Sulfonate esters nucleophilic substitution reactions

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 ... 

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 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... 

Sulfonic acids, like sulfuric acid, are much stronger acids than carboxylic acids. However, their chemical behavior resembles that of carboxylic acids in many other respects. Sulfonic acids form the same type of derivatives, sulfonyl chlorides, esters, amides, and so on, as do carboxylic acids. These derivatives are intercon-verted by nucleophilic substitution reactions that resemble those of carboxylic acid derivatives. 

The preparation of tosylate and other sulfonate esters for use as leaving groups in nucleophilic substitution reactions (see Section 8.9) employs the reaction of a sulfonyl chloride (an acid chloride of a sulfonic acid) with an alcohol. Another example is shown in the following equation. Note the similarity of this reaction to the reaction of an acyl chloride with an alcohol to form an ester. 

The vast literature on applications of PTC in substitution reactions is mainly restricted to nucleophilic substitution reactions with an anionic reagent. However, recently the use of PTC in electrophilic reactions, like diazotization andazocou-pling C-and N-nitrosation, C-alkylation, acid hydrolysis of esters, chloromethylation, nitrite-initiated nitrations, and so on have been reported(Velichko et al., 1992 Kachurin et al., 1995). Alkylbenzene sulfonates and lipophilic sodium tetrakis[3,5-bis(trifluoromethyl)phenylboranate are typical electrophilic PT catalysts. Lipophilic dipolar molecules of the betaine type and zwitterionic compounds also function well as PT agents for both nucleophilic as well as electrophilic reactions. 

D. H. Buss, L. D. Hall, and L. Hough, Some nucleophilic substitution reactions of primary and secondary sulfonate esters, J. Chem. Soc. (1965) 1616-1619. 

The benzoyl acid ester CD is an important intermediate in CD modification. Selecting the appropriate nucleophile (iodide, azide, thio-amyl acetate and hydroxylamine, alkyl amines) to attack the carbon atoms which connect with tosyl, can trigger nucleophilic substitution reaction. Then, series of functional CD sulfonate derivatives can be obtained. 

It is important to note that formation of the sulfonate ester does not affect the stereochemistry of the alcohol carbon, because the C — O bond is not involved in this step. Thus, if the alcohol carbon is a chirality center, no change in configuration occurs on making the sulfonate ester—the reaction proceeds with retention of configuration. On reaction of the sulfonate ester with a nucleophile, the usual parameters of nucleophilic substitution reactions become involved. 

Activating an alcohol by converting it to an alkyl halide with a hydrogen halide followed by reaction with a nucleophile forms a substitution product with the same conhguration as the alcohol, whereas activating an alcohol by converting it to a sulfonate ester followed by reaction with a nucleophile forms a substitution product with a conhguration opposite that of the alcohol. 

Organic sulfonate esters, like sulfonyl halides, also readily undergo nucleophilic substitution reactions as previously mentioned (p 23). For example, oxygen-labelled (-)menthyl phenylmethanesulfonate 18 reacted with / -tolylmagnesium bromide to give labelled benzyl p-tolyl sulfone 19 with inversion of stereochemical configuration at the chiral sulfur atom (Equation 16). 

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... 

The mechanisms by which sulfonate esters undergo nucleophilic substitution are the sfflne as those of alkyl halides. Inversion of configuration is observed in Sn2 reactions of alkyl sulfonates and predominant inversion accompanied by racernization in SnI processes. 

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. 

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. 

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