C. E. Banks et al. / Tetrahedron 61 (2005) 2365–2372
2371
argon at K78 8C. The resulting dark blue solution was
stirred for 1 h before the addition of bis(methoxyethyl)-
amine (5.90 mL, 40.0 mmol, 10.0 equiv) and dry tetrahy-
drofuran (20 mL). After 5 min isopropyl 1-(tert-
dichloromethane-light petroleum (bp 40–60 8C)]; R [ethyl
f
acetate-light petroleum (bp 40–60 8C) 20:80] 0.50; n
(solution cell)/cm 3370 (NH), 2978 (CH), 2936 (CCH3),
max
K1
1713 (CO), 1457 (CH ), 1441 (CH ), 1420 (CH ), 1250
2
2
3
2
butoxycarbonyl)pyrrole-2-carboxylate (1.01 g, 4.0 mmol)
(COC), 1043 (COC) and 1021 (COC); dH (400 MHz;
CDCl ) 5.63–5.60 (2H, m, NCH CH]CH), 4.46–5.40 (2H,
dissolved in dry tetrahydrofuran (30 mL) was added
dropwise over 5 min and stirred for a further 55 min, the
dark blue colour persisting throughout. Isoprene
3
2
m, NCH CH]CH), 4.97 (2H, sep, JZ6.3 Hz, OCH), 4.73–
2
4.69 (2H, br m, NH), 3.86–3.69 (4H, dm, NCH ), 3.27–3.52
(2H, m, CHCO ), 1.78–1.66 (2H, m, CHCH H ), 1.43
2
(
disappeared. On addition of diiodomethane (2.26 cm ,
w0.25 mL) was added until the dark blue colour
2
A B
3
(20H, apparent s, CMe and CHCH H ) and 1.22–1.19
3 A B
2
8.0 mmol, 7.0 equiv) the rapidly stirring solution turned
(12H, m, CHMe ); d (100.6 MHz; CDCl ) 172.7, 155.7,
2 C 3
dark brown and was allowed to stir for 15 min before the
addition of saturated ammonium chloride (5 mL). The
reaction was allowed to warm to ambient temperature and
130.1, 129.2, 79.3, 68.2, 44.0, 37.7, 29.6, 28.4, 21.7 and
21.6; dH (400 MHz; C D ) 5.46–5.36 (4H, m, CH]CH),
4.97, 4.96 (2H, sep, JZ6.3 Hz, OCH), 4.55, 4.45
6
6
K3
ammonia evaporated. Aqueous citric acid (1.0 mol dm ,
25 mL) was added and the solution stirred for 5 min before
(2H, s, NH), 3.90–3.79 (2H, NCH H ), 3.66–3.60 (2H, m,
NCH CH ), 3.33 (2H, s, CHCO ), 1.84–1.80 (2H, m,
A B 2
A
B
1
being separated. The aqueous layer was extracted with ether
CHCH H ), 1.58–1.49 (2H, m, CHCH H ), 1.44, 1.43
A
B
A B
(
(
4!150 mL), the combined organic extracts were dried
anhydrous magnesium sulfate) and evaporated under
(18H, s, CMe ) and 1.02, 1.00 (12H, d, JZ6.3 Hz, CHMe );
dC (100.6 MHz; C D ) 172.8, 155.9, 130.5, 130.4, 78.9,
6 6
3
2
reduced pressure. The residue was chromatographed
SiO , ethyl acetate-light petroleum (bp 40–60 8C), 5:95],
68.1, 44.4, 38.3, 30.2, 28.7, 22.0 and 21.9; m/z (CESI)
563 (100%, MNa ), 542 (1, MH ) and 442 (100,
MH –CO CMe ); (Found MH , 541.3488. C H N O
2 3 28 49 2 8
C
C
[
2
C
C
to give the dihydropyrrole 1 (1.49 g, 94%) as an oil; Rf
ethyl acetate-light petroleum (bp 40–60 8C), 5:95] 0.11;
nmax (thin film)/cm 2978 (CH), 2933 (CH), 2866, 1727
[
requires MH, 541.3489).
K1
(
CO), 1704 (NCO), 1550 (C]C), 1258 (COC), and 1177
5.2.3. 1-(tert-Butoxycarbonyl)-pyrrolidine. Pyrrolidine
(372 mg, 5.23 mmol) was dissolved in dichloromethane
(50 mL) and stirred at ambient temperature. Di-tert-butyl
dicarbonate (1.24 g, 5.69 mmol, 1.1 equiv) dissolved in
dichloromethane (10 mL) was added dropwise and the
reaction stirred under an atmosphere of argon for 2 h.
The mixture was evaportated under reduced pressure. The
(
COC); d (400 MHz; CDCl ) 6.11, 6.05 (1H, dt, JZ6.1,
H
3
2
.0 Hz, CH]CH–C), 5.42, 5.38 (1H, dt, JZ6.1, 2.0 Hz,
2
CH CH]CH), 4.99 (1H, sep, JZ6.3 Hz, OCH), 4.40, 4.12
(
1H, d, JZ10.6 Hz, CH H I), 4.31–4.12 (2H, m, NCH ),
A B 2
3
CMe ) and 1.25–1.19 (6H, m, CHMe ); d (100.6 MHz;
.85, 3.83 (1H, d, JZ10.6 Hz, CH H I), 1.47, 1.45 (9H, s,
A B
3
2
C
CDCl ) 168.0, 167.7, 153.1, 152.7, 130.4, 130.2, 129.4,
3
residue was chromatographed [SiO , ether-light petroleum
2
1
2
29.1, 80.9, 80.1, 75.1, 74.4, 69.8, 69.6, 55.4, 55.2, 28.4,
1.7, 21.6, 13.7, 13.4; m/z (CESI) 417 (23, MNa ) and 396
(bp 40–60 8C), 10:90], to give the carbamate (604 mg, 68%)
as an oil; dH (400 MHz; CDCl ) 3.30 (4H, d, JZ9.6 Hz,
C
3
C
C
(MH ); (Found MNa , 418.0482. C H NO INa requires
1
MNa, 418.0491).
NCH ), 1.83 (4H, m, CH ) and 1.46 (9H, s, CMe ). d
2
4
22
4
2
3
C
(100.6 MHz; CDCl ) 154.7, 78.8, 45.9, 28.5 and 25.0. All
3
1
6
data agreed with that previously published.
5
.2.2. (meso)-Diisopropyl 2,5-bis-(3-tert-butoxycarbonyl-
amino-propenyl)-hex-cis-enedioic-1-carboxylate 4.
Freshly cut lithium wire (20.8 mg, 3.00 mmol, 3.0 equiv)
was hammered out into a foil, cut into several small strips,
and placed in a Schlenk tube containing DBB (798 mg,
5.2.4. Isopropyl cyclohexanecarboxylate. Isopropyl alco-
hol (0.38 mL, 4.97 mmol) was dissolved in dichloro-
methane (30 mL) and triethylamine (2.20 mL, 15.8 mmol,
3.2 equiv) added. The reaction was cooled to 0 8C under an
atmosphere of argon and cyclohexane carbonyl chloride
(0.91 mL, 6.80 mmol, 1.4 equiv) was added dropwise and
allowed to warm to room temperature. After 4 h of stirring
the mixture was poured into saturated ammonium chloride
(50 mL) and the layers separated. The aqueous layer was
3
.00 mmol, 3.0 equiv) and some glass ‘antibumping’
granules. The tube was evacuated and purged with argon
several times. The contents of the Schlenk tube were then
stirred vigorously until the lithium foil had been completely
reduced to a powder (typically 0.5–2 h) under an atmo-
sphere of argon. The Schlenk tube was cooled to K78 8C
under an atmosphere of argon, and tetrahydrofuran (25 mL)
added, immediately resulting in a dark turquoise solution.
Pyrroline 1 (394 mg, 1.00 mmol) dissolved in dry tetra-
hydrofuran (30 mL) were added dropwise over a period of
3
extracted with ether (3!50 cm ), the combined organic
extracts were dried (anhydrous magnesium sulphate) and
evaporated under reduced pressure. The residue was
chromatographed [SiO
40–60 8C), 2:98], to give the ester (651 mg, 77%) as a
liquid; d (400 MHz; CDCl ) 4.99 (1H, hp, JZ6.3 Hz,
OCH), 2.24 (1H, tt, JZ11.2, 3.6 Hz, CHCO), 1.94–1.84
(2H, m, C , C ), 1.82–1.69 (2H, m, C
), 1.49–1.35 (2H, m, C , C ), 1.34–
1.12 (4H, m, C , C , and CH ), 1.66 (6H, d, JZ
6.3 Hz, OCHMe (100.6 MHz; CDCl ) 175.6, 67.0,
43.4, 29.0, 25.8, 25.4 and 21.8. All data agreed with that
, ethyl acetate-light petroleum (bp
2
2
–5 min. The turquoise colour persisted throughout the
H
3
course of the substrate addition. The reaction mixture was
stirred at K78 8C for a further 2 h and saturated ammonium
chloride (5 mL) was added. The reaction mixture was
H
A
H
H
A
H
H H ,
3 A B
2
B
6
B
C
H
A
H
H
H
B
H H
6 A B
5
B
2
A
separated and the aqueous layer extracted with ethyl acetate
3
H
A
H
B
H
5
A
H
B
2
3
3!15 cm ). The combined organic extracts were dried
anhydrous magnesium sulfate) and evaporated under
(
(
2
). d
C
3
1
7
reduced pressure. The residue was chromatographed
SiO , light petroleum (bp 40–60 8C), then ethyl acetate-
previously published.
[
2
light petroleum (bp 40–60 8C), 10:90], to give the carbamate
(198 mg, 79%) as needles, mp 87–90 8C [(from
5.2.5. 2(RS)-Methyl 1-(tert-butoxycarbonyl)-2-iodo-
methyl-2,5-dihydropyrrole-2-carboxylate 9. Ammonia
4