A convenient preparative method for new 1,3-bis(hetaryl)-2-chloropropen-1- ones using β-alkoxy-α-chloroalkenyllithium compounds

Article abstract of DOI:10.1002/ejoc.200600957

The 1,3-biaryl and 1,3-bis(hetaryl)propen-1-ones 14a-e, 16, 17a-c, 19, 20a and the corresponding acetals 15a-d, 18a and 21a-d were successfully synthesized by a stepwise process: the reaction of α-chloro-β- ethoxyethenylhthium compounds and aldehydes and

Full text of DOI:10.1002/ejoc.200600957

FULL PAPER
DOI: 10.1002/ejoc.200600957
A Convenient Preparative Method for New 1,3-Bis(hetaryl)-2-chloropropen-1-
ones Using β-Alkoxy-α-chloroalkenyllithium Compounds
Akinori Itoh,[a] Miho Sakai,[a] and Mitsuhiro Yoshimatsu*[a]
Keywords: 1-Aryl-2-chloro-1-ethoxyethene / 1,3-Biarylpropen-1-one / Alkenyllithium / Suzuki coupling
The 1,3-biaryl and 1,3-bis(hetaryl)propen-1-ones 14a–e, 16,
17a–c, 19, 20a and the corresponding acetals 15a–d, 18a and
21a–d were successfully synthesized by a stepwise process:
the reaction of α-chloro-β-ethoxyethenyllithium compounds
and aldehydes and ketones, and the successive hydration
with TMSOTf. Further palladium-catalyzed arylation of 1,3-
biaryl-2-chloroprop-2-enones proceeded with good yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
(Figure 1). We here report a new synthesis of 1,3-bis(het-
aryl)-2-chloropropen-1-ones using α-chloroethoxyethenyl-
lithiums bearing 2-thienyl, 2-furyl, and 2-pyridyl groups
and their transformations to 1,2,3-triaryl- and 1,2,3-tris-
(hetaryl)propen-1-ones.
Introduction
2-Halopropen-1-ones (2-haloenones) have been utilized
as an important intermediate in the syntheses of natural
products having interesting biological activities such as
prostacyclin,[1] α- and β-cuparenones,[2] pentalene and epi-
pentalene.[3] Furthermore, the significant transformations
of 2-chlorocyclopentenones to asymmetric cyclopenta-
nones, dialkylcyclopentanones and 1-acetoxy-3-alkyl-2-
chloropentenes have been reported by other groups.[4] In
particular, 1,3-biaryl-2-halopropen-1-ones (2-halochal-
cones) have been much investigated and easily accessed by
three general routes: condensation of aldehydes with α-
chloroacetophenones,[5] chlorination followed by dehydro-
chlorination of chalcones,[6] and Wittig and Horner–
Wadsworth–Emmons reactions;[7] however, the preparative
methods for 1,3-bis(hetaryl)-2-chloropropen-1-ones have
not been reported because it is difficult to prepare their pre-
cursors. Recently, much attention has been paid to 1-furyl-
3-pyridylpropen-1-ones which show cyclooxygenase (COX)-
Figure 1. Synthesis of α-chloro-α,β-unsaturated aryl ketones using
α-chloro-β-ethoxyalkenyllithiums.
We first prepared six kinds of 1-aryl-2-chloro-1-ethoxy-
ethenes, 1–6, according to our original method as shown in
Scheme 1.[10] Next, we performed the lithiation of 2-(2-
chloro-1-ethoxyethenyl)thiophene (1) and reaction with a
variety of aldehydes and ketones. The lithiation of 1 with
nBuLi proceeded at –78 °C, and the successive reaction with
benzaldehyde gave (Z)-2-(2-chloro-1-ethoxy-3-hydroxy-3-
phenylprop-1-enyl)thiophene (7a) in 85% yield. The reac-
tion of 1 in the presence of 1.5 equiv. of nBuLi afforded 7a
in 45% yield, accompanied by 29% of the diol 8, which
was obtained by the further lithiation and alkylation of the
intramolecular thiophene ring. We further performed the
reactions of 1 with a variety of aldehydes and ketones as
inhibiting
activity
(nonsteroidal
anti-inflammatory
drugs).[8] For the development of new COX-inhibitors, the
discovery of a new preparative method of 1,3-bis(hetaryl)-
propen-1-ones is of much importance.[9] Fortunately, we
were pleased to find that 1-aryl-2-chloro-1-ethoxyethenes
could be conveniently generated by a simple reaction of ar-
yllithiums with dichloroacetaldehyde diethyl acetals. The 1-
hetaryl-2-chloro-1-ethoxyethenes could be used as new pre-
cursors of β-alkoxyalkenyllithiums bearing a chlorine atom
and utilized for the synthesis of a wide variety of 1,3-bis-
(hetaryl)-2-chloropropen-1-ones by the electrophilic reac-
tions of aldehydes and ketones and successive hydration
[a] Department of Chemistry, Faculty of Education, Gifu Univer-
sity,
Yanagido 1-1, Gifu 501-1193, Japan
Fax: +81-58-293-2207
E-mail: yoshimae@cc.gifu-u.ac.jp
Scheme 1. Synthesis of 1-aryl-2-chloro-1-ethoxyethenes.
2006
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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New 1,3-Bis(hetaryl)-2-chloropropen-1-ones
FULL PAPER
Table 1. Preparation of 3-aryl-2-chloroprop-2-en-1-ols from aldehydes and ketones using lithiated α-aryl-β-chloro-α-ethoxyethenes.
[a] The dialkylated product, (E)-2-(2-chloro-1-ethoxy-3-phenylprop-1-enyl)-5-(hydroxyphenylmethyl)thiophene (8) was obtained in low
yield.
shown in Table 1. 2-(2-Chloro-1-ethoxyethenyl)-5-methyl- in low yield of the product 20a accompanied by recovery
thiophene 2, the furyl derivatives 3–4, phenyl derivative 5 of the enol ethers (entry 18), while the usual acetalization
and pyridyl derivative 6 also afforded the corresponding ad- improved the yield and provided the corresponding α,β-un-
ducts 9–10, 11a–c, 12, and 13a–d, respectively, in moderate saturated acetal 21a in up to 74% yield (entry 19). The
to high yields. The addition reaction of the alkenyllithiums other pyridyl ketones 21b–d were also obtained as acetals
proceeded with predominant E selectivity due to coordina- in good yields
tion of the β-alkoxy group with the lithium atom.
Having successfully determined a standard procedure
Next, we examined the hydrolysis of the thienyl alcohol for synthesizing 1,3-bis(hetaryl)-2-chloro-α,β-unsaturated
7a using a variety of acids (Table 2, entries 1–4), beginning ketones, we next examined the transformation of the α,β-
with trimethylsilyl trifluoromethanesulfonate (TMSOTf), unsaturated ketones bearing the chlorine atom and ex-
which gave high yield at low temperature in CH2Cl2 (entry plored the preparation of 1,2,3-tris(aryl) or tris(hetaryl)pro-
1). The structure of 14a was determined by the IR spectro- pen-1-ones with arylboronic acids. A few palladium-cata-
scopic data, showing the absorption of the carbonyl group lyzed arylations of alkenyl halides with arylboronic acids
1
at ν = 1641 cm–1, and the H NMR spectroscopic data, ex- have been reported:[11] one example is the cyclic system such
˜
hibiting a singlet olefinic proton at δ = 7.66 ppm, and the as indole, benzo[b]thiophene and benzo[b]furan and an-
MS and the elemental analytical data, showing the molecu- other is the 2-iodo-2-alkenones. The arylation of 2-chloro-
lar formula of C13H9ClS. On the other hand, the usual ace- 2-alkenones has not been reported. As illustrated in Table 3,
talization process provided the α,β-unsaturated acetals 15a– the coupling reaction of 16a with p-methoxyphenylboronic
b in good yields (entry 2 and 5). p-Toluenesulfonic acid gave acid proceeded smoothly in the presence of Pd(dppb) as the
rise to a low yield of 14a. Lewis acid-catalyzed formation best catalyst. Tetrakis(triphenylphosphane)palladium gave
of the α-chloro-α,β-unsaturated ketone 14a using scandium a low yield of the product. The palladium-catalyzed aryl-
triflate was successful (entry 4). 2-(p-Chlorophenyl-2-chlo- ation of 1,3-biaryl-2-chloropropen-1-ones with some aryl-
ropropenyl)thiophene 7b afforded α,β-unsaturated acetal boronic acids was examined. The coupling reaction of 16
15b (entry 5). Cycloalkanols also afforded the cycloalkylid- with p-chlorophenylboronic acid afforded 22b in good yield;
ene ketones 14c–e and the corresponding acetal 15d, respec- however, the method was not effective with 2-thienylboronic
tively (entries 6–10); however, 2-cyclohexen-1-ol gave a acid under the same conditions (entry 3). The phenyl deriv-
complex mixture (entry 11). 5-Methylthienyl 9, furyl 10 and ative provided 2-(p-methoxyphenyl)-3-phenyl-1-(2-thienyl)-
5-methylfuryl 11a–c were transformed to the α,β-unsatu- propen-1-one (22d) (entry 4). Pentamethylene derivative 22e
rated ketones 16, 17a–c, and 18a by the same method (en- was also obtained in high yields; however, the 3-(2-furyl)-
tries 12–16). 2-Chloro-1-phenylprop-2-enone 19 was ob- 1-(2-pyridyl)propen-1-one 22f was not. We performed the
tained in high yield (entry 17). The transformation of the coupling reaction of the pyridyl acetal 21d; however, the
pyridyl derivatives to the α,β-unsaturated ketones resulted reaction did not proceed, and 21d was recovered. The reac-
Eur. J. Org. Chem. 2007, 2006–2014
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2007

A. Itoh, M. Sakai, M. Yoshimatsu
FULL PAPER
Table 2. Acid-mediated preparation of aryl 2-chloroprop-2-enyl ketones.
tions with p-methoxyphenylboronic acid proceeded during chloropropen-1-ones with arylboronic acids; however, the
4h, while the reactions with the p-chlorophenylboronic acid stereoselectivities were found to be very low. The details for
took over 12h. As a whole, the electron-donating substitu- these coupling reactions were not clear, therefore, we can
ents gave satisfactory results in the palladium-catalyzed not mention the reaction mechanisms and the stereoselecti-
coupling reactions of 1,3-bis(aryl) and 1,3-bis(hetaryl)-2- vities.
Table 3. Pd-catalyzed reaction of 1,3-biaryl-2-chloroprop-2-enone with arylboronic acids.
Entry
2-Chloropropenone R1
R2
R3
R4
Yield (E:Z)
1
2
3
4
5
6
16
16
2-furyl
H
H
H
5-methyl-2-thienyl
5-methyl-2-thienyl
5-methyl-2-thienyl
2-thienyl
2-thienyl
2-pyridyl
p-MeOC6H4
p-ClC6H4
2-thienyl
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
22a (79 %) (71:29)
22b (72 %) (64:36)
22c (24 %) (100:0)
22d (quant.) (58:42)
22e (quant.)
2-furyl
2-furyl
Ph
16
19
14c
21d
H
–(CH2)5–
–(CH2)5–
22f (–)[a]
[a] 2-Chloro-3-furyl-1-(2-pyridyl)prop-2-enone (21d) was used as a starting material.
2008
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New 1,3-Bis(hetaryl)-2-chloropropen-1-ones
FULL PAPER
7.36 (m, 7 H, ArH), 7.41–7.44 (m, 4 H, ArH) ppm. MS: m/z = 400
(M+), 382 (M+ – H2O).
Conclusion
We have described the first access to 1,3-bis(hetaryl)-2-
chloropropenones from aldehydes and ketones using α-aryl-
β-chloro-α-ethoxyethenyllithiums. The attractive features of
this method include the versatility of the functional groups
on the propenones by using a wide variety of β-alkoxyalk-
enyllithiums. Furthermore, the chloropropenones could be
transformed into 1,2,3-triaryl- and 1,2,3-tris(hetaryl)pro-
penones by the palladium-catalyzed coupling reactions with
arylboronic acids. This process may be applied to the syn-
thesis of multifunctionalized alkenes as potential cyclooxy-
genase inhibitors.
(Z)- and (E)-2-[2-Chloro-3-(p-chlorophenyl)-1-ethoxyprop-1-enyl]thio-
phene (7b): IR (KBr): ν = 3427 (OH),1663, 1489, 710 (C–Cl) cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 1.32 (t, J = 7 Hz, Z-Me), 1.34
(t, J = 7 Hz, E-Me), 2.70 (br. d, J = 6 Hz, Z-OH), 2.74 (br. s, E-
OH), 3.76–4.14 (m, Z- and E-OCH2), 5.99 (d, J = 3 Hz, E-CHOH),
6.17 (d, J = 7 Hz, Z-CHOH), 6.83 (d, J = 4 Hz, E-ArH), 7.07–7.09
(dd, J = 4, 5 Hz, Z-ArH), 7.25–7.54 (m, Z- and E-ArH) ppm. The
isomer ratio is E/Z = 67:33. MS: m/z = 328 (M+), 293 (M+ – Cl);
HRMS: calcd. for C15H14Cl2O2S 328.0089; found 328.0056.
(E)-1-[1-Chloro-2-ethoxy-2-(2-thienyl)ethenyl]cyclohexanol (7c): IR
1
(KBr): ν = 3502 (OH),1446 (thienyl), 704 (C–Cl) cm–1. H NMR
˜
(500 MHz, CDCl3): δ = 1.28 (t, J = 7 Hz, 3 H, Me), 1.57–1.58 (m,
2 H, CH2), 1.65–1.90 (m, 6 H, CH2), 1.92–1.95 (m, 2 H, CH2), 3.74
(q, J = 7 Hz, 2 H, OCH2), 4.47 (s, 1 H, OH), 7.03 (dd, J = 4, 5 Hz,
1 H, 5-H), 7.26 (dd, J = 1, 4 Hz, 1 H, 3-H), 7.37 (dd, J = 1, 5 Hz,
1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.97 (q), 21.52
(tϫ2), 25.31 (t), 36.39 (tϫ2), 67.65 (t), 76.00 (s), 126.48 (d), 126.96
(d), 129.23 (s), 129.63 (d), 135.79 (s), 144.42 (s). MS: m/z = 286
(M+), 251 (M+ – Cl). C14H19ClO2S (286.82): calcd. C 58.63, H 6.33;
found C 59.69, H 5.41.
Experimental Section
General Experimental Methods: Melting points were determined on
a J-Science Labo micro melting point apparatus and are uncor-
rected. Elemental analyses were performed at the Center of Instru-
mentation of Gifu University. 1H and 13C NMR spectra were deter-
mined with Varian Inova 400 (400 MHz) and 500 (500 MHz) and
JEOL ECA500 (500 MHz) spectrometers at Gifu University.
Chemical shifts are expressed in parts per million (ppm) with re-
spect to tetramethylsilane as an internal standard. Splitting pat-
terns are designated as follows: s, singlet; d, doublet; t, triplet; q,
quartet. IR spectra were determined with a JASCO FT-IR
460PLUS infrared spectrometer and are expressed in reciprocal
centimeters. EI mass spectra (MS) were obtained using a JEOL
MS-700 spectrometer with a direct-insertion probe at 70 eV. All
high-resolution mass spectra were obtained using a JMSD300
JMA2000 on-line system. The 2-chloro-1-ethoxyethenes 1–6
were prepared according to our previous method.[10] The stereo-
chemistries of the alcohols 7a–f, 9, 10, 11a–c, 12, 13a–d and the
propen-1-ones 14a–e, 15a–d, 16, 17a–c, 18a, 19, 20a, 21a–d were
determined by the NOE experiments.
(E)-1-[1-Chloro-2-ethoxy-2-(2-thienyl)ethenyl]cyclopentanol (7d): IR
(KBr): ν = 3448 (OH), 2959, 2360, 1636, 1390, 1248, 1046, 851,
˜
705 (C–Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.29 (t, J =
7 Hz, 3 H, Me), 1.71–1.75 (m, 2 H, CH2), 1.86–1.90 (m, 2 H, CH2),
1.94–1.98 (m, 2 H, CH2), 2.10–2.17 (m, 2 H, CH2), 3.76 (q, J =
7 Hz, 2 H, OCH2), 4.10 (s, 1 H, OH), 7.04 (dd, J = 4, 5 Hz, 1 H,
ArH), 7.30 (dd, J = 1, 4 Hz, 1 H, ArH), 7.38 (dd, J = 1, 5 Hz, 1
H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.96 (q), 23.64
(t ϫ 2), 40.22 (t ϫ 2), 67.73 (t), 84.84 (s), 126.50 (s), 126.93 (d),
126.99 (d), 129.53 (d), 135.79 (s), 145.08 (s). HRMS: calcd. for
C13H17ClO2S 272.0638; found 272.0697.
(E)-1-[1-Chloro-2-ethoxy-2-(2-thienyl)ethenyl]cyclododecanol (7e):
IR (KBr): ν = 3445 (OH), 2929, 1707, 1470, 1248, 1061, 702 (C–
˜
Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.27 (t, J = 7 Hz, 3 H,
Me), 1.26–1.31 (m, 4 H, CH2), 1.38 (br. s, 10 H, CH2), 1.49–1.51(m,
2 H, CH2), 1.69–1.74 (m, 2 H, CH2), 1.83–1.95 (m, 2 H, CH2),
2.44–2.56 (m, 2 H, CH2), 3.71 (q, J = 7 Hz, 2 H, OCH2), 4.26 (s,
1 H, OH), 7.03 (br. t, J = 4 Hz, 1 H, 4-H), 7.23 (m, 1 H, 3-H), 7.39
(d, J = 4 Hz, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
14.96 (q), 19.77 (t), 22.02 (t), 22.29 (t), 22.49 (t), 24.17 (t), 24.55
(t), 24.69 (t), 26.08 (t), 26.32 (t), 34.83 (t), 40.30 (t), 67.18 (t), 78.32
(s), 126.48 (d), 126.95 (d), 128.45 (s), 129.63 (d), 135.41 (s), 144.88
(s) ppm. MS: m/z = 370 (M+). C20H31ClO2S (370.98): calcd. C
64.75, H 8.42; found C 64.57, H 8.38.
(E)-2-(2-Chloro-1-ethoxy-3-hydroxy-3-phenylprop-1-enyl)thiophene
(7a). Typical Procedure: To a solution of (E)-2-(2-chloro-1-ethoxy-
ethenyl)thiophene (1) (0.50 g, 2.65 mmol) in THF (6.0 mL) was
added nBuLi (1.02 mL, 2.65 mmol) at –78 °C under Ar. After
10 min stirring, a solution of benzaldehyde (0.19 g, 1.77 mmol) in
THF (1.0 mL) was added dropwise to the mixture. The resulting
mixture was stirred for 10 min and then poured into water (50 mL).
The usual work-up afforded compound 7a (0.39 g, 85%) as a yel-
low oil. IR (KBr): ν = 3733 (OH), 1612, 1052 (C–O), 701 (C–Cl)
˜
cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.31 (t, J = 7 Hz, 3 H,
Me), 2.97 (br. s, 1 H, OH), 3.75–3.90 (m, 2 H, OCH2), 6.20 (s, 1
H, CHOH), 7.04 (dd, J = 4, 5 Hz, 1 H, 4-H), 7.19–7.37 (m, 4 H,
ArH), 7.45–7.48 (m, 3 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 15.23 (q), 68.71 (t), 70.23 (d), 124.18 (s), 125.90 (dϫ2),
126.83 (d), 127.54 (d), 127.57 (d), 128.25 (dϫ2), 129.50 (d), 135.37
(s), 140.83 (s), 146.44 (s) ppm. MS: m/z = 294 (M+), 259 (M+ – Cl).
C15H15ClO2S (294.80): calcd. C 61.11, H 5.13; found C 60.89, H
5.10.
(E)-1-[1-Chloro-2-ethoxy-2-(2-thienyl)ethenyl]cyclohex-2-en-1-ol
(7f): IR (KBr): ν = 3448 (OH), 2933, 1617, 1246, 1041 (C–O), 851,
˜
706 (C–Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.29 (t, J =
7 Hz, 3 H, Me), 1.85–2.18 (m, 6 H, CH2), 3.73–3.79 (m, 2 H,
OCH2), 4.56 (s, 1 H, OH), 5.82–5.83 (m, 1 H, olefinic H), 5.84–
5.94 (m, 1 H, olefinic H), 7.05 (dd, J = 4, 5 Hz, 1 H, 4-H), 7.30
(dd, J = 1, 4 Hz, 1 H, ArH), 7.39 (dd, J = 1, 5 Hz, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ = 14.92 (q), 18.48 (t), 24.58 (t),
35.86 (t), 67.82 (t), 74.15 (s), 126.55 (d), 127.10 (d), 127.44 (s),
129.65 (d), 129.71 (d), 130.51 (d), 135.63 (s), 145.19 (s) ppm. MS:
m/z = 83 (thienyl). C14H17ClO2S (284.80): calcd. C 59.04, H 6.02;
found C 58.88, H 5.97.
(E)-2-(2-Chloro-1-ethoxy-3-phenylprop-1-enyl)-5-(hydroxyphenyl-
methyl)thiophene (8): IR (KBr): ν = 3390 (OH), 1604, 1493, 1450,
˜
1390, 1247, 1195, 1119, 1063, 700 cm–1 1H NMR (500 MHz,
.
CDCl3): δ = 1.29 (t, J = 7 Hz, 3 H, Me), 2.77 (br. s, 1 H, OH), (E)-2-[2-Chloro-1-ethoxy-3-hydroxy-3-(2-furyl)prop-1-enyl]-5-meth-
2.85 (br. s, 1 H, OH), 3.78–3.88 (m, 2 H, OCH2), 5.97 (s, 1 H,
CHO), 6.15 (s, 1 H, CHOH), 6.78 (d, J = 4 Hz, 1 H, ArH), 7.23–
ylthiophene (9): IR (KBr): ν = 3423 (OH), 2977, 1611, 1456, 1250,
˜
1064, 806, 744 (C–Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.30
Eur. J. Org. Chem. 2007, 2006–2014
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A. Itoh, M. Sakai, M. Yoshimatsu
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(t, J = 7 Hz, 3 H, Me), 2.49 (s, 3 H, Me), 3.00 (br. s, 1 H, OH),
(dϫ2), 129.08 (d), 129.54 (dϫ2), 132.76 (s), 133.52 (s), 151.59 (s),
3.86 (q, J = 7 Hz, 2 H, OCH2), 6.12 (d, J = 8 Hz, 1 H, CHOH), 159.05 (s) ppm. MS: m/z = 318 (M+), 283 (M+ – Cl). C18H19ClO3
6.34 (dd, J = 2, 3 Hz, 1 H, ArH), 6.39–6.40 (m, 1 H, ArH), 6.72 (318.80): calcd. C 67.82, H 6.01; found C 67.54, H 5.92.
(dd, J = 1, 4 Hz, 1 H, ArH), 7.28 (d, J = 4 Hz, 1 H, ArH), 7.37
(E)-2-[2-Chloro-1-ethoxy-3-hydroxy-3-(p-methoxyphenyl)prop-1-
(d, J = 1 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ =
enyl]pyridine (13a): IR (KBr): ν = 3422 (OH), 3205, 1614, 1589,
˜
15.07 (q), 15.17 (q), 65.64 (q), 68.90 (t), 106.94 (d), 110.23 (d),
120.65 (s), 125.14 (d), 129.74 (d), 132.70 (s), 142.09 (d), 142.54 (s),
146.99 (s), 153.56 (s) ppm. HRMS: calcd. for C14H15ClO3S
298.0430; found 298.0398.
1
1509 (pyridyl), 1468, 1434, 1299, 1242, 1084, 750 (C–Cl) cm–1. H
NMR (500 MHz, CDCl3): δ = 1.24 (t, J = 7 Hz, 3 H, Me), 3.59 (d,
J = 4 Hz, 1 H, OH), 3.61–3.71 (m, 2 H, OCH2), 3.78 (s, 3 H, OMe),
6.29 (d, J = 4 Hz, 1 H, CHO), 6.89 (d, J = 9 Hz, 2 H, ArH), 7.24–
7.27(m, 1 H, ArH), 7.48 (d, J = 9 Hz, 2 H, ArH), 7.57 (d, J =
8 Hz, 1 H, ArH), 7.70–7.74 (m, 1 H, ArH), 8.68–8.69 (m, 1 H,
(E)-2-[2-Chloro-1-ethoxy-3-hydroxy-3-(p-methoxyphenyl)prop-1-
enyl]furan (10): IR (KBr): ν = 3443 (OH), 2932, 1612, 1511 (furyl),
˜
1248, 1172, 1068, 1032 (C–O), 830, 748 (C–Cl) cm–1. 1H NMR ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.01 (q), 55.08 (q),
(500 MHz, CDCl3): δ = 1.31 (t, J = 7 Hz, 3 H, Me), 2.84 (d, J = 66.44 (t), 69.14 (d), 113.48 (dϫ2), 123.38 (d), 124.55 (s), 125.58
7 Hz, 1 H, OH), 3.77 (s, 3 H, OMe), 3.79–3.89 (m, 2 H, OCH2), (d), 127.13 (dϫ2), 133.18 (s), 136.09 (d), 149.36 (d), 149.75 (s),
6.15 (d, J = 7 Hz, 1 H CHOH), 6.46 (dd, J = 2, 3 Hz, 1 H, ArH), 151.78 (s), 158.81 (s) ppm. MS: m/z = 319 (small M+), 284 (M+ –
6.86–6.88 (m, 3 H, ArH), 7.38 (d, J = 8 Hz, 2 H, ArH), 7.47 (d, J
Cl). C17H18ClNO3 (319.79): calcd. C 63.85, H 5.67, N 4.38; found
= 2 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.17 C 63.60, H 5.58, N 4.36.
(q), 55.14 (q), 68.54 (t), 69.53 (d), 111.11 (d), 113.59 (dϫ2), 113.85
(E)-1-[1-Chloro-2-ethoxy-2-(2-pyridyl)ethenyl]cyclohexanol (13b):
(d), 124.04 (s), 127.10 (dϫ2), 132.94 (s), 142.62 (d), 142.92 (s),
146.51 (s) 158.96 (s). MS: m/z = 303.
IR (KBr): ν = 3449 (OH), 2930, 2361, 1585 (pyridyl), 1430, 1390,
˜
1294, 1071 (C–O), 966, 801, 749 (C–Cl), 636 cm–1
.
1H NMR
(E)-2-[2-Chloro-3-(p-chlorophenyl)-1-ethoxyprop-1-enyl]-5-methyl-
(500 MHz, CDCl3): δ = 1.25 (t, J = 7 Hz, 3 H, Me), 1.57–2.05 (m,
furan (11a): IR (KBr): ν = 3434 (OH), 2360, 1595, 1489, 1265, 10 H, CH2), 3.58–3.63 (m, 2 H, OCH2), 4.44 (s, 1 H, OH), 7.26–
˜
1088, 791, 730 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.32 (t, J = 7.29 (m, 1 H, ArH), 7.50 (d, J = 8 Hz, 1 H, ArH), 7.73–7.76 (m, 1
7 Hz, 3 H, Me), 2.34 (s, 3 H, Me), 2.79 (br. s, 1 H, OH), 3.79–3.97
(m, 2 H, OCH2), 6.07–6.08 (m, 1 H, ArH), 6.15 (s, 1 H, CHO),
H, ArH), 8.70 (d, J = 4 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.94 (q), 21.53 (tϫ2), 25.35 (t), 36.08 (tϫ2), 66.65
6.76 (d, J = 3 Hz, 1 H, ArH), 7.30 (d, J = 8 Hz, 2 H, ArH), 7.39 (t), 75.66 (s), 123.31 (d), 125.77 (d), 127.97 (s), 136.23 (d), 148.95
(d, J = 8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ =
(s), 149.48 (d), 152.77 (s) ppm. HRMS: calcd. for C15H20ClNO2
13.66 (q), 15.22 (q), 68.56 (t), 69.45 (d), 107.48 (d), 115.41 (d), 281.1182; found 281.1098.
121.79 (s), 127.34 (d ϫ2), 128.29 (d ϫ2), 133.20 (s), 139.49 (s),
(1E,4E)-2-(2-Chloro-1-ethoxy-3-hydroxy-5-phenylpenta-1,4-dienyl)-
143.55 (s), 144.35 (s), 153.03 (s) ppm. MS: m/z = 326 (M+).
C16H16ClO3 (327.21): calcd. C 58.73, H 4.92; found C 58.44, H
4.71.
pyridine (13c): IR (KBr): ν = 3399 (OH), 2978, 1587 (pyridyl), 1467,
˜
1
1431, 1298, 1074 (C–O), 967, 789, 752 (C–Cl), 696 cm–1. H NMR
(500 MHz, CDCl3): δ = 1.23 (t, J = 7 Hz, 3 H, Me), 3.68 (q, J =
7 Hz, 2 H, OCH2), 3.69 (br. s, 1 H, OH), 5.86 (s, 1 H, CHOH),
(E)-1-[1-Chloro-2-ethoxy-2-(5-methyl-2-furyl)ethenyl]cyclohexanol
(11b): IR (KBr): ν = 3504 (OH), 2930, 2361, 1594 (furyl), 1447, 6.40 (dd, J = 5, 16 Hz, 1 H, olefinic H), 6.78 (dd, J = 1, 16 Hz, 1
˜
1392, 1267, 1066, 1028 (C–O), 964, 787 (C–Cl) cm–1
.
1H NMR H, olefinic H), 7.20–7.31 (m, 4 H, ArH), 7.40–7.42 (m, 2 H, ArH),
(500 MHz, CDCl3): δ = 1.31 (t, J = 7 Hz, 3 H, Me), 1.55–1.57 (m, 7.56–7.58 (m, 1 H, ArH), 7.69–7.73 (m, 1 H, ArH), 8.68–8.70 (m,
2 H, CH2), 1.73–1.79 (m, 6 H, CH2), 1.87–1.90 (m, 2 H, CH2), 2.33
(s, 3 H, Me), 3.76 (q, J = 7 Hz, 2 H, OCH2), 4.45 (s, 1 H, OH),
6.04 (brs, 1 H, 4-H), 6.61 (d, J = 4 Hz, 1 H, 3-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 13.63 (q), 15.02 (q), 21.53 (tϫ2), 25.32 (t),
36.34 (tϫ2), 67.82 (t), 75.87 (s), 106.95 (d), 114.87 (d), 128.00 (s),
142.10 (s), 144.75 (s), 152.26 (s). MS: m/z = 284 (M+), 255 (M+ –
Et). C15H21ClO3 (284.78): calcd. C 63.26, H 7.43; found C 62.98,
H 7.17.
1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.09 (q), 66.61
(t), 69.31 (d), 123.40 (s), 123.51 (d), 125.49 (d), 126.62 (d ϫ2),
127.70 (d), 128.32 (d), 128.47 (dϫ2), 131.31 (d), 136.18 (d), 136.54
(s), 149.54 (d), 149.87 (s), 151.88 (s) ppm. HRMS: calcd. for
C18H18ClNO2 315.1026; found 315.0988.
(E)-2-[2-Chloro-1-ethoxy-3-(2-furyl)-3-hydroxyprop-1-enyl]pyridine
(13d): IR (KBr): ν = 3594 (OH), 2361, 1587, 1467, 1432, 1300,
˜
1
1089, 746 (C–Cl) cm–1. H NMR (500 MHz, CDCl3): δ = 1.22 (t,
(E)-2-[2-Chloro-1-ethoxy-3-hydroxy-3-(2-thienyl)prop-1-enyl]-5-
J = 7 Hz, 3 H, Me), 3.67 (q, J = 7 Hz, 2 H, OCH2), 3.69 (br. s, 1
H, OH), 6.25 (br. s, 1 H, CHOH), 6.36 (t, J = 2 Hz, 1 H, ArH),
6.44 (d, J = 3 Hz, 1 H, ArH), 7.27–7.30 (m, 1 H, ArH), 7.40 (s, 1
H, ArH), 7.60 (d, J = 8 Hz, 1 H, ArH), 7.74–7.77 (m, 1 H, ArH),
methylfuran (11c): IR (KBr): ν = 3434 (OH), 2978, 1594, 1438 (thi-
˜
enyl), 1266, 1073 (C–O), 704 (C–Cl) cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.31 (t, J = 7 Hz, 3 H, Me), 2.35 (s, 3 H, Ar-Me), 2.80
(d, J = 9 Hz, 1 H, OH), 3.82–3.93 (m, 2 H, OCH2), 6.09 (d, J = 8.70 (d, J = 5 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
3 Hz, 1 H, ArH), 6.31 (d, J = 9 Hz, 1 H, CHOH), 6.79 (d, J =
δ = 14.92 (q), 65.31 (t), 66.71 (d), 106.94 (d), 110.22 (d), 121.77 (s),
3 Hz, 1 H, ArH), 6.97 (t, J = 4 Hz, 1 H, ArH), 7.04 (d, J = 3 Hz, 123.55 (d), 125.52 (d), 136.20 (d), 142.05 (d), 149.44 (d), 150.50 (s),
1 H, ArH), 7.26 (d, J = 4 Hz, 1 H, ArH) ppm. MS: m/z = 298
151.65 (s), 153.61 (s) ppm. MS: m/z = 279 (M+). C14H14ClNO3
(M+), 263 (M+ – Cl). C14H15ClO3S (298.79): calcd. C 56.28, H 5.06; (279.72): C 60.11, H 5.04, N 5.01; found C 59.92, H 5.03, N 5.00.
found C 56.13, H 4.88.
Preparation of (Z)-2-Chloro-3-phenyl-1-(2-thienyl)prop-2-enone
(E)-2-Chloro-1-ethoxy-3-(p-methoxyphenyl)-1-phenylprop-1-en-3-ol
(12): IR (KBr): ν = 3437 (OH), 1612, 1511, 1249, 1173, 1071, 831,
(14a). Typical Procedure: To a solution of (Z)-2-(2-chloro-1-ethoxy-
3-hydroxy-3-phenylprop-1-enyl)thiophene (7a, 84 mg, 0.32 mmol)
˜
1
776, 701, 564 cm–1. H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = in CH2Cl2 (2.0 mL) was added TMSOTf (72 mg, 0.32 mmol) at
7 Hz, 3 H, Me), 2.59 (br. s, 1 H, OH), 3.59–3.76 (m, 2 H, OCH2), –78 °C under Ar. The reaction mixture was stirred for 10 min and
3.81 (s, 3 H, OMe), 6.18 (d, J = 8 Hz, 1 H CHO), 6.91 (d, J = then poured into a saturated NaHCO3 solution (50 mL). The or-
8 Hz, 2 H, ArH), 7.35–7.43 (m, 5 H, ArH), 7.52 (d, J = 8 Hz, 2 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.12 (q), 55.26 (q),
66.24 (t), 69.90 (d), 113.70 (dϫ2), 122.32 (s), 127.16 (dϫ2), 128.16
ganic layer was separated, and the aqueous layer was extracted with
CHCl3. The combined organic layer was dried with MgSO4. The
solvent was removed under reduced pressure. The residue was puri-
2010
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2006–2014

New 1,3-Bis(hetaryl)-2-chloropropen-1-ones
FULL PAPER
1064, 765 (C–Cl), 726 (C–Cl) cm–1. H NMR (500 MHz, CDCl3):
1
fied by column chromatography on silica gel, eluting with AcOEt/
n-hexane (1:100) to give 14a (70 mg, 87 %) as a yellow oil. IR
δ = 1.75–1.78 (m, 4 H, CH2), 2.55–2.59 (m, 4 H, CH2), 7.12–7.13
(KBr): ν = 1641, 1411 (thienyl), 1605, 1262, 1510, 1491, 1447, 1201, (m, 1 H, 4-H), 7.67–7.68 (m, 1 H, 5-H), 7.90 (t, J = 3 Hz, 1 H, 3-
˜
1
763 (C–Cl), 730, 691 cm–1. H NMR (500 MHz, CDCl3): δ = 7.17
(dd, J = 4, 5 Hz, 1 H, 4-H), 7.42–7.47 (m, 3 H, ArH), 7.66 (s, 1 H, 33.99 (t), 34.71 (t), 118.63 (s), 127.88 (d), 134.48 (d), 134.54 (d),
olefinic H), 7.74 (dd, J = 1, 5 Hz, 1 H, 5-H), 7.85–7.87 (m, 3 H,
142.45 (s), 155.86 (s), 182.51 (s) ppm. MS: m/z = 226 (M+), 191
ArH, 3-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 127.95 (d), (M+ – Cl). C11H11ClOS (226.72): calcd. C 58.27, H 4.89; found C
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.13 (t), 27.67 (t),
128.56 (dϫ2), 129.01 (s), 130.20 (d), 130.50 (d ϫ2), 132.85 (s),
134.54 (d), 134.74 (d), 137.07 (d), 141.49 (s), 182.25 (s) ppm. MS:
m/z = 248 (M+), 213 (M+ – Cl). C13H9ClOS (248.73): calcd. C
62.78, H 3.65; found C 62.64, H 3.56.
57.98, H 4.81.
2-Chloro-1,1-diethoxy-1-(2-thienyl)-2-(cyclopentylidene)ethane
(15d): IR (KBr): ν = 5746, 2973, 1637, 1231, 1058 (C–O), 699 (C–
˜
Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7 Hz, 6 H,
Me), 1.59–1.65 (m, 2 H, CH2), 1.69–1.75 (m, 2 H, CH2), 2.47 (t, J
= 8 Hz, 2 H, CH2), 2.73 (t, J = 7 Hz, 2 H, CH2), 3.37–3.41 (m, 2
H, OCH2), 3.48–3.51 (m, 2 H, OCH2), 6.94–6.97 (m, 1 H, 4Ј-H),
7.07 (dd, J = 1, 3 Hz, 1 H, 3Ј-H), 7.24 (d, J = 5 Hz, 1 H, 5Ј-H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 14.98 (qϫ2), 25.21 (t),
28.23 (t), 33.06 (t), 36.01 (t), 57.73 (tϫ2), 102.30 (s), 123.85 (s),
125.16 (d), 125.24 (d), 126.24 (d), 145.43 (s), 145.55 (s) ppm. MS:
m/z = 255 (M+ – OEt). C15H21ClO2S (300.84): calcd. C 59.89, H
7.04; found C 59.65, H 6.96.
Preparation of (Z)-2-Chloro-1,1-diethoxy-3-phenyl-1-(2-thienyl)-
prop-2-ene (15a). Typical Procedure for Acetalization: To a solution
of 7a (0.10 g, 0.34 mmol) in EtOH (1.0 mL) were added triethyl
orthoformate (0.28 g, 1.90 mmol) and p-TsOH (7.0 mg, 0.04 mmol)
at room temperature. The mixture was stirred for 30 min and then
poured into NaHCO3 (50 mL). The usual work-up afforded 15a
(72 mg, 66%) as a yellow oil. IR (KBr): ν = 2977, 2930, 2893,
˜
1491, 1441, 1403, 1391, 1233, 1197, 1146, 1098, 1056, 983, 819,
787, 702 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 7 Hz,
6 H, Me), 3.54–3.58 (m, 4 H, OCH2), 6.97 (t, J = 4 Hz, 1 H, 4-H),
7.13 (d, J = 4 Hz, 1 H, 3-H), 7.26–7.29 (m, 1 H, 5-H), 7.33–7.37
(m, 3 H, ArH), 7.49 (s, 1 H, olefinic H), 7.69–7.71 (m, 2 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ = 15.04 (qϫ2), 58.10 (tϫ2),
101.03 (s), 125.80 (d), 126.13 (d), 126.44 (dϫ2), 128.15 (dϫ3),
129.52 (dϫ2), 133.09 (s), 134.37 (s), 144.26 (s). MS: m/z = 322
(M+), 287 (M+ – Cl). C17H19ClO2S (322.85): calcd. C 63.25, H 5.93;
found C 62.97, H 5.79.
2-Chloro-2-(cycloundecylidene)-1-(2-thienyl)ethanone (14e): IR
(KBr): ν = 3440, 2931, 1649, 1514, 1469, 1409 (thienyl), 1354, 1269,
˜
723 (C–Cl) cm–1. H NMR (500 MHz, CDCl3): δ = 1.29–1.35 (m,
1
12 H, CH2), 1.43–1.50 (m, 4 H, CH2), 1.59–1.64 (m, 2 H, CH2),
2.15 (t, J = 8 Hz, 2 H, CH2), 2.43 (t, J = 8 Hz, 2 H, CH2), 7.14 (t,
J = 4 Hz, 1 H, 4Ј-H), 7.71–7.73 (m, 2 H, 5Ј-H and 3Ј-H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 21.97 (t), 22.41 (t), 22.73 (t), 22.79
(t), 22.86 (t), 23.88 (t), 25.55 (t), 25.58 (t), 25.73 (t), 28.34 (t), 29.59
(t), 121.14 (s), 128.16 (d), 135.04 (d), 135.29 (d), 142.35 (s), 143.80
(s), 183.94 (s) ppm. MS: m/z = 324 (M+). C18H25ClOS (324.91):
calcd. C 66.54, H 7.76; found C 66.40, H 7.68.
Reaction of 7a with p-TsOH in ClCH2CH2Cl: To a solution of 7a
(0.10 g, 0.38 mmol) in ClCH2CH2Cl (2.0 mL) was added p-TsOH
(6.5 mg, 0.04 mmol) at 0 °C. The reaction mixture was stirred for
12 h at room temperature. The usual work-up afforded 14a (41 mg,
43%).
(Z)-2-Chloro-3-(2-furyl)-1-(5-methyl-2-thienyl)propen-1-one (16): IR
(KBr): ν = 3138, 1637, 1468, 1385, 1280, 1181, 1151, 1087, 1025,
˜
944, 889, 827, 793, 766, 724, 686, 593, 459 cm–1 1H NMR
.
Reaction of 7a with Sc(OTf)3: To a EtOH/H2O (1:1, 1.0 mL) solu-
tion of 7a (0.10 g, 0.38 mmol) was added Sc(OTf)3 (19 mg,
0.04 mmol) at room temperature. The reaction mixture was heated
at reflux conditions for 70 min. The usual work-up afforded 14a
(61 mg, 61%).
(500 MHz, CDCl3): δ = 2.56 (s, 3 H, Me), 6.50–6.61 (m, 1 H, ArH),
6.83–6.84 (m, 1 H, ArH), 7.34 (d, J = 3 Hz, 1 H, ArH), 7.59 (dd,
J = 1, 2 Hz, 1 H, ArH), 7.65 (d, J = 4 Hz, 1 H, ArH), 7.67 (d, J
= 1 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.91
(q), 112.79 (d), 116.77 (d), 125.75 (d), 126.37 (s), 126.68 (d), 134.93
(d), 139.11 (s), 144.87 (d), 149.25 (s), 150.73 (s), 180.65 (s) ppm.
The molecular ion peak was not detected in the mass spectrum.
C12H9ClO2S (252.72): calcd. C 57.03, H 3.59; found C 56.84, H
3.63.
(Z)-2-[2-Chloro-3-(p-chlorophenyl)-1,1-diethoxyprop-2-enyl]thio-
phene (15b): IR (KBr): ν = 3429, 2976, 1490 (thienyl), 1233, 1196,
˜
1145, 1055 (C–O), 982, 818, 786, 702 (thienyl) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 1.25 (t, J = 7 Hz, 6 H, Me), 3.44–3.46 (m,
4 H, OCH2), 6.98 (dd, J = 3, 5 Hz, 1 H, 4Ј-H), 7.11 (dd, J = 1,
3 Hz, 1 H, 3Ј-H), 7.28 (dd, J = 1, 5 Hz, 1 H, 5Ј-H), 7.32 (d, J =
9 Hz, 2 H, ArH), 7.43 (s, 1 H, olefinic H), 7.64 (d, J = 9 Hz, 2 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.02 (qϫ2), 58.15
(tϫ2), 100.98 (s), 125.26 (d), 125.90 (d), 126.19 (d), 126.48 (d),
128.35 (dϫ2), 130.79 (d ϫ2), 132.82 (s), 133.83 (s), 133.89 (s),
144.04 (s) ppm. MS: m/z = 356 (M+), 321 (M+ – Cl). C17H18Cl2O2S
(357.30): calcd. C 60.51, H 5.08; found C 60.23, H 4.97.
(Z)-2-Chloro-3-(p-methoxyphenyl)-1-(2-furyl)propen-1-one (17a): IR
(KBr): ν = 3435, 3133, 2934, 2839, 1644, 1597 (furyl), 1509, 1462,
˜
1258, 1180, 1094, 1027 (C–O), 793 (C–Cl), 535 cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 3.86 (s, 3 H, OMe), 6.59 (dd, J = 2, 4 Hz,
1 H, 4Ј-H), 6.96 (d, J = 9 Hz, 2 H, ArH), 7.36 (d, J = 3 Hz, 1 H,
ArH), 7.69–7.70 (m, 1 H, 5-H), 7.84 (s, 1 H, olefinic H), 7.89 (d, J
= 9 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 55.41
(q), 112.25 (d), 114.12 (dϫ2), 120.57 (d), 125.70 (s), 126.65 (s),
132.95 (dϫ2), 137.98 (d), 147.14 (d), 150.91 (s), 161.35 (s), 176.86
(s) ppm. MS: m/z = 262 (M+), 227(M+ – Cl). C14H11ClO3 (262.69):
calcd. C 64.01, H 4.22; found C 63.82, H 4.24.
2-Chloro-2-(cyclohexylidene)-1-(2-thienyl)ethanone (14c): IR (KBr):
ν = 3448, 2932, 1645 (C=O), 1513, 1447, 1409 (thienyl), 1354, 1282,
˜
1230, 1059, 985, 772 (C–Cl), 724 (C–Cl) cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.52-1.72 (m, 6 H, CH2), 2.21 (t, J = 6 Hz, 2 H, CH2),
2.50 (t, J = 6 Hz, 2 H, CH2), 7.15 (dd, J = 4, 5 Hz, 1 H, ArH), 7.72
(m, 1 H, 3-H), 7.75–7.76 (m, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 25.90 (t), 26.93 (t), 27.49 (t), 30.66 (t), 32.11 (t), 117.81
(s), 128.26 (d), 134.95 (d), 135.39 (d), 142.56 (s), 142.74 (s), 183.94
(s) ppm. MS: m/z = 240 (M+), 205 (M+ – Cl). C12H13ClOS (240.75):
calcd. C 59.86, H 5.44; found C 59.63, H 5.41.
(Z)-2-[2-Chloro-3-(p-chlorophenyl)-1,1-diethoxyprop-2-enyl]-5-meth-
ylfuran (18a): IR (KBr): ν = 3436, 2982, 1491 (furyl), 1254, 1051
˜
(C–O), 948, 785 (C–Cl) cm–1. 1H NMR (500 MHz, CDCl3): δ =
1.24 (t, J = 7 Hz, 6 H, Me), 2.26 (s, 3 H, Me), 3.38–3.45 (m, 2 H,
OCH2), 3.50–3.95 (m, 2 H, OCH2), 5.95 (br. s, 1 H, ArH), 6.47(d,
J = 3 Hz, 1 H, ArH), 7.32 (d, J = 8 Hz, 2 H, ArH), 7.66 (d, J =
2-Chloro-2-(cyclopentylidene)-1-(2-thienyl)ethanone (14d): IR 8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.67
(KBr): ν = 3447, 2959, 1642 (C=O), 1411 (thienyl), 1353, 1267, (q), 15.01 (qϫ2), 57.90 (tϫ2), 99.45 (s), 106.19 (d), 111.38 (d),
˜
Eur. J. Org. Chem. 2007, 2006–2014
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2011

A. Itoh, M. Sakai, M. Yoshimatsu
FULL PAPER
126.29 (d), 128.31 (dϫ2), 130.84 (dϫ2), 131.75 (s), 132.88 (s),
133.77 (s), 149.34 (s), 152.16 (s) ppm. HRMS: calcd. for
C18H20Cl2O3 354.0789; found 354.0754.
= 6 Hz, 2 H, CH2), 2.56 (t, J = 6 Hz, 2 H, CH2), 3.26–3.34 (m, 2
H, OCH2), 3.50–3.58 (m, 2 H, OCH2), 7.15–7.19 (m, 1 H, ArH),
7.64–7.68 (m, 1 H, ArH), 7.72 (d, J = 8 Hz, 1 H, ArH), 8.64 (d, J
= 4 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.03
(q ϫ 2), 26.32 (t), 27.44 (t), 27.58 (t), 31.17 (t), 34.05 (t), 57.48
(tϫ2), 102.37 (s), 122.12 (d), 122.40 (d), 124.37 (s), 135.59 (d),
141.76 (s), 148.92 (d), 160.20 (s) ppm. MS: m/z = 263 (M+ – EtOH).
C17H24ClNO2 (309.84): calcd. C 65.90, H 7.81, N 4.52; found C
65.85, H 7.78, N 4.49.
2-Chloro-2-(cyclohexylidene)-1-(5-methyl-2-furyl)ethanone (17b): IR
(KBr): ν = 3447, 2931, 1652 (C=O), 1509 (furyl), 1448, 1368, 1306,
˜
1207, 1088, 1023, 787 (C–Cl), 734 cm–1 1H NMR (500 MHz,
.
CDCl3): δ = 1.35–1.61 (m, 4 H, CH2), 1.65–1.81 (m, 2 H, CH2),
2.21–2.23 (m, 2 H, CH2), 2.42 (s, 3 H, Me), 2.47–2.49 (m, 2 H,
CH2), 6.21–6.22 (m, 1 H, 4Ј-H), 7.17 (d, J = 4 Hz, 1 H, 3Ј-H) ppm.
13C NMR (100 MHz, CDCl3): δ = 14.09 (q), 25.85 (t), 26.85 (t),
27.42 (t), 30.78 (t), 31.99 (t), 109.37 (d), 117.44 (s), 123.56 (d),
143.36 (s), 149.89 (s), 159.74 (s), 178.14 (s) ppm. MS: m/z = 238
(M+), 203 (M+ – Cl). C13H15ClO2 (238.72): calcd. C 65.41, H 6.33;
found C 65.15, H 6.31.
(2Z,4E)-2-(2-Chloro-1,1-diethoxy-5-phenylpenta-2,4-dienyl)pyridine
(21c): IR (KBr): ν = 2977, 2360, 1585, 1436, 1170, 1057, 976, 752,
˜
695 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.27 (t, J = 7 Hz, 6 H,
Me), 3.32–3.40 (m, 2 H, OCH2), 3.49–3.57 (m, 2 H, OCH2), 6.83
(d, J = 16 Hz, 1 H, 5-H), 7.10 (dd, J = 11, 16 Hz, 1 H, 4-H), 7.15–
7.36 (m, 5 H, 3-H ArH), 7.44–7.46 (m, 2 H, ArH), 7.68–7.73 (m,
1 H, ArH), 7.82–7.85 (m, 1 H, ArH), 8.63–8.64 (m, 1 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ = 15.05 (qϫ2), 57.86 (tϫ2),
101.79 (s), 122.90 (d), 123.05 (d), 123.43 (d), 126.69 (dϫ2), 127.99
(d), 128.13 (d), 128.54 (dϫ2), 132.90 (s), 135.97 (d), 136.49 (d),
136.97 (s), 149.15 (d), 158.08 (s) ppm. MS: m/z = 343 (M+), 314
(M+ – Et), 308 (M+ – Cl), 298 (M+ – EtO). C20H22ClNO2 (343.85):
calcd. C 69.86, H 6.45, N 4.07; found C 69.63, H 6.33, N 4.12.
(Z)-2-Chloro-1-(5-methyl-2-furyl)-3-(2-thienyl)propen-1-one (17c):
IR (KBr): ν = 3433, 1637 (C=O), 1509 (furyl), 1416, 1365, 1286,
˜
1
1208, 1111, 1028, 860, 795 (C–Cl), 715 cm–1. H NMR (500 MHz,
CDCl3): δ = 2.44 (s, 3 H, Me), 6.22 (d, J = 4 Hz, 1 H, ArH), 7.15
(dd, J = 4, 5 Hz, 1 H, ArH), 7.33 (d, J = 3 Hz, 1 H, ArH), 7.52
(d, J = 4 Hz, 1 H, ArH), 7.62–7.63 (m, 1 H, ArH), 8.14 (s, 1 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.02 (q), 109.11
(d), 122.65 (d), 125.89 (s), 127.04 (d), 131.02 (d), 131.64 (d), 134.50
(d), 136.75 (s), 149.37 (s), 158.74 (s), 175.03 (s) ppm. MS: m/z =
252 (M+), 217 (M+ – Cl). C12H9ClO2S (252.72): calcd. C 57.03, H
3.59; found C 56.87, H 3.53.
(Z)-2-[2-Chloro-1,1-diethoxy-3-(2-furyl)prop-2-enyl]pyridine (21d):
IR (KBr): ν = 2978, 1644, 1586, 1482, 1464, 1434, 1385, 1190, 1141,
˜
1069, 960, 765, 692 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.27
(t, J = 7 Hz, 6 H, Me), 3.35–3.39 (m, 2 H, OCH2), 3.50–3.56 (m,
2 H, OCH2), 6.43 (br. s, 1 H, ArH), 6.94 (d, J = 3 Hz, 1 H, ArH),
7.19–7.21 (m, 1 H, ArH), 7.43 (br. s, 1 H, olefinic H), 7.57 (s, 1 H,
ArH), 7.71 (t, J = 8 Hz, 1 H, ArH), 7.84 (d, J = 7 Hz, 1 H, ArH),
8.63 (d, J = 4 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 15.01 (qϫ2), 57.89 (tϫ2), 101.79 (s), 111.45 (d), 111.63 (d),
117.61 (d), 122.92 (d), 123.04 (d), 129.63 (s), 135.98 (d), 142.12 (d),
149.15 (d), 150.00 (s), 157.97 (s) ppm. MS: m/z = 278 (M+ – Et),
262 (M+ – EtO). C16H18ClNO3 (307.78): calcd. C 62.44, H 5.89, N
4.55; found C 62.32, H 5.80, N 4.52.
(Z)-2-Chloro-3-(p-methoxyphenyl)-1-phenylpropen-1-one (19): IR
(KBr): ν = 1656 (C=O), 1598, 1509, 1421, 1258, 1178, 1086, 1073,
˜
1024, 828, 715, 655, 538 cm–1. 1H NMR (500 MHz, CDCl3): δ =
3.83 (s, 3 H, OMe), 6.94 (d, J = 9 Hz, 2 H, ArH), 7.44 (s, 1 H,
olefinic H), 7.45–7.48 (m, 2 H, ArH), 7.55–7.58 (m, 1 H, ArH),
7.73–7.75 (m, 2 H, ArH), 7.84 (d, J = 9 Hz, 2 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 55.32 (q), 114.04 (dϫ2), 125.42 (s),
128.27 (s), 128.32 (dϫ2), 129.28 (dϫ2), 132.08 (d), 132.80 (dϫ2),
137.29 (s), 140.12 (d), 161.37 (s), 191.29 (s) ppm. MS: m/z = 272
(M+), 237 (M+ – Cl). C16H13ClO2 (272.73): calcd. C 70.46, H 4.80;
found C 70.32, H 4.82.
Palladium-Catalyzed Arylation of 16 with (p-Methoxyphenyl)-
boronic Acid: To a solution of 16 (50 mg, 0.20 mmol) in toluene/
EtOH (1:1, 3.0 mL) was added [1,4-bis(diphenylphosphanyl)bu-
tane]palladium dichloride (18.0 mg, 0.016 mmol), water (1.0 mL),
Na2CO3 (34.0 mg, 0.32 mmol) and p-methoxyphenylboronic acid
(72 mg, 0.47 mmol). The reaction mixture was heated for 1 h under
reflux, and the usual work-up gave (E)-3-(2-furyl)-2-(p-meth-
oxyphenyl)-1-(5-methyl-2-thienyl)propen-1-one (22a) (35 mg, 54%)
and (Z)-22a (15 mg, 23%) as a yellow oil.
(Z)-2-Chloro-3-(p-methoxyphenyl)-1-(2-pyridyl)propen-1-one (20a):
IR (KBr): ν = 1659 (C=O), 1593, 1509, 1259, 1178, 1096, 1029,
˜
832, 672, 535 cm–1. 1H NMR (500 MHz, CDCl3): δ = 3.86 (s, 3 H,
OMe), 6.93 (d, J = 8 Hz, 2 H, ArH), 7.47–7.49 (m, 1 H, ArH),
7.87–7.93 (m, 4 H, ArH), 8.12 (s, 1 H, olefinic H), 8.70–8.71 (m, 1
H, ArH) ppm. HRMS: calcd. for C15H12ClNO2 273.0556; found
273.0539.
(Z)-2-[2-Chloro-1,1-diethoxy-3-(p-methoxyphenyl)prop-2-enyl]pyri-
(E)-22a: IR (KBr): ν = 1637, 1511, 1449, 1352, 1290, 1249, 1229,
˜
dine (21a): IR (KBr): ν = 3448, 2982, 2937, 2896, 2363, 1603, 1510,
˜
1
1181, 1032, 830, 741, 546 cm–1. H NMR (500 MHz, CDCl3): δ =
1
1285, 1250, 1184, 1069, 833 cm–1. H NMR (500 MHz, CDCl3): δ
2.50 (s, 3 H, Me), 3.79 (s, 3 H, OMe), 6.30 (dd, J = 2, 4 Hz, 1 H,
ArH), 6.35 (d, J = 3 Hz, 1 H, ArH), 6.68 (dd, J = 1, 3 Hz, 1 H,
ArH), 6.76 (s, 1 H, olefinic H), 6.84 (d, J = 10 Hz, 2 H, ArH),
6.86–6.87 (m, 1 H, ArH), 7.26–7.27 (m, 1 H, ArH), 7.39 (d, J =
10 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.56
(q), 55.29 (q), 110.01 (d), 111.65 (d), 114.27 (dϫ2), 114.62 (d),
127.03 (d), 127.19 (dϫ2), 129.49 (s), 135.40 (d), 136.89 (s), 142.97
(d), 150.94 (s), 151.07 (s), 159.65 (s), 190.34 (s) ppm. HRMS: calcd.
for C19H16O3S 324.0820; found 324.0785.
= 1.28 (t, J = 7 Hz, 6 H, Me), 3.36–3.42 (m, 2 H, OCH2), 3.53–
3.60 (m, 2 H, OCH2), 3.80 (s, 3 H, OMe), 6.87 (d, J = 8 Hz, 2 H,
ArH), 7.20 (dd, J = 5, 8 Hz, 1 H, ArH), 7.55 (s, 1 H, olefinic H),
7.70–7.72 (m, 1 H, ArH), 7.71 (d, J = 8 Hz, 2 H, ArH), 7.86 (br.
d, 1 H, J = 8 Hz, ArH), 8.63 (br. d, 1 H, J = 6 Hz, ArH) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 15.08 (qϫ2), 55.15 (q), 57.87 (tϫ2),
102.04 (s), 113.40 (dϫ2), 122.85 (d), 123.20 (d), 126.78 (d), 126.93
(s), 129.51 (s), 131.04 (dϫ2), 135.94 (d), 149.09 (d), 158.29 (s),
159.23 (s) ppm. MS: m/z = 347 (M+), 318 (M+ – Et), 302 (M+ –
OEt). C19H22ClNO3 (347.84): calcd. C 65.61, H 6.38, N 4.03;
found C 65.47, H 6.35, N 4.02.
(Z)-22a: IR (KBr): ν = 1631 (C=O), 1607, 1574, 1510, 1448, 1390,
˜
1362, 1087, 1065, 1027, 944, 885, 813, 748 cm–1
.
1H NMR
2-[2-Chloro-2-(cyclohexylidene)-1,1-diethoxyethyl]pyridine (21b): IR
(500 MHz, CDCl3): δ = 2.49 (s, 3 H, Me), 3.87 (s, 3 H, OMe), 5.95
(KBr): ν = 3435, 2928, 1586, 1432, 1390, 1270, 1226, 1064, 992, (dd, J = 1, 3 Hz, 1 H, ArH), 6.29–6.30 (m, 1 H, ArH), 6.66 (d, J
˜
750 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7 Hz, 6 H,
Me), 1.25–1.33 (m, 2 H, CH2), 1.45–1.56 (m, 4 H, CH2), 2.45 (t, J = 4 Hz, 1 H, ArH), 7.27 (d, J = 9 Hz, 2 H, ArH), 7.38–7.39 (m, 1
= 1, 4 Hz, 1 H, ArH), 6.97 (d, J = 9 Hz, 2 H, ArH), 7.10 (br. d, J
2012
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New 1,3-Bis(hetaryl)-2-chloropropen-1-ones
FULL PAPER
H, ArH), 7.45 (s, 1 H, olefinic H) ppm. The molecular ion peak
was not detected in the mass spectrum.
E-olefinic H), 7.14–7.24 (m, E- and Z-ArH), 7.33 (d, J = 9 Hz, E-
ArH), 7.39 (s, Z-olefinic H), 7.42–7.43 (m, E- and Z-ArH), 7.54–
7.58 (m, E- and Z-ArH) ppm. Precipitation of (E)- and (Z)-22d
afforded almost pure (E)-22d: 1H NMR (500 MHz, CDCl3): δ =
3.81 (s, 3 H, OMe), 6.88 (d, J = 9 Hz, 2 H, ArH), 6.94 (dd, J = 4,
5 Hz, 1 H, ArH), 7.08 (s, 1 H, olefinic H), 7.14–7.23 (m, 3 H, ArH),
7.33 (d, J = 8 Hz, 2 H, ArH), 7.43 (d, J = 8 Hz, 2 H, ArH), 7.55
(d, J = 4 Hz, 1 H, ArH), 7.58 (dd, J = 1, 5 Hz, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ = 55.24 (q), 114.20 (dϫ2), 127.61
(dϫ2), 127.78 (d), 128.18 (d), 128.38 (dϫ2), 128.62 (dϫ2), 130.28
(d), 131.15 (d), 134.95 (d), 135.07 (s), 135.56 (s), 140.14 (s), 144.11
(s), 159.69 (s), 191.61 (s) ppm. MS m/z 320 (M+). C20H16O2S
(320.41): calcd. C 74.97, H 5.03; found C 74.60, H 5.05.
Palladium-Catalyzed Arylation of 16 with (4-Chlorophenyl)boronic
Acid: To a solution of 16 (50 mg, 0.20 mmol) in toluene/EtOH (1:1,
1.0 mL) was added [1,4-bis(diphenylphosphanyl)butane]palladium
dichloride (12.0 mg, 0.02 mmol), water (1.0 mL), Na2CO3 (0.11 g,
1.00 mmol) and (p-chlorophenyl)boronic acid (93 mg, 0.59 mmol).
The reaction mixture was heated for 12 h under reflux, and the
usual work-up gave (E)-2-(p-chlorophenyl)-3-(2-furyl)-1-(5-methyl-
2-thienyl)propen-1-one (22b) (30 mg, 46 %) and (Z)-22b (17 mg,
26%).
(E)-22b: A yellow oil. IR (KBr): ν = 1637 (C=O), 1491, 1476, 1449,
˜
1348, 1270, 1229, 1094, 1059, 1013, 930, 885, 857, 827, 808, 760,
742 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.51 (s, 3 H, Me), 6.32
(dd, J = 2, 3 Hz, 1 H, ArH), 6.42 (d, J = 3 Hz, 1 H, ArH), 6.69
(d, J = 3 Hz, 1 H, ArH), 6.90 (s, 1 H, ArH), 7.28 (br. s, 1 H, ArH),
7.29 (d, J = 9 Hz, 2 H, ArH), 7.38 (s, 1 H, olefinic H), 7.39 (d, J
= 9 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.16
(q), 111.80 (d), 112.22 (d), 116.62 (d), 127.10 (dϫ3), 128.99 (dϫ2),
134.01 (s), 135.40 (s), 135.43 (d), 135.85 (s), 141.66 (s), 143.55 (d),
150.58 (s), 151.34 (s), 189.55 (s) ppm. MS: m/z = 328 (M+).
C18H13ClO2S (328.81): calcd. C 65.75, H 3.99; found C 65.49, H
3.95.
Palladium-Catalyzed Arylation of 14c with (p-Methoxyphenyl)-
boronic Acid: To a solution of 14c (50 mg, 0.20 mmol) in toluene/
EtOH (1:1, 3.0 mL) was added [1,4-bis(diphenylphosphanyl)bu-
tane]palladium dichloride (12.0 mg, 0.02 mmol), water (1.0 mL),
Na2CO3 (0.11 g, 1.00 mmol) and (p-methoxyphenyl)boronic acid
(91 mg, 0.60 mmol). The reaction mixture was heated for 12 h un-
der reflux, and the usual work-up gave 2-(p-methoxyphenyl)-2-(cy-
clohexylidene)-1-(2-thienyl)ethanone (22e) (62 mg, quant.) as a yel-
low oil. IR (KBr): ν = 2929, 2853, 1638 (C=O), 1606, 1509, 1459,
˜
1447, 1411, 1354, 1247, 1176, 1111, 1081, 1055, 1034, 984, 835,
1
799, 726 cm–1. H NMR (500 MHz, CDCl3): δ = 1.60–1.64 (m, 6
(Z)-22b: A yellow oil. IR (KBr): ν = 1631 (C=O), 1491, 1448, 1393,
˜
H, CH2), 2.22 (br. s, 2 H, CH2), 2.27–2.29 (m, 2 H, CH2), 3.76 (s,
3 H, OMe), 6.84 (d, J = 9 Hz, 2 H, ArH), 7.05 (d, J = 4 Hz, 1 H,
ArH), 7.23 (d, J = 9 Hz, 2 H, ArH), 7.58 (d, J = 5 Hz, 1 H, ArH),
7.64–7.65 (m, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ =
26.28 (t), 28.05 (t), 28.14 (t), 30.83 (t), 33.08 (t), 55.09 (q), 113.74
(dϫ2), 128.05 (d), 128.80 (s), 130.39 (dϫ2), 133.20 (s), 133.98 (d),
134.19 (d), 142.53 (s), 144.88 (s), 158.71 (s), 191.18 (s) ppm. MS:
m/z = 312 (M+). C19H20O2S (312.43): calcd. C 73.04, H 6.45; found
C 73.00, H 6.43.
1362, 1336, 1277, 1228, 1166, 1147, 1090, 1065, 1017, 943, 885,
802, 747 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.50 (s, 3 H, Me),
6.02 (d, J = 3 Hz, 1 H, ArH), 6.32 (d, J = 2 Hz, 1 H, ArH), 6.70
(d, J = 4 Hz, 1 H, ArH), 7.17 (d, J = 4 Hz, 1 H, ArH), 7.30 (d, J
= 9 Hz, 2 H, ArH), 7.37–7.41 (m, 3 H, ArH), 7.44 (s, 1 H, olefinic
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.92 (q), 112.23 (d),
114.98 (d), 126.60 (d), 126.90 (d), 128.99 (dϫ2), 131.15 (dϫ2),
134.27 (s), 134.62 (d), 135.25 (s), 141.74 (s), 143.57 (s), 144.36 (d),
150.18 (s), 150.85 (s), 185.65 (s) ppm HRMS: calcd. for
C18H13ClO2S 328.0324; found 328.0321.
Palladium-Catalyzed Arylation of 16 with 2-Thienylboronic Acid: To
a solution of 16 (50 mg, 0.20 mmol) in toluene/EtOH (1:1, 3.0 mL)
was added [1,4-bis(diphenylphosphanyl)butane]palladium dichlo-
ride (12.0 mg, 0.02 mmol), water (1.0 mL), Na2CO3 (0.11 g,
1.00 mmol) and 2-thienylboronic acid (78 mg, 0.60 mmol). The re-
action mixture was heated for 12 h under reflux, and the usual
work-up gave (E)-3-(2-furyl)-1-(5-methyl-2-thienyl)-2-(2-thienyl)-
Acknowledgments
We thank Gifu University for financial support of a part of this
work.
[1] H. Sasai, S. Arai, M. Shibasaki, J. Org. Chem. 1994, 59, 2661–
2664; S.-I. Narita, A. Takahashi, H. Sato, T. Aoki, S.-I. Yam-
ada, M. Shibasaki, Tetrahedron Lett. 1992, 33, 4041–4044.
[2] A. E. Greene, F. Charbonnier, M.-J. Luche, A. Moyano, J. Am.
Chem. Soc. 1987, 109, 4752–4753.
[3] G. Mehta, K. S. Rao, J. Am. Chem. Soc. 1986, 108, 8015–8021.
[4] A. E. Greene, F. Charbonnier, Tetrahedron Lett. 1985, 26,
5525–5528.
[5] J. M. Concellon, M. Huerta, Tetrahedron 2002, 58, 7775–7780.
[6] J.-P. Depres, A. E. Greene, J. Org. Chem. 1980, 45, 2037–2039;
M. C. Cabaleiro, N. N. Giagante, R. O. Garay, J. Chem. Res.
Synop. 1983, 240–241.
[7] J. Villieras, P. Perriot, J. F. Normant, Synthesis 1978, 29–31.
[8] G. Dannhardt, W. Kiefer, G. Kramer, S. Maehrlein, U. Nowe,
B. Fiebich, Eur. J. Med. Chem. 2000, 35, 499–510; J. Kankare,
J. Lukkari, P. Pasanen, R. Sillanpaa, H. Laine, K. Harmaa,
C. Visy, Macromolecules 1994, 27, 4327–4334; A. Badorc, J.
Courregelongue, D. Ducros, D. Frehel, A. Giudice, C. Serrad-
eil-Legal, Eur. Pat. Appl. 1993, p. 40 (CAN: 119: 160088);
D. G. Batt, R. Goodman, D. G. Jones, J. S. Kerr, L. R. Man-
tegna, C. McAllister, R. C. Newton, S. Nurnberg, P. K. Welch,
M. B. Covington, J. Med. Chem. 1993, 36, 1434–1442; K. K.
Hsu, Y. C. Lin, C. T. Su, E. J. Lien, Taiwan Yaoxue Zazhi, 1982,
34, 71–86 (CAN 99: 35870); J. C. Dore, C. Viel, J. Pharm. Belg.
1974, 29, 341–351.
propen-1-one (22c) (40 mg, 40%) as a yellow oil. IR (KBr): ν =
˜
1638, 1449, 1358, 1343, 1259, 1229, 1166, 1149, 1018, 927, 885,
1
806, 741, 700, 592 cm–1. H NMR (500 MHz, CDCl3): δ = 2.46 (s,
3 H, Me), 6.24 (dd, J = 2, 3 Hz, 1 H, ArH), 6.30 (d, J = 3 Hz, 1
H, ArH), 6.64 (d, J = 4 Hz, 1 H, ArH), 6.79 (s, 1 H, olefinic H),
6.84–6.88 (m, 2 H, ArH), 7.14 (d, J = 1 Hz, 1 H, ArH), 7.21 (d, J
= 1 Hz, 1 H, ArH), 7.40 (d, J = 3 Hz, 1 H, ArH) ppm. HRMS:
calcd. for C16H12O2S2 300.0276; found 300.0256.
Palladium-Catalyzed Arylation of 19 with (p-Methoxyphenyl)-
boronic Acid: To a solution of 19 (50 mg, 0.20 mmol) in toluene/
EtOH (1:1, 3.0 mL) was added [1,4-bis(diphenylphosphanyl)bu-
tane]palladium dichloride (12.0 mg, 0.02 mmol), water (1.0 mL),
Na2CO3 (0.11 g, 1.00 mmol) and (p-methoxyphenyl)boronic acid
(91 mg, 0.60 mmol). The reaction mixture was heated for 12 h un-
der reflux, and the usual work-up gave (E)- and (Z)-2-(p-meth-
oxyphenyl)-3-phenyl-1-(2-thienyl)propen-1-one (22d) (64 mg,
quant.) as a yellow oil. IR (KBr): ν = 1634 (C=O), 1593, 1512,
˜
1462, 1445, 1412, 1374, 1355, 1282, 1255, 1239, 1183, 918, 884, 857,
1
848, 826, 792, 758, 722, 690 cm–1. H NMR (500 MHz, CDCl3): δ
= 3.78 (s, Z-OMe), 3.81 (s, E-OMe), 6.88 (d, J = 9 Hz, E-ArH),
6.94 (dd, J = 4, 5 Hz, E-ArH), 7.01 (t, J = 4 Hz, Z-ArH), 7.07 (s,
Eur. J. Org. Chem. 2007, 2006–2014
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2013

A. Itoh, M. Sakai, M. Yoshimatsu
FULL PAPER
[9] Y. Jahng, L. Zhao, Y.-S. Moon, A. Basnet, E. Kim, H. W.
Chang, H. K. Ju, T. C. Jeong, E. Lee, Bioorg. Med. Chem. Lett.
2004, 2559–2562.
[10] M. Yoshimatsu, M. Sakai, E. Moriura, Eur. J. Org. Chem.
2007, 498–507.
[11] F. Bellina, A. Carpita, D. Ciucci, A. De Santis, R. Rossi, Tetra-
hedron 1993, 49, 4677–4698; J. Quintin, C. Roullier, S. Thoret,
G. Lewin, Tetrahedron 2006, 62, 4038–4051.
Received: November 2, 2006
Published Online: February 23, 2007
2014
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2006–2014