A Brief Review on the Synthesis of the -CF Motif in Heterocycles.

The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, -trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing -trifluoromethyl (-CF) motifs will be of great significance in pharmaceutical and agrochemical industries.

Tandem Reaction of Azide with Isonitrile and TMSCF(H): Access to N-Functionalized C-Fluoroalkyl Amidine.

N-Functionalized C-fluoroalkyl amidines are attracting great attention due to their potential in pharmaceuticals. Herein, we report a Pd-catalyzed tandem reaction of azide with isonitrile and fluoroalkylsilane via a carbodiimide intermediate, providing facile access to N-functionalized C-fluoroalkyl amidines. This protocol offers an approach toward not only N-sulphonyl, N-phosphoryl, N-acyl, and N-aryl but also C-CF, CF, and CFH amidines with a broad substrate scope.