2,2,2-trifluoroacetophenone

Smith and Calvert54 have provided evidence that at high temperatures, the photodecomposition of trifluoroacetone proceeds by a chain mechanism in which an alkyl radical is added to the ketone, the adduct then decomposing to form an ethane and a further radical. No satisfactory reaction scheme was advanced and an ingenious attempt to investigate the process by photolyzing mixtures of trifluoroacetone and 1,1,1-trifluoroacetophenone provided equivocal results. 

Finally, an efficient method130 for the synthesis of Mosher s acid has been reported this involves the addition of TMS trichloroacetate to 1,1,1-trifluoroacetophenone followed by hydrolysis. 

Reductive dunenzation to form fluorinated benzopinacols proceeds m the partly fluormated case either with zinc or by photolysis but is not observed with perfluorobenzophenone [651 (equation 53). Trifluoroacetophenone is reduced electrochemically in dimethylformamide to a stable radical anion, which, m the presence ot lithium ion, rapidly dunerizes to pinacol in higher yield than that available by photoreduction [66] (equation 54)... 

The McMurry reagent reductively couples trifluoroacetophenones to the eorresponding stilbenes [67] (equation 55), and cross-coupling of ketones is also reported [68] (equation 56). 

Ketones and alcohols are frequently used as alkylating agents Ketones often condense with two molecules of an aromatic compound through an alcohol intermediate [79, 20, 21] T,r,I -Trifluoroacetophenone and aniline afford 1,1 bis(4-ammophenyl) 1 phenyl 2,2,2-trifluoroethane [27] (equation 14)... 

Dihalo-5-fluoroben/oic acids, obtained by oxidation of the corresponding acetophenones, have received considerable attention as intermediates for antibac-tenal fluoroquinolones [3reacts with acetyl chloride to give 2,4,5-trifluoroacetophenone [29] (equation 19) 1,3,5-Tn-fluorobenzene and 1,2-difluorobenzene yield 2,4,6-trifluoroacetophenone and 3,4-difluoroacetophenone, respectively [30] (equations 20 and 21). 

What this implies is that given one equilibrium constant for addition of a nucleophile of known 7 to a carbonyl compound, one could estimate the equilibrium constant for addition of another nucleophile to the same carbonyl compound. This requires knowing the slope of the plot of log K versus y this slope is not very sensitive to the nature of the carbonyl compound, but it is at least known that A H2o/ MeOH depends on the electron-withdrawing power of the groups bonded to the carbonyl, and thus more information is needed to estimate an equilibrium constant for strongly electron-withdrawing substituents. From Ritchie s studies of nucleophile addition to trifluoroacetophenone," we can derive a slope for log K versus 7 of 0.42, distinctly less than the value of 1 for formaldehyde or simple benzaldehydes. 

Tributyltin hydride reduction of carbonyl compounds. The reduction of carbonyl compounds with metal hydrides can also proceed via an electron-transfer activation in analogy to the metal hydride insertion into TCNE.188 Such a notion is further supported by the following observations (a) the reaction rates are enhanced by light as well as heat 189 (b) the rate of the reduction depends strongly on the reduction potentials of ketones. For example, trifluoroacetophenone ( re<1 = —1.38 V versus SCE) is quantitatively reduced by Bu3SnH in propionitrile within 5 min, whereas the reduction of cyclohexanone (Erea — 2.4 V versus SCE) to cyclohexanol (under identical... 

Ramirez, F., Gulati, A.S., and Smith, C.P, Reactions of five-membered cyclic triaminophosphines with hexafluoroacetone, trifluoroacetophenone, and fluor-enone. Attack by phosphorus on carbonyl oxygen and isolation of crystalline 2,2,2-triamino-l,3,2-dioxaphospholanes, /. Am. Chem. Soc., 89, 6283, 1967. 

Sodium chlorodifluoroacetate, reaction with triphenylphosphine and a,a,a-trifluoroacetophenone, 48, 116... 

Although similar efforts have been devoted to related polymer systems (Overberger and Cho, 1968 Overberger and Dixon, 1977 Okamoto, 1978), large enantioselectivity has not been observed. Goldberg et al. (1978) conducted borohydride reduction of phenyl ketones in micelles of the chiral surfactant [44]. The result was disappointing, since the maximal enantioselectivity was only 1.66% for phenyl propyl ketone. A much better optical yield was reported when this reaction was carried out under phase-transfer conditions (Masse and Parayre, 1976). The cholic acid micelle and bovine serum albumin exhibited the relatively high enantioselectivity in the reduction of trifluoroacetophenone (Baba ef al., 1978). 

Triethyl phosphonoacetate, reaction of sodium derivative with cyclohexanone to yield ethyl cyclo-hexylideneacetate, 45, 4S Trifluoroacetic anhydride, 45, 98 a,a,a-Trifluoroacetophenone, reaction with triphenylphosphine and sodium chlorodifluoracetate, 48,116 m-Trifluoromethylaniline, methylation of with trimethylphosphate, 49, 111... 

Rate and equilibrium constants have been determined for the aldol condensation of a, a ,a -trifluoroacetophenone (34) and acetone, and the subsequent dehydration of the ketol (35) to the cis- and fraw -isomeric enones (36a) and (36b)." Hydration of the acetophenone, and the hydrate acting as an acid, were allowed for. Both steps of the aldol reaction had previously been subjected to Marcus analyses," and a prediction that the rate constant for the aldol addition step would be 10" times faster than that for acetophenone itself is borne out. The isomeric enones are found to equilibrate in base more rapidly than they hydrate back to the ketol, consistent with interconversion via the enolate of the ketol (37), which loses hydroxide faster than it can protonate at carbon. 

For hydration of an o -aminotetrahydropyranone, and the hydrate and hydrate anion of a,a,a-trifluoroacetophenone, see under Acetals and Aldols above, respectively. 

The authors presented one example of 2,2,2-trifluoroacetophenone as a coupling partner with 345 (Eq. 35), suggesting that the reaction proceeds through a pentava-lent silicon complex similar to that in Scheme 46. 

Much research has been done on the synthesis of perhalogenated P-sultones. The sulfonation of acyclic fluorovinyl ethers leads to a product that is stable up to slightly above room temperature. Thermolysis decomposes the ring structure under SO2 evolution and formation of acid fluorides and perfluorocyclopropane (Eq. 78). )S-Sultones have been synthesized by addition of sulfonyl chlorides to perhalogenated ketones in the presence of triethylamine. The formation of the l-oxa-2-thiacyclobutane 2,2-dioxides appears to require an activated but sterically unhindered carbonyl group because acetone, chloroacetone, trifluoroacetophenone, and p-nitroaceto-phenone did not yield the desired products. ... 

On heating, 4-(isopropoxy)-2-phenyl-2-(trifluoromethyl)-5(2/i/)-oxazolone 65 underwent decarboxylation to the alkoxy-substituted nitrile ylide 66 that was trapped in a 1,3-dipolar cycloaddition by trifluoroacetophenone to generate 68." Other dipolarophiles reacted similarly. In the absence of a dipolarophile, cyclization of 66 yielded the isoindole 67 (Scheme 7.16 Table 7.11, Fig. 7.12). 

Of the numerous nicotinamide model studies done since about 1970, the one that had perhaps the greatest impact on mechanistic thinking revealed a discrepancy between the kinetic deuterium isotope effect and the H/D ratio in the alcohol product formed upon reduction of trifluoroacetophenone by 4-protio- and 4-deuterio-A-alkyl-l,4-dihy-dronicotinamides (Scheme 2) (71JA6694). For example, while the reduction of... 

Hydrogenation of 2,2,2-trifluoroacetophenones catalyzed by fra s-RuCl2[(S)-XylBINAP][(S)-DAIPEN] with (CH3)3COK afforded the S trifluoro alcohols in 94-96% ee (Scheme 6) [6]. The presence of an electron-donating or electron-withdrawing group at the 4 position had little effect on the enantioselectivity. The sense of the enantioselection was the same as that observed in the reaction of simple acetophenone. 

Hydrogenation of 2,2,2-trifluoroacetophenone and its derivatives with a mixture of trans-RuCl2[(S)-xylbinap][(S)-daipen] and (CH3)3COK in 2-propanol gives the S alcohols quantitatively with a high optical purity (Scheme 1,64) [258]. Unlike with many chiral borane reagents [264], the sense of enantioface discrimination is the same as in hydrogenation of acetophenone. The electronic effects of 4 -substituents on the enantioselectivity are small. These chiral fluorinated alcohols are useful as components of new functionalized materials [265]. 

Cinchonidine-modified Pt/Al203 catalyzes hydrogenation of 2,2,2-trifluoroacetophenone to give the R alcohol with 56% ee [266]. 

---