Protection trifluoromethanesulfonic acid

Pyrazinyl ketones can be protected as the acetal by treatment with alkanediol in the presence of trifluoromethanesulfonic acid <1999JA8783> or 8-amino-l,3,6-pyrenetrisulfonic acid (APTS) <2005JOC2616>. 

Caution. Trifluoromethanesulfonic acid is harmful by inhalation, in contact with skin, and if swallowed. It causes bums. Precautions should be taken to minimize inhalation of the corrosive vapors given off from the acid. Trifluoro-methanesulfonatosilver(I) is an eye, respiratory system, and skin irritant. Methyl-diphenylphosphine is harmful by inhalation, in contact with skin, and if swallowed. Tetrahydrothiophene is an eye, respiratory system, and skin irritant. It is necessary to wear suitable protective clothing, gloves, and eye/face protection. All the reactions must be conducted in a well-ventilated fume hood. 

Caution. Trifluoromethanesulfonic acid (triflic acid) is one of the strongest acids known and is exceedingly corrosive. Extreme care should be used and protective clothing must be worn when handling this compound. 

Protection of phenols by the foregoing methods is complicated by the rapid Friedel-Crafts rearrangement of the nascent rm-butyl ether. By using trifluoro-methanesulfonic add at -78 PC, the rate of /erf-butyl ether formation is fast and the Friedel-Crafts alkylation does not compete [Scheme 4.126].226 Similarly, attempts to deprotect phenol ferf-butyl ethers with trifluoroacetic acid or titanium tetrachloride may give complex mixtures, again as a result of Friedel-Crafts alkylation of the phenol but this side reaction can be suppressed by using a catalytic amount of trifluoromethanesulfonic acid in 2.2,2-trifluoroethanol as solvent at -5 DC. 

Deprotection of O-methyltyrosine. O-Methylation of tyrosine (1) has represented an irreversible protection of the phenol group, since cleavage is accomplished only under drastic conditions. A new, mild method for deprotection involves treatment of 1 with thioanisole and trifluoromethanesulfonic acid in trifiuoroacetic acid. This method was used in the final step of a synthesis of a pentapeptide (43%... 

TFA at higher temperatures,or TFA/thioanisole where the push-pull mechanism remarkably increases the rate of acidolysis,f l liquid HF/pyridine,t °l BBrj/CHaQa, or BBrj/TFA for longer peptide fragments.By these procedures also the benzyl-type side-chain protection is cleaved as well as Arg(Tos). Additionally, numerous sulfonic acids were shown to efficiently remove the Z group, such as methanesulfonic acid, trifluoromethanesulfonic acid, or fluorosulfonic acid mainly in CH2CI2 or Since the acidolytic removal of the... 

A further urethane protecting group derived from a secondary alcohol is the 2-ada-mantyloxycarbonyl group.It is more stable toward acidic reaction conditions than the corresponding 1-adamantyloxycarbonyl group (1-Adoc, Section 2.1.2.2.3.3.2), but it is removed with trifluoromethanesulfonic acid or anhydrous HF in a few minutes at... 

To 300 mL of anhydrous methanol in a 1-L conical flask is added 20 g (0.33 mole) of ethylenediamine. Trifluoromethanesulfonic acid (50 g, 0.33 mole Aldrich Chemical Co.) is added very slowly from a dropping funnel to the rapidly stirred solution over a 1-hour period. The material is extremely hygroscopic, fumes in air, and reacts violently with most solvents. Caution. The use of a safety shield and protective clothing is recommended when handling this... 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34, 49, 64], Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64], Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, allyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the triflates and displaced by a variety of amines by treatment with trifluoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

Initially, the method was based on the differential reactivity conferred on each of the partners by the nature of the protecting groups and by the intrinsic nucleophilicity of the thioaryl leaving groups. However, as the method evolved, it became clear that the choice of the promoter was also an important factor to take into consideration. Indeed, it was demonstrated that a disarmed thioglycoside could be activated in the presence of powerful thiophilic promoters such as A-iodosuccinim-ide/trifluoromethanesulfonic acid (NIS/TfOH), whereas it remained inactivated in the presence of weak thiophilic reagent such as iodonium dicollidine perchlorate or methyl triflate [43,45]. 

Since it became obvious that liquid HF is not at all the detachment reagent of choice (see in contrast [35, p. 380]), the search for a similarly efficient reagent resulted recently in the utilization of boron tris (trifluoroacetate) [172], which in trifluoroacetic acid is reported to smoothly liberate peptides bound to the polymer support by benzyl ester type linkages. All above-mentioned protecting groups stable against trifluoroacetic acid are simultaneously cleavable. Trifluoromethanesulfonic acid [173] and pyridinium polyhydro-genfluoride are proposed for the same purpose [174] (Fig. 52). 

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