References and Notes
1
Lounasmaa M.
Somersalo P. In
Progress in the Chemistry of Organic Natural Products
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Herz W.
Grisebach H.
Kirby GW.
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1979.
p.1-45
2
Husson H.-P. In
The Alkaloids
Vol. 26:
Brossi A.
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1985.
Chap. 1.
3
Franck RW. In
Progress in the Chemistry of Organic Natural Products
Vol. 50:
Herz W.
Griesbach H.
Kirby GW.
Tamm C.
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1986.
p.27-56
4
Remers WA.
Dorr RT. In
Alkaloids: Chemical and Biological Perspectives
Vol. 6:
Pelletier SW.
Wiley;
New York:
1988.
Chap. 1.
5
Szantay C. In
The Alkaloids
Vol. 50:
Cordell GA.
Academic Press;
London:
1998.
Chap. 10.
6
Lounasmaa M.
Hankinen P.
Westersund M. In
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Vol. 52:
Cordell GA.
Academic Press;
London:
1999.
Chap. 2.
7a
Daly JW.
Spande TF. In
Alkaloids: Chemical and Biological Perspectives
Vol. 4:
Pelletier SW.
Wiley;
New York:
1986.
p.1-274
7b
Foder GB.
Colasanti B. In
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1985.
p.1-90
8a
Boger DL.
Weinreb SM.
Hetero Diels-Alder Methodology in Organic Synthesis
Academic Press;
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1987.
8b
Buomora P.
Olsen JC.
Oh T.
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6099
8c
Carruthers W. In
Cycloaddition Reactions in Organic Synthesis
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9a
Boger DL.
Combining C-C π-Bonds, In Comprehensive Organic Chemistry
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Paquette LA.
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9b
Ho T.-L.
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10
Ziegler FE.
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Chap. 7.3.
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Beifuss U.
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14
General Procedure for the Intramolecular Domino Knoevenagel Hetero-Diels-Alder Reaction:Method A: To a refluxing solution of activated ketones or 1,3-diones (1 mmol) in anhyd toluene (10 mL), the aldehydes 1a or 1b (1 mmol) was added and the reaction mixture was refluxed until the disappearance of the starting material as evidenced by TLC. After completion of the reaction, the solvent was evaporated in a rotary evaporator and the residue was subjected to flash column chromatography using hexane-EtOAc mixture.
Method B: A solution of activated ketones or 1,3-diones (1 mmol) and the corresponding aldehyde (1 mmol) in anhyd toluene was irradiated with microwave (600 W power) until the TLC showed the disappearance of the starting material. After removal of the solvent, the crude reaction mixture was subjected to flash column chromatography (silica gel) to yield the product.
Method C: A mixture of activated ketones or 1,3-dione (1 mmol), the corresponding aldehyde (1 mmol) and K-10 montmorillonite clay (1.0 g) was thoroughly ground in a mortar. The reaction mixture was irradiated with microwave until the disappearance of the starting material as evidenced by TLC. After completion of the reaction, the montmorillonite clay was separated by filtration after extracting the product with CH2Cl2 (2 × 15 mL). Removal of the solvent and purification of the crude reaction mixture by flash column chromatography gave the pure product.
3a,10b-
cis
-3,11,11-Trimethyl-1-phenyl-3a,10,10b,11-tetrahydroindolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[2,3-
c
]pyrazole (
3a): pale pink solid; mp 150-152 °C. IR (KBr): 1654 cm-1. 1H NMR (CDCl3): δ = 1.51 (s, 3 H), 1.56 (s, 3 H), 2.36 (s, 3 H), 3.16-3.20 (m, 1 H, Hb), 3.99 (dd, J = 7.2, 9.7 Hz, 1 H), 4.23 (dd, J = 8.0, 9.7 Hz, 1 H), 4.38 (d, J = 6.8 Hz, 1 H, Ha), 6.38 (s, 1 H), 7.04-7.70 (m, 9 H). 13C NMR: δ = 13.65, 25.47, 26.27, 31.64, 43.51, 51.60, 80.65, 94.11, 95.00, 109.34, 119.45, 120.56, 120.79, 120.99, 125.53, 128.97, 132.12, 132.51, 138.74, 143.71, 147.26, 158.19. MS: m/z = 369 [M+]. Anal. Calcd for C24H23N3O: C, 78.02; H, 6.27; N, 11.37. Found: C, 78.23; H, 6.41; N, 11.21.
3a,10b-
trans
-3,11,11-Trimethyl-1-phenyl-3a,10,10b,11-tetrahydroindolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[2,3-
c
]pyrazole (
4a): pink solid; mp 163-164 °C. IR (KBr): 1650 cm-1. 1H NMR (CDCl3): δ = 1.56 (s, 3 H), 1.61 (s, 3 H), 2.32 (s, 3 H), 3.21-3.25 (m, 1 H, Hb), 4.10 (dd, J = 7.0, 9.8 Hz, 1 H), 4.32 (dd, J = 8.0, 9.8 Hz, 1 H), 4.56 (d, J = 12.0 Hz, 1 H, Ha), 6.26 (s, 1 H), 7.15-7.85 (m, 9 H). 13C NMR: δ = 14.27, 24.15, 27.32, 32.65, 40.26, 53.15, 82.75, 96.23, 98.15, 110.56, 120.12, 121.55, 122.78, 124.56, 126.78, 128.16, 135.26, 137.25, 145.10, 148.21, 159.10. MS: m/z = 369 [M+].
4,5-Dihydro-5-(3-methylbut-2-enyl)-3-methyl-1-phenylindolo[3,2-
b
]pyrano[2,3-
c
]pyrazole (
5a): pale pink solid; mp 178-180 °C. IR (KBr): 1660 cm-1. 1H NMR (CDCl3): δ = 1.62 (s, 2 H), 1.73 (s, 3 H), 1.89 (s, 3 H), 2.28 (s, 3 H), 4.87 (d, J = 6.3 Hz, 2 H), 5.19 (t, J = 6.3 Hz, 1 H), 7.11-8.01 (m, 9 H). 13C NMR: δ = 13.24, 18.39, 25.66, 41.67, 110.10, 117.57, 119.16, 120.63, 121.16, 123.55, 123.86, 124.75, 127.05, 127.93, 128.86, 130.49, 132.36, 135.25, 138.72, 140.21, 150.06, 162.16. MS: m/z = 369 [M+]. Anal. Calcd for C24H23N3O: C, 78.02; H, 6.27; N, 11.37. Found: C, 78.19; H, 6.34; N, 11.45.
7a,14b-
cis
-7,7-Dimethyl-7a,8,14,14b-tetrahydro-indolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[1,2-
b
]indan-1-one (
11a): purple solid; mp 166-168 °C. IR (KBr): 1715 cm-1. 1H NMR (CDCl3): δ = 1.32 (s, 3 H), 1.35 (s, 3 H), 3.24-3.27 (m, 1 H, Hb), 3.69 (dd, J = 6.7, 9.8 Hz, 1 H), 3.90 (dd, J = 8.1, 9.8 Hz, 1 H), 4.21 (d, J = 6.8 Hz, 1 H, Ha), 6.13 (s, 1 H), 6.91-7.37 (m, 8 H). 13C NMR: δ = 23.37, 23.53, 35.91, 40.79, 47.28, 56.37, 109.07, 110.00, 117.72, 120.51, 121.93, 122.21, 122.30, 123.19, 123.83, 124.03, 125.81, 127.92, 130.10, 135.77, 193.51. MS: m/z = 341 [M+]. Anal. Calcd for C23H19NO2: C, 80.92; H, 5.61; N, 4.10. Found: C, 81.11; H, 5.76; N, 4.22.
7a,14b-
trans
-7,7-Dimethyl-7a,8,14,14b-tetrahydroindolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[1,2-
b
]indan-1-one (
12a): purple solid; mp 170-172 °C. IR (KBr): 1721 cm-1. 1H NMR (CDCl3): δ = 1.40 (s, 3 H), 1.43 (s, 3 H), 3.46-3.50 (m, 1 H, Hb), 3.84 (dd, J = 7.0, 10.0 Hz, 1 H), 4.20 (dd, J = 8.2, 10.0 Hz, 1 H), 4.53 (d, J = 12.2 Hz, 1 H, Ha), 6.10 (s, 1 H), 6.33-7.21 (m, 8 H). 13C NMR: δ = 22.92, 23.26, 37.20, 44.82, 49.17, 59.70, 110.94, 112.14, 119.26, 121.52, 122.50, 122.99, 123.08, 124.72, 125.92, 127.70, 128.81, 129.09, 130.23, 134.66, 136.16, 140.38, 200.17. MS: m/z = 341 [M+].
11,12-Dihydro-11-(3-methylbut-2-enyl) indolo[3,2-
b
]pyrano[2,1-
c
]indan-1-one (
13a): purple solid; mp 183-185 °C. IR (KBr): 1725 cm-1. 1H NMR (CDCl3): δ = 1.59 (s, 3 H), 1.63 (s, 3 H), 1.69 (s, 2 H), 4.37 (d, J = 5.7 Hz, 2 H), 5.32 (t, J = 5.7 Hz, 1 H), 6.74-7.03 (m, 8 H). 13C NMR: δ = 20.52, 23.93, 24.02, 43.41, 107.75, 110.66, 111.23, 119.82, 120.79, 120.97, 121.49, 121.87, 122.77, 124.22, 126.99, 127.71, 128.88, 132.92, 133.16, 134.98, 135.26, 139.18, 198.10. MS: m/z = 341 [M+]. Anal. Calcd for C23H19NO2: C, 80.92; H, 5.61; N, 4.10. Found: C, 81.07; H, 5.72; N, 4.23.
6a,13b-
cis
-3,3-Dimethyl-6-phenyl-6a,7,13,13b-tetrahydroindolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[1,2-
b
]cyclohexan-1-one (
19b): yellow solid; mp 162-163 °C. IR (KBr): 1734 cm-1. 1H NMR (CDCl3): δ = 1.15 (s, 3 H), 1.19 (s, 3 H), 1.93 (s, 2 H), 2.55 (s, 2 H), 3.49-3.52 (m, 1 H, Hb), 3.79 (dd, J = 7.3, 10.1 Hz, 1 H), 3.85 (dd, J = 8.2, 10.1 Hz, 1 H), 4.37 (d, J = 6.8 Hz, 1 H, Ha), 5.22 (d, J = 9.8 Hz, 1 H), 5.91 (s, 1 H), 6.37-7.19 (m, 9 H). 13C NMR: δ = 27.35, 27.90, 30.45, 37.00, 44.52, 48.73, 50.22, 53.77, 70.82, 113.14, 114.77, 115.24, 120.78, 122.37, 124.67, 125.05, 125.31, 127.92, 128.18, 129.42, 130.02, 130.83, 132.56, 133.82, 137.28, 193.72. MS: m/z = 383 [M+]. Anal. Calcd for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.61; H, 6.43; N, 3.52.
6a,13b-
trans
-3,3-Dimethyl-6-phenyl-6a,7,13,13b-tetrahydroindolo[2,1-
a
]pyrrolo[4′,3′:4,5]pyrano[1,2-
b
]cyclohexan-1-one (
20b): yellow solid; mp 155-157 °C. IR (KBr): 1735 cm-1. 1H NMR (CDCl3): δ = 1.20 (s, 3 H), 1.22 (s, 3 H), 1.84 (s, 2 H), 2.37 (s, 2 H), 3.42-3.44 (m, 1 H, Hb), 3.81 (dd, J = 7.0, 10.0 Hz, 1 H), 3.92 (dd, J = 8.3, 10.0 Hz, 1 H), 4.45 (d, J = 11.5 Hz, 1 H, Ha), 5.30 (d, J = 9.8 Hz, 1 H), 6.12 (s, 1 H), 6.45-7.01 (m, 9 H). 13C NMR: δ = 25.34, 26.07, 32.00, 35.58, 41.87, 48.23, 50.58, 56.81, 71.52, 119.19, 121.00, 121.82, 122.77, 123.45, 124.16, 125.41, 126.45, 127.78, 130.09, 131.70, 134.99, 135.68, 140.25, 143.39, 147.55, 192.85. MS: m/z = 383 [M+].
10-Cinnamyl-3,3-dimethyl-3,4,10,11-tetrahydro-indolo[3,2-
b
]chromen-1 (2
H
)-one (
21b): yellow solid; mp 160-162 °C. IR (KBr): 1727 cm-1. 1H NMR (CDCl3): δ = 1.21 (s, 3 H), 1.23 (s, 3 H), 1.69 (s, 2 H), 1.73 (s, 2 H), 2.41 (s, 2 H), 4.25 (d, J = 6.0 Hz, 2 H), 4.78 (dt, J = 6.0, 6.3 Hz, 1 H), 5.65 (d, J = 6.3 Hz, 1 H), 6.70-7.13 (m, 9 H). 13C NMR: δ = 22.57, 28.50, 28.91, 32.05, 43.00, 44.53, 52.69, 116.13, 120.65, 121.15, 121.58, 124.54, 124.90, 127.39, 127.65, 128.19, 129.09, 129.81, 131.95, 134.62, 136.61, 138.22, 139.05, 142.12, 192.37. MS: m/z = 383 [M+]. Anal. Calcd for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.58; H, 6.64; N, 3.53.