Homochiral dimers

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. 

Figure 69 shows the solid-state structure of the thermodynamically more stable homochiral dimer (7 , )-145,210 which features a highly puckered central (Zn-0)2 ring with almost isometric Zn-O bond lengths. 

Figure 69 Solid-state structure and partial labeling scheme of the homochiral dimer...

There is an equilibrium between the dimer and monomer, and molecular orbital study suggests that the heterochiral dimer is more stable than the homochiral isomer. The existence and behavior of the dimeric species were well confirmed by experiments such as cryoscopic molecular weight and NMR measurement. In the NMR study of a DAIB-catalyzed dialkylzinc addition reaction, noticeable changes were observed in the spectrum of the homochiral dimer on the addition of benzaldehyde, while the spectrum of the heterochiral complex remained the same. This may imply that the heterochiral complex is very stable and does not react, and the homochiral dimer leads to the reaction product. 

Figure 9. The torsional potential of trifluoroethanol (dashed line, g+/t/g, in analogy to the ethanol case shown in Fig. 4) is only distorted slightly if it acts as a hydrogen bond acceptor toward a g+ trifluoroethanol unit [30] (full line). Nevertheless, only the compact inserted homochiral dimer (left, i c hom) is observed in the jet experiment, not the compact associated heterochiral dimer (right, a c het).

It can be expressed as fhomo/. hetero = [Td-H] /[Td-To-H]+ / [To-H] + - -[T -H] /[To-T -H], where [To-H]" and [T -H]" correspond to the peak intensities of monomer ions produced by unimolecular decomposition of the relevant protonated dimer species. The experimental results (l homo/ hetero = 0-67 (diPT-D-tartrate - - diPT-D-tartrate-di4) 0.77 (diEt-D-tartrate - - diEt-D-tartrate-dio)) confirm the higher stability of the homochiral dimer relative to the heterochiral one by indicating that the latter has a higher tendency toward unimolecular decomposition. 

Kureshy, R. I. Singh, S. Khan, N. H. Abdi, S. H. R. Ahmad, I. Bhatt, A. Jasra R. V. (2005) Improved catalytic activity of homochiral dimeric cobalt salen complex in hydrolytie kinetic resolution of terminal racemic epoxides.. Chirality, 17 590-594. 

Lithio-Af-methylpiperidines and -pyrrolidines are chemically and configurationally stable for at least 45 min at —40 °C in THF/TMEDA. Structural studies in THF showed that the piperidine is a bridged monomer in both racemic and enantiopure form, whereas the pyrrolidine is a homochiral dimer in both enantiopure and racemic forms. The difference in aggregation state does not appreciably affect the temperatures at which racemization is avoided. These A-methyl heterocycles are considerably more robust than the... 

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. 

These deviations from linearity indicate the existence of an oligomeric distribution of chiral ligands. Noyori proposed a rationale as follows Due to the different dissociability (stability) of homochiral and heterochiral dimer, the enantiopurity of the remaining reactive catalyst (monomer) is improved as compared with that of the submitted chiral ligand 6 (Scheme 9.5) [11]. Heterochiral dimer is thermodynamically more stable than homochiral dimer, which is consistent with Noyori s rationale mentioned above [12a]. An ab initio molecular orbital study was also reported in a simplified model reaction between formaldehyde and dimethylzinc catalyzed by achiral 2-aminoethanol [12b]. 

Fig. 7 Constraints for autocatalysis by A monomeric (reservoir mechanism) and B dimeric catalysts where the homochiral dimer is the only active form, a Indicates the conditions and b the typical outcomes for enumeration under illustrative conditions...

In the presence of excess diisopropylzinc, the EXSY spectrum in both thf and toluene shows rapid interconversion between zinc-bound isopropyl groups of the zinc reagent and alkoxide dimer (Fig. 15). The reaction occurs for both racemic and homochiral dimers with comparable facility. In toluene, the rate... 

Similarly, there is the MLmodel invented by Kagan and coworkers [72-74]. In this case, no a priori difference in the thermodynamic stabilities between homochiral and heterochiral dimers is assumed, but the dimers instead of monomers are considered to be the catalytic species. The heterochiral and homochiral dimers are allowed to display different catalytic activities, where the heterochiral dimer is assumed to perform without any enantiose-lectivity. 

Fig. 6 Simulated time-evolution of heterochiral and homochiral dimers in the Soai reaction by using the minimal model, giving rise to a nearly 1 1 distribution of both types of species. Same initial conditions and parameters used as in Fig. 5...

The electron density analysis within the AIM methodology shows the presence of bond critical points due to the formation of the HB and, in some homochiral dimers, also between oxygen atoms of different molecules (Fig. 3.13). The presence of the latter bcps is associated to those complexes where the homochiral complex is more stable than the heterochiral one. 

The electron density and its Laplacian have been correlated exponentially with the HB distance. These results are in agreement with other reports that show the generality of this rule [120-122]. The dimers of a series of chiral and nonchiral a-aminoalcohols were studied by means of DFT methods (B3LYP/6-311++G ) (Scheme 3.14). Due to the flexibility of the molecules, twelve possible complexes can be proposed in the case of the chiral molecules. Half of them are mirror image of the other half, and thus, only six where considered. The six unique configurations studied for each dimer (Scheme 3.15) correspond to three homochiral dimers (RR or SS) and three heterochiral ones (RS or SR), and can be grouped in three chairs, Cl-3, and three boats, Bl-3, respectively. 

The energy results obtained with the two basis sets are very similar. In the cases treated, the heterochiral dimers (RS or SR) are always more stable than the homo-chiral ones (RR or SS). The largest relative energy is observed in the CF3 dimers, probably due to the combination of the steric hindrance and electronic repulsion in the homochiral dimer. The /-butyl dimers that present mainly steric hindrance show smaller relative energies. 

The chiral discrimination found in the minima and TS structures of these dimers are gathered in Table 3.3. Herein, no clear tendency was observed with a relatively large number of homochiral dimers (R,R or SS) being more stable than its corresponding heterochiral ones. Attempts to explain these results based on secondary interactions using the AIM methodology resulted in poor correlations with steric parameters such as Taft s Es, an indication that a more complex mechanism controls these energetic differences. 

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