Carboxylates reactions with alkyl sulfonates

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

The reactions of alkyl sulfonates with sodium, potassium or tetraalkylammonium carboxylates generally proceed with inversion of configuration. In the case of f-alkyl sulfonates, however, a varied amount of elimination products is invariably formed. Of all metal carboxylates, cesium salts (Scheme 43) have proved vastly superior with respect to reactivity and the suppression of undesirable side reactions. ... 

A second method of ester preparation involves the reaction of carboxylate salts with alkyl halides, sulfates, or sulfonates. Because carboxylate ions are relatively weak nucleophiles in protic solvents, this reaction is too slow to be convenient under many circumstances. Use of solvents such as dimethyl sulfoxide and hexamethylphosphoramide, however, which selectively activate anionic nucleophiles, results in much-improved reaction rates. Reaction of carboxylate salts with halides has been found to be a satisfactory preparative reaction in these solvents. The procedure has been found to be particularly useful for certain hindered acids. Scheme 5.4 lists some... 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

From oxidative cleavage of 1,2-diols and 1,2-amino alcohols Dibutyltin oxide, 95 By reaction of alkyl halides with sulfur-stabilized carbanions Methylthiomethyl p-tolyl sulfone, 192 From reduction of carboxylic acids Vilsmeier reagent, 341 From terminal alkenes by addition reactions... 

Generally, treatment with electron-deficient olefins such as nitroethylene or vinyl sulfone is effective for radical addition reactions, since alkyl radicals derived from O-acyl esters (2) are nucleophilic and take SOMO-LUMO interaction. However, treatment of O-acyl esters ) derived from perfluoroalkyl carboxylic acids (RfC02H) generates electrophilic radicals, Rf, which react preferably with electron-rich olefins such as vinyl ether, as shown in eq. 8.16 [52]. 

Now we can carry out an Sn2 reaction on the sulfonate with a carboxylate anion. A terra-alkyl ammonium salt is often used in the polar solvent DMF to get a clean reaction. This is the key step and we don t want any doubt about the outcome. 

Insertions of carbon dioxide, sulfur dioxide, and sulfur trioxide yield aluminum carboxylates, sulfinates, and sulfonates, respectively. Treatment of the resulting complexes with aqueous acid yields the corresponding aUcylcarboxylic, alkylsulphinic, and aUcylsulphonic acids. High pressure and temperatures of 220-240 °C are required for multiple insertions of CO2 to yield more than one equivalent of carboxyhc acid per aluminum. Excess aluminum trialkyl must be avoided or the initially formed carboxylate is completely alkylated to a trialkylcarbinol. Reaction of Ets A1 with CO2, for example, gives a 90% yield of triethylcarbinol. 

Elucidation of rates with variation in cation, solvent and halide ion indicates that the combination of alkyl iodides and cesium salts in HMPA offers the optimum alkylation conditions for preparative use. The reactions of cesium carboxylates with alkyl halides and sulfonates will be discussed in Section 1.1.2.5 in connection with inversion processes. 

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