Chiral crown ether, structure

Effect of the symmetry of the crown-ether structure on chiral recognition of RCH(COOCH3)NH,X atO°C ... 

In the solid state. X-ray crystallography has provided (32, 62) valuable structural information on a wide variety of chiral crown ethers and their complexes with a range of substrates. These include... 

Figure 17. Schematized structure of a chiral crown ether type CSP used for chromatographic resolution or methyl phenylalaninate hydrochloride. Reprinted with permission from ref 122b.

In an important new application of crown ethers Cram and Sogah have recently reported that potassium bases complexed to chiral crown ethers catalyze the stereoselective Michael addition of a /3- ketoester to methyl vinyl ketone in high optical yields (81CC625). With chiral crown (46), carbanion (47) gave alkylated products with an optical yield of about 99% enantiomeric excess. These impressive results were rationalized by complex structure (48) in which the crown-complexed K+ and the carbanion form an ion pair. One face of the associated carbanion is shielded from electrophilic attack by the flanking binaphthyl groups and the approach of methyl vinyl ketone occurs in a stereoselective manner. 

Telrasubstiluled-1 S-crown-6 crown ctlicr FIGURE 1 Chemical structures of the chiral crown ethers. 

Figure 22-14. The structure of chiral crown ether. (Reprinted from reference 66, with permission.)...

Kobuke et al. [40] demonstrated that the podand 28 only forms weak complexes with alkali metal ions. However, when a chiral macrocyclic crown ether structure is formed by complexation with boric acid, alkali metal ions are bound much more strongly (Scheme 10). Stiffening, provided by covalent B-O bonds, improves the preorganization of the ligands that is required for the complexation of metal ions. 

It can be concluded that stereoselective (and particularly enantioselective) separation can proceed by the simple apphcation of a chiral organic phase or in most cases by incorporation of carriers in the membrane phase. Sometimes, their structure is very complex and these molecules can act as real receptors for the enantiomers. Different types of transport mechanisms are involved in the separation and the most popular one is cotransport. This is a result of the fact that most frequently used carriers are based on crown ethers structure. The stereoselectivities by apphcation of carrier-mediated SLM separation are very different and depend on the structure of the guest and host molecules. The magnitudes of the stereoselectivity are in most cases moderate but similar to other membrane-based separation techniques for stereoisomers. 

Cram found that chiral crown ethers in the presence of alkali metal bases catalyzed the asymmetric Michael addition [46]. Ketoester 6 underwent addition to 7 in more than 99% ee in the presence of (S,S)-49 and KOf-Bu (4 mol %). Another crown ether, R)-50, and KNH2 promoted the addition of 41 to 42 giving (S)-43 in 60% ee. Since then, this reaction was examined using various optically active crown ethers [47,48,49,50,51,52,53,54,55,56], which are summarized in Scheme 10 showing the configuration and enantiomeric excess of 43. Slight changes in the structure of the crown ethers drastically affected the stereochemistry of the reaction. A brief structure-activity relationships may be presented. 

Chiral crown ethers derived from binaphthol, pentahelicene, bi-phenanthrol, and other natural precursors have been prepared in recent years. Their chiral recognition in complexation equilibria towards various primary alkylammonium and amino acids and ester salts as well as the structural requirements of this phenomenon have been investigated. The crown ethers based on 18-crown-6 structure are known to form most... 

The utilization of carbohydrates for the synthesis of chiral crown ethers has been further explored, giving derivatives with the general structures (12) and (13) using 4,-6-O-benzylidene derivatives of methyl a-o-galacto-, gluco-, and manno-pyranoside in a base-catalysed reaction with diethylene glycol bis-toluene-p-sulphonate. ... 

In the same line of thought, Lehn and Sirlin (148) have prepared a chiral macrocyclic molecular catalyst bearing cysteinyl residues. The catalyst complexes primary ammonium salts and displays enhanced rates of intramolecular thiolysis of the bound substrates with structural selectivity for dipeptide esters and high chiral recognition for the L-enantiomer (70 times faster) of a racemic mixture of glycylphenylalanine p-nitrophenyl esters. The representation below shows the complex between the chiral crown ether and the dipeptide glycylglycine p-nitrophenyl ester salt. 

The recent results reported by Cram are extremely important because his catalysts are chiral crown ethers, and represent one of the first attempts to develop novel structures without the inherent disadvantages of the ammonium salts described above. Such crowns yield products from Michael additions of 3-ketoesters to methyl vinyl ketone with optical purities up to 99%. A series of novel chiral onium salts derived from methionine have also been reported by Colonna and his coworkers. Although so far these have displayed no asymmetric induction in their reactions, they are important as an imaginative new series of catalysts. 

FIGURE 54.7. Structures of some chiral crown-ethers used as CS. While 10 (a) is used physically insolubilized (coated) onto the chromatographic matrix, similar compounds (b) are covalently bonded to it. 

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