A new synthesis of substituted 2,5-dihydro[b]-oxepines

Article abstract of DOI:10.3987/COM-02-9545

Based on Claisen rearrangement, Baeyer-Villiger oxidation, and ring-closing metathesis (RCM), a series of substituted 2,5-dihydrobenzo[b]-oxepines were synthesized from isovanillin in good over-all yields. Other appropriate substituted 2,5-dihydrobenzo[b]oxepines prepared from corresponding phenol derivatives were also described.

Full text of DOI:10.3987/COM-02-9545

HETEROCYCLES, Vol. 57, No. 11, 2002, pp. 1997 - 2010, Received, 24th June, 2002
A NEW SYNTHESIS OF SUBSTITUTED 2,5-DIHYDRO[b]-
OXEPINES
Eng-Chi Wang,* Ming-Kun Hsu, Yu-Li Lin, and Keng-Shiang Huang
School of Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
Abstract- Based on Claisen rearrangement, Baeyer-Villiger oxidation, and
ring-closing metathesis (RCM), a series of substituted 2,5-dihydrobenzo[b]-
oxepines were synthesized from isovanillin in good over-all yields. Other
appropriate
substituted
2,5-dihydrobenzo[b]oxepines
prepared
from
corresponding phenol derivatives were also described.
INTRODUCTION
Benzo[b]oxepine, a structural unit of some natural occurring sesquiterpines, attracts the attention of either
synthetic or natural product chemists for their activities. Just as heliannuol B isolated from Helianthus
annuus var. SH-222 and VYP exhibited allelopathic activity in the cultivated sunflower to make a defense
against dicotyledon species.1 Heliannuols D,1 a reduced form of heliannuol B, synthesized by Takabatake,
et al.2 has also revealed an alleochemical activity. Radulanin A, and its methyl ether isolated from Radula
complanata by Asakawa, et al.,3a and synthesized via Mitsunobu’s reaction by Yamaguchi, et al.,3b have
shown 5-lipoxygenase and calmodulin inhibitory activity, and vasopressin antagonist activity.3a However
those synthetic methods still have disadvantages including tedious reaction conditions, multi-synthetic
steps, low over-all yields, and commercial unavailable intermediate, which difficulty to prepared. Thus, to
build-up a brief and rationale synthetic method for those title compounds is requisite.
OR
HO
HO
O
O
O
OH
OH
heliannuol D
heliannuol B
radulanin A, R=H
radulanin A methyl ether, R=CH3
Since 1995 Grubbs et al.4 discovered a novel alkylidene-ruthenium complex as a catalyst for ring-closing
metathesis (RCM), it has been widely applied in organic synthesis in many aspects.5 Based on this
chemistry, we have recently reported a new route to N-aryl α,β-unsaturated lactams,6 substituted
*Correponding author: Eng-Chi Wang, Fax: 886-7-3125339; e-mail: enchwa@kmu.edu.tw

naphthalenes.7 Although ring-closing metathesis has been preliminarily applied for the synthesis 2,5-
dihydrobenzo[b]oxepines by Fuerstner, et al.,8a and Miyaki, et al.,8b but for their substituted derivatives
is only paid a little attention.8c In this our continuing studies, based on Claisen reaction, Baeyer-Villiger
oxidation and RCM, we herein reported a versatile synthesis of some new substituted
2,5-dihydrobenzo[b]oxepines, which started from isovanillin. Furthermore other appropriate new
substituted 2,5-dihydrobenzo[b]oxepines prepared from corresponding phenol derivatives were also
described. The synthetic scheme was shown in Scheme 1.
a. R=OCH3; Z=CHO, Y=Z=H
O
OH
b. R=Z=H; Y=CH3
c. R=Z=H; Y=Cl
R
R
d. R=NO2; Y=Z=H
e. R=Y=H; Z=OCH3
Z
Z
Y
Y
1
2
OR1
OR1
OR1
Br
CH3O
CH3O
CH3O
H2O2
R1-X
2a
K2CO3
K2CO3
CH3OH
OH
O
CHO
5
4
3
OR1
PCy3
Ru=
CH3O
Cl
Cl
Ph
Grubbs cat.
Grubbs cat.=
a. R1=Me; b. R1=Et; c. R1=Bn
H
O
PCy3
6
Z
O
Br
Y
R
Grubbs cat.
2b-e
K2CO3
X
O
X
Z
R
e. R=X=Z=H; Y=Cl
d. R=X=Z=H; Y=CH3
f. R=NO2; X=Y=Z=H
Y
g. R=X=Y=H; Z=OCH3
6
5
Scheme 1
RESULTS AND DISCUSSION
According to the general procedure,9 by the reflux of the corresponding phenols (1a-f) with allyl bromide
in the presence of anhydrous K2CO3 in acetone, it gave phenyl ethers (2a-f) in good yields. These phenyl
ethers were respectively heated to boil as previous study7, 10 to undergo Claisen rearrangement to give
2-allylphenols (2a-e) in good yields. The migration of allyl group to the ortho-position of corresponding
1
phenol was confirmed by H-NMR spectra. For example chemical shifts of 2a showed two aromatic
signals with doublet at δ 7.0, and 7.5 having coupling constant, J = 8.8 Hz, indicated ortho-couple of each
other. Thus, the evidence of the migration of allyl group from allyloxy to the ortho-position of phenolic
OH of 2a was confirmed.7 As the procedure previously described,7 these 2-allylphenols (2a) were
respectively alkylated with various alkyl iodide or bromide to give 2-allyl-3-alkoxy-4-methoxy-

benzaldehydes (3a-c) in good yields. Followed by undergoing Baeyer-Villiger oxidation,11 3a-c was
respectively converted into corresponding phenols (4a-c) in yields of 71-75 %. The structure of 4a-c was
1
13
confirmed by H-NMR and C-NMR spectrometry. For example, 4a exhibited a phenolic proton at δ
1
13
4.89 (D2O exchangeable), no formyl proton or carbon observed either in H-NMR or C-NMR spectra,
indicated the work of oxidation. Furthermore the molecular ion of 4a in EI-MS is m/z 194, which is
coincident with the calculated one for 4a, C11H14O3. Then, allylation of 4a-c and 2b-e was smoothly
carried out as general procedure10 to lead 5a-g in yields of 82-88 %. The structure of 5a-g was confirmed
1
13
by spectral data such as H-NMR, C-NMR, and EI-MS. For instance, 5b revealed two sets of allyl
1
group in H-NMR, one at δ 3.47 (dt, J 6.3, 1.9 Hz, 2H, ArCH2CH=CH2), 4.94 (ddt, J 10.2, 1.9, 1.9 Hz,
1H, ArCH2CH=CH2), 5.01 (ddt, J 17.5, 1.9, 1.9 Hz, 1H, ArCH2CH=CH2), and 5.99 (ddt, J 17.5, 10.2, 6.3
Hz, 1H, ArCH2CH=CH2), the other one at δ 4.46 (dt, J 5.0, 1.8 Hz, 2 H, ArOCH2CH=CH2), 5.23 (ddt, J
10.5, 1.8, 1.8 Hz, 1H, ArCH2CH=CH2), 5.40 (ddt, J 17.2, 1.8, 1.8 Hz, 1H, ArCH2CH=CH2), and 6.03 (ddt,
13
J 17.2, 10.5, 5.0 Hz, 1H, ArCH2CH=CH2). Furthermore fifteen lines were found in C-NMR spectra,
matched the carbon numbers for 5b. On the other hand, the molecular ion, m/z 248 was found in EI-MS,
which is coincident with the calculated one for 5b, C15H20O3. Finally 5a-f was respectively treated with
Grubbs’ catalyst in dichloromethane to undergo RCM reaction, it furnished substituted benzo[b]oxepines
1
(6a-g) in yields of 80-88 % yields. The structure of 6a-g was supported by the data of H-NMR,
13C-NMR, and EI-MS spectra. Such as 6c, two cis-olefinic protons at δ 5.36 (J 14.4, 5.3, 2.4 Hz, 1H, H-4),
1
and 5.68 (J 14.4, 8.1, 2.0 Hz, 1H, H-3) in H-NMR spectrum, and two olefinic carbons at δ 110.09 and
116.28 in 13C-NMR spectrum were found, respectively. The molecular ion, m/z 282 was found in EI-MS
spectrum, which is coincident with the calculated one for 6c, C18H18O3.
In conclusion, besides 6-methoxybenzo[b]oxepines (6g),8c such as 6-alkoxy-7-methoxybenzo[b]oxepines
(6a-c) 7-methyl or 7-chlorobenzo[b]oxepines (6d-e), and 9-nitrobenzo[b]oxepines (6f), which are all new
compounds, were synthesized in good over-all yields. Thus, our study gave a new and versatile route to
substituted benzo[b]oxepines from isovanillin, and various phenols. Furthermore the 1H-NMR, 13C-NMR,
EI-MS, and HRMS spectral data for those substituted benzo[b]oxepines (6a-g) were also established. The
synthesis of other new substituted benzo[b]oxepines is currently in progress in our lab.
EXPERIMENTAL
Melting points (Yanaco micro melting-point apparratus) are uncorrected. 1H-NMR and 13C-NMR spectra
were obtained on a Varian Gemini-200 or Varian Unity plus 400 or Bruker Avance 600 Spectrometer.
Chemical shifts are measured in parts per million with respect to TMS. Elemental analyses were recorded
on a Heraeus CHN-O Rapid analyzer. MS spectra were recorded on Chem/hp/middle instrument, and
HRMS were recorded on JEOL, JMSD-200 or on JEOL, JMS-SX. Silica gel (230-400 mesh) for column
chromatography, and precoated silica gel plates (60F-254) for TLC was purchased from E. Merck. UV
light (254 nm) was used to detect spots on TLC plates after development.
General procedure for o-allylation of corresponding phenolic compound to give allyloxyl

compounds (1a-e)
The corresponding phenols (20 mmol) were respectively reacted with allyl bromide as the known
procedure10 to give allyloxyl compounds (1a-e).
3-allyloxy-4-methoxybenzaldehyde (1a)12
1
Pure 1a (3.34 g, 87%) was obtained as colorless liquid, Rf 0.36 (ethyl acetate/n-hexane = 1/3); H NMR
(CDCl3, 400 MHz) δ 3.96 (s, 3H, OCH3), 4.67 (dt, J = 5.2 Hz, 1.2 Hz, 2H, OCH2CH=CH2), 5.32 (ddt, J =
10.4 Hz, 1.2 Hz, 1.2 Hz, 1H, OCH2CH=CH2), 5.45 (ddt, J = 17.2 Hz, 1.2 Hz, 1.2 Hz, 1H, OCH2CH=CH2),
6.09 (ddt, J = 17.2, 10.4, 5.2 Hz, 1H, OCH2CH=CH2), 6.99, 7.46 (each d, J = 8.0 Hz, 1H, ArH), 7.41 (s,
13
1H, ArH); C NMR (CDCl3, 100 MHz) δ 56.08, 69.64, 110.62, 110.82, 118.51, 126.72, 129.94, 132.44,
148.45, 154.77, 190.76.
1-Allyloxy-4-methylbenzene (1b)13
Pure 9a (2.58 g, 87%) was obtained as colorless liquid, Rf =0.89 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 2.25 (s, 3H, ArCH3), 4.46 (dt, J = 5.2 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.24 (dd,
J = 10.4 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.37 (dd, J = 17.2 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 6.02
(ddt, J = 17.2 Hz, 10.4 Hz, 5.2 Hz, 1H, ArOCH2CH=CH2), 6.79 (d, J = 8.4 Hz, 2H, ArH), 7.04 (d, J = 8.6
13
Hz, 2H, ArH); C-NMR (CDCl3, 100 MHz) δ 20.35, 68.73, 114.51, 117.25, 129.77, 129.88, 133.49,
156.43; EI-MS (70 eV) m/z 148 (M+, 100), 133 (65), 131 (4), 120 (5), 107 (76), 91 (17), 80 (6), 77 (54),
65 (12), 51 (12); HRMS calcd for C10H12O: 148.0888. Found: 148.0888.
Allyloxy-4-chlorobenzene (1c)14
Pure 1c (3.04 g, 90 %) was obtained as colorless liquid, Rf =0.87 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 4.47 (dt, J = 5.2 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.27 (ddt, J = 10.0 Hz, 1.6 Hz,
1.6 Hz, 1H, ArOCH2CH=CH2), 5.38 (ddt, J = 17.2 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 6.01 (ddt,
J = 17.2 Hz, 10.0 Hz, 5.2 Hz, 1H, ArOCH2CH=CH2), 6.81 (d, J = 8.8 Hz, 2H, ArH), 7.20 (d, J = 8.8 Hz,
2H, ArH); 13C-NMR (CDCl3, 100 MHz) δ 68.94, 115.95, 117.72, 125.58, 129.21, 132.87, 157.13; EI-MS
(70 eV) m/z 168 (M+, 100), 153 (13), 140 (4), 133 (81), 111 (12), 99 (60), 91 (4), 75 (31), 63 (26), 50 (14);
HRMS calcd for C9H9ClO: 168.0342. Found: 168.0339.
1-Allyloxy-2-nitrobenzene (1d)15
1
Pure 1d (3.19 g, 89%) was obtained as yellow liquid, Rf =0.41 (ethyl acetate/n-hexane=1/12); H-NMR
(CDCl3, 400 MHz) δ 4.68 (dt, J = 4.8 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.31 (ddt, J = 10.8 Hz, 1.6 Hz,
1.6 Hz, 1H, ArOCH2CH=CH2), 5.49 (ddt, J = 17.2 Hz, 1.6 Hz , 1.6 Hz, 1H, ArOCH2CH=CH2), 6.03 (ddt,
J = 17.2 Hz, 10.8 Hz, 4.8 Hz, 1H, ArOCH2CH=CH2), 7.02 (td, J = 8.0 Hz, 1.6 Hz, 1H, ArH), 7.08 (dd, J
= 8.0 Hz, 1.6 Hz, 1H, ArH), 7.51 (td, J = 8.0 Hz, 1.6 Hz, 1H, ArH), 7.82 (dd, J = 8.0 Hz, 1.6 Hz, 1H,
13
ArH); C-NMR (CDCl3, 100 MHz) δ 69.81, 114.76, 118.07, 120.35, 125.43, 131.62, 133.96, 139.91,
151.74; EI-MS (70 eV) m/z 179 (M+, 12), 139 (6), 123 (100), 106 (46), 92 (9), 78 (11), 63 (22), 51 (15);
HRMS calcd for C9H9NO3: 179.0582. Found: 179.0585.

1-Allyloxy-3-methoxybenzene (1e)16
Pure 1e (2.82 g, 86%) was obtained as colorless liquid, Rf = 0.59 (ethyl acetate/n-hexane=1/12), 1H-NMR
(CDCl3, 200 MHz) δ 3.75 (s, 3H, OCH3), 4.49 (dt, J = 5.3 Hz, 1.6 Hz, 2H, CH2CH=CH2), 5.26 (ddt, J =
10.5 Hz, 1.6 Hz, 1.6 Hz, 1H, CH2CH=CH2), 5.39 (ddt, J = 17.3 Hz, 1.6 Hz, 1.6 Hz, 1H, CH2CH=CH2),
6.04 (ddt, J = 17.3 Hz, 10.5 Hz, 5.3 Hz, 1H, CH2CH=CH2), 6.48 (s, 1H, ArH), 6.50 (dt, J = 7.6 Hz, 2.1
Hz, 2H, ArH), 7.15 (t, J = 7.6 Hz, 1H, ArH); 13C-NMR (CDCl3, 50 MHz) δ 55.11, 68.70, 101.17, 106.34,
106.79, 117.50, 129.76, 133.22, 159.78, 160.76; EI-MS (70 eV) m/z 164 (M+, 100), 149 (23), 136 (22),
121 (30), 109 (12), 105 (13), 95 (39), 77 (13), 64 (11), 52 (12); HRMS: Calcd for C10H12O2: 164.0837.
Found: 164.0835.
General procedure for the preparation of 2a-e via the Claisen rearrangement of 1a-e
The corresponding allyloxyl compounds 1a-e (15 mmol) were respectively heated to undergo Claisen
reaction as the known procedure7, 8, 10 to give 2a-e.
2-Allyl-3-hydroxy-4-methoxybenzaldehyde (2a)7, 8
1
Pure 2a (2.7 g, 94%) was obtained as pale yellow liquid; Rf 0.47 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.75 (dt, J = 6.0 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.77 (s, 3H, OCH3), 4.84 (dt, J =
18.8 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 4.88 (dt, J = 10.0 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.89 (ddt, J =
18.8 Hz, 10.0 Hz, 6.0 Hz, 1H, ArCH2CH=CH2), 6.28 (br s, 1H, OH), 6.71, 7.27 (each d, J = 8.4 Hz, 1H,
ArH), 9.90 (s, 1H, CHO); 13C NMR (CDCl3, 100 MHz) δ 28.08 (ArCH2CH=CH2), 55.76 (OCH3), 107.91,
114.96, 125.28, 127.31, 127.74, 136.07, 143.61, 150.80, 191.40 (CHO); EI-MS (70 eV) m/z (rel. intensity,
%) 192 (M+, 54), 177 (100), 159 (24), 149 (23), 143 (19), 131 (29), 115 (19), 103 (28), 91 (20), and 77
(23); HRMS calcd for C11H12O3: 192.0786. Found: 192.0789.
2-Allyl-4-methylphenol (2b)15
Pure 2b (1.96 g, 88%) was obtained as colorless liquid, Rf =0.32 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 200 MHz) δ 2.25 (s, 3H, ArCH3), 3.63 (d, J = 6.4 Hz, 2H, ArCH2CH=CH2), 4.98 (s, 1H, ArOH),
5.13 (dd, J = 11.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.14 (dd, J = 15.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2),
6.01 (ddt, J = 17.6 Hz, 9.7 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.69 (d, J = 8.7 Hz, 1H, ArH), 6.90 ( s, 1H,
ArH), 6.91 (d, J = 8.6 Hz, 1H, ArH); 13C-NMR (CDCl3, 50 MHz) δ 20.42, 35.03, 115.60, 116.24, 125.07,
128.17, 130.08, 130.92, 136.52, 151.69; EIMS (70 eV) m/z 148 (M+, 100), 133 (83), 131 (15), 105 (53),
91 (28), 77 (15), 65(6), 51(6); HRMS: Calcd for C10H12O: 148.0888. Found: 148.0890.
2-Allyl-4-chlorophenol (2c)15
Pure 2c (2.15 g, 85%) was obtained as colorless liquid, Rf =0.79 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 200 MHz) δ 3.37 (dt, J = 6.4 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 5.11 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6
Hz, 1H, ArCH2CH=CH2), 5.18 (ddt, J = 17.5 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.65 (br s, 1H,
ArOH), 5.98 (ddt, J = 17.5 Hz, 10.4 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.74, 7.04 (each d, J = 8.8 Hz, 1H,
13
ArH), 7.09 (s, 1H, ArH); C-NMR (CDCl3, 50 MHz) δ 34.57, 116.00, 116.82, 125.28, 127.37, 129.95,

130.20, 135.55, 152.69; EI-MS (70 eV) m/z 168(M+, 100), 153(36), 141(13), 133(98), 115(33), 105(79),
89(14), 77(62), 66(16), 51(47); HRMS: Calcd for C9H9OCl: 168.0342. Found: 168.0344.
2-Allyl-6-nitrophenol (2d)15
1
Pure 2d (2.07 g, 77%) was obtained as yellow liquid, Rf =0.77 (ethyl acetate/n-hexane=1/12); H-NMR
(CDCl3, 200 MHz) δ 3.48 (dt, J = 6.6 Hz, 1.3 Hz, 2H, ArCH2CH=CH2), 5.12 (ddt, J = 15.0 Hz, 1.3 Hz,
1.3 Hz, 1H, ArCH2CH=CH2), 5.11 (ddt, J = 17.7 Hz, 1.3 Hz, 1.3 Hz, 1H, ArCH2CH=CH2), 5.98 (ddt, J =
17.7 Hz, 15.0 Hz, 6.6 Hz, 1H, ArCH2CH=CH2), 6.92 (t, J = 8.0 Hz, 1H, ArH), 7.46 (dd, J = 8.0 Hz, 1.0
13
Hz, 1H, ArH), 7.97 (dd, J = 8.0 Hz, 1.0 Hz, ArH), 10.93 (s, 1H, ArOH); C-NMR (CDCl3, 50 MHz) δ
33.55, 116.75, 119.42, 123.02, 131.34, 133.56, 135.05, 137.42, 153.20; EI-MS (70 eV) m/z 179 (M+, 56),
162(11), 132(12), 116(14), 103(61), 89(11), 77(46), 65(7.0), 51(17); HRMS: Calcd for C9H9NO3:
179.0582. Found: 179.0582.
2-Allyl-3-methoxyphenol (2e)17
Pure 2e (1.85 g, 75%) was obtained as colorless liquid, Rf =0.47 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 200 MHz) δ 3.48 (dt, J = 6.3 Hz, 1.8 Hz, 1.7 Hz, 2H, ArCH2CH=CH2), 3.80 (s, 3H, OCH3), 5.07
(br s, 1H, OH), 5.08 (ddt, J = 10.4 Hz, 1.8 Hz, 1.8 Hz, 1H, ArCH2CH=CH2), 5.10 (ddt, J = 18.0 Hz, 1.8
Hz, 1.8 Hz, 1H, ArCH2CH=CH2), 5.98 (ddt, J = 18.0 Hz, 10.4 Hz, 6.3 Hz, 1H, ArCH2CH=CH2), 6.49 (dd,
J = 8.5 Hz, 2.0 Hz, 2 H, ArH), 7.08 (t, J = 8.5 Hz, 1H, ArH); 13C-NMR (CDCl3, 50 MHz) δ 27.32, 55.80,
103.33, 108.79, 113.61, 115.36, 127.51, 136.30, 155.14, 158.21; EI-MS (70 eV) m/z 164 (M+, 100), 149
(34), 135 (42), 121 (34), 107 (39), 103 (23), 91 (20), 77 (21), 65 (7), 51 (7); HRMS: Calcd for C10H12O2:
164.0837. Found: 164.0837.
General procedure for the preparation of 3a-c from 2a-c
The corresponding o-allylphenols (2a-c) (10 mmol) were respectively reacted with methyl iodide, ethyl
bromide, and benzyl bromide as the known procedure7, 8 to give allylalkoxy compounds (3a-c).
2-Allyl-3,4-dimethoxybenzaldehyde (3a)7, 18
1
Pure 3a (1.81 g, 88%) was obtained as pale yellow liquid, Rf 0.62 (ethyl acetate/n-hexane = 1/3); H
NMR (CDCl3, 200 MHz) δ 3.73, 3.85 (each s, 3H, OCH3), 3.78 (dt, J = 5.8, 1.8 Hz, 2H, CH2=CHCH2Ar),
4.84 (ddd, J = 17.0, 3.3, 1.8 Hz, 1H, CH2=CHCH2Ar), 4.93 (ddd, J = 10.3, 3.3, 1.8 Hz, 1H,
CH2=CHCH2Ar), 5.94 (dtd, J = 17.0, 10.3, 5.8 Hz, 1H, CH2=CHCH2Ar), 6.85 (d, J = 8.6 Hz, 1H, ArH),
7.54 (d, J = 8.6 Hz, 1H, ArH), 9.95 (s, 1H, CHO); 13C-NMR (CDCl3, 50 MHz) δ 28.41 (CH2=CHCH2Ar),
55.50, 60.60 (each, OCH3), 109.64, 115.24, 127.62, 128.88, 135.72, 136.91, 146.98, 157.22, 190.59
(CHO); EI-MS (70 eV) m/z (rel. intensity, %) 206 (M+, 58), 191 (100), 175 (39), 174 (19), 163 (22), 147
(23), 131 (28), 103 (33), 91 (33); HRMS calcd for C12H14O3: 206.0943. Found: 206.0935.
2-Allyl-3-ethoxy-4-methoxybenzaldehyde (3b)7
1
Pure 3b (1.76 g, 80%) was obtained as pale yellow liquid; Rf 0.55 (ethyl acetate/n-hexane=1/3); H-

NMR (CDCl3, 200 MHz) δ 1.36 (t, J = 7.0 Hz, 3H, OCH2CH3), 3.84 (dt, J = 5.8, 1.8 Hz, 2H,
CH2=CHCH2Ar), 3.89 (s, 3H, OCH3), 3.96 (q, J = 7.0 Hz, 2H, OCH2CH3), 4.88 (ddd, J = 17.0, 3.3, 1.8
Hz, 1H, CH2=CHCH2Ar), 4.98 (ddd, J = 10.3, 3.3, 1.8 Hz, 1H, CH2=CHCH2Ar), 5.99 (dtd, J = 17.0, 10.3,
5.8 Hz, 1H, CH2=CHCH2Ar), 6.88 (d, J = 8.5 Hz, 1H, ArH), 7.57 (d, J = 8.5 Hz, 1H, ArH), 10.02 (s, 1H,
CHO); 13C-NMR (CDCl3, 50 MHz) δ 16.09 (OCH2CH3), 29.33 (CH2=CHCH2Ar), 56.27 (OCH3), 110.26,
115.98, 128.43, 129.34, 136.69, 137.68, 146.96, 158.11, 191.47(CHO); EI-MS (70 eV) m/z (rel. intensity,
%) 220 (M+, 68), 205 (100), 192 (32), 191 (38), 177 (99), 164 (31), 159 (38), 143 (35), 135 (46), 131 (57),
103 (73), 91 (53); HRMS calcd for C13H16O3: 220.1099. Found: 220.1104.
2-Allyl-3-benzyloxy-4-methoxybenzaldehyde (3c)7, 19
Pure 3c (2.76 g, 98%) was obtained as pale yellow liquid, Rf 0.56 (ethyl acetate/n-hexane=1/3); 1H NMR
(CDCl3, 200 MHz) δ 3.88 (dt, J = 5.8, 1.8 Hz, 2H, CH2=CHCH2Ar), 3.92 (s, 3H, OCH3), 4.91 (ddd, J =
17.0, 3.3, 1.8 Hz, 1H, CH2=CHCH2Ar), 4.99 (s, 2H, OCH2C6H5), 5.02 (ddd, J = 10.3, 3.3, 1.8 Hz, 1H,
CH2=CHCH2Ar), 6.01 (dtd, J = 17.0, 10.3, 5.8 Hz, 1H, CH2=CHCH2Ar), 6.94 (d, J = 8.5 Hz, 1H, ArH),
7.34 (d, J = 7.5 Hz, 2H, OCH2C6H5), 7.42 (d, J = 7.5 Hz, 2H, OCH2C6H5), 7.48 (d, J = 7.5 Hz, 1H,
13
OCH2C6H5), 7.67 (d, J = 8.5 Hz, 1H, ArH), 10.06 (s, 1H, CHO); C-NMR (CDCl3, 50 MHz) δ 29.41
(CH2=CHCH2Ar), 56.37 (OCH3), 75.41 (OCH2C6H5), 110.49, 116.21, 128.57, 128.72, 128.85, 128.96,
129.69, 136.90, 137.71, 137.96, 146.59, 158.12, 191.42 (CHO); EI-MS (70 eV) m/z (rel. intensity, %) 282
(M+, 0.3), 192 (2), 191 (20), 177 (9), 163 (2), 159 (2), 135 (3), 131 (3), 105 (3), 103 (5), 92 (10), 91 (100);
HRMS calcd for C18H18O3: 282.1256. Found: 282.1259.
General procedure for the preparation of 4a-e from 3a-e via Baeyer-Villiger oxidation11
Compound (3a-e) (15 mmol) dissolved in methanol (45 mL) was added with 35% H2O2 (3 mL, 35 mmol),
and conc. H2SO4 (3 drops), and stirred at rt by monitoring with TLC until the disappearance of starting
material for 1.5 h. The solution was concentrated under vacuo to remove methanol. And then the residue
was suspended in water (20 mL), and extracted with ethyl acetate (20 mL x 3). The mixture of organic
phases was washed with brine (10 mL x 2), and then dried with anhydrous MgSO4. After filtration, the
filtrate was concentrated in vacuo to give the crude 4a-e. When subjected to chromatographic column
(ethyl acetate/n-hexane=1/6), it gave pure 4a-e in yields of 71-74 %.
2-Allyl-3,4-dimethoxyphenol (4a)20
1
Pure 4a (2.16 g, 74%) was obtained as colorless liquid, Rf =0.57 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.48 (ddd, J = 6.0 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.80 (s, 3H, ArOCH3),
3.81 (s, 3H, ArOCH3), 4.89 (br s, 1H, ArOH), 5.10 (ddt, J = 10.6 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArCH2CH=CH2), 5.11 (ddt, J = 17.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 6.01 (ddt, J = 17.6 Hz,
10.6 Hz, 6.0 Hz, 1H, ArCH2CH=CH2), 6.56, 6.71 (each d, J = 8.8 Hz, 1H, ArH); 13C-NMR (CDCl3, 100
MHz) δ 28.33, 56.32, 61.01, 110.56, 111.37, 115.75, 120.29, 136.37, 147.10, 147.80, 148.77; EI-MS (70
eV) m/z 194 (M+, 87), 179 (100), 163 (9), 147 (73), 123 (18), 119 (34), 107 (7), 91 (22), 77 (6), 55 (3);
HRMS: Calcd for C11H14O3: 194.0943. Found: 194.0941.

2-Allyl-3-ethoxy-4-methoxyphenol (4b)
1
Pure 4b (2.22 g, 71%) was obtained as white solid, Rf =0.60 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 200 MHz) δ 1.35 (t, J = 7.1 Hz, 3H, ArOCH2CH3), 3.49 (ddd, J = 6.0 Hz, 1.6 Hz, 1.6 Hz, 2H,
ArCH2CH=CH2), 3.79 (s, 3H, ArOCH3), 4.00 (q, J = 7.1 Hz, 2H, ArOCH2CH3), 4.91 (br s, 1H, ArOH),
5.10 (ddt, J = 10.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.11 (ddt, J = 17.6 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArCH2CH=CH2), 6.00 (ddt, J = 17.6 Hz, 10.6 Hz, 6.0 Hz, 1H, ArCH2CH=CH2), 6.54 (d, J = 8.8 Hz, 1H,
13
ArH), 6.7 (d, J = 8.8 Hz, 1H, ArH); C-NMR (CDCl3, 50 MHz) δ 15.62, 28.57, 56.37, 69.10, 110.42,
111.39, 115.74, 120.42, 136.40, 146.95, 147.19, 148.82; EI-MS (70eV) m/z 208 (M+, 100), 193 (28), 165
(85), 147 (23), 137 (67), 119 (33), 109 (16), 91 (13), 77 (4), 53 (3); HRMS: Calcd for C12H16O3: 208.1099.
Found: 208.1098; Anal. Calcd for C12H16O3: C, 69.21; H, 7.74. Found: C, 79.51; H, 7.56.
2-Allyl-3-benzyloxy-4-methoxyphenol (4c)
1
Pure 4c (3.04 g, 75%) was obtained as colorless liquid, Rf =0.45 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.43 (ddd, J = 6.0 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.83 (s, 3H, ArOCH3),
4.89 (s, 1H, ArOH), 4.99 (s, 2H, ArOCH2C6H5), 5.07 (ddt, J = 10.6 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArCH2CH=CH2), 5.08 (ddt, J = 17.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.87 (ddt, J = 17.6 Hz,
10.6 Hz, 6.0 Hz, 1H, ArCH2CH=CH2), 6.57, 6.74 (each d, J = 8.8 Hz, 1H, ArH), 7.29 (d, J = 7.8 Hz, 1H,
13
ArCH2C6H5), 7.36 (t, J = 7.8 Hz, 2H, ArCH2C6H5), 7.48 (d, J = 7.8 Hz, 2H, ArCH2C6H5); C-NMR
(CDCl3, 100 MHz) δ 26.62, 56.46, 75.03, 110.77, 111.58, 115.90, 120.47, 127.89, 128.24, 128.34, 136.32,
137.69, 146.48, 147.17, 148.87; EI-MS (70 eV) m/z 270 (M+, 16), 179 (25), 147 (16), 119 (8), 91 (100);
HRMS (EI, m/z): Calcd for C17H18O3: 270.1256. Found: 270.1254; Anal. Calcd for C17H18O3: C, 75.53; H,
6.71. Found: C, 75.88; H, 6.56.
General procedure for the preparation of 5a-g from 4a-c, and 2b-e via o-allylation
The corresponding phenols (4a-e) or (2b-e) (10 mmol) were respectively reacted with allyl bromide (10.5
mmol) to give 5a-g as the same process described for the preparation of 1a-e.
2-Allyl-1-allyloxy-3,4-dimethoxybenzene (5a)
1
Pure 5a (1.94 g, 83%) was obtained as colorless liquid, Rf =0.76 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.46 (ddd, J = 6.2 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.80 (s, 3H, ArOCH3),
3.81 (s, 3H, ArOCH3), 4.47 (ddd, J = 5.6 Hz, 1.6, Hz 1.6 Hz, 2H, ArOCH2CH=CH2), 4.95 (ddt, J = 10.5
Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.02 (ddt, J = 16.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2),
5.23 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.40 (ddt, J = 16.9 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArOCH2CH=CH2), 5.98 (ddt, J = 16.6 Hz, 10.5 Hz, 6.2 Hz, 1H, ArCH2CH=CH2), 6.03 (ddt, J = 16.9 Hz,
10.4 Hz, 5.6 Hz, 1H, ArOCH2CH=CH2), 6.55, 6.70 (each d, J = 8.8 Hz, 1H, ArH); 13C-NMR (CDCl3, 100
MHz) δ 28.27, 56.08, 60.77, 69.41, 107.04, 110.14, 114.45, 116.57, 123.53, 133.67, 137.05, 147.29,
147.98, 151.07; EI-MS (70 eV) m/z 234 (M+, 80), 219 (8), 193 (100), 178 (68), 162 (37), 150 (18), 135
(16), 107 (9), 105 (15), 79 (6); HRMS (EI, m/z) : Calcd for C14H18O3: 234.1256. Found: 234.1255; Anal.
Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 72.04; H, 7.58.

2-Allyl-1-allyloxy-3-ethoxy-4-methoxybenzene (5b)
1
Pure 5b (2.04 g, 82%) was obtained as colorless liquid, Rf =0.74 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 200 MHz) δ 1.37 (t, J = 7.1 Hz, 3H, ArOCH2CH3), 3.47 (ddd, J = 6.2 Hz, 1.6 Hz, 1.6 Hz, 2H,
ArCH2CH=CH2), 3.79 (s, 3H, ArOCH3), 4.01 (q, J = 7.1 Hz, 2H, ArOCH2CH3), 4.46 (ddd, J = 5.6 Hz,
1.6, Hz 1.6 Hz, 2H, ArOCH2CH=CH2), 4.94 (ddt, J = 10.5 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.01
(ddt, J = 16.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 5.23 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArOCH2CH=CH2), 5.40 (ddt, J = 16.9 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.99 (ddt, J = 16.6 Hz,
10.5 Hz, 6.2 Hz, 1H, ArCH2CH=CH2), 6.03 (ddt, J = 16.9 Hz, 10.4 Hz, 5.6 Hz, 1H, ArOCH2CH=CH2),
6.53, 6.69 (each d, J = 8.8 Hz, 1H, ArH); 13C-NMR (CDCl3, 50 MHz) δ 15.64, 28.51, 56.16, 68.80, 69.41,
106.84, 110.12, 114.32, 116.56, 123.68, 133.73, 137.10, 147.21, 147.45, 151.15; EI-MS (70 eV) m/z 248
(M+, 100), 207 (63), 192 (68), 178 (54), 163 (22), 147 (81), 119 (41), 91 (28), 79 (10); HRMS: Calcd for
C15H20O3: 248.1412. Found: 248.1415; Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.90; H,
8.48.
2-Allyl-1-allyloxy-3-benzyloxy-4-methoxybenzene (5c)
1
Pure 5c (2.64 g, 85%) was obtained as colorless liquid, Rf =0.75 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.46 (ddd, J = 6.2 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.81 (s, 3H, ArOCH3),
4.46 (ddd, J = 5.6 Hz, 1.6, Hz 1.6 Hz, 2H, ArOCH2CH=CH2), 4.93 (ddt, J = 10.5 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArCH2CH=CH2), 4.94 (ddt, J = 16.6 Hz, 1.6 Hz, 1.6 Hz, 1H, ArCH2CH=CH2), 4.99 (s, 2H,
ArOCH2C6H5), 5.23 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.39 (ddt, J = 16.9 Hz, 1.6
Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.95 (ddt, J = 16.6 Hz, 10.5 Hz, 6.2 Hz, 1H, ArCH2CH=CH2), 6.02
(ddt, J = 16.9 Hz, 10.4 Hz, 5.6 Hz, 1H, ArOCH2CH=CH2), 6.57, 6.73 (each d, J = 8.8 Hz, 1H, ArH), 7.30
(d, J = 7.8 Hz, 1H, ArCH2C6H5), 7.36 (t, J = 7.8 Hz, 2H, ArCH2C6H5), 7.48 (d, J = 7.8 Hz, 2H,
ArCH2C6H5); 13C-NMR (CDCl3, 100 MHz) δ 28.49, 56.23, 69.43, 74.69, 107.21, 110.27, 114.52, 116.62,
123.82, 127.71, 127.92, 128.27, 133.68, 137.02, 137.99, 146.87, 147.43, 151.16; EI-MS (70eV) m/z 310
(M+, 46), 269 (6), 219 (93), 191 (14), 178 (29), 131 (11), 105 (10), 91 (100), 65 (8); HRMS (EI, m/z):
Calcd for C20H22O3: 310.1569. Found: 310.1567; Anal. Calcd for C20H22O3: C, 77.39; H, 7.14. Found: C,
77.55; H, 7.40.
3-Allyl-4-allyloxytoluene (5d)
Pure 5d (1.62 g, 86%) was obtained as colorless liquid, Rf =0.91 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 2.25 (s, 3H, ArCH3), 3.38 (ddt, J = 6.4 Hz, 2.0 Hz, 2.0 Hz, 2H, ArCH2CH=CH2),
4.49 (ddt, J = 6.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.02 (ddt, J = 10.4 Hz, 2.0 Hz, 2.0 Hz, 1H,
ArCH2CH=CH2), 5.06 (ddt, J = 16.6 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.23 (ddt, J = 10.4 Hz,
1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.40 (ddt, J = 17.2 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2),
5.99 (ddt, J = 16.6 Hz, 10.4 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.03 (ddt, J = 17.2 Hz, 10.4 Hz, 6.8 Hz,
1H, ArOCH2CH=CH2), 6.71, 6.94 (each d, J = 7.0 Hz, 1H, ArH), 6.95 (s, 1H, ArH); 13C-NMR (CDCl3,
100 MHz) δ 20.53, 34.49, 69.02, 111.85, 115.31, 116.77, 127.49, 128.81, 129.95, 130.65, 133.81, 137.22,
154.21; EI-MS, (70 eV) m/z 188 (M+, 63), 147 (85), 132 (27), 119 (100), 91 (84), 77 (22),; HRMS (EI,

m/z): Calcd for C13H16O: 188.1201. Found: 188.1202; Anal. Calcd for C13H16O: C, 82.94; H, 8.57. Found:
C, 83.23; H, 8.89.
2-Allyl-1-allyloxy-4-chlorobenzene (5e)
Pure 5e (1.82 g, 87%) was obtained as colorless liquid, Rf =0.90 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 200 MHz) δ 3.42 (ddt, J = 6.4 Hz, 2.0 Hz, 2.0 Hz, 2H, ArCH2CH=CH2), 4.55 (ddt, J = 6.8 Hz,
1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.12 (ddt, J = 10.4 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.13
(ddt, J = 16.6 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.31 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArOCH2CH=CH2), 5.45 (ddt, J = 17.2 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.99 (ddt, J = 16.6 Hz,
10.4 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.07 (ddt, J = 17.2 Hz, 10.4 Hz, 6.8 Hz, 1H, ArOCH2CH=CH2),
6.78, 7.13 (each d, J = 7.0 Hz, 1H, ArH), 7.17 ( s, 1H, ArH); 13C-NMR (CDCl3, 50 MHz) δ 34.10, 69.01,
112.73, 116.15, 117.18, 125.46, 126.78, 129.62, 130.83, 133.07, 135.99, 154.78; EI-MS (70 eV) m/z
210 (M+2, 11), 208 (M+, 33), 167 (50), 132 (51), 115 (15), 103 (100), 89 (12), 77 (55), 51 (24); HRMS:
Calcd for C12H13OCl: 208.0655. Found: 208.0655; Anal. Calcd for C12H13OCl: C, 69.07; H, 6.28. Found:
C, 69.36; H, 6.50.
1-Allyl-2-allyloxy-3-nitrobenzene (5f)
1
Pure 5f (1.86 g, 85%) was obtained as yellow liquid, Rf =0.71 (ethyl acetate/n-hexane=1/12); H-NMR
(CDCl3, 200 MHz) δ 3.49 (ddt, J = 6.4 Hz, 2.0 Hz, 2.0 Hz, 2H, ArCH2CH=CH2), 4.49 (ddt, J = 6.8 Hz,
1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 5.09 (ddt, J = 10.4 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.13
(ddt, J = 16.6 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.27 (ddt, J = 10.4 Hz, 1.6 Hz, 1.6 Hz, 1H,
ArOCH2CH=CH2), 5.39 (ddt, J = 17.2 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.97 (ddt, J = 16.6 Hz,
10.4 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.07 (ddt, J = 17.2 Hz, 10.4 Hz, 6.8 Hz, 1H, ArOCH2CH=CH2),
7.16 (t, J = 8.0 Hz, 1H, ArH), 7.44 (dd, J = 8.0 Hz, 1.6 Hz, 1H, ArH), 7.67 (dd, J = 8.0 Hz, 1.6 Hz, 1H,
ArH); 13C-NMR (CDCl3, 50 MHz) δ 33.61, 75.94, 116.97, 118.60, 123.28, 123.93, 132.72, 134.94,
135.70, 136.58, 144.48, 149.99; EI-MS (70 eV) m/z 219(M+, 94), 202 (64), 172 (74), 129 (77), 128 (100),
77 (42), 65 (20); HRMS (EI, m/z) : Calcd for C12H13NO3: 219.0895. Found: 219.0897; Anal. Calcd for
C12H13NO3: C, 65.74; H, 5.98. Found: C, 65.95; H, 6.31.
2-Allyl-1-allyloxy-3-methoxybenzene (5g)
Pure 5g (1.80 g, 88%) was obtained as colorless liquid, Rf =0.68 (ethyl acetate/n-hexane=1/12), 1H-NMR
(CDCl3, 200 MHz) δ 3.45 (ddt, J = 6.4 Hz, 2.0 Hz, 2.0 Hz, 2H, ArCH2CH=CH2), 3.80 (s, 3H, OCH3),
4.53 (ddt, J = 6.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH2), 4.92 (ddt, J = 10.4 Hz, 2.0 Hz, 2.0 Hz, 1H,
ArCH2CH=CH2), 4.99 (ddt, J = 16.6 Hz, 2.0 Hz, 2.0 Hz, 1H, ArCH2CH=CH2), 5.24 (ddt, J = 10.4 Hz,
1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2), 5.41 (ddt, J = 17.2 Hz, 1.6 Hz, 1.6 Hz, 1H, ArOCH2CH=CH2),
5.96 (ddt, J = 16.6 Hz, 10.4 Hz, 6.4 Hz, 1H, ArCH2CH=CH2), 6.07 (ddt, J = 17.2 Hz, 10.4 Hz, 6.8 Hz,
1H, ArOCH2CH=CH2), 6.53 (d, J = 8.3 Hz, 1H, ArH), 6.54 (d, J = 8.3 Hz, 1H, ArH), 7.11 (t, J = 8.3 Hz,
13
1H, ArH); C-NMR (CDCl3, 50 MHz) δ 27.37, 55.78, 69.08, 103.97, 105.18, 114.04, 116.67, 117.03,
126.99, 133.63, 136.87, 157.18, 158.29; EI-MS (70 eV) m/z 204 (M+, 74), 189 (13), 161 (40), 147 (41),

131 (26), 115 (16.26, 105 (46), 91 (45), 77 (31), 51 (8); HRMS (EI, m/z): Calcd for C13H16O2: 204.1150.
Found: 204.1149; Anal. Calcd for C13H16O2: C, 76.44; H, 7.90. Found: C, 76.80; H, 8.03.
General procedure for the preparation of substituted 2,5-dihydrobenzo[b]oxepine (6a-g)
Compound (5a-g) (1 mmol) dissolved in anhydrous CH2Cl2 (20 mL), was added with Grubbs catalyst
(5mol %). The mixture was stirred for 12 h at ambient temperature under dry argon. Finally
dichloromethane was removed under reduced pressure, and the residue was subjected to a silica gel
column (3/1: hexane/MTBE) or to distill under vacuum to give 6a-g, respectively.
6,7-Dimethoxy-2,5-dihydrobenzo[b]oxepine (6a)
Pure 6a (0.2 g, 85%) was obtained as colorless liquid, Rf =0.64 (ethyl acetate/n-hexane=1/3); 1H-NMR
(CDCl3, 600 MHz) δ 3.55 (dd, J = 5.3 Hz, 2.0 Hz, 2H, ArCH2CH=CH), 3.77 (s, 3H, ArOCH3), 3.83 (s,
3H, ArOCH3), 4.54 (dd, J = 8.1 Hz, 2.4 Hz, 2H, ArOCH2CH=CH2), 5.44 (dtt, J = 14.4 Hz, 5.3 Hz, 2.4 Hz,
1H, ArCH2CH=CH), 5.84 (dtt, J = 14.4 Hz, 8.1 Hz, 2.0 Hz, 1H, ArOCH2CH=CH), 6.69, 6.80 (each d, J =
13
8.8 Hz, 1H, ArH); C-NMR (CDCl3, 75 MHz) δ 22.98, 56.01, 61.99, 71.82, 109.93, 116.24, 125.56,
127.81, 130.89, 145.73, 149.59, 152.96; EI-MS (70eV) m/z 206 (M+, 75), 191 (100), 175 (34), 159 (18),
131 (22), 115 (12), 103 (21), 91 (13), 77 (4), 55 (2); HRMS (EI, m/z): Calcd for C12H14O3: 206.0943.
Found: 206.0940; Anal. Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 70.14; H, 7.06.
6-Ethoxy-7-methoxy-2,5-dihydrobenzo[b]oxepine (6b)
1
Pure 6b (2.21 g, 82%) was obtained as colorless liquid, Rf =0.71 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 600 MHz) δ 1.36 (t, J = 7.2 Hz, 3H, ArOCH2CH3), 3.55 (dd, J = 5.3 Hz, 2.0 Hz, 2H,
ArCH2CH=CH), 3.81 (s, 3H, ArOCH3), 3.97 (q, J = 7.2 Hz, 2H, ArCH2CH3), 4.54 (dd, J = 8.1 Hz, 2.4 Hz,
2H, ArOCH2CH=CH), 5.43 (dtt, J = 14.4 Hz, 5.3 Hz, 2.4Hz, 1H, ArCH2CH=CH), 5.83 (dtt, J = 14.4 Hz,
13
8.1 Hz, 2.0 Hz, 1H, ArOCH2CH=CH), 6.68, 6.78 (each d, J = 8.8 Hz, 1H, ArH); C-NMR (CDCl3, 75
MHz) δ 15.53, 23.26, 56.05, 69.12, 71.82, 109.93, 116.02, 125.64, 127.74, 131.30, 144.74, 149.72,
152.91; EI-MS (70 eV) m/z 220 (M+, 100), 205 (96), 191 (20), 177 (84), 159 (17), 131 (15), 115 (8), 103
(18), 77 (11), 65 (5); HRMS: Calcd for C13H16O3: 220.1099. Found: 220.1098; Anal. Calcd for C13H16O3:
C, 70.89; H, 7.32. Found: C, 71.22; H, 7.58.
6-Benzyloxy-7-methoxy-2,5-dihydrobenzo[b]oxepine (6c)
1
Pure 6c (2.28 g, 88%) was obtained as colorless liquid, Rf =0.72 (ethyl acetate/n-hexane=1/3); H-NMR
(CDCl3, 400 MHz) δ 3.45 (dd, J = 5.3 Hz, 2.0 Hz, 2H, ArCH2CH=CH), 3.83 ( s, 3H, ArOCH3), 4.52 (dd,
J = 8.1 Hz, 2.4 Hz, 2H, ArOCH2CH=CH), 4.94 (s, 2H, ArCH2C6H5), 5.36 (dtt, J = 14.4 Hz, 5.3 Hz, 2.4
Hz, 1H, ArCH2CH=CH), 5.68 (dtt, J = 14.4 Hz, 8.1 Hz, 2.0 Hz, 1H, ArOCH2CH=CH), 6.72, 6.80 (each d,
J = 8.8 Hz, 1H, ArH), 7.32 (tt, J = 6.8 Hz, 2.0 Hz, 2H, ArCH2C6H5), 7.36 (tt, J = 6.8 Hz, 2.0 Hz, 2H,
13
ArCH2C6H5), 7.42 (d, J = 8.0 Hz, 1H, ArCH2C6H5); C-NMR (CDCl3, 75 MHz) δ 23.24, 56.11, 71.77,
75.23, 110.09, 116.28, 125.60, 127.51, 127.95, 128.34, 128.37, 131.30, 137.54, 144.49, 149.63, 152.94;
EI-MS (70 eV) m/z 282 (M+, 36), 192 (4), 191 (33), 159 (20), 131 (7), 103 (9), 91 (100), 65 (11); HRMS:

Calcd for C18H18O3: 282.1256. Found: 282.1259; Anal. Calcd for C18H18O3: C, 76.57; H, 6.43. Found: C,
72.04; H, 7.58.
7-Methyl-2,5-dihydrobenzo[b]oxepine (6d)
Pure 6d (0.15 g, 80%) was obtained as colorless liquid, Rf =0.83 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 2.27 (s, 3H, ArCH3), 3.43 (ddt, J = 4.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH),
4.54 (ddt, J = 5.0 Hz, 1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH), 5.44 (ddt, J = 11.6 Hz, 4.8 Hz, 1.6 Hz, 1H,
ArCH2CH=CH), 5.83 (ddt, J = 11.6 Hz, 5.0 Hz, 1.6 Hz, 1H, ArOCH2CH=CH), 6.89 (d, J = 8.4 Hz, 1H,
13
ArH), 6.94 (s, 1H, ArH), 6.96 (d, J = 8.4 Hz, 1H, ArH); C-NMR (CDCl3, 100 MHz) δ 20.65, 31.73,
71.25, 121.08, 125.73, 127.40, 128.15, 129.42, 133.35, 135.75, 156.50; EI-MS (70 eV) m/z 160 (M+, 76),
146 (11), 145 (100), 131 (19), 127 (31), 115 (35), 105 (8), 91 (23), 77 (12); HRMS: Calcd for C11H12O:
160.0888. Found: 160.0891; Anal. Calcd for C11H12O: C, 82.46; H, 7.55. Found: C, 82.80; H, 7.38.
7-Chloro-2,5-dihydrobenzo[b]oxepine (6e)
Pure 6e (0.17 g, 83%) was obtained as colorless liquid, Rf =0.79 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 3.44 (ddt, J = 4.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH), 4.56 (ddt, J = 5.0 Hz,
1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH), 5.47 (ddt, J = 11.6 Hz, 4.8 Hz, 1.6 Hz, 1H, ArCH2CH=CH), 5.82
(ddt, J = 11.6 Hz, 5.0 Hz, 1.6 Hz, 1H, ArOCH2CH=CH), 6.97 (d, J = 8.4 Hz, 1H, ArH), 7.08 (s, 1H, ArH),
13
7.13 (d, J = 8.4 Hz, 1H, ArH); C-NMR (CDCl3, 100 MHz) δ 31.47, 71.25, 122.79, 125.17, 127.42,
127.62, 128.68, 128.83, 137.81, 157.34; EI-MS (70eV) m/z 182 (M+2, 21), 180 (M+, 65), 165 (100), 145
(50), 115 (67), 114 (5), 89 (13), 63 (8); HRMS: Calcd for : C10H9OCl 180.0342. Found: 180.0345; Anal.
Calcd for C10H9OCl: C, 66.49; H, 5.02. Found: C, 66.77; H, 5.26.
9-Nitro-2,5-dihydrobenzo[b]oxepine (6f)
1
Pure 6f (0.18 g, 80%) was obtained as yellow liquid; Rf =0.86 (ethyl acetate/n-hexane=1/12); H-NMR
(CDCl3, 400 MHz) δ 3.54 (ddt, J = 4.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2-CH=CH), 4.79 (ddt, J = 5.0 Hz,
1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH), 5.53 (ddt, J = 11.6 Hz, 4.8 Hz, 1.6 Hz, 1H, ArCH2CH=CH), 5.86
(ddt, J = 11.6 Hz, 5.0 Hz, 1.6 Hz, 1H, ArOCH2CH=CH), 7.11 (t, J = 8.2Hz, 1H, Ar-H), 7.33 (d, J = 8.2
13
Hz, 1H, Ar-H), 7.65 (d, J = 8.2 Hz, 1H, Ar-H); C-NMR (CDCl3, 100 MHz) δ 31.38, 71.54, 122.90,
123.88, 124.46, 127.37, 127.49, 132.73, 140.39, 151.09; EI-MS (70 eV) m/z 191 (M+, 33), 174 (57), 144
(100), 135 (11), 115 (93), 91 (13), 89 (16), 63 (11), 51 (11); HRMS: Calcd for C10H9NO3: 191.0582.
Found: 191.0581; Anal. Calcd for C10H9NO3: C, 62.82; H, 4.74. Found: C, 63.02; H, 4.52.
6-Methoxy-2,5-dihydrobenzo[b]oxepine (6g)
Pure 6g (0.17 g, 82%) was obtained as colorless liquid, Rf = 0.59 (ethyl acetate/n-hexane=1/12); 1H-NMR
(CDCl3, 400 MHz) δ 3.55 (ddt, J = 4.8 Hz, 1.6 Hz, 1.6 Hz, 2H, ArCH2CH=CH2), 3.77 (s, 3H, ArOCH3),
4.55 (ddt, J = 5.0 Hz, 1.6 Hz, 1.6 Hz, 2H, ArOCH2CH=CH), 5.45 (ddt, J = 11.6 Hz, 4.8 Hz, 1.6 Hz, 1H,
ArCH2CH=CH), 5.83 (ddt, J = 11.6 Hz, 5.0 Hz, 1.6 Hz, 1H, ArOCH2CH=CH), 6.63 (d, J = 8.3 Hz, 1H,
ArH), 6.70 (d, J =8.3 Hz, 1H, ArH), 7.10 (t, J = 8.3 Hz, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) δ 22.17,

55.70, 71.10, 106.66, 113.98, 124.66, 126.02, 127.22, 127.49, 156.47, 159.87; EI-MS (70 eV) m/z 176
(M+, 96), 161 (100), 146 (27), 144 (19), 127 (79), 115 (35), 105 (16), 91 (17), 77 (83), 65 (15), 63 (14),
51 (32); HRMS: Calcd for C11H12O2: 176.0837. Found: 176.0838; Anal. Calcd for C11H22O2: C, 74.98; H,
6.86. Found: C, 75.21; H, 7.16.
ACKNOWLEDGEMENTS
We are indebted to the Emeritus Prof. Takao Yamazaki, Toyama Medical and Pharmaceutical University,
Prof. Hiroki Takahata, Tohoku Pharmaceutical University, and Prof. Yoshiro Hirai, Toyama University,
Japan for encouragement. We are also grateful to NSC, Taiwan for financial support, to Mr. Wen-Hsiung
Lu for measuring elemental analysis, and to Miss Chyi-Jia Wang for recording proton and carbon NMR
spectrum.
REFERENCES
1. F. A. Macias, J. M. G. Molinillo, R. M. Varela, A. Torres, and F. R. Fronczek, J. Org. Chem., 1994, 59,
8261.
2. K. Takabatake, I. Nishi, M. Shindo, and K. Shishido, J. Chem. Soc., Perkin Trans. 1, 2000, 1807.
3. a). Y. Asakawa, T. Hashimoto, K. Takikawa, M. Tori, and S. Ogawa, Phytochemistry, 1991, 30, 235. b)
S. Yamaguchi, K. Furihata, M. Miyazawa, H. Yokoyama, and Y. Hirai, Tetrahedron Lett., 2000, 41,
4787.
4. P. Schwab, M. B. France, J. W. Ziller, and R. H. Grubbs, Angew. Chem., Int. Ed. Engl., 1995, 34,
2039.
5. a). R. H. Grubbs and S. Chang, Tetrahedron, 1998, 54, 4413. b). A. Fürstner and A. Rumbo, J. Org.
Chem., 2000, 65, 2608. c). R. H. Grubbs and D. M. Lynn, J. Org. Chem., 1998, 63, 9904. d). R. H.
Grubbs, J. P. Sauvage, B. Mohr, M. Weck, J. Org. Chem., 1999, 64, 5463. e). R. H. Grubbs and M.
Ulman, J. Org. Chem., 1999, 64, 7202. f). C. Mioskowski, M. P. Heck, and C. Baylon, J. Org. Chem.,
1999, 64, 3354. g). J. D. Martin and M. Delgado, J. Org. Chem., 1999, 64, 4798. f). S. P. Nolan, H. J.
Schanz, L. Ackermann, O. R. Thiel, and A. Fürstner, J. Org. Chem., 2000, 65, 2204. g) S. P. Nolan, A.
Pancrazi, J. Mahuteau, and D. Bourgeois, Synthesis, 2000, 6, 869. h). M. T. Crimmins and K. A.
Emmitte, Synthesis, 2000, 6, 899. i). P. R. Jenkins, W. D. Barker, and D. J. Holt, J. Org. Chem., 2000,
65, 482. j). A. G. M. Barrett, P. A. Procopiou, M. Ahmed, S. P. Baker, S. P. D. Baugh, D. C. Braddock,
A. J. P. White, and D. J. Williams, J. Org. Chem., 2000, 65, 3716.
6. E. C. Wang, K. S. Huang, G. W. Lin, J. R. Lin, and M. K. Hsu, J. Chin. Chem. Soc., 2001, 48, 83.
7. a). K. S. Huang and E. C. Wang, Tetrahedron Lett. 2001, 42, 6155.
8. a). A. Fürstner, O. R. Thiel, L. ackermann, H. –J. Schanz, and S. P. Nolan, J. Org. Chem., 2000, 65,
2204. b). Y. Miyaki, T. Onishi, S. Ogoshi, and H. Kurosawa, J. Organomet. Chem., 2000, 616, 135. c).
M. Stefinovic and V. Snieckus, J. Org. Chem., 1998, 63, 2808.
9. B. S. Furniss, A. J. Hannaford, P. W. G. Smith, and A. R. Tatchell, Vogel’s Textbook of Practical
Organic Chemistry, 5th. Ed, John wiley & Sons, New York, 1989, p. 986.
10. B. S. Furniss, A. J. Hannaford, P. W. G. Smith, and A. R. Tatchell, Vogel’s Textbook of Practical

Organic Chemistry, 5th Ed, John wiley & Sons, New York, 1989, p 984.
11. J. Beyer, S. Lang-Fugmann, A. Muhlbauer, and W. Steglich, Synthesis, 1998, 1047.
12. N. J. Lawrence, D. Rennison, M. Woo, A. T. McGown, and J. A. Hadfield, Bioorg. Med. Chem. Lett.,
2001, 11, 51.
13. H. B. Mereyala, S. R. Gurrala, and S. K. Mohan, Tetrahedron, 1999, 55, 11331.
14. V. Satyanarayana, C. P. Rao, G. L. D. Krupadanam, and G. Srimannarayana, Synth. Commun., 1991,
21, 1455.
15. M. Yodo and H. Harada, Chem. Pharm. Bull., 1989, 37, 2361.
16. P. Anastasis and P. E. Brown, J. Chem. Soc., Perkin Trans.1, 1983, 1431.
17. J. M. Bruce and Y. Roshan-Ali, J. Chem. Soc., Perkin Trans.1, 1981, 2677.
18. A. W. White, R. Almassy, A. H. Calvert, N. J. Curtin, R. J. Griffin, Z. Hostomsky, K. Maegley, D. R,
Newell, S. Srinivasan, and B. T. Golding, J. Med. Chem., 2000, 43, 4084.
19. A. Reitz, M.A. Avery, M. S. Verlander, and M. Goodman, J. Org. Chem., 1981, 46, 4859.
20. J. W. Benbow and R. Katoch-Rouse, J. Org. Chem., 2001, 66, 4965.