Aminomethylation of Aryl Bromides by Nickel-Catalyzed Electrochemical Redox Neutral Cross Coupling

Abstract

We develop an electrochemical nickel-catalyzed aminomethylation of aryl bromides under mild conditions. The convergent paired electrolysis makes full use of anode and cathode processes, free of a terminal oxidant, a sacrificial anode, a metal reductant, and a prefunctionalized radical precursor. In addition, this method exhibits wide functional group tolerance (63 examples), including some sensitive substituents and aromatic heterocycles. This redox neutral cross coupling provides a more environmentally friendly and synthetic practical protocol for forging C(sp 2 )−C(sp 3 ) bonds.

Progress in Convergent Paired Electrolysis

“…In the work of Hu and Liu (pathway A), benzylic radicals (23) were produced by direct anodic oxidation of toluene derivatives and benzylic trifluoroborates, respectively. In contrast, in reports from Li and co-workers (pathway B), alcohols were transformed into alkyl bromides (25) through an anodic Appel reaction, which was then followed by nickel-catalyzed SET to afford alkyl radicals (26). The cathodic processes in these reactions employed similar pathways which involve sequential oxidative addition, singleelectron transmetalation and reductive elimination.…”

“…Sulfinates were unveiled as alternative thiolation reagents by Zhang with nickel catalysis strategy [24] . Ye and co‐workers have described a redox‐neutral coupling between an amine α‐C−H with aryl bromides by using a strategy of nickel‐enabled convergent paired electrolysis [25] . In these transformations, sulfinates and amines served as reactive anodic substrates to deliver the corresponding carbon or sulfur‐centered radicals.…”

Recent synthetic methods involving carbon radicals generated by electrochemical catalysis

“…Consequently, the reactive Ni species can undergo various reaction pathways involving oxidative addition to aryl halides or SET to alkyl halides that enables cross-electrophile coupling, C-H bond activation, alkene functionalization, and other C-heteroatom bonds formation. [37][38][39] In 2020, Ackermann and co-workers developed a method for Csp 2 -H alkylation of carboxylic acid derivatives with alkyl iodides (Fig. 17).…”

“…21). 37 This cross coupling reaction of ter- 54 Organic & Biomolecular Chemistry Review tiary amine and benzonitrile could be accomplished through convergent paired electrolysis, in which the anodically generated α-amino radical reacts with the arene radical anion formed at the cathode, yielding the final coupling product. TEMPO(2,2,6,6-Tetramethylpiperidine-1-oxyl)/TEMPO + redox couple, which has previously been utilized in various electrooxidation chemistries, 55 is used to promote the oxidation of amine 21-4 on the anodic side to form the radical cation species 21-5.…”

“…This radical intermediate is then rapidly captured by the Ni II complex 22-6, generating the high-valent Ni III intermediate 22-9. 37,56 Subsequent reductive elimination occurs to produce the coupling product 22-3 and regenerate the Ni I complex. Under these mild electrolysis conditions, a broad range of substrates bearing sensitive functional groups are well-tolerated with excellent selectivity.…”