Synthesis of C‐3‐Functionalized Imidazo[1,2‐a]pyridines via Direct para‐Position Arylation of Electron‐Rich Anilines under Transition‐Metal‐Free Conditions

Abstract

A multicomponent tandem arylation reaction was established under transition‐metal‐free conditions to synthesize structurally diverse imidazo[1,2‐a]pyridines. As N,N‐dimethylaniline is not only a reactant but also a methylation reagent, its use affords an alternative route for methylation. This approach features mild reaction conditions and good functional group tolerance, providing 29 compounds in acceptable yields.

Multicomponent Cross-Dehydrogenative Coupling of Imidazo[1,2-a]pyridine: Access to Abnormal Mannich and Mannich-Type Reaction

“…((Phenylimidazo[1,2-a]pyridin-3-yl)methyl)aniline (4aa). 22,33 According to the general procedure, compound 4aa was prepared; TLC (R f ): (PE/EA = 60:40) 0.…”

“…21 The very same year Ji's group approached a multicomponent tandem arylation reaction under transition-metal-free conditions (Scheme 1c). 22 Paturea et al in 2022 revealed an electrochemical system for amino methylation of imidazopyridine (Scheme 1d). In all of the cases, the substrate scope of N,N-dialkyl anilines was limited to para-substituted N,N-dimethylanilines.…”

“…In 2023, Cao et al proposed metal-free C-3 selective C­(sp 2 )–C­(sp 3 ) heteroarylation of aniline with imidazo­[1,2- a ]­pyridine derivatives via cross-dehydrogenative coupling (Scheme b) . The very same year Ji’s group approached a multicomponent tandem arylation reaction under transition-metal-free conditions (Scheme c) . Paturea et al in 2022 revealed an electrochemical system for amino methylation of imidazopyridine (Scheme d).…”