Hydrogenation of 2,2,2-trifluoroacetophenone

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]. 

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. 

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). 

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. 

Figure 1 Effect of pressure in the hydrogenation of trifluoroacetophenone 1. Standard conditions, in 1,2-dichlorobenzene with CD...

In the reduction of co.a+a+trifluoroacetophenone with (S)-2-phenyl-l,l,2-trideuteroethylmag-nesium bromide, deuterium transfer shows a higher asymmetric induction than hydrogen transfer (RD = 54.4% ee. SH = 47.1 % ee), although the hydrogen exceeds the deuterium transfer (H/D = 1.6)123. The result is rationalized in terms of a transition state A (preferred over B) in which the two phenyl groups are facing each other. 

To avoid the polymerization initiated by abstraetion of the a-hydrogen atom, Ramehandran et al. have foeused their attention on aryl tiifluoromethyl ketones. By eonsidering the match between the reactivities of the olefin and carbonyl partners, they succeeded in accomplishing the MBH reaction between moderately reactive electrophile e.g. trifluoroacetophenone, trifluoroacetylthiophene, 3-tiifluoroacetyl-indole, 2-chloro-2,2-difluoroacetophenone, 1,1,1 -trifluoro-4-phenyl-3-butyn-2-one and 4,4,5,5,6,6,6-heptafluoro-l-phenyl-l-hexyn-3-one) with moderately reactive olefins e.g. ethyl acrylate and acrylonitrile) in the presence of DABCO in high yields (Chapter 2.2.1). ... 

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