Thieno[2′,3′:5,6]azepino[2,1‐a]isoindolones from hydroxylactam‐alcohols via N‐acyliminium ion olefin cyclization

Abstract

A one pot synthesis of thienoazepinoisoindolones from the reaction of hydroxylactam‐alcohols, under acidic treatment, is described via an N‐acyliminium olefin cyclization.

Diversity-oriented synthesis of benzo[b]thiophenes fused to medium-sized N-heterocycles via Friedel–Crafts cyclization processes

“…13 C-NMR (100 MHz, CDCl3, δ, ppm): 29.0, 40.7, 49.2, 50.1, 122.5, 122.8, 123.4, 127.3, 128.3, 128.6 (2C), 135.4, 138.5, 139.3, 149.1, 151.9, 164.9, 191.5. MS (EI, 70 eV) m/z (%), 307 (M + +1, 27), 306 (M + , 4), 307 (26), 275 (26), 246 (12), 218 (4), 171 (22), 143 (100), 129 (24), 128 (28), 115 (74), 102 (18), 101 (19), 89 (13), 77 (25)…”

“…13 C-NMR (100 MHz, CDCl3, δ, ppm): 14.2, 29.0, 32.3, 39.2, 50.1 (2C), 61.2, 122.5, 122.8, 127.3, 127.6, 127.8), 128.1 (2C), 128.5 (2C), 136.2, 138.5, 139.3, 151.9, 171.7. MS (EI, 70 eV) m/z (%), 366 (M + +1, 5), 365 (M + , 1), 284 (3), 240 (10), 223 (19), 209 (3), 199 (10), 198 (54), 196 (57), 176 (9), 171 (67), 169 (100), 165 (27), 109 (16), 99 (42), 97 (74), 105 (5), 75 (9), 62 (25), 61 (24) 4 Hz, C β H2), 2.28 (1H, dddd, J 13.8, 4.3, 4.0, 1.9 Hz, C 3 Hb), 2.33 (2H, t, J 7. 4 Hz, C α H2), 3.16 (1H, ddd, J 13.9, 4.0, 1.8 Hz, C 2 Ha), 3.39 (1H, ddd, J 13.9, 9.9, 1.9 Hz, C 2 Hb), 3.50 (2H, t, J 7.5 Hz, C  H2), 4.10 (2H, q, J 7.1 Hz, CH2CH3), 4.12 (1H, dd, J 9.9, 4.3 Hz, C 4 H), 7.15 (1H, ddd, J 7.9, 7.6, 1.5 Hz), 7.20 (2H, dtd, J 7.8, 1.2, 0.5 Hz), 7.21 (1H, tt, J 7.7, 1.3 Hz), 7.29 (2H, ddd, J 8.6, 7.6, 1.4 Hz), 7.34 (1H, dddd, J 7.8, 7.7, 1.9, 0.5 Hz), 7.53 (1H, ddd, J 8.6, 1.5, 0.5 Hz), 7.82 (1H, ddd, J 7.9, 1.4, 0.5 Hz).…”

“…13 4 Hz, C α H2), 2.41 (1H, dddd, J 13.6, 4.3, 4.0, 1.9 Hz, C 3 Hb), 3.29 (1H, ddd, J 13.7, 4.0, 1.8 Hz, C 2 Ha), 3.39 (1H, ddd, J 13.7, 9.9, 1.9 Hz, C 2 Hb), 3.50 (2H, t, J 7.5 Hz, C  H2), 4.06 (1H, dd, J 9.9, 4.3 Hz, C 4 H), 4.10 (2H, q, J 7.1 Hz, CH2CH3), 7.15 (2H, ddd, J 7.4, 4.9, 1.2 Hz), 7.26 (1H, ddd, J 7.6, 1.2, 0.6 Hz), 7.29 (1H, ddd, J 8.6, 7.6, 1.4 Hz), 7.54 (1H, ddd, J 8.6, 1.6, 0.5 Hz), 7.68 (1H, ddd, J 7.6, 7.4, 1.9 Hz), 7.82 (1H, ddd, J 7.9, 1.4, 0.5 Hz), 8.52 (1H, ddd, J 4.9, 1.9, 0.6 Hz). 13 (24), 325 (86), 324 (37), 269 (21), 268 (100), 181 (5), 145 (12), 107 (14), 77 (3), 57 (20)…”

“…13 Given the large array of synthetic utility, structural complexity and astonishing biological profile of condensed thiophenes, a flexible route to regioselective access to these significant condensed scaffolds from readily available acyclic precursors is an attractive goal. In the literature, among the most important classical and modern synthetic approaches to functionalized thiophenes are the Paal-Knorr condensation of 1,4diketones, diesters, or dicarboxylates with P4S10 or elemental sulfur, 14 the Volhard-Erdmann cyclization of γoxo acids, 1,4-diketones or chloroacetyl-substituted esters with phosphorus pentasulfide, 15 the Fiesselmann condensation of thioesters with α-chlorocarbonyls, 16 the Gewald reaction of ketones or aldehydes with αcyanoesters in the presence of a sulfur source, 17 the Hinsberg reaction of dialkyl thioglycolate with αdiketones under basic conditions followed by decarboxylation reactions, 18 Heck or Ullmann couplings, 19 organometallic polycondensation, 20 electrochemical polymerization, 21 the domino fragmentation combined with intramolecular thia-anti-Michael addition from α-alkenyl-α'-carbamoyl ketene-(S,S)-acetals, 22 Fort's three-step approach starting from methylthiopyridines, 23 an N-acyliminium ion olefin cyclization of hydroxylactam-alcohols, 24 and Dong's combinatorial procedure from the treatment of 1,3-dicarbonyl compounds with CS2 in the presence of base. 25 Although these approaches are reliable methods, but they are all multi-step approaches and limited to synthesizing only one type of thiophene.…”