Sulfonates, esters, reactivity

Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

The utility of methanesulfinyl chloride lies in its great chemical reactivity. Through its ready hydrolysis, it serves as a convenient source of methanesulfinic acid. It reacts at low temperature with aromatic amines to form sulfinamides, and with alcohols to form sulfinate esters. When it is hydrolyzed in the presence of an equimolar quantity of sulfenyl chloride, a thiol-sulfonate ester is produced. 

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 ... 

Tertiary alcohols are more difficult to convert to sulfonate esters, and because of their high reactivity they are often difficult to isolate. ... 

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... 

This seeming unreactivity of vinyl halides in solvolytic processes and the lack of availability of more reactive precursors, such as sulfonate esters, until recently has discouraged early attempts at mechanistic investigations of vinyl cations generated by solvolyses. However, vinyl cations have been generated via vinyl diazonium ions derived from various precursors. 

The solvolytic behavior of arylvinyl sulfonate esters also has been investigated. Jones and Maness were the first to prepare fluorosulfonate esters, 153, from the corresponding triazenes (140). In the solvolytic reactivity... 

In the early solution phase syntheses of oligonucleotides, coupling of phosphate diesters was used. A mixed 3 -ester with one aryl substituent, usually o-chlorophenyl, was coupled with a deprotected 5 -OH nucleotide. The coupling reagents were sulfonyl halides, particularly 2,4,6-tri-i-propylbenzenesulfonyl chloride,53 and the reactions proceeded by formation of reactive sulfonate esters. Coupling conditions... 

Li et al. (1997) have discussed the use of catalytic antibodies to control the reactivity of carbocations. At an entry level, the acyclic olefinic sulfonate ester [72] is converted into the cyclic alcohol [73] (98%) using antibody 4C6 raised to hapten [73] with only 2% of cyclohexene produced (Appendix entry 15.1) (Li et al, 1994). 

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. 

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,... 

The most common synthesis of sulfonic esters, which can also be conducted on insoluble supports, is the sulfonylation of alcohols with sulfonyl chlorides under basic reaction conditions. Several examples of the sulfonylation of support-bound alcohols and of the reaction of support-bound sulfonyl chlorides with alcohols have been reported (Table 8.11). For the preparation of highly reactive sulfonates, bases of low nucleophilicity, such as DIPEA or 2,6-lutidine, should be used to prevent alkylation of the base by the newly formed sulfonate. This potential side reaction is, however, less likely to occur on cross-linked polystyrene than in solution, because quaternization on hydrophobic supports only proceeds sluggishly (see Section 10.2 and [155]). 

This section outlines three chemical transformations designed to allow further synthetic elaboration of the diols obtained from AD. The first and most broadly applicable method is the conversion of the diols into cyclic sulfates, a functionality that has reactive properties like an epoxide but is even more electrophilic than an epoxide [68]. The second approach to diol activation is the regioselective conversion of one of the hydroxyl groups into a sulfonate ester [69], This approach requires that the diol be substituted in a way that leads to regioselective derivatization of one of the two hydroxyl groups, and diol esters are a prime example of such... 

Methanolysis of die sulfonates (175)141 and the reaction of the sulfonate ester (102) with hydroxylamine (103)88 were looked at earlier. Yoh and co-workers have looked at die reactions of (Z)-phenylediyl (X)-benzenesulfonates with (Y)-pyridines in acetonidile under pressure and die structure-reactivity relationships established show that as die pressure is increased die mechanism moves from a dissociative 5n2 to early-type concerted 5k2.276 In otiier sdtdies also under pressure the same group found that a mechanistic change from associative, k 2 to late-type 5n2 occurs as the pressure is increased in die reaction of (Z)-phenacyl (X)-benzenesvdfonates with (Y)-pyridines in acetone.277... 

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