(10 cm3) for 5 h at 60 ЊC. The mixture was cooled, and the resin
was removed by filtration and washed with DMF (2 × 10 cm3),
THF : water 1 : 1 (3 × 10 cm3), CH2Cl2 (3 × 10 cm3) and
methanol (3 × 10 cm3). The resin was dried in air and in vacuo
to constant weight 1.52 g. The loading was determined to be
0.16 Meq gϪ1 by cleavage of a sample using neat TFA.
ation from EtOH–water, gave 14 (156 mg, 0.46 mmol, 83%).
Mp 200–202 ЊC (Found Mϩ Ϫ ZHNCHCO2H 135.0439;
C8H7O2 requires 135.0446); IR (KBr disc). 3309, 3031, 2960,
2673, 2551, 1689, 1539, 1425, 1286, and 1268; [α]D 14.2 (c 1.5,
EtOH); NMR δH 3.12 (1H, dd, J 14, 9.5), 3.34 (1H, dd, J 14, 5),
4.54–4.59 (1H, m), 5.02 (2H, s), 6.61 (1H, d, J 8.5), 7.26–7.35
(5H, m), 7.44 (2H, d, J 8.5), and 7.96 (2H, d, J 8.5); δC (125
MHz, acetone-d6) 38.1, 55.7, 66.6, 128.5, 128.6, 129.1, 129.8,
130.3, 130.5, 138.1, 143.9, 156.8, 167.5, and 173.0; m/z (EI)
135 (CH2C6H4COOHϩ, 100%), 107 (62), 91 (89, C7H7ϩ), and
79 (82).
Rink 4-iodobenzamide resin 10
Fmoc Rink amide resin (0.47 Meq gϪ1) (995 mg, 0.47 mmol)
was treated with piperidine in DMF (20% v/v, 10 cm3) for 30
min. The resin was washed with DMF (3 × 30 cm3), CH2Cl2
(3 × 10 cm3) and methanol (3 × 10 cm3) and dried in air and in
vacuo. The resin, 4-iodobenzoic acid (352 mg, 1.42 mmol),
DCC (309 mg, 1.50 mmol) and DMAP (17 mg, 0.14 mmol)
were combined in DMF (10 cm3) and stirred gently at 58–60 ЊC
for 3.5 h. The solvent was removed by filtration and the resin
washed with THF (3 × 10 cm3), toluene–EtOH 1 : 1 (3 × 10
cm3), CH2Cl2 (3 × 10 cm3) and methanol (3 × 10 cm3). The resin
was dried in air and in vacuo to constant weight 857 mg. The
loading was determined to be 0.43 Meq gϪ1 by cleavage of
a sample using 1% TFA in CH2Cl2.
Treatment of resin 9 (370 mg, 0.16 Meq gϪ1) with zinc reagent
3, according to the general procedure, gave 14 (19 mg, 93%).
4-[2Ј-(Fluoren-9Љ-ylmethoxycarbonylamino)-2Ј-(methoxy-
carbonyl)ethyl]benzoic acid 15
Treatment of resin 8 (202 mg, 1.1 Meq gϪ1) with zinc reagent 4,
according to the general procedure, followed by recrystallis-
ation from CH2Cl2–petrol, gave 15 (48 mg, 0.11 mmol, 69%).
Mp 172–174 ЊC; IR (KBr disc) 3315, 3065, 3018, 2672, 2554,
1735, 1695, 1533, 1287, and 740; [α]D 7.8 (c 1.0 in EtOH); NMR
δH 3.15 (1H, dd, J 6, 14), 3.22 (1H, dd, J 6, 14), 3.74 (3H, s), 4.21
(1H, t, J 7), 4.39 (1H, dd, J 7, 10.5), 4.48 (1H, dd, J 7, 10.5), 4.72
(1H, q, J 6), 5.44 (1H, d, J 8), 7.18 (2H, d, J 8), 7.29–7.34 (2H,
m), 7.40 (2H, t, J 7.5), 7.58 (2H, t, J 6.5), 7.77 (2H, d, J 7.5), and
8.03 (2H, d, J 8); δC 38.3, 47.2, 52.6, 54.6, 67.0, 120.0, 125.0,
127.1, 127.8, 128.3, 129.5, 130.5, 141.4, 142.1, 143.7, 155.6,
171.1, and 171.8; m/z (EI) 368 (58%), 206 (69), 178 (100), and
88 (61).
Preparation and coupling of alkylzinc iodides with solid-
supported electrophiles. General procedure
Zinc dust (5.5 equiv.) was suspended in dry THF (1 cm3). 1,2-
Dibromoethane (0.25 equiv.) was added and the slurry heated
to ∼65 ЊC. After cooling to room temperature TMS-Cl (0.05
equiv.) was added and the slurry stirred for 10 min. The alkyl
iodide was then added, and the zinc insertion process moni-
tored by TLC. After insertion was judged to be complete,
stirring was stopped and excess zinc was allowed to settle. The
solution of alkylzinc iodide (3 equiv.) was transferred to a flask
containing the solid-supported aryl or vinyl iodide, Pd2(dba)3
(0.05 equiv.) and P(o-tolyl)3 (0.2 equiv.) suspended in 2 cm3
solvent. The suspension was stirred gently overnight, then the
solid support was washed with THF (4 × 10 cm3), THF–water
(1 : 1, 3 × 10 cm3), THF (3 × 10 cm3), and CH2Cl2 (3 × 10 cm3).
The coupled products were released by treatment of the resins
with 50% TFA in dichloromethane (10 cm3) for 1 h. The resin
was washed with dichloromethane (3 × 10 cm3) and the com-
bined organic washings evaporated to give the products.
4-n-Pentylbenzamide 16
Treatment of resin 10 (176 mg, 0.43 Meq gϪ1) with zinc reagent
1, according to the general procedure, followed by recrystallis-
ation from petrol–ether, gave 16 (8 mg, 55%). Mp 149–150 ЊC
(lit.,17 147–148 ЊC, aq. EtOH); (Found Mϩ 191.1304, C12H17NO
requires 191.1310); IR (KBr disc) 3386, 3173, 2927, 2854, 1649,
1617, 1567, 1417, and 1398; NMR δH 0.89 (3H, t, J 7), 1.25–
1.36 (4H, m), 1.59–1.66 (2H, m), 2.65 (2H, t, J 7.5), 6.14 (2H, br
s), 7.25 (2H, d, J 8.5), and 8.00 (2H, d, J 8.5); δC 14.0, 22.5, 30.8,
31.4, 35.8, 127.5, 128.7, 130.4, 147.8, and 169.9; m/z (EI) 191
(Mϩ, 61%), 175 (100), 134 (49) and 91 (39).
4-n-Pentylbenzoic acid 12
4-(2Ј-Methoxycarbonylethyl)benzamide 17
Treatment of resin 8 (508 mg, 1.1 Meq gϪ1) with zinc reagent 1,
according to the general procedure, followed by recrystallis-
ation from EtOH–water, gave 12 (82 mg, 0.43 mmol, 78%).
Mp 86–89 ЊC (lit.,16 86–88 ЊC), liq. cryst.-isotropic transition
124–126 ЊC (lit.,16 126–127 ЊC).
Treatment of resin 10 (205 mg, 0.43 Meq gϪ1) with zinc reagent
2, according to the general procedure, gave 17 (56 mg, 0.27
mmol, 49%); (Found Mϩ 207.0887, C11H13NO3 requires
ϩ
207.0895); IR (KBr disc) 3375, 3003, 2998, 2959, 2924, 1725,
1672, 1414, 1402, 1287, 969 and 771; NMR δH 2.66 (2H, t, J
7.5), 3.01 (2H, t, J 7.5), 3.67 (3H, s), 6.40 (1H, br s), 6.55 (1H, br
s), 7.30 (2H, d, J 8.5), and 7.76 (2H, d, J 8.5); δC 30.7, 35.2, 51.7,
127.7, 128.6, 130.9, 145.3, 169.4, and 172.9; m/z (EI) 207
(Mϩ, 94%), 191 (54), 149 (78), 148 (94), 147 (100), 131 (95), 103
(44), and 91 (44).
Treatment of resin 9 (373 mg, 0.16 Meq gϪ1) with zinc reagent
1, according to the general procedure, gave 12 (10 mg, 87%).
4-(2Ј-Methoxycarbonylethyl)benzoic acid 13
Treatment of resin 8 (496 mg, 1.1 Meq gϪ1) with zinc reagent 2,
according to the general procedure, followed by recrystallis-
ation from CH2Cl2–petrol, gave 13 (113 mg, 0.54 mmol, 99%).
Mp 155–157 ЊC; (Found Mϩ 208.0739; C11H12O4 requires
208.0736); IR (KBr disc) 3442, 3000, 2954, 2850, 1725, 1687,
1428, and 1346; NMR δH 2.67 (2H, t, J 7.5), 3.03 (2H, t, J 7.5),
3.67 (3H, s), 7.31 (2H, d, J 8), and 8.04 (2H, d, J 8); δC 30.9,
35.1, 51.8, 127.5, 128.5, 130.5, 146.9, 172.0, and 173.0; m/z (EI)
208 (Mϩ, 58%), 148 (100), 135 (64), 103 (36), 77 (49), and 69
(82).
Wang (E )-3-iodoacrylate resin 18a
Wang resin (2.00 g, 1.29 Meq gϪ1), (E)-3-iodoacrylic acid
(1.633 mg, 8.25 mmol) and DMAP (107 mg, 0.88 mmol) were
suspended in CH2Cl2 (20 cm3) and cooled to Ϫ20 ЊC. DCC
(1.706 mg, 8.27 mmol) was added as a solution in CH2Cl2
(1 cm3) and the suspension stirred gently for 3.5 h at Ϫ20 ЊC.
The solvent was removed by filtration and the resin washed with
CH2Cl2 (3 × 10 cm3), EtOH–toluene (1 : 1, 4 × 10 cm3), CH2Cl2
(3 × 10 cm3), and methanol (3 × 5 cm3). The resin was dried in
air and in vacuo to constant weight, 2.595 g. The loading was
determined to be 1.22 Meq gϪ1 by cleavage of a sample using
1 : 1 (TFA–CH2Cl2). Another sample with loading 1.00 Meq
Treatment of resin 9 (384 mg, 0.16 Meq gϪ1) with zinc reagent
2, according to the general procedure, gave 13 (12 mg, 95%).
4-(2Ј-Benzyloxycarbonylamino-2Ј-carboxyethyl)benzoic acid 14
Treatment of resin 8 (502 mg, 1.1 Meq gϪ1) with zinc reagent 3,
according to the general procedure, followed by recrystallis-
g
Ϫ1 was also prepared.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 4 0 – 1 4 4
142