexes. 

For the reactive system the x-axis corresponds to pure R enantiomer containing only homochiral RR dimer, and the y-axis corresponds to pure S enantiomer containing only homochiral SS dimer. Racemic concentrations line on the bisection line. A mixture with excess R enantiomer lies in the lower half-plane and a mixture with excess S enantiomer lies in the upper half-plane. 

The relative stability of the homochiral and the heterochiral dimers arising from self-CI of an equimolar mixture of the L and the D enantiomers of dimethyl- and di-isopropyltartrate has been evaluated by Nikolaev et al. using the FT-ICR technique.366-369 The dimer chirality effect, Khomo/= 0.33 corresponds to a AAG°98 = — RT ln(Arhomo/Arhelero) = 0.65 kcal mol-1 value at 20 °C, a value which is slightly larger than those measured in the CIMS experiments (0.25-0.50 kcal mol-1).358,359 The lack of chirality effects, observed when the used tartrates are replaced by the L and the D enantiomers of methyl lactate, alaninamide, and Af-acetyl-a-methyl-benzylamine, is attributed to their extensive racemization after protonation. 

Figure 1.36. Dimeric 1,4-adducts of Cgo with a noninherently chiral functionalization pattern in each spheroid. Whereas the combination of homochiral moieties leads to a d, l pair of enantiomers, that of heterochiral cages gives rise to a meso form.

Thus, when a mixture of (-)- and (+)-52 was used, two types of dimeric species were formed homochiral 53-(S) and 53-(R) and heterochiral meso (5S,Sp,5 R,RTp ) dimer. The enantiomeric monomers are the active catalysts in this reaction and each one produces predominantly one enantiomer of phenyl propanol. In this alkylation with diethylzinc, it is logical to conclude that if dimers are formed the heterochiral that retains the minor enantiomer of the catalyst should be less implicated in the reaction, leaving the homochiral-enriched dimer free to operate as the active agent or its precursor. 

The optical purity is usually, but not always, equal to enantiomer excess. In order for the two to be equal, it is necessary that there be no aggregation. It is possible, for example, that a homochiral or heterochiral dimer (see Glossary, Section 1.6, for definitions) would refract the circularly polarized light differently than the monomer (or each other). In 1968 [19] Krow and Hill showed that the specific rotation of (S)-2-ethyl-2-methylsuccinic acid (85% ee) varies markedly with concentration, and even changes from levorotatory to dextrorotatory upon dilution. In 1969 [20], Horeau followed up on Krow and Hill s observation, and showed that the optical purity (at constant concentration) and enantiomer excess of (5)-2-ethyl-2-methylsuccinic acid were unequal except when enantiomerically pure or completely racemic. This deviation from linearity is known as the Horeau effect, and its possible occurence should be remembered when determining enantiomeric purity by polarimetry. 

As it turns out, the zinc alkoxide produced after the reaction of one equivalent of diethylzinc dimerizes (Scheme 4.6). When both enantiomers of the amino alcohol are present, both homochiral and heterochiral dimers may be formed. 

One possibility is that heterochiral dimerization of the ligand or the titanium complex produces an inactive catalyst this tends to sequester the minor enantiomer cf. Scheme 4.6). Another is that the catalyst is a dinuclear species, which is more reactive when homochiral. 

SCHEME 24. Enantiomer recognition of zinc alkoxides homochiral versus hetero-chiral dimerization. 

Hargcr ct a), reported the discrimination by NMR spectroscopy of both enantiomers of alkylphcnylphospinic amides The observed spectra can be rationalized in terms of dimerization through hydrogen bonds [Fig. 4a (top)]. In this system there was no marked preference for homochiral or heterochiral dimerization, and the partnerexchanging was fast on the NMR time scale. In an cnantiomcrically unbalanced sample, the major enantio-... 

An example of chiral recognition and amplification by molecular adsorbates was reported by Chen and Richardson who showed that adenine dimers form homochiral chains on Cu(l 10 [99]. Chains of one chirality are capable of recognizing one enantiomer of phenylglycine, while the opposite enantiomer is recognized by chains of the opposite chirality [99]. The recognition process is able to nucleate subsequent growth of ordered islands of enantiomerically pure phenylglycine [99]. 

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