Electrochemically Enabled, Nickel‐Catalyzed Amination

Abstract

Along with amide bond formation, Suzuki cross-coupling, and reductive amination, the Buchwald–Hartwig–Ullmann-type amination of aryl halides stands as one of the most employed reactions in modern medicinal chemistry. The work herein demonstrates the potential of utilizing electrochemistry to provide a complementary avenue to access such critical bonds using an inexpensive nickel catalyst under mild reaction conditions. Of note is the scalability, functional-group tolerance, rapid rate, and the ability to employ a variety of aryl donors (Ar–Cl, Ar–Br, Ar–I, Ar–OTf), amine types (primary and secondary), and even alternative X–H donors (alcohols and amides).

Organic Electrosynthesis: Applications in Complex Molecule Synthesis

“…Baran and coworkers developed an electrochemically enabled nickel‐catalyzed amination protocol . Among the many examples, the methodology was utilized for drug modification by N ‐arylation of amoxapine and paroxetine (Scheme ).…”

Nickel‐Catalyzed Thiolation of Aryl Halides and Heteroaryl Halides through Electrochemistry

“…[15] Thef ormation of at hiyl radical was further supported by trapping the thiyl radical with TEMPO,a ffording 11 in 30 %y ield. [15] Thef ormation of at hiyl radical was further supported by trapping the thiyl radical with TEMPO,a ffording 11 in 30 %y ield.…”

Elektrifizierung der organischen Synthese

“…[57] Starting from Ni II ,alow-valent Ni catalyst is formed in situ at the cathode to enable oxidative addition of the aryl halide.Concurrently,the anodic reaction is used for the intermediate formation of an ickel species in ahigh oxidation state to facilitate reductive elimination of the cross-coupling products.A side from secondary and primary amines,a mides and alcohols were used as nucleophiles.…”