Regio- and stereoselective multisubstituted enol ester synthesis

Article abstract of DOI:10.1021/jo201609r

Regio- and stereoselective cohalogenation of alkynes with NXS (X = Br, I) was achieved, and the stereoselectivity of the resulting alkenes was dependent on the substituent on the alkyne. Cohalogenation and successive cross-coupling gave multisubstituted e

Full text of DOI:10.1021/jo201609r

Note
pubs.acs.org/joc
Regio- and Stereoselective Multisubstituted Enol Ester Synthesis
Noriko Okamoto,†,‡ Yoshihisa Miwa,† Hideki Minami,† Kei Takeda,‡ and Reiko Yanada*,†
†Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan
‡Department of Synthetic Organic Chemistry, Graduate School of Medical Sciences, Hiroshima University, 1-2-3 Kasumi,
Minami-Ku, Hiroshima 734-8553, Japan
S
* Supporting Information
ABSTRACT: Regio- and stereoselective cohalogenation of
alkynes with NXS (X = Br, I) was achieved, and the
stereoselectivity of the resulting alkenes was dependent on
the substituent on the alkyne. Cohalogenation and successive
cross-coupling gave multisubstituted enol esters in a one-pot
process.
Scheme 1. Regio- and Stereoselective Multisubstituted Enol
Ester Synthesis
he regio- and stereoselective synthesis of multisubstituted
Talkenes has provided a particular challenge in organic
synthesis.1 Multisubstituted enol esters and ethers, members of
the multisubstituted alkenes, are important constituents in
drugs such as Nileprost,2 and also versatile synthons in organic
synthesis, readily engaging in a range of transformations
including regioselective Diels−Alder reactions,3 [3 + 2]
cycloaddition,4 asymmetric hydrogenation,5 and Pd-catalyzed
enantioselective allylations.6 Cohalogenation, the simultaneous
introduction of a halogen atom and a suitable nucleophile across
carbon−carbon multiple bonds, is a useful reaction.7 Alkenyl
halides obtained from cohalogenation reaction of alkynes are
important intermediates in multisubstituted alkene syntheses
because they can be further functionalized via transition-metal-
catalyzed cross-coupling reactions. If regio- and stereoselectivity
of cohalogenation could be controlled and if successive cross-
coupling could be conducted, this method would be ideally
suited for diversity-oriented8 multisubstituted alkene synthesis.
Although alkenyl iodides are suitable substrates for these cross-
coupling reactions, the examples of coiodination of alkynes are
mostly confined to intramolecular transformations, including
iodolactonization,9 in which an intramolecular nucleophile
attacks the activated alkyne leading to a cyclized product. We
herein report regio- and stereoselective cohalogenation of
alkynylbenzene derivatives. Furthermore, we conducted the
one-pot synthesis of multisubstituted enol esters via successive
cohalogenation and cross-coupling reactions (Scheme 1).
First, we examined the reaction of alkynes 1 having various
aromatic substituents with NXS (X = Cl, Br, I) as the electro-
philic halogenation reagent and AcOH as the nucleophile
(Table 1). Although NXS has been used to activate alkynes in
iodocyclizations,9 there are a few reports of the stereoselective
synthesis of iodoalkenes from alkynes, electrophilic iodine
reagent, and external nucleophile.10 The reaction with
alkynylbenzenes having electron-donating groups such as
OMe, NHCO2Et, or NHAc on the aromatic ring proceeded
smoothly to afford the iodoalkenes 2a−c in good to excellent
yields as a single E-isomer (vide infra) (entries 1−3). When
methyl-substituted 1d was used, reactivity and selectivity
decreased (entry 4). Unsubstituted 1e, p-fluoro- and p-nitro-
substituted 1f and 1g did not react under these conditions
(entries 5−7). To examine the effect of the substituent position
on the aromatic ring, the reaction was carried out using
alkynylbenzenes, having o- or m-methoxy group. o-Methoxy-
alkynylbenzene 1h gave the iodoalkene 2h as a single E-isomer
in 63% yield together with 2-butyl-3-iodobenzofuran 3 in 16%
yield (entry 8). It appears that intermolecular reaction with
AcOH is more favorable than intramolecular attack of oxygen
at the alkyne triple bond.11 As expected, the reaction with
m-methoxyalkynylbenzene 1i, NIS, and AcOH did not undergo
the cohalogenation reaction, resulting in recovery of starting
material (entry 9). When NBS was used, bromoalkene 2a′ was
obtained in 91% yield after prolonged reaction time (entry 10).
The use of NCS resulted in recovery of 1a (entry 11). Electron-
rich heteroaromatic-substituted alkyne 1j also participated in
this reaction, whereas electron-deficient pyridine-substituted 1k
led to complex mixture (entries 12 and 13). The electronic bias
Received: August 4, 2011
Published: September 28, 2011
© 2011 American Chemical Society
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Note
failed to afford the desired iodoalkenes under these conditions.
Halogenation with NXS often needs various NXS-activating
coreagent, such as BF3, CF3CO2H, p-TsOH, [hydroxy-
(tosyloxy)iodo]benzene, CF3SO3H.13 It is conceivable that
carboxylic acids behave not only as nucleophile but also as NIS-
activating reagent.
We could not determine the stereochemistry of the products
by NOE experiments. Fortunately, we were able to recrystallize
compounds 2l, 2m, 2n, and 2o and obtain the results of X-ray
analysis.14 Alkyl-substituted 2l and 2m were E-products (anti
addition products), while compounds 2n and 2o, which were
major products from aryl-substituted alkynylbenzenes, were
Z-products (syn addition products). The stereochemistries of
2p−r were confirmed by 1H NMR chemical shifts of the acetyl
protons as compared with the corresponding protons of 2n and
2o, namely the acetyl peaks of the E isomers were shifted to
upfield (Figure 1).
In an earlier report, the reaction of alkyne and electrophilic
iodine reagent (IPy2·BF4, ICl) yielded E-iodoalkene through
cyclic iodonium ion intermediates and nucleophilic anti-attack.
When the steric hindrance of alkynyl substituents increases,
nucleophiles will interact to a greater extent with the iodine atom
of the iodonium ion, hence yielding an overall syn-addition.10a,c
Spectroscopic and theoretical investigations of electrophilic
halogenation reactions of alkynes have also been reported.15
Recently, Laali and co-workers reported16 a theoretical study on
halogen addition to terminal alkynes by density functional theory
(DFT) and gauge-independent atomic orbital (GIAO)-DFT
calculations. To obtain further information on stereoselectivity,
we performed 1H NMR spectroscopic analysis using the reaction
of 1n with NIS and AcOH. After 10 min, approximately half of
the starting material 1n still remained: the E/Z ratio of 2n was
2:1. Over time, the amount of the Z-isomer gradually increased.
After the completion of the reaction (1 h), the final E/Z ratio
was 1:10. This observation indicates that the isomerization of the
double bond occurred under the reaction conditions. However,
the mechanistic basis for the different stereoselectivity remains
unclear.
Table 1. Effect of the Aromatic Substituent
time
(h)
entry
1
Ar
X
2
yield (%)
quant (E)
1
2
1a p-MeOC6H4
1b p-EtCO2NHC6H4
1c p-AcNHC6H4
1d p-MeC6H4
1e C6H5
I
1
1
2a
2b
2c
2d
2e
I
95 (E)
3
I
1
70 (E)
4
I
4
70 (E/Z = 10:1)
trace
5
I
4
6
1f p-FC6H4
I
22
22
1
recovery of 1f
recovery of 1g
7
1g p-NO2C6H4
1h o-MeOC6H4
1i m-MeOC6H4
1a p-MeOC6H4
1a p-MeOC6H4
1j 2-thiophenyl
1k 2-pyridyl
I
a
8
I
2h
2a′
2j
63 (E)
9
I
2
recovery of 1i
91 (E/Z = 10:1)
recovery of 1a
58 (E)
10
11
12
13
Br
Cl
I
4
3
2
I
2
decomposed
a
2-Butyl-3-iodobenzofuran 3 was obtained in 16% yield.
of the groups on both carbons of the triple bond plays an
important role in attack of the nucleophile. Regioselective
addition of AcOH was assumed to occur by preferential attack
on a more electrophilic carbon.12
We next explored the effects of the alkynyl substituent R and
the nucleophile NuH (Table 2). Alkynylbenzenes bearing alkyl
Table 2. Reaction of Alkynylbenzene 1 with NIS and
Nucleophile
The resulting iodoalkenes 2, which were stable at room temp-
erature, could be functionalized by cross-coupling reactions
(Scheme 2). Suzuki coupling of 2a with several boronic acids
gave multisubstituted enol esters 4a−c in good yields.
Finally, we undertook the one-pot synthesis of multisubstituted
enol esters 4 or 5 from alkynylbenzene 1a or 1n (Scheme 3).
After the formation of 2a or 2n was confirmed by TLC, an
aqueous solution of Na2S2O3 was added to the reaction mixture
to decompose extra NIS, then successive Suzuki coupling reac-
tion produced multisubstituted enol esters 4a−c or 5a−c in good
yields.
In summary, we have developed a regio- and stereoselective
cohalogenation of alkynylbenezenes, which have electron-
donating groups at the para-position on the aromatic ring.
The stereoselectivity of the reaction is dependent upon the sub-
stituent on the acetylene terminus. Alkyl-substituted alkynyl-
benzene proceeded via anti-addition, affording E-iodoalkene,
while aryl-substituted alkynylbenzene exhibited a preference
for syn-selectivity. The resulting iodoalkene was utilized for
the transformation through a Pd-catalyzed coupling reaction.
A one-pot regio- and stereoselective cohalogenation/Suzuki-
coupling reaction was also achieved.
a
Entries 1, 2, 8, and 9: NIS (1.3 equiv), RCO2H (1.3 equiv). Entries
3−7: NIS (2 equiv), RCO2H (2 equiv).
substituents on the acetylene terminus gave (E)-2 in good
yields (entries 1, 2, 8, and 9). In contrast to the results of alkyl-
substituted substrates, the reaction of aryl-substituted substrates
exhibited Z-selectivity and the ratios of E/Z were about 1:9
(entries 3−7). The use of alcohol instead of carboxylic acid
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Note
1
Figure 1. H NMR Chemical Shift of OCOCH3 of Compound 2. Footnote: (a) Determined by X-ray crystallography.
Scheme 2. Cross-Coupling Reaction Using Compound 2a
a
PdCl2(PPh3)2 was used for coupling with PhB(OH)2. Pd(OAc)2 and PPh3 (0.2 equiv) were used for coupling with 2-phenylvinylboronic acid or 1-
phenylvinylboronic acid.
Scheme 3. One-Pot Synthesis of Multisubstituted Enol Esters 4 and 5
a
b
1a: NIS (1.3 equiv), AcOH (1.3 equiv). 1n: NIS (2.0 equiv), AcOH (2.0 equiv). See Scheme 2.
mmol) and 1-hexyne (205 mL, 1.78 mmol) and stirred at room
EXPERIMENTAL SECTION
■
temperature under nitrogen. The reaction was monitored by TLC to
establish completion. Saturated aqueous NH4Cl solution was added
to the reaction mixture and extracted with AcOEt (three times). The
combined organic solution was washed with brine, dried over
anhydrous Na2SO4, and concentrated at the reduced pressure. Column
chromatography on silica gel using 10:1 hexanes/ethyl acetate as an
eluent afforded 314 mg (93%, two steps) of 1b as orange solid. Mp:
108−109 °C (colorless needles from CHCl3−AcOEt). 1H NMR
(CDCl3) δ: 7.34−7.29 (4H, m), 6.57 (1H, s), 4.22 (2H, q, J = 7.1 Hz),
2.39 (2H, t, J = 7.2 Hz), 1.60−1.55 (2H, m), 1.50−1.44 (2H, m), 1.31
(3H, t, J = 6.9 Hz), 0.94 (3H, t, J = 7.2 Hz). 13C NMR (CDCl3) δ:
153.3, 137.2, 132.3, 129.1, 118.9, 118.1, 89.7, 80.1, 61.4, 30.9, 22.0,
19.1, 14.5, 13.7. IR (CHCl3, cm−1): 3435, 2961, 2934, 1732, 1609,
1582, 1518, 1504, 1410, 1252, 1065, 837. MS (EI): m/z = 245 (M+).
HRMS (EI): m/z calcd for C15H19NO2 245.1416, found 245.1410.
N-(4-(Hex-1-yn-1-yl)phenyl)acetamide (1c). One drop of concd
H2SO4 was added to a stirred solution of 4-iodoaniline (300 mg,
1.15 mmol) in acetic anhydride (5 mL).26 The resulting mixture was
stirred at room temperature for 5 min, quenched with water, and
extracted with CH2Cl2 (three times). The combined organic layers
were washed with water, brine and dried with anhydrous Na2SO4. The
solvent was removed and the crude product was crystallized from
ethanol to give the N-acetyl derivative as a crystalline solid (293 mg,
83%). To a solution of the above compound (220 mg, 0.84 mmol) in
Et3N/MeCN (1:1, 6 mL) was added PdCl2(PPh)2 (21 mg, 0.03
mmol), CuI (5.7 mg, 0.03 mmol), and 1-hexyne (126 mL, 1.1 mmol)
and stirred at room temperature under nitrogen. The reaction was
monitored by TLC to establish completion. Saturated aqueous NH4Cl
solution was added to the reaction mixture and extracted with AcOEt
(three times). The combined organic solution was washed with brine,
General Experimental Methods. 1H NMR spectral data were
recorded in CDCl3 solutions on a 600 MHz spectrometer, and 13C
NMR were recorded in CDCl3 151 MHz spectrometer. Chemical
shifts (δ) are reported in parts per million (ppm), and the signals are
described as br (broad singlet), d (doublet), dd (doublet of doublet), m
(multiple), q (quartet), s (singlet), and t (triplet). Coupling constants
(J values) are given in Hz. Low-resolution mass spectra (MS) and
high-resolution mass spectra (HRMS) were recorded at an ionizing
voltage of 30 eV. Column chromatography was carried out on silica
gel (70−140 μM). All reactions were monitored using TLC on silica
gel plates. All of the reagents were used directly as obtained
commercially or synthesized according to literature procedures. NIS
and NCS were purchased from Tokyo Chemical Industry Co., Ltd.,
NBS was purchased from a commercial supplier. Alkynylbenzenes
1a,17 1d,17b 1f,17a 1g,18 1h,17c 1i,17c 1j,19 1k,20 1m,21 1n,17b17
,
21 1o,21,22
d
1p,21 1q,21 and 1r23 and benzofuran 324 are all known compounds.
1-Phenyl-1-hexyne (1e) was purchased from a commercial supplier.
Ethyl (4-(Hex-1-yn-1-yl)phenyl)carbamate (1b). 4-Iodoaniline
(300 mg, 1.37 mmol), ethyl chloroformate (522 mL, 5.48 mmol),
and K2CO3 (1.1 g, 8.22 mmol) were stirred in 5 mL of acetone at
room temperature for 2 h.25 Then the reaction mixture was diluted
with water. The organic phase was separated, and the aqueous phase
was extracted with AcOEt (three times). Theorganic fractions were
combined, washed with brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure. The solids were diluted with
chloroform and filtered through a short silica gel column
chromatography using 5:1 hexanes/ethyl acetate as an eluent. The
product was used in the following step without further purification.
To a solution of the above compound in Et3N/MeCN (1:1, 6 mL)
was added PdCl2(PPh)2 (29 mg, 0.041 mmol), CuI (8 mg, 0.041
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Note
dried over anhydrous Na2SO4, and concentrated at the reduced
pressure. Column chromatography on silica gel using hexanes/ethyl
acetate (5:1−2:1) as an eluent afforded 178 mg (98%) of 1c as orange
solid. 1H NMR (CDCl3) δ: 7.72 (1H, s), 7.44 (2H, d, J = 8.2 Hz), 7.32
(2H, d, J = 8.2 Hz), 2.39 (2H, t, J = 7.2 Hz), 2.15 (3H, s), 1.60−1.55
(2H, m), 1.50−1.45 (2H, m), 0.94 (3H, t, J = 7.2 Hz). 13C NMR
(CDCl3) δ: 168.5, 137.2, 132.2, 119.8, 119.4, 90.0, 80.1, 30.8, 24.5,
21.0, 19.1, 13.6. IR (CHCl3, cm−1): 3436, 3008, 2961, 2935, 1691,
1583, 1518, 1510, 1402, 1370, 1311, 1290, 1239, 1197, 1110, 1003,
842, 809. MS (EI): m/z = 215 (M+). HRMS (EI): m/z calcd for
C14H17NO 215.1310, found 215.1304.
1065, 841. MS (EI): m/z = 431 (M+). HRMS (EI): m/z calcd for
C17H22INO4 431.0594, found 431.0591.
(E)-1-(4-Acetamidophenyl)-2-iodohex-1-en-1-yl Acetate (2c).
Yellow solid. Mp: 132−134 °C (colorless plate from AcOEt). 1H
NMR (CDCl3) δ: 7.48 (2H, d, J = 8.9 Hz), 7.44 (2H, d, J = 8.9 Hz),
7.26 (1H, s), 2.53 (2H, t, J = 7.6 Hz), 2.18 (3H, s), 2.11 (3H, s), 1.58−
1.53 (2H, m), 1.39−1.35 (2H, m), 0.95 (3H, t, J = 7.2 Hz). 13C NMR
(CDCl3) δ: 168.5, 145.7, 138.3, 133.2, 130.5, 118.9, 96.7, 37.9, 31.0,
24.6, 21.6, 20.6, 13.9. IR (CHCl3, cm−1): 3435, 3036, 2959, 2932,
2874, 1753, 1694, 1589, 1514, 1402, 1369, 1312, 1240, 1192, 1180,
1076, 1015, 810. MS (EI): m/z = 401 (M+). HRMS (EI): m/z calcd
for C16H20INO3 401.0488, found 401.0483.
5-(4-Methoxyphenyl)pent-4-yn-1-yl 4-Methylbenzenesulfonate
(1l). To a solution of 4-iodoanisole (468 mg, 2 mmol) in Et3N/
MeCN (4:1, 5 mL) were added PdCl2(PPh)2 (42 mg, 0.06 mmol),
CuI (11 mg, 0.06 mmol), and 4-pentyn-1-ol (223 mL, 2.4 mmol) and
stirred at room temperature under nitrogen for 4.5 h. Saturated aqueous
NH4Cl solution was added to the reaction mixture and extracted with
AcOEt (three times). The combined organic solution was washed with
brine, dried over anhydrous Na2SO4, and concentrated at the reduced
pressure. Column chromatography on silica gel using hexanes/ethyl
acetate (3:1) as an eluent afforded 380 mg (quant) of alkynylated
product. Under an nitrogen atmosphere, to a solution of the above
compound (325 mg, 1.55 mmol) in CH2Cl2 (15 mL) were added
p-toluenesulfonyl chloride (414 mg, 2.17 mmol), Et3N (324 mL, 2.33
mmol), and 4-(N,N-dimethylamino)pyridine (114 mg, 0.93 mmol) and
stirred at room temperature for 4 h.27 The mixture was diluted with
AcOEt and washed with water (two times), saturated aqueous NH4Cl,
brine, dried (MgSO4), and concentrated. Purification by silica gel
column chromatography (hexane/AcOEt (5:1)) gave 1j (534 mg,
quant) as a colorless solid. Mp: 31−32 °C (colorless needles from
(E)-2-Iodo-1-(p-tolyl)hex-1-en-1-yl Acetate (2d). Yellow oil. 1H
NMR (CDCl3) δ: 7.37 (2H, d, J = 8.2 Hz), 7.15 (2H, d, J = 8.2 Hz),
2.53 (2H, t, J = 7.6 Hz), 2.35 (3H, s), 2.10 (3H, s), 1.58−1.53 (2H,
m), 1.40−1.35 (2H, m), 0.95 (3H, t, J = 7.2 Hz). 13C NMR (CDCl3)
δ: 168.3, 146.3, 138.8, 134.7, 129.6, 128.6, 96.5, 37.8, 31.1, 21.7, 21.4,
20.6, 13.9. IR (CHCl3, cm−1): 2959, 2930, 2874, 1753, 1510, 1456,
1369, 1236, 1196, 1182, 1076, 1016, 700. MS (EI): m/z = 358 (M+).
HRMS (EI): m/z calcd for C15H19IO2 358.0430, found 358.0429.
(E)-2-Iodo-1-(2-methoxyphenyl)hex-1-en-1-yl Acetate (2h). Or-
1
ange oil. H NMR (CDCl3) δ: 7.40 (1H, dd, J = 7.6, 1.7 Hz), 7.33
(1H, td, J = 7.9, 1.7 Hz), 6.96−6.90 (2H, m), 3.86 (3H, s), 2.53 (2H, t,
J = 7.4 Hz), 2.09 (3H, s), 1.59−1.54 (2H, m), 1.42−1.37 (2H, m),
0.96 (3H, t, J = 7.4 Hz). 13C NMR (CDCl3) δ: 168.3, 157.0, 144.1,
132.7, 130.5, 126.9, 120.1, 111.1, 100.0, 55.8, 37.1, 31.3, 21.6, 20.6,
13.9. IR (CHCl3, cm−1): 2960, 2934, 1751, 1598, 1490, 1465, 1436,
1369, 1288, 1257, 1236, 1195, 1114, 1077, 1050, 1018. MS (EI):
m/z = 374 (M+). HRMS (EI): m/z calcd for C15H19IO3 374.0379,
found 374.0378.
(E)-2-Iodo-1-(thiophen-2-yl)hex-1-en-1-yl Acetate (2j). Dark
brown oil. 1H NMR (CDCl3) δ: 7.43 (1H, q, J = 1.6 Hz), 7.33
(1H, q, J = 2.1 Hz), 7.02 (1H, dd, J = 4.8, 3.4 Hz), 2.56 (2H, t, J = 7.6
Hz), 2.20 (3H, s), 1.58−1.53 (2H, m), 1.39−1.34 (2H, m), 0.94 (3H,
t, J = 7.2 Hz). 13C NMR (CDCl3) δ: 168.23, 140.6, 138.3, 129.8,
126.7, 126.5, 97.3, 38.9, 31.1, 21.7, 20.5, 13.9. IR (CHCl3, cm−1):
2960, 2933, 2874, 1761, 1603, 1466, 1427, 1370, 1237, 1194, 1079,
1016, 965. MS (EI): m/z = 374 (M+). HRMS (EI): m/z calcd for
C12H15IO2S 349.9837, found 349.9839.
(E)-2-Iodo-1-(4-methoxyphenyl)-5-(tosyloxy)pent-1-en-1-yl Ace-
tate (2l). Pale yellow solid. Mp: 72−73 °C (colorless plates from
hexane−Et2O). 1H NMR (CDCl3) δ: 7.81 (2H, d, J = 6.9 Hz), 7.39−
7.35 (4H, m), 6.86 (2H, d, J = 8.2 Hz), 4.07 (2H, t, J = 6.2 Hz), 3.81
(3H, d, J = 1.4 Hz), 2.64 (2H, t, J = 7.2 Hz), 2.46 (3H, s), 2.13 (3H,
s), 1.92 (2H, t, J = 6.5 Hz). 13C NMR (CDCl3) δ: 168.5, 159.9, 147.6,
144.8, 133.1, 131.0, 129.9, 129.5, 127.9, 113.2, 93.0, 69.0, 55.2, 34.3,
28.2, 21.7, 20.6. IR (CHCl3, cm−1): 1754, 1609, 1510, 1366, 1298,
1245, 1176, 1027. MS (EI): m/z = 530 (M+). HRMS (EI): m/z calcd
for C21H23IO6S 530.0260, found 530.0253.
1
CHCl3−AcOEt). H NMR (CDCl3) δ: 7.80 (2H, d, J = 8.2 Hz), 7.30
(2H, d, J = 7.6 Hz), 7.22 (2H, d, J = 8.9 Hz), 6.80 (2H, d, J = 8.9 Hz),
4.20 (2H, t, J = 6.2 Hz), 3.79 (3H, s), 2.45 (2H, t, J = 6.9 Hz), 2.39 (3H,
s), 1.94−1.89 (2H, m). 13C NMR (CDCl3) δ: 159.1, 144.70, 132.9,
132.8, 129.8, 127.9, 115.5, 113.7, 85.9, 81.4, 69.0, 55.2, 28.0, 21.6, 15.6.
IR (CHCl3, cm−1): 2839, 1608, 1510, 1465, 1362, 1290, 1246, 1237,
1176, 1098, 1019, 978, 957, 932, 833, 811. MS (EI): m/z = 344 (M+).
HRMS (EI): m/z calcd for C19H20O4S 344.1082, found 344.1076.
General Procedure for Cohalogenation of Alkynylben-
zenes. To a solution of alkynylbenzene 1 (0.1 mmol) and NIS in
1,2-dichloroethane (0.5 mL) was added AcOH, and the mixture was
stirred at 70 °C. After completion of the reaction (TLC), 10% Na2S2O3
aqueous solution was added for quenching. The aqueous layer was
extracted with AcOEt (two times). The combined organic layers were
dried over Na2SO4 and concentrated. The crude product was purified
by column chromatography to give 2.
(E)-2-Iodo-1-(4-methoxyphenyl)hex-1-en-1-yl Acetate (2a). Pale
yellow oil. 1H NMR (CDCl3) δ: 7.42 (2H, d, J = 8.9 Hz), 6.86 (2H, d,
J = 8.9 Hz), 3.81 (3H, s), 2.52 (2H, t, J = 7.2 Hz), 2.11 (3H, s), 1.58−
1.53 (2H, m), 1.37 (2H, td, J = 14.8, 7.6 Hz), 0.95 (3H, t, J = 7.2 Hz).
13C NMR (CDCl3) δ: 168.4, 159.7, 146.1, 131.1, 130.0, 113.2, 96.4,
(E)-2-Cyclohexyl-2-iodo-1-(4-methoxyphenyl)vinyl Acetate
(2m). Pale yellow solid. Mp: 82−83 °C (colorless needles from
55.2, 37.9, 31.1, 21.7, 20.6, 13.9. IR (CHCl3, cm−1) 3034, 1753, 1607,
1510, 1296, 1175, 1022. MS (EI): m/z = 374 (M+). HRMS (EI): m/z
calcd for C15H19IO3 374.0379, found 374.0383.
1
hexane−Et2O). H NMR (CDCl3) δ: 7.39 (2H, d, J = 8.9 Hz), 6.86
(2H, d, J = 8.9 Hz), 3.81 (3H, s), 2.12 (3H, s), 2.01−1.96 (1H, m),
1.81 (2H, d, J = 6.9 Hz), 1.68 (1H, d, J = 12.4 Hz), 1.62−1.60 (2H,
m), 1.45−1.36 (4H, m), 1.22−1.17 (1H, m). 13C NMR (CDCl3) δ:
168.5, 159.6, 144.5, 131.4, 130.5, 113.2, 107.3, 55.2, 42.0, 33.1, 25.7,
25.6, 20.7. IR (CHCl3, cm−1): 2934, 2856, 1751, 1607, 1510, 1450,
1297, 1247, 1197, 1174, 1028, 912, 836. MS (EI): m/z = 400 (M+).
HRMS (EI): m/z calcd for C17H21IO3 400.0535, found 400.0527.
(E)-2-Iodo-1-(4-methoxyphenyl)-2-phenylvinyl Acetate ((E)-2n). Yel-
low needle. 1H NMR (CDCl3) δ: 7.59 (2H, d, J = 8.9 Hz), 7.41 (2H,
dd, J = 8.2, 1.4 Hz), 7.34 (2H, t, J = 7.9 Hz), 7.26 (1H, t, J = 7.6 Hz),
6.92 (2H, d, J = 8.9 Hz), 3.84 (3H, s), 1.83 (3H, s). 13C NMR
(CDCl3) δ: 168.7, 160.1, 147.1, 140.9, 131.1, 129.4, 128.5, 128.2,
113.4, 99.9, 88.2, 55.3, 20.4. IR (CHCl3, cm−1): 1757, 1608, 1370,
1299, 1250, 1196, 1174, 1046, 1031. MS (EI): m/z = 394 (M+).
HRMS (EI): m/z calcd for C17H15IO3 394.0066, found 394.0069.
(Z)-2-Iodo-1-(4-methoxyphenyl)-2-phenylvinyl Acetate ((Z)-
2n). Yellow solid. Mp: 126−128 °C (pale yellow plates from
hexane−Et2O). 1H NMR (CDCl3) δ: 7.28 (2H, d, J = 6.9 Hz),
(E)-2-Bromo-1-(4-methoxyphenyl)hex-1-en-1-yl Acetate (2a′). Pale
yellow oil. 1H NMR (CDCl3) δ: 7.46 (2H, d, J = 8.9 Hz), 6.87 (2H, d,
J = 8.9 Hz), 3.81 (3H, s), 2.52 (2H, t, J = 7.6 Hz), 2.13 (3H, s),
1.62−1.57 (2H, m), 1.40−1.34 (2H, m), 0.95 (3H, t, J = 7.2 Hz). 13
C
NMR (CDCl3) δ: 168.4, 159.6, 143.6, 130.6, 127.8, 118.7, 113.2, 55.2,
34.9, 29.8, 21.8, 20.7, 13.8. IR (CHCl3, cm−1): 2961, 1756, 1608, 1511,
1370, 1298, 1249, 1174, 1086, 1024. MS (EI): m/z = 326 (M+).
HRMS (EI): m/z calcd for C15H19BrO3 326.0518, found 326.0507.
(E)-1-(4-((Ethoxycarbonyl)amino)phenyl)-2-iodohex-1-en-1-yl
Acetate (2b). Pale yellow oil. 1H NMR (CDCl3) δ: 7.43 (2H, d,
J = 8.6 Hz), 7.36 (2H, d, J = 8.6 Hz), 6.74 (1H, s), 4.22 (2H, q,
J = 7.1 Hz), 2.52 (2H, t, J = 7.2 Hz), 2.11 (3H, s), 1.58−1.53 (2H, m),
1.40−1.34 (2H, m), 1.30 (3H, t, J = 7.2 Hz), 0.95 (3H, t, J = 7.6 Hz).
13C NMR (CDCl3) δ: 168.4, 153.4, 145.8, 138.4, 132.3, 130.6, 117.6,
96.6, 61.3, 37.9, 31.1, 21.6, 20.6, 14.5, 13.9. IR (CHCl3, cm−1): 3433,
2961, 1736, 1609, 1587, 1522, 1408, 1371, 1314, 1238, 1194, 1180,
9136
dx.doi.org/10.1021/jo201609r|J. Org. Chem. 2011, 76, 9133−9138

The Journal of Organic Chemistry
Note
7.22−7.17 (3H, m), 7.07 (2H, d, J = 8.9 Hz), 6.65 (2H, d, J = 8.2 Hz),
3.72 (3H, s), 2.29 (3H, s). 13C NMR (CDCl3) δ: 168.0, 159.6, 149.9,
140.8, 130.2, 130.1, 128.4, 128.1, 125.8, 113.5, 89.9, 55.1, 21.4. IR
(CHCl3, cm−1): 2840, 1764, 1606, 1511, 1464, 1443, 1369, 1300,
1253, 1195, 1174, 1059, 1032, 922. MS (EI): m/z = 394 (M+). HRMS
(EI): m/z calcd for C17H15IO3 394.0066, found 394.0067.
1.03−1.00 (2H, m), 0.95 (3H, t, J = 7.2 Hz), 0.92−0.89 (2H, m). 13
C
NMR (CDCl3) δ: 172.3, 159.6, 146.1, 131.1, 129.9, 113.1, 96.2, 55.2,
37.8, 31.0, 21.7, 13.9, 12.6, 8.8. IR (CHCl3, cm−1): 2960, 2933, 1743,
1740, 1608, 1510, 1465, 1457, 1385, 1297, 1244, 1235, 1176, 1142,
1099, 1033. MS (EI): m/z = 400 (M+). HRMS (EI): m/z calcd for
C17H21IO3 400.0535, found 400.0543.
(E)-2-Iodo-1-(4-methoxyphenyl)-2-(p-tolyl)vinyl Acetate ((E)-
(E)-2-Iodo-1-(4-methoxyphenyl)hex-1-en-1-yl Benzoate (2t). Col-
1
1
2o). Pale yellow plates. H NMR (CDCl3) δ: 7.58 (2H, d, J = 8.9
orless oil. H NMR (CDCl3) δ: 8.07 (2H, dd, J = 8.2, 1.4 Hz), 7.59
Hz), 7.31 (2H, d, J = 8.2 Hz), 7.14 (2H, d, J = 8.2 Hz), 6.92 (2H, d,
J = 8.9 Hz), 3.84 (3H, s), 2.35 (3H, s), 1.85 (3H, s). 13C NMR
(CDCl3) δ: 168.8, 160.0, 146.8, 138.1, 138.0, 131.1, 129.7, 128.9,
128.4, 113.4, 99.9, 88.8, 55.3, 21.3, 20.5. IR (CHCl3, cm−1): 1757,
1608, 1513, 1370, 1298, 1251, 1196, 1173, 1045, 1031. MS (EI):
m/z = 408 (M+). HRMS (EI): m/z calcd for C18H17IO3 408.0222,
found 408.0230.
(1H, t, J = 7.6 Hz), 7.52 (2H, d, J = 8.2 Hz), 7.46 (2H, t, J = 7.9 Hz),
6.86 (2H, d, J = 8.9 Hz), 3.79 (3H, s), 2.60 (2H, t, J = 7.6 Hz), 1.61−
1.56 (2H, m), 1.39−1.33 (2H, m), 0.91 (3H, t, J = 7.2 Hz). 13C NMR
(CDCl3) δ: 164.0, 159.8, 146.2, 133.6, 131.2, 129.0, 129.8, 129.1,
128.6, 113.2, 96.4, 55.2, 38.0, 31.2, 21.6, 13.9. IR (CHCl3, cm−1):
2960, 2933, 1733, 1608, 1507, 1465, 1452, 1297, 1270, 1242, 1175,
1085, 1066, 1025, 833, 810. MS (EI): m/z = 436 (M+). HRMS (EI):
m/z calcd for C20H21IO3 436.0535, found 436.0544.
General Procedure for One-Pot Synthesis of Multisubsuti-
tuted Enol Esters. To a solution of alkynylbenzene 1 (0.1 mmol)
and NIS in 1,2-dichloroethane (0.5 mL) was added AcOH, and the
mixture was stirred at 70 °C for 1 h. A 10% Na2S2O3 aqueous solution
was added for quenching and the mixture stirred for 5 min. Then
toluene, boronic acid (1.5 equiv), Pd catalyst (0.1 equiv), and K2CO3
(3 equiv) were added, and the mixture was stirred at 90 °C. The
aqueous layer was extracted with AcOEt (two times). The combined
organic layers were dried over Na2SO4 and concentrated. The crude
product was purified by column chromatography to give 4 and 5.
(E)-1-(4-Methoxyphenyl)-2-phenylhex-1-en-1-yl Acetate (4a). Pale
yellow oil. 1H NMR (CDCl3) δ: 7.21−7.11 (5H, m), 7.01 (2H, d, J =
8.9 Hz), 6.62 (2H, d, J = 8.9 Hz), 3.70 (3H, s), 2.44 (2H, t, J = 7.2
Hz), 2.21 (3H, s), 1.32−1.29 (4H, m), 0.86 (3H, t, J = 7.2 Hz). 13C
NMR (CDCl3) δ: 169.2, 158.6, 142.8, 139.5, 130.5, 130.1, 129.5,
128.2, 128.1, 126.6, 113.1, 55.0, 32.5, 29.4, 22.5, 21.0, 13.8. IR (CHCl3,
cm−1): 2959, 2932, 1751, 1609, 1510, 1464, 1443, 1369, 1296, 1250,
1238, 1196, 1177, 1090, 1036, 837. MS (EI): m/z = 324 (M+). HRMS
(EI): m/z calcd for C21H24O3 324.1725, found 324.1717.
(Z)-2-Iodo-1-(4-methoxyphenyl)-2-(p-tolyl)vinyl Acetate ((Z)-
2o). Yellow solid. Mp: 85−86 °C (yellow needles from hexane−
1
AcOEt). H NMR (CDCl3) δ: 7.17 (2H, d, J = 8.2 Hz), 7.08 (2H, d,
J = 8.9 Hz), 7.01 (2H, d, J = 7.6 Hz), 6.66 (2H, d, J = 8.9 Hz), 3.73
(3H, s), 2.30 (3H, s), 2.28 (3H, s). 13C NMR (CDCl3) δ: 168.0, 159.5,
149.5, 138.1, 137.9, 130.1, 130.0, 129.1, 125.9, 113.5, 90.3, 55.1, 21.4,
21.3. IR (CHCl3, cm−1): 2936, 1762, 1606, 1512, 1506, 1465, 1442,
1369, 1300, 1252, 1193, 1175, 1116, 1059, 1032, 922. MS (EI): m/z =
408 (M+). HRMS (EI): m/z calcd for C18H17IO3 408.0222, found
408.0223.
2-(4-Fluorophenyl)-2-iodo-1-(4-methoxyphenyl)vinyl Acetate
(2p). Compound 2p was obtained as a mixture of isomer. Yellow
oil. IR (CHCl3, cm−1): 1762, 1600, 1511, 1506, 1464, 1370, 1300,
1252, 1239, 1192, 1174, 1060, 1032, 922, 843, 811. MS (EI): m/z =
412 (M+). HRMS (EI): m/z calcd for C17H14FIO3 411.9972, found
411.9973. (Z)-2p: 1H NMR (CDCl3) δ: 7.26 (2H, td, J = 5.8, 2.7 Hz),
7.02 (2H, t, J = 8.6 Hz), 6.92−6.87 (2H, m), 6.66 (2H, d, J = 8.9 Hz),
3.72 (3H, s), 2.27 (3H, s). 13C NMR (CDCl3) δ: 167.9, 162.9, 161.3,
159.7, 150.3, 136.9, 136.9, 132.1, 132.0, 130.2, 125.6, 115.5, 115.4,
113.6, 88.5, 55.2, 21.34. (E)-2p: 1H NMR (CDCl3) δ: 7.57 (2H, d, J =
8.2 Hz), 7.40 (2H, q, J = 4.8 Hz), 7.02 (2H, t, J = 8.6 Hz), 6.92−6.87
(2H, m), 3.83 (3H, s), 1.84 (3H, s). 13C NMR (CDCl3) δ: 168.6,
160.2, 147.5, 132.4, 131.0, 130.4, 130.4, 129.2, 115.3, 115.1, 114.4,
113.4, 86.8, 55.3, 20.4.
2-Iodo-1,2-bis(4-methoxyphenyl)vinyl Acetate (2q). Compound
2q was obtained as a mixture of isomers. Yellow oil. IR (CHCl3,
cm−1): 1762, 1605, 1511, 1506, 1465, 1457, 1370, 1293, 1250, 1196,
1174, 1059, 1032, 838. MS (EI): m/z = 424 (M+). HRMS (EI): m/z
calcd for C18H17IO4 424.0172, found 424.0173. (Z)-2q: 1H NMR
(CDCl3) δ: 7.21 (2H, d, J = 8.9 Hz), 7.08 (2H, d, J = 8.2 Hz), 6.73
(2H, d, J = 8.2 Hz), 6.66 (2H, d, J = 8.9 Hz), 3.77 (3H, s), 3.72 (3H,
s), 2.27 (3H, s). 13C NMR (CDCl3) δ: 168.0, 159.5, 159.2, 149.3,
133.1, 131.5, 130.1, 126.0, 113.8, 113.5, 90.2, 55.2, 55.1, 21.4. (E)-2q:
1H NMR (CDCl3) δ: 7.57 (2H, d, J = 8.2 Hz), 7.36 (2H, d, J = 8.2
(E)-1-(4-Methoxyphenyl)-2-((E)-styryl)hex-1-en-1-yl Acetate
1
(4b). Yellow oil. H NMR (CDCl3) δ: 7.36 (2H, d, J = 8.9 Hz),
7.31−7.25 (4H, m), 7.19 (1H, t, J = 6.9 Hz), 6.92−6.90 (3H, m), 6.65
(1H, d, J = 16.5 Hz), 3.84 (3H, s), 2.41 (2H, t, J = 7.9 Hz), 2.19 (3H,
s), 1.57−1.41 (4H, m), 0.97 (3H, t, J = 7.6 Hz). 13C NMR (CDCl3) δ:
169.4, 159.6, 146.4, 137.7, 130.8, 128.9, 128.6, 127.9, 127.6, 127.2,
126.3, 126.1, 113.6, 55.3, 30.7, 26.7, 23.0, 21.0, 14.0. IR (CHCl3,
cm−1): 2960, 2934, 1747, 1606, 1510, 1465, 1369, 1296, 1251, 1193,
1175, 1101, 1054, 1033, 839. MS (EI): m/z = 350 (M+). HRMS (EI):
m/z calcd for C23H26O3 350.1882, found 350.1885.
(E)-1-(4-Methoxyphenyl)-2-(1-phenylvinyl)hex-1-en-1-yl Acetate
1
(4c). Yellow oil. H NMR (CDCl3) δ: 7.56 (2H, d, J = 6.9 Hz),
7.37−7.28 (5H, m), 6.70 (2H, d, J = 8.2 Hz), 5.49 (1H, s), 4.97 (1H,
s), 3.73 (3H, s), 2.22 (3H, s), 2.10 (2H, t, J = 7.6 Hz), 1.36−1.26 (4H,
m), 0.86 (3H, t, J = 7.2 Hz). 13C NMR (CDCl3) δ: 169.2, 159.0,
145.6, 143.9, 138.9, 130.5, 129.3, 128.5, 128.3, 127.8, 126.8, 116.1,
113.1, 55.1, 29.9, 29.4, 22.4, 20.9, 13.9. IR (CHCl3, cm−1) 2962, 2935,
1757, 1714, 1601, 1513, 1254, 1239, 1175, 1031. MS (EI): m/z = 350
(M+). HRMS (EI): m/z calcd for C23H26O3 350.1882, found 350.1884.
1-(4-Methoxyphenyl)-2,2-diphenylvinyl Acetate (5a). Pale yellow
Hz), 6.91 (2H, d, J = 8.2 Hz), 6.86 (2H, d, J = 8.2 Hz), 3.83 (3H, s),
3.82 (3H, s), 1.85 (3H, s). 13C NMR (CDCl3) δ: 168.7, 160.0, 159.3,
146.7, 133.2, 131.1, 129.9, 129.7, 113.5, 113.4, 88.6, 55.3, 55.3, 20.5.
2-Iodo-2-(3-methoxyphenyl)-1-(4-methoxyphenyl)vinyl Acetate
(2r). Compound 2r was obtained as a mixture of isomers. Yellow
oil. IR (CHCl3, cm−1) 1759, 1606, 1511, 1482, 1430, 1370, 1288,
1253, 1238, 1195, 1059, 811. MS (EI): m/z = 424 (M+). HRMS (EI):
1
1
solid. H NMR (CDCl3) δ: 7.33−7.23 (5H, m), 7.17−7.15 (5H, m),
m/z calcd for C18H17IO4 424.0172, found 424.0168. (Z)-2r: H NMR
7.10−7.08 (2H, m), 6.70 (2H, d, J = 8.9 Hz), 3.75 (3H, s), 1.98 (3H,
s). 13C NMR (CDCl3) δ: 169.9, 159.2, 143.8, 140.3, 140.0, 130.8,
130.3, 129.0, 128.1, 128.1, 128.1, 127.2, 127.0, 113.4, 55.1, 20.9. IR
(CHCl3, cm−1): 1754, 1608, 1512, 1444, 1370, 1293, 1250, 1237,
1170, 1055, 1033, 835. MS (EI): m/z = 344 (M+). HRMS (EI): m/z
calcd for C23H20O3 344.1412, found 344.1417.
(CDCl3) δ: 7.12−7.08 (3H, m), 6.85−6.84 (2H, m), 6.73 (1H, d, J =
7.6 Hz), 6.66 (2H, d, J = 8.2 Hz), 3.72 (3H, s), 3.70 (3H, s), 2.28 (3H,
s). 13C NMR (CDCl3) δ: 167.9, 159.6, 159.2, 149.9, 142.0, 130.0,
129.4, 125.8, 122.5, 115.3, 114.3, 113.5, 89.5, 55.2, 55.1, 21.4. (E)-2r:
1H NMR (CDCl3) δ: 7.59 (2H, d, J = 8.9 Hz), 7.24 (1H, t, J = 7.2
Hz), 7.00 (1H, d, J = 6.9 Hz), 6.95 (1H, s), 6.92 (2H, d, J = 8.2 Hz),
6.81 (1H, dd, J = 8.2, 2.7 Hz), 3.84 (3H, s), 3.81 (3H, s), 1.85 (3H, s).
13C NMR (CDCl3) δ: 168.7, 160.1, 159.2, 147.2, 131.1, 129.4, 129.2,
120.8, 114.3, 113.7, 113.4, 87.9, 55.3, 55.3, 20.5.
(1E,3E)-1-(4-Methoxyphenyl)-2,4-diphenylbuta-1,3-dien-1-yl Ace-
1
tate (5b). Yellow solid. H NMR (CDCl3) δ: 7.35−7.21 (11H, m),
7.01 (2H, d, J = 8.9 Hz), 6.63 (2H, d, J = 8.9 Hz), 6.22 (1H, d, J = 15.8
Hz), 3.72 (3H, s), 2.35 (3H, s). 13C NMR (CDCl3) δ: 169.1, 159.0,
144.6, 137.5, 136.8, 133.0, 131.1, 129.9, 129.1, 128.6, 128.5, 127.8,
127.7, 127.4, 126.6, 125.8, 113.2, 55.1, 21.1. IR (CHCl3, cm−1): 1755,
1603, 1510, 1492, 1443, 1370, 1296, 1253, 1237, 1176, 1125, 1040,
(E)-2-Iodo-1-(4-methoxyphenyl)hex-1-en-1-yl Cyclopropanecar-
1
boxylate (2s). Pale yellow solid. H NMR (CDCl3) δ: 7.41 (2H, d,
J = 8.9 Hz), 6.86 (2H, d, J = 8.9 Hz), 3.81 (3H, s), 2.53 (2H, t, J = 7.6
Hz), 1.70−1.66 (1H, m), 1.59−1.53 (2H, m), 1.41−1.34 (2H, m),
9137
dx.doi.org/10.1021/jo201609r|J. Org. Chem. 2011, 76, 9133−9138

The Journal of Organic Chemistry
Note
1022, 836. MS (EI): m/z = 370 (M+). HRMS (EI): m/z calcd for
C25H22O3 370.1569, found 370.1569.
(13) (a) Olah, G. A.; Wang, Q.; Sandford, G.; Prakash, G. K. S.
J. Org. Chem. 1993, 58, 3194−3195. (b) Bovonsombat, P.; McNelis, E.
Tetrahedron Lett. 1993, 34, 8205−8208. (c) Castanet, A.-S.; Colobert,
F.; Broutin, P.-E. Tetrahedron Lett. 2002, 43, 5047−5048. (d) Prakash,
G. K. S.; Mathew, T.; Hoole, D.; Esteves, P. M.; Wang, Q.; Rasul, G.;
Olah, G. A. J. Am. Chem. Soc. 2004, 126, 15770−15776.
(e) Bovonsombat, P.; Leykajarakul, J.; Khan, C.; Pla-on, K.; Krause,
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2664−2667.
(14) CCDC 831998 (2l), CCDC 831999 (2m), CCDC 832000
(2n), and CCDC 832001 (2o) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
(Z)-1-(4-Methoxyphenyl)-2,3-diphenylbuta-1,3-dien-1-yl Acetate
(5c). Orange oil. 1H NMR (CDCl3) δ: 7.50 (2H, d, J = 8.2 Hz), 7.30−
7.10 (10H, m), 6.69 (2H, d, J = 8.2 Hz), 5.64 (1H, s), 5.29 (1H, s),
3.73 (3H, s), 1.83 (3H, s). 13C NMR (CDCl3) δ: 169.1, 159.2, 147.6,
144.9, 139.9, 138.6, 130.4, 130.3, 128.3, 128.1, 128.0, 127.5, 127.0,
126.7, 117.0, 113.4, 113.4, 55.1, 20.6. IR (CHCl3, cm−1): 1761, 1654,
1600, 1511, 1258, 1167, 1032, 837. MS (EI): m/z = 370 (M+). HRMS
(EI): m/z calcd for C25H22O3 370.1569, found 370.1571.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of obtained compounds. Thermal
ellipsoid plots of the crystallographic structures of 2l−o. X-ray
data for compounds 2l−o (CIF). This material is available free
of charge via the Internet at http://pubs.acs.org.
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5644. (b) Schmid, G. H.; Modro, A.; Yates., K. J. Org. Chem. 1980, 45,
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ryanada@ps.hirokoku-u.ac.jp.
ACKNOWLEDGMENTS
■
(18) Zhang, X.; Larock, R. C. Org. Lett. 2003, 5, 2993−2996.
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2002, 67, 8416−8423.
We are grateful to Dr. M. Nishi at Setsunan University for
obtaining LRMS and HRMS data. This work was partially
supported by a Grant-in-Aid for Scientific Research (C) from
JSPS KAKENHI (23590032). N.O. is grateful to the Research
Foundation by Hiroshima International University.
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