6880
J.-L. Zhou et al. / Tetrahedron 65 (2009) 6877–6881
4.2.6. Dimethyl 2-(5-(tert-butoxycarbonyl)-2-methoxy-6,11-
dihydro-5H-benzo[b]carbazol-11-yl)malonate (2f)
LRMS–ESI (m/z): 460.2 (MþNa)þ; HRMS–ESI (m/z): [MþH]þ calcd
for C24H24NOþ7: 438.1553, found: 438.1563.
At 15 ꢀC, 15 h, colourless oil, 99% yield, 86% ee determined on
HPLC with Daicel Chiralcel OD-H column: hexane/iso-
4.2.10. Dimethyl 2-(1-(tert-butoxycarbonyl)-4,9-dihydro-1H-
benzo[f]indol-4-yl)malonate (2j)
20
propanol¼100:5, flow rate¼0.7 mL/min, 254 nm. [
a]
þ66.0 (c
D
0.955, CHCl3, 85% ee); 1H NMR (300 MHz, CDCl3):
d
7.92 (d,
At 15 ꢀC, 15 h, colourless oil, 99% yield, 26% ee determined on
J¼9.0 Hz), 7.36–7.33 (m, 1H), 7.26–7.24 (m, 1H), 7.17–7.13 (m, 2H),
6.99 (d, J¼2.1 Hz, 1H), 6.79 (dd, J¼9.0, 2.7 Hz, 1H), 5.02 (d, J¼7.2 Hz,
1H), 4.47 (ABd, J¼21.3 Hz, 1H), 4.22 (ABd, J¼21.3 Hz, 1H), 3.81 (s,
3H), 3.62 (d, J¼7.2 Hz, 1H), 3.43 (s, 3H), 3.41 (s, 3H), 1.65 (s, 9H); 13C
HPLC with Daicel Chiralcel AD-H column: hexane/iso-
20
propanol¼100:2, flow rate¼0.7 mL/min, 238 nm. [
a
]
þ4.3 (c 0.935,
D
CHCl3, 83% ee); 1H NMR (300 MHz, CDCl3):
d
7.30–7.15 (m, 5H), 6.12
(d, J¼3.0 Hz, 1H), 4.77 (d, J¼7.5 Hz, 1H), 4.39 (ABd, J¼21.3 Hz, 1H),
NMR (75 MHz, CDCl3):
d 168.55, 168.06, 155.74, 150.41, 136.79,
4.11 (ABd, J¼19.5 Hz, 1H), 3.62 (s, 3H), 3.61 (d, J¼7.5 Hz, 1H), 3.59 (s,
135.57, 135.06, 130.60, 129.12, 128.55, 128.32, 126.93, 126.24, 116.25,
115.87, 112.05, 101.13, 83.90, 58.43, 55.67, 52.49, 52.27, 38.50, 31.24,
28.28; IR (neat) 2977, 2952, 2834,1728,1613,1478,1453,1435,1403,
1370, 1312, 1258, 1220, 1192, 1164, 1135, 1108, 1040, 957, 847,
3H), 1.62 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 168.47, 168.05, 149.30,
135.37, 135.15, 129.33, 129.28, 128.35, 126.73, 126.12, 120.59, 120.06,
110.04, 83.56, 59.95, 52.33, 52.29, 39.90, 29.74, 28.01; IR (neat) 2979,
2952, 2852,1743,1495,1478,1458,1434,1394,1371,1345,1321,1286,
1261,1164,1134,1104,1021, 961, 940, 855, 752, 732 cmꢁ1; LRMS–ESI
(m/z): 422.2 (MþNa)þ; HRMS–ESI (m/z): [MþNa]þ calcd for
C22H25NO6: 422.1580, found: 422.1574.
754 cmꢁ1
;
LRMS–ESI (m/z): 502.3 (MþNa)þ. Anal. Calcd for
C27H29NO7: C, 67.63; H, 6.10; N, 2.92. Found: C, 67.51; H, 6.24; N,
2.72.
4.2.7. Dimethyl 2-(5-(tert-butoxycarbonyl)-3-methoxy-6,11-
dihydro-5H-benzo[b]carbazol-11-yl)malonate (2g)
Acknowledgements
At 5–8 ꢀC, 9 h, colourless oil, 94% yield, 74% ee determined on
We are grateful for the financial support from the National
Natural Science Foundation of China (Nos. 20821002 and
20672131), the Major State Basic Research Development Program
(Grant No. 2009CB825300) and The Chinese Academy of Sciences.
HPLC with Chiral AD-H column: hexane/isopropanol¼100:2, flow
20
rate¼0.7 mL/min, 238 nm. [
a
]
þ60.9 (c 0.85, CHCl3, 73% ee); 1H
D
NMR (300 MHz, CDCl3):
d
7.75 (d, J¼2.4 Hz, 1H), 7.47–7.40 (m, 2H),
7.34–7.31 (m, 1H), 7.25–7.20 (m, 2H), 6.89 (dd, J¼2.4, 8.7 Hz, 1H),
5.09 (d, J¼6.9 Hz, 1H), 4.51 (ABd, J¼21.3 Hz, 1H), 4.29 (ABd,
J¼21.9 Hz, 1H), 3.87 (s, 3H), 3.70 (d, J¼7.2 Hz, 1H), 3.52 (s, 3H), 3.48
Supplementary data
(s, 3H), 1.74 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 168.49, 168.04,
1H NMR, 13C NMR for new compounds, and HPLC spectra for 2a–
2j. Supplementary data associated with this article can be found in
157.24, 150.52, 137.05, 135.65, 135.10, 134.53, 129.09, 128.54, 126.84,
126.19, 121.42, 118.64, 115.81, 111.30, 100.39, 83.89, 58.59, 55.53,
52.46, 52.21, 38.43, 31.27, 28.28; IR (neat) 2926, 2853, 1731, 1686,
1616, 1579, 1492, 1442, 1367, 1310, 1285, 1141, 1034, 848, 805, 764,
737 cmꢁ1; LRMS–ESI (m/z): 502.3 (MþNa)þ; HRMS–ESI (m/z):
[MþNa]þ calcd for C27H29NO7: 502.1842, found: 502.1836.
References and notes
1. (a) Joule, J. A. Indole and its Derivatives. In Science of Synthesis: Houben-Weyl
Methods of Molecular Transformations; Thomas, E. J., Ed.; George Thieme:
Stuttgart, Germany, 2000; Vol. 10, Category 2, Chapters 10 and 13; (b) Bergman,
J.; Pelcman, B. Pure Appl. Chem. 1990, 62, 1967; (c) Rabindran, S. K.; He, H.;
Singh, M.; Collins, E.; Annable, K. I.; Greeberger, L. M. Cancer Res. 1998, 58, 5850;
(d) Sundberg, R. J. In Indoles; Academic: San Diego, CA, 1996; (e) Lounasmaa, M.;
Tolvanen, A. Nat. Prod. Rep. 2000, 17, 175.
4.2.8. Dimethyl 2-(5-(methoxycarbonyl)-6,11-dihydro-5H-
benzo[b]carbazol-11-yl)malonate (2h)
At 15 ꢀC, 7 h, colourless oil, 90% yield, 86% ee determined on
HPLC with Chiral OD-H column: hexane/isopropanol¼95:5, flow
2. For selected examples, see: (a) Takeda, A.; Kamijo, S.; Yamamoto, Y. J. Am. Chem.
Soc. 2000, 122, 5662; (b) Hiroi, K.; Hiratsuka, Y.; Watanabe, K.; Abe, I.; Kato, F.;
Hiroi, M. Synlett 2001, 263; (c) Palacios, F.; Alonso, C.; Amezua, P.; Rubiales, G. J.
Org. Chem. 2002, 67, 1941; (d) Kusama, H.; Takaya, J.; Iwasawa, N. J. Am. Chem.
Soc. 2002, 124, 11592; (e) Wilkie, G. D.; Elliott, G. I.; Blagg, B. S. J.; Wolkenberg,
S. E.; Soenen, D. R.; Miller, M. M.; Pollack, S.; Boger, D. L. J. Am. Chem. Soc. 2002,
124, 11292; (f) Huang, Q.; Campo, M. A.; Yao, T.; Tian, Q.; Larock, R. C. J. Org.
Chem. 2004, 69, 8251; (g) Heureux, N.; Wouters, J.; Marko´ , I. E. Org. Lett. 2005, 7,
5245; (h) Cutri, S.; Diez, A.; Bonin, M.; Micouin, L.; Husson, H.-P. Org. Lett. 2005,
7, 1911; (i) Banwell, M. G.; Ma, X.; Taylor, R. M.; Willis, A. C. Org. Lett. 2006, 8,
4959; (j) Liu, J.; Shen, M.; Zhang, Y.; Li, G.; Khodabocus, A.; Rodriguez, S.; Qu, B.;
Farina, V.; Senanayake, C. H.; Lu, B. Z. Org. Lett. 2006, 8, 3573; (k) Gaddam, V.;
Nagarajan, R. J. Org. Chem. 2007, 72, 3573; (l) Hulcoop, D. G.; Lautens, M. Org.
Lett. 2007, 9, 1761.
20
rate¼0.7 mL/min, 230 nm. [
a]
þ80.5 (c 0.95, CHCl3, 83% ee); 1H
D
NMR (300 MHz, CDCl3):
d 8.15–8.12 (m, 1H), 7.58–7.55 (m, 1H),
7.45–7.42 (m, 1H), 7.34–7.22 (m, 5H), 5.11 (d, J¼6.3 Hz, 1H), 4.48
(ABd, J¼21.6 Hz, 1H), 4.32 (ABd, J¼21.6 Hz, 1H), 4.09 (s, 3H), 3.73 (d,
J¼6.9 Hz, 1H), 3.50 (s, 3H), 3.47 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
168.46, 167.25, 152.38, 135.96, 135.92, 135.35, 134.87, 129.06,
128.60, 127.62, 126.96, 126.29, 123.97, 122.96, 118.25, 116.52, 115.52,
58.26, 53.57, 52.44, 52.23, 38.20, 30.86; IR (neat) 3022, 2956, 1737,
1454, 1440, 1365, 1251, 1146, 1043, 759 cmꢁ1; LRMS–ESI (m/z):
407.7 (MþH)þ, 430.1 (MþNa)þ. Anal. Calcd for C23H21NO6: C, 67.80;
H, 5.20; N, 3.44. Found: C, 67.81; H, 5.12; N, 3.28.
3. For indole Pictet–Spengler-Type annulation reaction: (a) Pictet, A.; Spengler, T.
Ber. Dtsch. Chem. Ges. 1911, 44, 2030; (b) Tatsui, G. J. Pharm. Soc. Jpn. 1928, 48, 92;
(c) Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 95, 1797.
4.2.9. Dimethyl 2-(2-methoxy-5-(methoxycarbonyl)-6,11-dihydro-
5H-benzo[b]carbazol-11-yl)malonate (2i)
4. For indole Friedel–Crafts-Type alkylation reaction: (a) Olah, G. A. In Friedel–
Crafts Chemistry; Olah, G. A., Ed.; Wiley: NewYork, NY, 1973; (b) Roberts, R. M.;
Khalaf, A. A. Friedel–Crafts Chemistry: A Century of Discovery; Marcel Kekker:
New York, NY, 1984; (c) Jørgensen, K. A. Synthesis 2003, 1117; (d) Bandini, M.;
Melloni, A.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2004, 116, 560; Angew.
Chem., Int. Ed. 2004, 43, 550; (e) Bandini, M.; Melloni, A.; Tommasi, S.; Umani-
Ronchi, A. Synlett 2005, 1199; (f) Poulsen, T. B.; Jørgensen, K. A. Chem. Rev. 2008,
108, 2903.
5. For recent enantioselective examples of Pictet–Spengler-Type annulation: (a)
Hino, T.; Nakagawa, M. Heterocycles 1998, 49, 499; (b) Yamada, H.; Kawate, T.;
Matsumizu, M.; Nishida, A.; Yamaguchi, K.; Nakagawa, M. J. Org. Chem. 1998, 63,
6348; (c) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558; (d)
Seayad, J.; Seayad, A. M.; List, B. J. Am. Chem. Soc. 2006, 128, 1086.
At 15 ꢀC, 15 h, colourless oil, 99% yield, 90% ee determined on
HPLC with Chiralcel OD-H column: hexane/isopropanol¼90:10,
20
flow rate¼0.9 mL/min, 280 nm. [
a
d
]
þ69.6 (c 1.7500, CHCl3, 90%
D
ee); 1H NMR (400 MHz, CDCl3):
8.00 (d, J¼9.2 Hz, 1H), 7.42 (dd,
J¼1.6, 7.2 Hz, 1H), 7.33 (d, J¼6.8 Hz, 1H), 7.26–7.19 (m, 2H), 7.06 (d,
J¼2.8 Hz, 1H), 6.87 (dd, J¼2.8, 9.2 Hz, 1H), 5.07 (d, J¼6.8 Hz, 1H),
4.39 (ABd, J¼55.6, 20.4 Hz, 2H), 4.07 (s, 3H), 3.89 (s, 3H), 3.69 (d,
J¼6.8 Hz, 1H), 3.48 (s, 6H); 13C NMR (100 MHz, CDCl3):
d 168.49,
6. For recent enantioselective examples of Intramolecular Friedel–Crafts-Type
alkylation of indoles: (a) Liu, C.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126,
3700; (b) Evans, D. A.; Fandrick, K. R.; Song, H. J. J. Am. Chem. Soc. 2005, 127,
8942; (c) Bandini, M.; Melloni, A.; Piccinelli, F.; Sinisi, R.; Tommasi, S.; Umani-
Ronchi, A. J. Am. Chem. Soc. 2006, 128, 1424; (d) Angeli, M.; Bandini, M.; Garelli,
168.00,156.02,152.29,136.63,135.35,134.96,130.47,129.09,128.59,
128.50, 126.98, 126.30, 116.50, 116.26, 112.25, 101.32, 58.29, 55.68,
53.50, 52.46, 52.26, 38.41, 30.90; IR (neat) 2954, 1736, 1477, 1440,
1403, 1369, 1313, 1261, 1219, 1139, 1108, 1027, 755, 665 cmꢁ1
;