E
T.-S. Jiang et al.
Paper
Synthesis
EtOAc. The organic extract was dried and concentrated under reduced
pressure. The residue was purified by flash chromatography using pe-
troleum ether and EtOAc as eluent to afford the title compound 1d.
(E)-3-(3-Methoxy-4-((3-methylbut-2-en-1-yl)oxy)phenyl)acrylal-
dehyde (2)22
By following the general procedure, 8 (69.7 mg, 0.3 mmol) dissolved
in DCE (1 mL) was added to a solution of DDQ (149.8 mg, 0.66 mmol),
H2O (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
50 °C for 3 h under air. After the work-up, the crude product was puri-
fied by flash column chromatography to afford the title compound 2.
Yield: 34.2 mg (88%); yellow solid.
1H NMR (600 MHz, CDCl3): δ = 9.61 (d, J = 7.8 Hz, 1 H), 7.34 (d,
J = 16.2 Hz, 1 H), 6.85 (d, J = 1.8 Hz, 1 H), 6.69 (d, J = 1.8 Hz, 1 H), 6.57
(dd, J = 16.2, 7.8 Hz, 1 H), 6.23 (br, 2 H), 3.91 (s, 3 H).
Yield: 53.2 mg (72%); yellow solid.
13C NMR (150 MHz, CDCl3): δ = 193.9, 153.6, 147.2, 144.2, 135.8,
1H NMR (600 MHz, CDCl3): δ = 9.64 (d, J = 7.8 Hz, 1 H), 7.40 (d,
J = 15.6 Hz, 1 H), 7.12 (dd, J = 8.4, 1.8 Hz, 1 H), 7.06 (d, J = 1.8 Hz, 1 H),
6.88 (d, J = 8.4 Hz, 1 H), 6.59 (dd, J = 15.6, 7.8 Hz, 1 H), 5.49 (t,
J = 6.6 Hz, 1 H), 4.62 (d, J = 6.6 Hz, 2 H), 3.89 (s, 3 H), 1.77 (s, 3 H), 1.73
(s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 193.5, 152.9, 151.3, 149.6, 138.4,
126.8, 126.5, 123.2, 119.1, 112.5, 110.0, 65.8, 55.9, 25.8, 18.2.
126.8, 126.1, 110.1, 103.5, 56.3.
(E)-2,6-Dimethoxy-4-(3-oxoprop-1-en-1-yl)phenyl Acetate (6e)20
By following the general procedure, 4-allyl-2,6-dimethoxyphenyl ac-
etate 5e (71.0 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to
the solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol)
in DCE (1 mL). The reaction was stirred at 50 °C for 3 h under air. After
the work-up, the crude product was purified by flash column chro-
matography to afford the title compound 6e.
4-Allyl-1-(allyloxy)-2-methoxybenzene (9)27
A suspension of eugenol 7 (3.28 g, 20 mmol), K2CO3 (5.53 g, 40.0
mmol), and allyl bromide (2.60 mL, 30 mmol) in acetone (60 mL) was
stirred at 60 °C for 12 h. After cooling to ambient temperature, the
suspension was filtered through a pad of Celite and washed with EtO-
Ac. The filtrate was evaporated and the crude product was purified by
flash column chromatography to furnish the title compound 9.
Yield: 52.6 mg (70%); yellow solid.
1H NMR (600 MHz, CDCl3): δ = 9.67 (d, J = 7.2 Hz, 1 H), 7.39 (d,
J = 16.2 Hz, 1 H), 6.78 (s, 2 H), 6.64 (dd, J = 16.2, 7.2 Hz, 1 H), 3.84 (s,
6 H), 2.34 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 193.4, 168.4, 152.5, 152.3, 132.2,
131.0, 128.7, 105.0, 56.2, 20.4.
Yield: 4.05 g (99%); colorless oil.
1H NMR (600 MHz, CDCl3): δ = 6.81 (d, J = 7.8 Hz, 1 H), 6.71 (s, 1 H),
6.69 (d, J = 7.8 Hz, 1 H), 6.11–6.04 (m, 1 H), 5.99–5.92 (m, 1 H), 5.40
(dd, J = 16.8, 1.2 Hz, 1 H), 5.26 (dd, J = 10.2, 1.2 Hz, 1 H), 5.09–5.05 (m,
2 H), 4.58 (d, J = 5.4 Hz, 2 H), 3.86 (s, 3 H), 3.33 (d, J = 7.2 Hz, 2 H).
13C NMR (150 MHz, CDCl3): δ = 149.4, 146.3, 137.6, 133.5, 133.1,
120.3, 117.8, 115.6, 113.6, 112.2, 70.0, 55.8, 39.8.
(E)-3-(4-Hydroxy-3,5-dimethoxyphenyl)acrylaldehyde (1e)20
A solution of 6e (50.0 mg, 0.2 mmol) in MeOH (2 mL) and water (2
mL) was treated with sodium bicarbonate (NaHCO3, 168.0 mg, 2.0
mmol) and stirred at 50 °C overnight under nitrogen atmosphere. The
solution was acidified with 10% hydrochloric acid and extracted with
EtOAc. The organic extract was dried and concentrated under reduced
pressure. The residue was purified by flash chromatography using pe-
troleum ether and EtOAc as eluent to afford the title compound 1d.
1,5-Diallyl-2-(allyloxy)-3-methoxybenzene (10)27
The above liquid compound 9 was heated to 170 °C for 8 h in a sealed
tube, the reaction was monitored by TLC. After cooling to ambient
temperature, the crude product was used directly without further
purification in the next step. The residue from the previous step was
dissolved in acetone (60 mL) and K2CO3 (5.53 g, 40.0 mmol), and allyl
bromide (2.60 mL, 30 mmol) were added. The reaction mixture was
heated to 60 °C for 12 h, then filtered through a short pad of Celite,
which was washed with EtOAc. The combined organic solutions were
evaporated in vacuo and the crude product was purified by flash col-
umn chromatography to afford the compound 10.
Yield: 31.2 mg (75%); yellow solid.
1H NMR (600 MHz, CDCl3): δ = 9.60 (d, J = 7.2 Hz, 1 H), 7.34 (d,
J = 15.6 Hz, 1 H), 6.77 (s, 2 H), 6.57 (dd, J = 15.6, 7.2 Hz, 1 H), 6.16 (br,
1 H), 3.88 (s, 6 H).
13C NMR (150 MHz, CDCl3): δ = 193.5, 153.3, 147.4, 138.2, 126.6,
125.5, 105.6, 51.4.
4-Allyl-2-methoxy-1-((3-methylbut-2-en-1-yl)oxy)benzene (8)26
A suspension of eugenol 7 (1.64 g, 10.0 mmol), K2CO3 (2.76 g, 20.0
mmol), and prenyl bromide (2.24 g, 15.0 mmol) in acetone (40 mL)
was heated at 60 °C for 12 h. The resulting suspension was filtered
through a pad of Celite, which was washed with EtOAc. The filtrate
was evaporated and the residue was purified by column chromatog-
raphy on silica, using petroleum ether and EtOAc mixtures as eluent,
to furnish compound 8.
Yield: 4.12 g (85% for two steps); colorless oil.
1H NMR (600 MHz, CDCl3): δ = 6.64 (s, 2 H), 6.14–6.09 (m, 1 H), 6.02–
5.95 (m, 2 H), 5.40 (dd, J = 16.8, 1.8 Hz, 1 H), 5.24 (dd, J = 10.8, 1.8 Hz,
1 H), 5.14–5.05 (m, 4 H), 4.49 (d, J = 6.0 Hz, 2 H), 3.85 (s, 3 H), 3.43 (d,
J = 6.6 Hz, 2 H), 3.35 (d, J = 6.6 Hz, 2 H).
13C NMR (150 MHz, CDCl3): δ = 152.6, 144.1, 137.5, 137.4, 135.7,
134.6, 133.8, 121.8, 117.0, 115.8, 115.5, 110.7, 73.8, 55.7, 40.1, 34.3.
Yield: 2.27 g (98%); colorless oil.
1H NMR (600 MHz, CDCl3): δ = 6.81 (d, J = 7.8 Hz, 1 H), 6.71–6.69 (m,
2 H), 5.98–5.94 (m, 1 H), 5.53 (t, J = 6.6 Hz, 1 H), 5.10–5.05 (m, 2 H),
4.55 (d, J = 6.6 Hz, 2 H), 3.84 (s, 3 H), 3.33 (d, J = 7.2 Hz, 2 H), 1.77 (s,
3 H), 1.72 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 149.1, 146.3, 137.4, 136.9, 132.4,
120.00, 119.98, 115.2, 113.0, 111.8, 65.5, 55.4, 39.5, 25.5, 17.8.
(E)-3-(3-Allyl-4-(allyloxy)-5-methoxyphenyl)acrylaldehyde (11)
By following the general procedure, compound 10 (73.3 mg, 0.3
mmol) dissolved in DCE (1 mL) was added to a solution of DDQ (149.8
mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction
was stirred at 50 °C for 3 h under air. After the work-up, the crude
product was purified by flash column chromatography to afford the
title compound 11.
Yield: 51.2 mg (66%); yellow solid; mp 76–78 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F