Fischer Carbene Complex Cyclization Reactions
J. Am. Chem. Soc., Vol. 121, No. 13, 1999 3071
3
7.5 Hz, 3H); 1.46 (m, 2H); 3.30 (t, J(H,H) ) 7.2 Hz, 2H); 3.90 (s,
Hydrolysis of Pyrrolodiazepine Complexes 17. Preparation of
Pyrrole-2-carboxaldehydes 19. A solution of complex 17 (0.5 mmol)
in 15 mL of a mixture of 01.M HCl-THF (1:1 v/v) was stirred at
room temperature for 2 h and then extracted with ethyl acetate (3 ×
20 mL). The organic layers were washed with brine and dried with
anhydrous sodium sulfate, and the solvents were removed under
vaccum. The crude thus obtained was purified by column chromatog-
raphy (silica gel, 10:1 hexanes/ethyl acetate) affording the correponding
pyrroles 19.
Methyl-(Z)-3-(2-formylpyrrole-1-yl)-2-heptenoate (19b): Yield:
79%. 1H NMR: δ ) 0.8 (m, 3H); 1.2-1.4 (m, 4H); 3.0 (t, 3J(H,H) )
7.0 Hz, 2H); 3.4 (s, 3H); 5.9 (s, 1H); 6.2 (m, 1H); 6.8 (m, 1H); 7.0 (m,
1H); 9.5 (s, 1H). 13C NMR (75 MHz): δ ) 178.0 (d); 156.0 (s); 146.0
(s); 131.6 (s); 131.1 (d); 124.4 (d); 114.6 (d); 110.0 (d); 52.1 (q); 36.1
(t); 24.4 (t); 21.9 (t); 13.6 (q). MS(70 eV) m/z: 235 (4) [M+], 205
(100), 190 (26), 176 (38), 162 (51). Anal. Calcd for C13H17NO3: C,
66.36; H, 7.28; N, 5.95. Found: C, 66.23; H, 7.45; N, 6.21.
Heating of Pyrrolodiazepine Complexes 17. Preparation of
Indolizines 20. A solution of pyrrolodiazepine 17 (0.5 mmol) in toluene
(15 mL) was refluxed for 6 h. The crude was filtered through Celite,
the solvent removed under vacuum, and the residue subjected to
column-chromatography purification (silica gel, 4:1 hexanes/ethyl
acetate) to afford the indolizines 20.
7-Methoxy-5-phenyl-8-propylaminoindolizine (20a). Yield: 84%.
1H NMR: δ ) 1.04 (t, 3J(H,H) ) 7.3 Hz, 3H); 1.67 (m, 2H); 3.46 (t,
3J(H,H) ) 7.4 Hz, 2H); 3.86 (s, 3H); 6.41 (s, 1H); 6.52 (m, 1H); 6.72
(m, 1H); 7.31 (m, 1H); 7.4-7.6 (m, 5H). 13C NMR (75 MHz): δ )
137.3 (s), 135.7 (s), 129.9 (s), 129.8 (s), 128.8 (d), 128.6 (d), 128.5
(d), 126.1 (s), 112.8 (d), 110.2 (d), 104.4 (d), 96.7 (d), 58.2 (q), 48.3
(t), 24.1 (t), 11.4 (q). Anal. Calcd for C18H20N2O: C, 77.11; H, 7.19;
N, 9.99. Found: C, 77.34; H, 7.09; N, 10.12.
Heating of Pyrrolodiazepine Complexes 17 under CO. Prepara-
tion of Bispyrrole 21. A solution of pyrrolodiazepine 17 (0.5 mmol)
in toluene (15 mL) was refluxed under CO pressure (120 bar) for 48
h. The residue was then filtered through Celite and the solvent removed
under vacuum. Purification by column chromatography (silica gel, 8:1
hexanes/ethyl acetate) afforded the bispyrrole 21 in 68% yield. 1H
NMR: δ ) 0.9 (t, 3J(H,H) ) 7.3 Hz, 3H); 1.67 (m, 2H); 3.76 (t, 3J(H,H)
) 7.5 Hz, 2H); 3.92 (s, 3H); 5.61 (s, 1H); 6.3 (m, 2H); 6.8 (m, 1H);
7.0-7.4 (m, 5H); 7.92 (broad s, 1H). 13C NMR (75 MHz): δ ) 148.9
(s); 136.2 (s); 128.1 (d); 126.8 (d); 124.9 (d); 122.3 (s); 120.1 (s); 117.8
(d); 114.0 (s); 109.7 (d); 108.9 (d); 82.7 (d); 57.3 (q); 43.9 (t); 23.9
(t); 11.1 (q). Anal. Calcd for C18H20N2O: C, 77.11; H, 7.19; N, 9.99.
Found: C, 77.14; H, 7.12; N, 10.11.
3
3H); 6.53 (s, 1H); 6.89 (d, J(H,H) ) 2.2 Hz, 1H); 7.3-7.5 (m, 5H);
7.62 (d, J(H,H) ) 2.2 Hz, 1H). 13C NMR (75 MHz): δ ) 147.3 (s),
3
146.3 (s), 143.6 (d), 140.0 (s), 129.5 (d), 128.6 (d), 127.1 (d), 126.2
(s), 126.0 (s), 118.4 (s), 106.0 (d), 104.1 (d), 55.7 (q), 49.4 (t), 23.7
(t), 11.3 (q). Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N, 4.98.
Found: C, 76.91; H, 6.98; N, 4.77.
General Procedure for the Preparation of Indolizines 14 and
Indolizinones 15. A solution of imine 8 (1 mmol) in acetonitrile (5
mL) was slowly added at room temperature to a solution of carbene 1
(1 mmol) in acetonitrile (40 mL). After being stirred for 8 h, the
resulting mixture was filtered through Celite and the solvent removed
under vacuum. The crude thus obtained was characterized by NMR to
be the indolizine 14. Column chromatography purification (silica gel,
4:1 hexanes/ethyl acetate) afforded the corresponding indolizinone 15.
trans-7-Phenyl-8-propylamino-7,8-dihydroindolizin-5-one 15a:
Yield: 58%. 1H NMR: δ ) 0.90 (t, 3J(H,H) ) 7.3 Hz, 3H); 1.42 (m,
2
2H); 1.7 (broad s, 1H); 2.65 (m, 2H); 2.94 (dd, J(H,H) ) 17.2 and
3J(H,H) ) 8.6 Hz, 1H); 3.23 (dd, J(H,H) ) 17.2 and J(H,H) ) 3.7
Hz, 1H); 3.48 (broad s, 1H); 4.17 (d, 1H, 3J(H,H) ) 7.2 Hz); 6.23 (m,
1H); 6.31 (m, 1H); 7.2-7.5 (m, 6H). 13C NMR (75 MHz): δ ) 167.3
(s), 140.0 (s), 133.9 (s), 128.8 (d), 127.2 (d), 127.1 (d), 116.5 (d), 112.9
(d), 110.6 (d), 56.9 (d), 48.0 (t), 44.9 (d), 37.6 (t), 23.3 (t), 11.5 (q).
Anal. Calcd for C17H20N2O: C, 76.09; H, 7.51; N, 10.44. Found: C,
75.87; H, 7.66; N, 10.55.
2
3
General Procedure for the Preparation of Pyrrolodiazepines 17.
To a solution of carbenes 2 and 3 (1 mmol) in hexane (20 mL), imine
8 (1 mmol) in hexane (5 mL) was slowly added at room temperature.
After 12 h the precipitate is filtered, washed with cold hexane (3 × 5
mL), and subjected to column-chromatography purification (silica gel,
4:1 hexanes/ethyl acetate) to afford the pyrrolodiazepines 17.
Pyrrolo[1,2-a]-1,4-diazepine chromiumpentacarbonyl complex
(17a): Yield: 93%. H NMR: δ ) 0.97 (t, J(H,H) ) 7.3 Hz, 3H);
1.8 (m, 2H); 3.2 (m, 1H); 4.0 (m, 1H); 4.16 (s, 3H); 4.67 (s, 1H); 5.6
(m, 2H); 6.2 (m, 2H); 7.4-7.8 (m, 5H). 13C NMR (75 MHz): δ )
224.5 (s), 220.8 (s), 161.2 (s), 155.7 (s), 144.9 (s), 135.9 (s), 131.9
(d), 130.5 (d), 129.0 (d), 122.5 (d), 113.9 (d), 103.7 (d), 98.0 (d), 59.1
(q), 55.1 (t), 50.8 (d), 21.3 (t), 12.0 (q). IR (CDCl3) υ[cm-1] ) 1906,
2052. Anal. Calcd for C23H20CrN2O6: C, 58.48; H, 4.27; N, 5.93.
Found: C, 58.10; H, 4.33; N, 6.13.
1
3
General Procedure for the Preparation of Pyrrolodiazepines (18).
To a solution of carbenes 2 and 3 (1 mmol) in THF (20 mL) imine 8
(1 mmol) in THF (5 mL) was slowly added at room temperature. After
12 h the crude was filtered through Celite and subjected to column-
chromatography purification (silica gel, 4:1 hexanes/ethyl acetate) to
afford the pyrrolodiazepines 18.
Acknowledgment. This research was supported by DGICYT
(Grants PB97-1271, PB94-1313, and PB96-0556). J.A.L.P.
thanks the FICYT for a doctoral fellowship.
Indolo[1,2-a]-1,4-diazepine Chromiumpentacarbonyl Complex
1
3
(18a). Yield: 33%. H NMR: δ ) 0.94 (t, J(H,H) ) 7.2 Hz, 3H);
1.83 (m, 2H); 3.16 (m, 1H); 4.02 (m, 1H); 4.16 (s, 3H); 4.72 (broad s,
1H); 5.2 (m, 2H); 7.0-7.6 (m, 9H). 13C NMR (75 MHz): δ ) 223.7
(s), 219.8 (s), 160.9 (s), 155.2 (s), 153.3 (s), 136.6 (s), 135.8 (s), 132.5
(s), 131.5 (d), 128.7 (d), 128.6 (d), 122.1 (d), 120.9 (d), 120.2 (d),
113.8 (d), 99.7 (d), 98.7 (d), 58.6 (q), 54.8 (t), 50.8 (d), 20.6 (t), 11.4
(q). IR (CDCl3) υ[cm-1] ) 1907, 2048. Anal. Calcd for C27H22-
CrN2O6: C, 62.07; H, 4.24; N, 5.36. Found: C, 61.75; H, 4.34; N,
5.55.
Supporting Information Available: Spectroscopic data and
elemental analyses for compounds 11, 12, 14a,b, 15b, 17b-d,
18b,c, 19a, 20b,c. Tables of crystal data, structure solution and
refinement, atomic coordinates, bond lengths and angles, and
anisotropic thermal parameters for 17b. This material is available
JA983692O