Sulfonate esters nucleophilic substitution

Alkyl sulfonate esters resemble alkyl halides m their ability to undergo ehmma tion and nucleophilic substitution... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

The mechanisms by which sulfonate esters undergo nucleophilic substitution are the same as those of alkyl halides Inversion of configuration is observed m 8 2 reac tions of alkyl sulfonates and predominant inversion accompanied by racemization m 8 1 processes... 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

An example of cleavage ol the sulfur-oxygen bond in trifluoromethane-sulfonic ester has been reported Tnfluororaethyl triflate reacts with neutral or anionic nucleophiles with elimination of carbonyl difluoride and formation of trifluoromethanesulfonyl fluoride [57] (equation 32) The mechanism of this reaction involves elimination of fluoride ion, which is a chain carrier in the substitution of fluorine for the trifluoromethoxy group... 

Conversion to p-toluenesulfonate esters (Section 8.14) Alcohols react with p-toluenesulfonyl chloride to give p-toluenesulfonate esters. Sulfonate esters are reactive substrates for nucleophilic substitution and elimination reactions. The p-toluenesulfonate group is often abbreviated —OTs. 

Although halides are common leaving groups in nucleophilic substitution for synthetic purposes, it is often more convenient to use alcohols. Since OH does not leave from ordinary alcohols, it must be converted to a group that does leave. One way is protonation, mentioned above. Another is conversion to a reactive ester, most commonly a sulfonic ester. The sulfonic ester groups tosylate, brosylate, nosylate, and mesylate are better leaving groups than... 

In a comparative study of fluorination of l,2 3,4-di-0-isopropyli-dene-6-O-p-tolylsulfonyl-a-D-galactopyranose with tetrabutylammonium fluoride in a variety of dipolar, aprotic solvents (as well as 1,2-eth-anediol, in which no reaction was observed), acetonitrile was found to give the highest proportion of substitution of the sulfonic esters relative to their elimination.106 Elimination is the major, competing reaction in these nucleophilic-substitution reactions, because of the high basicity and low nucleophilicity of the fluoride ion or, in terms of the... 

The reactions represented by (191) are all nucleophilic substitutions occurring at a sulfonyl sulfur. Besides cpdisulfones substitutions of this kind are also of frequent occurrence in the chemistry of many other types of sulfonyl derivatives such as sulfonyl halides, aryl esters of sulfonic acids, etc., and many of the general aspects of their behaviour and mechanism have been examined in considerable detail. Most of the remainder of this section will be devoted to consideration of the results of such studies. 

The first evidence that an elimination-addition mechanism could be important in nucleophilic substitution reactions of alkanesulfonyl derivatives was provided by the observation (Truce et al., 1964 Truce and Campbell, 1966 King and Durst, 1964, 1965) that when alkanesulfonyl chlorides RCH2S02C1 were treated in the presence of an alcohol R OD with a tertiary amine (usually Et3N) the product was a sulfonate ester RCHDS020R with exactly one atom of deuterium on the carbon alpha to the sulfonyl group. Had the ester been formed by a base-catalysed direct substitution reaction of R OD with the sulfonyl chloride there would have been no deuterium at the er-position. Had the deuterium been incorporated by a separate exchange reaction, either of the sulfonyl chloride before its reaction to form the ester, or of the ester subsequent to its formation, then the amount of deuterium incorporated would not have been uniformly one atom of D per molecule. The observed results are only consistent with the elimination-addition mechanism involving a sulfene intermediate shown in (201). Subsequent kinetic studies... 

Nucleophilic displacement using [ F] fluoride works well in aUphatic systems where reactive haUdes or sulfonates esters can undergo substitution at unhindered sites. In order to introduce a F fluorine atom in a secondary or tertiary position, a two steps strategy was developed. It involves a F-bromofluorination of alkenes, followed by reductive debromination (n-BujSnH, AIBN). [ F]BrF is usually generated in situ from [ F]potassium fluoride and l,3-dibromo-5,5-dimethylhydantoin (DBH) in sulfuric acid. This methodology was successfully applied to label steroids at the 11 and 6a positions [245] (Scheme 60) and to prepare [ F]fluorocyclohexanes [246]. 

It is often possible to predict the reactivity of a chlorosulfonyloxy group by a consideration of the steric and polar factors affecting the formation of the transition state,27-28 as indicated in Section 11,1 (see p. 227) for nucleophilic-replacement reactions of sulfonic esters of carbohydrate derivatives. Thus, it has been found that the presence of a vicinal, axial substituent or of a (3-trans-axial substituent on a pyranoid ring inhibits replacement of a chlorosulfonyloxy group also, a chlorosulfate group at C-2 has been observed to be deactivated to nucleophilic substitution by chloride ion. 

In the special case of nucleophilic substitution at a sulfonic ester RS020R where R is alkyl, R —O cleavage is much more likely than S—O cleavage because the OSOiR group is such a good leaving group (p. 353).1730 Many of these reactions have been considered previously (e.g., 0-4, 0-14, etc.), because they are nucleophilic substitutions at an alkyl carbon atom and not at a sulfur atom. However, when R is aryl, then the S—O bond is much more likely to cleave because of the very low tendency aryl substrates have for nucleophilic substitution.1731... 

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