An expeditious synthesis of 2,2'-Biindolyl

Synlett

Volumn 1995, Issue 8, 1995, Pages 859-860

  Shin, Kogyoku ^a   Ogasawara, Kunio ^a  

^a TOHOKU UNIVERSITY   (Japan)

Author keywords

2,2' biindolyl; cross coupling reaction; homo coupling reaction; indole synthesis; palladium catalyst

Indexed keywords

EID: 33750699807     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-1995-5110     Document Type: Article

References (14)

1. Bergman, J.; Koch, E.; Pelcman, B. Tetrahedron 1995, 51, 5631 and references cited therein
2. A pertinent review, see: Bergman, J. Studies in Natural Products Chemistry 1988, 1, 3.
3. Capuano, L.; Drescher, S.; Hammerer, V.; Hanisch, M. Chem. Ber. 1988, 121, 2259.
4. Pereira, E. R.; Prudhomme, M. Tetrahedron Lett. 1995, 36, 2477.
5. A recent review on indole ring synthesis, see: Gribble, G. W. Contemporary Organic Synthesis 1994, 1, 145.
6. Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles 1986, 24, 31.
7. Sonogashira, K.; Tohda, Y.; Hagiwara, N-Tetrahedron Lett. 1975, 4467.
8. Wender, P. A.; McKinney, J. A.; Mukai, C. J. Am. Chem. Soc. 1990, 112, 5369
9. Takano, S.; Sugihara, T.; Ogasawara, K. Synlett 1990, 451.
10. Takano, S.; Murakami, T.; Samizu, K.; Ogasawara, K. Heterocycles 1994, 39, 67.
11. Example of utilization of this indole formation reaction5 in natural product synthesis, see:
12. Takano, S.; Sato, T.; Inomata, K.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1991, 463.
13. Shin, K.; Ogasawara, K. Chem. Lett. 1995, 289.
14. Typical experimental procedure: Formation of the carbamate (6)-To a stirred solution of iodoaniline (5) (15.6 g, 71.2 mmol) in pyridine (100 ml) was added dropwise ethyl chlorocarbonate (8.17 ml, 85.4 mmol) at 0 C. After 40 min at the same temperature, the solvent was evaporated under vacuum and the residue was dissolved in ether. The ethereal solution was washed with 5% HC1, 5% NaHCOs, brine, dried over MgS04, and evaporated under reduced pressure. The residue was chromatographed on silica gel (300 g, elution: Et20/hexane, 1:5) to give the carbamate (6) (19.98 g, 96%) as colorless crystals, mp 47-48 C (hexane). IR (film): v=3390, 1737 cm'1; 'H NMR (90 MHz, CDC13): S=1.33 (t, 3H, 7=7.1 Hz), 4.24 (q, 2H, 7=7.1 Hz), 6.86 (td, 1H, 7=1.7, 7.8 Hz), 6.92 (br s, 1H), 7.32 (m, 1H), 7.75 (dd, 1H, 7=1.5, 7.8 Hz), 8.05 (dd, 1H, 7=1.5, 8.3 Hz). MS:m/z=291 (M+), 136 (100%). HRMS: m/z calc, for C9H10NOJ 290.9756, found 290.9759. Cross-coupling between the carbamate (6) and trimethylsilylacetylene-A solution of the carbamate (6) (2 g, 6.87 mmol) and trimethylsilylacetylene (1.09 ml, 7.56 mmol) in triethylamine (45 ml) was refluxed for 45 min in the presence of PdCl, (PPh3), (96.5 mg, 2 mol%) and Cul (6.5 mg, 0.5 mol%). The mixture was diluted with ether and washed with brine, dried over MgS04, and evaporated under reduced pressure. The residue was chromatographed on silica gel (150 g, elution: Et, 0/hexane, 1:8) to give the arylacetylene (7) (1.70 g, 95%) as a pale yellow oil. IR (film): v=3398, 2150, 1742 cm'1; 'H NMR (300 MHz, CDC13): 6=0.30 (s, 9H), 1.33 (t, 3H, 7=7.1 Hz), 4.25 (q, 2H, 7=7.1 Hz), 6.96 (td, 1H, 7=1.1, 7.7 Hz), 7.31 (td, 1H, 7=1.5, 8.4 Hz), 7.38 (dd, 1H, 7=1.5, 7.7 Hz), 7.44 (br s, 1H), 8.13 (d, 1H, 7=8.4 Hz). MS:m/z=261 (M+, 100%). HRMS: m/z calc, for C14H19NO, Si 261.1185, found 261.1205. Desilylation of the silylacetylene (7)-To a stirred solution of 7 (897 mg, 3.44 mmol) in MeOH (25 ml) was added K2C03 (571 mg, 4.12 mmol) at 0 C and the stirring was continued for 40 min at room temperature. The mixture was diluted with water and extracted with ether. The organic layer was separated and washed with brine, dried over MgS04, and evaporated under reduced pressure. The residue was chromatographed on silica gel (60 g, elution: Et, 0/hexane, 1:7) to give the terminal acetylene (8) (630 mg, 97%) as colorless needles, mp 52-53 C (Et, 0-hexane). IR (Nujol): v=3400, 3284, 2102, 1732 cm'1; 1/8 NMR (300 MHz, CDC13): 5=1.33 (t, 3H, 7=7.1 Hz), 3.48 (s, 1H), 4.25 (q, 2H, 7=7.1 Hz), 6.98 (td, 1H, 7=1.1, 7.3 Hz), 7.28-7.50 (m, 3H), 8.16 (d, 1H, 7=8.4 Hz). MS:m/z=189 (M+, 100%). HRMS: m/z calc, for CnHnNO, 189.0790, found 189.0805. Homo-coupling of the acetylene (8)-A solution of 8 (234 mg, 1.24 mmol) and Et3N (0.52 ml, 3.72 mmol) in DMF (4 ml) was stirred under atmosphere of oxygen for 4 h at room temperature in the presence of PdCl, (PPh3), (13.1 mg, 1.5 mol%) and Cul (4.7 mg, 2 mol%). The mixture was diluted with water and extracted with ether. The extract was washed with 5% NaHC03, brine, dried over MgS04, and evaporated under reduced pressure. The residue was chromatographed on silica gel (10 g, elution: Et, 0/hexane, 1:4) to give the diacetylene (9) (220 mg, 94%) as colorless needles, mp 130.5-131.5 C (CH2Cl,-hexane). IR (Nujol): v=3334, 2146, 1707 cm'1; 'H NMR (300 MHz, CDC13): 8=1.36 (t, 6H, 7=7.1 Hz), 4.28 (q, 4H, 7=7 Hz), 7.02 (td, 2H, 7=1.1, 7.7 Hz), 7.31 (br s, 2H), 7.39 (td, 2H, 7=1.5, 8.4 Hz), 7.49 (dd, 2H, 7=1.5, 7.7 Hz), 8.18 (d, 2H, 7=8.4 Hz). MS:m/z=376 (M+), 330 (100%). HRMS: m/z calc, for C2, H, 0N, O4 376.1423, found 376.1433. 2, 2'-Biindolyl (1)-To a solution of NaOEt (prepared in situ from Na, 459 mg, 20.0 atom) in EtOH (35 ml) was added 9 (500 mg, 1.33 mmol) and the mixture was stirred for 4.5 h. The mixture was diluted with water and extracted with CH2C12. The extract was washed with brine, dried over MgS04, and evaporated to leave a crystalline solid which was thoroughly washed with EtOH to give the biindolyl (1) (265 mg, 86%) as a pale gray solid, mp 295 C (lit.1: 260 C; 314 C). Spectroscopic data (IR, 'H NMR, MS) were identical with those reported.1 IR: v=3396 (Nujol) cm-1; 3402 (KBr) cm'1. 'H NMR (300 MHz, DMSO-d6): 5=6.90 (s, 2), 6.98 (t, 2H, 7=7.7 Hz), 7.90 (t, 2H, 7=7.3 Hz), 7.39 (d, 2H, 7=8.1 Hz), 7.53 (d, 2H, 7=7.7 Hz), 11.5 (br s, 2H. MS:m/z=232 (M+, 100%). HRMS: m/z calc, for C16H.,N2 232.1000, found 232.0992.