C. B. de Koning et al. / Tetrahedron Letters 45 (2004) 1117–1119
1119
Na2CO3 solution (3.6 cm3) was then added to the reaction
mixture, which was stirred at rt for a further 5 min before
being heated at reflux for 2 d. The mixture was cooled to rt
and quenched with H2O (20 cm3) after which the organic
material was extracted with CH2Cl2 (3 · 30 cm3) and the
solvent was evaporated under reduced pressure. The crude
product was subjected to column chromatography (5–10%
EtOAc–hexane) to afford the product 9 as a yellow solid
(0.313 g, 96%). mp 141–142 ꢁC (Found: Mþ, 387.1830.
C25H25NO3 requires 387.1834); mmax (CHCl3)/cmꢁ1 1725
and 1660 (C@O) and 1616, 1599, 1559 (ArC@C);
dH(300 MHz; CDCl3; Me4Si) 1.29 (9H, s, Boc), 2.10 (3H,
s, CH3), 2.72–2.82 (2H, m, CH2), 2.96–3.00 (2H, m, CH2),
6.78 (1H, d, J ¼ 7:8 Hz, ArH), 7.08–7.11 (1H, m, ArH),
7.25–7.45 (4H, m, 4 · ArH), 7.57 (1H, d, J ¼ 7:4 Hz, ArH),
8.29 (1H, d, J ¼ 8:3 Hz, ArH) and 9.70 (1H, s, CHO); dC
(75 MHz; CDCl3) 9.3 (ArCH3), 20.2 (CH2), 27.1 (CH2),
27.8 (Boc), 83.9 (C(Me)3), 115.7 (CH), 119.1 (CH), 120.7
(C), 123.0 (CH), 125.4 (CH), 126.7 (CH), 126.9 (CH),
128.0 (CH), 129.8 (C), 130.2 (CH), 134.5 (C), 135.5 (C),
136.5 (C), 137.8 (C), 146.5 (C), 149.5 (CO) and 192.9
(CHO); m=z (EI) 387 (Mþ, 47%), 287 (83), 273 (30), 272
(100), 270 (32), 269 (32), 258 (50), 130 (29) and 57 (62).
16. de Koning, C. B.; Michael, J. P.; Rousseau, A. L. J. Chem.
Soc., Perkin Trans. 1 2000, 787–797.
Acknowledgements
This work was supported by the National Research
Foundation (NRF, GUN 2053652), Pretoria, and the
University of the Witwatersrand (University Research
Council).
References and notes
1. Bentley, K. W. Nat. Prod. Rep. 2003, 20, 342–365.
2. Balasubramanian, M.; Scriven, E. F. V. Isoquinoline and
its derivatives. In Second Supplements to the 2nd Edition of
Rodd’s Chemistry of Carbon Compounds, Vol IV: Hetero-
cyclic Compounds, Parts F and G; Sainsbury, M., Ed.;
Elsevier: Amsterdam, 1998; pp 163–216.
3. Andreae, S. Isoquinolines (Benzo[b]pyridines). In Het-
eroarenes II, Part 1; Kreher, R.P., Ed.; Georg Thieme:
Stuttgart, 1991; Vol. E7a, pp 571–740.
4. Kathawala, F. G. Isoquinolines; New York: Wiley, 1990.
5. Scott, J. D.; Williams, R. M. Chem. Rev. 2002, 102, 1669–
1730.
6. For an extensive review see: Bringmann, G.; Pokorny, F.
In The Alkaloids. Chemistry and Pharmacology; Cordell,
G. A., Ed.; Academic: New York, 1995; Vol. 46, pp 127–
271.
17. de Koning, C. B.; Michael, J. P.; Rousseau, A. L. J. Chem.
Soc., Perkin Trans. 1 2000, 1705–1713.
7. de Koning, C. B.; van Otterlo, W. A. L.; Michael, J. P.
Tetrahedron 2003, 59, 8337–8345.
18. 12-Methyl-6-phenylindolo[2,1-a]isoquinoline 10b: KOBut
(0.119 g, 1.06 mmol), was added to 5 (0.105 g, 0.33 mmol)
dissolved in dry DMF (10 cm3). The mixture was heated
under N2 at 80 ꢁC while being irradiated with a high
pressure mercury lamp through a quartz filter for 10 min.
The reaction mixture was quenched with H2O (50 cm3)
and extracted with Et2O (3 · 50 cm3). The organic layer
was dried (MgSO4) and filtered. It was then evaporated
and subjected to column chromatography (5–20% EtOAc–
hexane) to afford the product 10b (0.076 g, 65%) as a
yellow solid. mp 96–98 ꢁC (Found: Mþ, 357.1518.
C27H19N requires 357.1518); mmax (CHCl3)/cmꢁ1, 1594
and 1551 (ArC@C), 1466, 1451 and 1388; dH (300 MHz;
CDCl3; Me4Si) 2.55 (3H, s, CH3), 6.53 (1H, s, Ar 5-H),
6.58 (1H, d, J ¼ 8:6 Hz, ArH), 6.95–7.00 (1H, m, ArH),
7.29–7.34 (1H, m, ArH), 7.52–7.65 (8H, m, 8 · ArH), 7.81
(1H, d, J ¼ 8:0 Hz, ArH), 7.90 (1H, d, J ¼ 8:4 Hz, ArH),
7.94 (1H, d, J ¼ 7:9 Hz, ArH) and 8.32 (1H, d, J ¼ 8:3 Hz,
ArH); dC (75 MHz; CDCl3) 14.5 (ArCH3), 108.2 (C), 111.3
(CH), 114.0 (CH), 118.3 (CH), 120.8 (CH), 121.7 (CH),
124.1 (CH), 125.1 (CH), 125.5 (CH), 127.9 (CH), 127.9
(CH), 128.3 (CH), 128.9 (CH), 128.9 (C), 129.0 (CH),
129.2 (CH), 129.7 (C), 131.2 (C), 131.6 (C), 132.9 (C),
137.0 (C) and 139.1 (C); m=z (EI) 358 (36%), 357 (Mþ,
100), 356 (54), 354 (21), 278 (11) and 171 (11).
8. de Koning, C. B.; Michael, J. P.; van Otterlo, W. A. L.
Synlett 2002, 2065–2067.
9. de Koning, C. B.; Michael, J. P.; van Otterlo, W. A. L.
J. Chem. Soc., Perkin Trans. 1 2000, 799–811.
10. For an approach to a 1,2-dihydroisoquinoline ring system
using ruthenium-mediated isomerization and ring-closing
metathesis see: van Otterlo, W. A. L.; Pathak, R.; de
Koning, C. B. Synlett 2003, 1859–1861.
11. (a) Orito, K.; Harada, R.; Uchiito, S.; Tokuda, M. Org.
Lett. 2000, 2, 1799–1801; (b) Meyers, A. I.; Sielecki, T. M.
J. Am. Chem. Soc. 1991, 113, 2789–2790.
12. Ambros, R.; Schneider, M. R.; von Angerer, S. J. Med.
Chem. 1990, 33, 153–160.
13. For example, see: de Koning, C. B.; Michael, J. P.;
Nhlapo, J. M.; Pathak, R.; van Otterlo, W. A. L. Synlett
2003, 705–707.
14. From the ongoing Ph.D of R. Pathak, University of the
Witwatersrand.
15. t-Butyl-2-(2-formyl-3,4-dihydro-1-naphthalenyl)-3-methyl-
1H-indole-1-carboxylate 9: A solution of 1-bromo-3,4-
dihydronaphthalene-2-carbaldehyde 8 (0.20 g, 0.84 mmol)
in DME (4 cm3) was deoxygenated by passing N2 through
the mixture for 5 min. The solution was then added to
Pd(PPh3)4 (10 mol %, 0.096 g, 0.083 mmol) and stirred
under N2 atmosphere for 10 min at rt. A solution of 1-(t-
19. Zhang, P.; Liu, R.; Cook, J. M. Tetrahedron Lett. 1995,
36, 3103–3106.
butoxycarbonyl)-3-methyl-1H-indol-2-ylboronic acid
7
(1.5 equiv, 0.346 g, 1.26 mmol) in Et2O (1.5 cm3) was
added to the reaction mixture, which was deoxygenated
by bubbling N2 through the solution. Presumably the
Et2O evaporated in the process. The mixture was then
stirred for a further 10 min. A deoxygenated 2 M aqueous
20. Choi, D.-S.; Huang, S.; Huang, M.; Barnard, T. S.;
Adams, R. D.; Seminario, J. M.; Tour, J. M. J. Org.
Chem. 1998, 63, 2646–2655.
21. Gilow, H. M.; Burton, D. E. J. Org. Chem. 1981, 46,
2221–2225.