Ditosylates, formation

Stoddart and his coworkers have reported syntheses of the trans-syn-trans and the trans-anti-trans isomers of dicyclohexano-18-crown-6 The synthesis of these two compounds from trans-l,2-cyclohexanediol was accomplished in two stages. First, the diols were temporarily linked on one side by formation of the formal, and this was treated with diethylene glycol ditosylate and sodium hydride to form the hemi-crown formal. Removal of the formal protecting group, followed by a second cychzation completed the synthesis. The synthesis of the trans-anti-trans compound is illustrated below m Eq (3 12) and the structures of the five possible stereoisomers are shown as structures 1—5. 

Coxon and Stoddart have directed their attention to the formation of penta-erythritol-derived cryptands. With these molecules, the strategy was to block one pair of hydroxyl groups as an acetal and form a crown from the remaining diol. In the first of the two reports cited above, this was accomplished by treating the 0-benzylidine derivative of pentaerythritol with base and diethylene glycol ditosylate. The crown was then treated with a mixture of UAIH4 and BF3 which gives partial reduction of the acetal as shown in (8.9), above. The monoprotected diol could now be treated in a fashion similar to that previously described and the benzyloxy cryptand (77) would result. The scheme is illustrated below as Eq. (8.10). 

A somewhat different method than those described above led to dithia[3.3.3]pro-pellane. When the same tetrol 54 was treated with p-TsCl in pyridine, the ditosylate 56 was formed at room temperature. At —5 °C the tetratosylate 57 was formed without formation of the five-membered ether ring 13). 

Normally, however, the reaction involving the formation of hydroxy-methylfurfural proceeds less readily than does the hydrogenation of glucose and fructose to mannitol and sorbitol, but its occurrence is detected by the fact that tetrahydrofuran derivatives have been isolated from the hydrogenation products. Thus, we have isolated tetrahydrofuran 2,5-dicarbinol (identified as its ditosyl derivative), 5-methyltetra-hydrofurfuryl alcohol and 2,5-dimethyltetrahydrofuran (VII) together with hydrogenolysis products of these compounds. 

Sometimes, it is possible to prepare sugar epoxides from ditosylates (Scheme 3.15b).83 For epoxide formation to occur, it is essential that one of the tosylates undergoes desulfonylation by S—O bond fission. Usually, this reaction occurs at the least hindered sulfonate. Then, the formed alkoxy will displace the remaining tosylate to provide the epoxide. Again, it is critical that the two reacting groups can attain a trans-diaxial relationship. 

Reactions of. yV-bis(chloromethyl(amides 139 (R = Me, H) with N,N -ditosylated 1,3-diaminopropane result in formation of the corresponding 1,3,5-trisubstituted 1,3,5-triazocanes 140 (Equation 26 <1998RCB2201>). 

Enyne derived from ditosyl o-phenylenediamine 257 formed in the presence of benzylidene ruthenium carbene complex a nine-membered ring 258 in 5% yield (Equation 30) <20000L543, 2001S654>. Dimerization was a major by-process (22% yield) along with formation of a small amount of 259 (5% yield), which was explained by /3-hydride elimination from the intermediary ruthenacyclobutane. 

The application of cesium fluoride as base in the synthesis of crown compounds from phenols and the ditosylates of polyethylene glycols was first described by Reinhoudt [44]. This method uses the high basicity of weakly solvated ( naked ) fluoride anions under aprotic conditions and is based on the formation of very stable H—F bonds (approx. 569 kJ/mol, H—Cl approx. 432 kJ/mol for comparison) [8],... 

Oxidation of 2-hydroxy-1,4-ditosyl-l,2,3,4-tetrahydropyrazine with Jones reagent surprisingly resulted in hydroxylation of the double bond with the formation of 2,3,5-trihydroxy- and 2,3-dihydroxy-1,4-ditosylpiperazine (1602). Despite numerous attempts, Eisner and Williams (1602) were unable to convert a series of... 

Under an inert atmosphere, prepare a suspension of sodium hydride (0.96 g, 20 mmol [50 per cent in mineral oil]) in dry THF (50 mL) in a 250 mL twonecked round-bottomed flask fitted with a reflux condenser and pressure equalized addition funnel. Stir for 30 min under an inert atmosphere. Slowly add a solution of 8-hydroxyquinoline (2.90 g, 20 mmol) in dry THF (50 mL) to this through the addition funnel. Make up a solution of triethylene glycol ditosylate, 2, (4.60 g, 10 mmol) in dry THF (50 mL), ensuring that no solids remain (filter if necessary) or the addition funnel may become blocked. Once the effervescence subsides following the formation of the sodium 8-hydroxyquinolinate salt, add the ditosylate solution and reflux for 24 h. After 24 h, allow the solution to cool to room temperature, filter off the precipitated sodium tosylate and remove the THF by rotary evaporation. Dissolve the residue in dichloromethane (30 mL) and wash with distilled water (3 x 30 mL). Dry the organic phase over anhydrous sodium sulphate, filter and remove dichloromethane by rotary evaporation to give the crude product, l,9-bis(8-quinolinyloxy)-3,6-dioxanonane (4) as a pale brown oil. Further purification may be afforded by column chromatography (silica, elute with acetone/dichloromethane). 

They reacted an excess of 1,2-dibromoethane with yV,N -ditosyl-l,5-diamino-3-oxapentane to form an open chain dibromide as shown. Use of an excess of the dibromide suppressed the formation of a nine-membered ring. The oxadiaza dibromide was then reacted with ammonia to form the product. 

Greene observed that the formation of 18-crown-6 from a ditosylate and a diol in the presence of f-butoxide salts was enhanced when a potassium cation was used (Greene, 1972). This template effect was operative for the synthesis of other polyether crown compounds using alkali or alkaline-earth metal cations. Template effects have also been observed for the preparation of aza-crown ethers, although the effect is less pronounced because the softer A-donor atoms form weaker complexes with the alkali metal cations (Frens-dorff, 1971). Richman and Atkins reported that high-dilution techniques were not required for the cyclization reaction of the disodium salt of a pertosylated oligoethylenepolyamine with sulfonated diols to form medium and large polyaza-crown compounds (Richman and Atkins, 1974 Atkins et al., 1978). 

Formation of two C—N bonds by a 1 1 cyclization of a bissulfonamide with a dihalide or a ditosylate. The sulfonamide groups include... 

Ring-closure reactions by the formation of two C—O bonds are not common for the preparation of the polyaza-crowns because preparation of the starting diols is often difficult. Tetraaza-24-crown-8 and 27-crown-9 ligands were prepared by the reaction of tetraazadiols and ditosylates or dimesylates (method P-1) (Krakowiak et al., 1989c). The cyclization reaction gave yields... 

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