Tosylates and Mesylates

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 tosyloxy groups which esterify primary hydroxyl groups may be replaced by an iodine atom when the ester is heated with an acetone or acetonylacetone solution of sodium iodide. Tosyloxy groups esterified with secondary hydroxyls usually remain unaffected by this treatment unless contiguous to a similar group esterified with a primary hydroxyl (117). When the latter condition exists, both groups may be removed with the formation of a double bond, erythritol tetratosylate forming butadiene (118). 

Creation of a double bond also may occur when there is a free hydroxyl adjacent to a tosyl group at a primary alcohol grouping as in 6-0-tosyl-n-glucofuranosides (119). Exceptions to the rule are the tosyl esters of 4so-mannide and isosorbide the tosyloxy groups of these compounds, although esterifying secondary hydroxyl groups, are replaced with iodine under the above conditions (see p. 397). 

The difference in ease of replacement of tosyloxy groups esterified with primary and secondary alcoholic groups is used to measure quantitatively the primary groups in a compound (120). This is done by tosylation of the material treatment of the ester with sodium iodide replaces the 0-tosyl groups esterified with primary alcoholic groups the iodo compound is treated with silver nitrate, and the iodine atoms are replaced quantitatively with nitrate groups the liberated iodide precipitates as silver iodide which 

Tosyl esters of the carbohydrates occuring within the rings, are not replaceable by acetate ion under vigorous conditions. 

---

Another excellent catalyst for coupling is a mixture of CuBr-S(CH3)2, LiBr, and LiSPh. This catalyst can effect coupling of a wide variety of Grignard reagents with tosylates and mesylates and is superior to Li2CuCl4 in coupling with secondary sulfonates.64... 

Alkyl tosylates and mesylates are cleaved on the action of KOj in DMSO and give rise to the corresponding alcohols. This reaction also proceeds with inversion of configuration at carbon atoms (Morkovnik and Okhlobystin 1979). Such process may be of importance in prostaglandin chemistry. 

Section 7.8). Other classes of derivatives are thus most conveniently prepared from the sulfonyl chloride. Reaction with an alcohol leads to formation of a sulfonate ester. Two common sulfonyl chloride reagents employed to make sulfonate esters from alcohols arep-toluenesulfonyl chloride, known as tosyl chloride, and methanesulfonyl chloride, known as mesyl chloride (see Section 6.1.4). Note the nomenclature tosyl and mesyl for these groups, which may be abbreviated to Ts and Ms respectively. 

The selective tosylation and mesylation of sugars with reducing groups have also been realized. 6-0-Tosyl-D-glucose,96 1,6-di-O-tosyl-D-fructose (LVII),n 2,3-0-isopropylidene-5-0-tosyl-L-rhamnose (LVIII),98 and 6-0-mesyl-D-glucose" have been prepared. By the reaction of two... 

Tosylates and mesylates are commonly used sulfonates that you need to know for the MCAT. The sulfonate ions are very weak bases and excellent leaving groups. When tosylates and mesylates are leaving groups, the reaction may proceed via an SN1 or SN2 mechanism. 

Very good leaving groups, such as triflate, tosylate and mesylate, stabilize an incipient negative charge. The delocalization of this charge is reflected in the fact that these ions are not considered to be nucleophilic. 

Triflate, tosylate and mesylate are the anions of strong acids. The weak conjugate bases are poor nucleophiles. Nucleophilicity increases in parallel with the base strength. Thus, amines, alcohols and alkoxides are very good nucleophiles. Base strength is a rough measure of how reactive the nonbonding electron pair is thus, it is not necessary for a nucleophile to be anionic. 

The use of the anions of sulfonamides to prepare linear polymers from several different 1-substituted A-tosyl- and -mesyl-aziridines has been reported.144... 

Longer-chain alkyl halides may not be commercially available, but they are readily made in one step from the corresponding alcohols (Larock, 1999), as are tosylates and mesylates. Similarly, longer-chain terminal alkynes are not commercially available, but can be readily made by reaction of alkyl halides with lithium acetylide-ethylene diamine complex in dry... 

Tosylate and mesylate displacements at C(2) of a-glycosides are very slow owing to unfavourable dipolar interactions in the SN2 transition state. Both polar bonds of the transition state are inclined at an angle of about 30° to permanent dipoles of the C(l)—0(1) and C(l)—0(5) bonds. Displacement of C(2) sulfonates of p-glycosides is much more facile because, in this case, the transition state experiences only one unfavourable dipolar interaction of the C(l)—0(1) bond.12d,e... 

An alternative approach for alkynyl carboxylates involved reaction between [bis(acyloxy)iodo]benzenes and lithium acetylides [59]. Alkynyl iodonium salts afforded with sodium carboxylates in the presence of water 1-acyloxyketones heating in an excess of acetic acid gave similarly a-acetoxy ketones [60], Alkynyl tosylates and mesylates were obtained from the thermal decomposition of isolable alkynyl iodonium sulphonates. 

Other good leaving groups have also been used. Many tosylates and mesylates were replaced with fluorine when KF in polyethylene glycol was employed50. Such a reaction was a key step for making various fluoroprostaglandins (equation 29)51. 

The presence of catalytic amounts of cuprous triflate or silver(I) sulfonates exerts a remarkable influence on the activation energy and regiochemistry of alkynyl(phenyl)-iodonium tosylate and mesylate decompositions5,6. Such reactions proceed in acetonitrile at room temperature and afford moderate yields of alkynyl tosylates and mesylates (equations 82 and 83)5,6. It is noteworthy, however, that the treatment of alkynyliodonium triflates (R = n-Bu, r-Bu) with cuprous triflate in acetonitrile does not afford alkynyl triflates6. Silver(I) catalysis has similarly been applied to the conversion of bis(alkynyliodo-nium) tosylates to bisalkynyl tosylates (equation 84)43. As might be expected, mono-tosylate esters are also produced in these reactions. 

In the synthesis, the diol was converted to the bis-tosylate (see Chapter 17 if you ve forgotten about tosylates and mesylates) and reacted with a phosphorus nucleophile. 

Tetrabutylammonium lluoride converts primary tosylates and mesylates smoothly and in high yield into the corresponding fluorides. The syntheses of 4-fluorobut-3-ynal. 8-fluorooctanoic acid, and 1-fluorooctane are recent examples. For secondary substrates it has been shown that the reaction proceeds via a clean Ss,2 mechanism, e.g. reaction of ( —)-(/ )-2-(losyloxy)-octane with anhydrous tetrabutylammonium fluoride gives (+ )-(S)-2-fluorooctane in 54% isolated yield, with an optictil purity + 14.2 (neat) which is higher than that reported... 

Variations in the nature of "leaving groups" have not been studied systematically in the steroid field. Both tosylates and mesylates have been widely used for preparative purposes and in mechanistic studies, although work in other fields suggests that the more reactive -bromo and -nitrobenzene sulphonates may be valuable in special cases. Recent work [18] has demonstrated the use of the acetylsulphate (AcO-SOg-O-)... 

The reaction sequence, which is as shown in equation 43, is analogous to that suggested for the formation of arsonium ylides from triphenylarsine oxide in acetic anhydride Crystalline bisacetoxytriphenylarsine (37) has been isolated and shown to react with amides to give arsinimines . Tosyl and mesyl amides and benzamide react with 37 at room temperature, but less nucleophilic amides required heating in boiling 1,2-dichloroethane for reaction to take place. ... 

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. 

Acetates, benzoates, tosylates, and mesylates exhibit analogous [l,2,3]-eliminations upon (gas phase) pyrolysis. Thus, Patchouli-acetate (104) reacts to 105 and 106 (52%, and 46%, resp.)65) and 57 yields 107 (low conversion) with migration of phenyl40). In the pyrolysis of bomyl benzoate (108) mainly (54 %) camphene (109)66) is formed, the atisine-derivative 110 (a or P) yields stereospecifically 111 (ot-epimer, 90 %) or 112 (P-epimer, 95 %)67), and the adamantane mesylate (113) yields the alkene 114 (38 %)68). 

Similar to this, luminescence appears in the galvanostatic pulse electrolysis of hexamethylphosphotriamide solutions of different salts without the separation of catholyte and anolyte. The authors of Ref. believe that the cation [(CHp NJj P OY, where Y stands for iodine or tosyl (Ts, p—CH CgH SOj") or mesyl (CHjSO ), appears at the anode. The iodine derivative was formed in a reaction between the solvent and the iodine liberated at the anode in potassium iodide solution. The other two compounds were obtained by adding tosyl and mesyl chlorides, respectively to the solution 2 . 

It is interesting to compare direct cathodic reduction with reduction of the same substance using solvated electrons. Thus, phosphine cations, which are formed in hexamethylphosphotriamide solutions of iodine, tosyl and mesyl chlorides (see above), and also N-tosylcarbazol during direct cathodic reduction (whose potential is by 2.5 and 0.8 V, respectively, more positive than the generation potential of solvated electrons) yield, unlike the reaction with solvated electrons, unexcited particles chemiluminescence is absent in this case Thus, investigation of... 

Ackermann L, Althammer A, Fenner S (2008) Palladium-catalyzed direct arylations of heteroarenes with tosylates and mesylates. Angew Chem Int Ed 48 201-204... 

---