Ni-Catalyzed Electro-Reductive Cross-Electrophile Couplings of Alkyl Amine-Derived Radical Precursors with Aryl Iodides

Abstract

In recent years, the “Escape-from-Flatland” trend has prompted the synthetic community to develop a set of cross-coupling strategies to introduce sp3-carbon-based fragments in organic compounds. This study presents a novel nickel-catalyzed electrochemical methodology for reductive cross-electrophile coupling. The method enables C(sp2)–C(sp3) linkages using inexpensive amine-derived radical precursors and aryl iodides. The use of electrochemistry as a power source reduces waste and avoids chemical reductants, making this approach a more sustainable alternative to traditional cross-coupling methods.

Recent Advances in Electrochemical, Ni‐Catalyzed C−C Bond Formation

“…[38][39][40][41][42] Noël and co-workers reported the coupling of aryl iodides with secondary alkylpyridinium (Katritzky) salts under constant current electrolysis (4 mA, 2 mA/cm 2 ) with a sacrificial SS anode (Figure 19). [43] Primary alkyl aminederived substrates were not tolerated.…”

Nickel-Catalyzed Electroreductive Coupling of Alkylpyridinium Salts and Aryl Halides

“…Given these advantages of electrochemical catalytic reactions, we sought to develop a nickel-catalyzed electroreductive coupling of alkylpyridinium salts with aryl bromides. Although electrochemical and electrophotochemical activation of alkylpyridinium salts has been demonstrated with various radical traps, such as Michael acceptors and heteroarenes, electrochemically driven Ni-catalyzed couplings of Katritzky salts with aryl bromides have remained elusive . A particular challenge in the development of electroreductive conditions for this nickel-catalyzed reaction is the relatively positive reduction potential of alkylpyridinium salts ( E 1/2 ∼ −1.4 V vs Fc/Fc + ) in comparison to the other alkyl electrophiles that have been used in electrochemical reductive couplings (alkyl halides and redox-active esters, Scheme A).…”

Primary vs. secondary alkylpyridinium salts: a comparison under electrochemical and chemical reduction conditions

“…6 Electroreductive couplings have been developed for alkyl halides, NHPI esters, 7 and very recently Katritzky pyridinium salts. 8 In these investigations, the reaction outcomes using electrochemical conditions are often compared to those using chemical reductants, with electrochemistry often providing complementary or improved results. However, a “mix and match” approach is often applied in scope studies, making systematic comparisons of the differences (or similarities) between scope for primary (1°) vs. secondary (2°) vs. tertiary (3°) alkyl substrates difficult.…”