Fluorosulfonates methyl fluorosulfonate

For both azole and benzazole rings the introduction of further heteroatoms into the ring affects the ease of quaternization. In series with the same number and orientation of heteroatoms, rate constants increase in the order X = 0requires stronger reagents and conditions methyl fluorosulfonate is sometimes used (78AHC(22)71). The 1-or 2-substituted 1,2,3-triazoles are difficult to alkylate, but methyl fluorosulfonate succeeds (7IACS2087). 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

The first use of chiral oxazolines as activating groups for nucleophilic additions to arenes was described by Meyers in 1984. " Reaction of naphthyloxazoline 3 with phenyllithium followed by alkylation of the resulting anion with iodomethane afforded dihydronaphthalene 10 in 99% yield as an 83 17 mixture of separable diastereomers. Reductive cleavage of 10 by sequential treatment with methyl fluorosulfonate, NaBKi, and aqueous oxalic acid afforded the corresponding enantiopure aldehyde 11 in 88% yield. 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

The ketones 1 and 3, or compounds with a similar structure, have been used for the preparation of methoxy derivatives of 1-benzoxepin. In the standard procedure for methylation, the 1-benzoxepinone is deprotonated by potassium tert-butoxide and subsequently reacted with methyl fluorosulfonate at low temperature.16 173 - 175 The yields are generally high. 

The different reactivity of the ketone functions has also been demonstrated by the reaction of 2,7-dimethyl-4-phenyl-l-benzoxepin-3,5(2f/,4//)-dione with diazomethane which gives a mixture of the two monomelhylated products 10 and 11. In both compounds, the second methyl group is introduced by deprotonation with potassium tm-butoxide followed by the addition of methyl fluorosulfonate.177... 

Benzothiepins react with strong alkylating agents, such as methyl fluorosulfonate (caution toxic), to give the corresponding 1-benzothiepinium salts 2.88... 

The lack of any difference in the rate of isomerization between fluoro-sulfonic acid solutions of 34 which had been thoroughly degassed, and those which were saturated with oxygen, suggests that the reaction does not proceed via a triplet mechanism. In fluorosulfonic acid no unproton-ated acid is detected, ruling out the possibility of n,7r excitation. Thus, there is little doubt in this case that it is the Tr,Tr singlet state which is the reactive species. Experiments carried out with a variety of methyl-substituted protonated cydohexadienones have likewise ruled out the... 

A similar effect is achieved by Af-methylation of the imidazolide with fluorosulfonic acid methyl estertl8] or methyl trifluoromethylsulfonatet ] as catalyst ... 

In fluorosulfonic acid the anodic oxidation of cyclohexane in the presence of different acids (RCO2H) leads to a single product with a rearranged carbon skeleton, a 1-acyl-2-methyl-1-cyclopentene (1) in 50 to 60% yield (Eq. 2) [7, 8]. Also other alkanes have been converted at a smooth platinum anode into the corresponding a,-unsaturated ketones in 42 to 71% yield (Table 1) [8, 9]. Product formation is proposed to occur by oxidation of the hydrocarbon to a carbocation (Eq. 1 and Scheme 1) that rearranges and gets deprotonated to an alkene, which subsequently reacts with an acylium cation from the carboxylic acid to afford the a-unsaturated ketone (1) (Eq. 2) [8-10]. In the absence of acetic acid, for example, in fluorosulfonic acid/sodium... 

Amino-3,5-dimethylisoxazole (372, R = H) gave an iV-tosyl derivative (372, R = tosyl), which by treatment with methyl fluorosulfonate followed by perchloric acid gave the salt 371, R = R = R = Me, R = tosyl, X = C104. Attempts to isolate the meso-ionic sul-fonamidate (370, R = R = R = Me, R = tosyl) by treatment of the salt with potassium hydroxide or triethylamine were unsuccessful, but spectroscopic evidence for its formation in solution has been offered. 

The reaction of 3-hydroxymethyIpyridine 1-oxide with methyl fluorosulfonate and potassium cyanide provides a direct method for 2,6-dicyanation (75JOC2092). However, the generality of this method is limited by the need for a 3-substituent that can form an anhydrobase. In this example (Scheme 138) the anhydrobase is formed by methylation of the 3-hydroxymethyl group followed by elimination either during or subsequent to attack by the second mole of cyanide. The use of such a powerful methylating agent overcomes... 

Cyclization of the diazonium salt (442) followed by treatment with base and then with acid gave (443 R1 = C02H) which was decarboxylated to give (443 R1 = H) (77MI51803). These products show typical phenylhydrazone unreactivity to alkylation at N-l but treatment of (443 R1 = H, R = Me) with methyl fluorosulfonate gave a relatively stable quaternary salt via methylation at N-2 this isomerized in acid to give l-imino-3-methylquinazolin-4-one (444) (79JHC1411). 

Both reagents are powerful methylating agents, reacting with O, N, and S. Read precautions carefully. The Methyl fluorosulfonate (Magic Methyl) is no longer commercially avai lable. Methyl triflate is extremely (sometimes violently) reactive towards amines. Except for extremely hindered or unactivated amines, not generally required for the task. 

By changing the reactivity of the alkylating agent, it is possible to vary the magnitude of an ortho steric effect. Thus, the reactivity of 2-substituted pyridines toward Mel in acetone is linearly related on a logarithmic scale to the reactivity of the same substrates toward methyl fluorosulfonate in benzene. The fluorosulfonate is about 104 times more reactive than the iodide, and so the transition state for quaternization occurs earlier. The earlier transition state gives rise to a smaller steric effect the slope of the plot demonstrating the dependence of the steric effect on reactivity is 0.69.76... 

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