Radical addition reactions with trifluoroacetic acid

Direct esr evidence for the intermediacy of radical-cations was obtained on flowing solutions of Co(III) acetate and a variety of substituted benzenes and polynuclear aromatics together in glacial acetic acid or trifluoroacetic acid solution . A p value of —2.4 was reported for a series of toluenes but addition of chloride ions, which greatly accelerated the reaction rate, resulted in p falling to —1.35. Only trace quantities of -CH2OAC adducts were obtained and benzyl acetate is the chief product from toluene, in conformity with the equation given above. 

The selective oxidation of C—H bonds in alkanes under mild conditions continues to attract interest from researchers. A new procedure based upon mild generation of perfluoroalkyl radicals from their corresponding anhydrides with either H2O2, m-CPBA, AIBN, or PbEt4 has been described. Oxidation of ethane under the reported conditions furnishes propionic acid and other fluorinated products.79 While some previously reported methods have involved metal-mediated functionalization of alkanes using trifluoroacetic acid/anhydride as solvent, these latter results indicate that the solvent itself without metal catalysis can react as an oxidant. As a consequence, results of these metal-mediated reactions should be treated with caution. The absolute rate constants for H-abstraction from BU3 SnH by perfluorinated w-alkyl radicals have been measured and the trends were found to be qualitatively similar to that of their addition reactions to alkenes.80 a,a-Difluorinated radicals were found to have enhanced reactivities and this was explained as being due to their pyramidal nature while multifluorinated radicals were more reactive still, owing to their electrophilic nature.80... 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

Reaction with unsaturated bicyclic hydrocarbons. From a study of the chlorination of unsaturated bicyclic compounds, Masson and Thuillier1 conclude that the reaction follows, a radical addition mechanism when initiated thermally or photo-chemically. The stereochemistry of the addition is markedly influenced by steric effects. No Wagner-Meerwein rearrangements are observed under these conditions. An ionic mechanism is involved without initiation or in the presence of trifluoroacetic acid in this case the usual carbonium ion rearrangements are observed. 

The classical Hunsdiecker conditions using Ag, and modifications using metals such as Hg, Tl, Pb, and Mn(II), are not very synthetically useful because of the use of toxic metals, requirement of high temperature, and poor yields. As a consequence, many variants of greener chemistry have been developed to replace heavy metals. In addition to Barton s radical approaches, Roy et al. developed a metal-free Hunsdiecker reaction where the acid was treated with A-bromosuccinamide (NBS) and a catalytic amount of LiOAc27 or the phase transfer catalyst (PTC) tetrabutylammonium trifluoroacetate (TBATFA).28-30 As shown below, cinnamic acid 26 was converted to (B-bromostyrene 27 in almost quantitative yield.28 The authors also found that a mixture of 93 7 MeCN/H20 was also a good solvent for the metal-free Hunsdiecker reaction.29 In place of TBATFA, another phase transfer catalyst Select flur was found to be an efficient catalyst for the metal-free Hunsdiecker reaction as well (e.g., 29—>30).31... 

Epithio compounds are obteuned from epoxides by reaction with sulphur-containing compounds such as thiourea, thiocyanogen, thiocyanates, potassium methyl xanthate and base, or 3-methylbenzothiazol-2-one and trifluoroacetic acid. 9,10-Epithiostearic acid melts at 58 °C (cis) and 64 °C (trans). Sulphur-containing compounds can also be made by radical addition (usually photolytic) of hydrogen... 

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