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.

Metal-Free Regioselective N2-Arylation of 1H-Tetrazoles with Diaryliodonium Salts.

We describe a simple, metal-free regioselective N2-arylation strategy for 5-substituted-1H-tetrazoles with diaryliodonium salts to access 2-aryl-5-substituted-tetrazoles. Diaryliodonium salts with a wide range of both electron-rich and previously challenged electron-deficient aryl groups are applicable in this method. Diversely functionalized tetrazoles are tolerable also. We have devised a one-pot system to synthesize 2,5-diaryl-tetrazoles directly from nitriles. The synthetic utility of this method is furthered extended to late-stage arylation of two biologically active molecules.

Metal-free S-arylation of 5-mercaptotetrazoles and 2-mercaptopyridine with unsymmetrical diaryliodonium salts.

Herein, we demonstrate the application of unsymmetrical iodonium salts towards S-arylation of heterocyclic thiols (especially tetrazole-5-thiols and pyridine-2-thiol) under metal-free conditions, affording a diverse range of di(hetero)aryl thioethers in moderate to good yields. A detailed study on the effects of counter-anions and the auxiliary of iodonium salts was conducted. Suitable auxiliary selection of the unsymmetrical iodonium salt offers flexibility for a wide range of aryl moieties and its incorporation into S-arylation. The DFT study supports the experimental observations of chemoselective arylation.