Oxidative trifluoromethylation

Similar to nitrile oxides, trifluoromethylated nitrilimines also provide cycloadducts with doubly activated methylene compounds. 

Albeit with less overall success, trifluoromethyl iodide has also been employed to effect oxidative trifluoromethylations of elemental copper and a few chromium and cobalt coordination complexes and to oxidatively cleave metal—metal bonds in complexes like Ni2(CO)2(Cp)2, Co2(CO)g, and GeMe3Fe(CO)2Cp. One of the first examples of this type of reaction is (22)... 

METHYLETHENE (115-07-1) Flammable gas (flash point - 162°F/- lOS C). Able to form unstable peroxides that may cause polymerization. Violent reaction with strong oxidizers, trifluoromethyl hypofluorite, fluoride, chlorine, and many other compounds. Incompatible with ammonium hydroxide. Forms explosive materials with nitrogen oxide compounds. May accumulate static electrical charges, and may cause ignition of its vapors. 

SCHEME 7.8 Copp>er-catalyzed oxidative trifluoromethylation of heteroarenes and arenes with di-ferf-butyl peroxide. 

SCHEME 7.9 Copper-catalyzed oxidative trifluoromethylation of indoles. 

Trifluoromethylated heteroarenes are widely applicable in the synthesis of pharmaceuticals. Using 10 mol% palladinm acetate as catalyst, TMSCF3 as trifluoro-methylating reagent, bidentate nitrogen-containing ligand L, and PhI(OAc)2 as oxidant, Liu and coworkers developed a novel palladium catalyzed oxidative trifluoromethylation of indoles at room temperatnre (Scheme 9.20). This reaction likely involves a palladium (II/IV) mechanism for the formation of the sp C—CF3 bond. 

Chu L, Qing F-L (2010) Copper-mediated oxidative trifluoromethylation of boronic adds. Org Lett 12 5060-5063... 

Oxidative trifluoromethylation with bis(trifluoroacetyl)peroxide provided a similar result, while the reaction with bis(heptafluorobutyryl)peroxide afforded 3-heptafluoropropylbenzo[fc]thiophene 176 as a major product (54 %) with some 7-substituted isomer 177 [50],... 

Chu L, Qing FL (2012) Copper-catalyzed direct C-H oxidative trifluoromethylation of... 

Some articles have described synthesis of 3-trifluoromethylquinoline (271) [161-165]. Catalytic oxidative trifluoromethylation of 3-qunolineboronic acid (270) resulted in 3-trifluoromethylquinoline in 49 % yield [161]. Use Togni s reagent (272) in reaction with boronic acids 270 resulted in increase yield of 271 up to 53 % [162]. 3-Trifluoromethylquinoline was also obtained by reaction of boronic acids 270 with CF3I [163] or with trifluoromethyl sulfonium salts [164] in 87 % yield. Interaction of 3-iodoquinoline (273) with sodium trifluoromethyl formate at presence Cu and AgjO also led to compound 271 [165] (Scheme 80). 

Jiang X, Chu L, Qing FL (2012) Copper-catalyzed oxidative trifluoromethylation of terminal tilkynes and aryl boronic adds using (trifluoromethyl)trimethylsiltme. J Org Chem 77 1251-1257... 

The generally accepted mechanistic alternatives (other than direct reductive elimination) are illustrated in Figure 4.12. In principle, the dimer could lose the acetate group and the corresponding cationic Pd(III) dimer would then lead to ArCl via reductive elimination. Alternatively, the dimer could disproportionate to Pd(IV) and Pd(II). Canty, Ritter, Sanford et al. demonstrated previously for oxidative trifluoromethylation reactions that dinuclear Pd and mononuclear Pd pathways are connected [48]. The Pd(IV) complex could then either directly eliminate ArCl or dissociate the acetate ion and reductively eliminate ArCl from the cation (see Figure 4.12). Using computational means, it is not trivial to answer whether the pathways via the cationic Pd complexes (Pd(III) dimer or Pd(IV) monomer) are favored over alternative pathways. It is possible to reproduce the... 

Chu L, Qing FL. Copper-mediated aerobic oxidative trifluoromethylation of terminal alkynes with MesSiCFs. J. Am. Chem. Soc. 2010 132 7762-7763. 

Yamakawa described an interesting iron-mediated oxidative trifluoromethylation of aromatic compounds using iodotrifluoromethane and an iron catalyst in the presence of hydrogen peroxide. The reaction was effective for an extensive range of (hetero)aromatic substrates, again with the production of regioisomers in some cases (Scheme 15.96). 

Scheme 15.96 Yamakawa s iron-mediated oxidative trifluoromethylation.

Oxidative trifluoromethylation of terminal alkenes with sp C-CF3 bond formation occurs under mild conditions using (thiophene-2-carbonyloxy)copper (CuTc) as a catalyst, DIAB as the oxidant, and nucleophilic CFgSiMeg as the source of... 

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