Trifluoromethyl iodide, synthesis

Direct introduction of the trifluoromethyl group provides another general route. Irradiation of a methanolic solution of trifluoromethyl iodide and imidazole produces a mixture of 2- and 4-trifluoromethylimidazoles and 2,4-bistrifluoromethylimidazole. This can be applied to simple imidazoles and substituted imidazoles. The photochemical procedure provides a convenient synthesis of trifluoromethyl derivatives of histidine and histamine. ... 

Other systems for generation of electrophilic perfluoroalkyl radicals were also applied to the synthesis of perfluoroalkylfurans. Thus, trifluoromethylation of furan and benzofuran with trifluoromethyl iodide in DMSO afforded the 2-trifluoromethyl derivatives in 16 and 30 % yield correspondingly [51], Better results were reported for the photocatalytic Ru(bpy)3Cl2-TMEDA system. Trifluoromethylation of... 

Heteroaromatic esters such as 493 and amides are produced by the carbo-nylation of heterocyclic bromides[347,348]. Even dichloropyrazine (494) and chloropyridine are carbonylated under somewhat severe conditions (120 C, 40 atm)[349]. The carbonylation of trifluoroacetimidoyl iodide (495) proceeds under mild conditions, and can be used for the synthesis of the trifluoromethyl-glycine derivatives 496 and 497(350]. 

In our laboratory, we find that the plasma reaction of trifiuoro-methyl radicals with mercuric iodide is an excellent source of bis(tri-fluoromethyDmercury. For those laboratories that lack access to radiofrequency (rf) equipment (a 100-W, rf source can at present be purchased for less than 1,000), synthesis of bis(trifluoromethyl)mercury by the thermal decarboxylation of (CFgCOjlzHg is also a functional, and quite convenient, source of bis(trifiuoromethyl)mercury (23). 

Similarly, Uneyama and Watanabe (91TL1459) have reported the synthesis of trifluoromethylated AI-aryl-1-azabutadienes by palladium-catalyzed coupling of trifluoroacetimidoyl iodides with alkenes as well as the transformation of the azadiene derived from methyl acrylate into the corresponding 4-methoxycarbonyl-2-trifluoromethylquinoline in quantitative yield. 

This indirect, two-step procedure for the synthesis of trifluoromethyl derivatives of transition metals was developed after it had become evident that the reaction of CF3I with metallate ions such as Mn(CO)5 resulted in the formation of the iodide rather than the expected trifluoromethyl derivative, as indicated in Eq. (3) (16). 

UV-light initiation is used for the perfluoroalkyl iodide addition to more fragile alkenes. The synthesis of 3-trifluoromethyl-substituted steroids is an example of such a photochemical addition. In the addition of trifluoroiodomcthanc to 5a-pregn-3-en-20-one. only one product 4 was isolated from the reaction mixture although eight isomeric adducts might be formed from this reaction. ... 

One of the most versatile methods for the synthesis of 1,1-difluorocyclopropanes is the decomposition of phenyl(trifluoromethyl)mercury, in the presence of an alkene, using sodium iodide at ca. 80"C (refluxing benzene) " (Houben-Weyl, Vol. E19b, pp 1471-1473). 

A new synthesis of 2,4,4,6-tetramethyl-4//-l,3-oxazine (155) simply involves a reductive cycloaddition of 4-methylpent-3-en-2-one and acetonitrile in the presence of trimethylsilyl chloride and sodium iodide (Scheme 42) <89TL4741>. Other cycloaddition reactions have been used previously to synthesize 4//-l,3-oxazines and this methodology has been extended to include cycloadditions between alkynes and l-oxa-3-azabuta-1,3-dienes. For example, phenylethyne and the A-benz-oylimine (156) afford 4,4-bis(trifluoromethyl)-2,6-diphenyl-4//-l,3-oxazine (157). The reaction proceeds through a Michael-type addition between the alkyne and the heterodiene giving an adduct which when heated to 80-90°C cyclizes to the oxazine (Scheme 43) <83CC945,89ZN(B)1298>. 

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