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A. E. Jensen et al. / Tetrahedron 56 (2000) 4197±4201
0.29 mmol) was added and the mixture was cooled to
2308C. Then butylzinc iodide (0.5 ml, 2.0 M in THF,
1.0 mmol) was added dropwise with stirring. The reaction
mixture was warmed up to 08C and stirred for 48 h. After the
reaction was completed as monitored by HPLC, the resin
was ®ltered, sequentially washed four times with THF,
DMF and MeOH, followed by four washings with CH2Cl2
and dried at 558C overnight. To determine the yield and
purity, 100 mg of the product resin was placed in a
5 mlÐsyringe equipped with a ®lter plate and TFA:CH2Cl2
1:1 (3 ml) was added for cleavage. The mixture was shaken
for 20 min. The ®ltrate was transferred into a ¯ask and the
solvents were removed in vacuo leading to the cross-
coupling product 2 with 94% HPLC purity as a white
with Ni(acac)2 (77 mg, 0.3 mmol). Dry THF (2 ml), NMP
(1 ml), ethyl 2-iodobenzoate 9a (825 mg, 3 mmol), 4-¯uoro-
styrene (74 mg, 0.6 mmol) and Bu4NI (3.3 g, 9 mmol) were
successively added at rt. The reaction mixture was cooled to
2358C before slowly adding a solution of pentylzinc iodide
(1.3 ml, 7 M, 9 mmol). The reaction mixture was then
allowed to warm up to 08C. The conversion was complete
in 16 h, after which it was quenched with saturated aqueous
NH4Cl solution (2 ml) and extracted with ether (4£50±
75 ml). The combined organic phase was dried (MgSO4)
and the solvents removed in vacuo. Flash chromatography
on silica gel (pentane/ether 20:1) furnished the cross-
coupling product 11a as a colourless oil (521 mg, 79%).
IR (KBr): 2958 (m), 2931 (m), 1721 (s), 1251 (s), 1098
1
1
solid (8.4 mg, 94%), mp: 80±828C. H NMR (300 MHz,
(s) cm21. H NMR (300 MHz, CDCl3): d 7.78±7.15 (m,
CDCl3): d 7.34 (d, J9 Hz, 1H), 7.27 (d, J6 Hz, 1H),
7.21±7.15 (m, 2H), 6.36 (br s, 1H), 5.82 (br s, 1H), 2.75
(m, 2H), 1.55±1.51 (m, 2H), 1.33±1.26 (m, 2H), 0.85 (t,
J7.5 Hz). MS (EI, 70 eV): 177 (36), 148 (100), 131 (40),
116 (27), 105 (23), 91 (24), 77 (26). HRMS: calcd 177.1154,
found: 177.1149. The products 5±7 were prepared accord-
ing to this method.
4H), 4.28 (q, J7.1 Hz, 2H), 2.85 (t, J7.8 Hz, 2H), 1.51±
1.25 (m, 9H), 0.84±0.80 (t, J7.1 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d 168.4, 144.8, 132.0, 131.2, 130.8,
130.4, 126.0, 61.1, 34.8, 32.3, 32.0, 23.0, 14.7, 14.4. MS (EI,
70 eV): 220 (70), 175 (100), 131 (98), 91 (48). Anal. Calcd for
C14H20O2: C, 76.33; H, 9.15. Found: C, 76.19; H, 9.17. The
products 11b±e were prepared according to this method.
2-(Cyanobenzyl)benzamide (5). Prepared from resin 1
(200 mg, 0.098 mmol) and 2-cyanobenzylzinc bromide
(0.9 ml, 1.1 M, 1 mmol). Reaction time: 72 h at 108C.
Cleavage with TFA from 100 mg of resin yielded 5 in
89% HPLC purity as white crystals (10.3 mg, 89%), mp:
Alternatively 11a can be prepared from ethyl 2-carbethoxy-
phenyl nona¯ate 10 (1.35 g, 3 mmol). Reaction time: 16 h at
08C (554 mg, 84%).
Ethyl 2-cyclohexylbenzoate (11b). Prepared from ethyl
2-iodobenzoate 9a (825 mg, 3 mmol) and cyclohexylzinc
iodide (1.5 ml, 6 M, 9 mmol). Reaction time: 16 h at
108C. Puri®cation by ¯ash chromatography (pentane/ether
9:1) yielded 11b as a colourless oil (495 mg, 72%). IR
(KBr): 2927 (s), 2852 (m), 1719 (s), 1228 (s), 1119 (m),
1
139±1438C. H NMR (200 MHz, CDCl3): d 7.65 (d, J
6.6 Hz, 1H), 7.58±7.23 (m, 6H), 7.15±7.08 (d, J6.6 Hz,
1H), 5.98 (br s, 2H), 4.41 (br s, 2H). MS (EI, 70 eV): 236
(4), 219(100), 207(14), 190 (36), 165 (12). HRMS: calcd
236.0950, found: 236.0947.
1
1072 (m) cm21. H NMR (200 MHz, CDCl3): d 7.73±7.21
2-(2-Carboethoxyethyl)benzamide (6). Prepared from
resin 1 (200 mg, 0.098 mmol) and 2-ethoxycarbonylethyl-
zinc iodide (0.5 ml, 2 M, 1 mmol). Reaction time: 60 h at
108C. Cleavage with TFA from 100 mg of resin yielded 6 in
(m, 4H), 4.37 (q, J7.1 Hz, 2H), 3.39±3.22 (m, 1H), 1.87±
1.38 (m, 10H), 1.40 (t, J7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 169.0, 148.7, 131.8, 130.9, 130.1, 127.1, 125.8,
61.4, 40.7, 34.8, 27.4, 27.0, 14.7. MS (EI, 70 eV): 232 (54),
186 (100), 168 (94), 157 (49), 145 (44), 135 (23), 91 (37).
Anal. Calcd for C15H20O2: C, 71.55; H, 8.68. Found: C,
71.15; H, 8.73.
1
92% HPLC purity as a colourless oil (9.5 mg, 87%). H
NMR (200 MHz, CDCl3): d 7.50±7.24 (m, 4H), 5.92 (br
s, 2H), 4.08 (q, J6.6 Hz, 2H), 3.10 (m, 2H), 2.74 (m, 2H),
1.18 (t, J6.6 Hz, 3H). MS (EI, 70 eV): 221 (6), 205 (48),
191 (11), 176 (100), 159 (24), 148 (42), 131 (73), 116 (19),
103 (42), 77 (25). HRMS: calcd 221.1052, found 221.1049.
Ethyl 2-(2-ethoxycarbonyl-ethyl)-benzoate (11c). Pre-
pared from ethyl 2-iodobenzoate 9a (825 mg, 3 mmol)
and 2-(ethoxycarbonyl)ethylzinc iodide (1.5 ml, 6 M,
9 mmol). Reaction time 16 h at 08C. Puri®cation by ¯ash
chromatography (pentane/ethyl acetate 95:5) yielded 11c as
a colourless oil (622 mg, 83%). IR (KBr): 2983 (m), 1732
(s), 1716 (s), 1257 (s), 1080 (m) cm21. 1H NMR (300 MHz,
CDCl3): d 7.84±7.18 (m, 4H), 4.28 (q, J7.1 Hz, 2H), 4.03
(q, J7.1 Hz, 2H), 3.19 (t, J7.8 Hz, 2H), 2.57 (t, J
7.8 Hz, 2H), 1.31 (t, J7.1 Hz, 3H), 1.14 (t, J7.1 Hz,
3H). 13C NMR (75 MHz, CDCl3): d 173.3, 167.7, 142.7,
132.4, 131.5, 131.2, 130.2, 126.8, 61.3, 60.7, 36.3, 30.3,
14.6, 14.6. MS (EI, 70 eV): 250 (3), 205 (42), 176 (100),
148 (52), 131 (53). Anal. Calcd for C14H18O4: C, 67.18; H,
7.25. Found: C, 67.12; H, 7.16.
2-Octylbenzamide (7). Prepared from resin 1 (200 mg,
0.098 mmol) and octylzinc iodide (0.5 ml, 2 M, 1 mmol).
Reaction time: 60 h at 58C. Cleavage with TFA from
100 mg of resin yielded the amide 7 in 92% HPLC purity
1
as a white solid (11.0 mg, 96%), mp: 95±988C. H NMR
(300 MHz, CDCl3): d 7.33 (d, J7.5 Hz, 1H), 7.28 (d,
J6.9 Hz, 1H), 7.20±7.11 (m, 2H), 6.13 (br s, 1H), 5.78
(br s, 1H), 2.74 (t, J7.8 Hz, 2H), 1.55±1.52 (m, 2H),
1.24±1.17 (m, 10H), 0.80 (t, J6.6 Hz,3H). 13C NMR
(75 MHz, CDCl3): d 193.9, 141.4, 130.3, 127.0, 125.7,
33.4, 31.8, 31.7, 29.6, 29.4, 29.2, 22.6, 14.1. MS (EI
70 eV): 233 (60), 217 (5), 204 (3), 148 (100), 135 (60).
HRMS: calcd 233.1780, found: 233.1776.
2-Pentyl-N,N-dimethylbenzamide (11d). Prepared from
2-iodo-N,N-dimethylbenzamide 9b (822 mg, 3 mmol) and
pentylzinc iodide (1.3 ml, 7 M, 9 mmol). Reaction time:
16 h at 258C. Puri®cation by ¯ash chromatography (pen-
tane/ethyl acetate 7:3) yielded 11d as a colourless oil
Typical procedure B: nickel-catalyzed cross-coupling
between alkylzinc iodide and aryl iodides in solution.
Preparation of ethyl 2-pentylbenzoate (11a). A dried
and argon-¯ushed 10 ml two-necked ¯ask was charged