Utilization of Aryl(TMP)iodonium Salts for Copper-Catalyzed N-Arylation of Isatoic Anhydrides: An Avenue to Fenamic Acid Derivatives and N,N?-Diarylindazol-3-ones

Herein, we report a general method for copper-catalyzed N-arylation of isatoic anhydrides with unsymmetrical iodonium salts at room temperature. The developed catalytic protocol is mild and operationally simple, and aryl(TMP)iodonium trifluoroacetate is employed as the arylating partner. The methodology offers the broad applicability of both structurally and electronically diverse aryl groups from aryl(TMP)iodonium salts to access N-arylated isatoic anhydrides in moderate to excellent yields (53-92%). Moreover, the substituted isatoic anhydrides are equally compatible with the protocol too. To demonstrate the synthetic utilities of the N-arylation process, we also report an alternative approach for biologically relevant fenamic acid derivatives and N,N '-diarylindazol-3-ones in a one-pot step economical system. In addition, the scale-up synthesis of flufenamic acid is also illustrated.

Automated summary

Here, a general method for copper-catalyzed N-arylation of isatoic anhydrides with unsymmetrical iodonium salts at room temperature is reported. The protocol is mild and simple, employing aryl(TMP)iodonium trifluoroacetate as the arylating partner, and provides access to N-arylated isatoic anhydrides with diverse aryl groups in moderate to excellent yields (53-92%). The methodology is also compatible with substituted isatoic anhydrides and can be used for the synthesis of biologically relevant fenamic acid derivatives and N,N'-diarylindazol-3-ones in a one-pot step economical system, as demonstrated here. The scale-up synthesis of flufenamic acid is also illustrated.