C–H functionalization of amines with aryl halides by nickel-photoredox catalysis

Abstract

We describe the functionalization of α-amino C–H bonds with aryl halides using a combination of nickel and photoredox catalysis. This direct C–H, C–X coupling uses inexpensive and readily available starting materials to generate benzylic amines, an important class of bioactive molecules. Mechanistically, this method features the direct arylation of α-amino radicals mediated by a nickel catalyst. This reactivity is demonstrated for a range of aryl halides and N-aryl amines, with orthogonal scope to existing C–H activation and photoredox methodologies. We also report reactions with several complex aryl halides, demonstrating the potential utility of this approach in late-stage functionalization.

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

“…As a rule, these reactions are based on α‐deprotonation of N ‐substituted pyrrolidines with organolithium compounds. Carbanions thus obtained are then involved into the Negishi cross‐coupling via a transmetallation with zinc halides followed by interaction with aryl halides . The other pathway within the same approach is a reaction of 2‐hydroxy‐, 2‐alkoxy‐ or 2‐acetoxypyrrolidines with organomagnesium or organolithium derivatives of aromatic compounds .…”

Aminomethylation of Aryl Halides Using α-Silylamines Enabled by Ni/Photoredox Dual Catalysis

“…This is in stark contrast to the success encountered by MacMillan, Doyle, Rueping, and others when using dialkylanilines, where carbon-centered radicals are generated by decarboxylative fragmentation, hydrogen atom transfer (HAT), or deprotonation. 10–12 The success incurred with these scaffolds can be attributed to their relatively low oxidation potentials coupled with α-amino radical stabilization. However, the same rationale for the successes with these systems ultimately highlight their restrictions, namely that only activated amines can succumb to visible light activation.…”

“…15 If successful, a dissonant mode of photochemical aminomethylation of aryl halides would be realized and complement existing Ni/photoredox strategies, which are limited to protected amines or aniline-based derivatives. 9–12 …”

Radikalische enantioselektive C(sp3)‐H‐Funktionalisierung

“…[6] Dies sind interessante Ansätze zur Kontrolle von enantioselektiv-radikalischen C(sp 3 )-H-Funktionalisierungen. [6] Dies sind interessante Ansätze zur Kontrolle von enantioselektiv-radikalischen C(sp 3 )-H-Funktionalisierungen.…”