An efficient approach to construct 2-arylbenzo[b]furans from 2-methoxychalcone epoxides

Article abstract of DOI:10.1016/j.tet.2013.12.050

An efficient and practical method for construction of 2-arylbenzo[b]furans from 2-methoxychalcone epoxides has been reported. Catalyzed by 2 mol % of BF₃·Et₂O, 2-methoxychalcone epoxides went through the Meerwein rearrangement, followed by deformylation in one-pot to successfully afforded 2-methoxydeoxybenzoins. Afterward, 2-arylbenzo[b]furans were obtained in high yields (87%-100%) via intermolecular cyclodehydration of 2-methoxydeoxybenzoins with 48% HBr. By utilization of this approach, the natural product stemofuran A and the key intermediate of eupomatenoid 6 have been synthesized conveniently.

Full text of DOI:10.1016/j.tet.2013.12.050

Accepted Manuscript
An efficient approach to construct 2-arylbenzo[b]furans from 2-methoxychalcone
epoxides
Libo Ruan, Min Shi, Shiwei Mao, Lifang Yu, Fan Yang, Jie Tang
PII:
S0040-4020(13)01918-2
10.1016/j.tet.2013.12.050
TET 25134
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 November 2013
Revised Date: 4 December 2013
Accepted Date: 17 December 2013
Please cite this article as: Ruan L, Shi M, Mao S, Yu L, Yang F, Tang J, An efficient approach to
construct 2-arylbenzo[b]furans from 2-methoxychalcone epoxides, Tetrahedron (2014), doi: 10.1016/
j.tet.2013.12.050.
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Graphical Abstract
An efficient approach to construct 2-arylbenzo[b]furans
Leave this area blank for abstract info.
from 2-methoxychalcone epoxides
Libo Ruan, Min Shi, Shiwei Mao, Lifang Yu, Fan Yang, Jie Tang
Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New
Drug Development, East China Normal University, 3663 North Zhongshan Road, Shanghai, China

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
An efficient approach to construct 2-arylbenzo[b]furans from 2-methoxychalcone epoxides
∗
∗
Libo Ruan, Min Shi, Shiwei Mao, Lifang Yu, Fan Yang , Jie Tang
Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Nor-
mal University, Shanghai 200062, China
ARTICLE INFO
ABSTRACT
Article history:
Received
An efficient and practical method for construction of 2-arylbenzo[b]furans from 2-
.
methoxychalcone epoxides has been reported. Catalyzed by 2mol% of BF
3
Et
2
O, 2-
Received in revised form
Accepted
Available online
methoxychalcone epoxides went through the Meerwein rearrangement, followed by
deformylation in one-pot to successfully afforded 2-methoxydeoxybenzoins. Afterwards, 2-
arylbenzo[b]furans were obtained in high yields (87%-100%) via intermolecular
cyclodehydration of 2-methoxydeoxybenzoins with 48% HBr. By utilization of this approach,
the natural product stemofuran A and the key intermediate of eupomatenoid 6 have been
synthesized conveniently.
Keywords:
2013 Elsevier Ltd. All rights reserved.
2
2
-Arylbenzo[b]furans
-Methoxychalcone epoxides
Deformylation
Cyclodehydration
Stemofuran A
1. Introduction
application scope of these versatile molecules. Previously, we
successfully used chalcone epoxides as a synthetic precursor for
the preparation of 3-aryl quinolines. Herein, we reported a new
practical synthetic route for the preparation of 2-
arylbenzo[b]furans from 2-methoxychalcone epoxides.
1
2
-Arylbenzo[b]furans widely exist in natural products, and
11
many compounds including 2-arylbenzo[b]furan structural unit
were found to possess attractive pharmacological activities, such
as antitumor, antiviral, antioxidative, and antifungal proper-
ties. Their broad range of biological activities and significant
2
3
4
5
pharmacological potentials have resulted in the development of
many methods for their synthesis. The palladium-catalyzed
2. Results and discussion
6
cross-coupling cyclization reaction 7 from alkynes and o-
halophenols was found to be efficient. Other approaches for the
synthesis of benzo[b]furans include cyclization of vinylic phe-
Asokan et al. observed that β−ketoaldehydes could react with
12
1,2-diaminoethane in THF to yield deoxybenzoins. However,
only 4-substitute substrates were tested. We considered that if
the 2-alkyloxysubstituted chalcone epoxides were used in these
reactions, 2-methoxydeoxybenzoins should be obtained con-
veniently, which could be further transformed to the corre-
sponding 2-arylbenzo[b]furans via cyclodehydration.
We firstly focused on the optimization of the reaction condi-
tions with 2,3-epoxy-3-(2-metoxy-phenyl)-1-phenylpropan-1-
one (1a) as a model substrate (Table 1). Meerwein rearrange-
8
nols through McMurry coupling reaction, [3,3]-sigmatropic
9
rearrangement of oxime ethers, palladium-catalyzed enolate
1
0
arylation.
The relative ease of preparation chalcone epoxides makes
them promising starting materials for preparation of a variety of
heterocyclic compounds. Our group is interested in extent the
—
——
∗
∗
Corresponding author. Tel.: +86-21-62232764; E-mail: fyang@chem.ecnu.edu.cn
Corresponding author. Tel.: +86-21-62232100; E-mail: jtang@chem.ecnu.edu.cn

ACCEPTED MANUSCRIPT
2
Tetrahedron
ment of chalcone epoxides to form β−ketoaldehydes has been
model substrate to examine its behavior under different de-
1
3
13
12
known for a long time, and 2 equiv or 1 equiv of BF
was used in the reaction. From the viewpoint of catalytic mecha-
nism, we attempted to carry out the reaction with catalytic
amount of BF
the amount of BF
the yield (Table 1, entries 2-5). When the catalyst was further
reduced to 0.5 mol% the yield of the product dropped to 21%
due to an incomplete rearrangement reaction (Table 1, entry 6).
Therefore, 2 mol% of BF ·Et O was chosen as the optimal cata-
3
·Et
2
O
methylation conditions (Table 2). There are very few reports
about the cyclodehydration of 2-alkyloxydeoxybenzoin to
afford benzo[b]furans, which was only carried out the reac-
o
14a
14c
3
·Et
2
O, and the results showed that the reduction of
·Et O from 100 mol% to 2 mol% did not affect
3 3
tion with BCl at -78 C, or with AlBr in benzene. To
our delight, treatment of 2a with 48% HBr in AcOH, deoxy-
benzoin 2a could be demethylated, and subsequently
cyclodehydrated to give the desired benzo[b]furan 3a in
quatitative yield (Table 2, entry 5). Treatment of 2a with
BBr in CH Cl at 0°C gave 3a in 43% yield due to side reac-
3
2
3
2
3
2
2
lyst amount for the following rearrangement reactions. Change
of the organic solvent of the rearrangement reaction indicated
that the solvent played a paramount role in terms of rates and
chemical yields, and DCM was still the best choice. The reaction
finished in 5 min at 25 °C (Table 1, entry 5). The reactions were
sluggish and gave lower yields in PhMe, MeCN, or THF due to
the incomplete rearrangement (Table 1, entries 7-9). The influ-
ence of temperature on the rearrangement reaction was also pre-
liminarily tested, and lower yield was obtained when decrease
tion (Table 2, entrie 1), and only trace of 3a was detected when
AlCl /Py or LiCl was used(Table 2, entries 2, 6). Although HI
3
and TMSI/KI were competent reagents for this reaction (Table 2,
entries 3, 4), from the standpoint of overall cost and for large
scale reactions, 48% HBr was chosen as the demethylation re-
agent in the following reaction.
Table 2. Optimization of reaction conditions for conversion of 2-
a
o
methoxydeoxybenzoins to benzo[b]furan
the temperature was decreased from 25 C to 0 °C (Table 1, en-
try 10).
In addition, we found that the deformylation reaction of 2-
methoxy-β−ketoaldehyde could also be carried out in DCM in-
stead of THF (Table 1, entry 11). Therefore the procedure was
further simplified by successively performing the deformylation
after the rearrangement of chalcone epoxides, and the two-step
reaction proceeded in one-pot to afford the desired product 2a in
good yield.
Entry Demethylation Solvent Time
reagents
Temp
(°C)
Yield
(%)
b
1
2
3
4
5
6
BBr
3
DCM
DCM
0.5 h
6 h
0 °
rt
43
trace
92
Table 1. Optimization of reaction conditions for synthesis of
AlCl /Py
3
2-methoxydeoxybenzoin from 2-methoxychalcone epoxide
HI
2
H O
6 h
reflux
reflux
reflux
110
TMSI/KI
48 % HBr
LiCl
MeCN
AcOH
DMF
6 h
88
6 h
100
trace
12 h
a
Reaction conditions: 1 mmol of 2a, 4 equivalents of demethylation reagents,
the progress of the reaction was monitored by TLC.
Isolated yields.
b
In order to examine the scope of this construction method for
2
-arylbenzo[b]furans, a variety of 2-arylbenzo[b]furans were
prepared through this two-step one-pot synthetic strategy, and
the results were shown in Table 3. The variation of R and R
1
2
a
Yield
b
Entry
BF
3
·Et
2
O
Solvent A Solvent B Temp (°C)
groups had little influence on the reaction yields, and moderate
to good overall yields were observed (Table 3, entries 1-11)
regardless of the steric (ortho, meta and para positions) and elec-
tronic properties (both electronic rich and deficient). Importantly,
heteroaromatic chalcone epoxide 1i was a suitable substrate,
giving the desired product 3i in 87% yield (Table 3, entry 9). It is
worth noting that the obtained halide products such as bromide
and iodide are very useful intermediates which could be further
functionalized to give avariety of derivatives (Table 3, entries 4-
(
%)
72
71
72
77
75
1
2
3
4
5
6
7
8
9
100 mol%
50 mol%
10 mol%
5 mol%
2 mol%
0.5 mol%
2 mol%
2 mol%
2 mol%
2 mol%
2 mol%
DCM
DCM
DCM
DCM
DCM
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
DCM
25
25
25
25
25
25
25
25
25
0
c
c
DCM
Toluene
MeCN
THF
21
64
32
56
57
72
7, 10, 11).
To expand the utilization of the method, we attempted to
construct a useful natural product stemofuran A and the key in-
termediate of natural product eupomatenoid 6, 4-(5-bromo-3-
methylbenzofuran-2-yl)phenol (4m). Stemofuran A was isolated
from a methanolic extract of Stemona collinsae root which was
c
1
1
0
1
DCM
DCM
25
2c
reported to have potential antifungal activity. Stemofuran A has
a
Raction conditions: 1 mmol of chalcone epoxides, 5 mL of solvent A, after
been synthesized by several groups using different ap-
9
,14a,14b
the rearrangement reaction was complete, the solvent A was removed in
vacuo, then added 5 mL solvent B , 1 equiv of 1,2-diaminoethane.
Isolated yields.
proaches.
4-(5-Bromo-3-methylbenzofuran2-yl)phenol
(
4m) is an important synthetic intermediate used in the produc-
b
c
9
tion of eupomatenoid 6, which was first isolated in 1969 from
Reaction conducted for 4 h.
the bark of Eupomatia laurina R. with a broad range of biologi-
1
4c-14e
To construct 2-arylbenzo[b]furan 3a, 2a was selected as a
cal activities.
4m was prepared by Naito and co-workers

ACCEPTED MANUSCRIPT
3
starting from oxime ethers through [3,3]-sigmatropic rear-
rangement reaction with 53% overall yield (4 steps).
dure for synthesis of stemofuran A and 4m is practical and
9
convenient, and all the substrates and reagents are cheap and
commercially available.
As illustrated in Scheme 1, stemofuran A was achieved with
an overall yield of 71% began with 2-methoxychalcone epoxide
According to our experimental results and the reported
1
3,14
(
1l) which was treated with 2 mol% of BF
3
·Et
2
O and then de-
literature,
a plausible reaction mechanism is proposed as
formylated to afford the desired compound (2l) in 76% yield. 2l
underwent demethylation and cyclodehydration reactions in the
presence of 48% HBr in acetic acid to give stemofuran A in ex-
cellent yield (94%). The spectral data of 3l are identical with
shown in Scheme 2, which includes: i) The chalcone epox-
ides A undergoes smooth Meinwald rearrangement reaction
3 2
with BF ·Et O to give β−ketoaldehyde B. ii) Reaction of
β
−Ketoaldehyde B with 1,2-diaminoethane gives the inter-
1
4b
those reported in the literature.
Similarly, 4-(5-bromo-3-
mediate C, which is possibly converted to intermediate D.
The intermediate D undergoes a [3,3]-sigmatropic rearrange-
ment type rearrangement produces the corresponding deoxy-
benzoin E. iii) Deoxybenzoin E is demethylated to form 2-(2-
hydroxyphenyl)-1-phenylethanone F, which is cyclized to
give the intermediate G, subsequent dehydrated of intermedi-
ate G form the desired 2-arylbenzo[b]furan.
methylbenzofuran2-yl)-phenol (4m) was synthesized in 64%
overall yield. The readily available 2-methoxychalcone epoxide
(
1m) was converted into the corresponding deoxybenzoin (2m)
by the sequence of Meerwein rearrangement, deformylation in
1% yield. The reaction of 2m with methyl iodide in the pres-
7
ence of potassium tert-butoxide in THF gave the compound 3m
in 100% yield. Compound 3m was then treated with 48% HBr
in acetic acid under reflux to give 4-(5-bromo-3-
methylbenzofuran2-yl)-phenol (4m) in 90% yield. The proce-
Table 3. Synthesis of 2-arylbenzo[b]furan from 2-methoxychalcone epoxide.
a
Entry
1
R
1
R
2
Starting material
Deoxybenzoins
Yield (%)
72
Benzofurans
Yield (%)
H
H
H
H
H
H
H
H
H
4-OCH
3-OCH
2-Br
1a
2a
3a
100
2
3
4
5
6
7
8
3
3
1b
1c
1d
1e
1f
2b
2c
2d
2e
2f
73
78
76
74
69
77
74
3b
3c
3d
3e
3f
98
95
100
96
3-Br
4-Br
98
4-I
1g
1h
2g
2h
3g
3h
96
4-Me
100
2
-
9
H
1i
1j
2i
2j
81
71
75
3i
3j
87
93
92
thiophyl
1
1
0
1
Br
Br
H
4-OCH
3
1k
2k
3k
a
Isolated yields.

ACCEPTED MANUSCRIPT
4
Tetrahedron
R3
R3
reagents used are readily available, the protocols are simple to
R2
R1
R2
R1
carry out and not involving metal catalysts. This methodology
will be a valuable addition to the existing methods in the field of
2-arylbenzo[b]furan synthesis.
O
(a)
X
X
O
O
O
O
4. Experimental
1
3
2
1
3
2
1
l: X=H, R =R =OCH3, R =H
2l: X=H, R =R =OCH3, R =H
4.1. General methods
1
3
2
1
3
2
1
m: X=Br,R =R =H, R =OCH
2m: X=Br,R =R =H, R =OCH
3
3
All reagents were purchased from commercial sources and
1
13
O
used without treatment. H and C NMR spectra were recorded
at 400 and 100 MHz, respectively, using TMS as the internal
standard. HRMS were recorded on a Bruker micrOTOF II spec-
trometer (ESI ionization).
2l
(
b)
Br
(c)
OH
OH
2m
O
O
3
m
4
.2. General Procedure for Synthesis of 2-
O
(b)
methoxydeoxybenzoins
Stemofuran A
To a solution of 2 mmol of the chalcone epoxide in CH
2
Cl
2
Br
.
(
10 mL) was added 2 mol% of BF
3
Et
2
O at 25 °C. The mixture
OH
was stirred for 5 min, then 1, 2-diaminoethane (120 mg, 2 mmol)
was added in one portion. The reaction mixture was stirred at 25
C until TLC indicated complete (about 5 min). The mixture was
O
4
m
°
poured into ice water. The organic phase was separated and the
water phase was extracted with dichloromethane for three times
(3×10 mL). The combined organic phases were dried over anhy-
drous Na SO . Removal of the solvent in vacuo, and the residue
was column chromatographed over silica gel to give pure deoxy-
benzoins.
Scheme 1. Synthesis of stemofuran A and 4-(5-bromo-3-methylbenzo-
furan-2-yl)phenol. Reagents and conditions: (a) 1) 2 mol% BF ·Et O, DCM,
min; 2) 1,2-diaminoethane, 5min (76% yield for 2l; 71% yield for 2m); (b)
8% HBr-AcOH, reflux, 8h (94% yield for stemofuran A; 90% yield for 4m);
3
2
5
4
2
4
(
c) t-BuOK, CH
3
I, THF, 0°C, 2h (100% yield for 3m).
NH2
H2N
NH2
NH2
4.2.1. 2-(2-Methoxyphenyl)-1-phenylethanone (2a). The title
compound was prepared according to the general procedure. The
product was obtained as white solid (324 mg, 72% yield, mp 59-
O
BF3
O
O-
O
1
5
1
O
O
6
1 °C; [Lit. 60-61 °C] ); H NMR (400 MHz, CDCl
3
) δ 8.04 (d,
O
O
J = 7.3 Hz, 2H), 7.53 (d, J = 7.3 Hz, 1H), 7.48-7.42 (m, 2H),
O
7
4
1
1
.28-7.22 (m, 1H), 7.17 (d, J = 7.3 Hz, 1 H), 6.95-6.86 (m, 2H),
.27 (s, 2H), 3.78 (s, 3H); C NMR (100 MHz, CDCl ) δ 197.9,
3
57.1, 136.9, 132.8, 130.9, 128.4 (2C), 128.3 (2C), 128.3, 123.6,
20.5, 110.5, 55.3, 39.9.
A
C
B
13
NH2
HN
O
O
H+
transfer
O
H
O
4.2.2.
2b). The title compound was prepared according to the general
procedure. The product was obtained as yellow solid (373 mg,
2-(2-Methoxyphenyl)-1-(4-methoxyphenyl)ethanone
HBr
(
O
OH
O
16
1
7
3% yield, mp 88–90 °C; [Lit. 89.5 °C] ); H NMR (400 MHz,
CDCl
8.01 (d, J = 8.8 Hz, 2H), 7.27-7.19 (m, 1H), 7.17 (d, J
7.3 Hz, 1H), 6.94-6.85 (m, 4H), 4.22 (s, 2H), 3.84 (s, 3H), 3.78
CH3
D
E
F
3
) δ
=
1
3
(
s, 3H); C NMR (100 MHz, CDCl
3
) δ 196.6, 163.4, 157.2,
H
H
H
131.0, 130.7 (2C), 130.1, 128.3, 124.1, 120.7, 113.7 (2C), 110.6,
H+
5
5.4, 55.3, 39.6.
OH2
O
O
4.2.3. 2-(2-Methoxyphenyl)-1-(3-methoxyphenyl)ethanone
(
2c) The title compound was prepared according to the general
G
procedure. The product was obtained as a colourless oil (400 mg,
Scheme 2. Possible reaction pathway
1
7
1
7
4
8% yield); H NMR (400 MHz, CDCl ) δ 7.62 (d, J = 7.5 Hz,
3
H), 7.55 (s, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.26-7.20 (m, 1H),
.16 (d, J = 7.0 Hz, 1H), 7.09-7.04 (m, 1H), 6.93-6.83 (m, 2H),
3. Conclusions
1
3
.24 (s, 2H), 3.80 (s, 3H), 3.75 (s, 3H); C NMR (100 MHz,
In conclusion, we developed a facile synthetic strategy for the
3
CDCl ) δ
197.6, 159.6, 157.0, 138.2, 130.8, 129.4, 128.2, 123.6,
synthesis of 2-arylbenzo[b]furan using commercially available,
120.9, 120.5, 119.2, 112.6, 110.4, 55.2, 55.2, 39.9.
suitably functionalized 2-methoxychalcone epoxides. Catalyzed
.
4.2.4. 1-(2-Bromophenyl)-2-(2-methoxyphenyl)ethanone (2d).
The title compound was prepared according to the general pro-
by 2 mol% of BF Et O, 2-methoxychalcone epoxides went through
3
2
the Meerwein rearrangement, followed by deformylation in one-pot
to successfully afforded 2-methoxydeoxybenzoins. Afterwards, 2-
arylbenzo[b]furan were obtained in high yields (87%-100%) by
intramolecular cyclodehydration of 2-methoxydeoxybenzoin with
cedure. The product was obtained as colorless oil ( 463 mg, 76%
1
yield); H NMR (400 MHz, CDCl
3
)
δ
7.57 (d, J = 8.0 Hz, 1H),
7
3
2
1
1
.41 (dd, J = 1.5, 7.5 Hz, 1H), 7.34-7.29 (m, 1H), 7.27-7.20 (m,
H), 6.92 (t, J = 7.5 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 4.20 (s,
4
8% HBr. The effectiveness of the protocol was demonstrated by
1
3
H), 3.75 (s, 3H); C NMR (100 MHz, CDCl3)
δ 201.7, 157.3,
the synthesis of stemofuran A and the key intermediate of
eupomatenoid 6, 4-(5-bromo-3-methylbenzofuran2-yl)-phenol.
The present method has several advantages including that the
41.8, 133.5, 131.4, 131.2, 128.7, 128.6, 127.1, 123.1, 120.6,
18.7, 110.4, 55.3, 44.4.

ACCEPTED MANUSCRIPT
5
4.2.5. 1-(3-Bromophenyl)-2-(2-methoxyphenyl)ethanone (2e).
CDCl3)
δ 8.03-7.96 (m, 2H), 7.36-7.27 (m, 2H), 6.93 (d, J =
The title compound was prepared according to the general pro-
8.5 Hz, 2H), 6.74 (d, J = 8.5 Hz, 1H), 4.18 (s, 2H), 3.86 (s, 3H),
3.75 (s, 3H); C NMR (100 MHz , CDCl3) δ 195.6, 163.5,
1
3
cedure. The product was obtained as white solid (451 mg, 74%
1
yield, mp 78 -79 °C); H NMR (400 MHz, CDCl
3
)
δ
8.18 (s,
156.4, 133.6, 130.9, 130.6 (2C), 129.8, 126.3, 113.7 (2C), 112.7,
112.2, 55.6, 55.4, 39.2. HRMS (ESI) calcd for C H BrO Na
1
H), 7.93 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.33-7.21
1
6
15
3
+
(
m, 2H), 7.16 (d, J = 7.0 Hz, 1H), 6.94-6.85 (m, 2H), 4.22 (s,
[M+Na] 357.0102, found 357.0110.
.3. General Procedure for Synthesis of 2-benzo[b]furan.
To a stirred solution of 2a-2k (1 mmol) in 48% HBr (4 mL)
1
3
2
1
1
H), 3.78 (s, 3H); C NMR (100 MHz, CDCl
38.6, 135.6, 131.5, 130.9, 130.0, 128.5, 126.9, 123.1, 122.7,
20.6, 110.6, 55.3, 39.9. HRMS (ESI) calcd for C15 Na
3
) δ 196.5, 157.0,
4
H13BrO
2
+
[
M+Na] 326.9997, found 326.9984.
was added AcOH (5 mL) and the mixture was heated to reflux.
The reaction was stirred until TLC indicated complete (about
4.2.6. 1-(4-Bromophenyl)-2-(2-methoxyphenyl)ethanone (2f).
8h). The reaction mixture was cooled to room temperature,
The title compound was prepared according to the general pro-
AcOH was removed under reduced pressure and the aqueous
part was extracted with extracted with EtOAc (2 × 100 mL),
washed with brine, dried (Na SO ), and concentrated to obtain
2 4
corresponding pure benzo[b]furans. Pure products of 3a, 3b, 3c,
3d, 3e, 3f, and 3h were obtained by simple extraction. The yields
of 3g, 3i, 3j, 3k, were determined after silica gel column chroma-
tography (petroleum ether / EtOAc).
cedure. The product was obtained as white solid (421 mg, 69%
1
yield, mp 90 -91 °C); H NMR (400 MHz, CDCl
3
)
δ
7.88 (d, J =
8.5 Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 7.28-7.21 (m, 1H), 7.16 (d,
J = 7.3 Hz, 1H), 6.95-6.84 (m, 2H), 4.22 (s, 2H), 3.77 (s, 3H);
13
C NMR (100 MHz, CDCl
3
) δ 197.1, 157.1, 135.7, 131.8, 131.0
(
2C), 130.0 (2C), 128.6, 128.0, 123.4, 120.7, 110.6, 55.4, 40.0.
+
HRMS (ESI) calcd for C15
found 326.9984.
2
H13BrO Na [M+Na] 326.9997, found
4.3.1. 2-Phenylbenzofuran (3a). The title compound was pre-
pared according to the general procedure. The product was ob-
tained as white solid (194 mg, 100% yield, mp 117-119 °C; [Lit.
4
.2.7 1-(4-Iodophenyl)-2-(2-methoxyphenyl)ethanone (2g).
The title compound was prepared according to the general pro-
cedure. The product was obtained as white solid (542 mg, 77%
yield, mp 118-120 °C); H NMR (400 MHz, CDCl )
17
1
119 °C] ); H NMR (400 MHz, CDCl
3
) δ 7.83 (d, J = 8.0 Hz,
1
2H), 7.54 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.43-7.36
δ 7.82-7.78
3
13
(
m, 2H), 7.34-7.15 (m, 3H), 6.96 (s, 1H); C NMR (100 MHz,
CDCl3) 155.9, 154.9, 130.4, 129.2, 128.7 (2C), 128.5, 124.9
2C), 124.2, 122.9, 120.9, 111.1, 101.3.
(
m, 2H), 7.74-7.71 (m, 2H), 7.28-7.22 (m, 1H), 7.15 (d, J = 7.3
13
δ
Hz, 1H), 6.94-6.85 (m, 2H), 4.21 (s, 2H), 3.77 (s, 3H); C NMR
(
(
100 MHz, CDCl
3
)
δ
197.3, 157.0, 137.8(2C), 136.2, 130.9,
1
29.8(2C), 128.5, 123.3, 120.7, 110.6, 100.7, 55.3, 39.9. HRMS
4
.3.2. 4-(Benzofuran-2-yl)phenol (3b). The title compound was
+
(
ESI) calcd for C15
2
H13IO Na [M+Na] 374.9858, found 374.9841.
prepared according to the general procedure. The product was
obtained as white solid (206 mg, 98% yield, mp 194-195 °C;
4.2.8. 2-(2-Methoxyphenyl)-1-(p-tolyl)ethanone (2h). The title
18
1
[
1
Lit. 194-195 °C ] ); H NMR (400 MHz, DMSO-d
H), 7.76 (d, J = 8.5 Hz, 2H), 7.58 (t, J = 6.8 Hz, 2H), 7.24
(quin, J = 7.1 Hz, 2H), 7.14 (s, 1 H), 6.92 (d, J = 8.5 Hz, 2H);
6
) δ 9.90 (s,
compound was prepared according to the general procedure. The
product was obtained as white solid (355 mg, 74% yield, mp 44-
1
4
7
2
1
5
2
5 °C); H NMR (400 MHz, CDCl
.27-7.12 (m, 4H), 6.93-6.82 (m, 2H), 4.23 (s, 2H), 3.75 (s, 3H),
.37 (s, 3H); C NMR (100 MHz, CDCl
34.6, 131.0, 129.2 (2C), 128.6 (2C), 128.3, 124.0, 120.7, 110.6,
5.4, 39.9, 21.7. HRMS (ESI) calcd for C16
63.1048, found 263.1039.
3
)
δ
7.92 (d, J = 8.0 Hz, 2H),
13
C NMR (100 MHz, DMSO-d6)
δ 158.3, 155.9, 153.9, 129.2,
1
3
126.4 (2C), 123.7, 123.0, 120.9, 120.6, 115.9 (2C), 110.8, 99.3.
3
) δ 197.6, 157.3, 143.6,
4.3.3. 3-(Benzofuran-2-yl)phenol (3c). The title compound was
prepared according to the general procedure. The product was
obtained as white solid (252 mg, 95% yield, mp 131-133 °C;
+
16 2
H O Na [M+Na]
1
9
1
[
Lit.131-132 °C] ); H NMR (400 MHz, DMSO-d
6
) δ 9.71 (s,
4.2.9. 2-(2-Methoxyphenyl)-1-(thiophen-2-yl)ethanone (2i).
1
H), 7.63 (dd, J = 7.8, 12.3 Hz, 2H), 7.39-7.23 (m, 6H), 6.82 (d,
The title compound was prepared according to the general pro-
cedure. The product was obtained as white solid (376 mg, 81%
yield, mp 75-76 °C); H NMR (400 MHz, CDCl )
13
J = 7.8 Hz, 1H); C NMR (100 MHz, DMSO-d
154.1, 130.9, 130.2, 128.8, 124.5, 123.2, 121.1, 116.0, 115.7,
11.2, 111.1, 101.9.
6
) δ 157.8, 155.3,
1
δ 7.78 (d, J =
3
1
3.8 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.27-7.19 (m, 2H), 7.08 (t,
J = 4.4 Hz, 1H), 6.94-6.84 (m, 2H), 4.19 (s, 2H), 3.77 (s, 3H);
4.3.4. 2-(2-Bromophenyl)benzofuran (3d). The title compound
13
C NMR (100 MHz, CDCl
3
)
δ
190.7, 157.1, 144.1, 133.3,
was prepared according to the general procedure. The product
1
1
32.2, 130.9, 128.4, 127.9, 123.3, 120.6, 110.6, 55.3, 40.5.
was obtained as colorless liquid (271 mg, 100% yield); H NMR
+
HRMS (ESI) calcd for C13
H
12
O
2
SNa [M+Na] 255.0456, found
3
(400 MHz, CDCl ) δ 7.94 (dd, J = 1.0, 8.0 Hz, 1H), 7.67 (d, J =
255.0445.
8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54-7.49 (m, 2H), 7.37 (t,
J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.26-7.20 (m, 1H),
4
.2.10. 2-(5-Bromo-2-methoxyphenyl)-1-phenylethanone (2j).
13
7
1
1
.18-7.12 (m, 1H); C NMR (100 MHz, CDCl3)
34.2, 131.0, 129.7, 129.3, 128.8, 127.4, 124.8, 122.9, 121.4,
20.7, 111.1, 107.0.
δ
154.2, 153.1,
The title compound was prepared according to the general pro-
cedure. The product was obtained as white solid (433 mg, 71%
yield, mp 68-69 °C); H NMR (400 MHz, CDCl
1
3
)
δ
8.02 (d, J =
7
2
1
1
1
.3 Hz, 2H), 7.59-7.53 (m, 1H), 7.50-7.43 (m, 1H), 7.34 (dd, J =
4.3.5. 2-(3-Bromophenyl)benzofuran (3e). The title compound
was prepared according to the general procedure. The product
was obtained as white solid (261 mg, 96% yield, mp 84-85 °C;
.3, 8.5 Hz, 1H), 7.28 (d, J = 2.3 Hz, 1H), 6.74 (d, J = 8.5 Hz,
13
3
H), 4.23 (s, 2H), 3.74 (s, 3H); C NMR (100 MHz, CDCl ) δ
2
0
1
[
Lit. 85 °C ] ); H NMR (400 MHz, CDCl )
δ
8.01-7.96 (m,
97.0, 156.4, 136.7, 133.7, 133.1, 131.0, 128.5 (2C), 128.3 (2C),
3
1
H), 7.74 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 7.3 Hz, 1H), 7.50 (d, J
25.9, 112.7, 112.2, 55.6, 39.6. HRMS (ESI) calcd for
+
=
8.0 Hz, 1H), 7.46-7.42 (m, 1H), 7.32-7.19 (m, 3H), 6.99 (s,
13
C H BrO Na[M+Na] 326.9997, found 326.9984.
1
5
13
2
1
1
1
3
H); C NMR (100 MHz ,CDCl ) δ 154.9, 154.1, 132.4, 131.3,
30.3, 128.9, 127.8, 124.7, 123.4, 123.1, 122.9, 121.1, 111.2,
02.4.
4.2.11. 2-(5-Bromo-2-methoxyphenyl)-1-(4-methoxyphenyl)-
ethanone (2k). The title compound was prepared according to
the genera procedure. The product was obtained as white solid
1
(
500 mg, 75% yield, mp 117-118 °C); H NMR (400 MHz,

ACCEPTED MANUSCRIPT
6
Tetrahedron
4.3.5. 2-(4-Bromophenyl)benzofuran (3f). The title com-
4.4.2. Stemofuran A. The title compound was prepared accord-
pound was prepared according to the general procedure. The
product was obtained as white solid (265 mg, 98% yield, mp
ing to the general procedure. The product was obtained as white
9
solid (212 mg, 94% yield, mp 181-182 °C [Lit. 182-183 °C] );
2
1
1
1
1
7
1
49-150 °C; [Lit. 149-150 °C] ); H NMR (400 MHz, CDCl
.71 (d, J = 8.5 Hz, 2H), 7.59-7.53 (m, 3H), 7.50 (d, J = 8.0 Hz,
H), 7.32-7.26 (m, 1H), 7.25-7.20 (m, 1H), 7.00 (s, 1H);
154.9, 154.8, 131.9 (2C), 129.4,
29.0, 126.3 (2C), 124.6, 123.1, 122.5, 121.0, 111.2, 101.8.
3
)
δ
6
H NMR (400 MHz, Acetone-d ) δ 8.43 (s, 2 H), 7.63 (dd, J =
0.8, 8.3 Hz, 1 H), 7.54 (dd, J = 0.8, 8.3 Hz, 1 H), 7.30 (ddd, J =
1.4, 7.2, 8.3 Hz, 1 H), 7.24 (ddd, J = 1.4, 7.2, 8.3 Hz, 1 H), 7.16
(d, J = 1.0 Hz, 1 H), 6.94 (d, J = 2.0 Hz, 2 H), 6.42 (t, J = 2.0 Hz,
1
3
C
3
NMR (100 MHz, CDCl ) δ
1
1
3
1 H); C NMR (100 MHz, Acetone-d
1
1
6
)
δ
160.2(2C), 157.2,
55.9, 133.4, 130.5, 125.6, 124.2, 122.2, 112.1, 104.7(2C),
04.5, 102.7.
4.3.7. 2-(4-Iodophenyl)benzofuran (3g). The title compound
was prepared according to the general procedure. The product
was obtained as white solid (361 mg, 96% yield, mp 180-181 °C;
H NMR (400 MHz, CDCl ) δ 7.76 (d, J = 8.3 Hz, 2H), 7.57 (d,
3
4.5. Synthesis of 4-(5-bromo-3-methylbenzofuran-2-yl)phenol
1
4
.5.1. 2-(5-Bromo-2-methoxyphenyl)-1-(4-methoxyphenyl)-
ethanone (2m). The title compound was prepared according to
J = 8.3 Hz, 3H), 7.50 (d, J = 8.3 Hz, 1H), 7.32-7.26 (m, 1H),
1
3
7
1
1
.25-7.20 (m, 1H), 7.01 (s, 1H); C NMR (100 MHz, CDCl
54.9, 154.8, 137.9 (2C), 129.9, 129.0, 126.4 (2C), 124.6, 123.1,
21.0, 111.2, 101.9, 94.1. HRMS (ESI) calcd for C14
3
) δ
the general procedure. The product was obtained as white solid (
1
4
76 mg, 75% yield, mp 117-118 °C); H NMR (400 MHz,
H
10IO
+
CDCl3)
δ 8.03-7.96 (m, 2H), 7.36-7.27 (m, 2H), 6.93 (d, J = 8.5
[
M+H] 320.9776, found 320.9761.
Hz, 2H), 6.74 (d, J = 8.5 Hz, 1H), 4.18 (s, 2H), 3.86 (s, 3H), 3.75
1
3
4.3.8. 2-(p-Tolyl)benzofuran (3h). The title compound was
(s, 3H); C NMR (100 MHz, CDCl3) δ 195.6, 163.5, 156.4,
prepared according to the general procedure. The product was
obtained as white solid (208 mg, 100% yield, mp 125-126 °C;
133.6, 130.9, 130.6 (2C), 129.8, 126.3, 113.7 (2C), 112.7, 112.2,
+
55.6, 55.4, 39.2. HRMS (ESI) calcd for C H BrO Na [M+Na]
1
6
15
3
22
1
[
Lit. 127-128.5 °C] ); H NMR (400 MHz, CDCl
3
)
δ
7.75 (d, J
357.0102, found 357.0110.
=
8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H),
1
3
4.5.2. 2-(5-Bromo-2-methoxyphenyl)-1-(4-methoxyphenyl)-
pro-pan-1-one (3m). To a suspension of potassium tert-butoxide
7
.29-7.18 (m, 4H), 6.94 (s, 1H), 2.38 (s, 3H); C NMR (100
MHz, CDCl 156.2, 154.8, 138.6, 129.5 (2C), 129.3, 127.7,
24.9 (2C), 124.0, 122.8, 120.7, 111.1, 100.5, 21.4.
3
) δ
(
161 mg, 1.44 mmol) in tetrahydrofuran (THF) was added a so-
1
lution of deoxybenzoin (2m) (400 mg, 1.2 mmol) in THF drop-
wise at 0 °C. Iodomethane (170 mg, 1.44 mmol) solution in THF
(2 mL) was added gradually. The reaction was then allowed to
warm to 25 °C. After 2 h of stirring at 25 °C, the reaction mix-
ture was slowly quenched with 2 N HCl and diluted with ethyl
4.3.9. 2-(Thiophen-2-yl)benzofuran (3i). The title compound
was prepared according to the general procedure. The product
was obtained as white solid (174 mg, 87% yield, mp 92-94 °C;
2
2
1
[
Lit. 94.1-95.1 °C] ); H NMR (400 MHz, CDCl
3
)
δ
7.53 (d, J =
7
7
.3 Hz, 1H), 7.51-7.45 (m, 2H), 7.32 (d, J = 4.8 Hz, 1H), 7.29-
acetate. 3m were obtained by simple extraction (colourless oil,
1
3
1
.18 (m, 2H), 7.08 (t, J = 4.3 Hz, 1H), 6.85 (s, 1H); C NMR
154.6, 151.3, 133.3, 129.1, 127.8, 125.8,
416 mg, 100% yield); H NMR (400 MHz, CDCl )
δ
7.97-7.90
3
(
100 MHz, CDCl
3
)
δ
(m, 2H), 7.28-7.22 (m, 2H), 6.89-6.82 (m, 2H), 6.72 (d, J = 9.3
Hz, 1H), 5.01 (d, J = 6.8 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 1.42
124.6, 124.3, 123.1, 120.7, 111.0, 101.1.
1
3
(
1
5
d, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl
3
)
δ
199.2, 163.2,
54.9, 132.6, 130.8 (2C), 130.7 (2C), 130.5, 113.6, 113.3, 112.4,
5.7, 55.3, 39.5, 17.6; HRMS (ESI) calcd for C H BrO Na
4.3.10. 5-Bromo-2-phenylbenzofuran (3j). The title compound
was prepared according to the general procedure. The product
was obtained as white solid (255 mg, 93% yield, mp 156-158 °C;
1
7
17
3
+
2
3
1
[M+Na] 371.0259, found 371.0244.
[
Lit.156-157 °C] ); H NMR (400 MHz, CDCl
3
)
δ
7.83 (d, J =
7
6
1
1
.5 Hz, 2H), 7.68 (s, 1H), 7.47-7.41 (m, 2H), 7.40-7.33 (m, 3H),
.93 (s, 1H); C NMR (100 MHz, CDCl ) δ 157.2, 153.6, 131.2,
3
29.9 (2C), 129.0, 128.8, 127.1, 125.0, 123.5, 116.0, 112.6,
00.6.
4.5.3. 4-(5-Bromo-3-methylbenzofuran-2-yl)phenol (4m). The
title compound was prepared according to the general procedure.
The product was obtained as white solid (272 mg, 90% yield,
1
3
9
1
mp155-156°C; [Lit. 157-159 °C] ); H NMR (400 MHz, DMSO-
d ) 10.02 (s, 1H), 7.93 (d, J = 1.5 Hz, 1H), 7.76 (d, J = 8.5 Hz,
H), 7.63 (d, J = 8.5 Hz, 1H), 7.52 (dd, J = 1.5, 8.5 Hz, 1H), 7.07
δ
6
4.3.11. 4-(5-Bromobenzofuran-2-yl)phenol (3k). The title
2
compound was prepared according to the general procedure. The
product was obtained as white solid (266 mg, 92% yield, mp
1
3
(
d, J = 8.5 Hz, 2H), 3.49 (s, 3H); C NMR (100 MHz, DMSO-
d ) 158.0, 152.1, 151.6, 133.2, 128.1 (2C), 126.3, 121.7, 121.0,
15.8, 114.9 (2C), 112.5, 108.5, 8.9.
24
1
6
δ
1
220-222 °C; [Lit. 221-223 °C] ); H NMR (400 MHz, DMSO-
d ) δ
6
9.93 (br. s, 1H), 7.77 (d, J = 2.0 Hz, 1H), 7.74 (d, J = 8.5
Hz, 2H), 7.54 (d, J = 8.5 Hz, 1H), 7.37 (dd, J = 2.0, 8.5 Hz, 1H),
1
3
Acknowledgments
7
.13 (s, 1H), 6.90 (d, J = 8.5 Hz, 2H); C NMR (100 MHz,
DMSO-d 158.7, 157.4, 152.8, 131.5, 126.6 (2C), 126.2,
22.9, 120.3, 115.9 (2C), 115.3, 112.8, 98.8.
6
) δ
This work was supported by Shanghai Science and Technology
council (No. 11142200702, 12142200802 and 13142200902).
We also thank “Lab of Organic Functional Molecules, THE
SINO-FRENCH INSTITUTE OF ECNU” for supports.
1
4.4. Total synthesis of Stemofuran A.
4.4.1. 1-(3,5-Dimethoxyphenyl)-2-(2-methoxyphenyl)ethan-
one (2l). The title compound was prepared according to the gen-
eral procedure. The product was obtained as colorless liquid (435
Supplementary Material
1
mg, 76% yield, mp106-107 °C); H NMR (400 MHz, CDCl
3
)
δ
7
.24 (s, 1 H), 7.20-7.15 (m, J = 2.3 Hz, 2H), 6.94-6.86 (m, 2H),
1
3
Supplementary data associated with this article can be found
in online version
6.64-6.62 (m, 1H), 4.23 (s, 2H), 3.80 (s, 6H), 3.78 (s, 3H);
C
NMR (100 MHz, CDCl
3
)
δ
197.6, 160.7 (2C), 157.0, 138.8,
30.9, 128.3, 123.6, 120.6, 110.5, 106.2 (2C), 105.3, 55.5(2C)+,
5.3, 40.0. HRMS (ESI) calcd for C H O Na [M+Na]
1
5
3
References and notes
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18.
Zhang, P; Yang, Y. W.; Huang, W. H.; Ma, Z.; Shen, Z. R.;
Zheng, X. L. Chem. Pharm. Bull. 2012, 60, 270-274.
(a) Liu, J.; Chen, W.; Ji, Y.; Wanga, L. Adv. Synth. Catal. 2012,
19. Cummins et al. Tetrahedron. 1963, 19, 499-508.
20. Hellwinkel, D.; Goeke, K. Synthesis, 1995, 9, 1135-1141.
21. Yang, J. G.; Chen, D. B.; Shen, G. D. Synth. Commun. 2013, 43,
837-847.
22. Liao, L. Y.; Shen, G.; Zhang, X.; Duan, X. F. Green Chemistry.
2012, 14, 695-701.
23. Liu, J.; Chen, W.; Wang, L.; Ji, Y. Adv. Synth Catal. 2012, 354,
1585-1592.
24. Dann, O.; Ruff, J.; Wolff, H. P.; Griessmeier, H. L. Justus Liebigs
Ann Chem. 1984, 409-425.
3
54, 1585-1592. (b) Leibeling, M.; Pawliczek, M.; Kratzert, D.;
Stalke, D.; Werz, D. B. Org. Lett. 2012, 14, 346-349. (c) Saha, D.;
Dey, R.; Ranu, B. C. Eur. J. Org. Chem. 2010, 31, 6067-6071. (d)
Zanardi, A.; Mata, J. A.; Peris, E. Organometallic. 2009, 28,
4
335-4339. (e) Lingam, V. S.; Vinodkumar, R.; Mukkanti, K.;
Thomas, A.; Gopalan, B. Tetrahedron Lett. 2008, 49, 4260-4264.
f) Csékei, M.; Novak, Z.; Kotschy. A. Tetrahedron. 2008, 64,
992-8996. (g) Fiandanese, V.; Bottalico,D. G.; Marchese, A. P.
(
8
Tetrahedron. 2008, 64, 53-60. (h) Bernini, R.; Cacchi, S.; Salve,
H. D.; Fabrizi, G. Synthesis. 2007, 6, 873-882. (i) Bates, C. G.;
Saejueng, P.; Murphy, J. M.; Venkataraman, D. Org. Lett. 2002,

ACCEPTED MANUSCRIPT
Supporting Information
An efficient approach to construct 2-arylbenzo[b]furans from
2
-methoxychalcone epoxides
Libo Ruan, Min Shi, Shiwei Mao, Lifang Yu, Fan Yang , Jie Tang

Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug
Development, East China Normal University, Shanghai 200062, China
Contents
1
1
1
1
13
H NMR and C NMR spectra of product 2a-2k……………………………………..2-24
13
H NMR and C NMR spectra of product 3a-3k…………………………………….25-45
13
H NMR and C NMR spectra of product Stemofuran A…………………………..46-51
13
H NMR and C NMR spectra of product 1m-4m………………………………….52-59
HRMS for new compounds…………………………………………………………….60-71

Corresponding author. Tel.: +86-21-62232764; E-mail: fyang@chem.ecnu.edu.cn; jtang@chem.ecnu.edu.cn

ACCEPTED MANUSCRIPT
13/8/2013 P2ꢀ20ꢀ2ꢁ
Acquisition iꢀmꢁsmcꢂ 3.ꢁ846
Coꢀꢀmnt
Datm
10PMa20131ꢁꢀ03ꢀ28
Datmꢃtaꢀꢄ
10PMa20131ꢁꢀ03ꢀ28
Filmꢅaꢀm
Origin
Eꢀ\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ30\1\Asꢊ
Frmqumncyꢁ(MHꢂ
Ownmr
400.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
16
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
root
ꢇointsCount
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
32768
2457.3428
zg30
Rmcmivmrꢈain
6ꢁ.ꢁ1
8223.68
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢊ
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
8223.43
mꢀꢄmraturmꢁꢉmgrmmCꢂ 26.275
1
H NMR (400MHz ,CHLOROFORM-d) d = 8.04 (d, J = 7.3 Hz, 2 H), 7.53 (d, J = 7.3 Hz, 1 H), 7.48 - 7.42 (m, 2 H), 7.28 - 7.22 (m, 1 H), 7.17 (d, J = 7.3 Hz,
1
H), 6.95 - 6.86 (m, 2 H), 4.27 (s, 2 H), 3.78 (s, 3 H)
RLB-Fu-30.001.esp
M02 M04
TMS
M01
M03M05M06
M07
M08
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
O
O
2
a
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
-0.5
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/8/2013 P3ꢀ13ꢀ0ꢁ
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3ꢁ31
Coꢀꢀmnt
Datm
0ꢁꢂAu20131ꢃꢀ1ꢄꢀ28
0ꢁꢂAu20131ꢃꢀ1ꢄꢀ28
Filmꢅaꢀm
Eꢀ\????????\????\?????Pꢂꢅꢅ\ꢆꢇꢈꢉꢊꢋꢉ1ꢃ3\1\sꢌꢍ
Frmqumncyꢁ(MHꢂ
Ownmr
100.ꢁ1
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
2ꢄꢁ
Origin
ꢅpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
327ꢁ8
root
ꢇointsCount
327ꢁ8
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zupu30
STꢂNDꢂꢆD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
189.81
2ꢃ037.73
2ꢃ038.ꢃꢁ
ꢃolvmnt
CHꢇOꢆOꢊOꢆPꢉꢍ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
100ꢃꢁ.ꢁꢃꢁꢄ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 2ꢄ.ꢃ8ꢃ
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 197.9, 157.1, 136.9, 132.8, 130.9, 128.4, 128.3, 128.3, 123.6, 120.5, 110.5, 55.3, 39.9
RLB-FU-143.001.ESP
M05
M06
M12
M03
M07 M10
CHLOROFORM-d
M01
M02
M04M08M09
M11
M13
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
O
O
2a
200
192
184
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
31/5/2013 Pꢀ81ꢁ810
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.9ꢀꢁ6
Coꢀꢀmnt
Datm
31PMa201315800816
31PMa201315800816
Filmꢅaꢀm
Origin
E8\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ6ꢊ\1\Asꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
ꢁ00.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢊ6ꢀ
root
ꢇointsCount
32ꢊ6ꢀ
2ꢁ53.ꢁꢊ51
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
31.69
ꢀ223.6ꢀ
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
ꢀ223.ꢁ3
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.629
1
H NMR (400MHz ,CHLOROFORM-d) d = 8.01 (d, J = 8.8 Hz, 2 H), 7.27 - 7.19 (m, 1 H), 7.17 (d, J = 7.3 Hz, 1 H), 6.94 - 6.85 (m, 4 H), 4.22 (s, 2 H), 3.84
(
s, 3 H), 3.78 (s, 3 H)
RLB-FU-67.001.esp
M02 M04
M03
M07
M01
M05 M06
O
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
O
O
2
b
12
11
10
9
8
7
6
5
4
3
2
1
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
15/8/2013 P10ꢀ55ꢀ30
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
31PMa201316ꢀ38ꢀ2ꢁ
31PMa201316ꢀ38ꢀ2ꢁ
Filmꢅaꢀm
Eꢀ\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ6ꢊ\33\sꢋꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
256
Origin
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢊ68
root
ꢇointsCount
32ꢊ68
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢂNDꢂꢄD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
189.81
2ꢁ03ꢊ.ꢊ3
2ꢁ038.ꢁ6
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
10051.0ꢁ00
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.5ꢊꢊ
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 196.5, 163.3, 157.1, 130.9, 130.7, 130.0, 128.2, 124.0, 120.6, 113.6, 110.5, 55.4, 55.3, 39.5
RLB-FU-67.033.ESP
M07
M05
M04 M08
M06 M09
M12
M13
M10
M11
CHLOROFORM-d
M01
M02 M03
M14
O
O O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2
b
0
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
5/6/2013 Pꢀ8338::
Acquisition iꢀmꢁsmcꢂ
Filmꢅaꢀm
3.9ꢀ:6
Coꢀꢀmnt
Datm
05ꢁJu201316832800
Datmꢃtaꢀꢄ
05ꢁJu201316832800
E8\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇꢊ5\1\Asꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
:00.13
root
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
16
Origin
ꢃpect
19.91
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢊ6ꢀ
ꢇointsCount
32ꢊ6ꢀ
zg30
Rmcmivmrꢈain
ꢃꢄmctruꢀ yꢄm
ꢀ223.6ꢀ
ꢀ223.:3
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
2::2.ꢊ522
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.:ꢊ2
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.62 (d, J = 7.5 Hz, 1 H), 7.55 (s, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.26 - 7.20 (m, 1 H), 7.16 (d, J = 7.0 Hz, 1 H),
7
.09 - 7.04 (m, 1 H), 6.93 - 6.83 (m, 2 H), 4.24 (s, 2 H), 3.80 (s, 3 H), 3.75 (s, 3 H)
RLB-FU-75.001.esp
M04
M01 M03M06
M02 M05M07
M10
O
M08 M09
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
O
O
2c
0
12.0
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
15/8/2013 P11ꢀ0ꢁꢀ:8
Acquisition iꢀmꢁsmcꢂ
1.3631
Coꢀꢀmnt
Datm
05ꢂJu20131ꢃꢀ31ꢀ::
Datmꢃtaꢀꢄ
05ꢂJu2013
1ꢃꢀ31ꢀ::
Filmꢅaꢀm
Eꢀ\????????\????\?????Pꢄꢅꢅ\ꢆꢇꢈꢉꢊꢋꢉꢃ5\2\Asꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
root
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
ꢇulsmꢃmqumncm
1ꢁ2
Origin
ꢅpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢃ68
ꢇointsCount
32ꢃ68
zgpg30
100:1.503ꢁ
Rmcmivmrꢈain
ꢃꢄmctruꢀ yꢄm
18ꢁ.81
2:038.:6
2:03ꢃ.ꢃ3
ꢃolvmnt
CHꢇOꢆOꢊOꢆPꢉꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢄNDꢄꢆD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.ꢃꢃꢃ
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 197.6, 159.6, 157.0, 138.2, 130.8, 129.4, 128.2, 123.6, 120.9, 120.5, 119.2, 112.6, 110.4, 55.2, 55.2, 39.9
RLB-FU-75.002.ESP
M11
M09
M06 M08
M07 M10
M15
M14
M05
M03
M02
M12
M13
O
CHLOROFORM-d
M01
M04
M16
O
O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2c
0
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
4/6/2013 Pꢀ81ꢁ842
Acquisition iꢀmꢁsmcꢂ
Filmꢅaꢀm
3.ꢁꢀ46
Coꢀꢀmnt
Datm
04ꢂJu2013108:284ꢀ
Datmꢃtaꢀꢄ
04ꢂJu2013108:284ꢀ
E8\????????\????\?????Pꢃꢄꢄ\ꢅꢆꢇꢈꢉꢊꢈꢋ1\1\Asꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
400.13
root
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
16
Origin
ꢄpect
6ꢁ.ꢁ1
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢋ6ꢀ
ꢇointsCount
32ꢋ6ꢀ
zg30
Rmcmivmrꢈain
ꢃꢄmctruꢀ yꢄm
ꢀ223.6ꢀ
ꢀ223.43
ꢃolvmnt
CHꢆOꢅOꢉOꢅPꢈꢌ
24:ꢀ.1ꢀ41
STꢃNDꢃꢅD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 2:.22:
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.57 (d, J = 7.8 Hz, 1 H), 7.41 (dd, J = 1.5, 7.5 Hz, 1 H), 7.34 - 7.29 (m, 1 H), 7.27 - 7.20 (m, 3 H), 6.92 (t, J =
7
.4 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 1 H), 4.20 (s, 2 H), 3.75 (s, 3 H)
RLB-FU-71.001.esp
M04
M01M03 M05
Br
O
M02
M06
M07
M08
O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2d
0
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
5/6/2013 P2ꢀ50ꢀ36
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
05ꢁJu201311ꢀ12ꢀ00
05ꢁJu201311ꢀ12ꢀ00
Filmꢅaꢀm
Origin
Eꢀ\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇꢊ1\&\Asꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
256
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢊ68
root
ꢇointsCount
32ꢊ68
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
Rmcmivmrꢈain
189.81
2&03ꢊ.ꢊ3
2&038.&6
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
10060.3320
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.885
1
3
C NMR (101MHz ,CHLOROFORM-d) d = 201.7, 157.3, 141.8, 133.5, 131.4, 131.2, 128.7, 128.6, 127.1, 123.1, 120.6, 118.7, 110.4, 55.3, 44.4
RLB-FU-71.004.esp
M04 M09
M06
M05
M11
Br
M08M10
M07 M12 M13
M01
M02
M03
M14
M15
O
O
2d
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
220
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
-20
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
18/6/2013 P12ꢀ::ꢀ:1
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.98:6
Coꢀꢀmnt
Datm
18ꢁJu201310ꢀ16ꢀ32
18ꢁJu201310ꢀ16ꢀ32
Filmꢅaꢀm
Origin
Eꢀ\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ10ꢊ\1\sꢋꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
:00.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢊ68
root
ꢇointsCount
32ꢊ68
2:50.:30ꢊ
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
31.69
8223.68
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
8223.:3
mꢀꢄmraturmꢁꢉmgrmmCꢂ 28.086
1
H NMR (400MHz ,CHLOROFORM-d) d = 8.18 (s, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.33 - 7.21 (m, 2 H), 7.16 (d, J = 7.0 Hz, 1 H),
.94 - 6.85 (m, 2 H), 4.22 (s, 2 H), 3.78 (s, 3 H)
6
RLB-FU-107.001.esp
M02
M04 M06
Br
M01 M03 M05
M07 M08
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
O
O
2e
13
12
11
10
9
8
7
6
5
4
3
2
1
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/8/2013 P3ꢀ:1ꢀꢁ3
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
18ꢂJu201310ꢀ31ꢀ28
18ꢂJu201310ꢀ31ꢀ28
Filmꢅaꢀm
Eꢀ\????????\????\?????Pꢃꢄꢄ\ꢅꢆꢇꢈꢉꢊꢈ10ꢋ\2\sꢌꢍ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
2:6
Origin
ꢄpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢋ68
root
ꢇointsCount
32ꢋ68
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢃNDꢃꢅD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
189.81
2ꢁ03ꢋ.ꢋ3
2ꢁ038.ꢁ6
ꢃolvmnt
CHꢆOꢅOꢉOꢅPꢈꢍ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
100ꢁ9.:ꢋ32
mꢀꢄmraturmꢁꢉmgrmmCꢂ 28.ꢁ3ꢋ
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 196.5, 157.0, 138.6, 135.6, 131.5, 130.9, 130.0, 128.5, 126.9, 123.1, 122.7, 120.6, 110.6, 55.3, 39.9
RLB-FU-107.002.ESP
M09
M06
M05
Br
M12
M14
M03 M07 M10
M04 M08 M11
CHLOROFORM-d
M01
M02
M13
M15
O
O
2e
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
220
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
-20
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
31/5/2013 Pꢀ805825
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.9ꢀ46
Coꢀꢀmnt
Datm
31PMa20131485ꢀ80ꢀ
31PMa20131485ꢀ80ꢀ
Filmꢅaꢀm
Origin
E8\????????\????\?????Pꢁꢂꢂ\ꢃꢄꢅꢆꢇꢈꢆ66\1\Asꢉ
Frmqumncyꢁ(MHꢂ
Ownmr
400.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢂpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
3276ꢀ
root
ꢇointsCount
3276ꢀ
2454.5ꢀ20
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
31.69
ꢀ223.6ꢀ
ꢃolvmnt
CHꢄOꢃOꢇOꢃPꢆꢉ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢁNDꢁꢃD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
ꢀ223.43
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.629
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.88 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.28 - 7.21 (m, 1 H), 7.16 (d, J = 7.3 Hz, 1 H), 6.95 - 6.84 (m,
H), 4.22 (s, 2 H), 3.77 (s, 3 H)
2
RLB-FU-66.001.esp
M03 M05
TMS
M01M02 M04
M06 M07
Br
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
O
O
2
f
0
12
11
10
9
8
7
6
5
4
3
2
1
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
31/5/2013 Pꢀ81081ꢁ
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
bossbossꢂ
Datm
31Pꢂa20131ꢁ823812
31Pꢂa20131ꢁ823812
Filmꢅaꢀm
E8\????????\????\?????Pꢃss\ꢄꢅꢆꢇꢈꢉꢇ66\33\ꢊꢋꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
251
Origin
spect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢁ6ꢀ
root
ꢇointsCount
32ꢁ6ꢀ
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢃNDꢃꢄD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
1ꢀ9.ꢀ1
2403ꢁ.ꢁ3
2403ꢀ.46
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
10060.3320
mꢀꢄmraturmꢁꢉmgrmmCꢂ 25.42ꢀ
1
3
C NMR (101MHz ,CHLOROFORM-d) d = 197.1, 157.1, 135.7, 131.8, 131.0, 130.0, 128.6, 128.0, 123.4, 120.7, 110.6, 55.4, 40.0
RLB-FU-66.033.esp
M06
M05
M04
M07 M10
M03 M08M09
Br
M01
M02
M11
M12
M13
O
O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2f
0
200
192
184
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/10/2013 P12ꢀ11ꢀ:3
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.98:6
Coꢀꢀmnt
Datm
08ꢁJu201319ꢀ03ꢀ28
08ꢁJu201319ꢀ03ꢀ28
Filmꢅaꢀm
Origin
Eꢀ\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ88\1\Asꢊ
Frmqumncyꢁ(MHꢂ
Ownmr
:00.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
root
ꢇointsCount
32768
2:56.075:
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
56.68
8223.68
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢊ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
8223.:3
mꢀꢄmraturmꢁꢉmgrmmCꢂ 26.8:5
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.82 - 7.78 (m, 2 H), 7.74 - 7.71 (m, 2 H), 7.28 - 7.22 (m, 1 H), 7.15 (d, J = 7.3 Hz, 1 H), 6.94 - 6.85 (m, 2 H),
4
.21 (s, 2 H), 3.77 (s, 3 H)
RLB-FU-88.001.esp
M01
M02
M03 M05
M04
I
M06 M07
O
O
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2g
0
12.0
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
-0.5
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/10/2013 P12ꢀ2ꢁꢀꢁ4
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
08ꢂJu201314ꢀ20ꢀ32
08ꢂJu201314ꢀ20ꢀ32
Filmꢅaꢀm
Eꢀ\????????\????\?????Pꢃꢄꢄ\ꢅꢆꢇꢈꢉꢊꢈ88\2\Asꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
256
Origin
ꢄpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
root
ꢇointsCount
32768
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢃNDꢃꢅD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
184.81
2ꢁ037.73
2ꢁ038.ꢁ6
ꢃolvmnt
CHꢆOꢅOꢉOꢅPꢈꢋ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
10053.47ꢁ6
mꢀꢄmraturmꢁꢉmgrmmCꢂ 27.227
1
3
C NMR (101MHz ,CHLOROFORM-d) d = 197.3, 157.0, 137.8, 136.2, 130.9, 129.8, 128.5, 123.3, 120.7, 110.6, 100.7, 55.3, 39.9
RLB-FU-88.002.esp
M06
M04 M05 M08
M03 M07 M09
M12
I
CHLOROFORM-d
M01
M02
M10
M11
M13
O
O
2g
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
27/6/2013 Pꢀ431411
Acquisition iꢀmꢁsmcꢂ
Filmꢅaꢀm
3.98ꢀ6
Coꢀꢀmnt
Datm
21ꢁJu2013124284ꢀ8
Datmꢃtaꢀꢄ
21ꢁJu2013124284ꢀ8
E4\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ117\1\sꢊꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
ꢀ00.13
root
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
16
Origin
ꢃpect
19.91
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
ꢇointsCount
32768
zg30
Rmcmivmrꢈain
ꢃꢄmctruꢀ yꢄm
8223.68
8223.ꢀ3
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
2ꢀꢀ1.5037
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 26.608
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.92 (d, J = 8.0 Hz, 2 H), 7.27 - 7.12 (m, 4 H), 6.93 - 6.82 (m, 2 H), 4.23 (s, 2 H), 3.75 (s, 3 H), 2.37 (s, 3 H)
RLB-FU-117.001.esp
M01
M02 M03
M04
M05
M06
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
O
O
2h
0
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
27/6/2013 Pꢀ43ꢀ4ꢀ0
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
21ꢁJu2013124ꢀ34ꢀꢀ
21ꢁJu2013124ꢀ34ꢀꢀ
Filmꢅaꢀm
Origin
E4\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ117\2\sꢊꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
235
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
root
ꢇointsCount
32768
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
Rmcmivmrꢈain
189.81
2ꢀ037.73
2ꢀ038.ꢀ6
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
10060.3320
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
mꢀꢄmraturmꢁꢉmgrmmCꢂ 27.067
1
3
C NMR (101MHz ,CHLOROFORM-d) d = 197.6, 157.3, 143.6, 134.6, 131.0, 129.2, 128.6, 128.3, 124.0, 120.7, 110.6, 55.4, 39.9, 21.7
RLB-FU-117.002.esp
M05
M08
M06M09
M01
M02
M03 M04 M07 M10
M11
M12
M13
M14
O
O
2h
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
220
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
-20
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
30/6/2013 Pꢀ81ꢁ806
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.9ꢀ46
Coꢀꢀmnt
Datm
1ꢀꢂJu20131380ꢁ804
1ꢀꢂJu20131380ꢁ804
Filmꢅaꢀm
Origin
E8\????????\????\?????Pꢃꢄꢄ\ꢅꢆꢇꢈꢉꢊꢈ10ꢀ\1\sꢋꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
400.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢄpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
3276ꢀ
root
ꢇointsCount
3276ꢀ
2447.ꢀꢁ33
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
31.69
ꢀ223.6ꢀ
ꢃolvmnt
CHꢆOꢅOꢉOꢅPꢈꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢃNDꢃꢅD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
ꢀ223.43
mꢀꢄmraturmꢁꢉmgrmmCꢂ 2ꢀ.64ꢀ
1
H NMR (400MHz ,CHLOROFORM-d) d = 7.78 (d, J = 3.8 Hz, 1 H), 7.57 (d, J = 5.0 Hz, 1 H), 7.27 - 7.19 (m, 2 H), 7.08 (t, J = 4.4 Hz, 1 H), 6.94 - 6.84 (m,
2
H), 4.19 (s, 2 H), 3.77 (s, 3 H)
RLB-FU-108.001.esp
M01 M03M05
M02 M04
M06 M07
S
O
O
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
2i
13
12
11
10
9
8
7
6
5
4
3
2
1
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/8/2013 Pꢀ42141ꢁ
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
18ꢂJu20131ꢃ42ꢃ428
18ꢂJu20131ꢃ42ꢃ428
Filmꢅaꢀm
E4\????????\????\?????Pꢄꢅꢅ\ꢆꢇꢈꢉꢊꢋꢉ108\33\sꢌR
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
2ꢁ6
Origin
ꢅpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢃ68
root
ꢇointsCount
32ꢃ68
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢄNDꢄꢆD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
189.81
2ꢀ03ꢃ.ꢃ3
2ꢀ038.ꢀ6
ꢃolvmnt
CHꢇOꢆOꢊOꢆPꢉR
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
100ꢀꢁ.90ꢀ3
mꢀꢄmraturmꢁꢉmgrmmCꢂ 29.ꢁ08
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 190.7, 157.1, 144.1, 133.3, 132.2, 130.9, 128.4, 127.9, 123.3, 120.6, 110.6, 55.3, 40.5
RLB-FU-108.033.ESP
M06
M05
M12
M04M08 M10
M07M09
CHLOROFORM-d
O
M01
M02
M03
M11
S
M13
O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2i
0
220
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
-20
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
27/6/2013 Pꢀ4ꢀ1402
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
3.98ꢀ6
Coꢀꢀmnt
Datm
21ꢁJu201311401420
21ꢁJu201311401420
Filmꢅaꢀm
Origin
E4\????????\????\?????Pꢂꢃꢃ\ꢄꢅꢆꢇꢈꢉꢇ116\1\sꢊꢋ
Frmqumncyꢁ(MHꢂ
Ownmr
ꢀ00.13
ꢅuclmus
1H
ꢅuꢀbmroꢆ ransimnts
16
ꢃpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32768
root
ꢇointsCount
32768
2ꢀ56.5317
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zg30
Rmcmivmrꢈain
31.69
8223.68
ꢃolvmnt
CHꢅOꢄOꢈOꢄPꢇꢋ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
STꢂNDꢂꢄD ꢃwmmꢄWiꢉtꢊꢁMHꢂ
8223.ꢀ3
mꢀꢄmraturmꢁꢉmgrmmCꢂ 26.568
1
H NMR (400MHz ,CHLOROFORM-d) d = 8.02 (d, J = 7.3 Hz, 2 H), 7.59 - 7.53 (m, 1 H), 7.50 - 7.43 (m, 1 H), 7.34 (dd, J = 2.3, 8.5 Hz, 1 H), 7.28 (d, J =
.3 Hz, 1 H), 6.74 (d, J = 8.5 Hz, 1 H), 4.23 (s, 2 H), 3.74 (s, 3 H)
2
RLB-FU-116.001.esp
M03
M02 M05
M04
M01
M06
M07
M08
Br
O
O
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
2j
0
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
13/8/2013 Pꢀ42ꢁ4:8
Acquisition iꢀmꢁsmcꢂ
Datmꢃtaꢀꢄ
1.3631
Coꢀꢀmnt
Datm
21ꢂJu20131140ꢁ4ꢀꢀ
21ꢂJu20131140ꢁ4ꢀꢀ
Filmꢅaꢀm
E4\????????\????\?????Pꢃꢄꢄ\ꢅꢆꢇꢈꢉꢊꢈ116\2\sꢋꢌ
Frmqumncyꢁ(MHꢂ
Ownmr
100.61
ꢅuclmus
13C
ꢅuꢀbmroꢆ ransimnts
12:
Origin
ꢄpect
OriginalꢇointsCount
ꢃWꢁcyclicalꢂꢁMHꢂ
32ꢁ68
root
ꢇointsCount
32ꢁ68
ꢇulsmꢃmqumncm
ꢃꢄmctruꢀ yꢄm
zgpg30
STꢃNDꢃꢅD
Rmcmivmrꢈain
ꢃwmmꢄWiꢉtꢊꢁMHꢂ
189.81
2ꢀ03ꢁ.ꢁ3
2ꢀ038.ꢀ6
ꢃolvmnt
CHꢆOꢅOꢉOꢅPꢈꢌ
ꢃꢄmctruꢀOꢆꢆsmtꢁMHꢂ
100:2.:0ꢁ8
mꢀꢄmraturmꢁꢉmgrmmCꢂ 26.9ꢀꢀ
1
3
C NMR (100MHz ,CHLOROFORM-d) d = 197.0, 156.4, 136.7, 133.7, 133.1, 131.0, 128.5, 128.3, 125.9, 112.7, 112.2, 55.6, 39.6
RLB-FU-116.002.ESP
M05 M09
M06
M12
M03 M07
M04M08
M11
M10
Br
CHLOROFORM-d
M01
M02
M13
O
O
2j
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
220
210
200
190
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
-10
-20
Chemical Shift (ppm)