Enantioselective complexation

The enantioselective inclusion complexation of the reaction product with lOa-c in aqueous medium is more efficient than that by the recrystallization method. For example, inclusion complexation of rac-65e with 10a,b did not occur by recrystallization from an organic solvent however, enantioselective complexation occurred efficiently in aqueous medium to give finally optically active 65e [12]. 

Schematic plots of the internal energy versus the reaction coordinate for both primary and secondary insertions and for generic aspecific, syndiospecific, and isospecific model complexes are sketched in Figures 1.11 a,b, and c, respectively. The minima at the centers and at the ends of the energy curves correspond to alkene-free intermediates, including a growing chain with n and n + 1 monomeric units, respectively. Movements from the central minima toward the left and the right correspond to possible reaction pathways leading to primary and secondary insertions, respectively. For the enantioselective complexes the reaction pathways for monomer enantiofaces being...

Yet, indirect information on enantioselective complexation by silica-bound antibiotics in HPLC can be extracted from the analysis of retention data of several ligands whose structure is systematically varied to explore chemical diversity in terms of functional groups, stereogenic elements, molecular complexity, and rigidity-flexibility. 

If the substrate contains two identical substituents at one terminus of the allylic position such as shown in Scheme 8E.26, the it-allyl intermediate can undergo enantioface exchange via the formation of a a-palladium species at that terminus. This process should occur faster than the nucleophilic addition, which is the enantio-determining step (fc, > 2[Nu ] and 2[Nu ]). Thus, enantioselection can be derived from the relative rate of the nucleophilic addition to each diastereomer the relative stabilities of the two diastereomeric complexes need not have a direct effect on the enantioselectivity (Curtin-Hammett conditions). Although the achiral allylic isomer 120 is expected to follow the same kinetic pathway as the racemic substrate 119, the difference between the results from the two systems often gives an indication as to the origin of enantioselection—complexation or ionization versus nucleophilic addition. 

Pieters, R. J. Diederich, F. Enantioselective complexation of excitatory amino acid derivatives by chiral, cage-like C3-symmetrical receptors, Chem. Commun. 1996, 2255-2256. 

The enantioselective complexation technique can also be applied as one step in the reaction sequence, providing chiral substrates for the next step. We will now discuss the example of Gabriel synthesis between potassium phthalimide 41 and alkyl bromide 42, which leads to optically active amines (Scheme 1) [51], Instead of the complicated preparation of chiral alkyl bromides (halides), imides (43), which are reaction intermediates, have been resolved. Upon treatment with hydrazine and KOH, these gave optically active amines. The chiral host (S,S)-(-)-6 or the chiral biaryl host (,S>(-j-40 was used for the effective resolution of the intermediates 43. Racemic mixtures 43a-d were resolved by complex formation with the host (S,S)-(-)-6 in a mixture of diethyl ether and light petroleum. 

The invertomers of the nitrogen pyramid 1-chloro-2,2-dimethylaziridine have been separated by enantioselective complexation GC on the chiral metal chelate nickel(II)-bis[(3-heptafluorobutanoyl)-( l.R>)-camphorate] (Ni-CAM2) in squalane (Schurig et al., 1979). The resolution of the chiral aziridine into two sharp peaks with a = 1.5 in 45 min at 60° C demonstrated the stereochemical integrity of the invertomers (cf. Figure 6). 

Schurig, V. (2002) Practice and theory of enantioselective complexation gas chromatography. J. Chromatogr. A 965, 315-356. 

Using the native cyclodextrin, the enantiomers of amino acid derivatives were enantioselectively complexed [21]. Further, for a more detailed analysis, zwitterionic tryptophan was employed [22]. For the complexation studies performed on this molecule the a-cyclodextrin was used, as its inner cavity is the smallest. The H NMR measurements showed that (R)-tryptophan formed a stronger complex with a-cyclodextrin compared with the (S) enantiomer. This is due to the number of hydrogen bonds which can be formed between each enantiomer and the host molecule. The NMR studies showed another very interesting fact the amino acid is very likely forming no intracavity complex. It has been suggested that it is coordinated near the rim of the cyclodextrin. 

M. Sawada et al., Enantioselective complexation of carbohydrate or crown ether hosts with organic ammonium ion guests detected by FAB mass spectrometry. J. Am. Chem. Soc. 115, 7381-7388 (1993)... 

Still and Liu reported the enantioselective complexation of amino acids and small peptide derivatives by a bowl-shaped C3 macrotricyclic receptor in chloroform (Figure 14). In all cases the receptor showed the largest hitherto reported chiral discrimination, with a preference for the L-configuration of the substrates (with e.g. 99% ee and a AAG 13 kJ/mol for Boc-val-NHMe). The observed free energies of binding were up to AG - 30 kJ/mol in the case of Me02C-ser-0tBu. 

Enantioselective complexation of cyanohydrin with brucine in solution has been reported [36]. In this case, racemic cyanohydrin is completely converted into one enantiomer by complexation and racemization through a brucine-catalyzed equilibrium (Scheme 2.2.4). Similar phenomena occurred in the solid state. When brucine and an equimolar amount of rac-64 was shaken for 24 h, a 1 1 complex was formed, which upon distillation gave (+)-64 of 6.3 % ee in almost quantitative yield [3]. This shows that(+)-64 is included preferentially. 

This enantioselective complexation in the solid state was proven by the following experiment. A mixture of finely powdered 4 c (1.2 g, 4.8 mmol) and roc-3 (1.2 g,... 

Seebach et al. met the challenge of synthesizing chiral dendrimers to investigate the influence of chiral building blocks on the chirality of the whole molecule and to determine whether enantioselective complexation was possible. [45] They achieved dendrimers with a chiral nucleus as well as dendrimers with additional chiral branches. The optical activity of dendrimers with only a chiral nucleus decreases with increasing... 

Enantioselective complexation between chiral host molecules and racemic guests was also achieved. One enantiomer of phenylethylammonium cation can be selectively complexed by optically pure i>A(binaphtho)-22-crown-6. The racemic ammonium salt, dissolved in water, and the chiral crown, dissolved in an immiscible solvent such as CHCI3, are shaken together. If one of the two diastereomeric complexes is favored, it can be detected (e.g., by NMR) or separated. When the chiral macrocycle is bound to a resin, a multi-plate, chiral organic separation is possible. 

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