Chiral glycol ethers

Scheme 4. Synthesis of chiral glycol ethers starting from (S)-ethyl lactate (13). DHP = dihydropyrane, THP = tetrahydro-pyranyl, Ts = tosyl, Bz = benzyl, THE = tetrahydrofuran, DMF = dimethylformamide.

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... 

The chiral crown ethers 101,102,104,105, and 152, andpodands 100 and 153 were formed from isomannide by introducing ethylene glycol units as... 

Ponzo, V. L. Kaufman, T. S. Diastereoselective alkoxymethylation of aromatic aldehydes with chiral lithiomefhyl ethers. Synthesis of optically active monoprotected glycols. Can. J. Chem. 1998, 76,1338-1343. 

To get more information about the SAR of acetogenin or its mimics, we synthesized 238a-d, which have no butenolide unit, and butenolides 239, which lack the THF ring or glycol ether unit. These compounds showed no or weak cytotoxicity, which indicated that both the butenolide segment and the glycol ether unit were indispensable. The stereochemistry of the chiral center in the butenolide... 

Many other chiral glycols have been prepared. These glycols were used to prepare various chiral crown ether ligands. A few of the chiral glycols are discussed in the next few pages. 

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. ... 

Very recently, the synthesis of a series of chiral poly(9,9 -spirobiflu-orene)crown ethers [e.g., (SS)-139, (SSSS)-140, (SSSSSS)-141, and (S55SSS5S)-142] with 26-, 52-, 78-, and 104-membered rings have been described (162). The last three are rare examples of compounds with C4, 5, and Cg synunetries, respectively. They were isolated chromatographically from a reaction mixture consisting of (S)-2,2 -bisbromomethyl-9,9 -spirobifluorene, ethylene glycol, KOr-Bu, and Csl in tolune. 

Although a large number of biscrown ethers based on the binaphthyl nucleus have been synthesized (157) many of these have only been isolated and characterized as their racemic modifications. An exception is provided (157) by (SS)-152, obtained from the chiral bisbinaphthyl-22-crown-6 derivative in which one of the binaphthyl units carries chloromethyl groups (in the 3 and 3 positions) capable of reacting, in the presence of base, with tetraethylene glycol. 

The first example of the use of a chiral-core dendrimer as enantioselective receptor in molecular recognition processes was reported by Diederich (see Fig. 4.70). This dendrimer, designated as a dendrocleff, acts as enantioselective receptor for monosaccharides. It bears a central axially chiral 9,9 -spirobi[9H-fluorene] unit which is linked via two 2,6-bis(carbonylamino)pyridine spacer groups, each in 2,2 position, with triethylene glycol monomethyl ether dendrons [14b]. Both... 

Abley and McQuillin (44) have reported asymmetric homogeneous hydrogenations catalyzed by rhodium complexes of chiral amides. In initial experiments the catalyst was generated in situ by treating trichlorotripyridylrhodium(III) with sodium borohydride in an optically active amide solvent (Fig. 20). In later work a 5% solution of the amide in diethylene glycol monoethyl ether was used and products with the same optical purities were obtained. This evidence indi-... 

The advantages of PTC reactions are moderate reaction conditions, practically no formation of by-products, a simple work-up procedure (the organic product is exclusively found in the organic phase), and the use of inexpensive solvents without a need for anhydrous reaction conditions. PTC reactions have been widely adopted, including in industrial processes, for substitution, displacement, condensation, oxidation and reduction, as well as polymerization reactions. The application of chiral ammonium salts such as A-(9-anthracenylmethyl)cinchonium and -cinchonidinium salts as PT catalysts even allows enantioselective alkylation reactions with ee values up to 80-90% see reference [883] for a review. Crown ethers, cryptands, and polyethylene glycol (PEG) dialkyl ethers have also been used as PT catalysts, particularly for solid-liquid PTC reactions cf. Eqs. (5-127) to (5-130) in Section 5.5.4. 

Asymmetric Acetoxylation of Esters. The silyl enol ether derived from CSA reacts with Lead(IV) Acetate to yield the a-acetoxy ester with good diastereoselectivity. Hydrolysis of the chiral auxiliary gives the a-hydroxy acid, whereas reduction affords the terminal a-glycol (eq 21). ... 

Carbohydrate crown ethers were obtained with ethylene spacers from a crown ether point of view, the carbohydrate vicinal diols are replacing one ethylene glycol unit [181,182], Cyclic compounds synthesized include bis-gluco-15-crown-5 82, bis-gluco-21-crown-7, and tetra-gluco-24-crown-8 (O Scheme 14). These chiral macrocycles could serve as catalysts in the asymmetric Michael addition of methyl a-phenylacetate to methyl acrylate. With the goal to study molecular interactions, P,P, and Q, Q -bis-maltosides with aliphatic two-, three-, or four-earbon spacers were synthesized [183]. Spaced cyclodextrins were prepared to study their supramolecular properties [184,185]. 

When the hydroxy group of amino alcohol was ccmverted into alkoxide, alkylation took place at the oxyanion in preference to the nitrogen atom. Thus, the sodium alkoxide derivative of (28) reacted with polyethylene glycol ditosylate or dichloride (29a-29c) to give the corresponding aminomethyl crown ethers (30). " Chiral amino alcohols (31) can be converted into amino ethers (32) via alkoxides. In contrast, treatment of iV-tosylamino alcohol (33) with NaH, followed by reaction with a fivefold excess of 1,2-dibromoethane afforded (34 Scheme 16).2 ... 

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