Preparation of Sulfonic Esters

Sulfonates of primary and secondary alcohols are strong alkylating agents, and are usually prepared on solid phase only as synthetic intermediates. Sulfonic esters of phenols are, however, sufficiently stable to serve as potential lead structures for various types of drug [154]. 

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]). 

Treatment of Wang resin with methanesulfonyl chloride in the presence of a weak base only yields the mesylate if the reaction is conducted at low temperature and for a short time (Entry 1, Table 8.11). Longer reaction times lead, in both DCM or DMF as 

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Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

Sulfonate displacement has been well established as a common method for introducing halogen atoms into carbohydrates. The high reactivity and easy preparation of sulfonic esters contribute to their use in carbohydrate chemistry. Triflate displacements are popular for the preparation of secondary halogenated carbohydrates and often give satisfactory results when mesylates and tosylates fail to give products. 

This chapter contains reactions that prepare the oxides of nitrogen, sulfur, and selenium. Included are /V-oxides, nitroso and nitro compounds, nitrile oxides, sulfoxides, selenoxides, and sulfones. Oximes are considered to be amines and appear in those sections. Preparation of sulfonic acid derivatives is described in Chapter 2 and the preparation of sulfonate esters in Chapter 10. 

Preparation of sulfonate esters is accomplished by treatment of a carbohydrate with a pyridine solution of an aryl or alkyl sulfonyl chloride (RSO2CI) or with 50% sodium hydroxide and the sulfonyl chloride at room temperature. Under these conditions, all of the hydroxyl groups may be esterified except those on the reducing (anomeric) carbons which are replaced by halide atoms. Thus, D-glucose gives tetra-O-tosyl-D-glucopy-ranosyl chloride. The primary hydroxyl group seems to be more easily esterified than the secondary hydroxyls (116). 

The Preparation of Halodeoxy Sugars by Displacement of Sulfonate Esters... 

Vinyl trifluoromethanesulfonates (triflates) are a new class of compounds, unknown before 1969, that have been used most extensively in solvolytic studies to generate vinyl cations.2,3,812 Three methods have been used to prepare these sulfonic esters. The first, involving the preparation and decomposition of acyltriazines,4 requires several steps to prepare the acyltriazines and is limited to the preparation of fully substituted vinyl triflates. The second method involves the electrophilic addition of trifluoromethanesulfonic acid to acetylenes5,8,15 and, consequently, is not applicable to the preparation of trisubstituted vinyl triflates and certain cyclic vinyl triflates. However, this second procedure is relatively simple and often gives purer products in higher yield than the subsequently discussed reaction with ketones. Table I lists vinyl triflates that have been prepared by this procedure. ... 

In addition to these physical studies at the Bureau, Tipson was able to return to his synthetic interests, both alone and in collaboration with other staff members. He was especially pleased to prepare D-talose in crystalline form, an accomplishment that had eluded Emil Fischer. Pursuing his longstanding interest in the reaction of sulfonic esters with iodide and following an earlier observation that the tetratosyl ester of erythritol is converted into butadiene by the action of sodium iodide and zinc, he demonstrated (with A. Cohen) that nonterminal unsaturation may be conveniently introduced into alditol derivatives by reaction of contiguous secondary sulfonates with sodium iodide and zinc dust in boiling A.A-dimethylformamide. This Tipson-Cohen reaction subsequently proved of great utility in other hands for the conversion of more complex carbohydrate structures into vicinal dideoxy derivatives. 

A. Cahn, H. Lemaire, R. Haass, Preparation of sulfonated fatty acid ester surface-active agents, US Patent 3 320 292 (1967). 

Sulfonic acids, R(Ar)S03H, form derivatives similar to those of carboxylic acids (see Table 16-3). These are sulfonyl chlorides, sulfonates (esters), and sulfonamides. The transsulfonylation reactions are similar to the transacylation reactions, except that the ester and amide cannot be made directly from the acid. See Problem 13.17 for preparation of sulfonyl chlorides and esters and Problem 13.18 for use of sulfonate esters as substrates in S l and S,42 reactions. 

To prepare alkyl sulfonate esters, sulfonic acids were treated with supported alkyl triazenes (entry 17).21 The acids decompose the triazenes to diazoalkanes, which subsequently alkylate the sulfonates in situ. These supported triazenes avoid the dangerous handling of pure diazoalkanes. 

The solvolysis of sulfonic esters, a much studied reaction, has not been applied in carbohydrate chemistry, presumably because most sugars are not stable enough to withstand the long heating required. Tosyl derivatives of inositols can, however, be solvolyzed in good yield. For example, 3-0-tosyl-feyo-inositol (5-0-tosyl-Zevo-inositol) (XLIV)—prepared from di-O-isopropylidene-fcvo-inositol (XXVIII) by tosylation and subsequent removal of the isopropylidene groups—affords aZZo-inositol when refluxed for... 

Hydrogen peroxide attacks the sulfur atom in preference to the double bond in allyl phenyl sulfide and allyl benzyl sulfide to give allyl phenyl sulfoxide (64%) and allyl benzyl sulfone (85%), respectively. Olefinic sulfones may also be obtained by dehydrohalogenation of /3-haloalkyl sulfones prepared by this method. Oxidation of sulfides has been utilized in the preparation of sulfones containing other common functional groups such as the amide, tro, amino, and ester groups. 

A -oxides) In sulfones, the sulfur bonds with a tetrahedral array, but since two of the groups are always oxygen, no chirality normally results. However, the preparation of an optically active sulfone (2) in which one oxygen is and the other illustrates the point that slight differences in groups are all that is necessary. This has been taken even further with the preparation of the ester 3, both enantiomers of which have been prepared. Optically active chiral phosphates 4 have similarly been made. ... 

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