Base-promoted formal [4 + 3] annulation between 2-fluorophenylacetylenes and ketones: A route to benzoxepines

Article abstract of DOI:10.1021/acs.joc.5b02487

The first base-promoted formal [4 + 3] annulation between 2-fluorophenylacetylenes and ketones has been disclosed. The reaction proceeds through a tandem α-vinylation of ketones followed by an intramolecular nucleophilic aromatic substitution (S_N

Full text of DOI:10.1021/acs.joc.5b02487

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Article
Base-Promoted Formal [4+3] Annulation between 2-
Fluorophenylacetylenes and Ketones: A Route to Benzoxepines
Lu Ouyang, Chaorong Qi, Haitao He, Youbin Peng, Wenfang Xiong, Yanwei Ren, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02487 • Publication Date (Web): 07 Jan 2016
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Base-Promoted Formal [4+3] Annulation between
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2-Fluorophenylacetylenes and Ketones: A Route to Benzoxepines
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Lu Ouyang, Chaorong Qi, * Haitao He, Youbin Peng, Wenfang Xiong, Yanwei Ren and Huanfeng
Jiang*
School of Chemistry and Chemical Engineering, State Key Lab of Luminescent Materials and Devices, South China University
of Technology, Guangzhou 510640, China
Fax: (+86) 20-8711-2906; E-mail: crqi@scut.edu.cn or jianghf@scut.edu.cn
O
R1
t-BuOK
R3
+
R2
R3
O
DMSO
R2
F
41 examples
up to 90% yield
Abstract: The first base-promoted formal [4+3] annulation between
2-fluorophenylacetylenes and ketones has been disclosed. The reaction proceeds
through a tandem -vinylation of ketones followed by an intramolecular nucleophilic
aromatic substitution (SNAr) reaction of the in-situ generated ,-unsaturated ketone
intermediates, providing a straightforward access to a wide range of functionalized
benzoxepines in moderate to high yields. The transition-metal-free methodology
featured a wide substrate scope, the use of easily available starting materials, and a high
functional group tolerance.
INTRODUCTION
Benzoxepines are an important class of seven-membered oxygen-containing
heterocycles widely distributed in a variety of natural products and biologically active
compounds,1 such as pterulinic acid1a, ptaeroxylin1b and artoristilbene1c (Figure 1).
Interestingly, some of the benzoxepine derivatives isolated from sunflower can serve
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as natural herbicides.2 Therefore, the development of facile and efficient strategies for
the straightforward construction of these important ring systems with simple and
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readily available starting materials is of great significance.3
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HO
OH
O
O
HO
Cl
O
O
O
O
O
O
HO
pterulinic acid
ptaeroxylin
artoristilbene
Figure 1. Representative natural products containing the benzoxepine skeleton.
In the past decades, many elegant transition-metal-catalyzed intramolecular
cyclization reactions have been developed for the synthesis of functionalized
benzoxepines,1d, such as osmium-catalyzed 7-endo heterocyclization of aromatic
4
alkynols,4a Rh-catalyzed intramolecular olefin hydroacylation,4c gold-catalyzed
tandem intramolecular cyclization of 2-(prop-2-ynyloxy)benzaldehydes.4f On the
other hand, transition-metal-catalyzed intermolecular [m+n] cyclization have also
proven to be a powerful tool for the assembly of these ring structures.5 For example,
Lu and co-workers reported cationic palladium-catalyzed [5+2] annulations of
2-aroylmethoxyarylboronic acids with alkynes or allenoates.5b-c Zhang et al.
developed
a
copper-catalyzed tandem [4+3] cyclization reaction of
trifluoromethyl-containing ortho-halo--chlorostyrenes with ketones for the synthesis
of a variety of 4-trifluoromethylbenzoxepines (Figure 2 a).5d Most recently, Mascareñ
and Gulías reported a rhodium-catalyzed formal [5+2] cycloaddition of
o-vinylphenols with alkynes, giving rise to the corresponding benzoxepines (Figure 2
b).6 In contrast, transition-metal-free synthetic strategies for preparing these
seven-membered heterocyclic compounds have been less explored.7 Thus, the
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development of general methods for constructing benzoxepine derivatives with wide
substrate scope under transition-metal-free conditions is highly appealing.8
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As part of our continuing interest in the development of efficient methods for the
synthesis of oxygen and/or nitrogen containing heterocyclic compounds,9 herein, we
wish to report a convenient method for the synthesis of benzoxepines via a base
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-promoted
[4+3]
cyclization
of
readily
available
ketones
and
2-fluorophenylacetylenes (Figure 2 c).
Previous works:
a) Cu-catalyzed [4+3] cyclization
CF3
R2
10 mol% CuBr
O
CF3
20 mol% ligand
R1
R1
R3
+
Cl
3equiv t-BuONa
DMSO, 100oC
R2
X
O
R3
X = Br, Cl
b) Rh-catalyzed [5+2] cyclization
R2
OH
2.5 mol% [Cp*RhCl2]2
R1
+
R2
R1
0.5 equiv Cu(OAc)2 H2O
air, CH3CN, 85 oC
R3
O
R3
This work:
c) base-promoted [4+3] cyclization
O
R1
1 equiv t-BuOK
R3
+
R1
R2
DMSO, 120 oC
R3
O
R2
F
Figure 2. Synthetic Strategies to benzoxepines.
RESULTS AND DISCUSSION
Our initial efforts focused on the reaction of 2-fluorophenylacetylene (1a) and
acetophenone (2a) under various reaction conditions, and the results are summarized
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Table 1. Optimization of the Reaction Conditionsa
5
6
7
O
base
+
8
9
solvent
O
F
Ph
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1a
2a
Solvent
3aa
Entry
1
Base
t-BuOK
CH3ONa
C2H5ONa
K2CO3
KOH
Temperature (oC)
Yield (%)b
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
120
120
120
120
120
120
120
120
120
120
120
120
120
120
100
92 (86)
81
2
3
43
4
68
5
88
6
DBU
75
7
Et3N
30
8
t-BuOLi
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
25
9c
10d
11
12
13
14
15
45
9
18
MeCN
trace
15
1,4-dioxane
toluene
trace
79
DMSO
a Reaction conditions: 1a (0.25 mmol), 2a (0.25 mmol) and base (0.25 mmol) in solvent (1 mL),
b
under an N2 atmosphere for 12 h. GC yield with dodecane as internal standard. Number in
c
d
parentheses is the yield of isolated product. with 0.5 equiv of t-BuOK.
The reaction was
conducted in air.
in Table 1. To our delight, when the reaction was performed in the presence of 1 equiv
of t-BuOK in DMSO at 120 oC for 12 h, the desired product 3aa,
2-phenylbenzo[b]oxepine, was obtained in 92% yield (entry 1). Further screening of
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bases showed that CH3ONa, KOH and DBU were also capable of promoting the
reaction to give the desired product in good yields while replacement of t-BuOK by
other organic or inorganic bases such as K2CO3, Et3N, or t-BuOLi led to low yields
(entry 2-8). Decreasing the loading of t-BuOK to 0.5 equiv decreased the yield to 45%
(entry 9). It should be pointed out that the reaction required a nitrogen atmosphere to
proceed; if the reaction was conducted in air, the product was obtained only in 9%
yield along with large amount of unidentified products (entry 10). It was also found
that the solvent have a great influence on the yield of 3aa. DMSO proved to be the
most suitable media for the reaction while other solvents such as DMF, MeCN,
1,4-dioxane or toluene retarded the formation of 3aa (entries 11-14). Further
optimization revealed that decreasing the reaction temperature from 120 oC to 100 oC
lead to an obvious decrease in the yield of the product (entry 15).
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With the optimized reaction conditions in hand, the base-promoted methodology
was first applied for the reactions of 2-fluorophenylacetylene (1a) with various
ketones. As can be seen from Table 2, the cyclization is efficient for a wide range of
alkyl aromatic, alkyl heteroaromatic, aliphatic and cycloaliphatic ketones. A variety of
acetophenones worked well with 1a to give the corresponding products in good yields.
Both electron-donating and electron-withdrawing groups such as methyl,
trifluoromethyl, dimethylamino and morpholino group were tolerated (3ab-3ac)
without any difficulty under the reaction conditions. In addition to monosubstituted
acetophenones, bis-substituted acetophenone 2e provided the desired product 3ae in
high yield as well. Remarkably, methyl ketones containing naphthyl, furan or
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Table 2. Substrate scope of ketonesa,b
O
1 equiv t-BuOK
R2
+
R1
DMSO, 120 oC
12 h, N2
R2
O
R1
F
1a
3
2
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O
O
O
O
N
3ae, 88%
N
R
3ab1, R = Me, 84%
3ab2, R= CF3, 64%
O
3ad, 84%
3ac, 91%
O
O
O
O
X
R
3ai1, R = H, 80%
3ai2, R = F, 78%
3ai3, R = Cl, 81%
3ai4, R = OMe, 72%
R
3ag1, X =O, 68%
3ag2, X = S, 60%
3ah1, R= H, 73%
3ah2, R= OMe, 76%
3af, 88%
OMe
MeO
3aj1, R = F, 76%
3aj2, R = Cl, 85%
3aj3, R = Br, 65%
3aj4, R = Me, 76%
3aj5, R = OMe, 83%
R
O
O
O
3ak, 72%
3al, 54%
O
O
O
O
O
3ap, 69%
3ao, 69%
3am, 80%
3an, 81%
N
O
O
O
O
3ar, 66% (13:1)
3aq, 74%
3as, 68%
3at, 54%
O
O
O
O
3av, 71%
3aw, 72%
3ax, 82%
3au, 78%
a
Reaction conditions: 2-fluorophenylacetylene (1a, 0.25 mmol), ketone 2 (0.25 mmol), and
o
b
t-BuOK (0.25 mmol), in DMSO (1 mL) at 120 C under an N2 atmosphere for 12 h. Isolated
yields.
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thiophene moiety are all suitable substrates for this transformation (3af-3ag). As
expected, other aromatic ketones such as propiophenones and deoxybenzoins with
different substitution patterns reacted well with 1a to form the corresponding
benzoxepines 3ah and 3ai in good yields. It should be pointed out that
1,4-diacetylbenzene failed to react with 2-fluorophenylacetylene to yield the desired
product under the standard reaction conditions, and a large amount of starting material
was recovered, although the reason is unclear.
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Pleasingly, a range of alkyl benzyl ketones underwent the cyclization smoothly
to afford the desired products in moderate to high yields (3aj-3ao). The results show
that the electronic nature of the substituents on the benzene ring affects the yields of
the desired products slightly. However, steric hindrance has a great impact on the
reaction. For instance, only 54% yield was obtained when (2-methoxyphenyl)acetone
reacted with 1a while its 4- and 3-substituted analogues gave higher yields (83% and
72%, respectively). (2-Furyl)acetone and (2-pyridyl)acetone successfully entered into
the reaction to furnish the corresponding products (3ap and 3aq) in satisfactory yields.
Note that the -aryl-substituted aliphatic ketone, 4-phenylbutan-2-one (2r), could
afford the product 3ar in good yield with excellent regioselectivity (13:1). Both
3-pentanone and 1-cyclopropylethanone were capable of taking part in the process,
although the later gave the desired product in a lower yield (54%). Encouraged by
these results, we further examined the scope of our new protocol with a series of
cycloaliphatic ketones. To our delight, all the three substrates examined, i.e.,
cyclohexanone, cycloheptanone and cyclooctanone, underwent smooth reaction with
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1a, affording the corresponding tricyclic products (3au-3aw) in good yields. To our
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surprise, the reaction of 2-tetralone
led
to
an unexpected outcome. A
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tetracyclic compound, 12,13-dihydrobenzo[b]naphtho[1,2-f]oxepine (3ax), was
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isolated in 82% yield, instead of the expected product 3ax' (Scheme 1). It seems that
3ax was formed through the aromatization of intermediate 3ax', which might be
attributed to the higher thermodynamical stability of 3ax than that of 3ax'. The
structures of the products 3ai3 and 3ax were confirmed unambiguously by X-ray
crystallography (Figure S1).10
Scheme 1. The formation of 3ax through the aromatization of 3ax'
standard
conditions
aromatization
O
+
O
O
F
2x
1a
3ax
3ax'
Subsequently, the scope of 2-fluorophenylacetylenes was examined (Table 3). To
our delight, a variety of electron-donating and electron-withdrawing substituents in
the benzene ring of the 2-fluorophenylacetylenes, including halide (Cl, Br), CN, and
methyl, are tolerated in this transformation, and the corresponding products (3ba-3fa
and 3bj2-3dj2) are obtained in high to excellent yields. Moreover,
3-ethynyl-2-fluoropyridine (1g) could undergo the annulation reaction with
acetophenone
(2a)
to
give
rise
to
the
corresponding
product
2-phenyloxepino[2,3-b]pyridine (3ga) in a moderate yield.
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Table 3. Substrate scope of 2-fluorophenylacetylenes a,b
5
6
7
8
O
t-BuOK
R1
R3
+
R2
R1
DMSO, 120 oC
12 h, N2
R3
O
R2
3ba-3ga, 3bj2-3dj2
F
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1b-g
2a and 2j2
Cl
Br
O
Cl
O
Cl
O
3ba, 90%
3bj2, 88%
3ca, 89%
Cl
Cl
NC
NC
O
O
Br
O
3cj2, 82%
3dj2, 83%
3da, 86%
N
O
O
O
3ea, 80%
3fa, 82%
3ga, 58%
a Reaction conditions: alkyne 1 (0.25 mmol), ketone 2 (0.25 mmol), and t-BuOK (0.25 mmol),
in DMSO (1 mL) at 120 oC under an N2 atmosphere for 12 h. b Isolated yields.
In order to further demonstrate the practicability and reliability of the developed
protocol, we also performed the reaction on a larger scale. Pleasingly, benzoxepine
product 3aa could be obtained in a satisfactory yield (75%) when the reaction was
conducted on a 5 mmol scale (Scheme 2).
Scheme 2. Synthesis of 3aa on a larger scale
O
t-BuOK (1 equiv)
O
+
DMSO (10 mL), 120 oC
N2, 12 h
F
1a, 5 mmol
2a, 5 mmol
3aa, 75% isolated yield
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To obtain more insights into the mechanism of this transformation, we attempted
to identify the reaction intermediates. Fortunately, when the reaction of
2-fluorophenylacetylene (1a) and 1-(furan-2-yl)ethanone (2g1) was interrupted after 1
h, an ,-unsatureated ketone product 4ag1 were observed in 48% yields by means of
GC-MS analysis (eq 1). After purification and subsequent treatment with t-BuOK
under standard conditions, 4ag1 was able to gave the product 3ag1 in a 78% yield
(eq 2), indicating that 4ag1 might be the key intermediate for the formation of 3ag1
and that the C-C bond formation would occur prior to the formation of C-O bond
during the cyclization process. Moreover, when 2-chlorophenylacetylene (5a) was
employed to to react with 2g1 under standard conditions, only a complex mixture was
observed without the formation of desired product (eq 3), suggesting that the presence
of a fluorine atom in the position ortho to the acetylenic group in molecules 1 is
crucial to the success of the transformation.
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O
O
t-BuOK (1 equiv)
+
(1)
O
+
O
O
DMSO, 120 oC
N2, 1 h
F
O
F
2g1
1a
4ag1, 48%
3ag1, 40%
O
t-BuOK (1 equiv)
(2)
O
O
DMSO, 120 oC
N2, 12 h
O
F
3ag1, 78%
4ag1
O
t-BuOK (1 equiv)
O
(3)
+
O
DMSO, 120 oC
N2, 12 h
O
Cl
3ag1
2g1
5a
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On the basis of the above results and previous literatures,11-12 a plausible mechanism
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is illustrated in Scheme 3. Initially, vinylation of ketone
2
with
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ortho-fluorophenylacetylene 1 would take place in the presence of a base, giving rise
to intermediate 4.11 The keto-enol tautomerism of 4 then occurred to yield an
intermediate 6, which was in equilibrium with its (Z)-isomer 7. Finally, intramolecular
nucleophilic aromatic substitution (SNAr) of 7 would afford the target product 3.12
Scheme 3. Proposed reaction mechanism
R3
O
R2
base
+
R1
R2
R1
O
R3
Vinylation
F
F
4
1
2
base
R3
R2
R3
R3
R1
R1
F
O
O
SNAr
O
R2
R2
F
3
7
6
CONCLUSION
In summary, we have successfully developed a facile and efficient protocol for the
straightforward assembly of a wide range of functionalized benzoxepines via a
base-promoted formal [4+3] annulation between 2-fluorophenylacetylenes and
ketones. The reaction was proposed to proceed through a tandem -vinylation of
ketones followed by an intramolecular nucleophilic aromatic substitution (SNAr)
reaction. The transition-metal-free methodology featured a wide substrate scope, the
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use of easily available starting materials, and a high functional group tolerance.
Further investigations into the mechanism and application of the method for
constructing more complex molecules are ongoing in our laboratory.
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EXPERIMENTAL SECTION
General methods. 1H and 13C NMR spectra were recorded by using a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm, respectively, and
CDCl3 is used as a solvent with TMS as the internal standard. Mass spectra were recorded on a
gas chromatograph-mass spectrometer. The data of HRMS was carried out on a high-resolution
mass spectrometer (LCMS-IT-TOF). IR spectra were obtained either as potassium bromide plates
or as liquid films between two potassium bromide plates with an infrared spectrometer. Melting
points were determined with a digital melting point measuring instrument. Compounds 1b-f were
synthesized according to the literature procedures.13 Other substrates were commercially
purchased and used without further purification.
General procedure for the preparation of benzoxepines (3): To a 25 mL dried Schlenk tube
were added the mixture of o-fluorophenylacetylene 1 (0.25 mmol), ketone 2 (0.25 mmol),
potassium tert-butoxide (0.25 mmol) in DMSO (1.0 mL) successively. The mixture was stirred at
120 °C for 12 h under an N2 atmosphere. After the reaction was completed, the mixture was
cooled to room temperature and diluted with H2O (15 mL), neutralized with NH4Cl, and extracted
with EtOAc (10 mL3). The organic extract was washed with H2O (10 mL3) and dried over
anhydrous Mg2SO4. After removal of the EtOAc in vacuum, the crude product thus obtained was
purified by column chromatography on silica gel with hexanes or petroleum ether/ethyl acetate
(2:1 to 50:1) to give the desired products 3.
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2-Phenylbenzo[b]oxepine (3aa).14 Yellow solid (47.3 mg, 86%), mp: 59–60 C. H NMR (400
MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2 H), 7.41 (t, J = 7.5 Hz, 2 H), 7.37–7.28 (m, 2 H), 7.19 (d, J
= 7.4 Hz, 1 H), 7.12 (dd, J = 14.8, 7.6 Hz, 2 H), 6.80 (d, J = 10.0 Hz, 1 H), 6.32–6.28 (m, 2 H).
13C NMR (100 MHz, CDCl3) δ 155.2, 154.9, 134.8, 132.1, 131.5, 130.3, 128.8, 128.6, 128.5,
127.5, 125.4, 124.8, 121.3, 110.1. IR (KBr): 3060, 3024, 2923, 2851, 1589, 1486, 1447, 1202,
1170, 752, 717, 687 cm-1. HRMS-ESI (m/z): calcd for C16H12NaO [M + Na]+ : 243.0780; found:
243.0775.
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2-(p-Tolyl)benzo[b]oxepine (3ab1). Yellow solid (49.1 mg, 84%), mp: 81–82 C. H NMR (400
MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 2 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.24–7.19 (m, 3 H), 7.13 (dd, J =
15.2, 7.6 Hz, 2 H), 6.79 (d, J = 10.8 Hz, 1 H), 6.34–6.29 (m, 1 H), 6.25 (d, J = 6.0 Hz, 1 H), 2.40 (s, 3
H). 13C NMR (100 MHz, CDCl3) δ 155.1, 155.0, 138.6, 132.1(4), 132.1(0), 131.0, 130.2, 129.2, 128.7,
127.6, 125.4, 124.7, 121.3, 109.2, 21.2. IR (KBr): 3062, 3025, 2920, 2856, 1633, 1588, 1484, 1449,
1264, 1203, 1171, 1047, 776, 754 cm-1. HRMS-ESI (m/z): calcd for C17H14NaO [M + Na]+ :
257.0937; found: 257.0938.
2-(4-(Trifluoromethyl)phenyl)benzo[b]oxepine (3ab2). Yellow solid (46.1 mg, 64%), mp:
126–128 oC. H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.1 Hz, 2 H), 7.66 (d, J = 8.1 Hz, 2 H),
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7.33 (t, J = 7.5 Hz, 1 H), 7.21–7.13 (m, 2 H), 7.08 (d, J = 8.1 Hz, 1 H), 6.85 (d, J = 10.8 Hz, 1 H),
6.36–7.28 (m, 2 H). 13C NMR (100 MHz, CDCl3) δ 155.1, 153.2, 138.1, 132.6, 131.8, 130.6,
130.2 (q, J = 32.0 Hz), 129.0, 127.0, 125.5, 125.4 (q, J = 3.0 Hz), 125.0, 122.7, 121.1, 112.1. IR
(KBr): 3056, 2987, 1613, 1487, 1329, 1265, 1111, 827, 764 cm-1. HRMS-ESI (m/z): calcd for
C17H12F3O [M + H]+ : 289.0835, found: 289.0831.
4-(Benzo[b]oxepin-2-yl)-N,N-dimethylaniline (3ac). Yellow solid (59.2 mg, 91%), mp: 120–121
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oC. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.5 Hz, 2 H), 7.31 (t, J = 7.8 Hz, 1 H), 7.21 (d, J =
7.3 Hz, 1 H), 7.13 (dd, J = 12.4, 7.6 Hz, 2 H), 6.80–6.72 (m, 3 H), 6.33 (dd, J = 10.9, 6.3 Hz, 1 H),
6.14 (d, J = 6.2 Hz, 1 H), 3.04 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 155.6, 154.8, 150.5, 132.4,
129.8, 129.4, 128.4, 128.0, 126.7, 124.5, 122.9, 121.3, 111.8, 106.3, 40.2. IR (KBr): 3023, 2925,
2805, 1610, 1521, 1445, 1362, 1199, 1165, 1048, 944, 816, 758 cm-1. HRMS-ESI (m/z): calcd for
C18H17NaNO [M + Na]+ : 286.1202; found: 286.1208.
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4-(4-(Benzo[b]oxepin-2-yl)phenyl)morpholine (3ad). Black solid (64.0 mg, 84%), mp: 83–84 oC.
1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.6 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 1 H), 7.13 (d, J = 7.2
Hz, 1 H), 7.08 (d, J = 7.2 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.91 (d, J = 7.4 Hz, 2 H), 6.70 (d, J =
11.0 Hz, 1 H), 6.25 (dd, J = 10.9, 6.2 Hz, 1 H), 6.11 (d, J = 6.2 Hz, 1 H), 3.84 (s, 4 H), 3.18 (s, 4
H). 13C NMR (100 MHz, CDCl3) δ 154.8, 132.2, 130.4, 130.3, 130.0, 129.0, 128.6, 127.7, 126.6,
124.6, 121.2, 115.1, 107.9, 99.8, 66.5, 48.8. IR (KBr): 3024, 2964, 2955, 1596, 1450, 1231, 1189,
1117, 823, 758 cm-1. HRMS-ESI (m/z): calcd for C20H20NO2 [M + H]+ : 306.1489; found:
306.1487.
2-(3,4-Dimethylphenyl)benzo[b]oxepine (3ae). Yellow oil (53.3 mg, 86%). 1H NMR (400 MHz,
CDCl3) δ 7.55 (d, J = 10.0 Hz, 2 H), 7.25 (t, J = 7.6 Hz, 1 H), 7.13 (d, J = 5.2 Hz, 2 H), 7.07 (dd, J
= 12.4, 8.0 Hz, 2 H), 6.73 (d, J = 10.8 Hz, 1 H), 6.26 (dd, J = 10.8, 6.4 Hz, 1 H), 6.19 (d, J = 6.0
Hz, 1 H), 2.27 (d, J = 9.2 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 155.1(4), 155.0(6), 137.5,
136.7, 132.6, 132.3, 131.0, 130.2, 129.9, 128.7, 127.7, 126.7, 124.7, 123.1, 121.4, 109.2, 20.0,
19.7. IR (KBr): 3024, 2969, 2917, 2855, 1634, 1589, 1482, 1448, 1266, 1204, 1020, 820, 754 cm-1.
HRMS-ESI (m/z): calcd for C18H16NaO [M + Na]+ : 271.1093; found: 271.1100.
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2-(Naphthalen-2-yl)benzo[b]oxepine (3af). Yellow oil (59.4 mg, 88%). H NMR (400 MHz,
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CDCl3) δ 8.39–8.32 (m, 1 H), 7.83 (t, J = 7.2 Hz, 2 H), 7.63 (d, J = 6.8 Hz, 1 H), 7.50–7.44 (m, 2
H), 7.39 (t, J = 7.6 Hz, 1 H), 7.16 (t, J = 6.8Hz, 2 H), 7.08 (t, J = 7.2 Hz, 1 H), 6.79 (d, J = 11.2 Hz,
1 H), 6.72 (d, J = 7.6 Hz, 1 H), 6.26 (dd, J = 11.2, 6.0 Hz, 1 H), 5.95 (d, J = 5.6 Hz, 1 H). 13C
NMR (100 MHz, CDCl3) δ 156.0, 155.7, 134.3, 133.9, 132.0, 131.6, 131.4, 130.3, 129.5, 128.9,
128.4, 127.4, 127.3, 126.7, 126.4, 126.1, 125.1, 124.9, 121.9, 115.6. IR (KBr): 3054, 2924, 1639,
1483, 1447, 1265, 1202, 1101, 951, 749 cm-1. HRMS-ESI (m/z): calcd for C20H14NaO [M + Na]+ :
293.0937; found: 293.0937.
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2-(Furan-2-yl)benzo[b]oxepine (3ag1). Black oil (35.7 mg, 68%). 1H NMR (400 MHz, CDCl3) δ
7.37 (s, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.17–7.11 (m, 2 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.81 (d, J =
2.8 Hz, 1 H), 6.73 (d, J = 11.2 Hz, 1 H), 6.47 (s, 1 H), 6.27 (dd, J = 10.8, 6.4 Hz, 1 H), 6.15 (d, J =
6.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3) δ 155.1, 150.1, 146.6, 143.0, 131.9, 131.2, 130.3,
129.0, 127.1, 125.0, 121.1, 111.6, 108.6, 108.5. HRMS-ESI (m/z): calcd for C14H10NaO2 [M +
Na]+ : 233.0573; found: 233.0565.
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2-(Thiophen-2-yl)benzo[b]oxepine (3ag2). Yellow oil (33.9 mg, 60%). H NMR (400 MHz,
CDCl3) δ 7.41 (d, J = 3.6 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.24 (d, J = 4.8 Hz, 1 H), 7.16–7.10
(m, 3 H), 7.03 (t, J = 3.6 Hz, 1 H), 6.73 (d, J = 11.2 Hz, 1 H), 6.22 (dd, J = 11.2, 6.0 Hz, 1 H),
6.10 (d, J = 6.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3) δ 154.9, 150.0, 139.9, 131.8, 131.2, 130.4,
128.9, 127.8, 127.0, 125.8, 125.0, 124.7, 121.3, 108.8. IR (KBr): 3071, 3025, 2922, 2850, 1628,
1516, 1483, 1254, 1196, 822, 750, 697 cm-1. HRMS-ESI (m/z): calcd for C14H10NaOS [M + Na]+ :
249.0345; found: 249.0341.
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3-Methyl-2-phenylbenzo[b]oxepine (3ah1). Yellow oil (42.7 mg, 73%). H NMR (400 MHz,
CDCl3) δ 7.61 (d, J = 7.6 Hz, 2 H), 7.38 (t, J = 7.2 Hz, 2 H), 7.34–7.29 (m, 1 H), 7.21 (t, J = 6.8
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Hz, 2 H), 7.10 (t, J = 7.2 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.80 (d, J = 11.2 Hz, 1 H), 6.27 (d, J
= 10.8 Hz, 1 H), 1.93 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.5, 149.1, 136.0, 133.2, 131.5,
130.0, 129.9, 129.1, 128.1(5), 128.1(3), 127.8, 124.4, 121.0, 120.9, 18.8. IR (KBr): 3057, 3018,
2919, 2852, 1641, 1483, 1447, 1264, 1170, 957, 758 cm-1. HRMS-ESI (m/z): calcd for C17H14NaO
[M + Na]+ : 257.0937; found: 257.0935.
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2-(4-Methoxyphenyl)-3-methylbenzo[b]oxepine (3ah2). Yellow oil (50.2 mg, 76%). H NMR
(400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2 H), 7.20 (t, J = 7.6 Hz, 2 H), 7.08 (t, J = 7.2 Hz, 1 H),
6.90 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.0 Hz, 1 H), 6.77 (d, J = 11.2 Hz, 1 H), 6.25 (d, J = 11.2 Hz,
1 H), 3.82 (s, 3 H), 1.93 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 159.3, 155.2, 148.7, 133.4, 131.6,
130.5, 129.9, 129.3, 128.6, 128.1, 124.3, 121.0, 119.7, 113.2, 55.2, 18.9. IR (KBr): 3055, 2987,
2916, 2836, 1605, 1509, 1263, 1170, 837, 737 cm-1. HRMS-ESI (m/z): calcd for C18H16NaO2
[M+Na]+ : 287.1043; found: 287.1036.
2,3-Diphenylbenzo[b]oxepine (3ai1).6 Yellow oil (59.2 mg, 80%). 1H NMR (400 MHz, CDCl3) δ
7.44 (d, J = 3.2 Hz, 2 H), 7.32 (d, J = 7.2 Hz, 1 H), 7.24–7.15 (m, 10 H), 6.98 (d, J = 10.8 Hz, 1
H), 6.91 (d, J = 7.6 Hz, 1 H), 6.43 (d, J = 10.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3) δ 154.7,
148.2, 139.2, 135.4, 132.2, 131.4, 130.7, 130.3, 130.1, 129.8, 128.3, 128.1, 127.5, 127.3(2),
127.2(6), 124.6, 121.0. IR (KBr): 3064, 3026, 2925, 2851, 1668, 1595, 1511, 1451, 1383, 1208,
1174, 947, 760 cm-1. HRMS-ESI (m/z): calcd for C22H16NaO [M + Na]+ : 319.1093; found:
319.1087.
2-(4-Fluorophenyl)-3-phenylbenzo[b]oxepine (3ai2). Yellow solid (61.2 mg, 78%), mp: 79–80
oC. 1H NMR (400 MHz, CDCl3) δ 7.37 (t, J = 6.8 Hz, 2 H), 7.30 (d, J = 7.2 Hz, 1 H), 7.24–7.20
(m, 4 H), 7.16–7.12 (m, 3 H), 6.95 (d, J = 11.2 Hz, 1 H), 6.86–6.80 (m, 3 H), 6.38 (d, J = 11.2 Hz,
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1 H). 13C NMR (100 MHz, CDCl3) δ 162.2 (d, J = 248.0 Hz), 154.6, 147.2, 139.0, 132.1, 131.8 (d,
J = 8.0 Hz), 131.7 (d, J = 3.0 Hz), 131.4, 130.7, 130.4, 130.1, 128.4(4), 128.3(9), 127.4, 127.2,
124.7, 121.0, 114.6 (d, J = 22.0 Hz). IR (KBr): 3057, 3023, 2922, 2851, 1598, 1503, 1446, 1269,
1231, 1174, 841, 758, 700 cm-1. HRMS-ESI (m/z): calcd for C22H15FNaO [M + Na]+ : 337.0999;
found: 337.0993.
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2-(4-Chlorophenyl)-3-phenylbenzo[b]oxepine (3ai3). Yellow solid (66.8 mg, 81%), mp:
119–120 oC. 1H NMR (400 MHz, CDCl3) δ 7.32–7.29 (m, 3 H), 7.24–7.21 (m, 4 H), 7.15–7.09 (m,
5 H), 6.95 (d, J = 11.2 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.37 (d, J = 11.2 Hz, 1 H). 13C NMR
(100 MHz, CDCl3) δ 154.6, 146.8, 138.8, 133.9(2), 133.8(9), 132.1, 131.3, 131.1, 131.0, 130.5,
130.0, 128.5, 128.4, 127.9, 127.8, 127.5, 124.8, 120.9. IR (KBr): 3058, 3023, 2958, 2922, 1594,
1484, 1446, 1384, 1208, 1173, 1118, 835, 760, 700 cm-1. HRMS-ESI (m/z): calcd for
C22H15ClNaO [M + Na]+ : 353.0704; found: 353.0701.
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2-(4-Methoxyphenyl)-3-phenylbenzo[b]oxepine (3ai4). Yellow oil (58.7 mg, 72%). H NMR
(400 MHz, CDCl3) δ 7.37 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 7.6 Hz, 1 H), 7.24–7.12 (m, 7 H), 6.94
(d, J = 11.2 Hz, 1 H), 6.89 (d, J = 8.0 Hz, 1 H), 6.69 (d, J = 8.4 Hz, 2 H), 6.40 (d, J = 11.2 Hz, 1
H), 3.75 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 159.3, 154.5, 148.0, 139.6, 132.4, 131.5, 131.4,
130.2(4), 130.1(5), 130.0, 128.3, 128.2, 128.0, 127.1, 125.9, 124.5, 121.1, 112.9, 55.1. IR (KBr):
3056, 3022, 2959, 2925, 2823, 1603, 1507, 1251, 1172, 1109, 1032, 836, 759, 701 cm-1.
HRMS-ESI (m/z): calcd for C23H18NaO2 [M + Na]+ : 349.1199; found: 349.1198.
3-(4-Fluorophenyl)-2-methylbenzo[b]oxepine (3aj1). Yellow oil (47.9 mg, 76%). 1H NMR (400
MHz, CDCl3) δ 7.34 (t, J = 7.2 Hz, 1 H), 7.23 (d, J = 7.2 Hz, 1 H), 7.17–7.15 (m, 3 H), 7.02 (t, J =
8.0 Hz, 3 H), 6.77 (d, J = 11.2 Hz, 1 H), 6.20 (d, J = 11.2 Hz, 1 H), 2.05 (s, 3 H). 13C NMR (100
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MHz, CDCl3) δ 161.9 (d, J = 245.0 Hz), 155.0, 151.8, 135.0 (d, J = 3.0 Hz), 131.4, 131.3, 130.9 (d,
J =8.0 Hz), 130.0, 129.5, 128.5, 124.8, 124.7, 121.1, 115.1 (d, J = 21.0 Hz), 18.8. IR (KBr): 3070,
2959, 2924, 2852, 1598, 1510, 1482, 1221, 1172, 958, 837, 759 cm-1. HRMS-ESI (m/z): calcd for
C17H13FNaO [M + Na]+ : 275.0843; found: 275.0843.
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3-(4-Chlorophenyl)-2-methylbenzo[b]oxepine (3aj2). Yellow oil (56.9 mg, 85%). 1H NMR (400
MHz, CDCl3) δ 7.35–7.28 (m, 3 H), 7.23 (d, J = 7.6 Hz, 1 H), 7.18 (d, J = 7.6 Hz, 1 H), 7.13 (d, J
= 7.6 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.78 (d, J = 10.8 Hz, 1 H), 6.18 (d, J = 11.2 Hz, 1 H),
2.05 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.0, 152.0, 137.6, 133.0, 131.3, 131.1, 130.6,
130.0, 129.7, 128.5, 128.4, 124.8, 124.6, 121.1, 18.9. IR (KBr): 3026, 2959, 2924, 2852, 1594,
1486, 1374, 1173, 1090, 760 cm-1. HRMS-ESI (m/z): calcd for C17H13ClNaO [M + Na]+ :
291.0547; found: 291.0553.
3-(4-Bromophenyl)-2-methylbenzo[b]oxepine (3aj3). Yellow oil (50.7 mg, 65%). 1H NMR (400
MHz, CDCl3) δ 7.46 (d, J = 8.0 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.23 (d, J = 7.6 Hz, 1 H), 7.17
(d, J = 7.2 Hz, 1 H), 7.07 (d, J = 8.0 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.77 (d, J = 11.2 Hz, 1 H),
6.17 (d, J = 11.2 Hz, 1 H), 2.05 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.0, 152.0, 138.1,
131.4, 131.3, 131.0(1), 130.9(9), 129.8, 128.6, 124.8, 124.7, 121.1, 18.93. IR (KBr): 3059, 3023,
2923, 2851, 1642, 1592, 1484, 1384, 1172, 956, 759 cm-1. HRMS-ESI (m/z): calcd for
C17H13BrNaO [M + Na]+: 335.0042 ; found: 335.0033.
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2-Methyl-3-(p-tolyl)benzo[b]oxepine (3aj4). Yellow oil (47.1 mg, 76%). H NMR (400 MHz,
CDCl3) δ 7.31 (t, J = 7.2 Hz, 1 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.16–7.12 (m, 3 H), 7.08 (d, J = 8.0
Hz, 2 H), 7.01 (d, J = 8.0 Hz, 1 H), 6.75 (d, J = 11.2 Hz, 1 H), 6.22 (d, J = 11.2 Hz, 1 H), 2.33 (s,
3 H), 2.06 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.1, 151.4, 136.7, 136.2, 131.9, 131.5, 129.8,
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129.2, 129.1, 128.9, 128.5, 125.4, 124.6, 121.1, 21.1, 18.9. IR (KBr): 3055, 3022, 2917, 2853,
1641, 1595, 1514, 1483, 1264, 1170, 957, 758 cm-1. HRMS-ESI (m/z): calcd for C18H16NaO [M +
Na]+ : 271.1093; found: 271.1087.
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3-(4-Methoxyphenyl)-2-methylbenzo[b]oxepine (3aj5). Yellow oil (54.8 mg, 83%). H NMR
(400 MHz, CDCl3) δ 7.31 (t, J = 7.6 Hz, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 7.2 Hz, 1 H),
7.11 (d, J = 7.6 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.85 (d, J = 8.0 Hz, 2 H), 6.75 (d, J = 11.2 Hz,
1 H), 6.21 (d, J = 10.8 Hz, 1 H), 3.79 (s, 3 H), 2.06 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 158.6,
155.0, 151.2, 131.9, 131.5, 131.4, 130.4, 129.8, 129.1, 128.5, 125.1, 124.6, 121.1, 113.6, 55.2,
18.8. IR (KBr): 3057, 2929, 2836, 1604, 1511, 1244, 1169, 736 cm-1. HRMS-ESI (m/z): calcd for
C18H16NaO2 [M + Na]+ : 287.1043, found: 287.1038.
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3-(3-Methoxyphenyl)-2-methylbenzo[b]oxepine (3ak). Yellow oil (47.5 mg, 72%). H NMR
(400 MHz, CDCl3) δ 7.32 (t, J = 7.2 Hz, 1 H), 7.25–7.21 (m, 2 H), 7.16 (t, J = 7.2 Hz, 1 H), 7.02
(d, J = 7.8 Hz, 1 H), 6.81–6.73 (m, 4 H), 6.23 (d, J = 11.2 Hz, 1 H), 3.78 (s, 3 H), 2.06 (s, 3 H).
13C NMR (100 MHz, CDCl3) δ 159.4, 155.1, 151.9, 140.6, 131.5, 131.4, 129.9, 129.3, 129.2, 128.5,
125.5, 124.7, 121.7, 121.1, 114.8, 112.7, 55.3, 19.0. IR (KBr): 3063, 2941, 2908, 2836, 1600,
1485, 1451, 1290, 1214, 1172, 967, 758, 736 cm-1. HRMS-ESI (m/z): calcd for C18H17O2 [M +
H]+ : 265.1223, found: 265.1225.
3-(2-Methoxyphenyl)-2-methylbenzo[b]oxepine (3al). Yellow solid (35.6 mg, 54%), mp: 87–89
oC. 1H NMR (400 MHz, CDCl3) δ 7.30 (t, J = 7.8 Hz, 1H), 7.24 (d, J = 7.0 Hz, 1H), 7.19 (d, J = 7.3
Hz, 1H), 7.13 (t, J = 7.2 Hz, 1H), 7.02 (dd, J = 13.9, 7.8 Hz, 2H), 6.90 (t, J = 6.5 Hz, 2H), 6.67 (d, J =
11.1 Hz, 1H), 6.17 (d, J = 11.1 Hz, 1H), 3.77 (s, 3H), 1.91 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
156.8, 155.3, 152.9, 131.9, 131.7, 131.2, 129.5, 128.7, 128.4, 128.3, 127.7, 124.5, 121.6, 121.1,
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120.4, 111.2, 55.5, 18.9. IR (KBr): 3068, 3023, 2909, 2834, 1598, 1488, 1456, 1260, 1172, 956,
756 cm-1. HRMS-ESI (m/z): calcd for C18H16NaO2 [M + Na]+ : 287.1043; found: 287.1037.
2-Isopropyl-3-phenylbenzo[b]oxepine (3am). Yellow solid (52.4 mg, 80%), mp: 115–117 oC. 1H
NMR (400 MHz, CDCl3) δ 7.34 (t, J = 7.2 Hz, 2 H), 7.29–7.26 (m, 2 H), 7.20 (d, J = 7.2 Hz, 2 H),
7.13–7.09 (m, 3 H), 6.59 (d, J = 11.2 Hz, 1 H), 6.12 (d, J = 11.2 Hz, 1 H), 2.71–2.64 (m, 1 H),
1.20 (d, J = 6.8 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 162.0, 157.8, 139.7, 132.3, 131.9, 129.5,
128.9, 128.8, 128.6, 128.4, 126.9, 124.5, 123.9, 121.7, 31.8, 20.7. IR (KBr): 3024, 2966, 2928,
2868, 2637, 1599, 1488, 1446, 1264, 1209, 1046, 958, 761, 700 cm-1. HRMS-ESI (m/z): calcd for
C19H18NaO [M + Na]+ : 285.1250; found: 285.1244.
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2-Butyl-3-phenylbenzo[b]oxepine (3an). Yellow oil (55.2 mg, 80%). 1H NMR (400 MHz, CDCl3)
δ 7.33–7.23 (m, 4 H), 7.16–7.10 (m, 4 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.68 (d, J = 11.2 Hz, 1 H),
6.18 (d, J = 10.8 Hz, 1 H), 2.27 (t, J = 7.6 Hz, 2 H), 1.74–1.67 (m, 2 H), 1.35–1.25 (m, 2 H), 0.85
(t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3) δ 156.5, 156.0, 139.3, 132.0, 131.6, 129.7,
129.0(4), 129.0(1), 128.5, 128.2, 126.9, 125.6, 124.6, 121.2, 32.3, 29.6, 22.5, 13.8. IR (KBr): 3059,
3024, 2959, 2925, 2858, 1598, 1487, 1205, 1168, 958, 760, 701 cm-1. HRMS-ESI (m/z): calcd for
C20H20NaO [M + Na]+ : 299.1406; found: 299.1412.
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2-Benzyl-3-phenylbenzo[b]oxepine (3ao). Yellow solid (53.5 mg, 69%), mp: 103–104 C. H
NMR (400 MHz, CDCl3) δ 7.40–7.27 (m, 10 H), 7.21–7.10 (m, 3 H), 6.77 (d, J = 11.2 Hz, 1 H),
6.51 (d, J = 7.6 Hz, 1 H), 6.28 (d, J = 11.2 Hz, 1 H), 3.70 (s, 2 H). 13C NMR (100 MHz, CDCl3) δ
156.0, 154.0, 139.1, 138.3, 131.6, 131.4, 129.8, 129.7, 129.2, 129.1, 128.5, 128.4, 127.3, 126.8,
126.4, 124.6, 121.4, 38.7. IR (KBr): 3056, 3025, 2923, 2851, 1596, 1488, 1264, 960, 738, 701
cm-1. HRMS-ESI (m/z): calcd for C23H19O [M + H]+ : 311.1430; found: 311.1430.
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3-(Furan-2-yl)-2-methylbenzo[b]oxepine (3ap). Black oil (38.6 mg, 69%). H NMR (400 MHz,
CDCl3) δ 7.40 (s, 1 H), 7.32 (t, J = 7.6 Hz, 1 H), 7.22 (d, J = 7.2 Hz, 1 H), 7.15 (t, J = 7.2 Hz, 1 H),
7.03 (d, J = 8.0 Hz, 1 H), 6.84 (d, J = 11.2 Hz, 1 H), 6.46–6.34 (m, 2 H), 6.24 (s, 1 H), 2.34 (s, 3
H). 13C NMR (100 MHz, CDCl3) δ 155.1, 153.6, 151.5, 141.6, 131.2, 130.2, 129.9, 128.7, 128.5,
124.9, 121.0, 116.4, 110.9, 108.6, 19.64. IR (KBr): 2998, 2923, 2852, 1670, 1598, 1485, 1449,
1383, 1212, 1177, 1032, 966, 731 cm-1. HRMS-ESI (m/z): calcd for C15H13O2 [M + H]+ : 225.0910;
found: 225.0910.
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2-(2-Methylbenzo[b]oxepin-3-yl)pyridine (3aq). Black oil (43.5 mg, 74%). 1H NMR (400 MHz,
CDCl3) δ 8.64 (s, 1 H), 7.70 (t, J = 7.2 Hz, 1 H), 7.33–7.26 (m, 2 H), 7.22–7.20 (m, 2 H), 7.15 (t, J
= 8.4 Hz, 1 H), 7.01 (d, J = 8.0 Hz, 1 H), 6.84 (d, J = 11.2 Hz, 1 H), 6.40 (d, J = 11.2 Hz, 1 H),
2.17 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 157.2, 155.1, 155.0, 148.9, 136.8, 131.3, 130.1(4),
130.0(9), 129.9, 128.6, 124.9(4), 124.8(5), 124.6, 121.9, 121.1, 19.27. IR (KBr): 2998, 2922, 2851,
1588, 1484, 1212, 1173, 964, 765 cm-1. HRMS-ESI (m/z): calcd for C16H14NO [M + H]+ :
236.1070; found: 236.1070.
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3-Benzyl-2-methylbenzo[b]oxepine (3ar). Yellow oil (40.9 mg, 66%). H NMR (400 MHz,
CDCl3) δ 7.31–7.22 (m, 3 H), 7.20–7.08 (m, 5 H), 6.99 (d, J = 8.0 Hz, 1 H), 6.64 (d, J = 11.2 Hz,
1 H), 6.03 (d, J = 11.2 Hz, 1 H), 3.43 (s, 2 H), 2.14 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.3,
151.8, 139.4, 131.8, 131.6, 129.6, 129.4, 128.4, 128.3(2), 128.2(7), 126.1, 124.5, 121.1, 120.9,
37.1, 17.8. IR (KBr): 3055, 2986, 2924, 1639, 1485, 1265, 892, 742 cm-1. HRMS-ESI (m/z): calcd
for C18H16NaO [M + Na]+ : 271.1093; found: 271.1095.
2-Ethyl-3-methylbenzo[b]oxepine (3as). Yellow oil (31.6 mg, 68%). 1H NMR (400 MHz, CDCl3)
δ 7.23–7.22 (m, 1 H), 7.10 – 7.05 (m, 2 H), 6.98 (d, J = 8.0 Hz, 1 H), 6.61 (d, J = 11.1 Hz, 1 H),
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6.05 (d, J = 11.1 Hz, 1 H), 2.37 (q, J = 7.4 Hz, 2 H), 1.72 (s, 3 H), 1.22 (t, J = 7.5 Hz, 3 H). 13C
NMR (100 MHz, CDCl3) δ 156.2, 155.6, 133.0, 131.7, 129.5, 128.7, 128.2, 124.3, 121.1, 116.9,
25.4, 16.8, 11.9. IR (KBr): 3066, 2925, 2854, 1715, 1589, 1484, 1449, 1268, 1206, 1102, 756 cm-1.
HRMS-ESI (m/z): calcd for C13H14NaO [M + Na]+ : 209.0937; found: 209.0934.
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2-Cyclopropylbenzo[b]oxepine (3at). Yellow oil (24.8 mg, 54%). 1H NMR (400 MHz, CDCl3) δ
7.23 (t, J = 7.3 Hz, 1 H), 7.09–7.02 (m, 2 H), 6.83 (d, J = 8.1 Hz, 1 H), 6.52 (d, J = 11.1 Hz, 1 H),
6.00 (dd, J = 11.0, 6.1 Hz, 1 H), 5.45 (d, J = 6.0 Hz, 1 H), 1.65–1.57 (m, 1 H), 0.98 (d, J = 2.9 Hz,
2 H), 0.73 (d, J = 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3) δ 160.7, 156.1, 132.0, 129.6, 129.5,
128.8, 127.5, 124.6, 121.1, 108.4, 15.0, 5.0. IR (KBr): 3021, 2925, 2852, 1648, 1486, 1383, 1204,
1168, 1046, 943, 754 cm-1. HRMS-ESI (m/z): calcd for C13H13O [M + H]+ : 185.0961; found:
185.0971.
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1,2,3,4-Tetrahydrodibenzo[b,f]oxepine (3au). Yellow oil (38.6 mg, 78%). H NMR (400 MHz,
CDCl3) δ 7.21–7.16 (m, 1 H), 7.07–6.99 (m, 2 H), 6.85 (d, J = 8.0 Hz, 1 H), 6.54 (d, J = 11.1 Hz,
1 H), 5.92 (d, J = 11.1 Hz, 1 H), 2.28 (s, 2 H), 2.03 (s, 2 H), 1.63–1.59 (m, 2 H), 1.54–1.50 (m, 2
H). 13C NMR (100 MHz, CDCl3) δ 155.4, 153.1, 131.8, 129.6, 128.9, 128.5, 124.3, 121.1, 119.6,
28.4, 28.2, 22.8, 22.3. IR (KBr): 3022, 2959, 2922, 2849, 1657, 1486, 1449, 1210, 1106, 773 cm-1.
HRMS-ESI (m/z): calcd for C14H14NaO [M+Na]+ : 221.0937; found: 221.0935.
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7,8,9,10-Tetrahydro-6H-benzo[b]cyclohepta[f]oxepine (3av). Yellow oil (37.6 mg, 71%). H
NMR (400 MHz, CDCl3) δ 7.27–7.25 (m, 1 H), 7.14–7.07 (m, 2 H), 6.96 (d, J = 8.0 Hz, 1 H), 6.60
(d, J = 10.9 Hz, 1 H), 6.08 (d, J = 11.0 Hz, 1 H), 2.59 (d, J = 8.0 Hz, 2 H), 2.17 (d, J = 8.6 Hz, 2
H), 1.70–1.57 (m, 6 H). 13C NMR (100 MHz, CDCl3) δ 156.8, 155.5, 133.5, 131.5, 129.5,
128.2(1), 128.1(5), 125.1, 124.3, 120.7, 34.6, 31.1, 31.0, 26.4, 25.3. IR (KBr): 2927, 1668, 1568,
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1461, 1392, 1227, 1159, 1023, 758 cm-1. HRMS-ESI (m/z): calcd for C15H16NaO [M + Na]+ :
235.1093, found: 235.1095.
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(Z)-6,7,8,9,10,11-Hexahydrobenzo[b]cycloocta[f]oxepine (3aw). Yellow oil (40.7 mg, 72%). H
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NMR (400 MHz, CDCl3) δ 7.24 (t, J = 7.4 Hz, 1 H), 7.11–7.05 (m, 2 H), 6.98 (d, J = 8.0 Hz, 1 H),
6.64 (d, J = 11.1 Hz, 1 H), 6.05 (d, J = 11.1 Hz, 1 H), 2.48 (d, J = 6.0 Hz, 2 H), 2.17 (d, J = 6.0 Hz,
2 H), 1.70–1.67 (m, 2 H), 1.57–1.51 (m, 2 H), 1.41 (t, J = 9.0 Hz, 4 H). 13C NMR (100 MHz,
CDCl3) δ 156.1, 154.2, 131.9, 131.4, 129.5, 129.3, 128.2, 124.2, 122.1, 120.9, 32.2, 30.4, 29.6,
29.1, 26.4, 26.0. IR (KBr): 3016, 2923, 2851, 1598, 1485, 1449, 1206, 1110, 969, 762 cm-1.
HRMS-ESI (m/z): calcd for C16H18NaO [M + Na]+ : 249.1250; found: 249.1251.
12,13-Dihydrobenzo[b]naphtho[1,2-f]oxepine (3ax). Yellow solid (50.4 mg, 82%), mp: 97–98
oC. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.67 (d, J =
8.8 Hz, 1 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.39 (t, J = 7.6 Hz, 2 H), 7. 14–7.24(m, 3 H), 7.06 (t, J =
7.2 Hz, 1 H), 3.50–3.47 (m, 2 H), 3.32–3.29 (m, 2 H). 13C NMR (100 MHz, CDCl3) δ 158.1, 154.4,
133.5, 133.3, 130.7, 129.5, 128.5, 127.9, 127.3, 126.4, 124.4(2), 124.3(7), 123.5, 123.0, 122.0,
120.6, 29.8, 27.4. IR (KBr): 2959, 2925, 2825, 1636, 1460, 1380, 1266, 1080, 760 cm-1.
HRMS-ESI (m/z): calcd for C18H15O [M + H]+ : 247.1117, found: 247.1117.
8-Chloro-2-phenylbenzo[b]oxepine (3ba). Yellow solid (57.1 mg, 90%), mp: 75–76 oC. 1H NMR
(400 MHz, CDCl3) δ 7.80 (d, J = 7.3 Hz, 2 H), 7.43 (t, J = 7.3 Hz, 2 H), 7.39–7.33 (m, 1 H),
7.15–7.06 (m, 3 H), 6.73 (d, J = 10.1 Hz, 1 H), 6.32–6.27 (m, 2 H). 13C NMR (100 MHz, CDCl3)
δ 155.2, 154.6, 135.3, 134.3, 130.7, 130.4, 129.3, 128.8, 128.6, 127.7, 125.3, 125.1, 121.7, 110.2.
IR (KBr): 3027, 2923, 2851, 1588, 1482, 1270, 1078, 1043, 824, 765, 721 cm-1. HRMS-ESI (m/z):
calcd for C16H11ClNaO [M + Na]+ : 277.0391; found: 277.0393.
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8-Chloro-3-(4-chlorophenyl)-2-methylbenzo[b]oxepine (3bj2). Yellow solid (66.4 mg, 88%),
mp: 91–93 oC. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.2 Hz, 2H), 7.18–7.10 (m, 4 H), 7.05 (s,
1 H), 6.72 (d, J = 11.1 Hz, 1 H), 6.18 (d, J = 11.1 Hz, 1 H), 2.05 (s, 3 H). 13C NMR (100 MHz,
CDCl3) δ 155.1, 151.9, 137.1, 135.1, 133.1, 131.4, 130.5, 129.8, 129.1, 128.7, 128.5, 125.1, 124.8,
121.6, 18.8. IR (KBr): 3028, 2911, 1591, 1483, 1174, 1085, 964, 834 cm-1. HRMS-ESI (m/z):
calcd for C17H12Cl2NaO [M + Na]+ : 325.0157, found: 325.0159.
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8-Bromo-2-phenylbenzo[b]oxepine (3ca). Yellow solid (66.3 mg, 89%), mp: 87–88 oC. 1H NMR
(400 MHz, CDCl3) δ 7.77 (d, J = 7.4 Hz, 2 H), 7.41–7.32 (m, 3 H), 7.24–7.22 (m, 2 H), 7.00 (d, J
= 7.9 Hz, 1 H), 6.69 (d, J = 10.7 Hz, 1 H), 6.31–6.23 (m, 2 H). 13C NMR (100 MHz, CDCl3) δ
155.2, 154.7, 134.3, 131.1, 130.5, 129.6, 128.9, 128.6, 128.0, 127.9, 125.4, 124.6, 123.1, 110.2. IR
(KBr): 3026, 2922, 2853, 1583, 1480, 1269, 1040, 920, 821, 764 cm-1. HRMS-ESI (m/z): calcd for
C16H11BrNaO [M + Na]+ : 320.9885; found: 320.9885.
8-Bromo-3-(4-chlorophenyl)-2-methylbenzo[b]oxepine (3cj2). Yellow solid (72.8 mg, 82%), mp:
97.2–98.7 oC. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.3 Hz, 3 H), 7.20 (s, 1 H), 7.13–7.07 (m,
3 H), 6.70 (d, J = 11.1 Hz, 1 H), 6.19 (d, J = 11.1 Hz, 1 H), 2.04 (s, 3 H). 13C NMR (100 MHz,
CDCl3) δ 155.2, 152.0, 137.1, 133.1, 131.5, 130.5, 130.3, 129.4, 128.7, 128.5, 128.0, 124.8, 124.5,
122.9, 18.8. IR (KBr): 3033, 2930, 2858, 1582, 1478, 1167, 1088, 957, 801 cm-1. HRMS-ESI
(m/z): calcd for C17H12BrNaClO [M + Na]+ : 368.9652, found: 368.9653.
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2-Phenylbenzo[b]oxepine-8-carbonitrile (3da). Yellow solid (52.7 mg, 86%), mp: 113–114 C.
1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.1 Hz, 2 H), 7.48–7.40 (m, 4 H), 7.37 (s, 1 H), 7.28 (d,
J = 3.5 Hz, 1 H), 6.79 (d, J = 11.0 Hz, 1 H), 6.46 (dd, J = 11.0, 6.3 Hz, 1 H), 6.34 (d, J = 6.3 Hz, 1
H). 13C NMR (100 MHz, CDCl3) δ 155.6, 154.5, 137.0, 133.9, 130.6, 129.9, 129.4, 128.7, 128.5, 125.5,
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125.2, 118.1, 113.1, 110.0. IR (KBr): 3027, 2920, 1600, 1489, 1226, 887, 834 cm-1. HRMS-ESI
(m/z): calcd for C17H11NNaO [M + Na]+ : 268.0733, found: 268.0735.
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3-(4-Chlorophenyl)-2-methylbenzo[b]oxepine-8-carbonitrile (3dj2). Yellow solid (60.8 mg,
83%), mp: 160–162 oC. 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.8 Hz, 1 H), 7.32–7.26 (m, 4 H),
7.11 (d, J = 8.2 Hz, 2 H), 6.73 (d, J = 11.2 Hz, 1 H), 6.30 (d, J = 11.2 Hz, 1 H), 2.05 (s, 3 H). 13C NMR
(100 MHz, CDCl3) δ 154.5, 153.0, 136.6, 136.1, 134.1, 133.4, 130.4, 129.2, 128.6, 128.5, 128.2,
124.8(8), 124.8(6), 118.1, 112.9, 18.9. IR (KBr): 2024, 2920, 1600, 1546, 1490, 1168, 1089, 976,
833 cm-1. HRMS-ESI (m/z): calcd for C18H12ClNNaO [M + Na]+ : 316.0500; found: 316.0507.
8-Methyl-2-phenylbenzo[b]oxepine (3ea). Yellow solid (46.8 mg, 80%), mp: 73–75 oC. 1H NMR
(400 MHz, CDCl3) δ 7.81 (d, J = 7.1 Hz, 2 H), 7.38 (t, J = 7.7 Hz, 2 H), 7.33–7.29 (m, 1 H), 7.03
(d, J = 7.6 Hz, 1 H), 6.91 (d, J = 10.4 Hz, 2 H), 6.73 (d, J = 10.1 Hz, 1 H), 6.27–6.18 (m, 2 H),
2.29 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 155.1, 154.4, 140.9, 134.9, 131.4, 129.2, 128.5,
128.4(7), 128.4(5), 126.5, 125.5, 125.4, 121.7, 110.2, 21.0. IR (KBr): 3026, 2922, 2853, 1607,
1497, 1448, 1266, 1323, 1150, 1045, 822, 769 cm-1. HRMS-ESI (m/z): calcd for C17H15O [M +
H]+ : 235.1117; found: 235.1116.
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7-Methyl-2-phenylbenzo[b]oxepine (3fa). Yellow oil (48.0 mg, 82%). H NMR (400 MHz,
CDCl3) δ 7.83 (d, J = 8.1 Hz, 2 H), 7.40 (t, J = 7.4 Hz, 2 H), 7.36–7.30 (m, 1 H), 7.10 (d, J = 8.2
Hz, 1 H), 6.99 (d, J = 7.1 Hz, 2 H), 6.76 (d, J = 10.1 Hz, 1 H), 6.28 (q, J = 6.1 Hz, 2 H), 2.31 (s, 3
H). 13C NMR (100 MHz, CDCl3) δ 154.9, 153.1, 134.8, 134.2, 131.6, 131.5, 130.9, 129.1, 128.5,
128.4, 127.4, 125.4, 120.9, 110.0, 20.6. IR (KBr): 3024, 2922, 2854, 1599, 1491, 1447, 1202, 752,
691 cm-1. HRMS-ESI (m/z): calcd for C17H14NaO [M + Na]+ : 257.0937; found: 257.0934.
2-Phenyloxepino[2,3-b]pyridine (3ga). Yellow oil (32.1 mg, 58%). 1H NMR (400 MHz, CDCl3)
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δ 8.31 (dd, J = 4.8, 1.8 Hz, 1 H), 8.05–7.97 (m, 2 H), 7.55 (dd, J = 7.4, 1.8 Hz, 1 H), 7.43–7.39 (m,
2 H), 7.35–7.32 (m, 1 H), 7.12 (dd, J = 7.4, 4.8 Hz, 1 H), 6.67–6.59 (m, 1 H), 6.38–6.31 (m, 2 H).
13C NMR (100 MHz, CDCl3) δ 159.3, 154.6, 148.7, 137.9, 134.7, 128.9, 128.6, 128.6, 128.3,
126.6, 126.0, 121.3, 109.5. IR (KBr): 3056, 2922, 2852, 1635, 1575, 1491, 1425, 1270, 1146, 732
cm-1. HRMS-ESI (m/z): calcd for C15H12NO [M + H]+ : 222.0913; found: 222.0911.
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(E)-4-(2-Fluorophenyl)-1-(furan-2-yl)but-3-en-1-one (4ag1). Yellow oil (23.6 mg, 41%). H
NMR (400 MHz, CDCl3) δ 7.59 (d, J = 5.0 Hz, 1 H), 7.46 (t, J = 7.7 Hz, 1 H), 7.25 (d, J = 3.6 Hz,
1 H), 7.20–7.16 (m, 1H), 7.09–6.98 (m, 2 H), 6.72 (d, J = 16.2 Hz, 1 H), 6.56–6.45 (m, 2H), 3.78
(d, J = 7.0 Hz, 2 H). 13C NMR (100 MHz, CDCl3) δ 186.6, 161.0 (d, J = 248.0 Hz), 152.3, 146.5,
128.8 (d, J = 9.0 Hz), 127.2 (d, J = 4.0 Hz), 126.2 (d, J = 4.0 Hz), 124.6 (d, J = 12.0 Hz), 124.4 (d, J
= 4.0 Hz), 124.0 (d, J = 3.0 Hz), 117.6, 115.5 (d, J = 20.0 Hz), 112.3, 42.9. IR (KBr): 30211, 2925,
1585, 1488, 1450, 1226, 1100, 1034, 755 cm-1. HRMS-ESI (m/z): calcd for C14H11FNaO2 [M +
Na]+ : 253.0635, found: 253.0635.
Acknowledgements
We thank the National Natural Science Foundation of China (21172078,
21420102003 and 21572071) and the Fundamental Research Funds for the Central
Universities (2015ZM0038) for financial support.
Supporting Information
1H and 13C NMR spectra of all synthesized compounds, X-ray structures and
crystallographic data (CIF files) of compound 3ai3 and 3ax. This material is available
free of charge via the Internet at http://pubs.acs.org.
REFERENCES
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1. (a) Spiteller, P. Chem. Eur. J. 2008, 14, 9100. (b) Bakthadoss, M.; Sivakumar, N.; Devaraj, A.
Tetrahedron Lett. 2015, 56, 4980. (c) Ren, Y.; Kardono, L. B. S.; Riswan, S.; Chai, H.; Farnsworth,
N. R.; Soejarto, D. D.; Carcache de Blanco, E. J.; Kinghorn, A. D. J. Nat. Prod. 2010, 73, 949. (d)
Yamaguchi, S.; Tsuchida, N.; Miyazawa, M.; Hirai, Y. J. Org. Chem. 2005, 70, 7505.
2. (a) Vyvyan J. R.; Looper, R. E. Tetrahedron Lett. 2000, 41, 1151. (b) El Marsni, Z.; Torres, A.;
Varela, R. M.; Molinillo, J. M. G.; Casas, L.; Mantell, C.; De la Ossa, E. J. M.; Macias, F. A. J.
Agric. Food Chem. 2015, 63, 6410. (c) Macías, F. A.; Varela, R. M.; Torres, A.; Molinillo, M. G.
Tetrahedron Lett. 1999, 40, 4725.
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3. Related reviews on the synthesis of oxepines see: (a) Hoberg, J. O. Tetrahedron 1998, 54,
12631. (b) Snyder, N. L.; Haines, H. M.; Peczuh, M. W. Tetrahedron 2006, 62, 9301.
4. (a) Varela-Fernández, A.; García-Yebra, C.; Varela, J. A.; Esteruelas, M. A.; Saá, C. Angew.
Chem. Int. Ed. 2010, 49, 4278. (b) Chan, P. W. H.; Teo, W. T.; Koh, S. W. Y.; Lee, B. R.; Ayers, B.
J.; Ma, D.-L.; Leung, C.-H. Eur. J. Org. Chem. 2015, 4447. (c) Coulter, M. M.; Dornan, P. K.;
Dong, V. M. J. Am. Chem. Soc. 2009, 131, 6932. (d) Calder, E. D. D.; Sharif, S. A. I.; McGonagle,
F. I.; Sutherland, A. J. Org. Chem. 2015, 80, 4683. (e) Bera, K.; Jalal, S.; Sarkar. S.; Jana, U. Org.
Biomol. Chem. 2014, 12, 57. (f) Sze, E. M. L.; Rao, W.; Koh, M. J.; Chan, P. W. H. Chem. Eur. J.
2011, 17, 1437. (g) Liu, J.; Liu, Y. Org. Lett. 2012, 14, 4742. (h) Ramachary, D. B.; Narayana, V.
V.; Ramakumar, K. Eur. J. Org. Chem. 2008, 3907.
5. (a) Lautens, M.; Paquin, J.-F.; Piguel, S. J. Org. Chem. 2002, 67, 3972. (b) Liu, G.; Lua, X. Adv.
Synth. Catal. 2007, 349, 2247. (c) Yu, X.; Lu, X. J. Org. Chem. 2011, 76, 6350. (d) Sun, L.-L.; Hu,
B.-L.; Tang, R.-Y.; Deng, C.-L.; Zhang, X.-G. Adv. Synth. Catal. 2013, 355, 377. (e) Friedman, A.
A.; Panteleev, J.; Tsoung, J.; Huynh, V.; Lautens, M. Angew. Chem. Int. Ed. 2013, 52, 9755.
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6. Seoane, A.; Casanova, N.; Quiñones, N.; Mascareñas, J. L.; Gulías, M. J. Am. Chem. Soc. 2014,
136, 834.
8
9
7. (a) Choi, Y. L.; Lim, H. S.; Lim, H. J.; Heo, J.-N. Org. Lett. 2012, 14, 5102. (b) Gharpure, S. J.;
Reddy, S. R. B. Eur. J. Org. Chem. 2013, 2981.
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8. Selective reviews on transition-metal-free coupling reactions, see: (a) Sun, C.-L.; Shi, Z.-J.
Chem. Rev. 2014, 114, 9219. (b) Mehta, V. P.; Punji, B. RSC Adv. 2013, 3, 11957. (c) Narayan, R.;
Matcha, K.; Antonchick, A. P. Chem. Eur. J. 2015, 21, 14678.
9. (a) He, H.; Qi, C.; Hu, X.; Ouyang, L.; Xiong, W.; Jiang, H. J. Org. Chem. 2015, 80, 4957. (b)
He, H.; Qi, C.; Ou, Y.; Xiong, W.; Hu, X.; Ren, Y.; Jiang, H. Org. Biomol. Chem. 2014, 12, 8128.
(c) Qi, C.; Jiang, H.; Huang, L.; Yuan, G.; Ren, Y. Org. Lett. 2011, 13, 5520. (d) Gao, Y.; Xiong,
W.; Chen, H.; Wu, W. ; Peng, J.; Gao, Y.; Jiang, H. J. Org. Chem. 2015, 80, 7456. (e) Li, J.; Yang,
W.; Yang, S.; Huang, L.; Wu, W.; Sun, Y.; Jiang, H. Angew. Chem. Int. Ed. 2014, 53, 7219. (f)
Huang, L.; Jiang, H.; Qi, C.; Liu, X. J. Am. Chem. Soc. 2010, 132, 17652.
10. CCDC-1422544 and CCDC-1423097 contain the supplementary crystallographic data for
compound 3ai3 and 3ax, respectively. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
11. (a) Trofimov, B. A.; Schmidt, E. Y.; Ushakov, I. A.; Zorina, N. V.; Skital’tseva, E. V.; Protsuk,
N. I.; Mikhaleva, A. I. Chem. Eur. J. 2010, 16, 8516. (b) Trofimov, B. A.; Schmidt, E. Y.; Zorina,
N. V.; Ivanova, E. V.; Ushakov, I. A. J. Org. Chem. 2012, 77, 6880. (c) Trofimov, B. A.; Schmidt,
E. Y.; Zorina, N. V.; Ivanova, E. V.; Ushakov, I. A.; Mikhaleva, A. I. Adv. Synth. Catal. 2012, 354,
1813.
12. (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119. (b) Sawyer, J. S. Tetrahedron 2000,
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13. (a) Thorand, S.; Krause, N. J. Org. Chem. 1998, 63, 8551. (b) Pearson, A. J.; Kim, J. B.
Tetrahedron Lett. 2003, 44, 8525.
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14. Igeta, H.; Arai, H.; Hasegawa, H.; Tsuchiya, T. Chem. Pharm. Bull. 1975, 23, 2791.
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