Palladium-catalyzed esterification-hydroarylation reactions of 2-alkynyl-benzaldehydes with aryl iodides in methanol

Article abstract of DOI:10.1055/s-2004-829056

The reaction of 2-alkynylbenzaldehydes with aryl iodides in the presence of Pd(PPh₃)₄ and K₂CO₃ in refluxing methanol for 24 hours gave the dehydrogenation-addition products, methyl 2-(2,2-disubstituted-vinyl)benzoates in modest yields; together with the cyclization products, 3-methoxy-1-monosubstituted-methylene-3- hydroisobenzofurans in 3-18% yields.

Full text of DOI:10.1055/s-2004-829056

LETTER
1497
Palladium-Catalyzed Esterification-Hydroarylation Reactions of 2-Alkynyl-
benzaldehydes with Aryl Iodides in Methanol
ons Wei,b,c Li-Mei Wei, Wen-Bin Pan, Ming-Jung Wu*
b
b
a
P
L
alladium-Catal
i
yze
d
E
-
sterifica
L
tion-Hydroaryla
a
tion Reacti
n
a
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medicial University, 807 Kaohsiung, Taiwan
E-mail: mijuwu@cc.kmu.edu.tw
b
c
Fooyin University, 831 Kaohsiung county, Taiwan
Graduate Institute of Pharmaceutical Science, Kaohsiung Medicial University, 807 Kaohsiung, Taiwan
Received 25 February 2004
H
Abstract: The reaction of 2-alkynylbenzaldehydes with aryl io-
OR
dides in the presence of Pd(PPh ) and K CO in refluxing methanol
3
4
2
3
H
for 24 hours gave the dehydrogenation-addition products, methyl 2-
2,2-disubstituted-vinyl)benzoates in modest yields; together with
cat. Pd(OAc)2
OR
H
OR
H
or
C
O
C
(
O
O
the cyclization products, 3-methoxy-1-monosubstituted-methyl-
ene-3-hydroisobenzofurans in 3–18% yields.
Equation 1
Key words: palladium, coupling, esterification-hydroarylation, 2-
alkynylbenzaldehydes
Ar
R
Ar
R
Pd(PPh3)4
R
+
ArI
+
O
H
O
K CO MeOH
O
OMe
The palladium-catalyzed sequential cyclization and cou-
pling reactions of acetylenic molecules containing a het-
eronucleophile with organic halides or triflates are a well
established strategy that has led to the successful synthesis
2
3,
OMe
1
2
1
of a variety of heterocycles. For example, the palladium-
Equation 2
induced intermolecular cyclization of acetylenic alcohols
has been shown to be an efficient route to exocyclic enol
2
The synthesis of starting material 2-(2-phenyleth-
ynyl)benzaldehyde (1a)10 is summarized in Scheme 1.
However, the first attempt for the generation of our pro-
posed annulation/coupling products, methylene-3-meth-
oxy-3-hydroisobenzofuran derivatives, was carried out by
treatment of 2-(2-phenylethynyl)benzaldehyde (1a) and
-iodotoluene (2a) in the presence of catalytic amount of
Pd(PPh and K CO as a base in refluxing MeOH for 24
hours to give the addition-oxidation product 2-[(1Z)-2,2-
diphenylvinyl]benzoate 3aa in 50% yield together with
the monosubstituted methylene-3-methoxy-3-hydroiso-
benzofuran 4a in 16% yield (Equation 3). The structure of
ethers. In the same manner, o-ethynylphenols have been
3
converted to 2-substituted benzo[b]furans. This method-
4
ology has also been applied to molecules bearing amino-,
5
6
carboxyl-, and carbo-nucleophiles. Recently we re-
ported an analogous palladium-promoted coupling of 2-
alkynylbenzonitriles with aryl iodides for the synthesis of
4
3
,4-disubstituted isoquinolines and diarylmethylide-
7
3
)
4
2
3
neisoindoles in one step. More recently, we also have es-
tablished a novel route to synthesize 2-(diarylmethylene)-
3
3
1
-benzofuranones by palladium-catalyzed cyclization of
-aryl-1-(2-tert-butyldimethylsilyoxy)phenyl-2-propyn-
8
-ones in moderate to good yields. Yamamoto et al. have
3
aa was unambiguously determined by X-ray crystallo-
reported that the Pd(II) catalyst can act both as a Lewis
acid and catalyst; whereby alkynyl aldehydes and ROH in
1
1
graphic analysis (Figure 1). Herein, we describe our
results on the tandem addition-oxidation of 2-alkynyl-
benzaldehydes with aryl iodides in MeOH leading to
regio- and stereoselective products, methyl 2-(2,2-disub-
stituted-vinyl)benzoates.
the presence of Pd(OAc) were found to afford the alkenyl
2
9
cyclic ethers in good to high yields (Equation 1). Our
continuing interest in the successive annulation/coupling
reaction of 2-alkynylbenzaldehydes 1 with aryl iodides 2
to give the coupling products encouraged us to further
examine the palladium-catalyzed addition/coupling se-
quences of acetylenic aldehydes (Equation 2).
Ph
I
Pd(PPh4)3
CuI, ether
+
Ph
OH
OH
5a
Ph
PCC
H
CH2Cl2
25 °C
SYNLETT 2004, No. 9, pp 1497–1502
Advanced online publication: 01.07.2004
2
2.
0
7.
2
0
0
4
O
1a
DOI: 10.1055/s-2004-829056; Art ID: U06004ST
Scheme 1
©
Georg Thieme Verlag Stuttgart · New York

1
498
L.-L. Wei et al.
LETTER
Ph
tolyl
2-(hexynyl)benzaldehyde (1c) with iodobenzene (2b)
afforded compound 3cb in 63% yield as the only product
(entry 10). Moreover, 2-[2-(4-trifluoromethylphe-
nyl)ethynyl]benzaldehyde (1d) has also been examined
and this gave cyclization product 4d in 100% based on re-
covered yield of 2 (entry 11). The above profile suggested
that the phenyl ring on the alkyne terminus carried an
electron-withdrawing group, deactivating the formation
of the complex between an aryl palladium and an acetyl-
ene. At the same time, it accelerated the rate of the cy-
clization reaction to form the uncoupled product 4d.
H
Ph
+
CH3
Ph
Pd(PPh3)4
H
+
O
H
MeOH, K2CO3
O
OMe
4a
O
I
OMe
1a
2a
3aa
Equation 3
Figure 1 X-ray spectrum of compound 3aa
Figure 2 X-ray spectrum of compound 4b
Thus, various aryl iodides bearing electron-donating or
electron-withdrawing groups on the phenyl ring were
reacted with aryl acetylenic benzaldehyde 1 using
Pd(PPh ) as a catalyst and K CO as the base in MeOH to
give the oxidation products 3 in 35–74% yields, along
with only the cyclization products 4 in 3–18% yields. The
results are summarized in Table 1. Iodobenzene (2b) af-
forded the ester 3ab in 44% yield and uncoupled product
To investigate the mechanism of this tandem oxidation-
reduction reaction, two reactions were carried out. Treat-
ment of 4-iodoanisole with 2-(2-phenylethynyl)benzalde-
3
4
2
3
hyde under the optimal conditions using CD OD as the
3
solvent gave the product 3ac¢ in 48% yield. No deuterium
incorporation was found in the vinylic position of the
product. However, the reaction of deuterium-labeled 1a
(
-CDO) with 4-iodoanisole in CH OH produced the
3
4
a was obtained in 18% yield (entry 2). The reaction of 4-
deutero adduct 3ac¢¢ in 56% yield.
methoxyiodobenzene (2c) produced 3ac and 4a in 53%
and 5% yields, respectively (Table 1, entry 3). 2-Meth-
oxyiodobenzene (2d) gave 3ad in 35% yield and simulta-
neously afforded 4a in 17% yield (entry 4), indicating that
steric hindrance may reduce the rate of the addition reac-
tion. In a further exploration of the substituent effect on
the alkyne terminus on compound 1, 2-alkynylbenzalde-
hydes derivatives 1b–d were prepared according to the
procedure described above. The reaction of 2-[2-(p-meth-
oxyphenyl)ethynyl]benzaldehyde (1b) with 4-iodotolu-
ene (2a) under the optimal reaction conditions gave the
methyl benzoate 3ba in 67% yield together with a small
amount of the adduct 4b in 5% yield (entry 5). Figure 2
OCH3
OCH3
Ph
Ph
H
O
D
O
OCD3
OCH3
3
ac'
3ac''
Figure 3
According to the above results and our previous work,13–15
we proposed a mechanism for this esterification/addition
process as shown in Scheme 2. This reaction pathway
involves: (a) the oxidative addition of aryl iodide to Pd(0)
to give an arylpalladium intermediate, (b) arylpalladium
coordination of the carbon-carbon triple bond of 1 and
subsequent regio- and stereoselective insertion of the 2-
alkynylbenzaldehydes to produce a vinylpalladium inter-
mediate 5, (c) addition of methoxide ion to the carbonyl
group to produce a cyclic oxypalladium complex 6, which
gives the palladium hydride species 7 by b-hydrogen
elimination, and (d) reductive elimination of 7 to afford
1
2
shows the crystal structure of 4b. Similar results were
obtained by employing other aryl iodides. Phenyl iodide
(
2b) afforded 3bb in 50% yield along with the product 4b
in 11% yield, and p-methoxyphenyl iodide (2c) gave 3bc
in 74% yield together with the minor product 4b in 3%
yield (entries 6 and 7). Aryl iodides with an electron with-
drawing group, such as 4-trifluorophenyl iodide (2e) and
2
-iodopyridine (2f) produced the cyclization product 4b
in 40% and 88% yields based on recovered yields of 2,
respectively (entries 8 and 9). However, the reaction of
Synlett 2004, No. 9, 1497–1502 © Thieme Stuttgart · New York

LETTER
Palladium-Catalyzed Esterification-Hydroarylation Reactions
1499
Table 1 Palladium-Catalyzed Addition-Oxidation Reactions of 2-Alkynylbenzaldehydes with Aryl Iodides
R
Ar
H
R
R
Pd(PPh3)4
MeOH, K CO3
H
O
+
ArI
+
O
H
2
O
OMe
OMe
1
2
3
4
Entry
2-Alkynylbenzaldehydes
Aryl iodides
Products (Yield, %)a
1
2
3
4
5
6
7
8
9
1a (R = C H )
2a (Ar = 4-tolyl)
3aa (50%)
3ab (44%)
3ac (53%)
3ad (35%)
3ba (67%)
3bb (50%)
3bc (74%)
4a (16%)
6
5
1a
1a
1a
2b (Ar = phenyl)
4a (18%)
4a (5%)
2c (Ar = 4-methoxyphenyl)
2d (Ar = 2-methoxyphenyl)
4a (17%)
4b (5%)
1b (R = 4-CH OC H )
2a
3
6
4
1b
1b
1b
1b
2b
4b (11%)
4b (3%)
2c
2e (Ar = 4-trifluoromethylphenyl)
4b (40%b)
4b (88%b)
2f (Ar = 2-pyridinyl)
1
1
0
1
1c (R = n-C H )
2b
3cb (63%)
4
9
1d (R = 4-CF C H )
2b
4d (100%b)
3
6
4
a
Yields refer to isolated yields. All of the compounds gave satisfactory H, 13C NMR and MS spectra data.
Based on recovered starting material.
1
b
the stereoisomer 3. The fact that no cyclization/coupling
products were observed suggests that b-hydrogen elimi-
nation of 6 is much faster than reductive elimination of a
C–O bond. Addition of hemiacetal anion to a palladacycle
also explains the fact that the aryl group coming from the
aryl iodide always ends up trans to the methyl benzoate
group. Meanwhile the isotope study supported the pro-
posed mechanism, which implied that the hydrogen
source for the reduction of an alkyne to an alkene comes
from formyl hydrogen of the aldehyde substituent of the
substrate. The other plausible reaction pathway involving
oxidation insertion into the aldehyde C–H bond to form a
palladium(IV) intermediate have been reported by several
1
ArPdI
ArI
R
Ar
Pd X
Pd(0)
O
R
Ar
H(D) –OMe
5
R
Ar
H(D)
O
R
Ar
1
6
research groups in the similar reactions. We feel that fur-
ther experiments are needed to prove the exact reaction
pathway.
Pd
O
PdH(D)
O
OMe
3
β-hydride
H(D)
elimination
OMe
OMe
6
7
In conclusion, the novel palladium(0)-catalyzed cascade
addition/oxidation reaction of 2-alkynylbenzaldehydes
with aryl iodides in MeOH affords one-step synthesis of
stereoisomerical methyl 2-(2,2-disubstituted-vinyl)ben-
zoates. These products are formed regio- and stereoselec-
tively in modest yields. This tandem process
simultaneously couples the oxidation of an aldehyde to an
ester with the hydroarylation of an alkyne to an alkene.
Scheme 2
Addition-Oxidation Reaction of 2-(2-Phenylethynyl)benzalde-
hydes with Aryl Iodides; Typical Procedure
A slurry of the 2-(2-phenylethynyl)benzaldehyde 1a (0.3 mmol),
Currently, the optimization of the selectivity of the tan- aryl iodides 2 (0.6 mmol), Pd(PPh ) (5 mol%) and K CO (1.5
3
4
2
3
dem transformations of 2-alkynylbenzaldehydes with aryl mmol) in refluxing MeOH (8 mL) was stirred for 24 h. The reaction
mixture was filtered through a short pad of silica gel to remove pre-
iodides to 2-vinylbenzoate derivatives is under investiga-
cipitated inorganic salts. The silica gel pad was washed three times
tion.
with a small amount of EtOAc and the combined solution was
Synlett 2004, No. 9, 1497–1502 © Thieme Stuttgart · New York

1
500
L.-L. Wei et al.
LETTER
evaporated to dryness under reduced pressure. The residue was
chromatographed on silica gel using n-hexane–EtOAc (v/v, 40:1) as
eluent to give the products 3 and 4.
H), 6.96–6.93 (m, 2 H), 6.70 (dt, J = 8.8, 2.4 Hz, 2 H), 3.56 (s, 3 H),
3.29 (s, 3 H), 2.23 (s, 3 H).
13
C NMR (100 MHz, C D ): d = 168.4, 160.1, 143.9, 142.1, 141.4,
6
6
1
1
38.1, 133.5, 133.3, 132.7, 132.1, 131.5, 131.3, 129.9, 129.3, 127.8,
27.1, 114.7, 55.2, 52.2, 21.8.
Methyl 2-[(1E)-2-(4-Methylphenyl)-2-phenylvinyl]benzoate
(
3aa)
+
MS (EI): m/z = 358 (100) [M ], 299 (14), 269 (15).
Compound 3aa was obtained in 50% yield as a white solid; mp 75–
7
6 °C.
HRMS (EI): m/z calcd for C H O : 358.1569; found: 358.1537.
2
4
22
3
1
H NMR (200 MHz, C D ): d = 7.96–7.92 (m, 1 H), 7.76 (s, 1 H),
6
6
Methyl 2-[(1Z)-2-(4-Methoxyphenyl)-2-(phenylvinyl)]benzoate
3bb)
Compound 3bb was obtained in 50% yield as a yellow solid; mp
7
.37 (dt, J = 8.2, 2.0 Hz, 2 H), 7.24–7.19 (m, 2 H), 7.07–6.93 (m, 6
(
H), 6.83–6.78 (m, 2 H), 3.45 (s, 3 H), 2.11 (s, 3 H).
1
3
C NMR (50 MHz, C D ): d = 168.2, 144.1, 141.6, 141.5, 141.0,
38.1, 132.7, 132.1, 132.0, 131.4, 131.2, 130.0, 129.1, 129.0, 128.5,
28.0, 127.2, 52.2, 21.7.
6
6
8
4–86 °C.
1
1
1
H NMR (400 MHz, C D ): d = 7.96–7.94 (m, 1 H), 7.70 (s, 1 H),
6
6
7
.47 (dt, J = 6.8, 1.6 Hz, 2 H), 7.15–7.09 (m, 6 H), 6.86–6.83 (m, 2
Anal. Calcd for C H O : C, 84.11; H, 6.14. Found: C, 84.09; H,
6
23
20
2
H), 6.59 (td, J = 8.8, 2.4 Hz, 2 H), 3.45 (s, 3 H), 3.19 (s, 3 H).
.13.
1
3
C NMR (100 MHz, C D ): d = 168.3, 160.1, 144.8, 144.0, 141.3,
6
6
1
1
33.3, 133.3, 132.7, 132.1, 131.5, 131.2, 129.4, 129.2, 128.6, 128.5,
27.2, 114.7, 55.2, 52.2.
Methyl 2-(2,2-Diphenylvinyl)benzoate (3ab)
Compound 3ab was obtained in 44% yield as a white solid; mp 98–
1
00 °C.
Anal. Calcd for C H O : C, 80.20; H, 5.86. Found: C, 80.20; H,
5.98.
2
3
20
3
1
H NMR (200 MHz, C D ): d = 7.91–7.86 (m, 1 H), 7.69 (s, 1 H),
6
6
7
6
.40–7.35 (m, 2 H), 7.15–7.00 (m, 6 H), 6.99–6.90 (m, 3 H), 6.79–
.73 (m, 2 H), 3.40 (s, 3 H).
Methyl 2-[2-(4-Methoxyphenyl)-2-(4-methoxyphenylvi-
nyl)]benzoate (3bc)
Compound 3bc was obtained in 74% yield.
1
3
C NMR (100 MHz, C D ): d = 168.2, 144.3, 144.2, 141.3, 140.9,
6
6
1
32.6, 132.1, 131.4, 131.2, 129.2, 129.1, 128.1, 127.3, 52.2.
1
H NMR (400 MHz, C D ): d = 7.98–7.95 (m, 1 H), 7.69 (s, 1 H),
6
6
Anal. Calcd for C H O : C, 84.04; H, 5.78. Found: C, 83.78; H,
5
22
18
2
7
.41 (dt, J = 9.2, 2.4 Hz, 2 H), 7.18–7.13 (m, 3 H), 6.87–6.83 (m, 2
.87.
H), 6.77 (dt, J = 9.2, 2.4 Hz, 2 H), 6.62 (dt, J = 8.8, 2.0 Hz, 2 H),
.48 (s, 3 H), 3.31 (s, 3 H), 3.20 (s, 3 H).
3
Methyl 2-[(1E)-2-(4-Methoxyphenyl)-2-phenylvinyl]benzoate
3ac)
Compound 3ac was obtained in 53% yield as a white solid; mp 90–
1
3
C NMR (100 MHz, C D ): d = 168.3, 160.7, 160.1, 143.7, 141.5,
(
6
6
1
1
37.3, 133.6, 133.4, 132.7, 132.1, 131.5, 131.3, 130.6, 127.0, 126.9,
14.7, 114.7, 55.5, 55.3, 52.2.
9
2 °C.
+
1
MS (EI): m/z = 374 (100) [M ], 314 (10).
H NMR (400 MHz, C D ): d = 7.95–7.92 (m, 1 H), 7.73 (s, 1 H),
6
6
7
.35 (dt, J = 8.8, 2.8 Hz, 2 H), 7.24–7.21 (m, 2 H), 7.06–6.97 (m, 4
HRMS (EI): m/z calcd for C H O : 374.1518; found: 374.1534.
2
4
22
4
H), 6.86–6.78 (m, 2 H), 6.73 (dt, J = 6.4, 3.2 Hz, 2 H), 3.47 (s, 3 H),
3
.30 (s, 3 H).
Methyl 2-[(1E)-2-Phenylhex-1-enyl]]benzoate (3cb)
Compound 3cb was obtained in 63% yield.
1
3
C NMR (100 MHz, C D ): d = 168.3, 160.6, 143.9, 141.6, 141.1,
36.9, 132.7, 132.1, 132.0, 131.4, 131.2, 130.4, 129.1, 128.1, 127.6,
27.1, 114.7, 55.5, 52.2.
6
6
1
1
1
H NMR (400 MHz, C D ): d = 8.03 (dd, J = 7.6, 1.2 Hz, 1 H), 7.62
6
6
(
dt, J = 7.6, 1.2 Hz, 2 H), 7.40 (s, 1 H), 7.29–7.11 (m, 5 H), 7.03–
6
2
.99 (m, 1 H), 3.46 (s, 3 H), 2.57 (t, J = 7.6 Hz, 2 H), 1.33–1.29 (m,
H), 1.13–1.08 (m, 2 H), 0.63 (t, J = 7.2 Hz, 3 H).
Anal. Calcd for C H O : C, 80.20; H, 5.86. Found: C, 80.27; H,
23
20
3
5
.87.
1
3
C NMR (100 MHz, C D ): d = 167.9, 143.9, 142.3, 141.4, 132.4,
6
6
Methyl 2-[(1E)-2-(2-Methylphenyl)-2-phenylvinyl]benzoate
3ad)
Compound 3ad was obtained in 35% yield as a white solid; mp
1
3
31.7, 131.6, 131.0, 129.7, 129.4, 128.0, 127.9, 127.5, 52.1, 31.5,
(
0.5, 23.2, 14.5.
+
MS (EI): m/z = 294 (73) [M ], 236 (38), 219 (100).
1
21–122 °C.
1
HRMS (EI): m/z calcd for C20H O : 294.1620; found: 294.1621.
22 2
H NMR (400 MHz, C D ): d = 7.94–7.92 (m, 1 H), 7.60 (s, 1 H),
6
6
7
7
3
.42 (dd, J = 7.6, 1.6 Hz, 1 H), 7.26 (dt, J = 6.4, 2.0 Hz, 2 H), 7.15–
.10 (m, 1 H), 6.98–6.82 (m, 7 H), 6.56 (dd, J = 8.4, 1.2 Hz, 1 H),
.41 (s, 3 H), 3.14 (s, 3 H).
3
-Methoxy-1-(phenylmethylene)-3-hydroisobenzofuran (4a)
Compound 4a was obtained in 5–18% yield.
1H NMR (200 MHz, C
): d = 7.99 (d, J = 7.4 Hz, 2 H), 7.34 (t,
J = 7.6 Hz, 2 H), 7.17–7.05 (m, 3 H), 7.02–6.96 (m, 2 H), 6.25 (s,
1
3
D
6 6
C NMR (100 MHz, C D ): d = 168.1, 158.7, 142.2, 141.5, 141.1,
6
6
1
1
32.9, 132.6, 132.1, 131.5, 131.2, 131.1, 131.0, 129.7, 128.8, 127.9,
27.5, 127.3, 121.6, 112.7, 55.9, 52.2.
1
H), 6.00 (s, 1 H), 3.15 (s, 3 H).
1
3
C NMR (50 MHz, C D ): d = 154.2, 138.3, 137.3, 136.8, 130.5,
6
6
Anal. Calcd for C H O : C, 80.20; H, 5.86. Found: C, 80.06; H,
5
23
20
3
1
29.6, 129.5, 129.5, 127.0, 124.0, 120.7, 108.5, 99.5, 54.4.
.83.
+
MS (EI): m/z = 238 (55) [M ], 206 (30), 178 (100).
Methyl 2-[(1Z)-2-(4-Methoxyphenyl)-2-(4-methylphenylvi-
nyl)]benzoate (3ba)
HRMS (EI): m/z calcd for C H O : 238.0994; found: 238.1003.
1
6
14
2
Compound 3ba was obtained in 67% yield.
3
-Methoxy-1-[(4-methoxyphenyl)methylene]-3-hydroisobenzo-
1
H NMR (400 MHz, C D ): d = 8.07–8.05 (m, 1 H), 7.81 (s, 1 H),
furan (4b)
6
6
7
.51 (dt, J = 8.0, 2.0 Hz, 2 H), 7.26–7.22 (m, 3 H), 7.10–7.08 (m, 2
Compound 4b was obtained in 3–88% yield as a white solid; mp
9
7–99 °C.
Synlett 2004, No. 9, 1497–1502 © Thieme Stuttgart · New York

LETTER
Palladium-Catalyzed Esterification-Hydroarylation Reactions
1501
1
+
H NMR (200 MHz, C D ): d = 7.94 (d, J = 8.8 Hz, 2 H), 7.21–6.93
MS (EI): m/z = 274 (100) [M ], 205 (79), 176 (83).
6
6
(
1
m, 6 H), 6.31 (s, 1 H), 6.01 (s, 1 H), 3.36 (s, 3 H), 3.19 (s, 3 H).
HRMS (EI): m/z calcd for C H OF : 274.0600; found: 274.0602.
1
6
9
3
3
C NMR (50 MHz, C D ): d = 159.3, 152.7, 138.0, 137.1, 134.3,
6
6
1
30.9, 130.5, 130.0, 124.0, 120.4, 115.1, 108.3, 99.4, 55.5, 54.2.
Acknowledgment
Anal. Calcd for C H O : C, 76.09; H, 6.01. Found: C, 75.79; H,
17
16
3
6
.31.
We thank the National Science Council of the Republic of China for
the financial support of this program.
3
-Methoxy-1-[(4-trifluoromethylphenyl)methylene]-3-hydro-
isobenzofuran (4d)
Compound 4d was obtained in 100% yield as a yellow solid; mp
References
5
5–57 °C.
(
1) Recent reviews: see (a) Cacchi, S. J. Organomet. Chem.
1999, 576, 42. (b) Zimmer, R.; Dinesh, C. U.; Nandanan, E.;
Khan, F. A. Chem. Rev. 2000, 100, 3067. (c) Bates, R. W.;
Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12. (d) Cacchi,
S.; Fabrizi, G.; Goggiomani, A. Heterocycles 2002, 56, 613.
2) Luo, F.-T.; Schreuder, I.; Wang, R.-T. J. Org. Chem. 1992,
1
H NMR (400 MHz, C D ): d = 7.76 (d, J = 8.0 Hz, 2 H), 7.50 (d,
6
6
J = 8.0 Hz, 2 H), 7.15–7.10 (m, 2 H), 7.03 (td, J = 7.2, 1.6 Hz, 1 H),
.99 (td, J = 7.2, 1.2 Hz, 1 H), 6.16 (s, 1 H), 5.81 (s, 1 H), 3.15 (s, 3
H).
6
(
(
1
3
C NMR (100 MHz, C D ): d = 156.0, 140.8, 138.6, 136.2, 130.6,
30.2, 129.4, 128.1, 126.3, 126.3, 124.1, 120.9, 108.8, 97.9, 54.7.
6
6
57, 2213.
1
3) (a) Arcadi, A.; Cacchi, S.; Marinelli, F. Synthesis 1986, 749.
(b) Arcadi, A.; Cacchi, S.; Del Rosario, M.; Marinelli, F.;
Fabrizi, G. J. Org. Chem. 1996, 61, 9280.
+
MS (EI): m/z = 306 (100) [M ], 275 (53), 274 (40).
HRMS (EI): m/z calcd for C H O F : 306.0862; found: 306.0867.
1
7
13
2 3
(
4) (a) Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett.
1
992, 33, 3915. (b) Luo, F.-T.; Wang, R.-T. Tetrahedron
2
-(2-Phenylethynyl)benzaldehyde (1a)
Lett. 1992, 33, 6835. (c) Saulnier, M. G.; Frennesson, D. B.;
Deshpande, M. S.; Vyas, D. M. Tetrahedron Lett. 1995, 36,
7841. (d) Cacchi, S.; Fabrizi, G.; Pace, P. J. Org. Chem.
Compound 1a was obtained in 88% yield.
1
H NMR (200 MHz, CDCl ): d = 10.66 (s, 1 H), 7.96 (dd, J = 7.6,
3
1
.5 Hz, 1 H), 7.69–7.53 (m, 4 H), 7.51–7.37 (m, 4 H).
1998, 63, 1001.
1
3
C NMR (50 MHz, CDCl ): d = 191.7, 135.9, 133.8, 133.2, 131.7,
(5) (a) Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.;
3
1
29.1, 128.6, 128.5, 127.3, 126.9, 122.3, 96.3, 84.9.
Marinelli, F.; Pietroni, B. R. J. Org. Chem. 1992, 57, 976.
(
b) Bouyssi, D.; Gore, J.; Balme, G.; Louis, D.; Wallach, J.
+
MS (EI): m/z = 206 (100) [M ], 205 (31), 178 (35), 176 (36).
HRMS (EI): m/z calcd for C H O: 206.0732; found: 206.0730.
Tetrahedron Lett. 1993, 34, 3129. (c) Cavicchioli, M.;
Bouyssi, D.; Gore, J.; Balme, G. Tetrahedron Lett. 1996, 37,
1
5
10
1
429. (d) Rossi, R.; Bellina, F.; Biagetti, M.; Catanese, A.;
2
-[2-(4-Methoxyphenyl)ethynyl]benzaldehyde (1b)
Mannina, L. Tetrahedron Lett. 2000, 41, 5281.
(6) (a) Fournet, G.; Balme, G.; Van Hemelryck, B.; Gore, J.
Tetrahedron Lett. 1990, 31, 5147. (b) Fournet, G.; Balme,
G.; Gore, J. Tetrahedron 1991, 47, 6293. (c) Bouyssi, D.;
Gore, J.; Balme, G. Tetrahedron Lett. 1991, 32, 6541.
Compound 1b was obtained in 92% yield as a yellow solid; mp 46–
4
7 °C.
1
H NMR (400 MHz, C D ): d = 10.82 (s, 1 H), 7.91 (dd, J = 8.0, 1.6
6
6
Hz, 1 H), 7.38–7.33 (m, 3 H), 6.93 (td, J = 7.6, 1.6 Hz, 1 H), 6.84 (t,
J = 8.0 Hz, 1 H), 6.62 (dt, J = 9.2, 2.4 Hz, 2 H), 3.19 (s, 3 H).
(d) Balme, G.; Bouyssi, D. Tetrahedron 1994, 50, 403.
(
e) Bruyere, D.; Gaignard, G.; Bouyssi, D.; Balme, G.;
1
3
C NMR (100 MHz, C D ): d = 191.3, 161.3, 137.1, 134.3, 134.1,
6
6
Lancelin, J. M. Tetrahedron Lett. 1997, 38, 827.
1
33.7, 129.0, 128.2, 128.0, 115.6, 115.2, 97.8, 85.2, 55.5.
(
(
(
7) Lin, C.-F.; Lu, W.-D.; Wang, I.-W.; Wu, M.-J. Synlett 2003,
+
2
057.
8) Wei, L.-M.; Lin, C.-F.; Wu, M.-J. Tetrahedron Lett. 2000,
1, 1215.
MS (EI): m/z = 236 (93) [M ], 221 (70), 165 (100).
HRMS (EI): m/z calcd for C H O : 236.0832 found: 236.0834.
1
6
12
2
4
9) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am.
Chem. Soc. 2002, 124, 764.
10) Treatment of 2-iodobenzyl alcohol with phenylacetylene in
2
-Hex-1-ynylbenzaldehyde (1c)
Compound 1c was obtained in 90% yield.
(
1
H NMR (400 MHz, C D ): d = 10.80 (s, 1 H), 7.90 (dd, J = 7.6, 1.2
the presence of catalytic amount of Pd(PPh ) and CuI, n-
BuNH as a base in Et O for 5 h gave compound 5a in 82%
yield. The 2-alkynylbenzaldehyde 1a was obtained by
oxidation of 5a with PCC in 91% yield.
6
6
3 4
Hz, 1 H), 7.30 (dd, J = 7.6, 1.2 Hz, 1 H), 6.92 (td, J = 7.6, 1.6 Hz, 1
H), 6.83 (t, J = 7.6 Hz, 1 H), 2.11 (t, J = 6.8 Hz, 2 H), 1.36–1.23 (m,
2
2
4
H), 0.77 (t, J = 7.2 Hz, 3 H).
1
3
(11) Crystal data for 3aa: C23H O ; M = 328.39 g/mol, crystal
20 2
C NMR (100 MHz, C D ): d = 191.6, 137.5, 134.1, 134.0, 134.0,
6
6
size: 0.50 × 0.50 × 0.50 mm, monoclinic, space group P2 /n,
1
1
27.9, 127.9, 98.8, 77.7, 31.4, 22.9, 20.0, 14.3.
l = 0.71073 Å, a = 9.7557 (6) Å, b = 11.9347 (7) Å, c =
+
MS (EI): m/z = 186 (13) [M ], 157 (29), 144 (96), 115 (100).
HRMS (EI): m/z calcd for C H O: 186.1039; found: 186.1042.
1
5.7626 (9) Å, a = 90°, b = 99.370 (1)°, g = 90°, V = 1810.77
3 3 –1
(
(
19) Å , Z = 4, D = 1.205 Mg/m . m = 0.076 mm , T = 295
1
3
14
2) K, q range: 2.15–27.50°, reflections collected: 17775,
independent reflections: 4167 (R = 0.0303), refinement
2
-[2-(4-Trifluoromethylphenyl)ethynyl]benzaldehyde (1d)
int
2
method: full-matrix least-squares on F , final R values[ I>
Compound 1d was obtained in 96% yield as a white solid; mp 57–
5
2
s(I) ]: R1 = 0.0499, wR2 = 0.1234. Diffractometer:
BRUKER SMART APEXCCD. Crystallographic data
excluding structure factors) for this structure have been
8 °C.
1
H NMR (400 MHz, C D ): d = 10.62 (s, 1 H), 7.84 (ddd, J = 8.0,
6
6
(
1
.6, 0.4 Hz, 1 H), 7.29 (ddd, J = 7.6, 1.2, 0.4 Hz, 1 H), 7.19–7.11
m, 4 H), 6.91 (td, J = 7.6, 1.6 Hz, 1 H), 6.86 (td, J = 7.6, 1.2 Hz, 1
H).
deposited at the Cambridge Crystallographic Data centre as
supplementary publication no. CCDC-223977, and may be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1ED, UK [fax: +44 (1223)336033;
e-mail deposit@ccdc.cam.ac.uk].
(
1
3
C NMR (100 MHz, C D ): d = 190.7, 137.4, 134.1, 133.9, 132.8,
6
6
1
29.9, 128.6, 126.3, 126.3, 126.2, 126.2, 126.2, 95.4, 88.4.
Synlett 2004, No. 9, 1497–1502 © Thieme Stuttgart · New York

1
502
L.-L. Wei et al.
LETTER
(
12) Crystal data for 4b: C H O ; M = 268.30 g/mol, crystal
(13) Wu, M.-J.; Wei, L.-M.; Lin, C.-F.; Leou, S.-P.; Wei, L.-L.
Tetrahedron 2001, 57, 7839.
(14) Wei, L.-L.; Wei, L.-M.; Pan, W.-B.; Leou, S.-P.; Wu, M.-J.
Tetrahedron Lett. 2003, 44, 1979.
(15) Wei, L.-M.; Wei, L.-L.; Pan, W.-B.; Wu, M.-J. Tetrahedron
Lett. 2003, 44, 595.
(16) (a) Meegalla, S. K.; Taylor, N. J.; Rodrigo, R. J. Org. Chem.
1992, 57, 2422. (b) Larock, R. C.; Doty, M. J. J. Org. Chem.
1993, 58, 4579. (c) Satoh, T.; Itaya, T.; Miura, M.; Nomura,
M. Chem. Lett. 1996, 823. (d) Muratake, H.; Nakai, H.
Tetrahedron Lett. 1999, 40, 2355. (e) Tanaka, K.; Fu, G. C.
Angew. Chem. Int. Ed. 2002, 41, 1607.
1
7
16
3
size: 0.27 × 0.23 × 0.02 mm, orthorhombic, space group
Pca2 , l = 0.71073 Å, a = 20.9353 (13) Å, b = 8.6773 (5) Å,
1
c = 7.7543 (5) Å, a = 90°, b = 90°, g = 90°, V = 1408.66 (15)
3
3
–1
Å , Z = 4, D = 1.265 Mg/m . m = 0.086 mm , T = 295 (2) K,
q range: 1.95–27.50°, reflections collected: 13064,
independent reflections: 3220 (R = 0.0619), refinement
method: full-matrix least-squares on F , final R values[ I >
int
2
2
s(I) ]: R1 = 0.0902, wR2 = 0.1693. Diffractometer:
BRUKER SMART APEXCCD. Crystallographic data
excluding structure factors) for this structure have been
(
deposited at the Cambridge Crystallographic Data center as
supplementary publication no. CCDC-231702.
Synlett 2004, No. 9, 1497–1502 © Thieme Stuttgart · New York