Trifluoroacetic acid Pyridinium trifluoroacetate

NMO NMP Nu PPA PCC PDC phen Phth PPE PPTS Red-Al SEM Sia2BH TAS TBAF TBDMS TBDMS-C1 TBHP TCE TCNE TES Tf TFA TFAA THF THP TIPBS-C1 TIPS-C1 TMEDA TMS TMS-C1 TMS-CN Tol TosMIC TPP Tr Ts TTFA TTN N-methylmorpholine N-oxide jV-methyl-2-pyrrolidone nucleophile polyphosphoric acid pyridinium chlorochromate pyridinium dichromate 1,10-phenanthroline phthaloyl polyphosphate ester pyridinium p-toluenesulfonate sodium bis(methoxyethoxy)aluminum dihydride (3-trimethylsilylethoxy methyl disiamylborane tris(diethylamino)sulfonium tetra-n-butylammonium fluoride f-butyldimethylsilyl f-butyldimethylsilyl chloride f-butyl hydroperoxide 2,2,2-trichloroethanol tetracyanoethylene triethylsilyl triflyl (trifluoromethanesulfonyl) trifluoroacetic acid trifluoroacetic anhydride tetrahydrofuran tetrahydropyranyl 2,4,6-triisopropylbenzenesulfonyl chloride 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane tetramethylethylenediamine [ 1,2-bis(dimethylamino)ethane] trimethylsilyl trimethylsilyl chloride trimethylsilyl cyanide tolyl tosylmethyl isocyanide meso-tetraphenylporphyrin trityl (triphenylmethyl) tosyl (p-toluenesulfonyl) thallium trifluoroacetate thallium(III) nitrate... 

The most intensively studied oxidizing system is that developed by Pfitzner and Moflatt in which the oxidation is carried out at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and a weak acid such as pyridinium trifluoroacetate or phosphoric acid. The DCC activates the DMSO which in turn reacts with the carbinol to give an oxysulfonium intermediate. This breaks down under mild base catalysis to give the desired ketone and dimethyl sulfide. 

The use of dichloroacetic acid instead of pyridinium trifluoroacetate increases the rate of oxidation considerably. This acid has been used in one case to obtain an optimum yield of the 11-ketoestrone (8) from the corresponding 1 la-hydroxy compound. ... 

Several acids salts have been proposed to replace tetrazole as the activator of phosphoroamidite coupling with alcohols. The most popular are benzimida-zolium [20a], imidazolium [20b], AT-methylimidazolium [20c], AT-methylani-line [20h] trifiates, pyridinium hydrochloride [20d,e], hydrobromide [20e], tetrafluorborate [20f], trifluoroacetate [20g] and 2,4,6-collidine trifiuoroac-etate [20i]. 

Some commonly used buffers, such as sodium and potassium phosphate, are incompatible with ELSD, but there are ready alternatives. For example, ammonium acetate has similar buffering properties to potassium phosphate, and ammonium carbonate, ammonium formate, pyridinium acetate, and pyridinium formate are options for different pH ranges. Typical mobile phase modifiers that do not meet the volatility criteria can be replaced by a wide variety of more volatile alternates. For example, phosphoric acid, commonly used as an acid modifier fo control pH and ionization, can be replaced by trifluoroacetic acid other acids that are sufficiently volatile for use with FLSD include, acetic, carbonic, and formic acids. Triethylamine, commonly used as a base modifier, is compatible with FLSD other base modifiers that can be used are ethylamine, methylamine, and ammonium hydroxide [78]. 

Acetic acid,127 pyridinium trifluoroacetate (PTFA)121 or pyridinium tosylate (PPTS)128 are often added in order to speed up PDC oxidations. Acetic acid, which is described as superior127a and very easy to remove, is used most often. Although this precludes the advantages of using an almost neutral PDC medium, it provides a very useful substantial acceleration of the oxidations. The combined employment of molecular sieves and an acid can provide a synergistic accelerating effect.127a... 

Moffatt et al. found that the optimized reaction conditions developed for the oxidation of testosterone (14), worked ideally in the oxidation of other alcohols. Later, researchers tended to apply, on reactions run at room temperature on very diverse alcohols, these optimized conditions involving 3 equivalents of DCC or other carbodiimide, 0.5 equivalents of pyridinium trifluoroacetate with some extra pyridine added, and neat DMSO or a mixture of DMSO and benzene as solvent. The only substantial changes to this standard protocol involve the growing use of the water-soluble carbodiimide EDC,17 instead of DCC, in order to facilitate the work-ups, and the occasional employment of dichloroacetic acid,18 which proved very effective in the oxidation of some complex polar alcohols, instead of pyridinium trifluoroacetate. 

Pyridinium trifluoroacetate can either be added as such, or formed in situ by the addition of pyridine (MW — 79.1, d — 0.98) and trifluoroacetic acid (MW — 114.0, d = 1.48). Very often pyridine is added in an excess of ca. 0.5-2 equivalents relative to trifluoroacetic acid for buffering purposes. 

During the oxidation of greatly hindered alcohols, it can be advisable to use 0.5 equivalents of ortophosphoric acid (MW = 98.0) (solid phosphoric acid) instead of pyridinium trifluoroacetate. This causes an acceleration of the oxidation, although it normally leads to greater amounts of side compounds. On some highly polar compounds, the use of 0.5 equivalents of dichloroacetic acid (DCAA) (MW = 128.9, d = 1.47) can provide best results. 

Pyridinium trifluoroacetate is such a mild acidic catalyst that it can hardly affect acid-sensitive functionalities. Thus, for example the very acid-sensitive Boc-protected amines49 and r-butyl esters,50 as well as glycosides51 and acetals,52 remain unchanged under Pfitzner-Moffatt conditions. 

Homoallylic alcohols are oxidized, in the presence of pyridinium trifluoroacetate, with no migration of the alkene into conjugation with the carbonyl, even in cases in which such migration can occur under very mild acidic catalyses. On the other hand, the stronger acid H3PO4 is able to produce such isomerizations.14b... 

Potassium superoxide. Pyridinium chlorochromate. Pyridinium dichromate. Pyridinium fluorochromate. Silver(I) oxide. Silver(II) oxide. Sodium chlorite. Sodium hypochlorite. Sodium periodate. Sodium peroxide. Thallium(in) trifluoroacetate. Trifluoroperacetic acid. 

When a mineral or Lewis acid replaces the carboxylic component in the Passerini reaction, the final products are usually a-hydroxyamides. Also in this case, when chiral carbonyl compounds or isocyanides are employed, the asymmetric induction is, with very few exceptions, scarce [18, 19]. For example, the pyridinium trifluoroacetate-mediated reaction of racemic cyclic ketone 14 with t-butyl isocyanide is reported to afford a single isomer [19] (Scheme 1.7). This example, together with those reported in Schemes 1.3 and 1.4, suggests that high induction may be obtained only by using rigid cyclic or polycyclic substrates. 

Pyridinium chlorochromate Trifluoroacetic anhydride 4-Toluenesulfonic acid... 

The pyridinium perchlorate (212), which is the precursor of the mesoionic oxazolone (213), is formed by the action of acetic anhydride and perchloric acid on l,2-dihydro-2-oxopyridin-l-acetic acid. The mesoion (213) is chemically unstable and is generated in solution for its reactions by treatment with a tertiary amine. Compound (213) is easily substituted at C-3, and with trifluoroacetic anhydride forms the stable 3-trifluoroacetyl mesoion (70JCS(C)1485). 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

Acid-catalysed hydrolysis is the most common method for deprotecting isopro-pylidene derivatives and the add strength and reaction time can vary widely. The mildest conditions involve gently heating the substrate with pyridinium p-toluenesulfonate in aqueous media or methanol [Scheme 3.2. 3 In most cases aqueous trifluoroacetic acid [Scheme 3.3]4 dilute HC1 in THF, or an ion exchange resin such as Dowex SOW [Scheme 3,4]5 will remove them rapidly. In the latter case, note that the less hindered dioxolane hydrolysed preferentially. 

Addition of small quantities of anhydrous acetic acid and fireshly activated sieves to oxidations of carbohydrates has also been found to increase the rate of oxidation. In comparison to the addition of pyridinium trifluoroacetate, reaction times were reduced from days to minutes (Scheme 1). The acetic acid and sieves appear to have a synergistic effect, since both are required to give the dramatic rate enhancement. 

The most commonly used anions have been dihydrogen phosphate, acetate, and trifluoroacetate. Because of their volatility, the weak organic acids such as acetic or trifluoroacetic acid, usually as the free acid, or the ammonium or pyridinium salts are useful for preparative separations However, these anions result (17, 77, 83, 95) in generally poorer peak shapes compared to phosphate systems and because of their high intrinsic absorbance at 210 nm at levels >0.1% v/v, they are not suited for very high-sensitivity detection of peptides at their isosbestic point. Deletion of... 

The trimethylsilyl ester of 3-pyridazinecarboxylic acid reacts with aldehydes and ketones through ipso substitution of the ester group to give 82. The silyl group can be removed in hot ethanol or with pyridinium trifluoroacetate to give 83 (88T3281). 

Dimethyl sulfoxide (DMSO), which is successfully used to dehydrogenate primary alcohols to aldehydes, converts secondary alcohols into ketones in very high yields and under very gentle conditions. The mechanism is discussed in a previous section. Dehydrogenation and Oxidation of Primary Alcohols to Aldehydes (equation 217). The first oxidations were carried out in the presence of dicyclohexylcarbodiimide and an acid catalyst such as pyridinium trifluoroacetate [1016], which protonates the diimide and facilitates the attack by dimethyl sulfoxide (equation 259). 

Finally, there are syntheses where the 3 and 4 positions of the triazole become incorporated in a new ring. 4-Amino-5-phenyltriazole, acetylacetone, and sodium hydroxide, when refluxed in ethanol, gave 5,7-dimethyl-3-phenyl-l,2,3-triazolo[3,4-fl]pyrimidine (lOI) (10 min, 91%) (three related examples also cited) [71JCS(C)2156], Similarly, 4-amino-5-phenyltriazole, ethyl acetoacetate, and piperidine, refluxed for 2 hr in ethanol, gave a mixture of 5-methyl-3-phenyl-l,2,3-triazolo[3,4-a]pyrimidin-7(4//)-one (68%) with the 7-methyl isomer (17%) [73JCS(P 1)943], 4-Amino-5-phenyltriazole, condensed with l-methylbut-2-en-l-ol in a mixture of trifluoroacetic and perchloric acids, produced 2,3-diphenyl-l,2,3-triazolo[l,5-a]pyridinium perchlorate (102) (78KGS1422). 

The Moffatt oxidation was utilized in the endgame of the total synthesis of (+)-paspalicine by A.B. Smith et al. The advanced intermediate hexacyclic homoallylic alcohol was subjected to the Moffatt oxidation conditions using pyridinium trifluoroacetate as the acid catalyst. Under these conditions, the desired p,y-unsaturated ketone and the rearranged a,p-unsaturated ketone (paspalicine) were formed in a 5 1 ratio. The final step was the Rh-catalyzed isomerization of the p,y-unsaturated ketone to the natural product. 

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