2180, 1740 and 1695; δH(60 MHz) 0.15 (9 H, s, SiMe3), 1.44
(9 H, s, But), 1.7–2.6 (8 H, m), 3.2–3.8 (2 H, m, 5-H2) and 3.67
(3 H, s, OMe).
3.40 (2 H, br, 5-H2), 3.79 (3 H, s, OMe), 7.07 (1 H, td, J 7.8, 1.8,
ArH), 7.21 (1 H, dd, J 7.8, 1.8, ArH), 7.39 (1 H, td, J 7.8, 0.9,
ArH) and 7.82 (1 H, d, J 7.8, ArH).
Methyl 1-(o-iodobenzoyl)-2-[4-(trimethylsilyl)but-3-ynyl]-
pyrrolidine-2-carboxylate 14
Radical cyclisation of compound 8
General procedure. To a stirred and boiling solution of 8 (405
mg, 0.86 mmol) in toluene (40 cm3) was added a solution of
Bu3SnH (326 mg, 1.12 mmol) and AIBN (14 mg, 0.09 mmol) in
toluene (40 cm3) via a syringe during 2 h, and the mixture was
refluxed for 2 h. The same procedure was repeated. After evap-
oration of the mixture, diethyl ether (20 cm3) and 8% aqueous
KF (20 cm3) were added to the residue, and the whole was
vigorously stirred at room temperature for 1 h. The organic
layer was separated, dried (MgSO4) and concentrated. The
residue was chromatographed on silica gel [hexane–AcOEt
(10:1)]. The first fraction gave a mixture of E and Z isomers
(ca. 1:1 ratio) of methyl 7-benzoyl-3-(trimethylsilylmethylene)-
7-azabicyclo[2.2.1]heptane-1-carboxylate 19 (230 mg, 78%) as a
colourless oil [Found: (M ϩ H)ϩ, 344.1691. C19H26NO3Si
requires m/z 344.1682]; νmax(CCl4)/cmϪ1 1740 and 1650; δH(300
MHz) (for a mixture of two isomers) Ϫ0.15, 0.07 (total 9 H,
both s, SiMe3), 1.56–1.68 (1 H, m), 1.80–1.91 (1 H, m), 2.03–
2.22 (1 H, m), 2.37 (1 H, dt, J 11.9, 3.6), 2.46 (1 H, dt, J 16.2,
2.7), 2.98–3.11 (1 H, m), 3.827, 3.834 (total 3 H, both s, OMe),
4.40 (1/2 H, d, J 4.6, 4-H), 4.63 (1/2 H, d, J 4.9, 4-H), 5.25 (1/2
H, t, J 2.25, olefinic H), 5.28 (1/2 H, br s, olefinic H), 7.38–7.52
(3 H, m, ArH) and 7.65–7.68 (2 H, m, ArH).
Following the procedure described for the preparation of 8, 14
(1.68 g, 77%) was obtained from 13 (1.60 g, 4.53 mmol) and
o-iodobenzoyl chloride (2.42 g, 9.06 mmol) as an oil [Found:
(M ϩ H)ϩ, 484.0794. C20H27INO3Si requires m/z 484.0805];
νmax(CCl4)/cmϪ1 2180, 1740 and 1645; δH(60 MHz) 0.16 (9 H, s,
SiMe3), 1.7–2.9 (8 H, m), 3.36 (2 H, t, J 6.0, 5-H2), 3.78 (3 H, s),
6.9–7.5 (3 H, m, ArH) and 7.78 (1 H, br d, J 8.0, ArH).
Methyl 1-(tert-butoxycarbonyl)-2-[3-hydroxy-5-(trimethylsilyl)-
pent-4-ynyl]pyrrolidine-2-carboxylate 15
A solution of ethynyltrimethylsilane (258 mg, 2.63 mmol) in
THF (2 cm3) was added to a 1 mol dmϪ3 solution of ethyl-
magnesium bromide in THF (2.63 cm3, 2.63 mmol) at Ϫ78 ЊC
under a nitrogen atmosphere and the mixture was stirred at
Ϫ78 ЊC for 30 min. After being stirred for 2 h at room temper-
ature, the mixture was treated with a solution of 11 (500 mg,
1.75 mmol) in THF (10 cm3), added at 0 ЊC. After the mixture
had been stirred at 0 ЊC for 1 h, it was diluted with saturated aq.
NH4Cl and extracted with diethyl ether. The extract was dried
(MgSO4) and concentrated. The residue was chromatographed
on silica gel [hexane–AcOEt (4:1)] to give 15 (621 mg, 93%) as
an oily diastereoisomeric mixture [Found: (M ϩ H)ϩ, 384.2203.
C19H34NO5Si requires m/z 384.2206]; νmax(CCl4)/cmϪ1 3660,
3450, 2175, 1740 and 1700; δH(60 MHz) 0.16 (9 H, s, SiMe3),
1.42 (9 H, s, But), 1.55–2.5 (9 H, m), 3.2–3.8 (2 H, m), 3.71 (3 H,
s, OMe) and 4.2–4.5 (1 H, m, CHOH).
The second fraction gave methyl 1-benzoyl-2-[3-(trimethyl-
silyl)prop-2-ynyl]pyrrolidine-2-carboxylate 20 (53 mg, 18%), mp
60–61.5 ЊC (from pentane) (Found: C, 66.7; H, 7.5; N, 4.0.
C19H25NO3Si requires C, 66.4; H, 7.3; N, 4.1%); νmax(CCl4)/cmϪ1
2175, 1740 and 1635; δH(60 MHz) 0.20 (9 H, s, SiMe3), 1.8–2.5
(4 H, m), 2.80 (1 H, d, J 17, CHHC᎐CTMS), 3.4–3.8 (2 H, m,
᎐
᎐
᎐
Methyl 1-(tert-butoxycarbonyl)-2-[3-bromo-5-(trimethylsilyl)-
pent-4-ynyl]pyrrolidine-2-carboxylate 16
5-H ), 3.66 (1 H, d, J 17, CHHC᎐CTMS), 3.74 (3 H, s, OMe)
᎐
2
and 7.2–7.6 (5 H, m, ArH).
Carbon tetrabromide (779 mg, 2.35 mmol) and triphenyl-
phosphine (615 mg, 2.35 mmol) were added to a solution of 15
(600 mg, 1.57 mmol) in dichloromethane (10 cm3) at 0 ЊC and
the whole was stirred at room temperature for 1 h. The mixture
was evaporated and the residue was chromatographed on silica
gel [hexane–AcOEt (4:1)] to give 16 (616 mg, 88%) as an
oily diastereoisomeric mixture [Found: (M ϩ H)ϩ, 446.1374.
C19H3379BrNO4Si requires m/z 446.1362]; νmax(CCl4)/cmϪ1 2175,
1740 and 1700; δH(300 MHz) 0.18 (9 H, s, SiMe3) 1.43, 1.45
(total 9 H, both s, But), 1.80–2.18, 2.32–2.42 (total 8 H, both
m), 3.37–3.79 (2 H, m, 5-H2), 3.71, 3.72 (total 3 H, both s, OMe)
and 4.46–4.59 (1 H, m, CHBr).
Methyl 7-benzoyl-3-methylene-7-azabicyclo[2.2.1]heptane-1-
carboxylate 21
A mixture of 19 (200 mg, 0.58 mmol) and toluene-p-sulfonic
acid monohydrate (55 mg, 0.29 mmol) in wet acetonitrile (10
cm3) was heated under reflux for 3.5 h. After evaporation of the
mixture, the residue was dissolved in diethyl ether (10 cm3). The
solution was washed with 5% aq. Na2CO3 and brine, dried
(MgSO4) and concentrated. The residue was chromatographed
on silica gel [hexane–AcOEt (7:1)] to give 21 (109 mg, 69%) as
a colourless oil [Found: (M ϩ H)ϩ, 272.1275. C16H18NO3
requires m/z 272.1287]; νmax(CCl4)/cmϪ1 1740 and 1650; δH(300
MHz) 1.65 (1 H, ddd, J 11.5, 9.3, 3.9), 1.87 (1 H, ddd, J 11.8,
9.3, 4.8), 2.13 (1 H, tt, J 11.9, 4.8), 2.40 (1 H, tt, J 11.9, 3.6), 2.47
(1 H, br d, J 15.9, 2-HH), 3.05 (1 H, dq, J 15.9, 2.7, 2-HH),
3.82 (3 H, s, OMe), 4.51 (1 H, d, J 4.8, 4-H), 4.78 (1 H, br s,
Methyl1-(tert-butoxycarbonyl)-2-[5-(trimethylsilyl)pent-4-ynyl]-
pyrrolidine-2-carboxylate 17
Bu3SnH (862 mg, 2.96 mmol) and AIBN (45 mg, 0.27 mmol)
were added to a solution of 16 (1.20 g, 2.69 mmol) in benzene
(20 cm3) and the mixture was refluxed for 1 h. After evaporation
of the mixture, the residue was chromatographed on silica gel
[hexane–AcOEt (4:1)] to give 17 (924 mg, 94%) as a colourless
oil [Found: (M ϩ H)ϩ, 368.2267. C19H34NO4Si requires m/z
368.2258]; νmax(CCl4)/cmϪ1 2180, 1745 and 1700; δH(300 MHz)
0.15, 0.18 (total 9 H, both s, SiMe3), 1.41, 1.43, 1.45 (total 9 H,
s each, But), 1.30–2.29 (8 H, m), 2.26 (2 H, t, J 7.1), 3.35–3.77
(2 H, m, 5-H2) and 3.71, 3.72 (total 3 H, both s, OMe).
C᎐CHH), 4.82 (1 H, t, J 2.7, C᎐CHH), 7.37–7.53 (3 H, m,
᎐
᎐
ArH) and 7.65–7.70 (2 H, m, ArH).
Methyl 7-benzoyl-3-oxo-7-azabicyclo[2.2.1]heptane-1-
carboxylate 22
4% Aq. osmium tetroxide (0.05 cm3, 2.54 mg as OsO4, 0.01
mmol) was added to a solution of 21 (100 mg, 0.37 mmol) in
THF–H2O (4:1) (5 cm3) at 0 ЊC and the whole was stirred for 5
min. To this mixture was added NaIO4 (237 mg, 1.11 mmol)
over a period of 30 min and the mixture was stirred at room
temperature overnight after which it was diluted with water and
extracted with diethyl ether. The extract was dried (MgSO4) and
concentrated. The residue was chromatographed on silica gel
[hexane–AcOEt (3:1)] to give 22 (55 mg, 55%), mp 109–110 ЊC
(from hexane–AcOEt) (Found: C, 65.5; H, 5.5; N, 4.9. C15-
H15NO4 requires C, 65.9; H, 5.5; N, 5.1%); νmax(CCl4)/cmϪ1
1760, 1750 and 1660; δH(300 MHz) 1.77 (1 H, ddd, J 12.9, 9.3,
4.3), 1.97 (1 H, ddd, J 12.2, 9.3, 4.3), 2.24 (1 H, tt, J 12.2, 5.1),
2.43 (1 H, d, J 17.6, 2-HH), 2.53 (1 H, tt, J 12.2, 3.9), 3.08 (1 H,
Methyl 1-(o-iodobenzoyl)-2-[5-(trimethylsilyl)pent-4-ynyl]-
pyrrolidine-2-carboxylate 18
Following the procedure described for the preparation of 8, 18
(681 mg, 77%) was obtained from 17 (630 mg, 1.72 mmol) and
o-iodobenzoyl chloride (687 mg, 2.58 mmol) as a colourless
oil [Found: (M ϩ H)ϩ, 498.0974. C21H29INO3Si requires m/z
498.0962]; νmax(CCl4)/cmϪ1 2180, 1745 and 1650; δH(300 MHz)
0.15 (9 H, s, SiMe3), 1.65–2.04 (4 H, m), 2.13–2.40 (1 H, m),
2.16 (2 H, t, J 6.9), 2.30 (2 H, q, J 6.9), 2.47–2.58 (1 H, m), 3.30–
3342
J. Chem. Soc., Perkin Trans. 1, 1997