Synthesis and properties of N-(trifluoromethyl)amides.

N-Trifluoromethylated amides combine the properties of two of the most important functional groups in medicinal chemistry: amides (found in >40% of all bioactive molecules) and fluorinated functional groups (found in in 23% of drugs). Therefore, it is not surprising that a growing number of publications are investigating potential N-(trifluoromethyl)amide drug targets. While the construction of amide bonds is the most common transformation in medicinal chemistry, the synthesis of N-(trifluoromethyl)amides has been a lot less straightforward until very recently. This review provides a critical overview of strategies for the synthesis of N-CF3 amides, highlighting recent advances, remaining challenges and promising avenues for future developments. A summary of the physical properties of N-CF3 amides is provided and their suitability as drug targets is evaluated.