Sodium iodide, trifluoromethylations

Reaction of Sodium Iodide. Trifluoromethyl iodide was obtained from the reaction between the title compound and the sodium iodide under reflux in quantitative yield (eq 16). ... 

Among the many methods of generating difluorocarbene, the treatment of bromodifluoromethylphosphonium bromides with potassium or cesium fluoride is particularly useful at room temperature or below [II, 12 13] The sodium iodide promoted decomposition of phenyl(trifluoromethyl)mercury is very effective at moderate temperatures [S, 14] Hexafluoropropylene oxide [/5] and chlorodifluo-roacetate salts [7] are excellent higher temperature sources of difluorocarbene... 

Treatment of 5-salt 17 with sodium iodide gave trifluoromethyl iodide (Eq. 30). Irradiation with a high-pressure Hg lamp readily produced trifluoromethyl iodide in the same yield. 

Trialkyl(trifluoromethyl)tin reacted with sodium iodide at 80 °C to form difluorocarbene in situ, which gave the difluorocyclopropane derivatives in the presence of olefins [108-110] (Scheme 39). 

Tnmethyl(trifluoromethyl)tin can also be prepared via in situ formation and capture of trifluoromethide by trimethyltin chlonde [13,14] (equation 9) This tin analogue has been used as a precursor for difluorocarbene either by thermal decomposition or by reaction with sodium iodide in 1,2-dimethoxyethane This carbene generation procedure has been used to study difluorocarbene selectivity with steroidal olefins [ii] (equation 10). 

Hexafluorocyclopropane (7) is also a source of difluorocarbene under conditions similar to those used with hexafluoropropylene oxide. It is also possible to generate difluorocarbene from the explosive difluoro-3//-diazirine (8) thermally or by photolysis with UV light. Difluorocarbene can be generated from trimethyl(trifluoromethyl)tin (McjSnCFj) by heating at a temperature of 150 or at a lower temperature of 80 C in the presence of sodium iodide. ° ... 

Difluorocarbene can be generated from trimethyl(trifluoromethyl)tin (Me3SnCF3) by heating at a temperature of 150 C2n or at a lower temperature of 80 C in the presence of sodium iodide.2021... 

Seyferth concludes that phenyl(trifluoromethyl)mercury is an excellent precursor for difluorocarbene. In the general procedure, 1 molar eq. of C6H5HgCF3, 2.5-3.0 molar eq. of well-dried sodium iodide, and 3.0 molar eq. of the dried olefin are used (N2). Benzene is distilled into the reaction flask directly from sodium benzophenone ketyl. The reaction mixture is stirred and heated at reflux under N2 for 12-18 hr. Filtration removes phenylmercuric iodide and Nal and NaF the gew-difluorocyclo-propanes are isolated by distillation or by gas chromatography, usually in good yield. 

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). 

The reaction of norbornadiene with fluorochlorocarbene (generated from sodium dichloro-fluoroacetate in diglyme at 140 °C) and difluorocarbene [from phenyl(trifluoromethyl)mercury and sodium iodide at 80 °C] gave, in addition to 1,2-addition products, 1,5-addition products 1 and 2 resulting from a linear homocheletropic reaction. ... 

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>. 

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... 

Fuller details have appeared regarding the use of anhydrous sodium iodide as the most appropriate agent for the liberation of difluorocarbene from phenyl(trifluoromethyl)mercury. ° This is probably the most convenient route to difluorocarbene and very satisfactory yields have been obtained for cycloaddition to a range of olefins. Benzylmercury iodide gives benzyl(iodo-methyl)mercury with diazomethane. This reagent has been reported to transfer methylene to olefins much faster than previously used organo-mercurials. An alternative reagent, which avoids the use of diazomethane, is... 

Conversion of C—Cl bonds into C—F requires more strenuous conditions, so conversion of PhHg CClg into PhHg-CFa entails heating the reaction mixture at 90 °C. Phenyl(trifluoromethyl)mercury resists thermal decomposition into phenylmercuric fluoride and difluorocarbene, but serves as an excellent source of the carbene when treated with sodium iodide in benzene or an excess of trapping agent ... 

Another way to prepare fluorinated sulfides is the photochemical alkylation of sulfides or disulfides by perfluoroalkyl iodides [69, 70, 71] (equations 62-64). Reaction of trifluoromethyl bromide with alkyl or aryl disulfides in the presence of a sulfur dioxide radical anion precursor, such as sodium hydroxymethanesulfi-nate, affords trifluoromethyl sulfides [72] (equation 65). 

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)... 

Cheaper sources of tnfluoromelhyl groups have been the goal of several groups The use of sodium tnfluoroacetate and copper (1) iodide in dipolar aprotic solvents gave regiospecific trifluoromethylation of aromatic halides [202] (equation 136)... 

Biphenylyl ditelluride 33 was treated with sodium borohydride/methanol in the presence of trifluoromethyl iodide or bromide in tetrahydrofuran (THF) to give trifluoromethyl biphenylyl telluride 34 (Eq. 7). 

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). 

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. 

The nucleophilic nature of this reagent is confirmed by the p-value + 0.46 obtained from the crude Hammett plot of the reaction of p-substituted iodoaromatics with the trifluoromethylating system sodium trifluoroacet-ate / copper iodide [88JCS(P1)921]. Consequently, electron-withdrawing substituents enhance reactivity, whereas electron-donating substituents (—OH, —NH2) inhibit the reaction. 

---