Ketones building block trifluoromethylation

Trifluoroacetic acid is a most useful building block for a wide range of tri-fluorocompounds, particularly trifluoromethyl ketones [206]. Esters are useful... 

The Henry nitro-aldol condensation involves the use of P-amino alcohols as the building blocks of fluoromethyl ketones. Although this method has been used extensively in the synthesis of monofluoropeptides (Table 2),19-121 it is more widely utilized as a method for synthesizing trifluoromethyl ketones and the details of the reaction will be discussed in Section 15.1.4.3.2. 

A versatile C4-building block, difluorinated Danishefsky s diene, was developed for the construction of fluorinated six-membered rings in the laboratory of K. Uneyama. The diene was prepared by the selective C-F bond cleavage of trifluoromethyl ketones. The reaction of this novel diene with benzaldehyde afforded the corresponding difluoro dihydropyrone in 92% ee in the presence of equimolar Ti(IV)-(R)-BINOL. ... 

Reaction of trifluoromethyl vinyl ketones with magnesium/MesSiCl leads to a di-fluoro analog of Danishefsky s diene (24) [34] (Scheme 2.200) which is a useful building block for synthesis of fluorinated heterocycles [35],... 

As the demand for optically active fluorinated compounds increases, the importance of the development of asymmetric synthetic methods for fluorinated building blocks grows. On the other hand, sulfur functionalities such as phenylthio and dithianyl groups have been used as useful reactive units for a variety of chemical transformations. Therefore, various trifluoromethyl ketones containing a sulfur functionality have been reduced with various microorganisms l182-185 . 

Fluoroalkyl P-amino alcohols are precursors of the corresponding fluoroalkyl peptidyl ketones which have been shown to be effective inhibitors of proteolytic enzymes, such as serine proteases/ (chymotrypsin/ elastases/ trypsin/ thrombin/ ) aspartyl proteasesor cysteine proteases, In some cases fluoroalkyl p-amino alcohols are themselves inhibitors of the same enzymes/ " This interest in these fluoroalkyl P-amino alcohols 1 aroused efforts for stereoselective and enantioselective synthetic methodsA number of approaches have been reported during these last years, either through the addition of trifluoromethyl equivalent anion to protected aldehyde or through the building block approach. However the main problem of all these approaches is the diastereoselectivity. 

---