Protonation by trifluoroacetic

The rate-determining step in the ionic hydrogenation reaction of carbon-carbon double bonds involves protonation of the C==C to form a carbocation intermediate, followed by the rapid abstraction of hydride from the hydride source (equation 45). ° There is a very sensitive balance between several factors in order for this reaction to be successful. The proton source must be sufficiently acidic to protonate the C—C to form the intermediate carbocation, yet not so acidic or electrophilic as to react with the hydride source to produce hydrogen. In addition, the carbocation must be sufficiently electrophilic to abstract the hydride from the hydride source, yet not react with any other nucleophile source present, i.e. the conjugate anion of the proton source. This balance is accomplished by the use of trifluoroacetic acid as the proton source, and an alkylsilane as the hydride source. The alkene must be capable of undergoing protonation by trifluoroacetic acid, which effectively limits the reaction to those alkenes capable of forming a tertiary or aryl-substituted carbocation. This essentially limits the application of this reaction to the reduction of tri- and tetra-substituted alkenes, and aryl-substituted alkenes. 

There has been no report on the success, or failure, of the attempted reduction of (Z C bonds by the ionic hydrogenation type of reaction. The reason for this is not clear. Carbon-carbon triple bonds are capable of being protonated by trifluoroacetic acid to produce what appear to be vinyl cationic species, which should be capable of abstracting a hydride from an organosilane. 

The most common reduction system for the ionic hydrogenation of double bonds is trifluoroacetic acid with an organosilane. The alkene must be capable of undergoing protonation by trifluoroacetic acid which limits the application of this reaction to the reduction of tri-and tetrasubstituted alkenes, as well as aryl-substituted alkenes. 

We first need to draw the cation that will be produced after protonation by trifluoroacetic acid (a strong acid) and loss of water. 

In contrast to pyridine derivatives, aryl- and alkyl-substituted A -phosphorins cannot be protonated by strong, non-oxidizing acids such as trifluoroacetic acid. Addition of trifluoroacetic acid to cyclohexane solutions of various A -phosphorins fails to produce any change in the UV spectra Similarly, alkylation by such strong agents as oxonium salts or acylation by acylchlorides cannot be induced at the P atom or any ring C atom. This behavior has also been discussed theoretically 55a)... 

In contrast to X -phosphorins, X -phosphorins can be protonated. The basicity is very much influenced by the nature of the substituents R and R at the phosphorus. 1.1-Dialkyl or 1.1-diaryl-X -phosphorins are even protonated by aqueous HCl the salts are deprotonated by aqueous NaOH. Strong acids in organic solvents, e. g. trifluoroacetic acid in hexane or benzene, (see p. 106), are required to proto-nate 1.1-dialkoxy-X -phosphorins. Addition of tert-butoxide deprotonates the salt. By studying the NMR spectra of 1. l-dimethoxy-2.4.6-tris-pentadeuterophenyl-X -phosphorin 185 in benzene solutions containing H and D-trifluoroacetic acid Stade could show that two different protonation products are formed in a ratio of 3 1. One product is the result of C—2 protonation 186 the other of C-4 protonation 187 (Fig. 38). Similar results were observed in the case of 1.1-bis-dimethylamino-2.4.6-triphenyl-X -phosphorin... 

Thiophenes are best converted to the tetrahydro derivatives by the so-called ionic hydrogenation. This depends on the successive addition of a proton (from trifluoroacetic acid) and a hydride ion (from triethylsilane) (75T311). A subsequent improvement involved the use of HC1/A1C13 to form the thiophenium ion and then reaction with triethylsilane (78T1703) best results are obtained with the substrate/Et3SiH/AlCl3 ratio of 1 3 0.3. The mechanism of the reaction is shown in Scheme 43. Evidence for this has been provided by the use of Et3SiD, when D enters positions 3 and 5 in the product. 

Similar results have been obtained in the reactions of 1 and sodium salts of p-cresol and - and /J-naphthols. Under SN2 conditions (DMF or DMSO solvent), the alkylation of sodium cresolate occurs exclusively at the oxygen atom. The addition of a protic solvent causes C-alkylation, though the yields of C-alkylated products are low. Thus in acetone-water or dioxane-water, the yield of C-alkylated products 251 and 252 increases only up to 2%. C-Alkylation has also been observed in the reactions catalyzed by trifluoroacetic acid or boron trifluoride etherate at room temperature. The observed C-alkylation in protic media may be a reflection of a mechanism that involves a protonated epoxide or a more polarized transition state than in an SN2 pathway. 

Protonation of l-ferrocenyl-2-trimethylsilylalkyne 365 by trifluoroacetic acid in SO2CIF at < —80 °C yielded the a-ferrocenyl /i-lrirnclhylsilylvinyl cation 366. Cation 366 decomposes slowly at — 80 °C to the parent a-ferrocenylvinyl cation 367 and trimethylsilyl trifluoroacetate (equation 59)144. 

The 1,4-photoaddition of aliphatic amines with benzene via photoinduced electron transfer was first reported by Bryce-Smith more than 30 years ago [375-378], In the photoreaction of triethylamine with benzene, the proton transfer from the radical cation of triethylamine to the radical anion of benzene is proposed as a probable pathway (Scheme 113). In the case of tertiary amines, the photoaddition is accelerated by the addition of methanol or acetic acid as a proton source. Similar photoaddition of diethyl ether to benzene takes place assisted by trifluoroacetic acid, where methanol is not affective [379], In these photoreactions, a-hydrogen next to the heteroatom moves to the radical anion of benzene as a proton, followed by radical ccoupling to give 1,4-addition products. Similar photoaddition of amines to the benzene ring has been reported by Ohashi et al. [380,381],... 

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. 

It is worth mentioning that movement of the CBPQT4 ring from the benzidine unit to the biphenol unit could also be effected by protonation of the benzidine nitrogen atoms by trifluoroacetic acid, making the unit a much weaker it-electron donor. The recovery stroke of the CBPQT4 ring could be effected by the addition of a stoichiometric amount of pyridine, which deprotonates the protonated benzidine unit. 

Removal of a proton by some base, such as trifluoroacetate anion, gives the final product, an ester. 

The [2]rotaxane 224+ can be switched (Figure 15) by controlling the pH. Upon addition of an excess of trifluoroacetic acid, the benzidine unit becomes protonated, generating the [2]rotaxane [22-2H]6+. The tetracationic cyclophane moves away from this newly generated dicationic unit because of electrostatic repulsion. In this case, the absorption spectrum lacks the 690 nm band, confirming the deprotonation of the benzidine unit and the relocation of the cyclophane to the biphenol unit. The [2]rotaxane [22-2H]6+ can be subsequently de-protonated by the addition of pyridine, regenerating the [2]rotaxane 224+. 

By constructing betaines (e.g. [51], [52]) in which the solvent-sensitive absorption band is displaced to longer wavelengths, Dimroth et al. (1963) were able to obtain directly a solvent polarity scale (Ej), including more polar solvents. Unfortunately, acidic solvents cannot be studied because the oxygen atom of the indicator is protonated by these solvents. Thus in two of the solvents (formic acid and trifluoroacetic acid), independent measures of solvent polarity, which would have been particularly helpful in analysing the results of rate correlations (e.g. Fig. 12), are not available. 

The observations that secondary amines, (Rf)2NH, do not react with boron trifluoride, hydrogen chloride or trifluoroacetic acid [13] also serve to indicate a lack of basic properties. Similarly, tertiary perfluoroalkylamines are quite without basic properties. Moreover, the oxygen atoms in perfluoroalkyl ethers and ketones are poor donors this is exemplified by the fact that hexafluoroacetone cannot be protonated by superacids in solution. Such findings parallel similar observations with unsaturated derivatives where the base strength is considerably reduced in, for example, perfluorop3Tidine or perfluoro-quinoline [14] in comparison with the parent compounds. 

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