O. Provot, M. Alami, et al.
MED
3H), 5.32 (m, 2H), 6.51 (s, 2H), 6.91 (d, J=8.3 Hz, 1H), 7.19 (s, 1H),
7.29 (m, 1H), 7.62 (d, J=8.0 Hz, 2H), 8.18 ppm (d, J=8.0 Hz, 2H);
13C NMR (CDCl3, 75 MHz): d=55.7, 56.2, 60.9, 105.7, 111.1, 113.2,
123.3, 128.0, 130.0, 130.4, 134.2, 137.1, 145.2, 149.1, 153.0,
156.2 ppm; IR: n=2934, 1731, 1579, 1343, 1235, 1126 cmÀ1; MS
(APCI+, m/z): 422 [M+H]+; Anal. calcd for C24H23NO6: C 68.40, H
5.50, N 3.32, found: C 68.21, H 5.32, N 3.21.
General procedure for the preparation of alkynes 17–22 and
24–26: NEt3 (1.2 mL), PdCl2(PPh3)2 (0.05 mmol), and CuI (0.1 mol)
were added to a solution of 5 (1 mmol) in THF (25 mL). The appro-
priate alkyne (3–6 mmol) in THF (25 mL) was then added to the
mixture and stirred at 608C for 16 h. After cooling, EtOAc (40 mL)
was added to the crude mixture, which was washed with a saturat-
ed NH4Cl solution. After extraction with CH2Cl2, the combined ex-
tracts were dried (MgSO4) and concentrated. Purification by flash
chromatography on silica gel afforded alkynes.
4’-Chloro-2-methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]biphenyl
(12): Colorless oil; Yield (320 mg, 78%); Rf =0.67 (cyclohexane/
EtOAc 7:3); 1H NMR (CDCl3, 300 MHz): d=3.78 (6H), 3.81 (s, 3H),
3.88 (s, 3H), 5.37 (m, 2H), 6.56 (s, 2H), 6.94 (m, 1H), 7.27–7.38 (m,
4H), 7.45 ppm (d, J=8.4 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d=
55.7, 56.2, 60.9, 105.7, 110.8, 112.9, 128.2, 128.9, 129.1, 130.5, 130.8,
133.0, 133.9, 136.7, 149.3, 137.3, 152.9, 156.2 ppm; IR: n=2952,
1589, 1510, 1465, 1421, 1125, 732 cmÀ1; MS (APCI+, m/z): 433, 435
[M+Na]+; Anal. calcd for C24H23ClO4: C 70.15, H 5.64, found: C
69.99, H 5.51.
3-{2-Methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}prop-2-
yn-1-ol (17): Brown oil; Yield (177 mg, 50%); Rf =0.23 (CH2Cl2/
1
EtOAc 9:1); H NMR (CDCl3, 300 MHz): d=3.75 (s, 6H), 3.81 (s, 3H),
3.84 (s, 3H), 4.46 (s, 2H), 5.28 (m, 2H), 6.45 (s, 2H), 6.78 (d, J=
8.5 Hz, 1H), 7.24 (m, 1H), 7.37 ppm (d, J=2.3 Hz, 1H), OH not
obsd; 13C NMR (CDCl3, 75 MHz): d=51.8, 55.9, 56.1, 60.9, 81.8, 91.0,
105.6, 110.3, 111.4, 113.2, 129.9, 133.5, 133.8, 137.1, 148.8, 152.9,
159.7 ppm; IR: n=3379, 2935, 1582, 1500, 1456, 1412, 1124,
1022 cmÀ1
;
MS (APCI+, m/z): 355 [M+H]+; Anal. calcd for
C21H22O5: C71.17, H 6.26, found: C 71.00, H 6.12.
4’-Fluoro-2-methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]biphenyl
(13): Colorless oil; Yield (201 mg, 51%); Rf =0.41 (cyclohexane/
EtOAc 8:2); H NMR (CDCl3, 300 MHz): d=3.82–3.88 (m, 12H), 5.38
4-{2-Methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}but-3-
yn-1-ol (18): Yellow oil; Yield (169 mg, 46%); Rf =0.20 (CH2Cl2/
EtOAc 6:4); 1H NMR (CDCl3, 300 MHz): d=2.42 (t, J=6.3 Hz, 2H),
2.64 (t, J=6.3 Hz, 2H), 3.73 (s, 6H), 3.79 (s, 3H), 3.81 (s, 3H), 5.26
(m, 2H), 6.44 (s, 2H), 6.75 (d, J=8.6 Hz, 1H), 7.15 (dd, J=8.6,
2.2 Hz, 1H), 7.32 ppm (d, J=2.2 Hz, 1H), OH not obsd; 13C NMR
(CDCl3, 75 MHz): d=24.1, 55.9, 56.1, 60.8, 60.9, 78.6, 91.0, 105.6,
110.2, 112.2, 113.1, 133.1, 133.7, 137.2, 137.8, 148.9, 152.9,
159.7 ppm; IR: n=3442, 936, 1579, 1499, 1461, 1411, 1342,
1
(m, 2H), 6.59 (s, 2H), 6.95 (d, J=9.0 Hz, 1H), 7.06–7.11 (m, 2H),
7.29–7.32 (m, 2H), 7.46–7.51 ppm (m, 2H); 19F NMR (CDCl3,
188 MHz, decoupled): d=À115.4 ppm; 13C NMR (CDCl3, 75 MHz):
d=55.7, 56.2, 60.9, 105.7 110.8, 112.8, 114.8, 115.0, 128.6, 129.3,
130.6, 131.0, 131.1, 133.9, 134.2, 137.4, 149.4, 152.9 156.2 ppm; IR:
n=1583, 1509, 1463, 1414, 1333, 1265, 1128, 732 cmÀ1; MS (APCI+
, m/z): 395 [M+H]+; Anal. calcd for C24H23FO4: C 73.08, H 5.88,
found: C 72.88, H 5.71.
1123 cmÀ1
;
MS (APCI+, m/z): 369 [M+H]+; Anal. calcd for
C22H24O5: C 71.72, H 6.57, found: 71.49, 6.33.
2,3’-Dimethoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]biphenyl (14):
Yellow oil; Yield (284 mg, 70%); Rf =0.60 (cyclohexane/EtOAc 7:3);
1H NMR (CDCl3, 300 MHz): d=3.77–3.79 (m, 12H), 3.83 (s, 3H), 5.33
(m, 2H), 6.54 (s, 2H), 6.81–7.03 (m, 1H), 7.05 (d, J=6.6 Hz, 1H),
7.03–7.06 (m, 2H), 7.20–7.31 ppm (m, 3H); 13C NMR (CDCl3,
75 MHz): d=55.2, 55.7, 56.1, 60.9, 105.7, 110.8, 112.4, 112.7, 115.4,
122.0, 128.5, 128.9, 130.1, 130.7, 133.7, 137.4, 137.8, 139.7, 149.4,
152.9, 156.3, 159.2 ppm; IR: n=2939, 2835, 1578, 1503, 1343, 1235,
5-{2-Methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}pent-4-
yn-1-ol (19): Yellow oil; Yield (206 mg, 54%); Rf =0.20 (CH2Cl2/
1
EtOAc 6:4); H NMR (CDCl3, 300 MHz): d=1.88 (q, J=6.8 Hz, 2H),
2.60 (t, J=6.8 Hz, 2H), 3.81 (m, 8H), 3.88 (s, 3H), 3.89 (s, 3H), 5.34
(m, 2H), 6.52 (s, 2H), 6.81 (d, J=8.6 Hz, 1H), 7.22 (dd, J=8.6,
2.3 Hz, 1H), 7.39 ppm (d, J=2.3 Hz, 1H), OH not obsd; 13C NMR
(CDCl3, 75 MHz): d=16.8, 31.3, 55.9, 56.15, 60.9, 62.3, 77.3, 93.9,
105.6, 110.1, 112.5, 113.0, 129.1, 133.1, 133.7, 137.2, 149.0, 152.9,
159.7 ppm; IR: n=3532, 2935, 1579, 1501, 1462, 141, 1344, 1271,
1237, 1126 cmÀ1; MS (APCI+, m/z): 383 [M+H]+; Anal. calcd for
C23H26O5: C 72.23, H 6.85, found: C 72.01, H 6.57.
1124 cmÀ1
;
MS (APCI+, m/z): 407 [M+H]+; Anal. calcd for
C25H26O5: C 73.87, H 6.45, found: C 73.52, H 6.20.
2-Methoxy-3’-nitro-5-[1-(3,4,5-trimethoxyphenyl)vinyl]biphenyl
(15): Yellow oil; Yield (60%); Rf =0.19 (cyclohexane/CH2Cl2 5:5);
1H NMR (CDCl3, 300 MHz): d=3.83 (s, 6H), 3.87 (s, 3H), 3.88 (s,
3H), 5.40 (m, 2H), 6.59 (s, 2H), 6.99 (d, J=7.9 Hz, 1H), 7.36 (m, 2H),
7.56 (t, J=7.9 Hz, 1H), 7.82–7.86 (m, 1H), 8.15–8.19 (m, 1H),
8.41 ppm (t, J=1.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=55.7,
56.2, 60.9, 105.7, 111.0, 113.2, 121.9, 124.6, 127.8, 128.9, 129.8,
130.4, 134.2, 135.6, 137.1, 140.0, 148.1, 149.1, 153.0, 156.2 ppm; IR:
n=2939, 1578, 1528, 1503, 1348, 1234, 1126 cmÀ1; MS (APCI+, m/
z): 422 [M+H]+; Anal. calcd for C24H23NO6: C 68.40, H 5.50, N 3.32,
found: C 68.26, H 5.35, N 3.20.
6-{2-Methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}hex-5-
yn-1-ol (20): Yellow oil; Yield (178 mg, 45%); Rf =0.17 (CH2Cl2/
1
EtOAc 6:4); H NMR (CDCl3, 300 MHz): d=1.73 (m, 4H), 2.51 (t, J=
6.5 Hz, 2H), 3.71 (t, J=5.5 Hz, 2H), 3.80 (s, 6H), 3.87 (s, 3H), 3.89 (s,
3H), 5.34 (m, 2H), 6.52 (s, 2H), 6.81 (d, J=8.6 Hz, 1H), 7.20 (dd, J=
8.6, 2.2 Hz, 1H), 7.39 ppm (d, J=2.2 Hz, 1H), OH not obsd; 13C NMR
(CDCl3, 75 MHz): d=19.5, 24.9, 31.9, 55.9, 56.1, 60.9, 62.3, 76.8,
94.4, 105.6, 110.2, 112.7, 112.9, 129.0, 133.3, 133.7, 137.2, 149.0,
152.9, 159.6 ppm; IR: n=3423, 2937, 1579, 1499, 1461, 1410, 1124,
1025, 1005 cmÀ1; MS (APCI+, m/z): 397 [M+H]+; Anal. calcd for
C24H28O5: C 72.70, H 7.12, found: C 72.48, H 6.99.
2,2’-Dimethoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]-1,1’-biphenyl
(16): Pale-yellow oil; Yield (288 mg, 71%); Rf =0.60 (cyclohexane/
3-{2-Methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}-N,N-di-
methylprop-2-yn-1-amine (21): Brown oil; Yield (156 mg, 41%);
Rf =0.11 (cyclohexane/EtOAc 1:9); 1H NMR (CDCl3, 300 MHz): d=
2.31 (s, 3H), 2.38 (s, 3H), 3.51 (s, 2H), 3.78 (s, 6H), 3.86 (s, 3H), 3.88
(s, 3H), 5.85 (m, 2H), 6.53 (s, 2H), 6.82 (d, J=8.5 Hz, 1H), 7.24 (dd,
J=8.5, 2.1 Hz, 1H), 7.46 ppm (d, J=2.1 Hz, 1H); 13C NMR (CDCl3,
75 MHz): d=44.1, 44.2, 48.8, 55.9, 56.1, 60.9, 81.3, 88.9, 105.6,
110.2, 112.1, 113.0, 129.4, 133.4, 133.6, 137.1, 148.9, 152.9,
1
EtOAc 7:3); H NMR (CDCl3, 300 MHz): d=3.74 (s, 3H), 3.77 (s, 3H),
3.80 (s, 6H), 3.84 (s, 3H), 5.33 (m, 2H), 6.58 (s, 2H), 6.89–6.99 (m,
3H), 7.30–7.19 ppm (m, 4H); 13C NMR (CDCl3, 75 MHz): d=55.7,
55.8, 56.2, 60.9, 105.8, 110.6, 111.2, 112.5, 120.4, 127.4, 127.6, 128.4,
128.7, 131.4, 133.1, 137.6, 149.5, 152.8, 156.9, 157.0 ppm; IR: n=
2935, 1578, 1503, 1461, 1237, 1124, 1029 cmÀ1; MS (APCI+, m/z):
407 [M+H]+; Anal. calcd for C25H26O5 C 73.87, H 6.45, found: C
73.54; H 6.21.
159.8 ppm; IR: n=2939, 1579, 1500, 1461, 1410, 1344, 1126 cmÀ1
;
2188
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ChemMedChem 2011, 6, 2179 – 2191