1826
D. J. Kerr and B. L. Flynn
(20 mL). The combined organic extracts were dried over MgSO4
and concentrated onto silica gel (2 g) under reduced pressure.
The solid residue was subjected to flash chromatography (silica
gel, sequential elution 78 : 22 - 7 : 3 hexane/ethyl acetate)
giving the title compound as a thick gum (109 mg, 70 %). nmax
(neat)/cmꢁ1 3065, 2958, 1777, 1673, 1475, 1386, 1200, 910,
727. dH (CDCl3, 300 MHz) 7.42 (2H, dd, J 8.0, 1.7), 7.35–7.22
(6H, m), 7.02 (2H, dd, J 7.2, 2.1), 5.93 (1H, s), 5.71 (1H, mc),
5.50 (1H, dd, J 9.2, 6.4), 5.43 (1H, br s), 5.24 (2H, s), 5.02–4.92
(2H, m), 4.72 (1H, app. t, Japp 9.0), 4.21 (1H, dd, J 9.0, 6.4), 3.51
(1H, dd, J 6.8, 2.9), 2.48–2.40 (2H, m), 2.03 (2H, app. q, Japp
7.1), 1.96 (1H, app. octet, Japp 6.7), 1.59 (2H, app. quin, Japp 7.7),
1.01 (3H, d, J 6.9), 0.97 (3H, d, J 6.9). dC (CDCl3, 75 MHz;
JMOD) 181.8 (C), 169.6 (C), 153.9 (C), 153.8 (C), 149.3 (C),
138.3 (C), 137.7 (CH), 137.3 (C), 131.3 (C), 129.1 (CH), 128.8
(CH), 128.4 (CH), 127.5 (CH), 126.9 (CH), 126.1 (CH), 115.4
(CH2), 105.3 (CH), 69.7 (CH2), 61.3 (CH), 58.7 (CH), 47.7
(CH2), 43.7 (CH), 33.2 (CH2), 31.7 (CH), 27.4 (CH2), 25.9
(CH2), 20.5 (CH3), 20.1 (CH3). m/z (ESI) 1038.7 (5 %, 2 ꢀ [M þ
NH4]þ), 533.4 (10 %, [M þ Na]þ), 511.4 (100 %, [MH]þ).
HRMS m/z 533.2409; calcd for C32H34N2NaOþ4 533.2416.
Minor isomer 24 was obtained as a thick gum (34 mg, 22 %).
nmax (neat)/cmꢁ1 3032, 2957, 1777, 1698, 1672, 1474, 1385,
1194, 911, 712. dH (CDCl3, 300 MHz) 7.44–20 (8H, m), 7.05
(2H, d, J 6.9), 5.96 (1H, s), 5.71 (1H, mc), 5.47 (1H, dd, J 8.3,
2.6), 5.43 (1H, d, J 3.0), 5.33–5.20 (2H, m), 5.02–4.93 (2H, m),
4.76 (1H, app. t, Japp 8.6), 4.29 (1H, dd, J 8.9, 2.6), 3.39 (1H, dd,
J 6.6, 3.0), 2.46 (2H, t, J 7.7), 2.05 (2H, app. q, Japp 7.1), 1.95
(1H, app. octet, Japp 6.7), 1.62 (2H, app. quin, Japp 7.7), 0.98
(3H, d, J 6.9), 0.93 (3H, d, J 6.6). dC (CDCl3, 75 MHz; JMOD)
183.0 (C), 169.8 (C), 154.2 (C), 154.0 (C), 149.6 (C), 139.5 (C),
137.7 (CH), 137.3 (C), 131.6 (C), 129.2 (CH), 128.8 (CH), 128.6
(CH), 127.6 (CH), 126.8 (CH), 125.7 (CH), 115.4 (CH2), 105.4
(CH), 69.9 (CH2), 60.6 (CH), 58.2 (CH), 47.7 (CH2), 44.9 (CH),
33.2 (CH2), 31.6 (CH), 27.4 (CH2), 25.9 (CH2), 20.3 (CH3), 20.1
(CH3). m/z (ESI) 1021.7 (5 %, 2 ꢀ [M þ H]þ), 533.4 (10 %,
[M þ Na]þ), 511.5 (100 %, [MH]þ). HRMS m/z 533.2404; calcd
for C32H34N2NaOþ4 533.2416.
m), 4.20 (2H, q, J 7.1), 3.21 (1H, dsept, J 9.9, 6.6), 2.51 (2H, t,
J 7.8), 2.07 (2H, app. q, Japp 7.1), 1.67 (2H, app. quin, Japp 7.5),
1.21 (3H, t, J 7.1), 1.09 (6H, d, J 6.6). dC (CDCl3, 75 MHz;
JMOD) 182.2 (C), 165.8 (C), 153.8 (CH), 144.3 (C), 138.3 (C),
137.7 (CH), 133.3 (C), 129.9 (C), 128.4 (CH), 126.9 (CH), 126.0
(CH), 122.4 (CH), 115.2 (CH2), 107.9 (CH), 60.6 (CH2), 48.2
(CH2), 33.1 (CH2), 28.5 (CH), 27.3 (CH2), 25.6 (CH2), 22.1
(CH3), 14.0 (CH3). m/z (ESI) 804.7 (25 %, 2 ꢀ [M þ NH4]þ),
394.5 (100 %, [MH]þ). HRMS m/z 394.2376; calcd for
C25H32NOþ3 394.2382.
trans-Ethyl 1-Benzyl-4-isopropyl-6-oxo-2-(pent-4-enyl)-
1,4,5,6-tetrahydrocyclopenta[b]pyrrole-5-carboxylate
(rac-27)
MeSO3H (0.70 mL, 10.5 mmol) was added dropwise to a stirred
solution of 26 (825 mg, 2.10 mmol) in DCM (11 mL) at room
temperature, and the mixture was stirred for 0.5 h. After this
time, the acid was quenched by gradual addition of NaHCO3
(5 % w/v aqueous, 60 mL). After stirring for 1 h, the mixture was
taken up in DCM (40 mL), and the organic phase was separated.
The aqueous phase was then re-extracted with DCM
(2 ꢀ 20 mL). The combined organic extracts were dried over
MgSO4 and concentrated to give the title compound as a thick oil
(817 mg, 99 %). nmax (neat)/cmꢁ1 2958, 1732, 1677, 1473, 1247,
1153, 1029, 725. dH (CDCl3, 300 MHz) 7.32–7.18 (3H, m), 7.08
(2H, d, J 7.5), 5.97 (1H, s), 5.73 (1H, mc), 5.35–5.22 (2H, m),
5.03–4.94 (2H, m), 4.23 (2H, q, J 7.1), 3.56 (1H, d, J 2.7), 3.31
(1H, dd, J 6.3, 2.7), 2.49 (2H, t, J 7.8), 2.06 (2H, app. q, Japp 7.1),
1.94 (1H, app. octet, Japp 6.7), 1.64 (2H, app. quin, Japp 7.5), 1.29
(3H, t, J 7.1), 1.00 (3H, d, J 6.6), 0.99 (3H, d, J 6.6). dC (CDCl3,
75 MHz; JMOD) 183.2 (C), 170.7 (C), 153.6 (C), 149.4 (C),
137.6 (CH), 137.2 (C), 132.2 (C), 128.6 (CH), 127.4 (CH), 126.8
(CH), 115.3 (CH2), 105.1 (CH), 62.7 (CH), 61.1 (CH2), 47.6
(CH2), 45.4 (CH), 33.1 (CH2), 31.8 (CH), 27.2 (CH2), 25.8
(CH2), 20.1 (CH3), 19.7 (CH3), 14.1 (CH3). m/z (ESI) 804.6
(20 %, 2 ꢀ [M þ NH4]þ), 394.5 (100 %, [MH]þ). HRMS m/z
394.2367; calcd for C25H32NOþ3 394.2382.
1-Benzyl-4-isopropyl-2-(pent-4-enyl)-4,5-
(Z)-Ethyl 2-[1-benzyl-5-(pent-4-enyl)-1H-pyrrole-2-
carbonyl]-4-methylpent-2-enoate (26)
dihydrocyclopenta[b]pyrrole-6(1H)-one (rac-28)
Sulfuric acid (680 mL, 12.9 mmol) was added dropwise to a
stirred mixture of ester rac-27 (817 mg, 2.08 mmol) and H2O
(1.2 mL) in ethanol (95 %, 8 mL). This solution was then
refluxed for 8 h. After this time, the reaction was cooled to room
temperature and quenched with aqueous NaHCO3 (5 % v/w
aqueous, 100 mL) before addition of DCM (30 mL) and sepa-
ration of the organic phase. The aqueous phase was re-extracted
with DCM (2 ꢀ 20 mL), and the combined organic extracts were
dried over MgSO4 and concentrated onto silica (3 g). Flash
chromatography (silica gel, sequential elution 9 : 1 - 88 : 12
hexane/ethyl acetate) gave the title compound as a discoloured
oil (601 mg, 90 %). nmax (neat)/cmꢁ1 3065, 2956, 1668, 1470,
1389, 1259, 911, 721. dH (CDCl3, 300 MHz) 7.32–7.20 (3H, m),
7.08 (2H, d, J 7.5), 5.94 (1H, s), 5.73 (1H, mc), 5.31 (2H, s),
5.02–4.94 (2H, m), 2.99 (1H, ddd, J ,6.6, 6.3, 1.6), 2.90 (1H,
dd, J 17.8, 6.3), 2.54 (1H, dd, J 17.8, 1.6), 2.48 (2H, t, J 7.8), 2.06
(2H, app. q, Japp 7.1), 1.84 (1H, app. octet, Japp 6.6), 1.64 (2H,
app. quin, Japp 7.5), 0.96 (6H, d, J 6.9). dC (CDCl3, 75 MHz;
JMOD) 190.1 (C), 154.2 (C), 147.9 (C), 137.7 (CH), 137.6 (C),
133.6 (C), 128.6 (CH), 127.3 (CH), 126.7 (CH), 115.2 (CH2),
104.8 (CH), 47.4 (CH2), 46.1 (CH2), 40.3 (CH), 33.1 (CH2), 32.1
(CH), 27.4 (CH2), 25.7 (CH2), 20.2 (CH3), 19.6 (CH3). m/z (ESI)
Bis(dibenzylideneacetone)palladium(0) (82 mg, 0.143 mmol)
was added to a stirred solution of triphenylphosphine (150 mg,
0.570 mmol) in THF (35 mL) and left to stir for 0.5 h at room
temperature. After this time, alkyne 25[9] (0.701 g, 5.00 mmol)
was added, followed by dropwise addition of Bu3SnH (1.40 mL,
5.0 mmol), and the mixture was then stirred for 0.5 h. Acid
chloride 16 (1.44 g, 5.0 mmol) and CuICl (350 mg, 3.5 mmol)
were then added, and the reaction stirred at room temperature for
24 h. After this time, potassium fluoride (10 % w/v in H2O,
30 mL) was added, and the triphasic mixture was stirred for 5 h.
To this mixture, H2O (20 mL) and Et2O (60 mL) were added.
After separation, the aqueous phase was re-extracted with Et2O
(30 mL), and the combined organic fractions were dried over
MgSO4 and concentrated onto silica gel (5 g) under reduced
pressure. The solid residue was subjected to flash chromato-
graphy (silica gel, sequential elution 94 : 6 - 87 : 13 hexane/
Et2O) giving the title compound as a discoloured oil (1.09 g,
55 %). nmax (neat)/cmꢁ1 3066, 2961, 1719, 1638, 1623, 1478,
1215, 1183, 1032, 727. dH (CDCl3, 300 MHz) 7.30–7.20
(3H, m), 6.95 (2H, d, J 7.5), 6.82 (1H, d, J 4.2), 6.27 (1H, d, J 9.9),
6.03 (1H, d, J 4.2), 5.74 (1H, mc), 5.68 (2H, s), 5.02–4.94 (2H,