Synthesis of 1,1-diarylethylenes

Article abstract of DOI:10.1016/j.tet.2016.04.018

A facile route toward 1,1-diarylethylenes 6 has been developed in good yields via mCPBA-promoted oxidation of β-hydroxysulfides 2, BF₃·OEt₂-mediated Friedel-Crafts reaction of the resulting β-hydroxysulfoxides 3 with oxygenated benze

Full text of DOI:10.1016/j.tet.2016.04.018

Accepted Manuscript
Synthesis of 1,1-Diarylethylenes
Meng-Yang Chang, Yi-Hsuan Huang, Heui-Sin Wang
PII:
S0040-4020(16)30271-X
10.1016/j.tet.2016.04.018
TET 27661
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 March 2016
Revised Date: 1 April 2016
Accepted Date: 6 April 2016
Please cite this article as: Chang M-Y, Huang Y-H, Wang H-S, Synthesis of 1,1-Diarylethylenes,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.04.018.
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Synthesis of 1,1-Diarylethylenes
Meng-Yang Chang* Yi-Hsuan Huang and Heui-Sin Wang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Y
Y
Y
1
OH
OH
O
S
5% Pd/C
mCPBA
S
O
S
1
1
Ar
Ph
Ar
Ph
BF OEt
3
2
1
Ar
Ph
Ar

ACCEPTED MANUSCRIPT
Tetrahedron
1
TETRAHEDRON
Pergamon
Synthesis of 1,1-Diarylethylenes
Meng-Yang Chang,* Yi-Hsuan Huang and Heui-Sin Wang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Abstract—A facile route toward 1,1-diarylethylenes 6 has been developed in good yields via mCPBA-promoted oxidation of
β-hydroxysulfides 2, BF3·OEt2-mediated Friedel-Crafts reaction of the resulting β-hydroxysulfoxides 3 with oxygenated
benzenes 4, followed by Pd/C-mediated [2,3]-sigmatropic rearrangement of sulfoxides 5. The protocol provides a short-term,
easy-operational, inexpensive reagent, mild condition and rapidly obtainable transformation.
1. Introduction
2. Results and discussion
Substituted germinal 1,1-diarylethylenes are present in
many pharmacophores,1 including tamoxifen,2 bexarotene,3
iso-combretastatin A (isoCA-4),4 and ratanhine.5 The use of
Wittig oelfination of diarylketone and Grignard addition of
arylketone followed by dehydration are two common and
traditional protocols for the synthesis of 1,1-diarylethylenes.
Recently, Alami and Barluenga have developed a series of
syntheses of diversified 1,1-diarylethylenes via palladium-
mediated cross-coupling of hydrozone with aryl halides.6-7
Other efficient approaches for preparing substituted 1,1-
diarylethylenes have been reported via various palladium
complexes promoting cross-coupling as the major pathways,
such as (i) the PdCl2-catalyzed Kumada-Corriu reaction of
styryl phosphates with ArMgX,8a (ii) the Pd2dba3 or
Pd(dba)2-catalyzed Negishi reaction of styryl phosphates
with ArZnX,8b-c (iii) the Pd(OAc)2 or Pd(Ph3P)4-catalyzed
Still reaction of styryl stannanes with ArX,9 and (iv) the
Pd(Ph3P)2Cl2-catalyzed Suzuki-Miyaura reaction of styryl
triflates with ArB(OH)2.10 Another route to nickel-mediated
Kumada-type cross-coupling styryl sulfides with ArMgX
has been documented.11
Based on our observations, we found that transition
metal mediated cross-coupling reactions provide some
dominant access to substituted 1,1-diarylethylenes among
these methodologies, as shown in Scheme 1. To the best of
our knowledge, for the synthesis of 1,1-diarylethylenes, no
examples on Pd/C-mediated intramolecular [2,3]-
sigmatropic rearrangement of sulfoxide has been reported.
Herein, we describe a highly effective three-step synthetic
route towards substituted 1,1-diarylethylenes 6 bearing the
electron-withdrawing aryl group, the electron-neutral aryl
group or the electron-donating aryl groups (Ar1 = Ph, 4-
MeC6H4, 2-naphthalene, 4-PhC6H4, 4-FC6H4, 4-MeOC6H4;
Ar-H = 1,3-(MeO)2C6H4, 1,2-(MeO)2C6H4, 1,2-CH2O2C6H4,
1,2,3-(MeO)3C6H3), including (i)
a mCPBA (meta-
chloroperoxybenzoic acid) promoted oxidation of β-
hydroxysulfides 212 (prepared by NaBH4 mediated
reduction of β-ketosulfides 1 at rt for 10 min) at rt for 10
min, (ii) a BF3·OEt2 mediated Friedel-Crafts reaction of β-
hydroxysulfoxides 3 with oxygenated benzenes 4 at rt 20
min and (iii) a Pd/C-mediated intramolecular [2,3]-
sigmatropic rearrangement of sulfoxides 5 at rt for 20 min
(Scheme 2).
Scheme 1. Synthetic routes of 1,1-diarylethylenes
Scheme 2. Our synthetic route of 1,1-diarylethylenes 6
H
N
O
P
OPh
[Pd]
Ar
[Pd]
OPh
O
Ar
N
Ar
Ts
X
Ar MgX
OH
Ar
6
OH
O
S
Ar
O
S
mCPBA
Ar H 4
Ph BF OEt Ar
5% Pd/C
Ar
EtOH
1
1
1
1
1
S
Ar
Ar
Ar
Me
Ar
Ar
1
1
refs 6-7
1
1
or
Ar ZnX
ref 8
[Pd]
Ar
Ph
Ar
Ph
3
2
CH Cl
2
2
CH Cl
2
2
rt, 10 min
rt, 20 min
[Pd]
2
3
5
rt, 20 min
OTf
Ar
Ar
SnBu
SPr
Ar
Ar
3
Ar B(OH)
Ar
ref 9
[Ni]
X
2
1
1
1
1
1
Ar = Ph, 4-MeC H , 2-naphthalene, 4-PhC H , 4-FC H , 4-MeOC H
6 4
Ar
Ar
Ar
6
4
6
4
6
4
Ar
Ar
ref 10
Ar-H = 1,3-(MeO) C H , 1,2-(MeO) C H , 1,2-CH O C H , 1,2,3-(MeO) C H
3 6 3
2
6
4
2
6
4
2
2
6
4
O
S
Ar
Ar MgX
5% Pd/C
this work
1
1
1
Ar
Ph
Ar
ref 11
To generate skeleton 6, the facile and simple
methodology provides short-term, easy-operational,
———
a
Keywords: 1,1-Diarylethylenes; Sigmatropic rearrangement; Sulfoxides.
*Corresponding author. Tel.: +886 7 3121101 ext 2220
e-mail: mychang@kmu.edu.tw
inexpensive reagent, mild condition and rapidly obtainable
transformation by a simple three-step synthetic sequence
starting with a selective oxidation between a hydroxyl and

ACCEPTED MANUSCRIPT
2
Tetrahedron
sulfide group, followed by a benzylic introduction of
oxygenated arenes and then, a sulfoxide elimination within
1 h under open-vessel room temperature conditions. The
key building blocks in numerous valuable bioactive
intermediates has led to the development of sulfoxide-
based synthetic approaches to the targets,13-14 for example,
Pradilla et al. developed a base-promoted intramolecular
SN2’ cyclization of sulfinyl dienols.15 On the basis of
observations, a sulfoxide-based synthetic route of 1,1-
diarylethylenes with the diversified aryl substituents is
developed.
which resulted in 50% β-ketosulfone, 30% β-
hydroxysulfone and 12% β-hydroxysulfoxide 3a. The low
yield of 3a was attributed to over-oxidation of mCPBA and
a longer reaction time. To address this concern, the purity
(washed by PH = 7.4 buffer solution) and equivalent of
mCPBA was adjusted (3.0 ꢀ 1.0 equiv) and time was
shortened (60 ꢀ 10 min). The reaction conditions provided
3a in
a quantitative yield with no side products.
Furthermore, treatment of 3a with a 2.0 equiv of 1,3-
dimethoxybenzene (4a) produced isomers 5a (80%) with a
1:1 ratio in the presence of BF3·OEt2 (1.0 equiv) at rt for 20
min. We assumed that two diastereoisomers are a result of
two chiral centers (carbon and sulfur atom) in the molecule
5a by a two-step route. There are different position on
aromatic 4a could possibly participate in the Friedel-Crafts
reaction of 3a, and this might lead to different isomers of
5a. However, we found that only para-position of methoxy
group on 4a participated Friedel-Crafts reaction of 3a to
generate 5a. During the procedure, no other isomers were
observed.16 Sulfoxide elimination of 5a under refluxing
toluene condition was examined next but traditional
thermolysis of 5a with two isomers afforded 6a in a 40%
yield along with 32% of an unknown polymer for 10 h. In a
subsequent attempt, 5% Pd/C (100 mg) was introduced as a
catalyst to improve the reaction reactivity. Pleasingly, the
isolated yield of 6a was increased to 89%, and the reaction
temperature and time were also decreased to rt and 20 min.
Increasing the amounts of 5% Pd/C (200 mg) also
generated similar yields of 6a (92%). To make three-step
sequence more practical, Pd/C-mediated elimination of
crude 5a was examined. Compared with the above work
(for 5a, 80%; for 6a, 89%), a lower yield of 6a (55%) was
provided.
Table 1. Synthesis of diarylmethyl sulfoxides 5a-x and 1,1-
diarylethylenes 6a-xa-b
OH
Ar
OH
O
S
Ar
O
S
mCPBA
Ar H 4
5% Pd/C
Ar
EtOH
S
1
1
1
1
Ar
Ph
Ar
Ph
Ar
2
Ph
BF OEt
3
CH Cl
2
2
CH Cl
2
2
rt, 10 min
rt, 20 min
2
3
5
6
rt, 20 min
entry 2, Ar1 =
4, Ar-H =
5, (%)c 6, (%)c
1
2
3
4
5
6
7
8
9
2a, Ph
2a, Ph
2a, Ph
2a, Ph
4a, 1,3-(MeO)2C6H4 5a, 80 6a, 89
4b, 1,2-CH2O2C6H4 5b, 87 6b, 80
4c, 1,2-(MeO)2C6H4 5c, 86 6c, 82
4d, 1,2,3-(MeO)3C6H3 5d, 90 6d, 89
2b, 4-MeC6H4 4a, 1,3-(MeO)2C6H4 5e, 78 6e, 81
2b, 4-MeC6H4 4b, 1,2-CH2O2C6H4 5f, 83 6f, 80
2b, 4-MeC6H4 4c, 1,2-(MeO)2C6H4 5g, 81 6g, 74
2b, 4-MeC6H4 4d, 1,2,3-(MeO)3C6H3 5h, 88 6h, 86
2c, 2-naphthyl 4a, 1,3-(MeO)2C6H4 5i, 80 6i, 81
10 2c, 2-naphthyl 4b, 1,2-CH2O2C6H4 5j, 84 6j, 76
11 2c, 2-naphthyl 4c, 1,2-(MeO)2C6H4 5k, 83 6k, 80
12 2c, 2-naphthyl 4d, 1,2,3-(MeO)3C6H3 5l, 92 6l, 85
According to the above synthetic sequences (mCPBA-
promoted oxidation, BF3·OEt2-mediated Friedel-Crafts
reaction with oxygenated benzenes and Pd/C-catalyzed
sulfoxide elimination), we explored the substrate scope,
and the results are shown in Table 1. To adjust the Ar1
group of 2a-f (Ar1 = Ph, 4-MeC6H4, 2-naphthalene, 4-
PhC6H4, 4-FC6H4, 4-MeOC6H4) and Ar-H group of 4a-d
13 2d, 4-PhC6H4
14 2d, 4-PhC6H4
15 2d, 4-PhC6H4
16 2d, 4-PhC6H4
17 2e, 4-FC6H4
18 2e, 4-FC6H4
19 2e, 4-FC6H4
20 2e, 4-FC6H4
4a, 1,3-(MeO)2C6H4 5m, 74 6m, 78
4b, 1,2-CH2O2C6H4 5n, 82 6n, 74
4c, 1,2-(MeO)2C6H4 5o, 80 6o, 80
4d, 1,2,3-(MeO)3C6H3 5p, 87 6p, 81
4a, 1,3-(MeO)2C6H4 5q, 72 6q, 76
4b, 1,2-CH2O2C6H4 5r, 80 6r, 87
4c, 1,2-(MeO)2C6H4 5s, 80 6s, 82
4d, 1,2,3-(MeO)3C6H3 5t, 84 6t, 83
(Ar-H
=
1,3-(MeO)2C6H4, 1,2-(MeO)2C6H4, 1,2-
CH2O2C6H4, 1,2,3-(MeO)3C6H3), 5a-x, with an unseparated
mixture (ratio 1:1 to 2:1), were provided in a range of
72~92% yields, as shown in entries 1-24. For the Ar1
groups of 2, the phenyl ring, with an electron-donating 4-
methoxyphenyl group (for 5u-x) provided better yields than
the electron-withdrawing 4-fluorophenyl group (5q-t), and
the phenyl ring, with an electron-neutral substituent, such
as Ph (5a-d), 4-MeC6H4 (5e-h), 4-PhC6H4 (5i-l), and 2-
naphthalene (5m-p) also provided modest to good yields.
For the substituents of Ar-H 4 in particular, 4d with a 1,2,3-
trimethoxyphenyl ring produced better results than 4a-c,
with two oxygenated motifs. With the optimized conditions
in hand, Pd/C-mediated sulfoxide elimination of 5a-x led to
6a-x in modest to good yields. All entries 1-24 performed
successfully in preparing a skeleton of 1,1-diarylethylenes.
The structural framework of 6w was determined by single-
crystal X-ray crystallography (Figure 1).17
21 2f, 4-MeOC6H4 4a, 1,3-(MeO)2C6H4 5u, 85 6u, 82
22 2f, 4-MeOC6H4 4b, 1,2-CH2O2C6H4 5v, 90 6v, 78
23 2f, 4-MeOC6H4 4c, 1,2-(MeO)2C6H4 5w, 90 6w, 78
24 2f, 4-MeOC6H4 4d, 1,2,3-(MeO)3C6H3 5x, 93 6x, 82
aThe synthesis of 5 was run on a 1.0 mmol scale with 2, mCPBA
(freshly purified, 173 mg, 1.0 equiv), CH2Cl2 (10 mL), 10 min, rt;
then 4 (1.0 equiv), BF3·OEt2 (142 mg, 1.0 mmol), 20 min, rt.
bThe synthesis of 6 was run on a 0.5 mmol scale with 5, 5% Pd/C
(100 mg), EtOH (10 mL), 20 min, rt.
cIsolated yields.
Our preliminary investigation started with an oxidation
of 2a (Ar1 = Ph) in CH2Cl2 with 3.0 equiv of commercially
available mCPBA (70~75%) as an oxidant at rt for 60 min,

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Tetrahedron
3
Figure 1: X-ray structure of 6w
limited routes appeared in the literature for establishing the
branched skeleton using some traditional functional group
transformations such as Grignard methylation of 1,3-
diaroylbenzene followed by dehydration or double Wittig
olefination of 1,3-diaroylbenzene. As shown in Table 2, our
analysis indicates that symmetrical 8a-e were generated by
oxidation of 2a-d or 2f with mCPBA, double Friedel-Crafts
reaction with 4a in the presence of BF3·OEt2, and Pd/C-
catalyzed sulfoxide elimination of 7a-f in 62-70% yields of
the three-step route. For the unsymmetrical 8f-i, a similar
route performed well via intermediates 7f-i. The provided
yields were distributed in a range of 57-69% yields. The
structure of 8a was determined by single-crystal X-ray
crystallography (Figure 2).17
Table 2. Synthesis of 1,3-bis(1-arylethenyl)benzenes 8a-ia-c
Figure 2: X-ray structure of 8a
1
1
MeO
Ar
MeO
Ar
O
S
(for 2a-d, 2f)
4a (0.5 eq)
Ph
OH
mCPBA
5% Pd/C
MeO
MeO
O
S
S
1
BF OEt
Ar
Ph
3
2
1
1
Ar
Ar
Ph
2 (0.5 mmol)
7a-e
8a-e
mCPBA
1
1
MeO
MeO
Ar
O
S
MeO
Ar
Ph
4a (1.0 eq)
3b-e (1.0 eq)
5% Pd/C
MeO
O
MeO
O
S
MeO
Ph
BF OEt
3
BF OEt
3
2
2
S
Ph
Ph
Ph
Ph
1
(for 2a, Ar = Ph)
5a
7f-i
8f-i
Me
MeO
Ph
Scheme 3. Synthesis of 1-(3,4-dimethoxyphenyl)-1-
phenylethylene 6a
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
OH
OH
O
S
MeO
O
S
Me
MeO
Ph
8a (68%)
8b (62%)
F
8c (70%)
Me
8d (68%)
Ph
8e (62%)
S
S
mCPBA
4a (2.0 eq)
5% Pd/C
2
Ph
Ph
Ph
Ph
Ph
Ph
BF OEt
3
2
MeO
(2.0 eq)
S
S
OH
9
OH
O
MeO
O
Ph
6a (88%)
10
11
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
Changing the starting substrate from 2a with a phenyl
group (thiophenol) to 9 with an alkyl group (1,2-
ethanedithiol), the three-step route provided 6a in an 88%
yield, as shown in Scheme 3. Interestingly, treatment of 9
with 2.0 equivalents of mCPBA yielded intermediate 10
with a bis-sulfoxide group, and no sulfone motif was
generated. By the involvement of 4a (2.0 equiv), 11 was
formed via a double intermolecular Friedel-Crafts reaction.
After the removal of sulfoxide, two equivalents of 6a were
obtained. In order to explore the application of 1,1-
diarylethylenes 6, synthesis of the benzofuran skeleton was
further tested. Development of a new single-step route for
simultaneous bond formation and ring-construction of
benzofurans still represented a continuing need in the
organic synthetic field.19 However, intramolecular
annulation was also a popular route to such benzofurans
among the existing methods.19-20 As shown in Scheme 4,
treatment of 6a, 6e, 6l, 6m, 6q and 6u with 10 mol% of
8f (57%)
8g (68%)
8h (69%)
8i (64%)
aThe synthesis of 8a-e was run on a 0.5 mmol scale with 2a-d or
2f, mCPBA (freshly purified, 87 mg, 1.0 equiv), CH2Cl2 (10 mL),
10 min, rt; 4a (35 mg, 0.5 equiv), BF3·OEt2 (71 mg, 1.0 equiv), 20
min, rt; 5% Pd/C (100 mg), EtOH (10 mL), 20 min, rt.
bThe synthesis of 8f-i was run on a 0.5 mmol scale with 2a (115
mg), mCPBA (freshly prepared, 87 mg, 1.0 equiv), CH2Cl2 (10
mL), 10 min, rt; 4a (69 mg, 1.0 equiv), BF3·OEt2 (71 mg, 1.0
equiv), 20 min, rt; 3b-e (1.0 equiv), BF3·OEt2 (71 mg, 1.0 equiv),
20 min, rt; 5% Pd/C (100 mg), EtOH (10 mL), 20 min, rt.
cIsolated yields.
To show the potential application of the current three-
step protocol, we embarked on the synthesis of branched
1,3-bis(1-arylethenyl)benzenes. For the formation of novel
functionalized materials, this core skeleton was also a key
monomer of styrene via tandem polymerization.18 Very

ACCEPTED MANUSCRIPT
4
Tetrahedron
Hg(OTf)2 in MeNO2 afforded 12a-f with a benzofuran
skeleton in modest yields (70-78%) via one-pot
intramolecular cycloisomerization.
Figure 3: X-ray structure of 13
Scheme 4. Synthesis of benzofurans 12a-f
MeO
MeO
Hg(OTf)
2
MeO
MeNO
O
1
2
1
Ar
6a, 6e, 6i, 6m, 6q, 6u
MeO MeO
Ar
12a-f
MeO
MeO
MeO
MeO
O
O
O
O
O
O
Me
Ph
F
MeO
12a (75%)
12b (70%)
12c (78%)
12d (73%) 12e (71%)
12f (73%)
4. Experimental section
4.1. General. All other reagents and solvents were obtained
from commercial sources and used without further
purification. Reactions were routinely carried out under an
atmosphere of dry nitrogen with magnetic stirring. Products
in organic solvents were dried with anhydrous magnesium
sulfate before concentration in vacuo. Melting points were
determined with a SMP3 melting apparatus. 1H and 13C NMR
spectra were recorded on a Varian INOVA-400 spectrometer
operating at 400 and at 100 MHz, respectively. Chemical
shifts (δ) are reported in parts per million (ppm) and the
coupling constants (J) are given in Hertz. High resolution
Scheme 5. Synthesis of 1,3-bis(1-phenylethenyl)benzene
13
OMe
OMe Ph
Ph OMe Ph
MeO
OMe
OH
mCPBA 4e (0.3 mmol) 5% Pd/C
MeO
Ph
OMe MeO
OMe
S
Ph
Ph
BF OEt
3
2
Ph
2a (0.9 mmol)
13 (40%)
14 (not detected)
By the current three-step route, the installation of the
tris-styryl group to the benzene skeleton was studied.
Controlling the involvement of 1,3,5-trimethoxybenzene
(4e. 1.0 equiv), 2a (3.0 equiv) was converted to 13 in a
40% yield via the above method, as shown in Scheme 5.
Under the reaction conditions, no desired 14 was observed.
Increasing the amounts of 2a (5 equiv), in attempts to
afford 14 still failed due to the decreased ability of the
electron-donating methoxy group and more steric hindrance
of the third styryl motif. The structural framework of 13
was determined by single-crystal X-ray crystallography
(Figure 3).17
mass spectra (HRMS) were measured with
a mass
spectrometer Finnigan/Thermo Quest MAT 95XL. X-ray
crystal structures were obtained with an Enraf-Nonius FR-
590 diffractometer (CAD4, Kappa CCD).
4.2. A representative synthetic procedure of compounds 5a-x
is as follows: Commercially available mCPBA (Alfa,
70~75%, 50 g) was dissolved in ether (250 mL) and washed
with buffer solution (4 × 250 mL, pH = 7.5; 410 mL of 0.1 M
NaOH, 250 mL of 0.2 M KH2PO4 and 340 mL of water). The
ether layer was dried and carefully evaporated under reduced
pressure to give ca. 30 g pure mCPBA (CAUTION! potential
explosive).21 Freshly purified mCPBA (173 mg, 1.0 mmol)
was added to a solution of β-hydroxysulfides 2a-f (1.0 mmol)
in CH2Cl2 (10 mL) at rt. The reaction mixture was stirred at rt
for 10 min. Oxygenated benzenes 4a-d (1.0 mmol) was
added to the reaction mixture at rt. Then, BF3·OEt2 (142 mg,
1.0 mmol) was added to the reaction mixture at rt. After the
reaction mixture was stirred at rt for 20 min, saturated
NaHCO3 solution (10 mL) was added to the reaction mixture.
The reaction mixture was extracted with CH2Cl2 (3 x 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product under reduced
pressure. Purification on silica gel (hexanes/EtOAc = 3/1~1/1)
afforded 5a-x.
3. Conclusion
In summary, we have developed a short-term, easy-
operational, inexpensive reagent, mild condition and
rapidly obtainable synthesis of substituted 1,1-
diarylethylenes 6 and 8 in moderate to good yields via an
mCPBA-promoted oxidation of β-hydroxysulfides 2, a
BF3·OEt2-mediated Friedel-Crafts reaction of the resulting
β-hydroxysulfoxides
followed by
3
with oxygenated benzenes 4,
a
Pd/C-mediated [2,3]-sigmatropic
rearrangement of sulfoxides 5. The structures of the key
products were confirmed by X-ray crystallography.
Synthesis of the benzofuran skeleton was further developed
via Hg(OTf)2-mediated intramolecular annulation of 1,1-
diarylethylenes 6. Further investigation regarding synthetic
applications of β-hydroxysulfides will be conducted and
published in due course.
4.2.1. Compound (5a). Two isomers (ratio ~ 1:1); Yield =
80% (293 mg); HRMS (ESI, M++1) calcd for C22H23O3S
1
367.1368, found 367.1372; H NMR (400 MHz, CDCl3): δ
7.64-7.59 (m, 2H), 7.53-7.46 (m, 3H), 7.34-7.16 (m, 5H),

ACCEPTED MANUSCRIPT
Tetrahedron
5
7.12 (d, J = 8.4 Hz, 1/2H), 7.08 (d, J = 8.0 Hz, 1/2H), 6.50- 4.2.8. Compound (5h). Two isomers (ratio ~ 1:1); Yield =
6.40 (m, 2H), 4.80 (dd, J = 6.0, 10.0 Hz, 1/2H), 4.74 (dd, J =
6.4, 10.0 Hz, 1/2H), 3.78 (s, 3/2H), 3.76 (s, 3/2H), 3.75 (s,
3/2H), 3.72 (s, 3/2H), 3.60-3.54 (m, 1H), 3.49-3.39 (m, 1H).
88% (361 mg); HRMS (ESI, M++1) calcd for C24H27O4S
411.1630, found 411.1633; 1H NMR (400 MHz, CDCl3): δ
7.64-7.60 (m, 2H), 7.54-7.47 (m, 3H), 7.20 (d, J = 8.4 Hz,
1H), 7.14-7.11 (m, 2H), 7.08 (d, J = 8.0 Hz, 1H), 6.94 (d, J
= 8.8 Hz, 1/2H), 6.87 (d, J = 8.8 Hz, 1/2 H), 6.66 (d, J =
8.8 Hz, 1/2H), 6.59 (d, J = 8.8 Hz, 1/2H), 4.77 (dd, J = 6.0,
10.0 Hz, 1/2H), 4.68 (dd, J = 6.8, 9.6 Hz, 1/2H), 3.84 (s,
3/2H), 3.83 (s, 3/2H), 3.81 (s, 3H), 3.66 (s, 3/2H), 3.63 (s,
3/2H), 3.50-3.34 (m, 2H), 2.31 (s, 3/2H), 2.28 (s, 3/2H).
4.2.2. Compound (5b). Two isomers (ratio ~ 1:1); Yield =
87% (305 mg); HRMS (ESI, M++1) calcd for C21H19O3S
351.1055, found 351.1059; 1H NMR (400 MHz, CDCl3): δ
7.63-7.60 (m, 2H), 7.53-7.47 (m, 3H), 7.37-7.17 (m, 5H),
6.86 (dd, J = 1.6, 8.0 Hz, 1/2H), 6.79 (d, J = 7.6 Hz, 1/2 H),
6.78 (d, J = 2.0 Hz, 1/2H), 6.70 (br s, 1H), 6.68 (d, J = 7.6
Hz, 1/2H), 5.93 (d, J = 1.2 Hz, 1/2H), 6.92 (d, J = 1.6 Hz,
1/2H), 5.88 (d, J = 1.2 Hz, 1/2H), 5.88 (d, J = 1.2 Hz,
1/2H), 4.54 (dd, J = 4.8, 10.8 Hz, 1/2H), 4.49 (dd, J = 5.6,
10.8 Hz, 1/2H), 3.47-3.30 (m, 2H).
4.2.9. Compound (5i). Two isomers (ratio ~ 2:1); Yield =
80% (333 mg); HRMS (ESI, M++1) calcd for C26H25O3S
417.1524, found 417.1526; 1H NMR (400 MHz, CDCl3): δ
7.82-7.61 (m, 6H), 7.54-7.35 (m, 5H), 7.14-7.11 (m, 1H),
6.50-6.41 (m, 3H), 4.98 (dd, J = 6.0, 10.0 Hz, 1/3H), 4.89
(dd, J = 6.8, 9.6 Hz, 2/3H), 3.79 (s, 2H), 3.77 (s, 1H), 3.76
(s, 1H), 3.73 (s, 2H), 3.67-3.48 (m, 2H).
4.2.3. Compound (5c). Two isomers (ratio ~ 1:1); Yield =
86% (315 mg); HRMS (ESI, M++1) calcd for C22H23O3S
367.1368, found 367.1369; 1H NMR (400 MHz, CDCl3): δ
7.61-7.58 (m, 2H), 7.50-7.45 (m, 3H), 7.37-7.32 (m, 2H),
7.28-7.15 (m, 3H), 6.92-6.82 (m, 3/2H), 6.76-6.71 (m,
3/2H), 4.56 (dd, J = 5.2, 10.8 Hz, 1/2H), 4.51 (dd, J = 5.2,
10.8 Hz, 1/2H), 3.85 (s, 3/2H), 3.84 (s, 3/2H), 3.80 (s,
3/2H), 3.79 (s, 3/2H), 3.48-3.34 (m, 2H).
4.2.10. Compound (5j). Two isomers (ratio ~ 1:1); Yield =
84% (336 mg); HRMS (ESI, M++1) calcd for C25H21O3S
401.1212, found 401.1215; 1H NMR (400 MHz, CDCl3): δ
7.86-7.61 (m, 6H), 7.53-7.30 (m, 6H), 6.93 (dd, J = 1.6,
8.0 Hz, 1/2H), 6.83 (d, J = 1.6 Hz, 1/2H), 6.82 (d, J = 8.0
Hz, 1/2H), 6.76 (dd, J = 1.6, 8.0 Hz, 1/2H), 6.75 (s, 1/2H),
6.72 (d, J = 8.0 Hz, 1/2H), 5.94 (d, J = 1.2 Hz, 1/2H), 5.92
(d, J = 1.2 Hz, 1/2H), 5.88 (d, J = 1.6 Hz, 1/2H), 5.87 (d, J
= 1.2 Hz, 1/2H), 4.73-4.68 (m, 1H), 3.59-3.41 (m, 2H).
4.2.4. Compound (5d). Two isomers (ratio ~ 1:1); Yield =
90% (356 mg); HRMS (ESI, M++1) calcd for C23H25O4S
397.1474, found 397.1480; 1H NMR (400 MHz, CDCl3): δ
7.64-7.59 (m, 2H), 7.52-7.45 (m, 3H), 7.31-7.15 (m, 5H),
6.97 (d, J = 8.8 Hz, 1/2H), 6.88 (d, J = 8.4 Hz, 1/2H), 6.67
(d, J = 8.4 Hz, 1/2H), 6.59 (d, J = 8.4 Hz, 1/2H), 4.80 (dd,
J = 6.0, 10.0 Hz, 1/2H), 4.74 (t, J = 8.4 Hz, 1/2H), 3.84 (s,
3H), 3.81 (s, 3/2H), 3.80 (s, 3/2H), 3.63 (s, 3/2H), 3.61 (s,
3/2H), 3.49 (d, J = 8.4 Hz, 1H), 3.43 (dd, J = 10.0, 12.8 Hz,
1H).
4.2.11. Compound (5k). Two isomers (ratio ~ 2:1); Yield =
83% (345 mg); HRMS (ESI, M++1) calcd for C26H25O3S
417.1524, found 417.1528; 1H NMR (400 MHz, CDCl3): δ
7.86-7.61 (m, 6H), 7.53-7.31 (m, 6H), 6.96 (dd, J = 2.0,
8.4 Hz, 1/3H), 6.88 (d, J = 8.4 Hz, 2/3H), 6.87 (d, J = 2.0
Hz, 1/3H), 6.82 (dd, J = 2.0, 8.4 Hz, 2/3H), 6.78 (s, 2/3 H),
6.77 (s, 1/3H), 4.76-4.70 (m, 1H), 3.87 (s, 2H), 3.85 (s,
2H), 3.82 (s, 1H), 3.80 (s, 1H), 3.61-3.44 (m, 2H).
4.2.5. Compound (5e). Two isomers (ratio ~ 1:1); Yield =
78% (296 mg); HRMS (ESI, M++1) calcd for C23H25O3S
381.1524, found 381.1530; 1H NMR (400 MHz, CDCl3): δ
7.64-7.59 (m, 2H), 7.53-7.46 (m, 3H), 7.23-7.02 (m, 5H),
6.48-6.40 (m, 2H), 4.76 (dd, J = 6.0, 10.0 Hz, 1/2H), 4.67
(dd, J = 6.8, 9.2 Hz, 1/2H), 3.78 (s, 3/2H), 3.76 (s, 3/2H),
3.75 (s, 3/2H), 3.72 (s, 3/2H), 3.58-3.36 (m, 2H), 2.31 (s,
3/2H), 2.28 (s, 3/2H).
4.2.12. Compound (5l). Two isomers (ratio ~ 1:1); Yield =
92% (410 mg); HRMS (ESI, M++1) calcd for C27H27O4S
447.1630, found 447.1633; 1H NMR (400 MHz, CDCl3): δ
7.83-7.61 (m, 6H), 7.55-7.34 (m, 6H), 7.00 (d, J = 8.4 Hz,
1/2H), 6.95 (d, J = 8.8 Hz, 1/2H), 6.68 (d, J = 8.8 Hz,
1/2H), 6.61 (d, J = 8.4 Hz, 1/2H), 4.99 (dd, J = 6.0, 10.0
Hz, 1/2H), 4.89 (dd, J = 6.8, 10.0 Hz, 1/2H), 3.85 (s, 3H),
3.82 (s, 3/2H), 3.81 (s, 3/2H), 3.63 (s, 3/2H), 3.61 (s, 3/2H),
3.66-3.47 (m, 2H).
4.2.6. Compound (5f). Two isomers (ratio ~ 1:1); Yield =
83% (302 mg); HRMS (ESI, M++1) calcd for C22H21O3S
365.1212, found 365.1215; 1H NMR (400 MHz, CDCl3): δ
7.63-7.61 (m, 2H), 7.53-7.48 (m, 3H), 7.23-7.07 (m, 4H),
6.87-6.69 (m, 3H), 5.93 (d, J = 1.6 Hz, 1/2H), 5.91 (d, J =
1.6 Hz, 1/2H), 5.87 (d, J = 1.2 Hz, 1/2H), 5.87 (d, J = 1.2
Hz, 1/2H), 4.51-4.45 (m, 1H), 3.46-3.29 (m, 2H), 2.34 (s,
3/2H), 2.29 (s, 3/2H).
4.2.13. Compound (5m). Two isomers (ratio ~ 2:1); Yield
= 74% (327 mg); HRMS (ESI, M++1) calcd for C28H27O3S
443.1681, found 443.1688; 1H NMR (400 MHz, CDCl3): δ
7.67-7.30 (m, 14H), 7.17 (d, J = 8.4 Hz, 1/3H), 7.12 (d, J =
8.0 Hz, 2/3H), 6.52-6.42 (m, 2H), 4.84 (dd, J = 6.4, 10.0
Hz, 2/3H), 4.80 (dd, J = 6.0, 9.6 Hz, 1/3H), 3.80 (s, 1H),
3.78 (s, 2H), 3.77 (s, 2H), 3.76 (s, 1H), 3.66-3.58 (m, 1H),
3.53-3.43 (m, 1H).
4.2.7. Compound (5g). Two isomers (ratio ~ 1:1); Yield =
81% (308 mg); HRMS (ESI, M++1) calcd for C23H25O3S
381.1524, found 381.1531; 1H NMR (400 MHz, CDCl3): δ
7.62-7.58 (m, 2H), 7.51-7.45 (m, 3H), 7.24-7.06 (m, 4H),
6.91-6.71 (m, 3H), 4.53-4.47 (m, 1H), 3.85 (s, 3/2H), 3.84
(s, 3/2H), 3.80 (s, 3/2H), 3.79 (s, 3/2H), 3.47-3.33 (m, 2H),
2.32 (s, 3/2H), 2.27 (s, 3/2H).
4.2.14. Compound (5n). Two isomers (ratio ~ 1:1); Yield =
82% (349 mg); HRMS (ESI, M++1) calcd for C27H23O3S
427.1368, found 427.1371; 1H NMR (400 MHz, CDCl3): δ
7.66-7.29 (m, 14H), 6.92 (dd, J = 2.0, 8.0 Hz, 1/2H), 6.85

ACCEPTED MANUSCRIPT
6
Tetrahedron
(d, J = 1.6 Hz, 1/2H), 6.83 (d, J = 8.0 Hz, 1/2H), 6.76 (m,
3/2H), 6.94 (d, J = 1.2 Hz, 1/2H), 6.93 (d, J = 1.2 Hz,
1/2H), 6.90 (d, J = 1.2 Hz, 1/2H), 6.88 (d, J = 1.2 Hz,
1/2H), 4.64-4.55 (m, 1H), 3.51-3.37 (m, 2H).
2H), 6.84 (d, J = 8.8 Hz, 1/2H), 6.67 (d, J = 8.4 Hz, 1/2H),
6.58 (d, J = 8.8 Hz, 1/2H), 4.81-4.71 (m, 1H), 3.84 (s,
3/2H), 3.83 (s, 3/2H), 3.80 (s, 3/2H), 3.79 (s, 3/2H), 3.63 (s,
3H), 3.50-3.30 (m, 2H).
4.2.15. Compound (5o). Two isomers (ratio ~ 1:1); Yield =
80% (354 mg); HRMS (ESI, M++1) calcd for C28H27O3S
443.1681, found 443.1685; 1H NMR (400 MHz, CDCl3): δ
7.65-7.29 (m, 14H), 6.97 (dd, J = 2.0, 8.0 Hz, 1/2H), 6.90
(br s, 1/2H), 6.89 (d, J = 8.0 Hz, 1/2H), 6.88 (d, J = 2.0 Hz,
1/2H), 6.81 (dd, J = 2.0, 8.0 Hz, 1/2H), 6.78 (dd, J = 2.0,
8.0 Hz, 1/2H), 4.64 (dd, J = 5.2, 10.8 Hz, 1/2H), 4.59 (dd,
J = 5.6, 10.4 Hz, 1/2H), 3.87 (s, 3/2H), 3.86 (s, 3/2H), 3.82
(s, 3/2H), 3.81 (s, 3/2H), 3.53-3.40 (m, 2H).
4.2.21. Compound (5u). Two isomers (ratio ~ 1:1); Yield =
85% (337 mg); HRMS (ESI, M++1) calcd for C23H25O4S
397.1474, found 397.1481; 1H NMR (400 MHz, CDCl3): δ
7.63-7.58 (m, 2H), 7.50-7.43 (m, 3H), 7.25 (d, J = 8.8 Hz,
1H), 7.17 (d, J = 8.8 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1/2H),
7.05 (d, J = 9.2 Hz, 1/2H), 6.84 (d, J = 8.8 Hz, 1H), 6.80 (d,
J = 8.4 Hz, 1H), 6.47-6.39 (m, 2H), 4.77 (dd, J = 6.0, 10.4
Hz, 1/2H), 4.66 (dd, J = 6.8, 10.0 Hz, 1/2H), 3.75 (s, 3/2H),
3.74 (s, 3/2H), 3.73 (s, 3H), 3.72 (s, 3/2H), 3.70 (s, 3/2H),
3.57-3.33 (m, 2H).
4.2.16. Compound (5p). Two isomers (ratio ~ 1:1); Yield =
87% (411 mg); HRMS (ESI, M++1) calcd for C29H29O4S
473.1787, found 473.1792; 1H NMR (400 MHz, CDCl3): δ
7.68-7.29 (m, 14H), 7.03 (d, J = 8.8 Hz, 1/2H), 6.93 (d, J =
8.8 Hz, 1/2H), 6.71 (d, J = 8.4 Hz, 1/2H), 6.62 (d, J = 8.8
Hz, 1/2H), 4.89 (dd, J = 6.0, 10.0 Hz, 1/2H), 4.84 (t, J =
8.4 Hz, 1/2H), 3.87 (s, 3/2H), 3.85 (s, 3/2H), 3.84 (s, 3/2H),
3.82 (s, 3/2H), 3.71 (s, 3/2H), 3.70 (s, 3/2H), 3.55-3.43 (m,
2H).
4.2.22. Compound (5v). Two isomers (ratio ~ 1:1); Yield =
90% (342 mg); HRMS (ESI, M++1) calcd for C22H21O4S
381.1161, found 381.1163; 1H NMR (400 MHz, CDCl3): δ
7.61-7.58 (m, 2H), 7.49-7.45 (m, 3H), 7.24 (d, J = 8.8 Hz,
1H), 7.11 (d, J = 8.8 Hz, 1H), 6.90-6.75 (m, 4H), 6.67 (br s,
1H), 5.89 (d, J = 1.2 Hz, 1/2H), 5.88 (d, J = 1.2 Hz, 1/2H),
5.84 (s, 1H), 4.46 (dd, J = 5.6, 12.0 Hz, 1H), 3.76 (s, 3/2H),
3.72 (s, 3/2H), 3.42-3.27 (m, 2H).
4.2.17. Compound (5q). Two isomers (ratio ~ 1:1); Yield =
72% (276 mg); HRMS (ESI, M++1) calcd for C22H22FO3S
385.1274, found 385.1278; 1H NMR (400 MHz, CDCl3): δ
7.62-7.57 (m, 2H), 7.52-7.46 (m, 3H), 7.29-7.26 (m, 1H),
7.21-7.18 (m, 1H), 7.10 (d, J = 8.4 Hz, 1/2H), 7.03 (d, J =
8.0 Hz, 1/2H), 7.00-6.91 (m, 2H), 6.49-6.39 (m, 2H), 4.77
(dd, J = 5.6, 18.8 Hz, 1/2H), 4.72 (dd, J = 2.4, 18.8 Hz,
1/2H), 3.79 (s, 3/2H), 3.77 (s, 3/2H), 3.74 (s, 3/2H), 3.73 (s,
3/2H), 3.57-3.48 (m, 1H), 3.41-3.31 (m, 1H).
4.2.23. Compound (5w). Two isomers (ratio ~ 1:1); Yield =
90% (356 mg); HRMS (ESI, M++1) calcd for C23H25O4S
397.1474, found 379.1479; 1H NMR (400 MHz, CDCl3): δ
7.60-7.58 (m, 2H), 7.50-7.44 (m, 3H), 7.25 (d, J = 8.8 Hz,
1H), 7.12 (d, J = 8.8 Hz, 1H), 6.89-6.69 (m, 5H), 4.50-4.46
(m, 1H), 3.84 (s, 3/2H), 3.83 (s, 3/2H), 3.79 (s, 3/2H), 3.78
(s, 3/2H), 3.77 (s, 3/2H), 3.72 (s, 3/2H), 3.44-3.30 (m, 2H).
4.2.24. Compound (5x). Two isomers (ratio ~ 1:1); Yield =
93% (396 mg); HRMS (ESI, M++1) calcd for C24H27O5S
427.1579, found 427.1582; 1H NMR (400 MHz, CDCl3): δ
7.63-7.57 (m, 2H), 7.51-7.43 (m, 3H), 7.23 (d, J = 8.4 Hz,
1H), 7.15 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 8.8 Hz, 1H),
6.85 (d, J = 8.8 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1/2H), 6.79 (d,
J = 8.8 Hz, 1/2H), 6.65 (d, J = 8.4 Hz, 1/2H), 6.57 (d, J =
8.4 Hz, 1/2H), 4.76 (dd, J = 5.6, 10.4 Hz, 1/2H), 4.66 (t, J
= 8.4 Hz, 1/2H), 3.82 (s, 3/2H), 3.81 (s, 3/2H), 3.79 (s,
3/2H), 3.78 (s, 3/2H), 3.74 (s, 3/2H), 3.72 (s, 3/2H), 3.64 (s,
3/2H), 3.62 (s, 3/2H), 3.45 (d, J = 8.0 Hz, 1H), 3.42-3.30
(m, 1H).
4.2.18. Compound (5r). Two isomers (ratio ~ 1:1); Yield =
80% (294 mg); HRMS (ESI, M++1) calcd for C21H18FO3S
369.0961, found 369.0962; 1H NMR (400 MHz, CDCl3): δ
7.61-7.58 (m, 2H), 7.51-7.47 (m, 3H), 7.30-7.26 (m, 1H),
7.17-7.13 (m, 1H), 7.05-7.00 (m, 1H), 6.96-6.91 (m, 1H),
6.83 (dt, J = 1.6 Hz, 8.0 Hz, 1/2H), 6.78 (d, J = 8.0 Hz,
1/2H), 6.74 (d, J = 1.6 Hz, 1/2H), 6.70 (dd, J = 0.4, 8.0 Hz,
1/2H), 6.66 (d, J = 1.6 Hz, 1/2H), 6.64 (s, 1/2H), 5.91 (d, J
= 1.2 Hz, 1H), 5.87 (d, J = 1.6 Hz, 1H), 4.55-4.47 (m, 1H),
3.42-3.27 (m, 2H).
4.2.19. Compound (5s). Two isomers (ratio ~ 1:1); Yield =
80% (307 mg); HRMS (ESI, M++1) calcd for C22H22FO3S
385.1274, found 385.1278; 1H NMR (400 MHz, CDCl3): δ
7.59-7.55 (m, 2H), 7.48-7.42 (m, 3H), 7.31-7.26 (m, 1H),
7.16-7.13 (m, 1H), 7.03-6.99 (m, 1H), 6.93-6.88 (m, 1H),
6.86 (d, J = 2.0 Hz, 1/2H), 6.84 (d, J = 8.4 Hz, 1/2H), 6.78
(d, J = 2.0 Hz, 1/2H), 6.74 (d, J = 8.4 Hz, 1/2H), 6.71 (dd,
J = 2.0, 8.4 Hz, 1/2H), 6.66 (d, J = 2.0 Hz, 1/2H), 4.56-
4.48 (m, 1H), 3.83 (s, 3/2H), 3.82 (s, 3/2H), 3.78 (s, 3/2H),
3.77 (s, 3/2H), 3.44-3.29 (m, 2H).
4.3. A representative synthetic procedure of compounds
6a-x is as follows: 5% Pd/C (100 mg) was added to a
solution of 5 (0.5 mmol) in EtOH (10 mL) at rt. The
reaction mixture was stirred at rt for 20 min. The reaction
mixture was filtered and washed by CH2Cl2 (2 x 10 mL).
The combined organic layers were dried, filtered and
evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc = 10/1~5/1)
afforded 6a-x.
4.3.1. Compound (6a). Yield = 89% (107 mg); Colorless
4.2.20. Compound (5t). Two isomers (ratio ~ 1:1); Yield =
84% (348 mg); HRMS (ESI, M++1) calcd for C23H24FO4S
415.1379, found 415.1382; 1H NMR (400 MHz, CDCl3): δ
7.62-7.58 (m, 2H), 7.52-7.45 (m, 3H), 7.29-7.26 (m, 1H),
7.21-7.17 (m, 1H), 7.00 (d, J = 8.4 Hz, 1/2H), 6.97-6.91 (m,
gum; HRMS (ESI, M++1) calcd for C16H17O2 241.1229,
1
found 241.1232; H NMR (400 MHz, CDCl3): δ 7.33-7.25
(m, 5H), 7.17 (d, J = 8.0 Hz, 1H), 6.54-6.50 (m, 2H), 5.68
(d, J = 1.6 Hz, 1H), 5.32 (d, J = 1.6 Hz, 1H), 3.85 (s, 3H),

ACCEPTED MANUSCRIPT
Tetrahedron
7
3.63 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.59,
137.39, 134.42, 128.72 (2x), 128.08 (2x), 120.82, 112.41,
158.11, 146.64, 141.48, 131.65, 129.65, 127.93 (2x),
127.16, 126.41 (2x), 115.05, 104.19, 99.00, 55.53, 55.34.
111.36, 110.60, 55.77, 55.74, 21.06.
4.3.8. Compound (6h). Yield = 86% (122 mg); Colorless
4.3.2. Compound (6b). Yield = 80% (90 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C18H21O3 285.1491,
gum; HRMS (ESI, M++1) calcd for C15H13O2 225.0916,
found 285.1493; H NMR (400 MHz, CDCl3): δ 7.21 (d, J
1
1
found 225.0920; H NMR (400 MHz, CDCl3): δ 7.37-7.32
= 8.4 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.8 Hz,
1H), 6.68 (d, J = 8.4 Hz, 1H), 5.60 (d, J = 1.6 Hz, 1H),
5.24 (d, J = 1.6 Hz, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.54 (s,
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.43
(2x), 151.64, 146.68, 142.29, 138.94, 137.13, 129.25,
128.75 (2x), 126.48 (2x), 125.15, 114.48, 106.82, 60.80,
60.57, 21.12.
(m, 5H), 6.85 (d, J = 1.6 Hz, 1H), 6.84 (dd, J = 1.6, 8.0 Hz,
1H), 6.78 (d, J = 8.0 Hz, 1H), 5.98 (s, 2H), 5.40 (d, J = 1.2
Hz, 1H), 3.37 (d, J = 1.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 149.60, 147.24, 141.60, 135.73, 129.04, 128.30
(2x), 128.12 (2x), 127.70, 122.00, 113.35, 108.63, 107.91,
101.05.
4.3.3. Compound (6c). Yield = 82% (98 mg); Colorless
4.3.9. Compound (6i). Yield = 81% (117 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H17O2 241.1229,
gum; HRMS (ESI, M++1) calcd for C20H19O2 291.1385,
1
1
found 241.1232; H NMR (400 MHz, CDCl3): δ 7.39-7.33
found 291.1386; H NMR (400 MHz, CDCl3): δ 7.80-7.72
(m, 5H), 6.91 (dd, J = 2.0, 8.8 Hz, 1H), 6.90 (s, 1H), 6.84
(d, J = 8.8 Hz, 1H), 5.43 (d, J = 1.2 Hz, 1H), 5.40 (d, J =
1.2 Hz, 1H), 3.91 (s, 3H), 3.84 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 149.68, 148.78, 148.51, 141.55, 134.29,
128.25 (2x), 128.06 (2x), 127.66, 120.88, 113.11, 111.39,
110.70, 55.84, 55.81.
(m, 2H), 7.30 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 1.6 Hz, 1H),
7.52 (dd, J = 1.6, 8.8 Hz, 1H), 7.43-7.39 (m, 2H), 7.21 (d,
J = 8.0 Hz, 1H), 6.54 (dd, J = 2.8, 8.4 Hz, 1H), 6.51 (d, J =
2.4 Hz, 1H), 5.80 (d, J = 1.6 Hz, 1H), 5.40 (d, J = 1.2 Hz,
1H), 3.85 (s, 3H), 3.58 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 160.68, 158.19, 146.60, 138.93, 133.35, 132.80,
131.75, 128.20, 127.46, 127.42, 125.83, 125.58, 125.36,
124.89, 123.75, 115.66, 104.23, 99.01, 55.53, 55.34.
4.3.4. Compound (6d). Yield = 89% (120 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C17H19O3 271.1334,
1
found 271.1336; H NMR (400 MHz, CDCl3): δ 7.35-7.25
4.3.10. Compound (6j). Yield = 76% (104 mg); Colorless
(m, 5H), 6.99 (d, J = 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H),
5.63 (d, J = 1.6 Hz, 1H), 5.32 (d, J = 1.6 Hz, 1H), 3.90 (s,
3H), 3.87 (s, 3H), 3.53 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 153.46, 151.53, 146.91, 142.21, 141.84, 129.00,
127.96 (2x), 127.30, 126.54 (2x), 125.08, 115.18, 106.78,
60.68, 60.40, 55.88.
gum; HRMS (ESI, M++1) calcd for C19H15O2 275.1072,
1
found 275.1077; H NMR (400 MHz, CDCl3): δ 7.87-7.81
(m, 4H), 7.52-7.49 (m, 3H), 6.91 (dd, J = 2.0, 5.2 Hz, 1H),
6.88 (d, J = 1.6 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.00 (s,
2H), 5.52 (d, J = 1.2 Hz, 1H), 5.51 (d, J = 0.8 Hz, 1H); 13
C
NMR (100 MHz, CDCl3): δ 149.58, 147.55, 147.32,
139.00, 135.71, 133.24, 132.94, 128.15, 127.63, 127.56,
127.27, 126.45, 126.13, 126.00, 122.12, 113.90, 108.74,
107.98, 101.08.
4.3.5. Compound (6e). Yield = 81% (103 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C17H19O2 255.1385,
1
found 255.1388; H NMR (400 MHz, CDCl3): δ 7.23 (d, J
= 8.4 Hz, 2H), 7.17 (dd, J = 0.8, 8.0 Hz, 1H), 7.11 (d, J =
8.0 Hz, 2H), 6.53 (dd, J = 2.4, 8.0 Hz, 1H), 6.53 (br s, 1H),
5.68 (d, J = 1.6 Hz, 1H), 5.28 (d, J = 1.6 Hz, 1H), 3.86 (s,
3H), 3.66 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 160.49, 158.11, 146.38, 138.55, 136.84, 131.62,
128.64 (2x), 126.28 (2x), 123.98, 114.21, 104.14, 98.98,
55.56, 55.29, 21.07.
4.3.11. Compound (6k). Yield = 80% (116 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C20H19O2 291.1385,
1
found 291.1386; H NMR (400 MHz, CDCl3): δ 7.88-7.80
(m, 3H), 7.60-7.32 (m, 4H), 6.98-6.94 (m, 2H), 6.87 (d, J =
8.4 Hz, 1H), 5.54 (d, J = 1.6 Hz, 1H), 5.53 (d, J = 1.2 Hz,
1H), 3.93 (s, 3H), 3.84 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 149.66, 148.83, 148.54, 136.51, 134.27, 129.34,
128.71, 128.11, 127.55, 127.52, 127.21, 126.42, 126.08,
125.95, 120.96, 113.67, 111.45, 110.74, 55.84, 55.81.
4.3.6. Compound (6f). Yield = 80% (95 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H15O2 239.1072,
1
found 239.1074; H NMR (400 MHz, CDCl3): δ 7.25 (d, J
4.3.12. Compound (6l). Yield = 85% (136 mg); Colorless
= 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 6.90-6.80 (m, 3H),
5.93 (s, 2H), 5.31 (d, J = 1.2 Hz, 1H), 5.28 (d, J = 1.2 Hz,
1H), 2.33 (s, 3H).
gum; HRMS (ESI, M++1) calcd for C21H21O3 321.1491,
1
found 321.1493; H NMR (400 MHz, CDCl3): δ 7.84-7.77
(m, 2H), 7.81 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 1.6 Hz, 1H),
7.56 (dd, J = 1.6, 8.8 Hz, 1H), 7.46-7.44 (m, 2H), 7.04 (d,
J = 8.4 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 5.78 (d, J = 1.6
Hz, 1H), 5.42 (d, J = 1.6 Hz, 1H), 3.93 (s, 3H), 3.89 (s,
3H), 3.52 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.59,
151.67, 146.82, 142.31, 139.22, 133.25, 132.83, 128.98,
128.13, 127.58, 127.49, 125.96, 125.69, 125.48, 125.21,
124.96, 115.82, 106.90, 60.75, 60.54, 55.95.
4.3.7. Compound (6g). Yield = 74% (94 mg); Colorless
o
solid; mp = 109-110 C (recrystallized from hexanes and
EtOAc); HRMS (ESI, M++1) calcd for C17H19O2 255.1385,
1
found 255.1392; H NMR (400 MHz, CDCl3): δ 7.28 (d, J
= 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.92 (dd, J = 2.0,
8.4 Hz, 1H), 6.91 (s, 1H), 6.84 (d, J = 8.4 Hz, 1H), 5.38 (s,
2H), 3.91 (s, 3H), 3.85 (s, 3H), 2.39 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 149.48, 148.66, 148.42, 138.59,
4.3.13. Compound (6m). Yield = 78% (123 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C22H21O2 317.1542,

ACCEPTED MANUSCRIPT
8
Tetrahedron
1
found 317.1538; H NMR (400 MHz, CDCl3): δ 7.67-7.64
(m, 2H), 7.59-7.54 (m, 2H), 7.49-7.34 (m, 5H), 7.24 (d, J =
8.0 Hz, 1H), 6.58 (dd, J = 2.4, 8.0 Hz, 1H), 6.57 (br s, 1H),
5.79 (d, J = 1.2 Hz, 1H), 5.38 (d, J = 1.2 Hz, 1H), 3.89 (s,
3H), 3.69 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.63,
158.10, 140.79, 140.37, 139.84, 131.65, 128.68 (2x),
127.11, 126.88 (2x), 126.80 (2x), 126.62 (2x), 126.16,
123.68, 115.04, 104.21, 98.98, 55.53, 55.31.
148.58, 148.54, 147.35, 137.63 (d, J = 3.0 Hz), 135.50,
129.89 (d, J = 8.4 Hz, 2x), 121.92, 114.97 (d, J = 20.5 Hz,
2x), 113.25, 108.51, 107.94, 101.08.
4.3.19. Compound (6s). Yield = 82% (106 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H16FO2 259.1134,
1
found 259.1138; H NMR (400 MHz, CDCl3): δ 7.34-7.30
(m, 2H), 7.03-6.99 (m, 2H), 6.87 (dd, J = 2.0, 8.8 Hz, 1H),
6.86 (br s, 1H), 6.82 (d, J = 8.8 Hz, 1H), 5.38 (d, J = 0.8
Hz, 1H), 5.33 (d, J = 1.2 Hz, 1H), 3.89 (s, 3H), 3.83 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 162.34 (d, J = 244.8
Hz), 148.57, 148.46, 137.53 (d, J = 3.7 Hz), 136.43,
129.78 (d, J = 7.5 Hz, 2x), 129.44, 120.71, 114.83 (d, J =
21.2 Hz, 2x), 112.92, 111.17, 110.63, 55.74, 55.70.
4.3.14. Compound (6n). Yield = 74% (111 mg); Colorless
o
solid; mp = 99-100 C (recrystallized from hexanes and
EtOAc); HRMS (ESI, M++1) calcd for C21H17O2 301.1229,
1
found 301.1230; H NMR (400 MHz, CDCl3): δ 7.64-7.56
(m, 4H), 7.48-7.34 (m, 5H), 6.88 (d, J = 0.8 Hz, 1H), 6.87
(dd, J = 1.2, 7.6 Hz, 1H), 6.80 (dd, J = 1.2, 7.6 Hz, 1H),
5.99 (s, 2H), 5.43 (d, J = 1.2 Hz, 1H), 5.41 (d, J = 1.2 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ 149.20, 147.52,
147.30, 140.71, 140.57, 140.52, 128.77 (2x), 135.68,
128.68 (2x), 127.32, 127.02 (2x), 126.85 (2x), 122.07,
113.40, 108.72, 107.97, 101.08.
4.3.20. Compound (6t). Yield = 83% (120 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C17H18FO3 289.1240,
1
found 289.1245; H NMR (400 MHz, CDCl3): δ 7.31-7.26
(m, 2H), 7.01-6.95 (m, 3H), 6.68 (d, J = 8.4 Hz, 1H), 5.55
(d, J = 1.6 Hz, 1H), 5.27 (d, J = 1.2 Hz, 1H), 3.89 (s, 3H),
3.86 (s, 3H), 3.54 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
162.15 (d, J = 244.8 Hz), 153.57, 151.39, 145.94, 142.20,
137.91 (d, J = 3.0 Hz), 128.66, 128.05 (d, J = 7.5 Hz, 2x),
124.94, 114.94, 114.71 (d, J = 21.3 Hz, 2x), 106.81, 60.61,
60.36, 55.79.
4.3.15. Compound (6o). Yield = 80% (126 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C22H21O2 317.1542,
1
found 317.1543; H NMR (400 MHz, CDCl3): δ 7.67-7.55
(m, 4H), 7.50-7.32 (m, 5H), 6.97 (dd, J = 2.0, 8.0 Hz, 1H),
6.96 (br s, 1H), 6.88 (d, J = 8.0 Hz, 1H), 5.49 (d, J = 1.6
Hz, 1H), 5.43 (d, J = 1.2 Hz, 1H), 3.93 (s, 3H), 3.87 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 149.20, 148.76,
148.48, 140.40, 136.45, 134.16, 129.30, 128.68 (2x),
128.59 (2x), 127.24, 126.86 (2x), 126.71 (2x), 120.89,
113.11, 111.39, 110.68, 55.78 (2x).
4.3.21. Compound (6u). Yield = 82% (111 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C17H19O3 271.1334,
1
found 271.1335; H NMR (400 MHz, CDCl3): δ 7.25 (d, J
= 8.8 Hz, 2H), 7.15 (dd, J = 0.8, 8.0 Hz, 1H), 6.82 (d, J =
8.8 Hz, 2H), 6.52 (dd, J = 2.4, 8.0 Hz, 1H), 6.51 (s, 1H),
5.61 (d, J = 1.6 Hz, 1H), 5.20 (d, J = 1.6 Hz, 1H), 3.85 (s,
3H), 3.81 (s, 3H), 3.65 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 160.48, 158.90, 158.06, 145.92, 133.97, 132.13,
131.58, 127.52 (2x), 123.99, 113.27 (2x), 104.13, 98.94,
55.56, 55.31, 55.15.
4.3.16. Compound (6p). Yield = 81% (140 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C23H23O3 347.1647,
1
found 347.1648; H NMR (400 MHz, CDCl3): δ 7.65 (d, J
= 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, 2H), 7.49-7.44 (m, 4H),
7.39-7.35 (m, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.74 (d, J =
8.4 Hz, 1H), 5.74 (d, J = 1.2 Hz, 1H), 5.38 (d, J = 1.2 Hz,
1H), 3.94 (s, 3H), 3.93 (s, 3H), 3.63 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 153.49, 151.55, 146.36, 142.21,
140.68, 140.62, 140.03, 128.86, 128.64 (2x), 127.11,
126.93 (2x), 126.82 (2x), 126.65 (2x), 125.10, 115.18,
106.83, 60.71, 60.53, 55.87.
4.3.22. Compound (6v). Yield = 78% (99 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H15O3 255.1021,
1
found 255.1022; H NMR (400 MHz, CDCl3): δ 7.28 (d, J
= 8.8 Hz, 2H), 6.89-6.77 (m, 5H), 5.97 (s, 2H), 5.30 (d, J =
1.2 Hz, 1H), 5.29 (d, J = 1.2 Hz, 1H), 3.83 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 159.30, 149.04, 147.41,
147.16, 136.02, 134.06, 129.40 (2x), 121.96, 113.45 (2x),
112.04, 108.69, 107.86, 101.01, 55.24.
4.3.17. Compound (6q). Yield = 76% (98 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H16FO2 259.1134,
4.3.23. Compound (6w). Yield = 78% (105 mg); Colorless
1
found 259.1139; H NMR (400 MHz, CDCl3): δ 7.37-7.32
o
solid; mp = 102-103 C (recrystallized from hexanes and
(m, 2H), 7.23 (d, J = 7.6 Hz, 1H), 7.05-6.99 (m, 2H), 6.59
(dd, J = 2.8, 8.4 Hz, 1H), 6.57 (br s, 1H), 5.67 (d, J = 1.2
Hz, 1H), 5.36 (d, J = 1.2 Hz, 1H), 3.88 (s, 3H), 3.66 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 162.08 (d, J = 244.1
Hz), 160.68, 157.93, 145.70, 137.59 (d, J = 3.0 Hz),
131.47, 127.90 (d, J = 8.3 Hz, 2x), 123.40, 114.68, 114.59
(d, J = 21.2 Hz, 2x), 104.14, 98.85, 55.23, 55.10.
EtOAc); HRMS (ESI, M++1) calcd for C17H19O3 271.1334,
1
found 271.1336; H NMR (400 MHz, CDCl3): δ 7.30 (d, J
= 8.8 Hz, 2H), 6.92-6.82 (m, 5H), 5.33 (d, J = 1.2 Hz, 1H),
5.31 (d, J = 1.2 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.83 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 159.25, 149.11,
148.67, 148.42, 134.57, 133.99, 129.36 (2x), 120.82,
113.40 (2x), 111.76, 111.42, 110.63, 55.82, 55.78, 55.18.
Single-crystal X-Ray diagram: crystal of compound 6w
was grown by slow diffusion of EtOAc into a solution of
compound 6w in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the monoclinic crystal system,
space group P 21/c, a = 13.4937(12) Å, b = 16.3772(15) Å,
c = 6.6323(5) Å, V = 1435.9(2) Å3, Z = 4, dcalcd= 1.250
4.3.18. Compound (6r). Yield = 87% (105 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C15H12FO2 243.0821,
1
found 243.0823; H NMR (400 MHz, CDCl3): δ 7.34-7.30
(m, 2H), 7.06-7.01 (m, 2H), 6.83-6.77 (m, 3H), 5.98 (s,
2H), 5.38 (d, J = 0.8 Hz, 1H), 5.32 (d, J = 0.8 Hz, 1H); 13
C
NMR (100 MHz, CDCl3): δ 162.47 (d, J = 244.8 Hz),

ACCEPTED MANUSCRIPT
Tetrahedron
9
g/cm3, F(000) = 576, 2θ range 1.540~26.437o, R indices
(all data) R1 = 0.0814, wR2 = 0.1178.
(4x), 126.27 (4x), 123.20, 114.39 (2x), 96.29, 55.82 (2x),
21.07 (2x).
4.3.24. Compound (6x). Yield = 82% (123 mg); Colorless
4.4.3. Compound (8c). Yield = 70% (141 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C18H21O4 301.1440,
gum; HRMS (ESI, M++1) calcd for C26H27O4 403.1909,
1
1
found 301.1445; H NMR (400 MHz, CDCl3): δ 7.26 (d, J
found 403.1915; H NMR (400 MHz, CDCl3): δ 7.27 (d, J
= 8.8 Hz, 2H), 6.96 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 8.8 Hz,
2H), 6.68 (d, J = 8.4 Hz, 1H), 5.56 (d, J = 1.6 Hz, 1H),
5.20 (d, J = 1.6 Hz, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.79 (s,
3H), 3.57 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.93,
153.27, 151.43, 146.12, 142.10, 134.19, 129.08, 127.56
(2x), 124.97, 113.40, 113.22 (2x), 106.70, 60.60, 60.42,
55.76, 54.97.
= 8.8 Hz, 4H), 7.11 (s, 1H), 6.82 (d, J = 8.8 Hz, 4H), 6.50
(s, 1H), 5.60 (d, J = 1.6 Hz, 2H), 5.21 (d, J = 1.2 Hz, 2H),
3.81 (s, 6H), 3.70 (s, 6H); 13C NMR (100 MHz, CDCl3): δ
158.94 (2x), 157.63 (2x), 145.74 (2x), 134.01 (2x), 133.61
(2x), 127.58 (4x), 123.32, 113.55 (2x), 113.33 (4x), 96.35,
55.94 (2x), 55.22 (2x).
4.4.4. Compound (8d). Yield = 68% (168 mg); Colorless
o
4.4. A representative synthetic procedure of compounds
8a-e is as follows: Freshly prepared mCPBA (87 mg, 0.5
mmol) was added to a solution of 2a-d or 2f (0.5 mmol) in
CH2Cl2 (10 mL) at rt. The reaction mixture was stirred at rt
for 10 min. 4a (35 mg, 0.25 mmol) was added to the
reaction mixture at rt. Then, BF3·OEt2 (71 mg, 0.5 mmol)
was added to the reaction mixture at rt. After the reaction
mixture was stirred at rt for 20 min, saturated NaHCO3
solution (10 mL) was added to the reaction mixture. The
reaction mixture was extracted with CH2Cl2 (3 x 20 mL).
The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product under
reduced pressure. Without further purification, 5% Pd/C
(100 mg) was added to the resulting reaction mixture in
EtOH (10 mL) at rt. The reaction mixture was stirred at rt
for 20 min. The reaction mixture was filtered and washed
by CH2Cl2 (2 x 10 mL). The combined organic layers were
dried, filtered and evaporated to afford crude product under
solid; mp = 180-181 C (recrystallized from hexanes and
EtOAc); HRMS (ESI, M++1) calcd for C36H31O2 495.2324,
1
found 495.2326; H NMR (400 MHz, CDCl3): δ 7.67-7.58
(m, 8H), 7.49-7.33 (m, 10H), 7.25 (s, 1H), 6.59 (s, 1H),
5.80 (d, J = 1.2 Hz, 2H), 5.42 (d, J = 1.2 Hz, 2H), 3.76 (s,
6H); 13C NMR (100 MHz, CDCl3): δ 157.79 (2x), 145.89
(2x), 140.80 (2x), 140.33 (2x), 139.90 (2x), 133.65 (2x),
128.70 (4x), 127.13 (2x), 126.90 (4x), 126.84 (4x), 126.67
(4x), 123.01, 115.33 (2x), 96.27, 55.87 (2x). Single-crystal
X-Ray diagram: crystal of compound 8d was grown by
slow diffusion of EtOAc into a solution of compound 8d in
CH2Cl2 to yield colorless prisms. The compound
crystallizes in the triclinic crystal system, space group P - 1,
a = 8.414(10) Å, b = 12.311(14) Å, c = 27.28(3) Å, V =
2808(6) Å3, Z = 4, dcalcd= 1.170 g/cm3, F(000) = 1048, 2θ
range 1.502~26.141o, R indices (all data) R1 = 0.1260,
wR2 = 0.1471.
4.4.5. Compound (8e). Yield = 62% (137 mg); Colorless
reduced
pressure.
Purification
on
silica
gel
gum; HRMS (ESI, M++1) calcd for C32H27O2 443.2011,
(hexanes/EtOAc = 10/1~5/1) afforded 8a-e.
1
found 443.2015; H NMR (400 MHz, CDCl3): δ 7.88-7.80
4.4.1. Compound (8a). Yield = 68% (116 mg); Colorless
(m, 8H), 7.62 (dd, J = 2.0, 8.8 Hz, 2H), 7.52-7.46 (m, 4H),
7.32 (s, 1H), 6.61 (s, 1H), 5.87 (d, J = 1.2 Hz, 2H), 5.51 (d,
J = 1.6 Hz, 2H), 3.73 (s, 6H); 13C NMR (100 MHz, CDCl3):
δ 157.90 (2x), 146.37 (2x), 138.95 (2x), 133.81 (2x),
133.35 (2x), 132.82 (2x), 128.21 (2x), 127.49 (2x), 127.45
(2x), 125.86 (2x), 125.61 (2x), 125.39 (2x), 124.95 (2x),
123.03, 115.97 (2x), 96.27, 55.86 (2x).
o
solid; mp = 105-106 C (recrystallized from hexanes and
EtOAc); HRMS (ESI, M++1) calcd for C24H23O2 343.1698,
1
found 343.1702; H NMR (400 MHz, CDCl3): δ 7.44-7.41
(m, 4H), 7.38-7.29 (m, 6H), 7.23 (s, 1H), 6.57 (s, 1H), 5.75
(d, J = 1.6 Hz, 2H), 5.41 (d, J = 1.6 Hz, 2H), 3.73 (s, 6H);
13C NMR (100 MHz, CDCl3): δ 157.69 (2x), 146.38 (2x),
141.38 (2x), 133.57 (2x), 127.91 (4x), 127.16 (2x), 126.38
(4x), 123.05, 115.24 (2x), 96.26, 55.76 (2x). Single-crystal
X-Ray diagram: crystal of compound 8a was grown by
slow diffusion of EtOAc into a solution of compound 8a in
CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group
C 2/c, a = 28.8343(16) Å, b = 11.4926(6) Å, c =
23.0676(13) Å, V = 7574.7(7) Å3, Z = 16, dcalcd= 1.208
g/cm3, F(000) = 2944, 2θ range 1.425~26.437o, R indices
(all data) R1 = 0.1101, wR2 = 0.1990.
4.5. A representative synthetic procedure of compounds 8f-
i is as follows: Freshly prepared mCPBA (87 mg, 0.5 mmol)
was added to a solution of 2a (115 mg, 0.5 mmol) in
CH2Cl2 (10 mL) at rt. The reaction mixture was stirred at rt
for 10 min. 4a (69 mg, 0.5 mmol) was added to the
reaction mixture at rt. Then, BF3·OEt2 (71 mg, 0.5 mmol)
was added to the reaction mixture at rt. After the reaction
mixture was stirred at rt for 20 min, 3b-e (0.5 mmol) and
BF3·OEt2 (71 mg, 0.5 mmol) in CH2Cl2 (1 mL) was added
to the reaction mixture at rt. Saturated NaHCO3 solution
(10 mL) was added to the reaction mixture. The reaction
mixture was extracted with CH2Cl2 (3 x 20 mL). The
combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product under
reduced pressure. Without further purification, 5% Pd/C
(100 mg) was added to the resulting reaction mixture in
EtOH (10 mL) at rt. The reaction mixture was stirred at rt
4.4.2. Compound (8b). Yield = 62% (115 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C26H27O2 371.2011,
1
found 371.2018; H NMR (400 MHz, CDCl3): δ 7.32 (d, J
= 8.0 Hz, 4H), 7.17 (d, J = 8.0 Hz, 4H), 6.58 (s, 2H), 5.73
(d, J = 1.2 Hz, 2H), 5.35 (d, J = 1.2 Hz, 2H), 3.75 (s, 6H),
2.41 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 157.61 (2x),
146.13 (2x), 138.45 (2x), 136.82 (2x), 133.59 (2x), 128.63

ACCEPTED MANUSCRIPT
10
Tetrahedron
for 20 min. The reaction mixture was filtered and washed
by CH2Cl2 (2 x 10 mL). The combined organic layers were
dried, filtered and evaporated to afford crude product under
128.21, 127.97 (2x), 127.49, 127.44, 127.22, 126.46 (2x),
125.84, 125.60, 125.37, 124.93, 123.14, 123.02, 115.92,
115.35, 96.32, 55.85 (2x).
reduced
pressure.
Purification
on
silica
gel
4.6. A representative synthetic procedure of compounds
12a-f is as follows: Hg(OTf)2 (50 mg, 0.1 mmol) was
added to a solution of 6a, 6e, 6l, 6m, 6q and 6u (0.5 mmol)
(hexanes/EtOAc = 10/1~5/1) afforded 8f-i.
4.5.1. Compound (8f). Yield = 57% (103 mg); Colorless
solid; mp = 94-95 C (recrystallized from hexanes and
o
o
in MeNO2 (5 mL) at 25 C. The reaction mixture was
EtOAc); HRMS (ESI, M++1) calcd for C24H22FO2
361.1604, found 361.1608; 1H NMR (400 MHz, CDCl3): δ
7.43-7.29 (m, 7H), 7.22 (s, 1H), 7.06-7.00 (m, 2H), 6.56 (s,
1H), 5.75 (d, J = 1.6 Hz, 1H), 5.66 (d, J = 1.2 Hz, 1H),
5.41 (d, J = 1.2 Hz, 1H), 5.38 (d, J = 1.2 Hz, 1H), 3.73 (s,
6H); 13C NMR (100 MHz, CDCl3): δ 162.13 (d, J = 244.1
Hz), 157.83, 157.60, 146.32, 145.46, 141.34, 137.56 (d, J
= 3.0 Hz), 133.45, 127.96 (d, J = 9.1 Hz, 2x), 127.91 (2x),
127.18, 126.36 (2x), 123.09, 122.76, 115.26, 114.99,
114.67 (d, J = 21.2 Hz, 2x), 96.16, 55.71, 55.65. Single-
crystal X-Ray diagram: crystal of compound 8f was grown
by slow diffusion of EtOAc into a solution of compound 8f
in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P
21/n, a = 10.9062(8) Å, b = 23.0224(16) Å, c = 15.7346(11)
Å, V = 3927.7(5) Å3, Z = 8, dcalcd= 1.219 g/cm3, F(000) =
1520, 2θ range 1.574~26.427o, R indices (all data) R1 =
0.1704, wR2 = 0.1560.
stirred at 25 oC for 8 h. The reaction mixture was
concentrated and extracted with CH2Cl2 (3 x 10 mL). The
combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product under
reduced
pressure.
Purification
on
silica
gel
(hexanes/EtOAc = 20/1~8/1) afforded 12a-f.
4.6.1. Compound (12a).22a Yield = 75% (84 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C15H13O2 225.0916,
1
found 225.0917; H NMR (400 MHz, CDCl3): δ 7.75 (d, J
= 8.8 Hz, 1H), 7.74 (s, 1H), 7.69-7.65 (m, 2H), 7.52-7.48
(m, 2H), 7.42-7.37 (m, 1H), 7.12 (d, J = 2.4 Hz, 1H), 6.99
(dd, J = 2.4, 8.8 Hz, 1H), 3.90 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 158.14, 156.81, 140.27, 132.17, 128.88
(2x), 127.32, 127.30 (2x), 122.06, 120.50, 119.75, 112.04,
96.13, 55.65.
4.6.2. Compound (12b). Yield = 70% (83 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H15O2 239.1072,
1
found 239.1079; H NMR (400 MHz, CDCl3): δ 7.69 (d, J
4.5.2. Compound (8g). Yield = 68% (121 mg); Colorless
= 8.4 Hz, 1H), 7.69 (s, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.28
(d, J = 8.4 Hz, 2H), 7.08 (d, J = 2.4 Hz, 1H), 6.95 (dd, J =
2.4, 8.8 Hz, 1H), 3.88 (s, 3H), 2.42 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 158.10, 156.79, 140.03, 137.13, 129.60
(2x), 129.24, 127.21 (2x), 121.97, 120.54, 119.94, 111.97,
96.13, 55.71, 21.22.
gum; HRMS (ESI, M++1) calcd for C25H25O2 357.1855,
1
found 357.1859; H NMR (400 MHz, CDCl3): δ 7.37-7.24
(m, 7H), 7.14 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 6.51 (s, 1H),
5.68 (d, J = 1.6 Hz, 1H), 5.70 (d, J = 1.6 Hz, 1H), 5.34 (d,
J = 1.2 Hz, 1H), 5.28 (d, J = 1.2 Hz, 1H), 3.71 (s, 3H), 3.69
(s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
157.75, 157.63, 146.44, 146.14, 141.45, 138.47, 136.93,
133.64, 128.69 (2x), 127.95 (2x), 127.19, 126.44 (2x),
126.31 (2x), 123.30, 123.09, 115.27, 114.47, 96.35, 55.93,
55.86, 21.13.
4.6.3. Compound (12c). Yield = 78% (107 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C19H15O2 275.1072,
1
found 275.1078; H NMR (400 MHz, CDCl3): δ 8.12 (s,
1H), 7.94 (d, J = 8.8 Hz, 1H), 7.90 (dt, J = 1.6, 8.4 Hz, 2H),
7.84 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.74 (dd, J = 1.6, 8.4
Hz, 1H), 7.56-7.59 (m, 2H), 7.12 (d, J = 2.4 Hz, 1H), 7.00
(dd, J = 2.4, 8.8 Hz, 1H), 3.91 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 158.22, 156.93, 140.71, 133.70, 132.63,
129.64, 128.56, 127.90, 127.74, 126.40, 125.90, 125.67
(2x), 122.07, 120.63, 119.82, 112.16, 96.20, 55.71.
4.5.3. Compound (8h). Yield = 69% (144 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C30H27O2 419.2011,
1
found 419.2020; H NMR (400 MHz, CDCl3): δ 7.64-7.61
(m, 2H), 7.56-7.54 (m, 2H), 7.46-7.27 (m, 10H), 7.18 (s,
1H), 6.53 (s, 1H), 5.75 (d, J = 1.2 Hz, 1H), 5.70 (d, J = 1.6
Hz, 1H), 5.36 (d, J = 1.2 Hz, 1H), 5.35 (d, J = 1.6 Hz, 1H),
3.72 (s, 3H), 3.70 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
157.79, 157.75, 146.41, 145.92, 141.42, 140.84, 140.33,
139.91, 133.65, 128.71 (2x), 127.97 (2x), 127.23, 127.15,
126.93 (2x), 126.83 (2x), 126.68 (2x), 126.44 (2x), 123.14,
122.98, 115.33, 115.30, 96.29, 55.90, 55.87.
4.6.4. Compound (12d). Yield = 73% (110 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C21H17O2 301.1229,
1
found 301.1223; H NMR (400 MHz, CDCl3): δ 7.81-7.67
(m, 8H), 7.54-7.51 (m, 2H), 7.45-7.41 (m, 1H), 7.15 (d, J =
2.0 Hz, 1H), 7.03 (dd, J = 2.4, 8.8 Hz, 1H), 3.92 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 158.16, 156.86, 140.95,
140.36, 140.08, 131.15, 128.79 (2x), 127.54 (2x), 127.33,
127.18, 126.93 (2x), 121.64, 120.53, 119.68, 112.10, 96.15,
96.15, 55.62.
4.5.4. Compound (8i). Yield = 64% (125 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C28H25O2 393.1855,
1
found 393.1859; H NMR (400 MHz, CDCl3): δ 7.87-7.81
(m, 3H), 7.77 (d, J = 1.6 Hz, 1H), 7.60 (dd, J = 1.6, 8.4 Hz,
1H), 7.51-7.46 (m, 1H), 7.44-7.29 (m, 7H), 6.58 (s, 1H),
5.86 (d, J = 1.6 Hz, 1H), 5.74 (d, J = 1.6 Hz, 1H), 5.49 (d,
J = 1.6 Hz, 1H), 5.42 (d, J = 1.6 Hz, 1H), 3.75 (s, 3H), 3.70
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 157.82, 146.42,
146.37, 141.46, 138.92, 133.72, 133.35, 132.82, 128.66,
4.6.5. Compound (12e). Yield = 71% (86 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C15H12FO2 243.0821,
1
found 243.0822; H NMR (400 MHz, CDCl3): δ 7.67 (s,
1H), 7.64 (d, J = 8.8 Hz, 1H), 7.60-7.57 (m, 2H), 7.19-7.14
(m, 2H), 7.08 (d, J = 2.4 Hz, 1H), 6.96 (dd, J = 2.4, 8.8 Hz,

ACCEPTED MANUSCRIPT
Tetrahedron
11
1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 162.16
References and notes
(d, J = 244.9 Hz), 158.21, 156.75, 140.10, 128.87 (d, J =
8.4 Hz, 2x), 128.17 (d, J = 3.0 Hz), 121.18, 120.23, 119.66,
115.85 (d, J = 21.2 Hz, 2x), 112.15, 96.13, 55.67.
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4.6.6. Compound (12f).22b Yield = 73% (93 mg); Colorless
gum; HRMS (ESI, M++1) calcd for C16H15O3 255.1021,
1
found 254.0934; H NMR (400 MHz, CDCl3): δ 7.71 (d, J
= 8.8 Hz, 1H), 7.68 (s, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.11
(d, J = 2.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 6.98 (dd, J =
2.0, 8.8 Hz, 1H), 3.89 (s, 3H), 3.88 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 158.94, 158.04, 156.69, 139.59, 128.37
(2x), 124.51, 121.58, 120.38, 119.94, 114.30 (2x), 111.86,
96.06, 55.56, 55.18.
4.7. Compound (13). Freshly prepared mCPBA (156 mg,
0.9 mmol) was added to a solution of 2a (207 mg, 0.9
mmol) in CH2Cl2 (10 mL) at rt. The reaction mixture was
stirred at rt for 10 min. 4e (50 mg, 0.3 mmol) was added to
the reaction mixture at rt. Then, BF3·OEt2 (130 mg, 0.9
mmol) was added to the reaction mixture at rt. After the
reaction mixture was stirred at rt for 20 min, saturated
NaHCO3 solution (10 mL) was added to the reaction
mixture. The reaction mixture was extracted with CH2Cl2
(3 x 20 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude
product under reduced pressure. Without further
purification, 5% Pd/C (100 mg) was added to the resulting
reaction mixture in EtOH (10 mL) at rt. The reaction
mixture was stirred at rt for 20 min. The reaction mixture
was filtered and washed by CH2Cl2 (2 x 10 mL). The
combined organic layers were dried, filtered and
evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc = 10/1~5/1)
afforded 13. Yield = 40% (45 mg); Colorless solid; mp =
100-102 oC (recrystallized from hexanes and EtOAc);
HRMS (ESI, M++1) calcd for C25H25O3 373.1804, found
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1
373.1805; H NMR (400 MHz, CDCl3): δ 7.42-7.40 (m,
4H), 7.33-7.23 (m, 6H), 6.43 (s, 1H), 5.98 (d, J = 1.2 Hz,
2H), 5.35 (d, J = 1.2 Hz, 2H), 3.77 (s, 6H), 3.35 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 157.88 (2x), 157.49,
141.25 (2x), 140.96 (2x), 128.05 (4x), 127.18 (2x), 125.83
(4x), 117.28 (2x), 116.59 (2x), 91.85, 61.03, 56.00 (2x).
Single-crystal X-Ray diagram: crystal of compound 13 was
grown by slow diffusion of EtOAc into a solution of
compound 13 in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the orthorhombic crystal system,
space group P n a 21, a = 20.8499(13) Å, b = 12.3895(7) Å,
c = 7.9367(4) Å, V = 2050.2(2) Å3, Z = 4, dcalcd= 1.207
g/cm3, F(000) = 792, 2θ range 1.912~26.398o, R indices
(all data) R1 = 0.1245, wR2 = 0.1742.
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Acknowledgments
The authors would like to thank the Ministry of Science
and Technology of the Republic of China for its financial
support (MOST 104-2113-M-037-012).

ACCEPTED MANUSCRIPT
12
Tetrahedron
Jia, T.; Zhang, M.; Sagamanova, I. K.; Wang, C. Y.; Walsh, P. J.
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for this paper. This data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-
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Supplementary Material
Experimental procedure and scanned photocopies of NMR
(CDCl3) spectral data were supported.