Tosylate ester reactions

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

Other examples of the successful displacement of tosylates are the preparation of 31 -, 16a-,16j - and27- labeled steroids. This displacement reaction fails, however, with certain C-18 and C-19 alcohol derivatives which give mainly O—S instead of C—O bond cleavage. Unsatisfactory results were also obtained with sterically hindered tosylate esters at C-11, C-12 and C-20, which give considerable amounts of olefinic products in addition to O—S bond cleavage. ... 

The elimination of water from a fluorinated compound generally follows a reaction path similar to that of its nonfluorinated counterpart, although the presence of the highly electronegative fluorine atoms may have unexpected effects Various monofluoro alcohols can be dehydrated via their tosyl esters at 75 C by using potassium rert-butoxide [80] (equation 50)... 

The inference is that the hydrofuranol ring of XL can never be directly formed by the saponification of a 3-tosyl ester of D-glucose, but only indirectly by the intermediate formation and scission of an anhydro ring of the ethylene oxide type. The sequence of reactions involved in the conversion of methyl 3-tosyl-jS-D-gIueoside into methyl 3,6-anhydro-n-glucoside is shown by XXXVI to XL. 

A rapid O-tosylation of a primary alcohol with tosyl chloride (1 equivalent) in the presence of 4-(N,N-dimethylamino)pyridine (1 equivalent) has been reported by Botta and coworkers (Scheme 6.118) [236], Microwave heating of the reaction mixture at 50 °C for 5 min provided the desired tosyl ester in 95% yield. 

Scheme 22) and not the 3-tosyl ester that had originally been claimed in 1971 by Jezo as the major product of this reaction. Indeed, when Richardson repeated Jezo s exact conditions, which involved heating 6,l 6 -tri-0-tritylsucrose with TsCl and pyridine at 55 °C, the product obtained had identical spectroscopic properties to those reported for the Jezo product, and this material was, in turn, shown to be identical to the 2-tosyl ester prepared in improved yield under Richardson s new conditions (Scheme 22). 

Thiophene-fused benzoquinones, such as 23, can be easily alkylated to produce dialkoxybenzodithiophene compounds 111 on reaction with tosyl esters (Equation 28) <2002SM(130)139>. 

Problem 13.18 (a) Why are sulfonate esters such as p-toluenesulfonyl (tosyl) esters widely used in S 2 reactions (b) How is this reaction used for indirect displacement of —OH from ROH ... 

Probitm 16.95 Reaction of the (R)-tosyl ester of a-phenylethyl alcohol (C H,CHMeOTs) with CH,COOH yields a mixture of (S)- and rac-acetate. Explain. 

Alcohols react with sulphonyl chlorides to yield sulphonate esters via Sn2 reaetions. Tosylate esters (alkyl tosylates) are formed from alcohols from the reaetion with p-toluenesulphonyl ehloride (TsCl). The reaction is most commonly carried out in the presenee of a base, e.g. pyridine or triethyla-mine (Et3N). 

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to aldehydes easily and in good yields with dimethyl sulfoxide.311 Tosyl esters of primary alcohols can be similarly converted to aldehydes,312 and epoxides313 give a-hydroxy ketones or aldehydes.314 The reaction with tosyl esters is an indirect way of oxidizing primary alcohols to aldehydes (9-3). This type of oxidation can also be carried out without isolation of an intermediate ester The alcohol is treated with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC),315 and anhydrous phosphoric acid.316 In this way a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

One of the most important of the properties of tosyl esters is the ease of cleavage of those derived from primary alcohols. In this regard the formation of an iodo compound by reaction with sodium iodide in... 

Under appropriate conditions, Raney nickel can also cause reductive desulfonylation (compare, p. 156). Two procedures284 have been worked out, both involving, for tosyl esters, the over-all reaction ... 

Results of a PM3 semiempirical study of the quaternary benzenesulfonamide salt of /raw.v-3-(hydroxymcthyl)-2-phcnyl-l -mcthylpyrrolidinc indicate that it fragments in a stepwise manner via an intermediate benzylic cation. The unexpected formation of a ring-opened sulfonamide rather than the expected tosylate ester on reaction of the 2-aryl-3-hydroxymethylpyrrolidine with R"S02C1 is thereby explained.95... 

Isopropylidine adenosine was converted to the p-toluene sulphonyl (tosyl) ester by reaction with tosyl chlorine solution, following the method of Clark et al. (1951) [J. Chem. Soc. 2952]. Because of its tendency to cyclization, the reagent was used directly it was ready. A reaction flask with separating funnels was set up in such a way that the whole system could be evacuated and filled with pure nitrogen two or three times, to eliminate all oxygen, and reagents could then be added when desired, in the closed system. 

An interesting paper, which appears to be at variance with the above results and of which we have not been able to obtain full details, was published in 1949 by Valentin and Tomkuljak.90 From a reaction mixture containing xylitol, acetone and concentrated sulfuric acid, these authors claim to have isolated 3,5-isopropylidene-D,L-xylitol and 1,2 3,5-diisopropylidene-D,L-xylitol, both as sirups. The tosyl ester of the diketal had a melting point (71-73°) very similar to that recorded by... 

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. 

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 ... 

The Sn2 reaction of the tosylate ester with acetate ion in acetone as solvent produced an ester with [a] = —0.83. (Again, the configuration of the product cannot be determined solely on the basis of this experiment.)... 

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