A convenient route to spiropyrrolidinyl-oxindole alkaloids via C-3 substituted ene-pyrrolidine carbamate radical cyclization

Construction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids

“…[44] Cossy used a very similar approach to access spiro[pyrrolidine-3,3Ј-oxindoles]. [45] Scheme 15. Synthesis of (Ϯ)-horsfiline by radical cyclization (AIBN ϭ 2,2Ј-azoisobutyronitrile)…”

DMD Mediated Formal Synthesis of (±)-Coerulescine

“…1 H NMR (300 MHz, CDCl 3 ): 9.26, 9.17 (1H, brs, H-1), 7.24 (1H, t, J = 8.2 Hz, H-6), 7.17 (1H, d, J = 8.5 Hz, H-4), 7.05 (1H, t, J = 7.6 Hz, H-5), 6.97 (1H, d, J = 7.7 Hz, H-7), 3.78 (1H, m, H-8), 3.56 (1H, m, H-8'), 4.0-3.5 (2H, m, H-10), 2.40 (1H, m, H-11), 2.10 (1H, m H-11'), 1.53, 1.47 (9H, s, CO 2 C[Me] 3 ). 13…”

“…However, when the N2,N9-dicarbomethoxylated β-carboline 6 was treated with 2.5 equiv of DMD, generated in situ from oxone in acetone, oxidation of the C4a=C9a double bond occurs, affording the rearranged oxindole 13 in 90% yield (Scheme 2) 6: Removal of the N-methoxycarbonyl group in 13 with methanolic potassium hydroxide afforded 15 in 74% yield, while removal of the Boc protecting group from 14 with t-BuNH 2 /MeOH [12] gave the N9-Boc protected oxindole 16 in 98% yield. In addition, it is known that treatment of 16 with TFA affords 15 in quantitative yield [13]. Since (±)-coerulescine 1 has been prepared from 15 [4] by treatment with HCHO-AcOH-NaBH 3 CN in 91% yield, the above procedure constitutes a formal total synthesis of 1.…”

“…The resultant crude product was purified by column chromatography eluting with EtOAc/hexane 1:3 to give 4 as a white solid (130 mg, 97%).MP: 194-196°C (EtOAc/hexane). 1 H NMR (400 MHz, DMSO-d 6 ): 10.90 (1H, brs, H9), 7.43 (1H, d, J = 7.3 Hz, H-5), 7.37 (1H, d, J = 7.8 Hz, H-8), 7.10 (1H, t, J = 7.3 Hz, H-7), 7.01 (1H, t, J = 7.8 Hz, H-6), 4.66 (2H, s, H-1), 3.76 (2H, brt, J = 5.4 Hz, H-3), 3.71 (3H, s, CO 2 CH 3 ), 2.73 (2H, brt, J = 13.4 Hz, H-4) 13. C NMR (100 MHz, DMSO-d 6 ): 155.7 (C=O), 136.0 (C-8a), 130.9 (C-9a), 126.6 (C-4b), 120.8 (C-7), 118.5 (C-6), 117.5 (C-5), 111.0 (C-8), 106.8 (C-4a), 52.5 (CO 2 CH 3 ), 41.9 (C-1 and C-3), 20.9 (C4).2,9-Dimethoxycarbonyl-1,2,3,4-tetrahydro-β-carboline (6): To a solution of 3 (100 mg, 0.58 mmol), or 100 mg of 4 (0.434 mmol), in dimethyl carbonate (4-6 mL) were added 0.3 equiv of DBU and the mixture was heated under reflux during 18 h for 3, and during 24 h for 4.…”

Natürliche Pyrrolidinylspirooxindole als Vorlagen für die Entwicklung medizinischer Wirkstoffe

“…[8] 2003 publizierten Carreira und Marti eine Über-sicht zur Synthese von Naturstoffen, die dieses kondensierte heterocyclische System enthalten. [9] Die Autoren diskutierten Zugänge, die auf intramolekularen Mannich-Reaktionen beruhen, [10, 19c] verschiedene Methoden, die eine klassische oxidative Umlagerung von Tetrahydro-b-carbolinen einbeziehen, [11, 19a, b] radikalische Cyclisierungen, [12] intramolekulare Heck-Reaktionen, [13] eine Nitroolefinierungsstrategie, [14] eine neuartige Umlagerung von 3-[(Aziridinyl)(methylthio)methylen]-2-oxindolen [15] und dipolare Cycloadditionen [16] sowie ihre eigene MgI 2 -katalysierte Ringerweiterungsmethode. [17,[20][21][22] Seit Erscheinen dieser Übersicht wurden mehrere alternative Methoden beschrieben.…”