Electrochemical Decarboxylative Coupling of N‐Substituted Glycines under Air: Access to C3‐Aminomethylated Imidazo[1,2‐a]pyridines

Abstract

An electrochemical decarboxylative aminomethylation reaction of imidazo[1,2a]pyridines with various N-substituted glycines in acetonitrile at room temperature has been described. The reaction could be conducted under light-free, catalyst-free, oxidant-free, and air conditions, affording the C3-aminomethylated imidazo[1,2a]pyridines in good to high yields. Remarkably, Naryl, N,N-dialkyl, and N-alkyl-N-aryl glycines are all well-tolerated in this easily handled protocol, which further expands the chemical space of bioactive imidazo[1,2-a]pyridine derivatives.

Electrochemical Decarboxylative Addition of N‐Aryl Glycines to Enaminones: Access to C3‐Aminomethyl Chromones

“…With inspiration from literature reports [16a,b,d] and mechanistic studies, a plausible reaction mechanism was proposed (Scheme 6). The N ‐phenyl glycine 2 a undergoes sequential anodic oxidation and deprotonation to form a carboxyl radical A , which then discharges carbon dioxide to generate the primary carbon radical B .…”

“…[15b] Furthermore, N-substituted gly-cines have also been confirmed as eligible aminomethyl moieties in electrosynthesis. [16] Continuing our interest in N-aryl glycines, [16a] herein we will disclose an approach to access C3aminomethyl chromones using electron as the traceless oxidant under mild conditions.…”

Electrocatalytic synthesis: an environmentally benign alternative for radical-mediated aryl/alkenyl C(sp2)–C(sp3) cross-coupling reactions

“…In 2022, Cheng et al described an intriguing electrochemical radical-based decarboxylative C(sp 2 )–C(sp 3 ) cross-coupling of imidazo[1,2- a ]pyridines with N -substituted glycines (Scheme 10). 28 This protocol exhibited excellent substrate compatibility, providing a powerful tool for constructing structurally diverse C3-aminomethylated imidazo[1,2- a ]pyridines. Disappointingly, 3-anilinopropionic acid was inert, indicating that the carboxymethylene moiety directly adjacent to the nitrogen atom is essential to ensure the smooth generation of the alkyl radical.…”

Paraformaldehyde as C1 Synthon: Electrochemical Three‐Component Synthesis of Tetrahydroimidazo[1,5‐a]quinoxalin‐4(5H)‐ones in Aqueous Ethanol

“…[13] . Despite the high efficiency of the above mentioned methods, one of the main disadvantages of these strategies is the usage of large excess of N-arylglycines as the C1 synthon, [14] , which not only produced super-stoichiometric amounts of aromatic amine byproducts but also diminished the appeal of practical application.…”