W. G. Skene, W. D. Lubell et al.
THF (1 mL) was added dropwise to a 08C solution of potassium tert-but-
oxide (15 mg, 0.13 mmol, 3.2 equiv) and [18]crown-6 ether (2 mg,
0.008 mmol, 0.1 equiv) in THF (1 mL), stirred for 30 min, and treated
with allyl iodide (11 mL, 1.2 mmol, 1.2 equiv). The ice bath was removed
and the solution was allowed to warm to room temperature, with stirring
overnight. The reaction mixture was partitioned between water (3 mL)
and EtOAc (5 mL). The layers were separated and the aqueous layer was
extracted with EtOAc (2 mL). The organic layers were combined,
washed with brine, dried over MgSO4, filtered, and concentrated under
vacuum to a residue that was purified by column chromatography on
silica gel (Rf =0.3; 50% EtOAc/hexanes). Evaporation of the collected
fractions gave the allyl bipyrrole 3 as a green oil (9 mg, 52%). 1H NMR
(300 MHz, CDCl3): d=7.56–7.52 (m, 5H), 6.91 (d, J=2.1 Hz, 1H), 6.74
(t, J=2.4 Hz, 1H), 6.14 (t, J=3.6 Hz, 1H), 6.00 (d, J=2.1 Hz, 1H), 5.89–
5.87 (m, 2H), 5.12 (d, J=1.5 Hz, 1H), 5.03 (d, J=1.5 Hz, 1H), 4.22 (m,
2H), 3.75 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=151.2, 139.1,
135.2, 134.4, 129.5 (2C), 128.2 (2C), 126.4, 123.0, 122.4, 118.1, 113.9,
111.9, 108.3, 103.9, 58.4, 50.5 ppm; HRMS: m/z calcd for C18H19N2O3S:
343.1110 [M+H]+; found: 343.1121.
6.53(dd, J=1.5, 2.5 Hz, 1H), 6.32 (s, 1H), 3.88 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=180.7, 179.7, 159.1, 136.3, 134.7, 134.5, 134.3,
129.2, 128.2, 127.1, 121.1, 120.4, 115.2, 107.1, 59.0 ppm; HRMS: m/z calcd
for C17H15N2O5S: 359.0696 [M+H]+; found: 359.0708.
4-Methoxy-5,5’-bisformyl-2,2’-bipyrrole (8): This compound was prepared
according to method B from bipyrrole 1 (40 mg, 0.24 mmol) without pu-
rification by chromatography. Dialdehyde 8 was obtained as a green oil
(26 mg, 50%). Rf =0.54 (50%EtOAc/hexanes); 1H NMR (300 MHz,
(CD3)2CO): d=9.56 (s, 1H), 9.53 (s, 1H), 7.07 (d, J=4 Hz, 1H), 6.93 (m,
2H), 6.85 (br, 1H), 6.65 (s, 1H), 3.91 ppm (s, 3H); HRMS: m/z calcd for
C11H11N2O3: 219.0764 [M+H]+; found: 219.0754.
4-Methoxy-1-phenylsulfonyl-1’-allyl-5-formyl-2,2’-bipyrrole (14): This
compound was prepared according to method B from bipyrrole 3 (7 mg,
0.03 mmol) as a green oil (4 mg, 53%). Rf =0.3 (50% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3): d=10.23 (s, 1H), 7.59–7.41 (m, 5H), 6.92
(s, 1H), 6.25 (t, J=3.2 Hz,1H), 6.17 (t, J=2 Hz, 1H), 6.08 (s, 1H), 5.89
(m, 1H), 5.16 (d, J=10.4 Hz, 1H), 5.08 (d, J=16.8 Hz, 1H), 4.56 (d, J=
5.6 Hz, 2H), 3.87 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=181.5,
160.2, 137.4, 136.6, 135.1, 134.7, 129.7 (2C), 128.4 (2C), 125.7, 123.1,
121.1, 118.7, 114.8, 109.1, 107.9, 59.7, 51.6 ppm; HRMS: m/z calcd for
C19H19N2O4S: 371.1060 [M+H]+; found: 371.1070.
4-Methoxy-1-phenylsulfonyl-1’-butyl-2,2’-bipyrrole (4): This compound
was obtained using Method A from 4-methoxy-1-benzenesulfonyl-2,2’-bi-
pyrrole (2, 30 mg, 0.1 mmol) and 1-iodobutane (17 mL, 0.14 mmol) as a
brown oil (31 mg, 86%), after chromatography. Rf =0.5 (20% EtOAc/
hexanes); 1H NMR (300 MHz, CDCl3): d: 7.56–7.41 (m, 5H), 6.93 (t, J=
1.5 Hz, 1H), 6.77 (d, J=0.9 Hz, 1H), 6.12 (d, J=2.1 Hz, 1H), 6.02 (d, J=
1.5 Hz, 1H), 5.81 (t, J=1.2 Hz, 1H), 3.77 (s, 3H), 3.69–3.65 (m, 2H), 1.58
(m, 2H), 1.21 (m, 2H), 0.88–0.84 ppm (m, 3H); 13C NMR (100 MHz,
CDCl3): d=151.2, 139.1, 134.3, 129.5 (2C), 128.3 (2C), 126.9, 122.8, 122.5,
113.5, 111.9, 107.8, 103.9, 58.5, 47.9, 33.9, 20.9, 14.4 ppm: HRMS: m/z
calcd for C19H23N2O3S: 359.1423 [M+H]+; found: 359.1425.
4-Methoxy-1-benzenesulfonyl-1’-butyl-5,5’-bisformyl-2,2’-bipyrrole
and 4-methoxy-1-benzenesulfonyl-1’-butyl-5,4’-bisformyl-2,2’-bipyrrole
(11): These compounds were prepared according to method B from bi-
pyrrole (27 mg, 0.08 mmol) and separated during purification by
column chromatography on silica gel. First to elute was 5,5’-dialdehyde
10 as brown oil (7 mg, 23%): Rf =0.27 (40% EtOAc/hexanes);
(10)
4
a
1H NMR (300 MHz, CDCl3): d=10.28 (s, 1H), 9.67 (s, 1H), 7.63 À7.43
(m, 5H), 6.98 (d, J=4.2 Hz, 1H), 6.22 (s, 1H), 6.18 (d, J=4.2 Hz, 1H),
4.33 (br, 2H), 3.90 (s, 3H), 1.58 (m, 2H), 1.18 (m, 2H), 0.83 ppm (m,
3H); 13C NMR (100 MHz, CDCl3): d=181.4, 180.3, 159.6, 137.6, 135.7,
134.4, 133.3, 131.9, 130.0 (2C), 128.3 (2C), 124.1, 121.5, 114.6, 108.9, 59.7,
47.9, 34.2, 20.5, 14.6 ppm; HRMS: m/z calcd for C21H23N2O5S: 415.1322
[M+H]+; found: 415.1329. Second to elute was 5,4’-dialdehyde 11 as a
yellow oil (19 mg, 61%). Rf =0.17 (40% EtOAc/hexanes); 1H NMR
(300 MHz, CDCl3): d=10.2 (s, 1H), 9.8 (s, 1H), 7.62–7.43 (m, 6H), 6.54
(d, J=1.8 Hz, 1H), 6.18 (s, 1H), 4.08 (t, J=6.9 Hz, 2H), 3.88 (s, 3H),
1.68 (m, 2H), 1.28 (m, 2H), 0.90 ppm (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=185.8, 181.4, 159.9, 137.2, 135.7, 134.2, 132.2,
130.0 (2C), 128.3 (2C), 126.3, 126.08, 121.3, 112.6, 109.1, 59.5, 49.6, 33.3,
20.7, 14.3 ppm; HRMS: m/z calcd for C21H23N2O5S: 415.1322 [M+H]+;
found: 415.1330.
4-Methoxy-1-phenylsulfonyl-1’-octyl-2,2’-bipyrrole (5): This compound
was obtained using Method A from 4-methoxy-1-benzenesulfonyl-2,2’-bi-
pyrrole (2, 25 mg, 0.08 mmol) and 1-iodooctane (22 mL, 0.12 mmol) as a
brown oil (26 mg, 76%), after chromatography. Rf =0.53 (20% EtOAc/
hexanes); 1H NMR (300 MHz, CDCl3): d=7.55–7.41 (m, 5H), 6.93 (t,
J=1.5 Hz, 1H), 6.77 (d, J=0.9 Hz, 1H), 6.12 (d, J=2.1 Hz, 1H), 6.01 (d,
J=1.5 Hz, 1H), 5.82 (t, J=1.2 Hz, 1H), 3.77 (s, 3H), 3.66 (m, 2H), 1.58
(m, 2H), 1.23 (m, 10H), 0.90–0.88 ppm (m, 3H); 13C NMR (100 MHz,
CDCl3): d=151.2, 139.1, 134.4, 129.6 (2C), 128.3 (2C), 126.9, 122.8, 122.3,
113.4, 111.8, 107.7, 103.9, 58.3, 48.2, 32.5, 31.7, 29.9, 29.9, 27.5, 23.3,
14.9 ppm; HRMS: m/z calcd for C23H31N2O3S: 415.2050 [M+H]+; found:
415.2051.
4-Methoxy-1,1’-biphenylsulfonyl-2,2’-bipyrrole (6): This compound was
prepared using Method A from 4-methoxy-1-benzenesulfonyl-2,2’-bipyr-
role (2, 25 mg, 0.08 mmol) and benzenesulfonyl chloride (49 mL,
0.23 mmol) as a white solid (18 mg, 50%) after chromatography. Rf =0.79
(50% EtOAc/hexanes); 1H NMR (400 MHz, CDCl): d=7.62 (m, 6H),
7.48 (m, 5H), 6.94 (d, J=2 Hz, 1H), 6.31 (t, J=1.2 Hz, 1H), 5.99 (d, J=
1.6 Hz, 1H), 5.77 (s, 1H), 3.78 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=149.2, 138.4, 138.4, 133.5, 133.3, 128.7 (2C), 128.6 (2C), 127.1
(2C), 126.9 (2C), 123.9, 122.2, 121.6, 118.9, 11.4, 110.7, 103.4, 57.3 ppm;
HRMS: m/z calcd for C21H19N2O5S2: 443.0730 [M+H]+; found: 443.0730.
4-Methoxy-1-benzenesulfonyl-5,5’-bisformyl-1’-octyl-2,2’-bipyrrole
and 4-methoxy-1-benzenesulfonyl-5,4’-bisformyl-1’-octyl-2,2’-bipyrrole
(13): These compounds were prepared according to method B from bi-
pyrrole (21 mg, 0.05 mmol) and separated during purification by
(12)
5
column chromatography on silica gel. First to elute was 5,5’-dialdehyde
12 as a clear oil (5 mg, 21%): Rf =0.32 (40% EtOAc/hexanes); 1H NMR
(300 MHz, CDCl3): d=10.28 (s, 1H), 9.67 (s, 1H), 7.65–7.42 (m, 5H),
6.98 (d, J=3.9 Hz, 1H), 6.21 (s, 1H), 6.18 (d, J=3.8 Hz, 1H), 4.32 (br,
2H), 3.90 (s, 3H), 1.58 (m, 2H), 1.24 (m, 10H), 0.86 ppm (m, 3H);
13C NMR (100 MHz, CDCl3): d=181.3, 180.6, 159.3, 137.7, 135.4, 134.3,
133.4, 132.0, 129.9 (2C), 128.4 (2C), 123.8, 121.5, 114.7, 109.0, 59.9, 48.1,
32.6, 31.9, 30.0, 29.9, 27.5, 23.4, 14.9 ppm; HRMS: m/z calcd for
C25H31N2O5S: 471.1948 [M+H]+; found: 471.1951. Second to elute was
5,4’-dialdehyde 13 as an orange oil (12 mg, 50%). Rf =0.22 (40% EtOAc/
hexanes); 1H NMR (300 MHz, CDCl3): d=10.11 (s, 1H), 9.78 (s, 1H),
7.83 (d, J=1.5 Hz, 1H), 7.75 (m, 1H), 7.61 (m, 4H), 6.61 (s, 1H), 6.55 (d,
J=1.5 Hz, 1H), 4.12 (m, 2H), 3.88 (s, 3H), 0.83–1.71 ppm (m, 15H);
13C NMR (100 MHz, CDCl3): d=185.7, 181.3, 159.7, 137.2, 135.6, 134.1,
132.4, 130.0 (2C), 128.2 (2C), 126.3, 126.2, 121.3, 112.5, 109.1, 59.7, 49.9,
32.5, 31.1, 29.9, 29.8, 27.3, 23.4, 14.9 ppm; HRMS: m/z calcd for
C25H31N2O5S: 471.1948 [M+H]+; found: 471.1950.
Representative Method B
4-Methoxy-1-benzenesulfonyl-5,5’-bisformyl-2,2’-bipyrrole (9): Phospho-
ryl chloride (49 mL, 0.52 mmol, 4 equiv) was added to dimethylformamide
(0.1 mL, 1.3 mmol, 10 equiv) at 5–108C and stirred for 30 min. A solution
of 4-methoxy-1-benzenesulfonyl-2,2’-bipyrrole (2, 40 mg, 0.13 mmol,
1 equiv) in 1.6 mL of dichloromethane was cooled to À158C, and treated
dropwise with the preformed solution of Vilsmeier reagent. The reaction
mixture was stirred at À158C for 30 min, at 08C for 9 h, at room temper-
ature overnight, treated with a saturated aqueous sodium acetate solution
(3 mL) and heated to a reflux for 2 h. The layers were separated and the
aqueous layer was extracted with EtOAc. The organic layers were com-
bined, washed with brine, dried (MgSO4), and concentrated to a residue
that was purified by chromatography on silica (60% EtOAc in hexanes).
Evaporation of the collected fractions yielded dialdehyde 9 as a green oil
(43 mg) in 90% yield. 1H NMR (300 MHz, CDCl3): d=10.17 (m, 2H),
9.62 (s, 1H), 7.55 (m, 1H), 7.37 (m, 4H), 7.00 (dd, J=1.5, 2.5 Hz, 1H),
4-Methoxy-1,1’-diphenylsulfonyl-5-formyl-2,2’-bipyrrole (15): This com-
pound was prepared according to method B from bipyrrole 6 (15 mg,
0.03 mmol). Purification by column chromatography on silica gel afford-
ed 15 as a brown solid (15 mg, 94%). Rf =0.27 (50% EtOAc/hexanes);
m. p. 156–1588C; 1H NMR (300 MHz, CDCl3): d=10.22 (s, 1H), 7.75–
10886
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 10879 – 10888