7756
S.M. Allin et al. / Tetrahedron 64 (2008) 7745–7758
pyrrole 4-H), 6.92 (1H, ddd, J 3.8, 2.5, 1.3, pyrrole 3-H) and 7.04 (1H,
ddd, J 2.5, 2.9, 1.3, pyrrole 5-H).
tetrahydroindolizine-3-carboxylate 45a as a clear, colourless liquid
(61%). (Found: Mþ, 193.1104. C11H15NO2 requires 193.1102.) nmax
(neat)/cmꢁ1 3374, 2940, 1701, 1541, 1489, 1444, 1428, 1401, 1368,
1347, 1304, 1230, 1187, 1142, 1092, 1068, 1042, 996, 922, 872 and
751; dH 1.31 (3H, t, J 4.3, Me), 1.76–1.83 (2H, m, 7-H), 1.90–1.99 (2H,
m, 6-H), 2.80 (2H, t, J 6.3, 8-H), 4.25 (2H, q, J 4.3, OCH2), 4.32 (2H, t,
J 6.1, 5-H), 5.86 (1H, d, J 4.0, 1-H) and 6.92 (1H, d, J 4.0, 2-H); dC
(62.5 MHz) 14.6 (Me), 20.1 (7-C), 23.0 (6-C), 24.2 (8-C), 45.6 (5-C),
59.4 (OCH2), 106.0 (1-C), 117.5 (2-C), 128.8 (3-C), 137.0 (8a-C) and
161.3 (C]O); m/z 194 (Mþ1, 11%), 193 (Mþ, 73%), 192 (9), 165 (17),
164 (45), 148 (54), 121 (54), 120 (100), 118 (19), 106 (16), 91 (20), 82
(14), 65 (16), 55 (14) and 49 (17).
A repeat reaction for 3 h afforded ethyl 5,6,7,8-tetrahydro-3-
indolizinecarboxylate 45a as a clear liquid (37%), ethyl 1-butyl-1H-
pyrrole-2-carboxylate 46a as an orange liquid (13%) and unaltered
ethyl 1-(4-bromobutyl)-1H-pyrrole-2-carboxylate 44a (51%). The
TLC, 1H NMR and IR spectra were identical to those of the authentic
materials.
3.6.5. 4-Bromo-1-[1-(phenylsulfonyl)-1H-pyrrol-2-yl]butan-
1-one 38
4-Bromobutyryl chloride (2.8 cm3, 24.0 mmol) was added to
a stirred solution of boron trifluoride etherate (3.0 cm3, 24.0 mmol)
in dichloromethane (50 cm3). Stirring was maintained at room
temperature for 10 min and N-(phenylsulfonyl)-1H-pyrrole
(2.48 cm3, 12.0 mmol) in dichloromethane (10 cm3) was added over
20 min and the reaction mixture was stirred for 4 days The reaction
was quenched with ice-water (100 cm3), the aqueous phase
was extracted with further portions of dichloromethane. The com-
bined organic extracts were washed with sodium hydroxide solution
(0.1 M), water and dried (Na2SO4). Evaporation of solvent yielded
4-bromo-1-[1-(phenylsulfonyl)-1H-pyrrol-2-yl]butan-1þ-one
38
(2.25 g, 53%) as a white solid, mp 68–69 ꢂC. (Found: M , 354.9884.
C
14H14BrNO3S requires 354.9878.) nmax (thin film)/cmꢁ1 1676, 1364
and 1174; dH 2.07–2.18 (2H, m, 2-H), 2.88 (2H, t, J 7.0, 3-H), 3.37 (2H, t,
J 6.4, 1-H), 6.35–6.37 (1H, m, pyrrole 4-H), 7.11–7.12 (1H, m, pyrrole
3-H), 7.50–7.54 (2H, m), 7.59–7.61 (1H, m), 7.81–7.83 (1H, m, pyrrole
5-H) and 7.97–8.00 (2H, m); dC 27.0 (2-C), 33.2 (3-C), 37.1 (1-C), 110.5
(pyrrole 4-C), 123.7 (pyrrole 5-C), 128.1 (CH), 128.7 (CH), 130.4 (pyr-
role3-C),133.0(pyrrole2-C),133.7(CH),138.8 (C)and187.1 (4-C);m/z
355 (Mþ, 4%), 234 (100), 185 (38), 141 (65), 94 (46) and 77 (100).
Ethyl 1-(4-bromobutyl)-1H-pyrrole-2-carboxylate 44a (0.20 g,
0.73 mmol), sodium cyanoborohydride (68.76 mg, 1.09 mmol) and
tri-n-butyltin chloride (24 mg, 0.1 equiv) were dissolved in tert-bu-
tanol (100 cm3) and stirred under reflux for 3 h. AIBN was added
independently every hour. After cooling to room temperature and
evaporating to dryness, the crude yellow oil was subjected to flash
column chromatography using light petroleum and DCM as eluents
to yield ethyl 5,6,7,8-tetrahydro-3-indolizinecarboxylate 45a (57 mg,
40%) and ethyl 1-butyl-1H-pyrrole-2-carboxylate 46b (32 mg, 23%).
Cyclisation of 1-(4-bromobutyl)pyrrole-2-carboxaldehyde 44b.
The same procedure was used to yield 5,6,7,8-tetrahydro-3-indo-
lizinecarbaldehyde 45b (91%). The reaction was repeated using
EtOH in place of tert-butanol and gave 5,6,7,8-tetrahydro-3-indo-
lizinecarbaldehyde 45b (40%) and 1-butylpyrrole-2-carbox-
aldehyde 46b (60%).
3.6.6. Cyclisation of 4-bromo-1-[1-(phenylsulfonyl)-1H-pyrrol-2-
yl]butan-1-one 38
Tributyltin hydride (0.59 cm3, 2.2 mmol) and AIBN (0.36 g,
4.6 mmol) in toluene (50 cm3) was added over 7 h to a solution
of 4-bromo-1-[1-(phenylsulfonyl)-1H-pyrrol-2-yl]butan-1-one 38
(0.39 g, 1.1 mmol) in acetonitrile (250 cm3) heated under reflux.
The reaction mixture was heated under reflux for 9 h, cooled to
room temperature and evaporated to dryness under reduced
pressure. Purification using gradient elution column chromatog-
raphy yielded 1-(phenylsulfonyl)-1,4,5,6-tetrahydro-indol-7-one
(10% by 1H NMR spectral correlation to reported data49) and
1-phenylsulfonyl-2-(tetrahydrofuran-2-yl)-1H-pyrrole 41 (0.210 g,
69%) as a colourless oil. (Found: Mþ, 277.0768. C14H15NO3S requires
277.0773.) nmax (thin film)/cmꢁ11368 and 1178; dH (400 MHz) 1.60–
1.66 (1H, m, 4-H), 1.92–1.96 (2H, m, 3-H), 2.24–2.29 (1H, m, 4-H),
3.77–3.81 (1H, m, 5-H), 3.87–3.90 (1H, m, 5-H), 5.27–5.28 (1H, m,
2-H), 6.22–6.26 (2H, m, pyrrole 3,4-H), 7.26–7.28 (1H, m, pyrrole 5-
H), 7.46–7.49 (2H, m), 7.55–7.57 (1H, m) and 7.80–7.82 (2H, m); dC
25.5 (3-C), 32.8 (4-C), 68.1 (5-C), 73.5 (2-C),111.7 (pyrrole 4-C),112.0
(pyrrole 5-C), 123.4 (pyrrole 3-C), 126.8 (CH), 129.2 (CH), 133.7 (CH),
137.0 (pyrrole 2-C) and 139.5 (C).
3.6.8. Cyclisation of phenyl 3-(1H-pyrrol-1-yl)propane-
selenoate 4715
The standard procedure for acyl radical cyclisations under an
atmosphere of CO yielded 2,3-dihydro-1H-pyrrolizidin-1-one 49
(23%) as a clear semi-solid. (Found: Mþ, 121.0529. C7H7NO requires
121.0528.) nmax (thin film)/cmꢁ11697; dH 3.09 (2H, t, J 6.2, 2-H), 4.34
(2H, t, J 6.2, 3-H), 6.51–6.54 (1H, m, 6-H), 6.73–6.75 (1H, m, 7-H)
and 7.04–7.07 (1H, m, 5-H); dC 39.4 (2-C), 42.1 (3-C), 107.6 (6-C),
117.0 (7-C), 122.8 (5-C) and 130.3 (7a-C); m/z 121 (Mþ, 81%) and 93
(100).
3.6.9. Cyclisation of 2-methyl-1-[4-(phenylselenyl)butyl]-1H-
imidazole 50
Cyclisation of 4-bromo-1-[1-(phenylsulfonyl)-1H-pyrrol-3-yl]butan-
1-one 42. 1-Phenylsulfonyl-3-(tetrahydrofuran-2-yl)-1H-pyrrole 43
(0.193 g, 64%), colourless oil. (Found: Mþ, 277.0775. C14H15NO3S
requires 277.0773.) nmax (thin film)/cmꢁ1 1370, 1175; dH (400 MHz)
1.73–1.76 (1H, m, 4-H), 1.88–1.93 (2H, m, 3-H), 2.11–2.14 (1H, m, 4-
H), 3.74–3.80 (1H, m, 5-H), 3.89–3.94 (1H, m, 5-H), 4.72–4.74 (1H,
m, 2-H), 6.25–6.26 (1H, m, pyrrole 4-H), 7.11–7.13 (2H, m, pyrrole
2,5-H), 7.41–7.45 (2H, m), 7.51–7.54 (1H, m) and 7.82–7.84 (2H, m);
dC 25.8 (3-C), 32.9 (4-C), 68.0 (5-C), 74.7 (2-C), 112.4 (pyrrole 4-C),
117.3 (pyrrole 5-C), 121.3 (pyrrole 2-C), 126.4 (CH), 129.4 (CH), 131.4
(pyrrole 3-C), 133.9 (CH) and 138.9 (C); m/z 277 (Mþ, 33%), 276 (26),
234 (22), 141 (37), 136 (57), 94 (42) and 77 (100).
The standard procedure for azole radical cyclisation using
Bu3SnH (added by syringe pump over 3 h) and AMBN in refluxing
cyclohexane gave 1-butyl-2-methyl-1H-imidazole 52 as a yellow oil
(32%) (characterised by comparison with independently syn-
thesised material) and 3-methyl-5,6,7,8-tetrahydroimidazo[1,5-
a]pyridine 51 as a pungent smelling yellow oil (35%). (Found: Mþ,
136.1000. C8H12N2 requires 136.1000.) nmax (neat)/cmꢁ1 3052, 2953,
1419, 1388, 1265, 736 and 703; dH 1.73–1.78 (2H, m, 6-H), 1.80–1.83
(2H, m, 7-H), 2.34 (3H, s, Me), 2.74 (2H, t, J 6.3, 8-H), 3.79 (2H, t, J 6.1,
5-H) and 6.64 (1H, s, 1-H); dC 12.6 (Me), 20.3 (6-C), 21.2 (7-C), 23.2
(8-C), 42.6 (5-C), 121.7 (1-C), 127.6 (8a-C) and 142.7 (3-C); m/z 137
(Mþ1, 56%), 136 (Mþ, 81%), 135 (100), 121 (14), 108 (25), 95 (21), 94
(14), 91 (34), 81 (12), 67 (17), 56 (19), 55 (21), 41 (17) and 40 (11).
3.6.7. Cyclisation of ethyl 1-(4-bromobutyl)-1H-pyrrole-2-
carboxylate 44a
3.7. Mechanistic investigations
The general procedure for radical cyclisations with cyclohexane
as solvent was used with 6 h reaction time. AMBN was added in-
dependently every hour. Purification by column chromatography
using light petroleum and DCM as eluents gave ethyl 5,6,7,8-
3.7.1. Dimethyl 2,20-hydrazinobisisobutyrate (59, R¼Me, Z¼CO2Et)
Hydrazine hydrate (0.26 g, 4.4 mmol) in ethanol (10 cm3) was
added to a stirred solution of dimethyl 2,20-azobisisobutyrate (57,