Construction of the Azepinoindole Core Tricycle of the Stemona Alkaloids

Abstract

The azepinoindole substructure common to a number of Stemona alkaloids is constructed by employing a 7-endo radical cyclization of a readily available N-alkylated hydroindolone substrate. The indolone precursors are prepared via [1 + 4] cycloaddition between a vinyl isocyanate and either dimethoxycarbene or cyclohexylisocyanide.

The domino way to heterocycles

“…In this sequence, α-diazo ketones 262a,b were heated to effect a Wolff rearrangement, giving rise to ketenes 263 (Scheme 54). 91 The authors propose that a [1,5]hydride shift then provided 264, and a subsequent cyclization gave 265a,b in 88 and 75% yields, respectively. Thiophene derivative 266 was also found to rearrange to 267 in 75% yield.…”

“…1 Accordingly, novel strategies for the stereoselective synthesis of hetero-polycyclic ring systems continue to receive considerable attention in the field of synthetic organic chemistry. 2,3,4,5,6,7,8 The efficiency with which heterocycles can be constructed is important not only because it affects the production costs for the desired material, but also the environmental impact associated with waste disposal, conservation of source materials like petroleum stocks, and energy consumption. The rate of increase in molecular intricacy as one progresses from simple starting materials to the final product can serve as a measure of efficiency.…”

The rhodium(II) carbenoid cyclization–cycloaddition cascade of α-diazo dihydroindolinones for the synthesis of novel azapolycyclic ring systems

“…The organic extracts were filtered and concentrated under reduced pressure. The crude residue was subjected to flash silica gel chromatography to give 1.9 g (65%) of carboline 12 as a white solid; mp 229-230 °C; IR (neat) 3301, 2934, 1687, 1663, and 1287 cm −1; 1 H-NMR (400 MHz, CDCl 3 ) δ 9.10 (brs, 1H), 7.64 (d,1H,J = 8.3 Hz),7.45 (d,1H,J = 8.7 Hz), 7.39 (t, 1H, J = 8.3 Hz), 7.19 (t, 1H, J = 8.7 Hz), 4.35 (t, 2H, J = 6.4 Hz), 3.07 (t, 2H, J = 6.4 Hz), and 2.67 (s, 3H); 13 C-NMR (100 MHz, CDCl 3 ) δ 20. 8, 27.3, 43.9, 112.5, 120.8, 121.1, 124.1, 124.8, 126.4, 126.7, 138.6, 161.8, and 173.1 4.1.2 3-(2-Acetyl-1-oxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)-2-diazo-3-oxopropionic Acid Ethyl Ester (13)-To a suspension of 0.47 g (12 mmol) of NaH in 20 mL of THF cooled to 0 °C was added 1.8 g (8 mmol) of carboline 12 dissolved in 30 mL of THF via cannula.…”

“…The resulting mixture was heated at reflux for 1 h and the solvent was removed under reduced pressure. The crude residue was subjected to trituration with Et 2 O to give 0.09 g (75%) of cycloadduct 16 as a white solid: mp 246-247 °C; IR (neat) 2975, 1788, 1755, 1731, and 1662 cm −1; 1 H-NMR (400 MHz, CD 3 CN) δ 8.17 (d, 1H, J = 7.0 Hz), 7.65 (d,1H,J = 7.6 Hz),2H),3H),3H) …”

“…The resulting mixture was heated at reflux for 1 h and the solvent was removed under reduced pressure. The crude residue was subjected to flash silica gel chromatography to give 0.09 g (77%) of cycloadduct 17 as a white solid: mp 176-177 °C; IR (neat) 2987,2953,1755,1736,1655,1455, and 1385 cm −1; 1 H-NMR (400 MHz, CDCl 3 ) δ 8.20 (d, 1H, J = 7.9 Hz), 7.51 (d,1H,J = 7.9 Hz),2H),1H),2H), 3.75 (s, 4H), 3.45-3.40 (m, 2H), 2.90-2.72 (m, 3H), 2.26 (s, 3H), and 1.37 (t, 3H, J = 7.0 Hz); 13 C-NMR (100 MHz, CDCl 3 ) δ 14.0, 20. 4, 25.1, 33.7, 40.9, 49.8, 53.0, 62.9, 85.0, 116.1, 119.6, 125.1, 126.3, 127.9, 134.6, 164.2, 164.9, and 170.3.…”