Preparation of Trifluoromethyl Compounds

The conversion of a carboxylic group into CF3 with and the chlorine-fluorine 

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Kubota T, Aoyagi R, Sando H, Kawasumi M, Tanaka T (1987) Preparation of Trifluoromethylated Compounds by Anodic Oxidation of 3-Hydroxy-Trifluoromethyipropionic acid. ChemLett 1435-1438... 

The state of the synthetic art in this area, in 1979, is much more satisfactory. During the past decade, several new synthetic developments have occurred such that we are closer to the point where the limitations upon synthesis of trifluoromethyl compounds are related more to stability problems in isolated cases, and are not nearly so much due to lack of widely applicable synthetic techniques. We find ourselves, for example, in a position in 1979 where the germanium compound, Ge(CF3)4, which in the past decade, was considered by many workers to be of insufficient stability to permit isolation, has been prepared by four independent methods and is known to be stable to over 100°C. Many of these new synthetic techniques have emerged from studies conducted in our laboratory at the University of Texas and previously... 

What reference to Tables I—III does not indicate, however, is any indication of a compound containing more than two trifluoromethyl groups attached to a metal atom, or many examples of early transition metal trifluoromethyl derivatives. The early results of a number of synthetic techniques designed to ultimately result in more general routes to the preparation of trifluoromethylated transition metal compounds are presented below. 

H and F NMR studies of the reaction between (CF3)2Cd and Me2Zn have also demonstrated that ligand exchange occurs to give MeZn(CF3) and (CF3)2Zn. A summary of trifluoromethyl compounds that have been prepared from (CF3)2Cd is provided in Table 4. ... 

Preparation of Polycyclic Compounds.—number of routes to bi- and tri-cyclic heterocycles containing the tetrafluorobenzo-moiety have been described (see pp. 381, 390, 397, 400, and 410, and Schemes 20, 22—26, 29. 34, and 39). Ethyl trifluoroacetoacetate and m-anisidine condmse in the presence of acid to give equal amounts of 5- and 7-methoxy-2-trifluoro-methylquinol-4-ones. 8-(Trifluoromethyl)quino]ine derivatives are reported to have anti-inflammatory and analgesic activity. Reaction of CozfCO) ... 

Non-fluoride initiators have been employed satisfactorily as well, including Lewis bases (amines, amine A-oxides, carbonates and phosphates," LiOAc," " f-BusF ), Lewis acids," A-heterocyclic carbenes, or even without initiator in DMSO as solvent. The addition of TMSCF3 to carbonyl compounds in the presence of a chiral initiator allows the enantioselective preparation of trifluoromethyl alcohols. For this purpose, quaternary ammonium fluorides derived from cinchona alkaloids (1) have been employed, affording moderate (up to 51% ee) " to high enantioselectivities (up to 92% ee). Also, the corresponding bromides were used in combination with an external fluoride source (KF or TMAF, up to 94% ee) or with disodium (R)-binaphtholate (up to 71% ee), or simply a cinchonidine-derived ammoniumphenoxide (up to 87% ee). Moreover, the use of a chiral TASF derivative (2) has also been reported (up to 52% ee). ... 

Free radicals generated under photochemical conditions from thiohydroxamates add readily to the NN double bond of diaziridines and in particular to the 3-bromo or 3-trifluoromethyl-3-phenyldiazirine to produce diaziridinyl radicals (Scheme 25) these intermediates undergo dimerization and fragmentation to yield the corresponding imines, which can be hydrolyzed to the corresponding amines. Barton esters can also be used for the direct preparation of nitroso compounds. From a synthetic standpoint, the yields are moderate and the method is limited to primary and secondary carboxylic acids, which form dimers as an end product. Tertiary nitroso compounds do not dimerize and further react with the radical present under the reaction conditions. 

Cyclic and Polymeric Substances Containing Arsenic—Arsenic Bonds. A number of organoarsenic compounds containing rings of four, five, or six arsenic atoms have been prepared (cycHc polyarsines). The first such four-membered ring compound to be adequately characterized, tetrakis (trifluoromethyl) tetrarsetane [7547-15-17, was obtained by the interaction of a diiodoarsine and mercury (107,108) ... 

A number of unusual aliphatic trifluoromethyl compounds have been obtained from 4-hexafluoroisopropylidene-2-phenyl-5-oxazolone (4) 10 The latter was prepared as shown in Eq. (2). The ease of formation... 

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