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

Abstract

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.

Ligand-free Ullmann-type arylation of oxazolidinones by diaryliodonium salts

“…Reactions with electron-rich heterocycles succeed under mild conditions without the addition of transition metal-based catalysts. For example, diaryliodonium salts have been used as a source of carbon-centered electrophiles for the arylation of tetrazoles, 19 pyrazoles, 20 indolines, 21 and other cyclic amines. 22 In fact, the reactivity of diaryliodonium salts is slightly decreased with respect to electron-deficient azaheterocycles.…”

Preparation of 2,5‐Disubstituted Tetrazoles using a Copper‐Catalysed Regioselective Direct Coupling of Tetrazoles with Free NH Groups and Boronic Acid Derivatives

“…[2,21] In particular, 2,5-disubstituted tetrazoles are often used as pharmacophores and photosensitive materials and a convenient precursor for the preparation of a variety of N-heterocycles. [22][23][24] Despite its numerous uses, there are only few synthetic methodologies developed so far for N-arylation of tetrazoles with aryl boronic acids. The traditional approach to access 2aryl-5-substituted tetrazoles was via Kakehi methodology, where potentially explosive aryl diazonium salts and phenyltosylhydrazones were used.…”

“…[30,31] Moreover, when diaryliodonium salts were used as the coupling partner to generate 2,5-disubstituted tetrazoles, such methods were not only operationally tedious, but also generated stoichiometric amounts of the respective aryliodide. [23] Another route for N 2 -arylation used arylbismuthas the arylating source under copper catalysis. [32] Other multi-step procedures based on various cyclization protocols for the synthesis of 2,5-disubstituted tetrazole derivatives have also been reported.…”

“…Lam and co‐workers used stoichiometric amount of Cu(OAc) 2 for reaction between 5‐phenyltetrazole and p ‐tolylboronic acid that required longer reaction time (Scheme 1). [30,31] Moreover, when diaryliodonium salts were used as the coupling partner to generate 2,5‐disubstituted tetrazoles, such methods were not only operationally tedious, but also generated stoichiometric amounts of the respective aryliodide [23] . Another route for N 2 –arylation used arylbismuthas the arylating source under copper catalysis [32] .…”

Ligand-Free Ullmann-Type Arylation of Oxazolidinones by Diaryliodonium Salts

“…Reactions with electron-rich heterocycles succeed under mild conditions without the addition of transition metal-based catalysts. For example, diaryliodonium salts have been used as CAr electrophiles for the arylation of tetrazoles, 24 pyrazoles, 25 indolines, 26 and other cyclic amines. 27 In fact, the reactivity of diaryliodonium salts is slightly decreased with respect to electron-deficient azaheterocycles.…”