Trifluoroacetophenones

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. 

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]. 

Perfluoroalkyl ketones have been reduced in high ee using a simple alkoxide lithium (S)-l-phenylethoxide, for example, reduces 2,2,2-trifluoroacetophenone to its (5>carbinol in 80% ee and 61% yield at 0°C, with acetophenone produced as by- ... 

Although electrophilic reactions involving dications with deactivated arenes may suggest the formation of superelectrophilic intermediates, there are a number of well-known examples of monocationic electrophiles that are capable of reacting with benzene or with deactivated aromatic compounds. For example, 2,2,2-trifluoroacetophenone condenses with benzene in triflic acid (eq 12).13 A similar activation is likely involved in the H2SO4 catalyzed reaction of chloral (or its hydrate) with chlorobenzene giving DDT (eq 13). 

The reactivity of acyl cyanides versus carbonyl oxides could be compared in competition experiments with other 1,3-dipolarophiles. Thus when enol ether 109 was ozonized in the presence of an equimolar amount of benzoyl cyanide and 2,2,2-trifluoroacetophenone in diethyl ether at —70°C, a mixture of two ozonides 110 and 111 was obtained in yields of 32% and 45%, respectively, as shown by Equation (11). 

With trifluoromethyl kclones. cycloaddition requires high pressure " however, with highly reactive siloxybutadienes and 2,2.2-trifluoroacetophenone (5) the reaction occurs readily under mild conditions and provides, after desilylation, a tetrahydropyranone. e.g. formation of 6. ... 

Rosenfeld and Kilsheimer (1974) prepared several 2,2,2-trifluoroacetophenone oxime methylcarbamates substituted on the ring. Among these, o-methoxy-2,2,2-trifluoroacetophenone oxime N-methylcarbamate (54) and o-fluoro-2,2,2-tri-fluoroacetophenone oxime N-methylcarbamate (55) are the most efficient. Their insecticidal action is nearly identical to that of carbaryl (3), white their cholinesterase-inhibiting effect surpasses substantially that of carbaryl. 

The 1,3,2,4,6-dithiatriazines 21 were prepared in moderate yields (17-37%) from 2,2,2-trifluoroacetophenone oximes by treatment with tetrasulfur tetranitride in refluxing toluene. The aminosulfenamides 128 and sulfur were also formed as by-products (see Equation 3) <1996JHC295>. 

Dithiatriazines. (1) Reaction of 2,2,2-trifluoroacetophenone oximes with S4N4 (Section 9.14.8.2.2) - moderate yields, limited range of products, and significant aminosulfenamide by-product (2) reaction of tris(trimethylsi-lyl)amidines and (NSGOs (Scheme 37) only provides derivatives with sulfur diimide bridge. 

When 2,2,2-trifluoroacetophenone was introduced as a coupling partner, the corresponding products could also be obtained in good yield (Scheme 7.51) [72]. 

Water-soluble as well as water-insoluble ketones were hydrogenated by H-transfer from aqueous HCOOH catalyzed by [Ir(Cp )(bipy)H] at 70°C. The highest TOF (525 h ) was observed with 2,2,2-trifluoroacetophenone, whereas aliphatic ketones were found less reactive (TOF 150 h for 2-butanone). The activity of the catalyst depended on the pH, with an optimum at around pH 2. This unusual behavior was rationalized by assuming proton catalysis of hydride transfer from [Ir(Cp )(bipy)H]+ to the substrates (119). 

The similar alkoxide- or hydroxide-induced trifluoromethylation was also found to work with other electrophiles. Diphenyl disulfide can be trifluoromethylated to give trifluoromethyl phenyl sulfide in 87% yield (eq 4). Methyl benzoate can be trifluoromethylated to generate 2,2,2-trifluoroacetophenone in 30% yield at temperatures between —50°C and —20°C. Trifluo-romethylcopper (CF3CU) can be generated in situ with trifluoromethyl sulfone, f-BuOK, and copper iodide (Cul), and it then further reacts with iodobenzene at 80 °C for 20 h to give a,a,a-trifluorotoluene in 26% 3neld. ... 

Using traditional organic cosolvents, the bioreduction of para-bromo-2,2,2-trifluoroacetophenone 83 (Scheme 6.34) was limited to a maximum product concentration of 10 g/L due to substrate-induced deactivation of the R. eryth-ropolis (ADH RE) biocatalyst. However, by employing 10% (v/v) [BMP][NTf2], a water immiscible ionic liquid, more than 5 times the ketone was converted to the chiral alcohol in less than 24 h. The ionic liquid improved the initial reaction rate by more than four times in the presence of ionic liquid compared to an aqueous-only reaction. Moreover, the ionic liquid improved the stability of both the ADH RE and the GDH coenzyme compared to reactions with either organic cosolvents or aqueous buffer systems [59]. 

Another example of screening the culturable microorganism is to find catalysts to convert 2,2,2-trifluoroacetophenone to the corresponding (S)-alcohol in the presence of 2-propanol as a hydrogen donor [5]. By screening of styrene-assimilahng bacteria ( 900 strains) isolated from soil samples, Leifsonia sp. strain S749 was found to have an enzyme to reduce 2,2,2-trifluoroacetophenone to (S)-l-phenyltrifluoro-ethanol and also acetophenone to (R)-l-phenylethanol both in >99% and 99% ee, respectively. 

Solvent effect in the enantioselective hydrogenation of 2,2,2-trifluoroacetophenone on cinchonine-modified Pt/Al203 was studied in 10 different solvents. Application of strongly basic solvents inverted the sense of enantiodifferentiation from (5)-alcohol. 

We developed fi-chlorodiisopinocamphOTlborane (Aldrich DIP-Chloride , 1) as an excellent leagrat for the asymmetric reduction of aiall l and a-hindeied ketones (JO). Examination of the reduction of 2,2,2-trifluoroacetophenone with (-)-l exhibited... 

Figure 1. Comparison of asymmetric reduction of acetophenone, pivalophenone, and 2,2,2-trifluoroacetophenone with DIP-Chloride ...

Reduction of Aryl Fluoroalkyl Ketones. As mentioned earlier, 2,2,2-trifluoroacetophenone is reduced to die product alcohol in 90% ee (5 ) with (-)-l. 

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