Copper‐Promoted Annulation of Terminal Alkynes with 2‐Aminopyridines to Assemble 2‐Halogenated Imidazo[1,2‐a]pyridines

Abstract

Copper‐promoted annulation reactions of terminal alkynes with 2‐aminopyridines have been developed for the synthesis of 2‐halogenated imidazo[1,2‐a]pyridines using copper halide as the halogen source. A variety of substrates survived under the reaction conditions and gave the desired products in good yields. This reaction features advantages such as easily available starting materials, broad substrate scope, and mild reaction conditions.

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

“…Encouraged by them, Liu et al . in 2019 reported copper‐promoted annulation reactions of terminal alkynes 217 with 2‐aminopyridine derivatives 216 for the synthesis of 2‐halogenated imidazo[1,2‐ a ]pyridines 218 using copper halide as the halogen source [171] . They synthesized a series of 2‐halogenated imidazo[1,2‐ a ]pyridines 218 in good yields.…”

“…[170] Encouraged by them, Liu et al in 2019 reported copper-promoted annulation reactions of terminal alkynes 217 with 2-aminopyridine derivatives 216 for the synthesis of 2-halogenated imidazo[1,2-a]pyridines 218 using copper halide as the halogen source. [171] They synthesized a series of 2-halogenated imidazo [ To synthesize a new hybrid scaffold by the combination of different scaffolds to obtain a biologically active moiety, Ashok's group [172] The transformations at the C3-substituents of the imidazo[1,2-a]pyridine ring enhanced the bioactivity. [173] To develop convergent synthetic methods towards complex imidazo[1,2-a]pyridines, Vuillermet et al [174] in 2021 reported the synthesis of imidazo [1,2-a]…”

Application of 2-Aminopyridines in the Synthesis of Five- and Six-Membered Azaheterocycles

“…可以使用卤化铜 [56] 和 Cu(OAc) 2 [57] 等二价铜催化剂 进行催化. 以炔酸 [58] 为底物, 在二价铜催化剂的作用下 得到卤代咪唑并[1,2-a]吡啶 16 (Scheme 8, Method 2).…”

Visible light-mediated copper catalyzed regioselective diamination of terminal alkynes at room temperature: a facile synthesis of substituted imidazo[1,2-α]pyridines

“…2 Moreover, a variety of imidazo[1,2-α] pyridine-derived analogues have been studied as HIF-1α prolyl hydroxylase inhibitors, MCH1R antagonists, 5-lipoxygenase inhibitors, histamine H2 receptor antagonists, and cyclin dependent kinase inhibitors. 3 Thus, due to their importance, several thermal methods have been developed for the synthesis of imidazo[1,2-α]pyridine compounds using various transition metal catalysts (such as Pd, 4 Au, 5 Cu, 6 Ag, 7 Fe, 8 and others 9 ), metal-free 10 reaction conditions, and N-atom containing precursors, such as 2-aminopyridines 4,6–10 and 2-aminopyridine- N -oxides. 5…”

“…Typically, imidazo[1,2-α]pyridine products were obtained by intermolecular cyclization of 2-aminopyridine 4–10 (used as a primary precursor) with other reactants or substrates, including phenacyl bromide, 11 ketones, 6 a acetophenones, 12 carboxylic acids, 12 b nitro olefins, 8 b 1-haloalkynes, 6,8,9 terminal alkynes, 7 etc ., under thermal reaction conditions. Among them, intermolecular cyclizations of 2-aminopyridine with 1-haloalkyne or terminal alkyne substrates have been extensively exploited for the formation of 2- or 3-haloimidazo[1,2-α]pyridines only (eqn (a), Scheme 1).…”