Esters, trifluoromethanesulfonic anhydride

C[iH4F,iN20gS2 157875-58-6) see Imiquimod trifluoromethanesulfonic acid triethylsilyl ester (C7Hi5F303SSi 79271-56-0) see Tacrolimus trifluoromethanesulfonic anhydride (C2F(,05S2 358-23-6) see Imiquimod Zanamivir... 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

The third procedure illustrated by this preparation involves the reaotion of ketones with trifluoromethanesulfonic anhydride in a solvent such as pentane, methylene chloride, or carbon tetrachloride and in the presence of a base such as pyridine, lutidine, or anhydrous sodium carbonate.7-11,15 This procedure, which presumably involves either acid-catalyzed or base-catalyzed enolization of the ketone followed by acylation of the enol with the acid anhydride, has also been used to prepare other vinyl sulfonate esters such as tosylates12 or methanesulfonates.13... 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

Primary and secondary amides and thioamides react with alkyl chlorofoimates with loss of CO2 or COS, forming iminium chlorides (82 equation 52). In some cases this method is complementary to the Pinner imido ester hydrochloride synthesis. The iminium salt (83 Scheme 6) formed by action of ethyl chloroformate on DMF is labile and decomposes rapidly to ethyl chloride. If the reaction is performed in the presence of NaBp4, the iminium salt (85) is isolable. Aryl chlorofoimates react in the same fashion with DMF or DMA, but in these cases the aryloxymethyleneiminium compounds are fairly stable, so this reaction is an important method for the preparation of compounds of this type. - Succinic acid monoamides, phthalic acid monoamides and related compounds are cyclized to iminium salts (86 equation 53) by treatment with acetic anhydride and HC104. ° With the aid of trifluoromethanesulfonic anhydride lactams and amides can be converted to dication ether salts (87) and (88 Scheme 7).22i.222... 

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)... 

The highly reactive trifluoromethylsulfonyloxy (triflate) group is introduced into malate esters by treatment of 2 or 3 with trifluoromethanesulfonic anhydride at —78 °C in the presence of 2,6-lutidine [70,71,72], or at 0 °C in the presence of pyridine [73]. Yields are generally high, often exceeding 90%. Triflates 197 can be generated in situ, and need not be isolated. 

The desired sulfonate ester is usually prepared by reaction of the alcohol in pyridine with the appropriate sulfonyl chloride, that is, methanesulfonyl chloride (mesyl chloride) for a mesylate, y)-toluenesulfonyl chloride (tosyl chloride) for a tosylate, or trifluoromethane-sulfonyl chloride [or trifluoromethanesulfonic anhydride (triflic anhydride)] for a triflate. Pyridine (C5H5N, pyr) serves as the solvent and to neutralize the HCI formed. Ethanol, for example, reacts with methanesulfonyl chloride to form ethyl methanesulfonate and with yj-toluenesulfonyl chloride to form ethyl /-toluenesulfonate ... 

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). 

Esters of very strong protonic acids (trifluoromethanesulfonic, fluoro-sulfonic, perchloric), however, are sufficiently strong alkylating agents to initiate the polymerization of even weakly nucleophilic monomers (cyclic acetals, ethers) [2-6], Also their anhydrides (e.g., triflic anhydride) are efficient initiators. This last compound is especially interesting, because in the polymerization of cyclic ethers it leads to macromolecules with two identical growing chain ends (difunctional initiator) [30] ... 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

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... 

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