Trifluoro methyl derivatives

Very soon after the reactivity of Cd(CF3)2DME toward main group halides (31) and group 10 dihalides (32) had been established, we set out to determine if the cadmium reagent was effective in trifluoromethylating representative organometallic compounds. One of the first substrates chosen was CpCo(CO)I2, which was selected because the mono-trifluoro-methyl derivative was known, but the disubstituted compound was not. The results of this reaction are (60)... 

This appears to be the first authentic evidence for the generation of perfluoro alkyl derivatives of cadmium unsuccessful attempts to prepare trifluoro-methyl derivatives directly from cadmium and trifluoroiodomethane were made in the pioneering days of fluorocarbon-element chemistry. ... 

These kinetic observations of Calderazzo and Cotton concerning the carbonylation-decarbonylation reaction are consistent with observations of other workers. For example, Coffield et al. (102) reported that the trifluoro-methyl derivative CF3Mn(CO)5 could not be carbonylated to the trifluoro-acetyl derivative CF3COMn(CO)s. In addition, the material, m.p. 58° C, obtained from Na[Mn(CO)5] and ethyl iodide and originally thought to be ethylmanganese pentacarbonyl (93), was later demonstrated to be the pro-pionyl derivative C2H5COMn(CO)s (151). The carbonylation reaction is... 

The quaternary ammonium salt 48 derived from (+)-ephedrine was utilized for the enantioselective addition of diethyl zinc to aldehydes.1421 The chiral ammonium fluorides 7 (R=4-CF3 or 2,4-(CF3)2, X=F) were also useful for the enantioselective trifluoro-methylation of aldehydes and ketones with moderate enantioselectivity,1431 shown in Scheme 17... 

Another interesting example of resolution through formation of diastereo-mers is the isolation of four stereoisomers of 3-amino-2-methyl-3-trifluoro-methyl butanoic acid [55]. In this process, the chemical-enzymatic method by the combination of chemical and enzymatic reaction is a very convenient. At first, -phenylacetyl derivatives 61a and 61b were prepared in excellent isolated yields via the Schotten-Baumann procedure. After these materials were hydrolysed with penicillin acylase (EC 3.5.1.11) from Escherichia coli until attainment of 50% conversion, enzymatically unconverted -phenylacetyl derivatives 62 a and 62 b (organic layer) and amino acids 63 b and 63 d (aqueous layer) were separated. Acidic hydrolysis of unconverted materials produced other stereoisomers 63 a and 63 c in high optical pure form. 

A -(2,2-Diethoxyethyl)anilines are potential precursors of 2,3-unsubstituted indoles. A fair yield of 1-methylindole was obtained by cyclization of A -methyl-A-(2,2-diethoxyethyl)aniline with BF3, but the procedure failed for indole itself[2]. Nordlander and co-workers alkylated anilines with bromo-acetaldehyde diethyl acetal and then converted the products to A-trifluoro-acetyl derivatives[3]. These could be cyclizcd to l-(trifluoroacetyl)indoles in a mixture of trifluoroacetic acid and trifluoroacetic anhydride. Sundberg and... 

Phenylenediamine and 2-aminophenol initially give N-arylimidoyl fluoride. Elimination of hydrogen fluoride from the product and further intramolecular nucleophilic cyclization lead to perfluoroalkyl derivatives of benzimidazole and benzoxazole, respectively. In the case of 2-aminothio-phenol, the reaction occurs at the sulfur atom and forms a carbanion. If RF is fluorine, then the carbanion is destabilized by the interaction of the lone electron pairs of fluorine with the center, and the stabilization reactions occur with participation of the proton. If, however, RF is the trifluoro-methyl group, the negative charge is stabilized by it. The fluoride ion is eliminated with further intramolecular nucleophilic cyclization. 

It was shown (78JFC(12)193) that the product of the reaction of perfhioro-2-methylpent-2-ene with potassium ethyldithiocarbamate in dimethylformamide is 5,5-bis(trifhioromethyl)-5-(tetrafluoroethylidene)-2-fhioro-2-ethoxy-l,3-dithiolane. Analogously, the reaction of 1,1,1-trifluoro-methyl-2-bromoprop-2-ene with thiourea and its N-substituted derivatives yields 5-trifhioromethyl-2-thione-thiazolidines 57 (92JFC(58)365). 

Thus reactions of perfluoro-2-methylpent-2-ene and perfluoro-5-azanon-4-ene with urea in the presence of triethylamine in dipolar aprotic solvents (MeCN, DMF) form 6-fluoro-4-pentafluoroethyl-5-trifluoro-methyl-l//-pyrimidin-2-one 93 and an s-triazine derivative, respectively (00JFC(103)105, 80/82JAP(K)85377). 

Pyridine and its derivatives react with 1,3-pentadienes forming cyclic products. This type of cyclization was observed by the authors of 95JFC(72)49. They showed that in the reaction of (Z)-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene 117 with pyridine the products are [ S,9aR]- and [lS,9tfS]-3-fluoro-9<2-hydro-l,2-bis(trifluoro-methyl)-l-phenyl-4//-quinolizin-4-ones 118 and 119 with 54 and 21% yields, respectively. The structure of the compounds was confirmed by X-ray analysis. Similarly, the reaction of (Z)-l,l,2,5,5,5-hexafluoro-4-iodo-3-trifhioromethyl-l,3-pentadiene 120 with 4-substituted pyridines gives the derivative of 4//-quinolizin-4-one 121 with quinoline, the product is derivative 122. 

Hexafluoroacetoneazine (47, 276a) and hexafluoroacetonebis(trifluoro-methyl)hydrazone (55) have been synthesized similarly. Dehydration has been achieved with phosphorus oxychloride (47) or oleum (276a) for the ketazine and oleum for the hydrazone. S-Arylsulfinamides also react only via cleavage of an N—H bond (46). Derivatives of 96a are available from (phenylimino)triphenylphosphorane via aminals 97 (293,295). 

C —Br and C l bond polarization in perfluoroalkyl- and polyfluoroaryl-containing derivatives may be promoted by reagents other than phosphorus derivatives. When tetrakis-(dimethylamino)cthene is treated with bromotrifluoromethane or trifluoroiodomethane in the presence of chlorotrimethylsilane under similar conditions" only traces of trimethyl(trifluoro-methyl)silane are obtained, but dimethylbis(trifluoromethyl)silanecan be prepared from trifluoroiodomethane and dichlorodimethylsilane in 63 "/u yield. " ... 

In the last time we also investigated the reductive coupling of the prepared a,co-bis[(trifluoro-methyl)sulfonyloxy]-substituted organosilicon derivatives with alkali metals. We found, that these coupling reactions did not occur completely. The isolated polymers always contained siloxy units after hydrolysis of the reaction mixture. Therefore we looked for a better reducing agent. 

Ethyl diazoacetate is a frequently encountered carbene donor for the methylenation of imines. For example, the imine derived from -chlorobenzaldehyde 589 is converted to the tfr-aziridinyl ester 590 upon treatment with ethyl diazoacetate in the presence of lithium perchlorate <2003TL5275>. These conditions have also been applied to a reaction medium of the ionic liquid l- -butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) with excellent results <2003TL2409>. An interesting enantioselective twist to this protocol has been reported, in which a diazoacetate derived from (iJ)-pantolactone 591 is used. This system was applied to the aziridination of trifluoro-methyl-substituted aldimines 593, which were prepared in situ from the corresponding aminals 592 under the catalysis of boron trifluoride etherate to give aziridines 594 (Scheme 143) <2003TL4011>. 

Ultraviolet and H-NMR measurements supported these assignments. The UV absorption of 6- and 9-methyl-8-azapurine cations (which do not undergo detectable hydration) give the same values in anhydrous trifluoro-acetic acid as they do in dilute hydrochloric acid. By contrast, the cations of 8-azapurine and its 1-, 2-, 7-, and 8-methyl derivatives have different UV spectra in these two solvents (a large shift of to shorter wavelengths occurs in the presence of water ). This shift indicated conversion of a double bond to a single bond by hydration. Similarly the H-NMR spectrum of the anhydrous cation showed peaks at S 9.60 and 10.69 (for H-6 and H-2, respectively), whereas corresponding peaks for the hydrated cation (in DjO, DCl) were at d 6.81 and 8.54, respectively. ... 

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