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DOI: 10.1055/s-2008-1042764
A Facile Synthesis of Telisatin A via Microwave-Promoted Annulation and Reformatsky Reaction
Publication History
Publication Date:
12 February 2008 (online)
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Abstract
A facile one-pot synthesis of 2,3-dioxopyrrolo[2,1-a]isoquinolines is reported involving the ring formation of aryl pyruvate derivatives with 3,4-dihydroisoquinolines under basic conditions and utilizing the Reformatsky reaction. Using microwave irradiation, the required compounds were obtained in moderate to good yields.
Key words
microwave - annulation - Reformatsky reaction - dioxopyrrolo[2,1-a]isoquinoline - dioxoaporphine
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References and Notes
Synthesis of 2,3-Dioxopyrrolo[2,1-
a
]isoquinoline 2; Typical Procedure (Conditions C): A mixture of imines 4 (0.1 mmol), aryl pyruvates 5 (0.1 mmol) and NaOMe (0.1 mmol) in DMF (1 mL) was irradiated using microwave. The microwave run time was set to 2 min, with power at 300 W, temperature at 150 °C, and pressure at 100 psi, and the conditions were maintained for 10 min. The reaction was quenched with H2O and extracted with EtOAc, dried (Na2SO4) and evaporated in vacuo to yield a red residue. The residue was purified by column chromatography, affording crystals of 2 after recrystallization in moderate yields (54-78%).
Conditions D: A mixture of imines 4 (0.1 mmol), aryl pyruvates 5 (0.1 mmol), copper powder (0.1 mmol) and zinc powder (0.1 mmol) in DMF (1 mL) was irradiated using microwave. The microwave run time was set to 2 min, with power at 300 W, temperature at 150 °C, and pressure at 100 psi, and the conditions were maintained for 10 min. The reaction was quenched with H2O and extracted with EtOAc, dried (Na2SO4) and evaporated in vacuo to yield a red residue. The residue was purified by column chromatog
raphy, affording crystals of 2 after recrystallization in moderate to good yields (60-82%). Compound 2a: deep-red solid; mp 178-179 °C (EtOAc-hexane). IR (CHCl3): 3020, 1745, 1701, 1580, 1492, 1290 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.09 (t, J = 6.2 Hz, 2 H), 3.33 (s, 3 H), 3.85 (t, J = 6.2 Hz, 2 H), 3.96 (s, 3 H), 6.77 (s, 1 H), 6.95 (s, 1 H), 7.37 (m, 5 H). 13C NMR (50 MHz, CDCl3): δ = 28.6, 36.6, 55.3, 56.2, 111.2, 112.2, 116.8, 127.9, 128.9, 130.2, 130.3, 132.8, 147.9, 153.5, 157.4, 158.3, 165.9, 183.1. MS (EI): m/z (%) = 263 (7), 306 (100), 307 (26), 335 (58) [M+]. HRMS (FAB): m/z [M + H+] calcd for C20H17NO4: 336.1236; found: 336.1234.
Compound 2b: wine-red solid; mp 198-199 °C (EtOAc-hexane; lit
[8c]
176-178 °C). IR (KBr): 1746, 1692, 1575, 1514, 1396, 1290, 1223 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.11 (t, J = 6.2 Hz, 2 H), 3.30 (s, 3 H), 3.89 (t, J = 6.2 Hz, 2 H), 3.95 (s, 3 H), 6.65 (s, 1 H), 6.78 (s, 1 H), 7.31 (m, 3 H), 7.71 (d, J = 7.2 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 28.4, 36.4, 55.2, 56.2, 107.9, 111.2, 111.5, 116.9, 125.9, 128.0, 129.9, 132.5, 132.8, 133.2, 148.3, 153.8, 158.1, 158.4, 181.6. MS (EI): m/z (%) = 306 (83), 334 (100), 384 (34), 386 (31), 413 (31) [M+], 415 (31) [M+ + 2]. HRMS (FAB): m/z [M + H+] calcd for C20H16BrNO4: 414.0341; found: 414.0343.
Compound 2c: deep-red solid; mp 178-179 °C (EtOAc-hexane). IR (CHCl3): 2941, 1742, 1692, 1573, 1472, 1403, 1343, 1299, 1111, 1029 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.10 (t, J = 6.2 Hz, 2 H), 3.30 (s, 3 H), 3.81 (t, J = 6.2 Hz, 2 H), 3.89 (s, 3 H), 3.95 (s, 3 H), 6.82 (s, 1 H), 7.34 (m, 3 H), 7.37 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 21.7, 36.1, 55.2, 61.0, 61.1, 109.1, 119.3, 125.6, 128.0, 128.9, 130.1, 130.2, 147.1, 147.7, 150.5, 151.9, 157.1, 157.9, 183.4. MS (EI): m/z (%) = 237 (37), 336 (100), 365 (60) [M+]. HRMS (FAB): m/z [M + H+] calcd for C21H19NO5: 366.1341; found: 366.1338.
Compound 2d: wine-red solid; mp 153-155 °C (EtOAc-hexane). IR (KBr): 1747, 1703, 1576, 1467, 1425, 1397, 1341, 1109, 1024 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.11 (t, J = 6.6 Hz, 2 H), 3.20 (s, 3 H), 3.75 (t, J = 6.2 Hz, 2 H), 3.81 (s, 3 H), 3.87 (s, 3 H), 6.46 (s, 1 H), 7.20 (m, 2 H), 7.33 (t, J = 7.0 Hz, 1 H), 7.64 (d, J = 7.2 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 21.7, 36.2, 55.2, 61.0, 61.1, 108.6, 119.4, 125.4, 125.8, 128.0, 129.9, 132.3, 132.7, 133.2, 147.0, 150.6, 152.3, 157.9, 158.0, 182.0. MS (EI): m/z (%) = 336 (54), 364 (100), 414 (34), 416 (36), 443 (93) [M+], 445 (95) [M+ + 2]. HRMS (FAB): m/z [M + H+] calcd for C21H18BrNO5: 444.0447; found: 444.0449.