Triflates alcohols

Phenyltrifluoromethanesulfonimide (Tf2NPh) is widely used to triflate alcohols and amines. As a milder triflating agent compared to triflic anhydride (Tf20), it proves to be useful for the selective formation of triflates. A primary alcohol was transformed into its triflate in the presence of a secondary alcohol and subsequently reacted to form an oxetane of the desired stereochemistry (eq 9). Inflation of a secondary over a tertiary alcohol allows dehydration to form a conjugated olefin (eq 10). Tf20 induced partial decomposition in this case. ... 

The alkenyloxirane 126 in excess reacts with aryl and alkenyl halides or triflates in the presence of sodium formate to afford the allylic alcohol 127[104], Similarly, the reaction of the alkenyloxetane 128 gives the homo-allylic alcohol 130[105]. These reactions can be explained by insertion of the double bond in the Ar—Pd bond, followed by ring opening (or /3-eliraination) to form the allylic or homoallylic alkoxypalladium 129, which is converted into the allylic 127 or homoallylic alcohol 130 by the reaction of formate. The 3-alkenamide 132 was obtained by the reaction of the 4-alkenyl-2-azetizinone 131 with aryl iodide and sodium formate [106]. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

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. 

The submitters state that the copper(I) triflate is quite air stable In solution In the presence of the allyllc alcohol. 

Benzyl and allyl alcohols which can generate stabilized caibocations give Friedel-Crafts alkylation products with mild Lewis acid catalysts such as scandium triflate. ... 

Tnflrc anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive triflates can be generated m situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoqumolines (equation 45) and synthesis of Al-hydroxy-a-amino acid denvatives (equation 46) via the intermediate covalent triflates... 

THP ethers can be converted directly to TBDMS and TES ethers using the silyl hydride and Sn(OTf)2 or the silyl triflate (70-95% yield). The use of TMSOTf gives the free alcohols upon isolation. ... 

TBDMSOTf, CH2CI2, rt, 24 h, 82% yield. The use of a catalytic amount of the triflate will give the alcohol. If the triflate is used stoichiometrically and the reaction worked up with 2,6-lutidine, the TBDMS ether is isolated (98% yield). "... 

The second element of general importance in the synthesis of a task-specific ionic liquid is the source of the functional group that is to be incorporated. Key to success here is the identification of a substrate containing two functional groups with different reactivities, one of which allows the attachment of the substrate to the core, and the other of which either is the functional group of interest or is modifiable to the group of interest. Functionalized alkyl halides are commonly used in this capacity, although the triflate esters of functionalized alcohols work as well. 

Bonhote and co-workers [10] reported that ILs containing triflate, perfluorocar-boxylate, and bistrifylimide anions were miscible with liquids of medium to high dielectric constant (e), including short-chain alcohols, ketones, dichloromethane, and THF, while being immiscible with low dielectric constant materials such as alkanes, dioxane, toluene, and diethyl ether. It was noted that ethyl acetate (e = 6.04) is miscible with the less-polar bistrifylimide and triflate ILs, and only partially miscible with more polar ILs containing carboxylate anions. Brennecke [15] has described miscibility measurements for a series of organic solvents with ILs with complementary results based on bulk properties. 

Scheme 5.1-27 The zinc triflate-catalyzed coupling of alkynes with aldehydes to give propargyl alcohols in an ionic liquid.

In the case of Lewis acids, protic solvents such as water or alcohol can strongly influence their reactivity, cause it to react via an alternative path to the one desired, or even cause decomposition. Recently, rare earth metal triflates were used to develop water tolerant Lewis acids that can be used in many organic reactions. ... 

The reaction between epoxides and ammonia is a general and useful method for the preparation of P-hydroxyamines. " Ammonia gives largely the primary amine, but also some secondary and tertiary amines. The useful solvents, the ethanolamines, are prepared by this reaction. For another way of accomplishing this conversion, see 10-54. The reaction can be catalyzed with Yb(OTf)3 and in the presence of a-BINOL is l,l -bi-2-naphthol derivative gives amino alcohols with high asymmetric induction. A variation used Yb(OTf)3 at lOkbar or at ambient pressure. Lithium triflate can also be used. Primary and secondary amines give, respectively, secondary and tertiary amines, for example. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

Difunctional reagents, for example the very cheap dimethyldichlorosilane 48, which is produced on a large technical scale, and the much more reactive and expensive dimethylsilyl bis(O-triflate) 49 [65-67] (Scheme 2.8) convert alcohols or phenols 11 in the presence of bases, for example triethylamine or DBU, into the silylated compounds 50. Thus 48 and 49 and other bifunctional reagents such as di-tert-butyldichlorosilane [68] or di(tert-butylsilyl)-bis(0-triflate) [69] and the subsequently described 51 and 52 combine two alcohols to silicon-tethered molecules 50, which can undergo interesting intramolecular reactions [70-74]. 

The use of the enolsilyl ether of 1-menthone [16, 19, 21-23] and of some free triflic acid favors the formation of the thermodynamically controlled products as with free 2,2 -dihydroxydiphenyl [22] and only subsequently added HMDS 2 [22]. On reacting silylated alcohols and carbonyl compounds with pure trimethylsilyl triflate 20 under strictly anhydrous conditions no conversion to acetals is observed [24]. Apparently, only addition of minor amounts of humidity to hydrolyze TMSOTf 20 to the much stronger free triflic acid and hexamethyldisiloxane 7 or addition of traces of free triflic acid [18-21, 24, 26] or HCIO4 [25] leads to formation of acetals. 

To obtain this compound the key step consisted in the epimerization of the C-5 in compound 6. This was acomplished by triflation of the alcohol 6 and nucleophilic substitution of the triflate by a large excess of tetrabutylammonium acetate in dichloromethane. A controlled (4 °C, 3 h) basic methanolysis of the enol benzoate led to the keto-ester 11" whose hydroxyl functions at C-4 and C-6 were simultaneously deprotected under acidic conditions to furnish 12. Finally a Zemplen deprotection of the 5-acetoxy group led to 13 obtained in five steps and 11% overall yield from 6 (figure 4). 

As for the synthesis of 5-e/j/-KDG, compound 6 seemed to be a suitable precursor of the methyl ester of 5-deoxy-KDG 20 since only the C-5 hydroxyl was unprotected. In this case the key step was not the epimerization but the removal of that hydroxyl. Our attempts of radicalar deoxygenation of 6 were unsuccessful because the intermediate radical was intramolecularly trappy by the C-2.C-3 double bound. Therefore we first reduced the double bond and then converted the resulting diastereoisomeric alcohols 14 into the corresponding triflates 15 which were submitted to the action of sodium iodide. Finally the iodides 16 Aus obtained were hydrogenolyzed in the presence of diisopropylethylamin to give 17. 

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