1.3- Ditosylates

Diethylene glycol ditosylate [7460-82-4] recrystn from Me2CO and dried in a vacuum. 

Tlie first suggestion of a template effect which was offered in the literature was made by Greene in 1972 °. Tlie illustration of this concept is approximately that shown in Eq. (2.2), above. Greene presented several pieces of evidence in addition to the concept itself. First, he noted that when the final concentration of 18-crown-6 in a reaction mixture (MejSO) was increased from 0.04 At to 0.09 Af, the yield of crown dropped only slightly (84% to 75%). In a competition experiment, equal amounts of 18-crown-6 and 21-crown-7 were formed when one molar equivalent each of triethylene glycol and tetra-ethylene glycol were allowed to compete for triethylene glycol ditosylate (KO-t-Bu/THF). 

When K.yba, Cram and coworkers attempted the synthesis of dibinaphthyl-22-crown-6 from binaphthol and diethylene glycol ditosylate. the reagent ratio was as described either by V or X (Eqs. 3.1 or 3.3). The intent was to make the 22-membered ring. Some of the 11-membered ring was isolated as well (Eq. 3.5). None was apparently observed for the benzo case because the nine-membered ring is less favorable. In short, it is not the intent of the synthesis but the reaction dynamics which determine the product. 

At the same time, Dale and Kristiansen reported a successful synthesis of 18-crown-6 from the diol and ditosylate just as shown in Eq. (3.2), but using benzene as solvent. They obtained the product as its potassium tosylate complex (mp 164°) in 33% yield. The free macrocycle was liberated by chromatography over a column of alumina, eluting with a benzene-cliloroform mixture. Dale and Kristiansen note that the cyclic ether cannot be liberated from its complex by simple heating . ... 

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. 

Not long thereafter, Tarnowski and Cram reported the first example of a hinged bis-crown ether. The compound was prepared in the usual Williamson reaction by heating a mixture of 2,2, 3,3 -tetrahydroxy-l, r-binaphthyl with pentaethylene glycol ditosylate and KOH in aqueous THF solution. The product (mp 159.5—161°) shown in Eq. (3.30) was obtained in 30% yield. This compound was shown to complex bis-ammonium cations of several varieties . 

Boujlel and Simonet used an electrochemical method to prepare a group of similar compounds, including compound ]5, shown in Eq. (3.41). In a typical case, benzil was reduced in DMF solution at the dropping mercury electrode in the presence of tetrabutylammonium iodide, used in this case as a supporting electrolyte rather than phase transfer catalyst. In the presence of diethylene glycol ditosylate, compound 15 (mp 77— 78°) was isolated in 10% yield. Using the same approach, acenaphthenedione was reduc-tively cyclized with triethylene glycol ditosylate to afford the product (mp 84—85°, 42% yield) shown in Eq. (3.42). 

In Cram s first synthesis of a chiral bis-binaphthyl system, optically pure binaph-thol and diethylene glycol ditosylate were heated at reflux in tetrahydrofuran solution for 15 h with potassium f-butoxide, two products were obtained. The 1 + 1 product (mp 230—231°) was isolated in 5% and the 2 + 2 product (mp 123—126°) was obtained in 31% yield. The reaction is shown in Eq. (3.51). 

Greene reported the preparation of monoaza-18-crown-6 (i) in 1972. His approach was direct, involving condensation of N-trityldiethanolamine with tetraethylene glycol ditosylate. Removal of the protecting group could be achieved by acid cleavage. Unfortunately, neither details of the synthesis nor physical properties were included in this report. 

The synthesis of 1 was accomplished by stirring N-benzyldiethanolamine in the presence of NaH/DMF and tetraethylene glycol ditosylate at 25 °C for 48 h. After chromatography, N-benzyl-7 was isolated in 25% yield as a yellow oil. Debenzylation (Hj/Pd)... 

Pure, discrete diethylene, triethylene and tetraethylene glycols are all commercially available from a variety of sources. Pentaethylene glycol and longer polyoxyethylene glycols are generally prepared by condensation of two equivalents of a shorter glycol with a diol dichloride or ditosylate. Such methods have been reported by Pedersen", Cornforth , and Krespan . The approach is illustrated in Eq. (7.1), below. 

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 study of nonsteroidal examples has led to the suggestion that the elimination of vicinal ditosylates involves nucleophilic displacement of one tosy-late by iodide. Reductive elimination then occurs if the geometry is correct otherwise, a second displacement occurs which then gives the required trans arrangement. The reason for the failure of reaction with 2jS (axial) isomers is not clear. 

Replacement of one tosyloxy group m 2-fluoro-2-nitro-l,3-propanediol ditosylate by azide ion occurs easily [S5] (equation 75)... 

The double a substitution of enamines with propane-1,3-dithiol ditosylate has provided a route for the introduction of a thioketal, which has found use as a blocking group in modified steroid 476) and terpene 477) syntheses. 

A crystalline 5,5 -diene, or bis (vinyl ether), derivative of sucrose has been prepared from 6,6 -dideoxy- 6,6 -diiodo-sucrose hexa-acetate, derived from the 6,6 -ditosylate, by treatment with silver fluoride in pyridine (26). 

There have been a number of different synthetic approaches to substituted PTV derivatives proposed in the last decade. Almost all focus on the aromatic ring as the site for substitution. Some effort has been made to apply the traditional base-catalyzed dehydrohalogenation route to PTV and its substituted analogs. The methodology, however, is not as successful for PTV as it is for PPV and its derivatives because of the great tendency for the poly(u-chloro thiophene) precursor spontaneously to eliminate at room temperature. Swager and co-workers attempted this route to synthesize a PTV derivative substituted with a crown ether with potential applications as a sensory material (Scheme 1-26) [123]. The synthesis employs a Fager condensation [124] in its initial step to yield diol 78. Treatment with a ditosylate yields a crown ether-functionalized thiophene diester 79. This may be elaborated to dichloride 81, but pure material could not be isolated and the dichloride monomer had to be polymerized in situ. The polymer isolated... 

Semirigid phosphonamide ligands have been synthesized from the corand precursors by the reaction of 1,3-propanediol ditosylate or 1,2-dichloroethane <96JOC8904>. 

In the skeleton of many chelating diphosphines, the phosphorus atoms bear two aryl substituents, not least because the traditional route to this class of compounds involves the nucleophilic substitution with alkali metal diarylphosphides of enantiopure ditosylates derived from optically active natural precursors, approach which is inapplicable to the preparation of P-alkylated analogs. The correct orientation of these aryl substituents in the coordination sphere has been identified as a stereo chemically important feature contributing to the recognition ability of the metal complex [11,18-20]. 

They also prepared valienamine derivative (+)-227 from the ditosylate (294) derived from 286. The spiro epoxide (295) obtained from 294 was converted into 296 by treatment with selenoxobenzothiazole-tri-... 

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