Mesyl esters

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

The almost instantaneous intramolecular ether formation by reaction of phenoxy anions, generated from the silyl ethers with a stoichiometric amount of tetra-n-butylammonium fluoride, on mesylate esters has been used to synthesize labile benzo-0-2-isocephams (>90%) [20]. 

The purpose of the first reaction with methanesulfonyl chloride (mesyl chloride) is to form a mesylate ester, a derivative with a better leaving group than hydroxide. Then, the Sn2 reaction can proceed more favourably. Esterification with mesyl chloride is mechanistically analogous to esterification with acetyl chloride. 

The iodo derivative is a useful intermediate for the preparation of a wide variety of different types of compounds. Primary mesyl esters also react with sodium iodide in acetone, but the selectivity of this cleavage is less because of the greater reactivity of secondary mesyl esters. oa( ) Methyl 2,3,4-tri-0-acetyl-6-0-mesyl-a-D-glucopyranoside is converted into methyl 2,3,4,6-tetra-O-acetyl-a-D-glucopyranoside with acetic anhydride and potassium acetate. Replacements of a primary mesyloxy group with fluorine by use of potassium fluoride in methanol,106 with chlorine by use of lithium chloride,102 and with pyridine to form a pyri-dinium deoxy derivative,106 have been reported. Primary tosyloxy groups have been replaced by hydrogen,106 by thiocyanate,107 and by... 

The corresponding 1-O-mesyl ester has been obtained24 by shaking a dry benzene solution of the same bromide with finely powdered silver meth-anesulfonate for two days at room temperature. 

On standing, LXXIXb undergoes a rearrangement, apparently with the formation of an iminium cation (LXXX)—a reaction analogous to the formation of an ethyleneiminium cation from V-alkyl-V,./V -bis(2-chloroethyl)-amine.184 The di-O-mesyl ester (LXXXI) of LXXVIII is remarkably resistant to catalytic de-O-acetylation. 

Primary and secondary alcohols are readily converted to mesylate or tosylate esters by reaction with the corresponding sulfonyl chloride. The mesylate and tosylate esters derived from tertiary alcohols are too reactive and cannot be isolated. (Although we will not go into the mechanism of these reactions in detail at this point, the reactions involve the attack of the oxygen [the nucleophile] of the alcohol at the sulfur [the electrophile], ultimately displacing chloride [the leaving group].) Pyridine is often used as a solvent for these preparations in order to react with the HC1 that is produced as a by-product. An example of the preparation of a methanesulfonate (mesylate) ester is shown in the following equation ... 

Normal-phase separations at -30°C enabled the determination of the impurity profile of a mesylated ester, which underwent in-column cyclization at room temperature, to be determined [86]. Subambient temperatures down to -10°C were used by LoBrutto et al. [87] to generate a single product from the on-column derivatization of an acetylenic aldehyde with diethylamine. 

Instead of p-toluenesulfonyl chloride, methanesulfonyl chloride may be used advantageously for esterification. Mesyl esters ordinarily react even more rapidly with sodium iodide than do tosyl esters. ... 

Terminally fluorinated carbohydrates may be obtained by treating the tosyl esters, or the more reactive mesyl esters, with potassium fluoride in methanol. Because of the alkaline reaction of potassium fluoride, the remaining hydroxyl groups must be protected, as for example, by acetal formation,... 

The formation of these charged complexes in solution has been used as the basis for an electrophoretic separation of the Schardinger dextrins. Beckmann and Forster also found that complex formation with a-dextrin enhances approximately 2J- -fold the ultraviolet absorption maxima in iodine-iodide solutions at 290 and 350 m/i. It is probable that the colored complexes of iodine with methyl ethers and with the tosyl and mesyl esters of the Schardinger dextrins are also inclusion compounds of the same general type. 

The synthesis of stereodefined acyclic alkenes via 3-elimination reactions—such as (1) dehydration of alcohols, (2) base-induced eliminations of alkyl halides or sulfonates (tosyl or mesyl esters), and (3) Hofmann eliminations of quaternary ammonium salts—often suffers from a lack of regio- and stereoselectivity, producing mixtures of isomeric alkenes. 

Sulfoxides are readily available via oxidation of sulfides with peroxycarboxylic acids (e.g., mCPBA, 1.0 eq) or sodium or potassium periodate. The sulfides themselves can be prepared by nucleophilic displacement of tosylate or mesylate esters with sodium alkyl- or phenylsulfides. In the example shown below, the sulfoxide approach worked better than direct E2 elimination of the mesylate precursor. ... 

Figure 14.2 Synthesis of 9-(3-[18F]fluoropropyl)-9-desmethyF(+)-(a)-dihydrotetrabenazine (f18F]FP-DTBZ) by a single-step nucleophilic aliphatic substitution of a mesylate ester leaving group.

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