12158
G. L. Thomas et al. / Tetrahedron 61 (2005) 12153–12159
(500 MHz, CDCl3) 5.85–5.76 (1H, m, CH]CH2), 5.65 (1H,
s, NH), 5.14 (1H, dd, JZ17.0, 1.5 Hz0, CH]CHH0), 5.09
(1H, dd, JZ10.0, 1.0 Hz, CH]CHH ), 3.83 (2H, t, JZ
5.5 Hz, HNCH2), 2.26–2.23 (1H, m, CHCO), 1.90–1.83
(2H, m, cycloheptane ring) 1.80–1.46 (10H, m, cyclohep-
tane ring); dC (125 MHz, CDCl3) 176.09 (C), 133.57 (CH),
115.06 (CH2), 46.52 (CH), 40.70 (CH2), 30.75 (CH2), 27.12
(CH2), 25.62 (CH2); LCMS (MeCN): 182.1 (MHC); mp 44–
46 8C; HRMS (ES) found 204.1428 C11H19NONa (MNaC)
required 204.1436.
triphenylphosphine (0.5 mmol) and carbon tetrabromide
(97 mg, 0.29 mmol) in dry CH2Cl2 (3 ml) was stirred under
nitrogen at room temperature for 3 h. The beads were
filtered and the solvent removed in vacuo. To a solution of
4-methoxy-benzylamine (0.05 ml, 0.39 mmol) in sodium
carbonate solution (2 M, 3 ml) was added the bromide in dry
CH2Cl2 (3 ml). The polymer-bound aldehyde (3) was added
and the reaction stirred overnight. The beads were removed
by filtration and the organic layer was separated and washed
with sodium bicarbonate solution (!2), brine (!2), dried
(MgSO4) and the solvent was removed in vacuo to yield the
title compound as a pale yellow solid (48 mg, 80%). Rf: 0.26
(SiO2; Hexane/Ethyl acetate; 2:1); nmax (neat) cmK1 3315
(N–H), 2934 (C–H), 1636 (C]O), 1509 (C]C), 1244
(C–H); dH (500 MHz, CDCl3) 7.79 (2H, dd, JZ7.5, 1.0 Hz,
ArH), 7.52–7.50 (1H, m, ArH), 7.44 (2H, t, JZ7.5 Hz,
ArH), 7.28 (2H, d, JZ8.0 Hz, ArH), 6.90 (2H, d, JZ8.0 Hz,
ArH), 6.52 (1H, br s, NH), 4.57 (2H, d, JZ5.5 Hz, NHCH2),
3.81 (3H, s, OCH3); dC (125 MHz, CDCl3) 167.28 (C),
159.13 (C), 134.49 (C), 131.48 (CH), 130.33 (C), 129.30
(CH), 128.55 (CH), 126.97 (CH), 114.17 (CH), 55.32
(CH3), 43.63 (CH2); LCMS (MeCN): 241 (MHC); mp 91–
94 8C, lit. 87–88 8C.20,21
4.4.2. Cycloheptanecarboxyl cyclohexylamide (8).19
A
mixture of cycloheptane carboxylic acid (0.03 ml,
0.26 mmol), polymer-bound triphenylphosphine (644 mg,
0.58 mmol) and carbon tetrabromide (96 mg, 0.29 mmol) in
dry CH2Cl2 (5 ml) was stirred under nitrogen at room
temperature for 3 h. The beads were removed by filtration
and the solvent removed in vacuo. To a solution of
cyclohexylamine (0.045 ml, 0.39 mmol) in sodium carbon-
ate solution (2 M, 5 ml) was added the bromide in dry
CH2Cl2 (5 ml). The mixture was stirred over night at room
temperature. The polymer-bound aldehyde (3) was added
and the reaction stirred overnight. The beads were removed
by filtration and the organic layer was separated and washed
with sodium bicarbonate solution (!2), brine (!2), dried
(MgSO4) and the solvent was removed in vacuo to yield the
title compound as a light yellow solid (46 mg, 79%). Rf:
0.23 (SiO2; Hexane/Ethyl acetate; 10:4); nmax (neat) cmK1
3296 (N–H), 2923 (C–H), 1635 (C]O); dH (400 MHz,
CDCl3) 5.32–5.01 (1H, br s, NH), 3.79–3.70 (1H, m,
HNCH), 2.16–2.15 (1H, m, CHCO), 1.89–1.84 (4H, m),
1.79–1.35 (15H, m), 1.12–1.11 (3H, m); dC (125 MHz,
CDCl3) 175.29 (C), 47.75 (CH), 47.71 (CH), 32.27 (CH2),
30.81 (CH2), 27.12 (CH2), 25.69 (CH2), 24.61 (CH2), 23.89
(CH2); mp 153–157 8C; HRMS (ES) found 246.1848
C14H25NONa (MNaC) required 246.1858.
4.5. Wittig reaction22
4.5.1. Stilbene (11). Benzyl bromide (0.22 ml, 1.8 mmol)
was added dropwise with stirring to a suspension of a
polymer-bound triphenylphosphine (1.0 g, 0.9 mmol) in
N,N-dimethylformamide (15 ml). The mixture was stirred
over 48 h at 70 8C, cooled, filtered, washed with toluene (!
10), CH2Cl2 (!10), diethyl ether (!10) and dried to yield
the phosphonium salt as white solid (954 mg).
To a suspension of polymer-bound phosphonium salt
(533 mg, 0.375 mmol) in THF at K10 8C was added a
suspension of sodium methoxide (54 mg, 1.02 mmol) in
methanol dropwise. After 3 h of stirring at room tempera-
ture the reaction was cooled down to 10 8C, and
benzaldehyde (0.11 ml, 1.03 mmol) was added dropwise.
The mixture was stirred over night at room temperature,
refluxed for 3 h, filtered and washed with THF (!10),
CH2Cl2 (!10) and diethyl ether (!10). The combined
organic layers were dried (MgSO4), filtered through a pad of
silica and concentrated in vacuo to give the title compound
as a 49:51 ratio of E/Z isomers (32 mg, 48%).
4.4.3. N-Isobutyl-benzamide (9).20 A mixture of benzoic
acid (30 mg, 0.25 mmol), polymer-bound triphenylphos-
phine (0.5 mmol) and carbon tetrabromide (97 mg,
0.29 mmol) in dry CH2Cl2 (3 ml) was stirred under nitrogen
at room temperature for 3 h. The beads were filtered and the
solvent removed in vacuo. To a solution of isobutylamine
(0.04 ml, 0.39 mmol) in sodium carbonate solution (2 M,
3 ml) was added the bromide in dry CH2Cl2 (3 ml). The
polymer-bound aldehyde (3) was added and the reaction
stirred overnight. The beads were removed by filtration and
the organic layer was separated and washed with sodium
bicarbonate solution (!2), brine (!2), dried (MgSO4) and
the solvent was removed in vacuo to yield the title
compound as a white solid (30 mg, 68%). Rf: 0.28 (SiO2;
Hexane/Ethyl acetate; 2:1); nmax (neat) cmK1 3321 (N–H),
2960 (C–H), 1639 (C]O), 1541 (C]C); dH (500 MHz,
CDCl3) 7.77 (2H, d, JZ7.0 Hz, ArH), 7.53–7.50 (1H, m,
ArH), 7.43 (2H, t, JZ7.5 Hz, ArH), 6.18 (1H, br s, NH),
3.31 (2H, t, JZ6.5 Hz, NHCH2), 1.92 (1H, sept, JZ6.5 Hz,
NHCH2CH), 1.00 (6H, d, JZ6.5 Hz, CH3); dC (125 MHz,
CDCl3) 167.62 (C), 134.97 (C), 131.32 (CH), 128.58 (CH),
126.81 (CH), 47.36 (CH2), 28.65 (CH), 20.18 (CH3); LCMS
(MeCN): 178 (MHC); mp 52–54 8C, lit. 55 8C.20
4.5.2. (Z)-stilbene (Z)-11. Colourless oil; Rf: 0.28 (SiO2;
Hexane); dH (400 MHz, CDCl3) 7.27–7.19 (10H, m, CH
aryl), 6.61 (2H, s, CHPh).
4.5.3. (E)-stilbene (E)-11. White solid; Rf: 0.23 (SiO2;
Hexane); dH (400 MHz, CDCl3): 7.53 (4H, d, JZ8.0 Hz,
CH aryl), 7.37 (4H, t, JZ8.0 Hz, CH aryl), 7.27 (2H, t, JZ
7.25 Hz, CH aryl), 7.12 (2H, s, CHPh); mp 102–104 8C.22
4.5.4. (E)-2-Methyl-3-phenyl-acrylic acid ethyl ester
(12).23 Ethyl-2-bromo-propioate (0.23 ml, 1.8 mmol) was
added dropwise with stirring to a suspension of a polymer-
bound triphenylphosphine (1.0 g, 0.9 mmol) in N,N-
dimethylformamide (15 ml). The mixture was stirred over
48 h at 70 8C, cooled, filtered, washed with toluene (!10),
4.4.4. N-(4-Methoxy-benzyl)-benzamide (10).20,21 A mix-
ture of benzoic acid (30 mg, 0.25 mmol), polymer-bound