Pyridinium trifluoroacetate

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. ... 

Pyridinium trifluoroacetate in oxidation of cholane-24-ol with dimethyl sulfoxide and dicyclohexylcar-bodiimide, 47,25... 

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. 

Very often more than 0.5 equivalents of pyridinium trifluoroacetate (MW — 191.1) are added. This practice is not advisable, as it can lead to a substantial decrease in the yield of the aldehyde or ketone. For instance, during the oxidation of testosterone (14), Moffatt el al. found that on changing from 0.5 to 2.0 equivalents of pyridinium trifluoroacetate, a decrease of ca. 20% occurs.14b On the other hand, the quantity of pyridinium trifluoroacetate can be diminished to 0.1 equivalents with no erosion of the yield, although leading to a slower reaction. 

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. 

If the substrate possesses a basic site, like an amine, this can neutralize the pyridinium trifluoroacetate and prevent the oxidation. In such cases, 1.5 equivalents of pyridinium trifluoroacetate must be added. 

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... 

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. 

One of the simplest demonstrations of the effect incarceration has on a guest s reactivity is the measurement of the basicity of included amine ligands. Solutions of pyridine in CDC13 may be shown by H NMR spectroscopy to be readily protonated by CF3C02D. An analogous reaction of the pyridine hemicarceplex of the open portal hemicarcerand 6.101 results in the pyridine remaining unprotonated. This means that incarcerated pyridine is a much weaker base than the free molecule. This difference is explained most reasonably by the fact that the host has only a very limited ability to solvate the pyridinium ion and will sterically inhibit the formation of pyridinium-trifluoroacetate contact ion pairs. 

C-(w-propyl)-N-phenylnitrone to N-phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami-noacetone hydrochloride, 45,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47,1 /8-chloro-og3-unsaturated, from ketones and dimethylformamide-phosphorus oxychloride, 46, 20 from alkyl halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodiimide, and pyridinium trifluoroacetate, 47, 27 Alkylation, of 2-carbomethoxycyclo-pentanone with benzyl chloride, 45, 7... 

Initially, Corey and Schmidt found that by addition of pyridinium trifluoroacetate (0.4 equiv.) to their reactions, there was an increase in rate and the amount of PDC needed for complete oxidation diminished. Subsequently, several other techniques have been devised to improve the rate and efficacy of PDC oxidations (most frequently in the field of carbohydrate research). 

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 behavior of PDC in CH2CI2 is considerably different. Primary alcohols are oxidized only to aldehydes. Oxidation of secondary alcohols is also satisfactory and can be catalyzed by addition of pyridinium trifluoroacetate. Allylic alcohols are oxidized readily. ... 

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). 

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