NBS-mediated cyclization of trans-cinnamic alcohols

Article abstract of DOI:10.1016/j.tet.2013.05.110

An efficient and straightforward three-step synthetic route toward 2,4-disubstituted-3-bromooxetanes 5 with the trans-trans contiguous stereogenic centers is developed from functionalized chalcones 3 via NaBH ₄-mediated reduction of chalcones 3

Full text of DOI:10.1016/j.tet.2013.05.110

Tetrahedron 69 (2013) 6364e6370
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
NBS-mediated cyclization of trans-cinnamic alcohols
*
Meng-Yang Chang , Chung-Yu Tsai, Ming-Hao Wu
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and straightforward three-step synthetic route toward 2,4-disubstituted-3-bromooxetanes 5
with the transetrans contiguous stereogenic centers is developed from functionalized chalcones 3 via
NaBH4-mediated reduction of chalcones 3, followed by NBS-mediated electrophilic cyclization of the
resulting trans-cinnamic alcohols 4 in good yield. Skeleton 3 is prepared by ClaiseneSchmidt condensation
of substituted arylaldehydes 1 and aryl methyl ketones or tert-butyl methyl ketones 2. The synthetic route
obtained high yields, and the total reaction procedure took only one day. The substituent effect of skeleton
3, various reaction conditions, and plausible mechanism were well-investigated.
Received 26 March 2013
Received in revised form 20 May 2013
Accepted 27 May 2013
Available online 31 May 2013
Keywords:
Oxetanes
Cinnamic alcohols
Electrophilic cyclization
N-Bromosuccinimide
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
observed and the major complicated polymers were isolated under
the reaction conditions, as shown in Scheme 1.
Halodecarboxylation of functionalized cinnamic acids (
saturated carboxylic acids) is a useful methodology in the organic
field for preparing diversified
-halostyrenes (vinyl halides).1,2
a,b-un-
Br
O
b
Br(collidine) PF
2
R
R
6
Ph
α
R
1
2
1
Ph
There are many protocols and reagents reported for the bromo-
decarboxylation of cinnamic acids;2 however, the modified Huns-
diecker reaction is the most popular approach among the existing
methods.3 In comparison with reports in the related studies on the
bromination of cinnamic acids, few reports focus on the bromina-
tion of cinnamic alcohols. In a previous work, Rousseau and co-
workers found that the bromination of cinnamyl alcohols (pre-
pared from addition of lithium phenylacetylide to carbonyl com-
pounds, followed by reduction of the resulting alkyne) in CH2Cl2 in
the presence of bis(collidine)bromide(I) hexafluorophosphate
ðBrþðcollidineÞ2PF6ꢀÞ yielded 3-bromooxetanes; they suggested
that cinnamyl tertiary alcohols possessing a gem-disubstituted
group could provide better yields by the endo-trig electrophilic
cyclization via carbocationic intermediate. But, secondary alcohols
led mainly to degradation; oxetanes were only obtained in low
HO
R
2
CH Cl
2
2
R
R
= H, R = H, 48~88%
2
= H, R = H, 15~29%
2
cinnamic alcohol
1
1
Scheme 1. Rousseau’s bromocyclization of cinnamic alcohols.
To continue our recent investigation of the ClaiseneSchmidt
condensation for the preparation of oxygenated and benzannulated
rigid molecules (e.g., benzo[g]indazoles, azahomoisotwistanes),5
a facile, stereochemical, high-yield, easy-operation route for NBS-
mediated synthesis of 2,4-disubstituted-3-bromooxetanes was
studied next.
2. Results and discussion
To initiate the synthetic work, chalcone 3a was prepared via
ClaiseneSchmidt condensation of 4-methoxybenzaldehyde (1a)
with acetophenone (2a) in a qualitative yield under an aqueous
alkaline methanolic solution, as shown in Scheme 2. In an attempt
to develop a practical method of oxetane skeleton 5, an NaBH4-
mediated reduction of compound 3a followed by the N-bromo-
succinimide (NBS)-mediated intramolecular electrophilic cycliza-
tion of the resulting trans-cinnamic alcohol 4a provided the sole
2,4-diphenyloxetane 5a in a 78% yield. We found that product 5a
possessed the stereochemical transetrans orientation at the con-
tiguous chiral center of the C2eC3eC4 position.
yields.4 It was also observed that no
b-bromostyrene was isolated
from the brominative cyclization of cinnamyl alcohols. Further
screening of reaction substrates revealed that bromination of cin-
namyl secondary alcohols with
a-substituent was insufficient to
produce the moderate yields of the oxetane skeleton; however, the
formation of poor yields of the corresponding oxetanes was
* Corresponding author. Tel.: þ886 7 3121101x2220; e-mail addresses: mychang@
kmu.edu.tw, mychang624@yahoo.com.tw (M.-Y. Chang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.110

M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
6365
using single-crystal X-ray analysis.6 The overall three-step synthetic
procedure is a straightforward, efficient, and high-yield route to
prepare compounds 5aep, and involves (1) one purification (by
column chromatography), (2) short reaction time (1 day), and (3)
two quantitative-yield reactions.
O
O
CHO
NaOH,
MeOH
+
MeO
MeO
3a (~100%)
1a
2a
trans
trans
Br
3
OH
NaBH
NBS
MeCN
4
O
4
2
Table 2
MeOH/THF
MeO
Synthesis of compounds 5aepa
MeO
4a (~100%)
5a (78%)
Br
O
1) NaBH , MeOH/THF
H
H
4
Scheme 2. Synthesis of compound 5a.
Ar
1
Ar
2
O
Ar
1
Ar
2) NBS, MeCN
2
3a-3p
5a-5p
After compound 4a was treated with 1.0 equiv of N-chlor-
osuccinimide (NCS) in MeCN, we found that the compound 4a re-
covery was complete at 0 ꢁC for 1 h, as shown in Table 1. By the
elevated reaction temperature (0 ꢁC, rt, reflux) and time (1 h, 4 h), no
reaction and an unknown mixture were observed (entries 1e4). In
the reaction of compound 4a with N-iodosuccinimide (NIS), only
compound 3a was isolated under different conditions (entries 5 and
6). A similar phenomenon was also shown in entries 7 and 8 via the
N-selenosuccinimide (NSeS)-mediated oxidation of compound 4a.
From the experimental results, we found that no desired oxetane
skeleton was formed. For the distribution of products, three events
can be summarized: (1) NCS exhibited a poorer chloronium ion
source for the electrophilic cyclization of cinnamic alcohol 4a; (2) the
NIS-mediated oxidative ability regarding the reaction of cinnamic
alcohol 4a was stronger than that of NSeS; and (3) the oxidation
reaction of cinnamic alcohol 4a with NIS and NSeS was preferred to
proceed, in comparison with the electrophilic cyclization.
Entry
Products 5/Yield (%)b
Br
O
1
MeO
5a / 78
Br
O
O
O
2
3
5b / 76
Br
O
MeO
5c / 69
Br
O
Table 1
4
5
Reaction conditions of compound 4aa,b
O
5d / 70
Br
OH
MeO
O
O
3a
O
NXS (1.0 equiv)
or / and
OH
Me
F
MeCN, temp., time
MeO
5e / 72
4a
(X = Cl, I, Se)
MeO
4a
Br
O
O
Entry
NXS
Temp
Time (h)
Yield (%)
6
7
O
4a
3a
Complex mixture
5f / 70
1
2
3
4
5
6
7
8
NCS
NCS
NCS
NCS
NIS
NIS
NSeS
NSeS
0
0
ꢁC
ꢁC
1
4
4
4
1
1
1
4
w100c
w100c
95
d
d
d
d
90
82
77
90
d
d
d
95d
d
d
d
d
Br
rt
O
O
Reflux
ꢁC
Reflux
d
O
0
d
d
5g / 68
0
ꢁC
15
d
Br
rt
OMe
OMe
a
O
O
The reactions were run on a 1.0 mmol scale with compound 4a.
The product ratios were determined by 1H NMR analysis.
The starting material 4a was recovered in quantitative yields.
The unknown mixture was obtained with different amounts.
8
9
b
c
O
OMe
d
5h / 65
Br
OMe
OMe
O
Changing two aryl substituents (Ar1 and Ar2) of skeleton 3, the
skeleton of different 2,4-diaryl-1-bromooxetanes 5aep was isolated
via the abovementioned protocol (see Table 2). Diversified chalcone
skeleton 3 provided quantitative yields via ClaiseneSchmidt con-
densations of arylaldehydes 1 and aryl methyl ketones 2. We ob-
served that the equivalent of NaOH (2.5 equiv) and the reaction time
(6 h) would be the key factors for the optimal reaction conditions.
Next, quantitative yields of skeleton 4 were derived via an NaBH4-
mediated reduction of skeleton 3. Without further purification,
NBS-mediated bromination of crude skeleton 4 was examined. With
the facile and high-yield procedure, the reaction of skeleton 4 with
NBS provided skeleton 5 with 60e78% yields in MeCN at 0 ꢁC for 1 h
(see entries 1e16). The structure of compound 5k was constructed
MeO
OMe
OMe
5i / 67
Br
MeO
MeO
OMe
OMe
O
10
11
OMe
5j / 62
Br
MeO
MeO
O
5k / 69
(continued on next page)

6366
M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
Table 2 (continued )
trifluoromethylphenyl (4-CF3Ph) and 4-nitrophenyl (4-NO2Ph)
group or nitrogen-containing heterocyclic groups (3-indole, 2-
quinoline, 2-pyrrole, 4-pyridine) on the chalcone skeleton, at-
tempts at establishing the desired oxetane skeleton failed under the
above two-step conditions. Comparing the shown yields in Tables 2
and 3, we believed that the Ar1 functionality of these substrates
should be electron-rich (bearing the electron-donating group) or
easy to delocalization (naphthalenyl or bis-phenyl group) for the
benzylic cation, and favored the attack of inner hydroxyl from the
less hindrance face. Therefore, it is easy to unstandard that the
stability (life time) of planar benzylic carbocation generated during
the reaction is crucial to achieve such stereoselectivity (via steric
interactions).
Entry
Products 5/Yield (%)b
Br
MeO
O
12
MeO
Me
5l / 72
Br
O
MeO
MeO
13
14
OMe
5m / 67
Br
MeO
MeO
OMe
OMe
O
Table 3
Synthesis of compounds 5qeva
OMe
Br
O
5n / 60
H
H
1) NaBH , MeOH/THF
4
Ar
O
1
Ar
1
2) NBS, MeCN
Br
O
MeO
MeO
5q-5v
3q-3v
15
Entry
1
Products 5/Yield (%)b
5o / 62
Br
O
Br
O
MeO
MeO
OMe
OMe
MeO
16
5q / 92
5p / 66
Br
a
For the best two-step reaction conditions: compounds 3aep (1.0 mmol), NaBH4
(70 mg, 2.0 mmol), MeOH/THF (v/v¼1/1, 10 mL), rt, 1 h, and NBS (178 mg,
1.0 mmol), 0 ꢁC, 1 h.
O
O
O
2
b
Compounds 5aep was >95% pure as determined by 1H NMR analysis.
5r / 91
Br
O
The possible mechanism for the formation of skeleton 5 is de-
scribed in Scheme 3. The initial event can be considered the preferred
formation of intermediate A with the bromonium ions by the possible
intramolecular chelation between the bromonium ions and the hy-
droxyl group. Intermediate B could not be generated easily due to the
possible repulsion at the same face between the aryl group of skeleton
4 and the involvement of the bromo group. During the equilibrium of
intermediates A and C, the oxygen lone pair promoted ring-opening of
the bromonium ion on intermediate A, followed by an intramolecular
ring-closure of intermediate C. After a proton exchange of in-
termediate D, skeleton 5 with the 3-bromo group was produced.
3
4
5
S
5s / 92
Br
O
5t / 88
Br
O
MeO
MeO
OMe
chelation
steric hindrance
repulsion
5u / 94
Ar
NBS
2
Br
Ar
2
Br
Ar
2
Ar
1
Br
Ar
Ar
1
OH
1
OH
OH
MeCN
or
H
H
H
O
4
A (favored)
B
6
Br
Br
Br
H
H
Ar
5v / 90
2
Ar
1
OH
Ar
Ar
2
1
O
Ar
O
5
Ar
2
a
1
For the best two-step reaction conditions: compounds
3qev (1.0 mmol), NaBH4 (70 mg, 2.0 mmol), MeOH/THF (v/
v¼1/1, 10 mL), rt, 1 h, and NBS (178 mg, 1.0 mmol), 0 ꢁC, 1 h.
H
H
D
C
Factors for ring-closure of skeleton 4:
(1) repulsion between bromonium ion and Ar group
(2) chelation between lone pair of OH with bromonium ion
b
The isolated products 5qev were >95% pure as de-
2
termined by 1H NMR analysis.
Scheme 3. The possible reaction mechanism of skeleton 5.
After reducing compound 3w with 1.0 equiv of NaBH4 at rt for
1 h, the NBS-mediated cyclization of the resulting alcohol obtained
compound 5w in only 25% yield (see Scheme 4). We thought both of
the internal olefins competed with the bromonium ion to form
major unknown products.
To further examine synthetic route, Ar2 group (skeleton 3) was
changed to tert-butyl group. Compounds 5qev were isolated in
excellent 88%e94% yields by the above conditions (see Table 3). But,
while changing the aromatic group (Ar1 or Ar2) from the phenyl to 4-

M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
6367
Me
Me
magnetic stirring. Products in organic solvents were dried over
anhydrous MgSO4 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 oper-
Br
O
O
1) NaBH
2) NBS
4
MeO
MeO
MeO
MeO
ating at 200/400 and at 100 MHz, respectively. Chemical shifts (d)
3w
5w (25%)
are reported in parts per million (ppm) and the coupling constants
(J) are given in Hertz. High resolution mass spectra (HRMS) were
measured with a mass spectrometer Finnigan/Thermo Quest MAT
95XL. X-ray crystal structures were obtained with an EnrafeNonius
FR-590 diffractometer (CAD4, Kappa CCD). Elemental analyses were
carried out with Heraeus Vario III-NCSH, Heraeus CHN-OS-Rapid
Analyzer or Elementar Vario EL III.
Scheme 4. Reaction of compound 3w.
When compound 3x (Ar2¼9-anthracenyl group) was treated
with 1.0 equiv of NaBH4 at rt for 1 h, the olefinic motif of compound
6 was regioselectively reduced with a 97% yield in the co-solvent of
MeOH and THF (see Scheme 5). The conjugation loss should be the
major reason to yield compound 6 because reduction to chalcone 6
involved less conjugation loss than reduction to the alcohol. When
the reaction substrate was changed to tertiary cinnamic alcohol 7
(generated from the Grignard addition of compound 3k with
phenylmagnesium bromide in THF), the NBS-mediated intra-
molecular electrophilic cyclization of compound 7 provided the
recovery of the starting material at 0 ꢁC for 1 h. By increasing the
reaction temperature, compound 8 was detected in refluxing MeCN
in 40% yield, as shown in Scheme 6.
4.2. A representative synthetic procedure of skeleton 3 is as
follows
NaOH (160 mg, 4.0 mmol) was added to a solution of substituted
benzaldehydes 1 (2.0 mmol) in MeOH (20 mL) at rt. Then aryl methyl
ketones 2aep (2.05 mmol) or tert-butyl methyl ketones 2qev
(2.05 mmol) was added to the reaction mixture. The reaction mixture
was stirred at reflux for 6 h. The reaction mixture was concentrated to
yield the residue. The residue was extracted with EtOAc (3ꢂ30 mL).
The combined organic layers were washed with brine, dried, filtered,
and evaporated to afford crude skeleton 3 with quantitative yields.
Without further purification, reduction of crude skeleton 3 was
treated with NaBH4 in the next step. Synthesis of skeleton 3 is
a known protocol and the related analytical data are consistent with
those in the literature.5a,b
O
O
MeO
MeO
MeO
MeO
NaBH
4
MeOH / THF
rt, 1 h
3x
6 (97%)
Scheme 5. Reaction of compound 3x.
A representative data of (E)-3-(3,4-dimethoxy-2-((E)-prop-1-enyl)
phenyl)-1-phenylprop-2-en-1-one (3w). Yield¼w100% (615 mg);
HRMS (ESI, Mþþ1) calcd for C20H21O3 309.1491, found 309.1493; 1H
NMR (400 MHz, CDCl3):
d
8.06 (d, J¼15.6 Hz, 1H), 8.01e7.98 (m, 2H),
OH
MeO
PhMgBr
THF
7.58e7.54 (m, 1H), 7.51e7.47 (m, 3H), 7.33 (d, J¼15.6 Hz, 1H), 6.86 (d,
J¼8.4 Hz,1H), 6.59(dq, J¼1.6, 16.0 Hz, 1H), 5.87 (dq, J¼6.4,16.0Hz,1H),
3.90 (s, 3H), 3.77 (s, 3H), 1.96 (dd, J¼1.6, 6.4 Hz, 3H); 13C NMR
3k
MeO
7
NBS, MeCN
reflux, 1 h
NBS, MeCN
o
(100 MHz, CDCl3):
d 190.82, 154.05, 146.51, 144.72, 138.44, 134.97,
0
C, 1 h
134.52, 132.40, 128.46 (3ꢂ), 128.37 (2ꢂ), 126.92, 123.64, 123.57,
121.33, 60.20, 55.79,19.31; Anal. Calcd for C20H20O3: C, 77.90; H, 6.54.
Found: C, 78.12; H, 6.65. Single-crystal X-ray diagram: crystal of
compound 3wwasgrownbyslow diffusionofEtOAc intoa solutionof
compound 3w in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the orthorhombic crystal system, space group Pbca,
major compound 7
was recovery
MeO
MeO
Br
8 (40%)
Scheme 6. NBS-mediated reaction of compound 7.
3
ꢀ
ꢀ
ꢀ
ꢀ
a¼7.3376(7) A, b¼11.2660(10) A, c¼38.619(4) A, V¼3192.5(5) A , Z¼8,
dcalcd¼1.283 g/cm3, F(000)¼1312, 2
q
range 1.05e26.40ꢁ, R indices (all
3. Conclusion
data) R1¼0.0485, wR2¼0.1115.
In summary, we have successfully presented an efficient and
straightforward three-step synthetic route for the stereochemical
synthesis of 2,4-disubstituted-3-bromooxetanes 5aew with the
transetrans orientation via NaOH-mediated ClaiseneSchmidt
condensation, NaBH4-mediated reduction, and NBS-mediated
electrophilic cyclization. The synthetic route obtained high yields
from the three-step route, and the total reaction procedure took
only 1 day. The substituent effect of skeleton 3, various NXS-
mediated reaction conditions, and plausible mechanism were
well-investigated. Further investigation regarding enantioselective
bromocyclization7 of cinnamic alcohol analogues will be conducted
and published in due course.
4.3. A representative synthetic procedure of skeleton 5 is as
follows
NaBH4 (70 mg, 2.0 mmol) was slowly added to a solution of the
resulting skeleton 3 (1.0 mmol) in the co-solvent of MeOH (5 mL)
and THF (5 mL) at rt. The reaction mixture was stirred at rt for 1 h.
Saturated NaHCO3(aq) (5 mL) was added to the reaction mixture and
the solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with EtOAc (3ꢂ20 mL). The
combined organic layers were washed with brine, dried, filtered,
and evaporated to afford crude product. Without further purifica-
tion, NBS (178 mg, 1.0 mmol) was added to a solution of the
resulting crude skeleton 4 in MeCN (5 mL) at 0 ꢁC. The reaction
mixture was stirred at 0 ꢁC for 1 h. Saturated NaHCO3(aq) (5 mL) was
added to the reaction mixture and the solvent was concentrated.
The residue was diluted with water (10 mL) and the mixture was
extracted with EtOAc (3ꢂ20 mL). The combined organic layers were
washed with brine, dried, filtered, and evaporated to afford crude
product. Purification on silica gel (hexanes/EtOAc¼10/1 to 6/1)
afforded skeleton 5.
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

6368
M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
4.3.1. 3-Bromo-2-(4-methoxyphenyl)-4-phenyloxetane
(5a). Yield¼78% (248 mg); Colorless solid; mp¼53e54 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C16H16BrO2 319.0334, found 319.0339; 1H NMR (400 MHz, CDCl3):
C
d
20H16BrO3 383.0283, found 383.0288; 1H NMR (400 MHz, CDCl3):
7.98 (s, 1H), 7.94e7.87 (m, 3H), 7.62 (dd, J¼1.6, 8.4 Hz, 1H),
7.56e7.51 (m, 2H), 7.09 (d, J¼1.6 Hz, 1H), 7.03 (dd, J¼1.6, 8.0 Hz, 1H),
6.87 (d, J¼8.0 Hz, 1H), 6.00 (br s, 2H), 5.96 (d, J¼7.2 Hz, 1H), 5.78 (d,
J¼7.2 Hz, 1H), 4.50 (t, J¼7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
7.56e7.54 (m, 2H), 7.49e7.37 (m, 5H), 6.98e6.95 (m, 2H), 5.81 (d,
J¼7.6 Hz,1H), 5.76 (d, J¼7.6 Hz,1H), 4.45 (t, J¼7.6 Hz,1H), 3.84 (s, 3H);
13C NMR (100 MHz, CDCl3):
160.25, 139.25, 131.03, 128.83, 128.73
d
148.23, 148.10, 136.42, 133.47, 133.06, 132.83, 128.80, 128.21, 127.80,
d
126.53, 126.49, 124.81, 122.77, 119.99, 108.41, 106.42, 101.30, 87.20,
86.64, 50.11.
(2ꢂ), 127.60 (2ꢂ),125.54 (2ꢂ),114.11 (2ꢂ), 87.00, 86.51, 55.32, 50.28.
4.3.2. 5-(3-Bromo-4-phenyloxetan-2-yl)benzo[1,3]dioxole (5b). Yield¼76%
(252 mg); Colorless solid; mp¼73e74 ꢁC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C16H14BrO3 333.0126,
4.3.8. 5-[3-Bromo-4-(3,4,5-trimethoxyphenyl)oxetan-2-yl]benzo[1,3]
dioxole (5h). Yield¼65% (274 mg); Colorless oil; HRMS (ESI,
Mþþ1) calcd for C19H20BrO6 423.0443, found 423.0438; 1H NMR
found 333.01267; 1H NMR (400 MHz, CDCl3):
d 7.54e7.51 (m, 2H),
(400 MHz, CDCl3):
d
8.20e7.01 (d, J¼1.6 Hz, 1H), 6.97 (ddd, J¼0.4,
7.47e7.37 (m, 3H), 7.04 (d, J¼2.0 Hz, 1H), 6.99 (ddd, J¼0.4, 2.0,
8.0 Hz, 1H), 6.85 (d, J¼8.0 Hz, 1H), 6.00e5.99 (m, 2H), 5.79 (d,
J¼7.6 Hz, 1H), 5.71 (dd, J¼0.8, 7.2 Hz, 1H), 4.41 (t, J¼7.2 Hz, 1H); 13C
1.6, 8.4 Hz, 1H), 6.83 (d, J¼8.0 Hz, 1H), 6.71 (s, 2H), 5.98e5.97 (m,
2H), 5.70 (d, J¼6.8 Hz, 1H), 5.68 (d, J¼7.2 Hz, 1H), 4.38 (t, J¼7.2 Hz,
1H), 3.89 (s, 6H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3):
NMR (100 MHz, CDCl3):
d 148.20, 148.07, 139.06, 132.87, 128.87,
d
153.55 (2ꢂ), 148.22, 148.09, 138.18, 134.78, 132.71, 119.85,
128.75 (2ꢂ),125.52 (2ꢂ),119.89,108.38,106.35,101.27, 87.00, 86.53,
108.31, 106.23, 102.12 (2ꢂ), 101.27, 86.85, 86.45, 60.78, 56.11 (2ꢂ),
50.21.
50.04.
4.3.3. 3-Bromo-2-(6-methoxynaphthalen-2-yl)-4-phenyloxetane
(5c). Yield¼69% (254 mg); Colorless solid; mp¼140e142 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C20H18BrO2 369.0490, found 369.0491; 1H NMR (400 MHz,
4.3.9. 3-Bromo-2-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)ox-
etane (5i). Yield¼67% (273 mg); Colorless solid; mp¼64e66 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C19H22BrO5 409.0651, found 409.0658; 1H NMR (400 MHz,
CDCl3):
d
8.30 (d, J¼8.8 Hz, 1H), 7.91 (d, J¼1.2 Hz, 1H), 7.88 (d,
CDCl3):
d
7.45 (d, J¼8.8 Hz, 2H), 6.95 (d, J¼8.8 Hz, 2H), 6.73 (s,
J¼8.8 Hz, 1H), 7.71 (dd, J¼1.6, 8.8 Hz, 1H), 7.57e7.54 (m, 2H),
7.48e7.38 (m, 4H), 7.33 (d, J¼9.2 Hz, 1H), 5.99 (d, J¼7.2 Hz, 1H), 5.90
(d, J¼7.2 Hz, 1H), 4.52 (t, J¼7.2 Hz, 1H), 4.05 (s, 3H); 13C NMR
2H), 5.73 (d, J¼7.6 Hz, 1H), 5.72 (d, J¼7.2 Hz, 1H), 4.43 (t, J¼7.2 Hz,
1H), 3.90 (s, 6H), 3.86 (s, 3H), 3.82 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
160.26 (2ꢂ), 153.57, 134.97 (2ꢂ), 130.86, 127.57 (2ꢂ),
(100 MHz, CDCl3):
d 154.27, 139.01, 134.94, 133.34, 129.37, 129.28,
114.11 (2ꢂ), 102.18 (2ꢂ), 86.86, 86.45, 60.81, 56.13 (2ꢂ), 55.29,
129.02 (2ꢂ), 128.82 (2ꢂ), 127.15, 125.70 (2ꢂ), 125.21, 124.86, 114.11,
50.11.
87.20, 86.83, 57.03, 49.83.
4.3.10. 3-Bromo-2,4-bis-(3,4,5-trimethoxyphenyl)oxetane
(5j). Yield¼62% (290 mg); Colorless solid; mp¼98e100 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C21H26BrO7 469.0862, found 469.0866; 1H NMR (400 MHz, CDCl3):
4.3.4. 2-Biphenyl-4-yl-3-bromo-4-phenyloxetane
(5d). Yield¼70%
(255 mg); Colorless solid; mp¼118e119 ꢁC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C21H18BrO 365.0541,
found 365.0545; 1H NMR (400 MHz, CDCl3):
d 7.69e7.54 (m, 8H),
d
6.72 (s, 4H), 5.73 (d, J¼7.2 Hz, 2H), 4.41 (t, J¼7.2 Hz, 1H), 3.88 (s,
12H), 3.85 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
153.59 (4ꢂ), 138.37
7.49e7.36 (m, 6H), 5.89 (t, J¼7.6 Hz, 1H), 5.87 (d, J¼7.6 Hz, 1H), 4.51 (t,
J¼7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 141.93, 140.55, 139.08,
137.98, 128.95, 128.84 (2ꢂ), 128.77 (2ꢂ), 127.56, 127.51 (2ꢂ), 127.14
(2ꢂ), 134.65 (2ꢂ), 102.38 (4ꢂ), 86.87 (2ꢂ), 60.82 (2ꢂ), 56.09 (4ꢂ),
49.87.
(2ꢂ), 126.20 (2ꢂ), 125.67 (2ꢂ), 87.00, 86.84, 50.04.
4.3.11. 2-(2-Allyl-3,4-dimethoxyphenyl)3-bromo-4-phenyloxetane
(5k). Yield¼69% (268 mg); Colorless solid; mp¼80e81 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C20H22BrO3 389.0752, found 389.0755; 1H NMR (400 MHz,
4.3.5. 5-(3-Bromo-4-p-tolyloxetan-2-yl)benzo[1,3]dioxole(5e). Yield¼72%
(249 mg); Colorless solid; mp¼90e92 ꢁC (recrystallized from hexanes
and EtOAc); HRMS (ESI, Mþþ1) calcd for C17H16BrO3 347.0283, found
347.02833; 1H NMR (400 MHz, CDCl3):
d
7.43 (d, J¼8.0 Hz, 2H), 7.26 (d,
CDCl3):
d
7.54e7.50 (m, 2H), 7.48 (d, J¼8.4 Hz, 1H), 7.45e7.35 (m,
J¼8.0 Hz, 2H), 7.07 (d, J¼1.6 Hz, 1H), 7.01 (dd, J¼1.6, 8.0 Hz, 1H), 6.86 (d,
J¼8.0 Hz, 1H), 6.00 (s, 2H), 5.76 (d, J¼7.6 Hz, 1H), 5.70 (d, J¼7.6 Hz, 1H),
3H), 6.92 (d, J¼8.8 Hz, 1H), 6.07e5.97 (m, 1H), 6.01 (d, J¼7.2 Hz,
1H), 5.80 (d, J¼7.2 Hz, 1H), 5.07 (dq, J¼1.6, 10.0 Hz, 1H), 4.95 (dq,
J¼1.6, 17.2 Hz, 1H), 4.45 (t, J¼7.2 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H),
4.42 (t, J¼7.6 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 148.13,
3.60e3.56 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 152.95, 147.22,
148.03, 138.83, 136.02, 132.95, 129.38 (2ꢂ), 125.68 (2ꢂ), 119.84, 108.34,
106.32, 101.23, 86.78, 86.57, 50.36, 21.24.
139.30, 136.66, 131.07, 130.81, 128.83, 128.71 (2ꢂ), 125.78 (2ꢂ),
121.92, 115.52, 110.54, 86.72, 83.74, 60.87, 55.68, 49.92, 30.15;
Anal. Calcd for C20H21BrO3: C, 61.71; H, 5.44. Found: C, 61.88; H,
5.61. Single-crystal X-ray diagram: crystal of compound 5k was
grown by slow diffusion of EtOAc into a solution of compound 5k
in CH2Cl2 to yield colorless prisms. The compound crystallizes in
the monoclinic crystal system, space group P 1 21/c 1, a¼9.4758
4.3.6. 5-[3-Bromo-4-(3-fluorophenyl)oxetan-2-yl]benzo[1,3]dioxole
(5f). Yield¼70% (244 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd
for C16H13BrFO3 351.0032, found 351.0031; 1H NMR (400 MHz,
CDCl3):
d 7.43e7.38 (m, 1H), 7.28e7.22 (m, 2H), 7.10e7.05 (m, 1H),
7.00e6.96 (m, 2H), 6.85 (d, J¼8.0 Hz, 1H), 6.00 (s, 2H), 5.77 (d,
3
ꢀ
J¼7.2 Hz, 1H), 5.71 (d, J¼7.2 Hz, 1H), 4.36 (t, J¼7.6 Hz, 1H); 13C NMR
(2) A, b¼24.6475(5) A, c¼15.2361(3) A, V¼3491.77(12) A , Z¼8,
ꢀ
ꢀ
ꢀ
(100 MHz, CDCl3):
d
163.02 (d, J¼246.3 Hz), 148.32, 148.12, 141.69
dcalcd¼1.481 g/cm3, F(000)¼1600, 2
q
range 2.14e26.40ꢁ, R indices
(d, J¼6.8 Hz), 132.53, 130.48 (d, J¼8.1 Hz), 120.83 (d, J¼3.1 Hz),
119.92, 115.72 (d, J¼20.5 Hz), 112.35 (d, J¼22.7 Hz), 108.43, 106.30,
101.33, 87.18, 85.63, 49.87.
(all data) R1¼0.0437, wR2¼0.0784.
4.3.12. 2-(2-Allyl-3,4-dimethoxyphenyl)-3-bromo-4-p-tolyloxetane
(5l). Yield¼72% (289 mg); Colorless viscous gum; HRMS (ESI, Mþþ1)
calcd for C21H24BrO3 403.0909, found 403.0906; 1H NMR (400 MHz,
4.3.7. 5-(3-Bromo-4-naphthalen-2-yloxetan-2-yl)benzo[1,3]dioxole
(5g). Yield¼68% (260 mg); Colorless solid; mp¼120e122 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
CDCl3):
d
7.49 (d, J¼8.4 Hz, 1H), 7.40 (d, J¼8.0 Hz, 2H), 7.23 (d,
J¼8.0 Hz, 2H), 6.92 (d, J¼8.4 Hz, 1H), 6.07e5.97 (m, 1H), 5.99 (d,

M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
6369
J¼7.2 Hz, 1H), 5.75 (d, J¼7.2 Hz, 1H), 5.07 (dq, J¼1.6, 10.0 Hz, 1H), 4.95
(dq, J¼1.6, 17.2 Hz, 1H), 4.44 (t, J¼7.2 Hz,1H), 3.89 (s, 3H), 3.82 (s, 3H),
C
d
14H18BrO3 313.0439, found 313.0442; 1H NMR (400 MHz, CDCl3):
6.94 (d, J¼2.0 Hz, 1H), 6.89 (dd, J¼2.0, 8.0 Hz, 1H), 6.80 (d, J¼8.0 Hz,
3.60e3.56 (m, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
152.90,
1H), 5.97 (s, 2H), 5.49 (d, J¼7.6 Hz, 1H), 4.56 (d, J¼7.6 Hz, 1H), 4.33 (t,
147.22, 138.81, 136.66, 136.26, 131.04, 130.92, 129.36 (2ꢂ), 125.96
(2ꢂ), 121.91, 115.49, 110.53, 86.77, 83.53, 60.85, 55.68, 50.08, 30.15,
21.26.
J¼7.6 Hz, 1H), 1.02 (s, 9H); 13C NMR (100 MHz, CDCl3):
d
147.94 (2ꢂ),
133.04, 119.53, 108.31, 106.12, 101.18, 93.42, 86.13, 43.59, 34.16, 24.44
(3ꢂ).
4.3.19. 3-Bromo-2-tert-butyl-4-thiophen-2-yloxetane (5s). Yield¼92%
(252 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C11H16BrOS
4.3.13. 2-(2-Allyl-3,4-dimethoxyphenyl)-3-bromo-4-(4-methoxyphenyl)
oxetane (5m). Yield¼67% (280 mg); Colorless solid; mp¼75e77 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H24BrO4 419.0858, found 419.0862; 1H NMR (400 MHz,
275.0105, found 275.0108; 1H NMR (400 MHz, CDCl3):
d 7.37 (dd,
J¼1.2, 5.2 Hz, 1H), 7.13 (dd, J¼1.2, 3.2 Hz, 1H), 7.01 (dd, J¼3.2, 5.2 Hz,
1H), 5.77 (d, J¼7.6 Hz, 1H), 4.56 (d, J¼7.6 Hz, 1H), 4.48 (t, J¼7.6 Hz, 1H),
CDCl3):
d
7.50 (d, J¼8.8 Hz, 1H), 7.45 (d, J¼8.8 Hz, 2H), 6.95 (d,
1.04 (s, 9H); 13C NMR (100 MHz, CDCl3):
93.16, 81.93, 44.31, 34.09, 24.29 (3ꢂ).
d
142.25, 126.92 (2ꢂ), 126.38,
J¼8.8 Hz, 2H), 6.93 (d, J¼8.8 Hz, 1H), 6.08e5.98 (m, 1H), 5.98 (d,
J¼7.2 Hz, 1H), 5.72 (d, J¼7.2 Hz, 1H), 5.08 (dq, J¼1.6, 10.0 Hz, 1H),
4.96 (dq, J¼1.6, 17.2 Hz, 1H), 4.46 (t, J¼7.2 Hz, 1H), 3.89 (s, 3H), 3.83
(s, 3H), 3.82 (s, 3H), 3.61e3.58 (m, 2H); 13C NMR (100 MHz, CDCl3):
4.3.20. 3-Bromo-2-tert-butyl-4-naphthalen-2-yloxetane
(5t). Yield¼88% (280 mg); Colorless solid; mp¼61e62 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C17H20BrO 319.0698, found 319.0697; 1H NMR (400 MHz, CDCl3):
d
160.14, 152.83, 147.19, 136.60, 131.18, 130.96, 130.92, 127.68 (2ꢂ),
121.75,115.43,114.02 (2ꢂ), 110.47, 86.68, 83.25, 60.79, 55.62, 55.27,
50.11, 30.13.
d
7.89e7.84 (m, 4H), 7.56e7.50 (m, 3H), 5.82 (d, J¼7.6 Hz, 1H), 4.70
(d, J¼7.6 Hz, 1H), 4.44 (t, J¼7.6 Hz, 1H), 1.06 (s, 9H); 13C NMR
4.3.14. 2-(2-Allyl-3,4-dimethoxyphenyl)-3-bromo-4-(3,4,5-
trimethoxyphenyl)oxetane (5n). Yield¼60% (287 mg); Colorless
viscous gum; HRMS (ESI, Mþþ1) calcd for C23H28BrO6 479.1069,
(100 MHz, CDCl3):
d 136.67, 133.36, 133.09, 128.58, 128.15, 127.77,
126.39, 126.30, 124.48, 122.72, 94.00, 86.20, 43.38, 34.20, 24.43
(3ꢂ).
found 479.1075; 1H NMR (400 MHz, CDCl3):
d
7.46 (d, J¼8.8 Hz, 1H),
6.90 (d, J¼8.8 Hz, 1H), 6.72 (s, 2H), 6.07e5.97 (m, 1H), 5.99 (d,
J¼7.2 Hz, 1H), 5.73 (d, J¼7.2 Hz, 1H), 5.07 (dq, J¼1.6, 10.0 Hz, 1H),
4.94 (dq, J¼1.6, 17.2 Hz, 1H), 4.43 (t, J¼7.2 Hz, 1H), 3.89 (s, 9H), 3.86
(s, 3H), 3.82 (s, 3H), 3.59e3.56 (m, 2H); 13C NMR (100 MHz, CDCl3):
4.3.21. 3-Bromo-2-tert-butyl-4-(3,4,5-trimethoxyphenyl)oxetane
(5u). Yield¼94% (337 mg); Colorless solid; mp¼83e84 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C16H24BrO4 359.0858, found 359.0863; 1H NMR (400 MHz, CDCl3):
d
153.56 (2ꢂ), 152.99, 147.29, 138.26, 136.63, 135.00, 131.17, 130.72,
d
6.64 (s, 2H), 5.52 (d, J¼7.6 Hz, 1H), 4.58 (d, J¼7.6 Hz, 1H), 4.30 (t,
121.78, 115.52, 110.44, 102.55 (2ꢂ), 86.74, 83.67, 60.86, 60.85, 56.18
(2ꢂ), 55.69, 49.84, 30.14.
J¼7.6 Hz,1H), 3.86(s, 6H), 3.83(s, 3H),1.01 (s, 9H);13C NMR (100 MHz,
CDCl3):
d
153.39 (2ꢂ),137.96,134.85,102.07 (2ꢂ), 93.52, 86.06, 60.72,
55.99 (2ꢂ), 43.51, 34.13, 24.32 (3ꢂ).
4.3.15. 2-(2-Allyl-3,4-dimethoxyphenyl)-3-bromo-4-(naphthalen-
2-yl)oxetane (5o). Yield¼62% (272 mg); Colorless solid;
mp¼106e108 ꢁC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C24H24BrO3 439.0909, found 439.0912; 1H
4.3.22. 2-Biphenyl-4-yl-3-bromo-4-tert-butyloxetane (5v). Yield¼90%
(310 mg); Colorless solid; mp¼87e88 ꢁC (recrystallized from hexanes
and EtOAc); HRMS (ESI, Mþþ1) calcd for C19H22BrO 345.0854, found
345.0856; 1H NMR (400 MHz, CDCl3):
d 7.64e7.59 (m, 4H), 7.52e7.44
NMR (400 MHz, CDCl3):
d 7.97 (s, 1H), 7.92e7.86 (m, 3H), 7.63 (dd,
J¼1.6, 8.8 Hz, 1H), 7.57e7.51 (m, 3H), 6.94 (d, J¼8.8 Hz, 1H), 6.09 (d,
J¼7.2 Hz, 1H), 6.09e6.01 (m, 1H), 5.99 (d, J¼7.2 Hz, 1H), 5.10 (dq,
J¼1.6, 10.0 Hz, 1H), 4.99 (dq, J¼1.6, 17.2 Hz, 1H), 4.55 (t, J¼7.2 Hz, 1H),
3.89 (s, 3H), 3.84 (s, 3H), 3.64e3.61 (m, 2H); 13C NMR (100 MHz,
(m, 4H), 7.39e7.35 (m, 1H), 5.68 (d, J¼7.6 Hz, 1H), 4.65 (d, J¼7.6 Hz, 1H),
4.41 (t, J¼7.6 Hz, 1H), 1.05 (s, 9H); 13C NMR (100 MHz, CDCl3):
d 141.59,
140.62, 138.17, 128.80 (2ꢂ), 127.47 (2ꢂ), 127.38 (2ꢂ), 127.11, 125.88 (2ꢂ),
93.82, 85.97, 43.44, 34.19, 24.43 (3ꢂ).
CDCl3): d 152.96, 147.22, 136.67, 136.62, 133.45, 133.06, 131.11, 130.75,
128.71, 128.18, 127.78, 126.48, 126.45, 125.03, 123.02, 121.98, 115.53,
110.57, 86.79, 83.90, 60.85, 55.66, 49.79, 30.15.
4.3.23. 3-Bromo-2-(3,4-dimethoxy-2-propenylphenyl)-4-
phenyloxetane (5w). Yield¼25% (97 mg); Colorless solid;
mp¼63e65 ꢁC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C20H22BrO3 389.0752, found 389.0759; 1H NMR
4.3.16. 2,4-Bis-(2-allyl-3,4-dimethoxyphenyl)-3-bromo-oxetane
(5p). Yield¼66% (322 mg); Colorless solid; mp¼131e133 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C25H30BrO5 489.1277, found 489.1282; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d 7.54e7.50 (m, 3H), 7.46e7.36 (m, 3H), 6.92 (d,
J¼8.4 Hz, 1H), 6.48 (dq, J¼1.6, 16.0 Hz, 1H), 6.11 (dq, J¼6.4, 16.0 Hz, 1H),
6.03 (d, J¼7.2 Hz,1H), 5.80 (d, J¼7.2 Hz,1H), 4.53 (t, J¼7.2 Hz,1H), 3.89 (s,
3H), 3.78 (s, 3H),1.98 (dd, J¼1.6, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
7.46 (d, J¼8.4 Hz, 2H), 6.90 (d, J¼8.4 Hz, 2H), 6.07e5.95 (m, 2H), 5.98
(d, J¼7.2 Hz, 2H), 5.06 (dq, J¼1.6, 10.0 Hz, 2H), 4.95 (dq, J¼1.6, 17.2 Hz,
2H), 4.47 (t, J¼7.2 Hz, 1H), 3.88 (s, 6H), 3.82 (s, 6H), 3.59e3.58 (m, 4H);
d
152.81, 146.46, 139.39, 133.64, 132.15, 129.72, 128.72, 128.66
(2ꢂ), 125.65 (2ꢂ), 123.27, 122.49, 110.67, 86.50, 83.79, 60.07, 55.78,
13C NMR (100 MHz, CDCl3):
d
152.82 (2ꢂ), 147.13 (2ꢂ), 136.63 (2ꢂ),
50.14, 19.15.
131.14 (2ꢂ), 130.87 (2ꢂ), 122.01 (2ꢂ), 115.43 (2ꢂ), 110.42 (2ꢂ), 83.28
(2ꢂ), 60.78 (2ꢂ), 55.59 (2ꢂ), 49.78, 30.09 (2ꢂ).
4.4. 3-(2-Allyl-3,4-dimethoxyphenyl)-1-anthracen-9-yl-
propan-1-one (6)
4.3.17. 3-Bromo-2-tert-butyl-4-(4-methoxyphenyl)oxetane
(5q). Yield¼92% (274 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd
for C14H20BrO2 299.0647, found 299.0651; 1H NMR (400 MHz,
NaBH4 (70 mg, 2.0 mmol) was slowly added to a solution of
compound 3x (2.0 mmol) in the co-solvent of MeOH (5 mL) and THF
(5 mL) at rt. The reaction mixture was stirred at rt for 1 h. Saturated
NaHCO3(aq) (5 mL) was added to the reaction mixture and the sol-
vent was concentrated. The residue was diluted with water (10 mL)
and the mixture was extracted with EtOAc (3ꢂ20 mL). The com-
bined organic layers were washed with brine, dried, filtered, and
evaporated to afford crude product. Purification on silica gel
CDCl3):
J¼7.6 Hz, 1H), 4.57 (d, J¼7.6 Hz, 1H), 4.36 (t, J¼7.6 Hz, 1H), 3.81 (s,
3H), 1.03 (s, 9H); 13C NMR (100 MHz, CDCl3):
160.01, 131.17, 127.28
d
7.37 (d, J¼8.8 Hz, 2H), 6.92 (d, J¼8.8 Hz, 2H), 5.53 (d,
d
(2ꢂ), 114.00 (2ꢂ), 93.38, 86.13, 55.29, 43.63, 34.18, 24.45 (3ꢂ).
4.3.18. 3-Bromo-2-tert-butyl-4-(3,4-methylenedioxyphenyl)oxetane
(5r). Yield¼91% (284 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for

6370
M.-Y. Chang et al. / Tetrahedron 69 (2013) 6364e6370
(hexanes/EtOAc¼8/1 to 4/1) afforded compound 6. Yield¼97%
(795 mg); Colorless viscous gum; HRMS (ESI, Mþþ1) calcd for
C28H27O3 411.1960, found 411.0963; 1H NMR (400 MHz, CDCl3):
d 152.80, 147.19, 136.29, 135.12, 131.05, 129.08, 121.91, 115.55,
110.50, 105.90, 60.90, 55.68, 30.40.
d
8.47 (s, 1H), 8.04e8.01 (m, 2H), 7.72e7.68 (m, 2H), 7.50e7.44 (m,
Acknowledgements
4H), 6.97 (d, J¼8.4 Hz, 1H), 6.75 (d, J¼8.4 Hz, 1H), 5.98 (m, 1H), 4.93
(dq, J¼1.6, 10.4 Hz, 1H), 4.85 (dq, J¼1.6, 17.2 Hz, 1H), 3.84 (s, 3H),
3.80 (s, 3H), 3.47 (dt, J¼1.6, 6.0 Hz, 2H), 3.33e3.29 (m, 2H),
The authors would like to thank the National Science Council of
the Republic of China for its financial support.
3.20e3.16 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 209.61, 151.19,
137.07 (2ꢂ), 134.10 (2ꢂ), 132.20, 131.03, 128.77 (2ꢂ), 128.17 (2ꢂ),
127.20,126.93, 126.67 (2ꢂ), 125.44 (2ꢂ), 124.57, 124.29 (2ꢂ), 115.02,
110.48, 60.76, 55.68, 47.70, 30.55, 26.27.
Supplementary data
Scanned photocopies of 1H and 13C NMR spectral data were
supported. Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.tet.2013.05.110.
4.5. (E)-2-Allyl-1-(2-bromovinyl)-3,4-dimethoxybenzene (8)
References and notes
A solution of phenylmagnesium bromide (1.0 M in THF, 1.5 mL,
1.5 mmol) was added to a stirred solution of compound 3k
(308 mg, 1.0 mmol) in THF (10 mL) at 0 ꢁC. The reaction mixture
was stirred at rt for 5 h. Water (5 mL) was added to the reaction
mixture and the mixture was filtered through a short plug of
Celite. The filtrate was concentrated under reduced pressure. The
residue was extracted with EtOAc (3ꢂ50 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evapo-
rated to afford different crude product under reduced pressure.
Without further purification, NBS (178 mg, 1.0 mmol) was added
to a solution of the resulting crude compound 7 in MeCN (5 mL)
at rt. The reaction mixture was stirred at reflux for 1 h. Saturated
NaHCO3(aq) (5 mL) was added to the reaction mixture and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with EtOAc (3ꢂ20 mL).
The combined organic layers were washed with brine, dried, fil-
tered, and evaporated to afford crude product. Purification on
silica gel (hexanes/EtOAc¼10/1 to 6/1) afforded compound 8.
Yield¼40% (113 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C13H16BrO2 283.0334, found 283.0338; 1H NMR (400 MHz,
1. For preparation of vinyl halides, see: for vinyl fluorides: (a) van Steenis, J. H.; van
der Gen, A. J. Chem. Soc., Perkin Trans. 1 2002, 2117 and references cited herein;
(b) Shen, Y. J. Organomet. Chem. 2006, 691, 1452 For vinyl chlorides and
bromides; (c) Li, W.; Li, J.; Wan, Z.-K.; Wu, J.; Massefski, W. Org. Lett. 2007, 9, 4607
and references cited herein; (d) Ye, C.; Shreeve, J. M. J. Org. Chem. 2004, 69, 8561.
2. For halodecaboxylation of cinnamic acids, see: (a) Telvekar, V. N.; Takale, B. S.
Tetrahedron Lett. 2011, 52, 2394; (b) Mueller, D.; Alexakis, A. Org. Lett. 2012, 14,
1842; (c) Chen, X.; Rappoport, Z. J. Org. Chem. 1998, 63, 5684; (d) Fursule, R. A.;
Patil, P. O.; Shewale, B. D.; Kosalge, S. B.; Deshmukh, P. K.; Patil, D. A. Chem.
Pharm. Bull. 2009, 57, 1243; (e) You, H.-W.; Lee, K.-J. Synlett 2001, 105; (f) Wang,
C.; Bao, W.; Zhang, X. J. Chem. Res., Synop. 2005, 10, 617; (g) Huang, Y.-L.; Cheng,
Y.-H.; Hsien, K.-C.; Chen, Y.-L.; Kao, C.-L. Tetrahedron Lett. 2009, 50, 1834; (h)
Homsi, F.; Rousseau, G. J. Org. Chem. 1999, 64, 81.
3. Kuang, C.; Senboku, H.; Tokuda, M. Synthesis 2000, 1439.
4. (a) Albert, S.; Robin, S.; Rousseau, G. Tetrahedron Lett. 2001, 42, 2477; (b) Perez-Ruiz,
R.; Saez, J. A.; Domingo, L. R.; Jimenez, M. C.; Miranda, M. A. Org. Lett. 2012, 14, 5700.
5. (a) Chang, M.-Y.; Tai, H.-Y.; Chen, Y.-L.; Hsu, R.-T. Tetrahedron 2012, 68, 7941; (b)
Chang, M.-Y.; Wu, M.-H.; Tai, H.-Y. Org. Lett. 2012, 14, 3936; (c) Chang, M.-Y.; Wu,
M.-H. Tetrahedron 2012, 68, 9616.
6. CCDC 903763 (5k) and 903764 (3w) contain the supplementary crystallographic
data 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: þ44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).
7. (a) Tan, C. K.; Zhou, L.; Yeung, Y.-Y. Org. Lett. 2011, 13, 2738; (b) Chen, J.; Zhou, L.;
Tan, C. K.; Yeung, Y.-Y. J. Org. Chem. 2012, 77, 999; (c) Zhou, L.; Tan, C. K.; Jiang, X.;
Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2010, 132, 15474; (d) Zhou, L.; Chen, J.; Tan,
C. K.; Yeung, Y.-Y. J. Am. Chem. Soc. 2011, 133, 9164; (e) Cheng, Y. A.; Chen, T.; Tan,
C. K.; Heng, J. J.; Yeung, Y.-Y. J. Am. Chem. Soc. 2012, 134, 16492; (f) Chen, F.; Tan,
C. K.; Yeung, Y.-Y. J. Am. Chem. Soc. 2013, 135, 1232.
CDCl3):
d
7.21 (d, J¼13.6 Hz, 1H), 7.07 (d, J¼8.4 Hz, 1H), 6.78 (d,
J¼8.4 Hz, 1H), 6.51 (d, J¼14.0 Hz, 1H), 5.99e5.89 (m, 1H), 5.04 (dq,
J¼1.6, 10.4 Hz, 1H), 4.90 (dq, J¼1.6, 17.2 Hz, 1H), 3.87 (s, 3H), 3.79
(s, 3H), 3.47 (dt, J¼1.6, 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):