Macrocyclic ligands chirality

Fig. 8-2. Schematic representation of the separation of enantiomers R and S using a supported chiral macrocyclic ligand host.

In the presence of benzylamine, which coordinates trans to an active site, and quinine, the noncoordinated chiral component, optical purities up to 80% ee were again attained for hydrogenation of benzil. Convincing evidence was presented for the mechanism outlined in Eqs. (56)-(58), where L is the macrocyclic ligand, Q is quinine, and R = Ph (benzylamine, and charges of the complexes are omitted) ... 

In the preceding section it was shown that the stability of crown-ether complexes with alkylammonium salts depends on the relationship between the structures of the crown ethers and the ammonium ions. How critically this relationship determines the complex stability will become clear in this section, which deals with the discrimination between the two enantiomers of racemic salts by chiral macrocyclic ligands. 

A variety of macrocycles with asymmetric centers have been reported, examples of which are shown in (57) to (66). Chiral discrimination has been observed in the study of thiolysis of activated ester bonds with tetracysteinyl[18]crown-6 (67), e.g. Gly-L-Phe reacts up to 80 times faster than Gly-D-Phe with this ligand.231 The chiral macrocyclic ligand (66) is also capable of enantiomeric discrimination, by assisting in the selective reduction of carbonyl compounds with high optical yields.232,233... 

Figure 6-16. Co-ordination of the four nitrogen atoms of a tetraaza macrocyclic ligand to a metal results in a restricted inversion at each nitrogen. The filled circles represent a substituent lying above the plane of the paper, and the open circles one lying below the plane. In the case of cyclam, with hydrogen substituents, the barriers to inversion are relatively low, but with bulkier substituents on the nitrogen the different diastereomers are readily isolable. Note also that the isomers labelled II and V are chiral and will exist in two enantiomeric forms.

Potential Separations of Enantiomeric Amines Using Silica Gel-Bound Chiral Macrocyclic Ligands... 

Table II. Differences in free energy of activation values (AG, kcal mol for the interaction of chiral macrocyclic ligands with (R)- and (5)-1-(1-naphthyl) ethyl ammonium perchlorate as determined experimentally (NMR) and as calculated from empirical energy functions. ...

The inorganic lanthanide triflate complexes Ln(OTf)3 (made in aqueous solution) have been shown by Kobayashi to be efficient Lewis-acid catalysts for hydroxy-methylation (using commercial aqueous formaldehyde solutions) of silicon enolates in aqueous medium (water -i- THF) or even in water alone in the presence of a surfactant. In these reactions, activation proceeds by coordination of the aldehyde oxygen atom by the Ln center that is a strong Lewis acid due to its hard character. Among the lanthanide triflates, ytterbium triflate was found to be the most active catalyst, but scandium triflate can sometimes also be efficiently used. Enantio-selective versions are also known in the presence of chiral macrocyclic ligands. The water-soluble catalyst is recovered in water after extraction of the organic products. 

Gao, J., Martell, A.E. Self-assembly of chiral and chiral macrocyclic ligands synthesis, protonation constants, conformation and asynunetric catalysis. Org. Biotnol. Chem. 2003, 7(15), 2795-2800. 

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