Trifluoromethyl fluoroformate

A number of imines have also been fluorinated. Typical reactions are the fluorination of N-(trifluoromethyl)difluoromethanimine (21) and 7V,7V,N -tris(trifluoromethyl)fluoroform-imidamide (22).103... 

Trifluoromethyl fluoroformate decomposes on strong heating in a quartz vessel to produce carbonyl difluoride, carbon dioxide and tetrafluoromethane [94]. The reaction may proceed by two separate pathways, as indicated below ... 

Unlike COClj (see Section 9.1.3.1), carbonyl difluoride can be dimerized to trifluoromethyl fluoroformate, FC(0)0CF3, and trimerized to bis(trifluoromethyl)carbonate, 0=C(OCF3)j, by means of a base-catalysed reaction conducted at -50 to -110 C in the presence of activated charcoal [45b]. The dimer is formed in 45-60% conversion, whereas the trimer is only formed in about 1% yield [45b]. 

An ab initio calculation of vibrational wavenumbers was reported for fluoro-fluoroxydioxirane, (7), and other CF2O3 isomers. Matrix IR spectra were obtained for syn and anti rotamers of trifluoromethyl fluoroformate, CF30C(0)F, and syn,syn and syn,anti rotamers of perfluorodimethyl carbonate, (CF30)2C0. The assignments were helped by ab initio calculations, e.g. vC=0 1893, 1916 cm respectively for the former pair, and 1858, 1870 cm for the latter pair. ... 

Depending on the ring substituent, trifluoromethoxyben2enes can be made by the sequential chlorination—fluorination of anisole(s) (351—354). A one-step process with commercial potential is the BF (or SbF2)-cataly2ed reaction of phenol with carbon tetrachloride/hydrogen fluoride (355). Aryl trifluoromethyl ethers, which may not be accessible by the above routes,may be made by fluorination of aryl fluoroformates or aryl chlorothioformates with sulfur tetrafluoride (348) or molybdenum hexafluoride (356). 

Tris(trifluoromethyl)germanium iodide is unstable in 3M base, however, and yields fluoroform quantitatively. All of the compounds showed good thermal stability (15). 

Fluoroform (CHF3) efficiently trifluoromethylates aromatic aldehydes to the corresponding alcohols when deprotonated by potassium DMSylate in DMF. This is surprising, as species such as KCF3 have carbenoid character, and tend to be unstable. However, the reaction fails for solvents such as THF, and appears to depend on a highly specific role for DMF. It is proposed that CFs is trapped in situ by the solvent to form the gem-amino alcoholate (70), which acts as a stable, masked form of the anion, which then attacks the aldehyde, regenerating DMF. 

It has been shown that the tetrahedral oxyanion formed on addition of the conjugate base of fluoroform to solvent DMF acts as a masked form of FsC with which to effect trifluoromethylation of aldehydes. " ... 

Trifluoromethyl phenylsulfone is accessible from fluoroform and diphenyldisul-fide, and it has been proposed as a donor of CF3. However, the reaction must be performed in basic medium (f-BuOK) and is then limited to nonenolizable aldehydes and ketones. But it can also be used as a precursor of the Ruppert reagent. This latter... 

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

In the same way as a,a,(Z-trihalogenated carbonyl compounds are cleaved hydrolytically to produce haloforms, the fluorinated analogs also react by release of trifluoromethane. The fluoroform reaction has been described with aldehydes such as trifluoroacetaldehyde, alkyl trifluoromethyl ketones, and aryl trifluoromethyl ketones, e.g. l-(2,4-dihydroxyphcnyl)-... 

Reaction with phenols and alcohols. Carbonyl fluoride reacts with a phenol or alcohol (autoclave, 100-200°) to form the fluoroformate (10). In a second step the fluoroformate on reaction with sulfur tetrafluoride (150-200°) affords the aryl(alkyl) trifluoromethyl ether. ... 

Probably the most efficient way to generate CFf from the view point of atom economy is deprotonation of inexpensive CHFj with a strong base [59]. Unfortunately, this route poses two problems. First, the low boiling point of fluoroform (—82.2 °C) creates - at least on the laboratory scale - the practical problem of handling a gas. The second problem is the need to trap and stabilize the trifluoromethyl anion immediately after its generation, to suppress fragmentation. This second complication, in particular, impeded the apparently straightforward preparative... 

Nearly all trifluoromethyl arsenicals are hydrolyzed quantitatively by base affording fluoroform. This reaction has been of value in the analysis of these compounds. Exceptions are the compounds (CF3)2AsH, CF3ASH2, and (CF3)2As— As(CF3)2 which give fluoride and carbonate as well as fluoroform. Hydrolysis of the diarsine is believed to involve hydrolytic fission of the As— As bond (30). 

Fluoroform is also produced from trifluoromethyl arsenicals on ammono-lysis and aminolysis, the results of ammonolysis studies apparently paralleling those of hydrolysis (68, 256, 257). Sodium methoxide in methanol also liberates fluoroform, although ethanol and methanol react only slowly, if at all, with tris(trifluoromethyl)arsine (256). 

Silicon.—-The simple volatile trifluoromethyl derivative CFa-SiFa has definitely been synthesized at last, and fully characterized spectroscopically it was obtained by sub-zero fluorination of the iodosilane CFa-SiFal with antimony trifluoride (AsFa or AgF may be used at 25 C) and shown partly to release its perfluoroalkyl group as fluoroform on contact with moisture and to give tetrafiuoroethylene (mainly) plus perfluorocyclopropane when pyrolysed. The latter decomposition occurs slowly at 78 °C (half-life at 100 °C and 50 Torr w 7 min) and presumably involves difluorocarbene ... 

Bromothiazole 70 undergoes trifluoromethylation with fluoroform-derived CUCF3 under nuld conditions to furnish the desired trifluorometh-ylated product 71 in moderate yield (13JOC11126). These trifluoromethyl-substituted thiazoles could serve as versatile building blocks in medicinal chemistry research. 

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]. 

Sodium trifluoroacetate, in the presence of copper(l) iodide, was also used as trifluoromethyl source to replace halogen by trifluoromelhyl group in the thiophene system. Sodium trifluoroacetate was decarboxylated, forming fluoroform, when heated alone in aqueous N-methylpyrrolidin-2-one. The addition of copper(l) iodide increased the rate of decarboxylation dramatically. The mechanism of this process was explored and an intermediate [CFsCul] was proposed. Introduction of higher perfluoroalkyl groups from their corresponding sodium perfluoroalkane carboxyl-ates was also shown to be possible [58],... 

The reaction of direct cupration of fluoroform provides a source for the introduction of the trifluoromethyl group into organic molecules, including thiophene [63]. 

Grushin also very recently demonstrated that fluoroform can undergo C-H activation in the presence of [(dppp)Pd(Ph)(OH)] and n-BusP as a Lewis basic promoter (Scheme 17.6B). Although this has not yet led to eatalytie trifluoromethylation reactions using fluoroform, it is a significant advance towards this important goal for sustainable trifluoromethylation ehemistry. 

Scheme 17.6 (A) KHMDS-mediated trifluoromethylation with fluoroform. (B) Pd-...

Table 19 Trifluoromethylation of diazine bromides with fluoroform-derived CuCFj...

Lishchynskyi A, Novikov MA, Martin E, Escudero-Adan EC, Novak P, Grushin VV (2013) Trifluoromethylation of aryl and heteroaryl halides with fluoroform-derived CUCF3 scope, limitations, and mechanistic features. J Org Chem 78 11126-11146... 

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