Chiral crown ethers synthesis

Among the 1,4-di-O-substituted-L-threitol derivatives (Figure 14a) the one that has found most use in chiral crown ether synthesis is the 1,4-dibenzyl ether. Not only has it provided (88, 106, 107) a ready entry into the chiral tetrasub-stituted 18-crown-6 derivatives ll-31 to ll-34, but it has also proved to be a usehil chiral precursor for the preparation of chiral disubstituted 9-crown-3 (107), 12-crown-4 (108), 15-crown-5 (108), and 18-crown-6 (109) derivatives l-57, l-58, l-59, and l-60, respectively. In the preparation of l-S8 the base-promoted cyclization with triethylene glycol ditosylate is best carried out (108) with a... 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

Problem In the synthesis of a chiral crown ether, compound (19) was needed. Suggest a synthesis for it. 

We shall now consider the synthesis of chiral crown ethers from the viewpoints of strategies and some recent accomplishments. For a detailed discussion of the earlier work on the synthesis of chiral crown ethers from natural product precursors, the reader is referred to reviews (91, 92) that appeared in the literature in 1981 and 1982. 

The incoiporation of two asymmetric precursors into chiral crown ethers with C2 symmetiy must be carried out with total constitutional and stereochemical control during the reaction sequence. This has been accomplished elegantly during the synthesis of the three chiral benzo-15-crown-5 derivatives (SS)-79, and (5S)- 0 from (S)-lactic acid (122, 123). 

The third chapter, by J. F. Stoddart, is concerned with a very hot subject, namely, the stereochemical aspects of crown ether chemistry. Many chapters have been written on this topic Stoddart s concentrates on the synthesis of a variety of chiral crown ethers and surveys some of their uses in different areas of physical, chemical, and biological science. 

Apart from their obvious utility in separating mixtures of cations,68 crown ethers have found much use in organic synthesis (see the discussion on p. 363). Chiral crown ethers have been used for the resolution of racemic mixtures (p. 121). Although crown ethers are most frequently used to complex cations, amines, phenols, and other neutral molecules have also been complexed69 (see p. 133 for the complexing of anions).70... 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Synthesis of l,l, 4,4 -tetra-0-benzyl-2,2 3,3 -bis-0-oxydiethylene-di-L-threitol, a chiral crown ether... 

The synthesis of chiral crown ethers is generally approached by exploiting the chiral pool, that is, naturally occurring materials which are available in enantiomerically pure form. 

In recent years, many chiral catalysts for the enantioselective synthesis of optical active 1,5-dicarbonyl compounds have been developed, such as chiral crown ethers with potassium salt bases and chiral palladium complexes, including bimetallic systems. Nakajima and coworkers reported on enantioselective Michael reactions of S-keto esters to a,/3-unsaturated carbonyl compounds in the presence of a chiral biquinoline N,N dioxide-scandium complex, which catalyzed the additions in high yields and with enan-tioselectivities up to 84% ee . Kobayashi and coworkers found that the combination of Sc(OTf)3 with the chiral bipyridine ligand 149 (equation 41) was also effective as a chiral catalyst for asymmetric Michael additions of 1,3-dicarbonyl compounds 147 to a,/3-unsaturated ketones 148. The corresponding Michael adducts 150 were obtained in good to high yields with excellent enantiomeric excesses in most cases (Table 10). 

The compounds thus obtained have been used as starting materials for chiral crown ethers h 3> 15 (see Section 5.2.), having applications as enantioselective catalysts in Michael additions (Sections D.1.5.2.1. and D.1.5.2.4.). 3,3 -Dimethyl- and 3,3 -diphenyl-2,2 -dihydroxy-l,T-binaph-thyls 8 and 3 have been applied as ligands for the synthesis of chiral Lewis acids used as stereoselective catalysts in the Diels Alder reaction (Section D.1.6.1.1.1.3.). 

Recently reported uses of optically pure stilbene diol in asymmetric synthesis include. (1) the dimethyl ether as a ligand for effecting enantioselective conjugate addition 6 (2) the preparation of a,p-unsaturated ketals for achieving diastereoselective Simmons-Smith cyclopropanation 10 (3) the preparation of enantiomercially pure p-halohydrlns 11 and (4) the preparation of chiral crown ethers.12... 

Multi-Functionalized Chiral Crown Ethers as Enzyme Models for the Synthesis of Peptides. 

Key words. Chiral, crown ether, enzyme model, peptide synthesis, chiral recognition, molecular recognition, thiolysis, aminolysis, thiol, thioester. 

Sasaki, S. and K. Koga - Multi-functionaUzed chiral crown ethers as enzyme models for the synthesis of peptides. Multiple chiral recognition in the enzyme model 267 Schuette, J. M. see Kaifer, A. E. et al. 107 See, K. A. - see Gutsche, C. D. et al. 61... 

Thus within the past few years there has been an increasing interest in the use of sugars as chiral synthons. In this article we describe some recent achievements but since the emphasis here is in the area of natural product synthesis, some elegant studies such as those of Incm on chiral phosponates (29, 42) and Stoddart on chiral crown ethers as enzyme analogues 13) will have to be omitted. 

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. ... 

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