Trifluoromethylation of aryl iodide

Addition of HMPA or potassium fluoride to the CF3Cu/DMF solution suppressed the oligomerization and allowed this reagent to be employed for the trifluoromethylation of aryl iodides even at elevated temperature [92-94] (Scheme 32). 

Trifluoromethylation of aryl iodides was carried out by the fluoride ion in duced cross-coupling reaction of aromatic iodides with trifluoromethyltnalkyl-silanes in the presence of copper salts [219] (equation 147) Some pentafluoro- ethyl derivative was also formed This methodology was extended to pentafluoroethyl-and heptafluoropropyltnethylsilanes [219]... 

Trifluoromethylation of aryl iodides or nitroarenes with Cd(Cu) reagents (see 1st edition). 

BURTON Trifluoromethylation Trifluoromethylation of aryl iodides with Cd (Cu) reagents. 

The trifluoromethylation of aryl iodides has been achieved using the reaction with (trifluoromethyl)-trimethoxyborate and a copper(I)/phenanthroline catalyst." A copper chloride/phenanthroline catalyst has also been used together with (TMP2Zn), zinc bis-tetramethylpiperidide, in the reaction of aryl iodides with perfluoroalkyl derivatives to yield arylperfluoroalkanes. The mechanism is thought to involve initial formation of bis(perfluoroalkyl)zinc species followed by rate-limiting transmetalation with copper halide and reaction with the aryl iodide to give the coupled product." ... 

Trifluoromethylation of Aryl Iodides. Complex 1 is an efficient trifluoromethylating reagent of iodoarenes. The reaction takes place at 80 °C, employing dimethylformamide (DMF) as the solvent, due to the good solubility of complex 1 in this solvent (eq 1). Remarkably, a large excess of the iodoarene is not necessary. Thus, a variety of aryl iodides (substituents include methyl, methoxy, chloro, fluoro, nitro, nitrile, trifluoromethyl in the para-position, as well as 2-iodopyridine) undergo trifluoromethylation in good yields (60-85%). 

Weng Z, Lee R, Jia W, Yuan Y, Wang W, Feng X, Huang KW. Cooperative effect of silver in copper-catalyzed trifluoromethylation of aryl iodides using MesSiCFs. Organometal-... 

Scheme 15.101 Xiao s Cu-mediated trifluoromethylation of aryl iodides using tri-fluoromethyl sulfonium salts.

Tnfluorometltylation of aryl, alkenyl, and alkyl halides can be accomplished by heating methyl fluorosulfonyldifluoroacetate and the appropriate halide precursor with copper(I) iodide at 60-80 °C in DMF [27 7] (equation 145). Similar trifluoromethylations of aryl, benzyl, and vinyl halides can be carried out with fluorosulfonyldifluoromethyl iodide and copper metal in DMF at 60-80 °C [2 75] (equation 146). 

Trifluoromethylation is the most important perfluoroalkylation reaction. Kobayashi and co-workers reported the trifluoromethylation of aryl, vinyl, alkyl halides with trifluoromethyl iodide in the presence of copper powder in aprotic solvents such as HMPA at 120-150 °C [83,84], and this methodology has been applied to the preparation of fluorinated pyrimidine and purine nucleosides [85,86] (Scheme 27). 

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. 

Also, Vicic and co-workers developed an impressive NHC-Cu-mediated reaction allowing to couple a trifluoromethyl group with aryl iodides. Even though the method was not catalytic in NHC opper reagent, it represents a real breakthrough in Cu-CFs chemistry, a species that had remained elusive until this report and, more generally, in trifluoromethylation reactions. A variety of aryl iodides could be converted to their CF3 analogues in the presence of [(NHC)Cu(CF3)] 6 as shown in Scheme 11.2. 

Morimoto H, Tsubogo T, Litvinas N, Hartwig J (2011) A broadly appUcable copper reagent for trifluoromethylations and perfluoroalkylations of aryl iodides and bromides. 

Aromatic perfluoroaLkylation can be effected by fluorinated aUphatics via different techniques. One category features copper-assisted coupling of aryl hahdes with perfluoroalkyl iodides (eg, CF I) (111,112) or difluoromethane derivatives such as CF2Br2 (Burton s reagent) (113,114), as well as electrochemical trifluoromethylation using CF Br with a sacrificial copper anode (115). Extmsion of spacer groups attached to the fluoroalkyl moiety, eg,... 

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)... 

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. 

Due to the cost of trifluoromethyl iodide, other cheaper sources have been investigated for trifluoromethylation. Sodium trifluoroacetate reacted with aryl iodide in the presence of copper (I) iodide in NMP at 140 -160 °C to afford the corresponding coupling product [87]. No trifluoromethylation was observed without Cul. Under similar reaction conditions, sodium pentafluoropro-pionate worked well to give the pentafluoroethylated compounds [88, 89] (Scheme 28). 

A CF3Cu solution can also be prepared by the reaction of bis (trifluoromethyl) mercury [90] or AT-trifluoromethyl-AT-nitrosotrifluoromethanesulfonamide (TNS-Tf) [91] with activated copper powder in dipolar aprotic solvents. Reaction with aryl iodides gave the corresponding trifluoromethylated aromatics in good yields. (Scheme 29). 

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... 

Perfluorophenyl)copper exhibits high reactivity towards organic substrates. and reacts with fluorinated or nonfluorinated aryl iodides (e.g., formation of 5), fluorinated vinyl iodides, al-kynyl bromides and iodides, allyl halides, alkanoyl halides, and iodomethane to afford the corresponding coupled products in good yields. (Perfluorophenyl)copper readily undergoes addition in a syn fashion to perfluorobut-2-yne to form a perfluorovinylcoppcr reagent 6, which can be quenched by electrophiles (e.g. formation of 7). Recall that (per-fluorophcnyl)coppcr reacts with (trifluoromethyl)copper to form (perfluorophenethyl)copper (Section 2.1.1.3.3.). 

Arylphosphonate esters are conveniently prepared from aryl iodides and potassium dialkyl phosphites on photolysis in ammonia, Eq. (29). Isolated yields of products containing methyl, methoxy, trifluoromethyl or halogen substituents range from 87 to... 

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... 

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