Electrochemical C–H Amination: Synthesis of Aromatic Primary Amines viaN-Arylpyridinium Ions

Abstract

We have developed a new method for C-H amination of aromatic compounds based on electrochemical oxidation of aromatic compounds in the presence of pyridine followed by the reaction of the resulting N-arylpyridinium ions with an alkylamine. This new transformation serves as a powerful method for synthesizing aromatic primary amines from aromatic compounds without using metal catalysts and harsh chemical reagents. High chemoselectivity of the present method is demonstrated by C-H amination of aromatic compounds bearing a nitro group to give a key intermediate for the synthesis of VLA-4 antagonist.

Elektrifizierung der organischen Synthese

“…[41][42][43] Upon anodic oxidation at acarbon felt anode and nucleophilic trapping of the generated radical cations with pyridine,p yridinium intermediates were obtained. Overoxidation was prevented by the strongly electron-withdrawing effect of the positive charge.S ubsequent aminolysis with piperidine released the free anilines (Scheme 5).…”

“…Electrochemical CÀHaminationo fa ctivated arenes. [41][42][43] Scheme 6. Electrochemical CÀHamination of less activated alkylated arenes at BDD anodes.…”

Synthesis, characterization and catalytic activity of gold complexes with pyridine-based selone ligands

“…Moreover, the catalytic activities using gold complexes with selone ligands are better than those of gold complexes with thione ligands [38] and HAuCl 4 . Then, the complex 3 was chosen as the optimal catalyst to screen the various solvents (Table 3, entries [8][9][10][11][12]. High yield of 95% of the desired products was achieved within 3 h in water solvent.…”

“…Therefore, a variety of protocols for synthesizing functionalized anilines have been developed [7][8][9][10][11][12][13][14][15][16][17][18][19]. The desirable method for the synthesis of functionalized anilines is the reduction of nitroarenes using transition metal catalysts in the presence of sodium tetrahydroborate (NaBH 4 ) [20].…”

Reaction Integration Using Electrogenerated Cationic Intermediates

“…The present approach using N-arylpyridnium ions solves the problem. 19 The radical cations generated by the electrochemical oxidation are trapped by pyridine to give N-arylpyridinium ions (Scheme 8). Overoxidation is suppressed because of the strong electron-withdrawing effect of a positive charge on the pyridinium nitrogen.…”