3-Polystyrylpropionic acid 2-[2-(3-pyridylmethyl)amino-2-
phenylethyl]allyl ester (29b)
dd, J = 6.5, 15.9 Hz), 2.53 (1H, ddq, J = 10.3, 16.2, 2.2 Hz); 13
C
NMR (75 MHz, CDCl3) 150.03, 148.57, 146.24, 142.13, 136.48,
134.76, 128.81, 127.77, 123.48, 105.32, 69.93, 58.74, 55.41,
42.79; m/z (ES) (rel. intensity) 251.2 (100[M ϩ H]ϩ); HRMS
m/z (ES) 251.1543 C17H19N2 ([MϩH]ϩ) requires 251.1543.
Using the procedure described for 25 using the following
amounts: 3-pyridinecarboxaldehyde (410 µL, 4.3 mmol), AcOH
(200 µL), resin 24 (600 mg) in DCE (10 mL), Me4NB(AcO)3H
(1.63 g, 6.2 mmol) in AcOH (200 µL) and DCE (10 mL)
afforded a white solid (629 mg). νmax (on-bead)/cmϪ1 3027m,
2922m, 2852w, 1731s, 1595s.
1-(Cyclohexylmethyl)-4-methylene-2-phenylpyrrolidine (30c).
From resin 29c (500 mg, 260 µmol). Purification by flash
chromatography (1.5 × 5.0 cm silica), eluting with Et2O :
hexane (3 : 97), afforded a colourless oil (10 mg, 39 µmol, 15%
from 20). νmax (film)/cmϪ1 3012w, 2934m, 2840m, 1648w,
3-Polystyrylpropionic acid 2-[2-(cyclohexylmethyl)-2-
phenylethyl]allyl ester (29c)
1
1602m; H NMR (400 MHz, CDCl3) 7.43–7.21 (5H, m), 4.92
Using the procedure described for 25 using the following
amounts: cyclohexane carboxaldehyde (360 µL, 3.0 mmol),
AcOH (100 µL), resin 24 (600 mg), Me4NB(AcO)3H (0.8 g,
3.0 mmol) in DCE (10 mL) afforded a white solid (641 mg).
νmax (on-bead)/cmϪ13031m, 2916s, 2846m, 1729s, 1604m.
(1H, s), 4.87 (1H, s), 3.90 (1H, d, J = 13.9 Hz), 3.36 (1H, dd,
J = 6.5, 10.5 Hz), 2.85 (1H, br d, J = 13.9 Hz), 2.76 (1H, dd,
J = 6.5, 16.4 Hz), 2.43–2.33 (1H, m), 2.27 (1H, t, J = 11.4 Hz),
2.07 (1H, br d, J = 13.4 Hz), 1.88 (1H, dd, J = 3.5, 11.4 Hz),
1.73–1.59 (3H, m), 1.53 (1H, br d, J = 12.4 Hz), 1.48–1.33 (1H,
m), 1.29–1.02 (3H, m), 0.85–0.64 (2H, m); 13C NMR (100 MHz,
CDCl3) 147.99, 143.72, 128.70, 127.95, 127.45, 104.68, 70.82,
61.84, 59.58, 43.45, 37.20, 32.42, 31.64, 27.25, 26.66, 26.45; m/z
(ES) (rel. intensity) 256.2 (100[M ϩ H]ϩ); HRMS (ES) m/z
256.2069 C18H26N ([M ϩ H]ϩ) requires 256.2065.
3-Polystyryl-propionic acid 2-[2-benzylamino-2-
(4-chlorophenyl)-ethyl]-allyl ester (29d)
Using the procedure described for 25 using the following
amounts: benzaldehyde (380 µL, 3.5 mmol), AcOH (160 µL),
resin 28 (350 mg) in DCE (8 mL), Me4NB(AcO)3H (730 mg,
2.8 mmol) in AcOH (160 µL) and DCE (8 mL) afforded a white
solid (359 mg). νmax (on-bead)/cmϪ1 3027m, 2917m, 1730s
1-Benzyl-2-(4-chlorophenyl)-4-methylenepyrrolidine
(30d).
From resin 29d (200 mg, 102 µmol). Purification by flash
chromatography (1.5 × 5.0 cm silica), eluting with Et2O :
hexane (2 : 98), afforded a colourless oil (20 mg, 70 µmol, 70%
from 20). νmax (film)/cmϪ1 2987m, 1638m, 1605m; 1H NMR (300
MHz, CDCl3) 7.51–7.40 (1H, m), 7.39–7.15 (8H, m), 4.87 (2H,
s), 3.83 (1H, d, J = 13.4 Hz), 3.64 (1H, d, J = 13.9 Hz), 3.55 (1H,
dd, J = 6.5, 9.9 Hz), 3.03 (1H, d, J = 13.4 Hz), 2.94 (1H, d,
J = 13.9 Hz), 2.83 (1H, dd, J = 6.5, 16.4 Hz), 2.55–2.40 (1H, m);
13C NMR (75 MHz, CDCl3) 146.54, 141.40, 139.15, 133.08,
129.07, 128.88, 128.68, 128.39, 127.10, 105.08, 69.07, 58.76,
58.13, 42.95; m/z (ES) (rel. intensity) 284.2 (100[M ϩ H]ϩ);
HRMS m/z (ES) 284.1203 C18H19ClN ([M ϩ H]ϩ) requires
284.1206.
(C᎐O), 1600m.
᎐
3-Polystyrylpropionic acid 2-[2-(3-pyridylmethyl)amino-2-
(4-chlorophenyl)ethyl]allyl ester (29e)
Using the procedure described for 25 using the following
amounts: 3-pyridinecarboxaldehyde (240 µL, 2.5 mmol), AcOH
(160 µL), resin 28 (350 mg) in DCE (8 mL), Me4NB(AcO)3H
(950 mg, 3.6 mmol) in AcOH (160 µL) and DCE (8 mL)
afforded a white solid (371 mg). νmax (on-bead)/cmϪ13027m,
2922s, 1725s, 1595m.
General procedure for pyrrolidines 30a–e.
1-(3-Pyridylmethyl)-4-methylene-2-(4-chlorophenyl)-pyrrol-
idine (30e). From resin 29e (200 mg, 102 µmol). Purification by
flash chromatography (1.5 × 5.0 cm silica), eluting with Et2O :
hexane (60 : 40), afforded a colourless oil (9 mg, 32 µmol, 31%
from 20). νmax (film)/cmϪ1 3029m, 1621m, 1597m; 1H NMR (300
MHz, CDCl3) 8.53 (2H, br s), 7.66 (1H, d, J = 8.1 Hz), 7.44 (2H,
d, J = 6.8 Hz), 7.34 (2H, d, J = 6.8 Hz), 7.24 (1H, dd, J = 4.4, 7.4
Hz), 4.90 (2H, s), 3.81 (1H, d, J = 14.0 Hz), 3.62 (1H, d, J = 14.0
Hz), 3.57 (1H, dd, J = 6.6, 10.3 Hz), 3.10 (1H, d, J = 14.0 Hz),
2.94 (1H, br dd, J = 2.2, 14.0 Hz), 2.86 (1H, br dd, J = 6.6,
16.2 Hz), 2.45 (1H, ddq, J = 10.3, 16.2, 3.0 Hz); 13C NMR
(75 MHz, CDCl3) 150.30, 148.82, 146.58, 142.50, 136.73,
135.03, 129.73, 128.01, 123.73, 105.54, 70.19, 59.04, 55.70,
43.10; m/z (ES) (rel. intensity) 285.1 (100[M ϩ H]ϩ); HRMS
(ES) m/z 285.1160 C17H18ClN2 ([M ϩ H]ϩ) requires 285.1159.
A mixture of Pd(acac)2 (5.5 mg, 18.0 µmol), dppe (21.3 mg,
53.5 µmol) and resin 29a–e (500 mg, 0.26 mmol based on load-
ing of resin 20) in THF (10 mL) was heated at reflux for 12 h.
The resin was collected by filtration and washed with CH2Cl2
(50 mL). The filtrate solvent was removed in vacuo to afford the
crude product.
1-(2-Furylmethyl)-4-methylene-2-phenylpyrrolidine
(30a).
Purification by flash chromatography (1.5 × 5.0 cm silica), elut-
ing with CH2Cl2, afforded a colourless oil (19 mg, 79 µmol, 30%
from 20). νmax (film)/cmϪ13054m, 1644m, 1597m; 1H NMR (300
MHz, CDCl3) 7.48–7.25 (6H, m), 6.31 (1H, dd, J = 1.7, 3.2 Hz),
6.13 (1H, d, J = 3.2 Hz), 4.91 (1H, br s), 4.88 (1H, br s), 3.76
(2H, d, J = 14.4 Hz), 3.56 (1H, dd, J = 6.7, 10.3 Hz), 3.27 (1H, d,
J = 14.4 Hz), 3.13 (1H, br d, J = 14.0 Hz), 2.81 (1H, br dd,
J = 6.7, 16.2 Hz), 2.51 (1H, m); 13C NMR (100 MHz, CDCl3)
152.84, 146.73, 142.34, 128.98, 128.05, 127.90, 110.45, 108.53,
105.37, 69.08, 58.83, 49.37, 43.02; m/z (ES) (rel. intensity)
240.3 (100[M ϩ H]ϩ); HRMS m/z (ES) 240.1389 C16H18NO
([M ϩ H]ϩ) requires 240.1388.
tert-Butyl 3-methyl-1-phenylbut-3-enylcarbamate (32)
Pd(acac)2 (1.5 mg, 4.9 µmol, 20 mol%), dppe (5.8 mg, 14.6
µmol, 60 mol%) and Me4NB(AcO)3H (63 mg, 240 µmol) were
added to a solution of 22 (50 mg, 26 µmol) in THF (2 mL). The
yellow solution was stirred, under nitrogen, at room temper-
ature for 18 h. The resin was collected by filtration and washed
with CH2Cl2 (70 mL) and CH3OH (30 mL) and the filtrate
solvent removed in vacuo. Purification by flash chromatography
(1.5 × 5.0 cm silica), using a CH2Cl2 : hexane (1 : 1) eluent
system, afforded a white solid (4.8 mg, 18.0 µmol, 69%). Mp
106-109 ЊC; νmax (soln)/cmϪ1 3386m, 2975m, 2930m, 1681s,
1518s, 1251m, 1173s, 1018m; 1H NMR (300 MHz, CDCl3)
7.28–7.14 (5H, m), 4.76–4.68 (3H, m), 4.66 (1H, s), 2.42–2.27
(2H, m), 1.65 (3H, s), 1.21 (9H, s); 13C NMR (100 MHz,
CDCl3) 154.24, 140.90, 127.46, 126.06, 125.09, 112.77, 78.43,
1-(3-pyridylmethyl)-4-methylene-2-phenylpyrrolidine
(30b).
From resin 29b (175 mg, 91 µmol). Purification by flash
chromatography (1.5 × 5.0 cm silica), eluting with an Et2O :
hexane mixture (60 : 40), afforded a colourless oil (16 mg, 64
µmol, 70% from 20). νmax (film)/cmϪ1 3023m, 1652w, 1605m;
1H NMR (300 MHz, CDCl3) 8.51 (2H, br s), 7.65 (1H, d,
J = 8.1 Hz), 7.50 (2H, d, J = 7.3 Hz), 7.43–7.28 (3H, m), 7.24
(1H, dd, J = 4.1, 7.0 Hz), 4.89 (2H, s), 3.84 (1H, d, J = 13.2 Hz),
3.64 (1H, d, J = 13.3 Hz), 3.62 (1H, dd, J = 6.6, 10.0 Hz), 3.11
(1H, d, J = 13.4 Hz), 2.95 (1H, dd, J = 2.0, 13.2 Hz), 2.86 (1H,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 6 9 9 – 2 7 0 9
2706