Microwave-assisted facile synthesis of [a]-annelated pyrazolopyrroloindoles via intramolecular azomethine imine 1,3-dipolar cycloaddition

Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds

“…7,11b-Dihydro-6H-imidazo-6H-imidazo[1,5-a]isoquinolino[1,2c]quinoxaline (3a): brown solid (46 mg, 72%); mp 198−200 °C; IR (MIR-ATR, 4000−600 cm −1 ) ν max 3112,2923,2854,1710,1600,1507,1462,1351,1109,746,653; 1 H NMR (400 MHz, CDCl 3 ) δ 2.86 (d,J = 16.1 Hz,1H),1H),1H), 3.97 (ddd, J a = 12.5, J b = 5.4 and J c = 2.2 Hz, 1H), 5.53 (s, 1H), 6.92−6.97 (m, 2H), 7.05 (d,J = 7.8 Hz,1H),4H),1H), 7.43 (dd, J a = 7.8 and J b = 1 Hz, 1H), 8.0 (s, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 27. 1, 43.7, 54.7, 114.7, 115.7, 119.7, 124.6, 124.7, 126.3, 126.9, 127.4, 127.52, 129.3, 131.5, 133.1, 133.9, 137.6 3.92 (m, 1H), 5.45 (s, 1H), 6.94−6.96 (m, 2H), 7.01 (d, J = 1.5 Hz, 1H), 7.…”

“…13−7.16 (m, 1H), 7.19−7.22 (m, 2H), 7.24−7.25 (m, 1H), 7.30−7.33 (m, 1H), 7.97 (d, J = 1 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 20.7, 27.1, 43.9, 54.9, 115.2, 116.3, 124.7, 124.8, 126.2, 126.9, 127.3, 127.4, 127.7, 129.3, 129.8, 131.5, 133.1, 134.0, 135.4 10-Bromo-7,11b-dihydro-6H-imidazo[1,5-a]isoquinolino[1,2-c]quinoxaline (3c): brown solid (56 mg, 68%); mp 168−170 °C; IR (MIR-ATR, 4000−600 cm −1 ) ν max = 3049, 2922, 1718, 1604, 1509, 1475, 1347, 1273, 813, 739, 651; 1 H NMR (400 MHz, CDCl 3 ) δ 2.78−2.82 (m, 1H), 3.2 (ddd, J a = 16.9, J b = 11.5 and J c = 5.9 Hz, 1H), 3.42 (ddd, J a = 13.2, J b = 11.7 and J c = 4.4 Hz, 1H), 4.02−4.07 (m, 1H), 5.56 (s, 1H), 6.92 (td, J a = 7.7 and J b = 1.2 Hz, 1H), 7.00−7.05 (m, 3H), 7.17−7.20 (m, 1H), 7.32 (dd, J a = 8.3 and J b = 1.5 Hz, 1H), 7.41−7.45 (m, 2H), 8.03 (d, J = 1 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 25.8, 43.9, 54.6, 114.8, 115.8, 119.8, 119.9, 124.4, 125.2, 126.1, 127.0, 129.7, 130.6, 131.0, 131.7, 132.9, 135.8, 136.7 7,11b-Dihydro-6H-isoquinolino[2,1-a]pyrrolo[2,1-c]quinoxaline (3d): brown solid (45 mg, 71%); mp 120−122 °C; IR (MIR-ATR, 4000−600 cm −1 ) ν max = 3052, 2902, 2829, 1506, 1337, 1288, 1221, 738, 701, 643; 1 H NMR (400 MHz, CDCl 3 ) δ 2.8 (d, J = 16.1 Hz, 1H), 3.19−3.27 (m, 1H), 3.31−3.38 (m, 1H), 3.90−3.95 (m, 1H), 5.46 (s, 1H), 6.07−6.08 (m, 1H), 6.32−6.34 (m, 1H), 6.84−6.88 (m, 1H), 6.97−6.99 (m, 1H), 7.05−7.20 (m, 5H), 7.31−7.34 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 27. 1, 44.0, 56.2, 105.7, 110.0, 114.5, 115.1, 115.1, 119.7, 125.0, 126.0, 127.0, 127.5, 127.7, 128.5, 129.2, 134.2, 134.4, 137.6 = 3044, 2918, 2847, 1505, 1337, 1289, 1164, 741, 701, 610, 549; 1 H NMR (400 MHz, CDCl 3 ) δ 2.29 (s, 3H), 2.78 (d,J = 15.7 Hz,1H),1H), 3.34 (td, J a = 12 and J b = 3.9 Hz, 1H), 3.9−3.96 (m, 1H), 5.44 (s, 1H), 6.09 (d, J = 2.9 Hz, 1H), 6.34 (t, J = 3.2 Hz, 1H), 6.85−6.89 (m, 1H), 6.98−7.03 (m, 2H), 7.05−7.09 (m, 1H), 7.14 (s, 1H), 7.17 (dd, J a = 2.7 and J b = 1.7 Hz, 1H), 7.23 (s, 1H), 7.33 (dd, J = 7.8 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 21. 3, 26.6, 44.1, 56.14, 105.7, 110.0, 114.4, 115.0, 115.1, 119.6, 124.9, 127.6, 127.8, 128.5, 129.0, 131.0, 134.1, 135.5, 137.6 = 3048, 2919, 2833, 1508, 1340, 1165, 741, 703, 657, 538; 1 H NMR (400 MHz, CDCl 3 ) δ 2.75 (d, J = 17.6, 1H), 3.16−3.24 (m, 1H), 3.38 (ddd, J a = 13.1, J b = 11.6 and J c = 4.2 Hz, 1H), 3.99 (ddd, J a = 13.2, J b = 5.6 and J c = 2.2 Hz, 1H), 5.47 (s, 1H), 6.13 (dd, J a = 3.2 and J b = 1.2 Hz, 1H), 6.36 (t, J = 3.2 Hz, 1H), 6.87 (td, J a = 7.6 and J b = 1.5 Hz, 1H), 6.96−6.99 (m, 2H), 7.05−7.09 (m, 1H), 7.18 (dd, J a = 2.9 and J b = 1.…”

“…In connection with our broader interests in developing synthetic strategies for diverse and complex polyheterocycles involving cascade annulations in a one-pot manner, herein we are pleased to disclose a cascade sequence involving a highly reactive iminium intermediate and further Pictet–Spengler-type cyclization for accessing three-dimensional privileged THIQ compounds as a branching double-annulation cascade (BDAC).…”