D. Mostowicz et al. / Tetrahedron Letters 45 (2004) 6011–6015
6015
Bailey, P. D.; Morgan, K. M.; Smith, D. I.; Vernon, J. M.
Tetrahedron 2003, 59, 3369–3378.
12. Othoman, M.; Pigeon, P.; Decroix, B. Tetrahedron 1997,
53, 2495–2504.
13. Shoemaker, H. E.; Speckamp, W. N. Tetrahedron 1980,
36, 951–958.
14. Hiemstra, H.; Speckamp, W. N. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 2, pp 1047–1082.
Selected data for 12b; mp 211–212 ꢁC (EtOAc/hexane);
½aꢁ )27.0 (c 1, CH2Cl2); IR (CH2Cl2): 3066, 1755,
D
1708 cmꢂ1
;
1H NMR (500 MHz, CDCl3) (d, ppm): 1.90
and 2.02 (2s, 6H), 2.64 (m, 1H), 2.98 (m, 1H), 3.18 (m,
1H), 3.83 and 3.88 (2s, 6H), 4.21(m, 1H), 5.22 (d, 1H,
J ¼ 2:7 Hz), 5.99 (d, 1H, J ¼ 2:7 Hz), 6.64 and 6.81 (2s,
2H), 7.27–7.36 (m, 5H); 13C NMR (125.76 MHz, CDCl3)
(d, ppm): 20.51, 20.92, 27.50, 36.55, 55.80, 55.95, 69.12,
75.35, 76.91, 110.72, 111.58, 125.97, 127.02, 127.19,
128.11, 128.55, 141.83, 146.90, 148.36, 167.20, 169.29,
169.66; HRMS (LSIMS+) m=z: (M + Hþ) calcd for
C24H26O7N: 440.1709. Found: 440.1713.
15. Bernardi, A.; Micheli, F.; Potenza, D.; Scolastico, C.;
Villa, R. Tetrahedron Lett. 1990, 31, 4949–4952.
16. All compounds gave satisfactory spectroscopic and ana-
lytical data. Typical procedure for 12a and 12b: To a
solution of imide 7 (439 mg, 1 mmol) in dry THF (5 mL),
freshly prepared PhMgBr (2 mmol) in THF (5 mL) was
added at 0 ꢁC, and gradually warmed up to rt. The
resulting mixture was stirred at rt until TLC indicated the
disappearance of 7 (approx. 0.5 h), then was poured into
ice-cold semi-saturated aqueous NaHCO3 (30 mL) and
extracted with t-butyl methyl ether (3 · 20 mL). The
combined extracts were washed with ice-cold water, dried
(MgSO4), filtered and evaporated in vacuo. The crude
hydroxy-lactam 8 obtained was dissolved in dry MeCN
(5 mL), and after cooling to 0 ꢁC, dimethylaminopyridine
(135 mg, 1.1 mmol) and Ac2O (378 lL, 4 mmol) were
added. The cooling bath was removed and stirring was
continued at rt for 2 h, then BF3ÆEt2O (507 lL, 4 mmol)
was added in one portion. The mixture was stirred at rt for
10 min then cooled to 0 ꢁC, quenched with saturated
aqueous NaHCO3 (5 mL) and extracted with CH2Cl2
(3 · 20 mL). The combined extracts were washed with
water (2 · 20 mL), dried (MgSO4), filtered and evaporated
in vacuo. The product was purified by flash column
chromatography on silica gel (EtOAc/hexane ¼ 1:1) to
yield pyrroloisoquinolines 12a and 12b as a 3:1 mixture in
82% yield. The mixture of 12a and 12b (220 mg, 0.5 mmol)
obtained was dissolved at rt in dry MeOH (10 mL)
containing MeONa (16 mg, 0.3 mmol). The solution was
stirred until TLC indicated the disappearance of the
substrate (ꢀ0.5 h), then the reaction was quenched by the
addition of a small piece of dry ice and evaporated in
vacuo. The product was purified by flash column chro-
matography on silica gel (EtOAc/hexane/MeOH, 7.5:4:1)
to give 10a (107 mg, 60% yield) and 10b (32 mg, 18%
yield). Dihydroxy-pyrroloisoquinolines 10a and 10b were
acetylated (Py/Ac2O) and crystallized to yield analytically
pure acetates 12a and 12b.
Typical procedure for the preparation of pyrroloisoquin-
olines 23a and 23b: To a stirred solution of the crude
reaction mixture of 10a and 10b obtained as above from
12a, 12b (220 mg, 0.5 mmol), imidazole (102 mg, 1.5 mmol)
in DMF (3 mL) was added followed by tert-butyldimeth-
ylchlorosilane (150 mg, 1 mmol) and the mixture was
stirred for 24 h at room temperature. The mixture was
poured into water, extracted with ethyl acetate
(2 · 10 mL), washed with water and brine then dried over
MgSO4, and evaporated under reduced pressure. The
residue was purified by flash column chromatography
(EtOAc/hexane, 35:65) to give 23a, (167 mg, 71% yield)
and 23b (54 mg, 23% yield).
Selected data for 23a: oil; ½aꢁ )120.2 (c 1.1, CH2Cl2); IR
D
(CH2Cl2): 3683, 1705, 1608 cmꢂ1
.
1H NMR (500 MHz,
CDCl3) (d, ppm): 0.14 and 0.20 (2s, 6H), 0.93 (s, 9H), 1.64
(d, 1H, J ¼ 10:0 Hz), 2.45 (m, 1H), 2.72 (m, 1H), 3.57 (m,
1H), 3.71 (m, 1H), 3.86 and 3.98 (2s, 6H), 4.23 (d, 1H,
J ¼ 8:3 Hz), 4.57 (dd, 1H, J ¼ 8:3, 10.0 Hz), 6.62 and 7.34
(2s, 2H), 7.16–7.20 (m, 2H), 7.29–7.38 (m, 3H); 13C NMR
(125.76 MHz, CDCl3) (d, ppm): 18.37, 25.76, 26.26, 37.75,
55.96, 56.41, 66.39, 76.60, 82.10, 108.94, 111.35, 126.6,
127.54, 128.21, 128.86, 132.85, 137.77, 147.87, 148.53,
170.24. HRMS (EI) m=z: (Mþ) calcd for C26H35O5NSi:
469.2287. Found: 469.2285.
Selected data for 23b: mp 216–218 ꢁC; ½aꢁ )4.4 (c 1.2,
D
1
CH2Cl2); IR (CH2Cl2): 3559, 1705, 1611 cmꢂ1. H NMR
(500 MHz, CDCl3) (d, ppm): 0.15 and 019 (2s, 6H), 0.88 (s,
9H), 2.00 (d, 1H, J ¼ 3:9 Hz), 2.27 (m, 1H), 2.89 (m, 1H),
3.10 (m, 1H), 3.87 and 3.88 (2s, 6H), 4.11 (m, 1H), 4.20 (d,
1H, J ¼ 3:1), 4.55 (dd, 1H, J ¼ 3:1, 3.9 Hz), 6.67 and 7.08
(2s, 2H), 7.22–7.29 (m, 3H), 7.35–7.39 (m, 2H); 13C NMR
(125.76 MHz, CDCl3) (d, ppm): 18.11, 25.64, 27.46, 35.78,
55.87, 56.27, 69.54, 77.70, 80.89, 110.61, 112.34, 126.67,
127.57, 127.64, 128.23, 128.75, 142.75, 147.50, 148.61,
171.03. HRMS (EI) m=z: (Mþ) calcd for C26H35O5NSi:
469.2287. Found: 469.2279.
Selected data for 12a; mp 230–231 ꢁC (ethanol); ½aꢁ )57.2
D
1
(c 2.4, CH2Cl2); IR (CH2Cl2): 3055, 1753, 1713 cmꢂ1; H
NMR (500 MHz, CDCl3) (d, ppm): 1.86 and 2.13 (2s, 6H),
2.47 (m, 1H), 2.82 (m, 1H), 3.43 (m, 1H), 3.87 (m, 1H),
3.88 and 3.91 (2s, 6H), 5.72 (d, 1H, J ¼ 6:8 Hz), 5.99 (d,
1H, J ¼ 6:8 Hz), 6.65 and 7.14 (2s, 2H), 7.07–7.10 (m, 2H),
7.27–7.34 (m, 3H); 13C NMR (125.76 MHz, CDCl3) (d,
ppm): 20.60, 20.67, 26.12, 37,59, 55.94, 56.20, 67.86, 74.59,
78.27, 109.19, 111.68, 126.63, 127.42, 128.02, 128.31,
131.06, 138.45, 147.75, 147.68, 166.18, 169.82, 170.17;
HRMS (EI) m=z: (Mþ) calcd for C24H25O7N: 439.1631.
Found: 439.1642.
17. The crystallographic data for compound 12a has been
deposited with the Cambridge Crystallographic Data
Center as supplementary publication number CCDC
222580. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK [fax: +44(0)-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk].
18. Saito, T.; Suzuki, T.; Morimoto, M.; Akiyama, C.;
Ochiai, T. J. Am. Chem. Soc. 1998, 120, 11633–
11644.