Alkenes direct trifluoromethylation

Unlike alkenes directly substituted with fluorine atoms (see Section 2.1.1.6.1.2.), fluoroalkyl-substituted alkenes are not prone to undergo [2 + 2] cycloadditions. An early report concerns the peculiar case of 2-[bis(trifluoromethyl)methylene]propanedinitrile(l) which reacts remarkably easily with electron-rich alkenes, such as methyl vinyl ether and styrene derivatives. ... 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Another convenient entry to fused cyclobutene-1,2-diesters was via site selective modification of the norbomene rt-bond in Smith s fe-alkene 49, e.g. treatment with 3,6-di(2 -pyridyl)-s-tetrazine 51 followed by DDQ oxidation afforded the cyclobutene-derivative 53 <97AA119>, while direct coupling with 3,5-f> (trifluoromethyl)-l,3,4-oxadiazo]e 54 furnished the tas(cyclobutene-l,2-diester) 55 (Scheme 6) <97SL196>. 

A particularly useful reaction of this type involves the direct formation of hexakis(trifluoromethyl)cyclopentadiene (71) (Scheme 31), or the corresponding cyclopentadienide (72), from the diene (38) by a fluoride ion induced reaction with pentafluoropropene [67-69]. Recent work [54] has shown that very active sources of fluoride ion can be generated by direct reaction of amines, especially TDAE (43), with perfluorinated alkenes or perfluorinated aromatic compounds and these essentially solventless systems promote both oligomerisations (see above) and polyfluoroalkylations. The absence of solvent makes recovery of product very easy, e.g. in high-yielding formation of (73), (74) or (75) (Scheme 32). 

Friedel—Crafts alkylation. Alkenes (styrenes and trisuhstituted alkenes) alkylate indoles at the 3-position in CH2CI2 containing 5 mol% of TfOH (or an Au(III) species). Benzyl trifluoromethyl carhinols are obtained from reaction of arenes with trifluoro-methyl epoxides. The direction of epoxide ring opening is determined by the electron-withdrawing trifluoromethyl group. ... 

Cohen and co-workers have reported a facile synthesis of 2-(trifluoro-methyl)histamine and 2-(trifluoromethyl)-L-histidine using histamine and L-histidine as starting materials, repectively. The desire to use histamine and histidine was mainly due to ready availability, which would lead to rapid synthetic sequences and a direct entry into the fluorinated L-amino acid series. cw-l,2-Dibenzamido-l-alkenes (34) prepared by the Bamberger imidazole cleavage of corresponding imidazoles (33) were condensed with trifluoroacetic anhydride at reflux (40 °C) to yield 2-trifluoromethyl substituted imidazoles (35) in about 70% yield. 

A full account of the synthesis of the mercurials PhHg-CXCI-CF, (X = Br or Cl) and their plications in synthesis as direct thermal sources of chloro(trifluoromethyl)carbene (Vol. 1, p. 87) is also available now. The bromide (X = Br) is the preferred reagent since it decomposes at a lower temperature (used at 130—140 °C) than the chloride (X = Cl slow at 160 C), and examples of its use in the preparation of 1-chloro-l-(trifluoro-methyl)cyclopropanes, l-chloro-2,2,2-trifluoroethylsilanes (see p. 197), and l-chloro-l-(trifluoromethyl)alkenes [PhHgCBrCICFs... 

CFa-attached heteroaromatics can easily be synthesized as well. Very importandy, trifluoromethylated alkenes, of which diere have been limited studies on the direct synthetic methods, can participate very well in the cross coupling, although a decrease of the yields can be observed and in addition the alkenes are partially isomerized during the reaction. 

---