Trifluoromethanesulfonic acid alcohols

Trifluoromethanesulfonic acid is miscible in all proportions with water and is soluble in many polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and acetonitrile. In addition, it is soluble in alcohols, ketones, ethers, and esters, but these generally are not suitably inert solvents. The acid reacts with ethyl ether to give a colorless, Hquid oxonium complex, which on further heating gives the ethyl ester and ethylene. Reaction with ethanol gives the ester, but in addition dehydration and ether formation occurs. 

Alkyl esters of trifluoromethanesulfonic acid, commonly called triflates, have been prepared from the silver salt and an alkyl iodide, or by reaction of the anhydride with an alcohol (18,20,21). Triflates of the 1,1-dihydroperfluoroalkanols, CF2S020CH2R can be prepared by the reaction of perfluoromethanesulfonyl fluoride with the dihydroalcohol in the presence of triethylamine (22,23). Triflates are important intermediates in synthetic chemistry. They are among the best leaving groups known, so they are commonly employed in anionic displacement reactions. 

Esters of / fZ-amyl alcohol can be obtained by acylation of 2-methyl-2-butene in the presence of trifluoromethanesulfonic acid (44). The esters produced, in high yields, from reaction of amyl alcohols with carboxyHc anhydrides, are used as intermediates for preparation of pyryflum salts (45,46) and alkaloids (47). Tria2oles prepared by acylation of 3-methyl-1-butanol are useful as herbicides (48). 

Opening by trimethylsilyl trifluoromethanesulfonate yields an adduct (54) from which trifluoromethanesulfonic acid can be eliminated to give an allylic alcohol (Scheme 47) (79JA2738) [cf. base-promoted isomerization to allylic alcohols (Section 5.05.3.2.2)]. 

Acids that are used in addition to trifluoroacetic acid include trifluoroacetic acid with added sulfuric acid203 or boron trifluoride etherate,210,211 perfluorobu-tyric acid,212 hydrogen chloride/aluminum chloride,136,146,213 perchloric acid in chloroform,214 p-loluenesull onic acid alone134 or with aluminum bromide or aluminum chloride,192 concentrated sulfuric acid in two-phase systems with dichloromethane, alcohol, or ether solvents,209,215 trifluoromethanesulfonic acid,216 chlorodifluoroacetic acid,134 and the monohydrate of boron trifluoride... 

The formylmethyl complex 21 also serves as a source of free acetaldehyde, and one equivalent of trifluoromethanesulfonic acid in CH2CI2 releases it from 21 within one hour at room temperature. Acetaldehyde was identified by its 2,4-dinitrophenylhydrazone (isolated in 42% yield), and was determined directly (48%) by quantitative analysis of its IR v 1716 cm"l absorption. The protonation of 21 presumably generates a n2-vinyl alcohol compound 19 (R=H) [IR observable v 1983 cm" ], which then dissociates acetaldehyde. We have overall converted selectively two carbonyls on CpFe(CO)3+ (1) to acetaldehyde. 

Oxidation. This reagent is prepared by reaction of CAN with K2C03 (2 equiv.) to form Ce(C03)2, which is then treated with trifluoromethanesulfonic acid (4 equiv.). This oxidant is effective for oxidation of benzylic alcohols to aldehydes (72-92% yield), and of alkylarenes to aldehydes or ketones (65-70% yield). 

Activation of a side-chain primary alcohol function with trifluoromethanesulfonic acid anhydride led to exclusive C-alkylation resulting in a cationic ring closure to afford the tetrahydroindoles (A)-584 (Equation 140) <2004T1197>. When R = H the N-Tf-substituted compound (5)-584 was formed as a side product in 18% yield. It was important to conduct the reaction in the presence of 4-methyl-2,6-di-/-butylpyridine as a sterically demanding and effective proton scavenger. 

Gassman first observed the intermediacy of allyl cations as dienophiles in connection with efforts to extend the aminium cation-radical catalyzed Diels-Alder reaction to intramolecular cases. It was found that the cyclization of tetraene (26) performed in the presence of 0.2 equiv. of tris(p-bromophe-nyl)aminium hexachloroantimonate [ArsN+ CleSb ] was in fact catalyzed by protic acid. - A better means of catalyzing the cyclization of (26) involves use of 4 mol % trifluoromethanesulfonic acid at -23 C for 6 min, which provides the trans-fused cycloadduct in 88% yield (98% isomeric purity). Similar treatment of (27), however, provided a mixture of cis- and trans-fused products. A subsequent report revealed that allylic alcohols and allylic ethers are useful precursors to the allyl cation dienophiles with... 

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... 

Conversion of alcohols to sulfonate esters is a way of labilising them to nucleophilic substitution and elimination. The common leaving groups are arenesulfonates, particularly p-toluenesulfonate (tosylate), methanesulfonates (mesylate) and trifluromethanesulfonate (triflate) they are introduced by reaction of the acid chlorides (or, in the case of the trifluoromethanesulfonates, acid anhydrides) in a basic solvent such as pyridine. Traditionally, the reactions are carried out in pyridine as solvent, but both this solvent and the liberated... 

Polymer-bound reagents for silylation have been reported. Murata and Noyori treated Nation, a perfluorinated resin-sulfonic acid, with trimethylsilyl chloride to afford a polymer-bound trimethylsilyl ester that functions as a polymer-bound equivalent of trimethylsilyl trifluoromethanesulfonate, converting alcohols, eth-anethiol and diethylamine into the corresponding silylated compounds in high yields (Scheme 6.16) [70]. Acetic acid could also be silylated, albeit with moderate conversion. The corresponding polystyrene-bound reagent is commercially available. 

Benzyl 2.2,2-trichloroacetimidate (bp 106-114 00.07 kPa) alkylates alcohols in the presence of trifluoromethanesulfonic acid. Esters, imides, isopropylidene and benzylidene acetals are unaffected. This method allows the formation of benzyl ethers in molecules that are base-sensitive. In the example [Scheme 4.167],2 benzylation of the p-hydroxy ester 167.L1 under the usual basic conditions would lead to retro-aldol reactions and/or elimination. A synthesis of the cellular messenger L-a-phosphatidyl-D-/nyo-inositol 3,4-bisphosphate exemplifies the use of trityl cation-promoted benzylation of two adjacent hydroxyls [Scheme 4.168]. ... 

---