I₂-catalyzed intramolecular oxidative amination of C(sp³)–H bond: efficient access to 3-acylimidazo[1,2-a]pyridines under neat condition

Abstract

An efficient and green protocol for the synthesis of 3-acylimidazo[1,2-a]pyridines utilizing I2 as a catalyst and H2O2 as an oxidant under neat condition or in water was developed.

I2-Catalyzed Three-Component Consecutive Reaction for the Synthesis of 3-Aroylimidazo[1,2-a]-N-Heterocycles

“…Imidazo[1,2-a]pyridin-3-yl(phenyl)methanone (3aa). 16 Petroleum ether/ethyl acetate = 1:1; pale brown powder (yield: 164 mg, 74%); mp 96−97 °C; 1 H NMR (400 MHz, chloroform-d) δ 9.76 (d, J = 9.2 Hz, 1H), 8.22 (s, 1H), 7.89 (d, J = 6.8 Hz, 2H), 7.82 (d, J = 9.2 Hz, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.58−7.52 (m, 3H), 7.16 (t, J = 6.8 Hz, 1H). 13 C{H} NMR (101 MHz, δ 184.…”

“…(4-Chlorophenyl)(imidazo[1,2-a]pyridin-3-yl)methanone (3ae). 16 Petroleum ether/ethyl acetate = 1:1; pale brown powder (yield: 197 mg, 77%); mp 192−193 °C; 1 H NMR (400 MHz, chloroform-d) δ 9.72 (d,J = 6.8 Hz,1H),8.19 (s,1H),3H), 7.57 (t, J = 8.0 Hz, 1H), 7.52 (d,J = 8.4 Hz,2H), 7.17 (t, J = 8.0 Hz, 1H). 13 C{H} NMR (101 MHz,149.3,145.6,138.4,137.6,130.…”

“…(4-Bromophenyl)(imidazo[1,2-a]pyridin-3-yl)methanone (3af). 16 Petroleum ether/ethyl acetate = 1:1; pale brown powder (yield: 199 mg, 78%); mp 204−205 °C; 1 H NMR (400 MHz, chloroform-d) δ 9.73 (d,J = 5.6 Hz,1H),8.19 (s,1H),7.82 (d,J = 9.2 Hz,1H),7.76 (d,J = 8.0 Hz,2H),7.69 (d,J = 8.4 Hz,2H), 7.58 (t, J = 7.2 Hz, 1H), 7.17 (t, J = 4.0 Hz, 1H). 13 C{H} NMR (101 MHz,149.3,145.6,138.0,131.9,130.4,129.7,128.9,126.9,123.3,117.9,115. Imidazo[1,2-a]pyridin-3-yl(4-nitrophenyl)methanone (3ag).…”

“…Imidazo[1,2-a]pyridin-3-yl(m-tolyl)methanone (3ah). 16 Petroleum ether/ethyl acetate = 1:1; pale brown powder (yield: 172 mg, 73%); mp 123−124 °C; 1 H NMR (400 MHz, chloroform-d) δ 9.75 (d, J = 6.0 Hz, 1H), 8.21 (s, 1H), 7.81 (d,J = 8.8 Hz,1H),2H), 7.55 (t, J = 6.4 Hz, 1H), 7.43 (d,J = 4.8 Hz,2H), 7.16 (t, J = 7.2 Hz, 1H), 2.46 (s, 3H). 13 C{H} NMR (101 MHz,149.1,145.7,139.3,138.5,132.8,129.4,129.4,128.9,128.4,126.1,123.6,117.8,115.1,21.4.…”

“…15 Recently, He's group developed intramolecular oxidative α-amination of carbonyl compounds by I 2 /H 2 O 2 to give 3aroylimidazo[1,2-a]pyridines (Scheme 1B, route c). 16 Similarly, Wen et al demonstrated copper-catalyzed intramolecular oxidative amination of enaminones for the synthesis of 3aroylimidazo[1,2-a]pyridines (Scheme 1B, route d). 17 Despite these findings, developing a convenient method is still desirable in hit-to-lead drug discovery, which requires quick -a]pyridines in moderate to good yields (3aa−3am).…”