10.1002/ejoc.202000256
European Journal of Organic Chemistry
FULL PAPER
1H NMR (400.13 MHz, CDCl3): δ10b = 2.46 (mC, 2H, 3-H2), 2.95 (t, J2,3
=
1-(2,3,4-Trimethoxy-6-vinylphenyl)pent-4-en-1-one (10d) in a 65:35
Mixture With 3,4,5-Trimethoxystyrene (debromo-47)
2
E
7.1 Hz, 2H, 2-H2), 3.84 (s, 3H, 5‘-OCH3), 5.01 (ddt, J5-H ,4 =10.2 Hz, J5-
4
2
J5-H ,3 = 1.3 Hz, 1H, 5-HE), 5.06 (ddt, J5-H ,4 =17.1 Hz, J5-H
=
E
Z
E
Z
Z
E
H
,5-H
,5-H
O
MeO
MeO
1
2
4
3'
2'
1'
MeO 4'
6'
J5-H ,3 = 1.6 Hz, 1H, 5-HZ), 5.23 (dd, J2‘‘-H ,1‘‘ =11.0 Hz, 2J2‘‘-H
Hz, 1H, 2‘‘-HE), 5.53 (dd, J2‘‘-H ,1‘‘ =17.4 Hz, J2‘‘-H
HZ), 5.86 (ddt, J4,5-H
6.96 (dd,
C16H20O4
MeO
MeO
=
=
1.3
Z
E
E
Z
,2‘‘-H
C11H14O3
5'
2'
3
5'
4'
276.33 g/mol
2
194.23 g/mol
4
=
Z
Z
E
,2‘‘-H
1.2 Hz, 1H, 2‘‘-
E = 10.2 Hz, J4,3 = 6.5 Hz, 1H, 4-H),
J4,5-H
E = 10.9 Hz, 1H, 1‘‘-H), 6.98 (dd, J4‘,3‘ =
1
2
1'
6'
3'
MeO
1''
5 HZ
2''
Z H
10d
ZH
debromo-47
HE
Z = 16.7 Hz,
EHE
H
Z = 17.9 Hz,
J1‘‘,2‘‘-H
J1‘‘,2‘‘-H
8.6 Hz, J4‘,6‘ = 2.7 Hz, 1H, 4‘-H), 7.02 (d, J6‘,4‘ = 2.6 Hz, 1H, 6‘-H), 7.50 (d,
n-BuLi (1.6
M in hexane, 3.25 mL, 5.20 mmol, 1.5 equiv.) was added to a
stirred solution of the bromostyrene 47 (1.17 mg, 4.33 mmol, 1.25 equiv.)
in THF (11 mL) at –78°C. The resulting yellow solution was stirred at that
temperature for 20 min, before a solution of anhydrous ZnCl2 (756 mg,
5.55 mmol, 1.6 equiv.) in THF (6 mL) was added at –78°C. The mixture
was allowed to warm up to 0°C and stirred for 1 h. The clear colorless
solution was transferred to a mixture of PdCl2(PPh3)2 (97 mg, 0.14 mmol,
4 mol-%) and S-ethyl pent-4-enethioate (44; 500 mg, 3.47 mmol) in
toluene (22 mL) at room temp. . The resulting mixture was stirred at the
same temperature for 18 h, filtered over a pad of celite, and washed with
EtOAc (50 mL). The solvents were removed in vacuo. The residue was
purified via flash-chromatography on silica gel[21] (d = 4.0 cm, h = 15 cm,
F = 50 mL; c-C6H12/EtOAc 10:1) to give a 64:36-mixture (mol:mol; F8-22,
J3‘,4‘ = 8.6 Hz, 1H, 3‘-H) ppm.−
δallyl-38 = 2.50 (mC, 2H, 3-H2), 3.06 (t, J2,3
=
2
E
7.2 Hz, 1H, 2-H2), 3.86 (s, 3H, 3‘-OCH3), 5.01 (ddt, J5-H ,4 =10.3 Hz, J5-
4
2
J5-H ,3 = 1.3 Hz, 1H, 5-HE), 5.09 (ddt, J5-H ,4 =17.0 Hz, J5-H
=
E
H
Z
,5-H
E
Z
Z
,5-H
E
4
J5-H ,3 = 1.6 Hz, 1H, 5-HZ), 5.90 (ddt, J4,5-H
=
Z = 16.9 Hz,
E = 10.3 Hz,
J4,5-H
Z
J4,3 = 6.6 Hz, 1H, 4-H),
7.11 (ddd, J6’,5’ = 8.3 Hz, J6’,2’ = 2.7 Hz, J6’,4’ = 1.0
Hz, 1H, 6’-H)*, 7.37 (ddd, J5’,6’ = 8.0 Hz, J5’,4’ = 7.6 Hz, J5’,2’ = 0.4 Hz, 1H,
5’-H), 7.49 (dd, J2’,6’ = 2.6 Hz, J2’,4’ = 1.5 Hz, 1H, 2’-H), 7.54 (ddd, J4’,5’
=
7.6 Hz, J4’,2’ = 1.6 Hz, J4’,6’ = 1.0 Hz, 1H, 4’-H)* ppm; *assignment
interchangeable.
13C NMR (100.61 MHz, CDCl3): δ10b = 28.44 (C-3), 41.52 (C-2), 55.60 (5‘-
OCH3), 113.07 (C-6‘), 115.12 (C-2‘‘), 115.54 (C-5), 116.69 (C-4‘), 128.63
(C-3‘), 129.68 (C-2‘), 134.81 (C-1‘‘), 137.10 (C-4), 139.46 (C-1‘), 158.95
Rf, 4:1 = 0.38, 842 mg) of 10d (607 mg, 51%) and debromo-47 (235 mg,
−
(C-5‘), 204.36 (C-1) ppm. δallyl-38 = 28.32 (C-3), 37.98 (C-2), 55.54 (3‘-
28%) as a yellow oil.
OCH3), 112.46 (C-2‘), 115.38 (C-5), 119.55 (C-6‘)*, 120.75 (C-4‘)*, 129.66
(C-5‘), 137.38 (C-4), 138.49 (C-1‘), 159.99 (C-3‘), 199.33 (C-1) ppm;
*assignment interchangeable.
1H NMR (400.13 MHz, CDCl3, NMR-file: 2018: 20181108-4220): δ10d
2.40–2.47 (m, 2H, 3-H2), 2.85 (t, J2,3 = 7.2 Hz, 2H, 2-H), 3.86 (s, 3H, 3'-
OCH3)i, 3.878 (s, 3H, 2'-OCH3)i, 3.90 (s, 3H, 4'-OCH3)ii, 4.99 (ddt,
=
Jgem = 4J5-H ,3 = 1.3 Hz,
1H,
5-HE),
5.06
(ddt,
E
Jcis = 10.2 Hz,
Jtrans = 17.1 Hz, Jgem = 4J5-H ,3 = 1.7 Hz, 1H, 5-HZ), 5.25 (dd, Jcis = 10.9 Hz,
J
Z
1-(3,4,5-Trimethoxyphenyl-2-vinyl)pent-4-en-1-one (10c)
gem = 0.9 Hz, 1H, 2''-HE), 5.59 (dd, Jtrans = 17.4 Hz, Jgem = 1.0 Hz, 1H, 2''-
HZ), 5.86 (ddt, Jtrans = 16.6 Hz, Jcis = 10.1 Hz, J4,3 = 6.4 Hz, 1H, 4-H), 6.58
(dd, Jtrans = 17.4 Hz, Jcis = 11.0 Hz, 1H, 1''-H), 6.83 (s, 1H, 5'-H) ppm.−
δdebromo-47 = 3.85 (s, 3H, 4'-OCH3), 3.88 (s, 6H, 3'-OCH3, 5'-OCH3), 5.21
(dd, Jcis = 10.8 Hz, Jgem = 0.8 Hz, 1H, 2-HE), 5.65 (dd, Jtrans = 17.6 Hz,
O
1
2'
5'
2
3'
1'
MeO
MeO
C16H20O4
3
4
276.33 g/mol
6'
4'
1''
Hb
Z
H
2''
5
MeO
EHa
H
J
gem = 0.9 Hz, 1H, 2-HZ), 6.64 (s, 2H, 2'-H, 6'-H), 6.64 (dd, Jtrans = 17.6 Hz,
n-BuLi (1.6
M in hexane, 7.15 mL, 11.4 mmol, 1.5 equiv.) was added to a
Jcis = 10.7 Hz, 1H, 1-H) ppm.
stirred solution of the styrene 43 (2.58 g, 9.53 mmol, 1.25 equiv.) in THF
(24 mL) at –78°C. The resulting red solution was stirred at that temperature
for 20 min, before a solution of anhydrous ZnCl2 (1.66 g, 12.2 mmol,
1.6 equiv.) in THF (12 mL) was added. The cooling bath was exchanged
by an ice bath and the mixture was stirred at 0°C for 1 h. The clear
colorless solution was transferred to a solution of PdCl2(PPh3)2 (214 mg,
305 µmol, 4 mol-%) and S-ethyl pent-4-enethioate (44; 1.10 g, 7.63 mmol)
in toluene (48 mL) at room temp. . The resulting mixture was stirred at the
same temperature for 16 h and filtered over a pad of celite (d = 2 cm, h =
3 cm). The filter residue was washed with EtOAc (50 mL). The solvents
were removed in vacuo and the residue was purified by flash-
chromatography on silica gel[21] [d = 6.0 cm, h = 14 cm, F = 50 mL; c-
C6H12/EtOAc 20:1 (F1-35); c-C6H12/EtOAc 10:1 (F36-57)] to give the target
compound (F34-55, Rf, 4:1 = 0.29, 1.75 g, 83%) as a yellow oil.
HRMS (pos. ESI): calcd. for C16H21O4 [M10d+H]+ = 277.14344; found
277.14385 (+1.48 ppm); calcd. for C11H15O3 [Mdebromo-47+H]+ = 195.10157;
found 195.10116 (−2.10 ppm).
1-(2,3,4-Trimethoxy-6-vinylphenyl)pent-4-en-1-one (10d)
OMe O
5
3
2'
2
MeO
3'
1'
C16H20O4
1
4
276.33 g/mol
2''
MeO 4'
6'
1''
5'
This reaction was performed in a very similar manner to that described for
compound 73 utilizing Dess-Martin periodinane (6.00 g, 14.1 mmol), 48
(1.97 g, 7.07 mmol) in moist DCM (50 mL, saturated with H2O). A similar
work-up afforded
a residue which was purified by flash column
1H NMR (400.13 MHz, CDCl3): δ = 2.34-2.40 (m, 2H, 3-H2), 2.82 (t,
J = 7.3 Hz, 2H, 2-H2), 3.82 (s, 3H, 5'-OCH3), 3.86 (s, 3H, 3'-OCH3), 3.90
chromatography on silica gel (10% EtOAc/hexane) to give the diene 10d
(1.80 g, 6.50 mmol, 92%) as a light reddish-colored liquid.
(s, 3H, 4'-OCH3), 4.97 (ddt, Jcis = 10.1 Hz, Jgem = 1.6 Hz, 4J5-H ,3 = 1.3 Hz,
a
1H NMR (300 MHz; CDCl3): δ = 2.47-2.40 (m, 2H, 3-H), 2.85 (t, J = 7.5 Hz,
2H, 2-H), 3.86 (s, 3H, OMe), 3.88 (s, 3H, OMe), 3.90 (s, 3H, (OMe), 5.10-
4.97 (m, 2H, 5-H), 5.25 (d, J = 10.8 Hz, 1H, cis 2ꞌꞌ-H), 5.59 (d, J = 17.2 Hz,
1H, trans 2ꞌꞌ-H), 5.88 (ddt, Jtrans H-4-H-5 = 16.8, Jcis H-4-H-5 = 10.2, JH-4-H-3 = 6.5
Hz, 1H, 4-H), 6.58 (dd, Jtrans H-1ꞌꞌ-H-2ꞌꞌ = 17.2, Jcis H-1ꞌꞌ-H-2ꞌꞌ = 10.8 Hz, 1H, 1ꞌꞌ-H),
6.83 (s, 1H, 5ꞌ-H) ppm.
1H, 5-Ha), 5.02 (ddt, Jtrans = 17.1 Hz, Jgem = 1.7 Hz, 4J5-H ,3 = 1.7 Hz, 1H, 5-
b
Hb), 5.32 (dd, Jtrans = 17.7 Hz, Jgem = 1.5 Hz, 1H, 2’'-HZ), 5.41 (dd,
Jcis = 11.3 Hz, Jgem = 1.5 Hz, 1H, 2'’-HE), 5.81 (ddt, Jtrans = 17.0 Hz,
Jcis = 10.3 Hz, J4,3 = 6.6 Hz, 1H, 4-H), 6.66 (s, 1H, 2'-H), 6.88 (dd,
J
trans = 17.7 Hz, Jcis = 11.3 Hz, 1H, 1’'-H) ppm.
13C NMR (100.61 MHz, CDCl3): δ = 29.01 (C-3), 42.44 (C-2), 56.18 (3'-
OCH3), 60.85 (5'-OCH3), 61.00 (4'-OCH3), 106.80 (C-5'), 115.33 (C-5),
120.44 (C-2’'), 124.32 (C-6'), 130.94 (C-1’'), 136.37 (C-1'),137.11 (C-4),
144.04 (C-4'), 151.67 (C-5'), 152.75 (C-3'), 206.40 (C-1) ppm.
IR (film): ν = 3080, 2975, 2935, 2845, 1690, 1585, 1490, 1455, 1380,
1355, 1330, 113,1115, 1025, 915, 840, 745 cm-1.
13C NMR (75 MHz; CDCl3): δ = 27.8 (C-3), 44.3 (C-2), 56.0 (OMe), 60.9
(OMe), 61.7 (OMe), 104.5 (C-5ꞌ), 115.1 (C-5), 116.0 (C-2ꞌꞌ), 128.4 (C-1ꞌ),
130.6 (C-1ꞌꞌ), 133.4 (C-6ꞌ), 137.2 (C-4), 141.5 (C-2ꞌ)*, 150.3 (C-3ꞌ)*, 154.3
(C-4ꞌ)*, 205.5 (CO) ppm; *assignments interchangeable.
IR (neat): ꢀ = 2937, 1696, 1589, 1558, 1487, 1399, 1320, 1249, 1196 cm-
1
.
HRMS (pos. APCI): calcd. for C16H21O4 (M+H ) = 277.14344; found
277.14283 (∆ = −2.2 ppm).
Elemental analysis:
HRMS: calcd for C16H21O4 (M++H) = 277.1434, found: 277.1436 (∆ =
+0.72 ppm).
C16H20O4 (276.3 g/mol)
calc. C 69.55
found C 69.12
H 7.30
H 7.27
13
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