Trifluoroacetic acid reaction with alkenes

Trifluoroacetic acid adds to alkenes without the necessity of a stronger acid catalyst. The mechanistic features of this reaction are similar to those of addition of water catalyzed by strong acids. For example, there is a substatial isotope effect when CF3CO2D is used, and the reaction rates of substituted styrenes are correlated with... 

Benzoic acid and substituted benzoic acids are readily thallated by thallium(III) trifluoroacetate. Subsequent reaction with palladium chloride and simple alkenes, allylic or vinyl halides, or vinyl esters result in the formation of isocoumarins eg ... 

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

A hydroxy and an arylthio group can be added to a double bond by treatment with an aryl disulfide and lead tetraacetate in the presence of trifluoroacetic acid." Manganese and copper acetates have been used instead of Pb(OAc)4. ° Addition of the groups OH and RSO has been achieved by treatment of alkenes with O2 and a thiol (RSH)." Two RS groups were added, to give vie- dithiols, by treatment of the alkene with a disulfide RSSR and Bp3-etherate."° This reaction has been carried... 

The triethylsilane/trifluoroacetic acid reagent system reduces alkenes to alkanes in poor to excellent yields depending largely on the ability of the alkene to form carbocations upon protonation. Under these conditions the more substituted olefins are reduced in better yields and styrene double bonds are reduced in high yields.127,202,207,221-228 The reduction of 1,2-dimethylcyclohexene with this reagent gives a mixture of cis- and trans- 1,2-dimethylcyclohexane.229 The formation of the trifluoroacetate esters is a side reaction.205,230... 

Trisubstituted Alkenes. With very few exceptions, trisubstituted alkenes that are exposed to Brpnsted acids and organosilicon hydrides rapidly undergo ionic hydrogenations to give reduced products in high yields. This is best illustrated by the broad variety of reaction conditions under which the benchmark compound 1-methylcyclohexene is reduced to methylcyclohexane.134 146,192 202 203 207-210 214 234 When 1-methylcyclohexene is reduced with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50°, methylcyclohexane-... 

Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55° and followed by hydrolytic workup (Eq. 205).203... 

Many hydroxy compounds would not survive such harsh treatment therefore other methods must be used. Some alcohols were hydrogenolyzed with chloroalanes generated in situ from lithium aluminum hydride and aluminum chloride, but the reaction gave alkenes as by-products [605], Tertiary alcohols were converted to hydrocarbon on treatment at room temperature with triethyl- or triphenylsilane and trifluoroacetic acid in methylene chloride (yields 41-92%). Rearrangements due to carbonium ion formation occur [343]. 

The triphenyl derivative (91, R = R = R = Ph, R = H) is formed in a mechanistically interesting reaction between benzoyl formic acid anil (Ph-N=CPh-C02H), trifluoroacetic anhydride, and pyridine. Its 1,3-dipolar cycloaddition reactions with alkynes and alkenes have been reported. ... 

Amino-3-chloro-5-trifluoromethylpyridine with electron-rich alkenes and formaldehyde in the presence of trifluoroacetic acid in boiling acetonitrile for 1 h yielded 6a,7,8,9,10,10a-hexahydro-6//-pyrido[l,2-a]-quinazolines (326) (96TL2615). The regiochemistry is dictated by the reaction of formaldehyde at the primary amino group. 

Thallium(lII) trifluoroacetate is a versatile oxidant for organic compounds [55, 56, 57] It reacts with alkenes at room temperature to form oxiranes, ketones, and 1,2 diols [55] Usually these oxidations are accompanied by cyclizations and rearrangements The reaction of thallium(III) trifluoroacetate with substituted cinnamic acids results in instantaneous oxidative dimerization leading to bislactone lignans, which belong to a naturally occurring family of compounds [56] (equation 26)... 

The effect of monofluorination on alkene or aromatic reactivity toward electrophiles is more difficult to predict Although a-fluonne stabilizes a carbocation relative to hydrogen, its opposing inductive effect makes olefins and aromatics more electron deficient. Fluorine therefore is activating only for electrophilic reactions with very late transition states where its resonance stabilization is maximized The faster rate of addition of trifluoroacetic acid and sulfuric acid to 2-fluoropropene vs propene is an example [775,116], but cases of such enhanced fluoroalkene reactivity in solution are quite rare [127] By contrast, there are many examples where the ortho-para-dueeting fluorine substituent is also activating in electrophilic aromatic substitutions [128]... 

The addition of trifluoroacetic acid to the palladium or platinum peroxide adducts with electrophilic alkenes results in the formation of epoxide in high yield and with high stereoselectivity.143,148 The mechanism shown in equation (51) has been suggested for this reaction.148... 

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... 

O-Alkyl oximes are excellent precursors of COs as they react more slowly with ozone than alkenes. Initially <1995LA1571>, as added carbonyl species, acyl cyanides and esters of trifluoroacetic acid were used and the ozonides could be isolated usually in 25-60% yields. In an extension of this reaction, trapping could be performed by a variety of carbonyl compounds. 

Cocyclization of 3,4-dicyano-l,2,5-selenodiazole 81 and alkene 234 by reaction with Mg(OBu)2 in BuOH, and subsequent demetalation by trifluoroacetic acid and metalation with MnCl2, led to a porphyrazine containing one 1,2,5-selenodiazole ring Mn complex 235 in 59% yield (Equation 29) <2003AGE462, 2003JOC1665>. 

The reaction of 3,4-dicyano-l,2,5-selenodiazole 81 and alkene 236 with Li or MglO-zr-CsHuL in boiling -penta-nol and subsequent demetalation by either acetic acid (Li) or trifluoroacetic acid (Mg) gave unsymmetrical porphyr-azine with 1,2,5-selenodiazole 89 (Equation 30) <2001MC45>. The structure of product 89 was elucidated by single crystal X-ray diffraction. 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

Cleavage with an ensuing Heck reaction was developed by using the T1 triazene linker [51] (Scheme 6.1.20). On cleavage with trifluoroacetic acid a diazonium ion is first formed this can couple to an added alkene under the action of palladium catalysis. The coupling proceeds well with simple terminal alkenes, styrenes, and di- and even trisubstituted alkenes. The advantage of this process is clearly the possibility of using volatile alkenes (and alkynes) without contamination by any salt or other less volatile by-product, particularly with the use of palladium on charcoal as the catalyst. 

In support of the electron transfer mechanism [Eqs. (139)—(141)], the ESR spectra of various radical cations have been observed during reaction of alkenes with Co(III) in trifluoroacetic acid mixtures.218 However, a very different situation may obtain in the cobalt-catalyzed autoxidation of olefins in neutral non-... 

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