Trifluoromethylations aryl halides

Recently reported by Cottet and Schlosser regioselective synthesis of tri-fluoromethyl pyridines and -quinolines" " " is based on the trifluoromethylation of iodoheteroarynes using CF3Si(CH3)3/KF/CuI system originally applied by Urata and Fuchikami for trifiuromethylation of aryl halides." Trifluoromethyl copper in this... 

Ullman type coupling occurs between aryl halides and trifluoromethyl copper species generated by the action of copper iodide on sodium tnfluoroacetate [168, 169] or on methyl fluorosulfonyldifluoroacetate [170] (equation 145) Similarly the pentafluoroethyl group can be introduced from potassium pentafluoropropion-ate [171] (equation 146)... 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Coupling of aryl iodides has also been effected with perfluoroalkylcoppers and perfluo-rovinylcopper reagents51,13. The former reaction may also be accomplished by employing the perfluoroalkylsilane, the aryl iodide and stoichiometric amounts of KF2. Trifluoromethylation may also be accomplished, in more modest yields, by decarboxylation of sodium trifluoroacetate in.the presence of Cul and an aryl iodide71. Stannylation has been accomplished of aryl halides by the use of h.o. stannylcyanocuprates (equation 50)72. 

Corrosion inhibitors, [1.2,4]triazino[4,3-ojbenzimidazoles, 59, 155 Coulson-Rushbrook theorem, 55, 273 Coumarins, see l-Benzopyran-2-ones Coupling reactions, trifluoromethyl iodide with aryl halides, 60, 12 Covalent hydration in 6-nitro-l 1,2,4]triazolo[ 1,5-a)-pyrimidines, 57, 107 of coordinated ligands, 58, 138 Creutz-Taube ion, 58, 124 Criss-cross cycloadditions, of... 

The cross-coupling reaction of alkenyl(fluoro)silanes with aryl halides sometimes produces, in addition to the desired ipso-cowpled products, small amounts of cmc-coupled products [14]. The czne-coupling is often striking in the reaction with organotin compounds. The isomer ratio of products produced by the reaction of l-fluoro(dimethyl)silyl-l-phenylethene with aryl iodides is found to depend on the electronic nature of a substituent on aryl iodides (Eq. 11) an electron-withdrawing group like trifluoromethyl and acetyl favors the formation of the ipso-coupled product. To explain the substituent effect, the mechanism depicted in Scheme 3 is proposed for the transmetalation of alkenylsilanes with palladium(ll) complexes. It is considered that an electron-donating substituent on Ar enhances... 

Table 4. Aryl Trifluoromethyl Sulfides 3 from Copper Trifluoromethanethiolate and Aryl Halides "...

Organobismuth(III) halides may be prepared by elimination of aryl halide from triarylbismuth(V) dichlorides or dibromides upon heating (equation 4). Presumably, a bis-muth(V) compound is the intermediate when triarylbismuth compounds are treated with iodine or when trialkylbis-muth complexes are treated with chlorine, bromine, or iodine, but the intermediates have not been isolated and organobismuth halides are obtained directly (equation 5). The tris(trifluoromethyl)bismuth behaves like the trialkyl compounds without the observation of a bismuth(V) intermediate. ... 

Some examples of electrosyntheses based on the reduction of monohalobenzenes are now cited. Reduction of iodobenzene and bromobenzene at mercury in carbon dioxide-saturated DMF containing TEAP affords benzoic acid in up to 40% yield [178]. Bromobenzene, 3-methoxybromobenzene, 4-bromofluorobenzene, 4-(trifluoromethyl)-chlorobenzene, and 1,2,4-trichlorobenzene can be converted into aldehydes at a cadmium-coated stainless-steel cathode in DMF containing TBABr [179]. In the presence of trimethylchlorosilane, silylation products arise from the reduction of various aryl halides at platinum in DMF containing TEAOTs [100]. Reduction of p-iodoanisole at... 

It should be noted here, however, that trifluoromethyl Cd compounds are becoming increasingly widely used in organic chemistry, particularly for the trifluoromethylation of organic (aryl) halides (90). One simple illustration of the versatility of the Cd reagfent in carbon chemistry is that in CH2C12, Cd(CF3)2DME fluorinates PhC(0)Cl in 86% yield, and the liber-... 

Scheme 2.121 Cross-coupling of perfluoroalkyl copper(l) and aryl halides or perfluoroiodo olefins [52-54], The CF3CU used for the upper two reactions was generated by metathesis of trifluoromethyl cadmium and copper(l) salts.

Trifluoromethyl aryl sulfides. The preparation of these substances from aryl halides requires a Cu(I)-catalyzed reaction with sulfur and methyl fluorosulfonyldi-fluoroacetate in HMPA or A(-methylpyrrolidinone. 

This reaction was initially reported by Finkelstein in 1910. It is a preparation of alkyl iodide from alkyl bromide or chloride with potassium or sodium iodide in acetone. Therefore, this reaction is generally known as the Finkelstein reaction. Occasionally, it is also referred to as the Finkelstein halide exchange, Finkelstein displacement, or Conant-Finkelstein reaction. Mechanistically, this reaction is a simple nucleophilic substitution (often via Sn2), as iodide is a stronger nucleophile than bromide or chloride. The yield of this reaction is very high and can be quantitative if occurs in DMF. It was found that the trifluoromethyl group retards the displacement of bromide when it presents as an a- or /3-substituent but accelerates the reaction as a substituent in an allylic chloride. Under normal conditions, this type of halide displacement does not occur for aryl halides. For dihalides, unsaturated or cyclic compounds may form via carbocation intermediates, which form transient covalent iodides or are reduced directly by iodide to free radicals. However, the aromatic halide exchange reacts smoothly when 10% Cul is present in the reaction... 

Electroreduction of aryl halides generates aryl anion, which also acts as EGB. For example, the electroreduction of iodobenzene (Ph-I) gives phenyl anion, which deprotonates fluoroform. The trifluoromethyl anion derived from the fluoroform reacts with aldehydes to give the trifluoromethylated alcohols as coupling products (Eqs. 18 and 19) [13]. 

Traditionally, aryl bromides/iodides/triflates are employed for coupling with boronates. For example, a-trifluoromethyl vinylboronic acids 129 were utilized for coupling with wide variety of aryl halide substrates such as phenyl, naphthyl, and pyrazyl halides under standard conditions to provide trifluoromethyl-a-arylalkenes 130 (Scheme 28.35). Similarly, 5-vinylboronates 131 were also coupled with aryl halides to provide arylpiperidines 132 (Scheme 28.36). ... 

Jiang, B. Wang, Q-F. Yang, C-G. Xu, M. 2001. a-(Trifluoromethyl)ethenyl boronic acid as a useful trifluoromethyl containing building block. Preparation and palladium-catalysed coupling with aryl halides. Tetrahedron Lett. 42 4083-4085. 

Halogenated imidazoles were also suitable substrates for [Pd(phen)2](PF6)2-catalyzed direct arylation with aryl halides. Thus, dibromoimidazole 8 reacted selectively at the C-2 position with 3-iodopyridine in 74% yield (eq 9). The reaction also tolerated aryl substituents, such as nitro, cyano, ester, methoxy, or trifluoromethyl. Aryl bromides reacted in lower yields. 

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