Sulfonic esters displacement reactions

Nucleophilic Displacement. - Sulfonate ester displacement reactions continue to be widely applied in amino-sugar syntheses. The 3-amino-S-thioglucofuranose derivative 20 was obtained from the corresponding allofuranose 3-mesylate by displacement with azide ion and reducdon (liAlHJ (see also section 2.6)." The 2,3-epimino-a-D-lyxopyranoside 21 was prepared in 11 steps from diacetoneglucose via 3-azido-3-deoxy-1.2-O-isoprc ylidene-a-D-glucofriranose. Key steps were... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

The most common leaving groups are sulfonate esters and halides. For the sake of convenience, the discussion of certain dehalogenation reactions is also included in this section even though they may not involve 8 2 type displacement. Benzylic alcohols are also known to be displaced by hydrides or deuterides, but there is no evidence for the application of these reactions to the steroid field. 

Only one of these methods, namely the reaction of halides with lithium aluminum deuteride, is a true displacement reaction, following the same course as the previously discussed displacement of sulfonate esters (section Vl-A). Thus, lithium aluminum deuteride treatment of 7a- and 7jS-bromo-3 -benzoyloxy-5a-cholestanes (195) and (196) gives the corresponding deuterium labeled cholestanols (197) and (198) respectively." ... 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

The use of tetra-n-butylammonium fluoride (54) in an aprotic solvent such as acetonitrile may be more advantageous. Foster and colleagues (19, 37) have effected an SN2 type of reaction using this reagent in the conversion of l,2 5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-D-allofura-nose into the C-3 epimeric fluorodeoxy derivative. Note that whereas potassium fluoride is ineffective in displacing secondary sulfonate esters in sugars, tetra-n-butylammonium fluoride is capable of effecting a displacement with Walden inversion even in a furanose drivative. 

The group of Caddick has described the synthesis of functionalized sulfonamides by microwave-assisted displacement of pentafluorophenyl (PFP) sulfonate esters with amines (Scheme 6.159) [306]. Their ease of handling due to their higher crystallinity, along with their long shelf-life and their ability to react under aqueous reaction conditions, makes these an attractive alternative to sulfonyl chlorides. The microwave-assisted reaction of alkyl PFP esters with amines is a facile process which proceeds cleanly and in good yields with a number of different amines, including primary, secondary, and sterically hindered amines, and anilines. Optimum condi-... 

Another example of the fact that primary displacement of sulfonic esters is not always facile101,103-105 is the discovery that vigorous conditions were required for fluorination of l,2 3,5-di-0-isopropylidene-6-0-(methylsulfony])-a-D-galactofuranose with potassium fluoride dihydrate in methanol,85,88 and a comparatively long reaction-time was necessary for the fluorination of the 6-O-p-tolylsulfonyl derivative with tetrabutylammonium fluoride in acetonitrile.106... 

Deoxyhalogeno sugars are susceptible to nucleophilic attack, leading either to displacement, elimination, or anhydro-ring formation. The ease of displacement decreases in the order I > Br> Cl > F the iodo and bromo derivatives have, therefore, been especially utilized in such reactions, although several reactions with chlorodeoxy sugars have now been reported as a result of the increased availability of these compounds. The approach delineated in Section 11,1 (see p. 227) for predicting the reactivity of sulfonic esters can be expected also to be applicable, in an approximate and qualitative way,... 

For the reaction leading to the 2,5-anhydride, it has been postulated that initial esterification to give the 5-sulfonic ester is followed by intramolecular displacement of the 5-substituent by 0-2, either directly or during processing of the reaction mixture in an aqueous medium.67 Another hypothesis, which supposes a dehydration without passage through an intermediate sulfonic ester, has also been advanced.73... 

Problem 13.18 (a) Why are sulfonate esters such as p-toluenesulfonyl (tosyl) esters widely used in S 2 reactions (b) How is this reaction used for indirect displacement of —OH from ROH ... 

Bimolecular, nucleophilic-displacement reactions of sulfonic esters of carbohydrates have been reviewed.77,78... 

TBAF has been modified structurally around the anion to reduce its hygroscopic property. Several such reagents have been reported and their reaction with organic halides and sulfonate esters have been described. Tetrabutylammonium difluoride is ascribed to be a stable reagent and easily displaces halides and sulfonate esters.215 1-Dodecyl tosylate (18) is thus converted into 1-fluorododecane (19) in 96% yield. 

Nucleophilic Displacement Reactions of lmidazole-1-Sulfonate Esters... 

J. M. Sugihara and W. J. Teerlink, Stereochemical effects in the nucleophilic displacement reactions of primary carbohydrate benzene sulfonate esters with sodium iodide, J. Org. Chem. 29 550 (1964). 

Sulfonate esters are useful intermediates in displacement reactions (Section 8-7C) and provide a route for the conversion of an alcohol, ROH, to RX by the sequence ... 

For example, when sulfonate esters are hydrolyzed with ieO-enriched hydroxide (Reaction 4.38) the product sulfonic acids contain ieO but the starting material recovered after 50 percent reaction does not.75 By the arguments outlined on p. 200 this might be evidence for either a one-step displacement or a two-step mechanism with the first step rate-determining. The latter is made more... 

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