Tandem Reaction of Azide with Isonitrile and TMSCnFm(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-CF3, C2F5, and CF2H amidines with a broad substrate scope. The accomplishment of further transformations and Celebrex derivatization in gram scale and biological evaluation reveals the important utility of this strategy.

Automated summary

In this study, a palladium-catalyzed tandem reaction of azide with isonitrile and fluoroalkylsilane was developed to access N-functionalized C-fluoroalkyl amidines. This protocol allows for the synthesis of a broad range of N-sulphonyl, N-phosphoryl, N-acyl, N-aryl, C-CF3, C2F5, and CF2H amidines. The successful gram-scale synthesis and biological evaluation of Celebrex derivatives demonstrate the utility of this strategy.