Lewis acid-catalyzed [4 + 2] benzannulation between enynal units and enols or enol ethers: Novel synthetic tools for polysubstituted aromatic compounds including indole and benzofuran derivatives

Article abstract of DOI:10.1021/jo060597m

The reaction of enynals 1, including o-(alkynyl)benzaldehydes, and carbonyl compounds 2, such as aldehydes and ketones, in the presence of a catalytic amount of AuBr₃ in 1,4-dioxane at 100 °C gave the functionalized aromatic compounds 3 in high yields. Similarly, the AuBr₃-catalyzed reactions of 1 with acetal compounds 5 afforded the corresponding aromatic compounds 3 in good yields. On the other hand, when the reaction was carried out in the presence of a catalytic amount of Cu(NTf₂)₂ and 1 equiv of H₂O in (CH₂Cl)₂ at 100 °C, the decarbonylated naphthalene products 4 were obtained selectively over 3. Benzofused heteroaromatic compounds, such as indole derivatives 13 and benzofuran derivatives 15, were also synthesized by using the present benzannulation methodology.

Full text of DOI:10.1021/jo060597m

Lewis Acid-Catalyzed [4 + 2] Benzannulation between Enynal Units
and Enols or Enol Ethers: Novel Synthetic Tools for
Polysubstituted Aromatic Compounds Including Indole and
Benzofuran Derivatives
Naoki Asao* and Haruo Aikawa
Department of Chemistry, Graduate School of Science, Tohoku UniVersity, Sendai 980-8578, Japan
asao@mail.tains.tohoku.ac.jp
ReceiVed March 18, 2006
The reaction of enynals 1, including o-(alkynyl)benzaldehydes, and carbonyl compounds 2, such as
aldehydes and ketones, in the presence of a catalytic amount of AuBr
functionalized aromatic compounds 3 in high yields. Similarly, the AuBr
acetal compounds 5 afforded the corresponding aromatic compounds 3 in good yields. On the other
hand, when the reaction was carried out in the presence of a catalytic amount of Cu(NTf and 1 equiv
of H O in (CH Cl) at 100 °C, the decarbonylated naphthalene products 4 were obtained selectively over
. Benzofused heteroaromatic compounds, such as indole derivatives 13 and benzofuran derivatives 15,
were also synthesized by using the present benzannulation methodology.
3
in 1,4-dioxane at 100 °C gave the
3
-catalyzed reactions of 1 with
2 2
)
2
2
2
3
Introduction
together with a novel synthetic method of benzofused heteroaro-
matic compounds, such as indole and benzofuran derivatives
eq 2).
(
Stereodefined synthesis of polysubstituted aromatic com-
pounds is highly important in modern organic chemistry. Since
Reppe’s pioneering work on metal-catalyzed benzannulations
1
using [2 + 2 + 2] cyclotrimerization of alkynes, a number of
synthetic methods using transition-metal catalysts have been
2
reported. However, efficient synthetic methods are still needed
from the viewpoint of atom economy or environmental concern.
Recently, we have communicated the novel gold-catalyzed [4
+
2] benzannulation between enynal units, including
o-(alkynyl)benzaldehydes, and carbonyl compounds, which
produces aromatic ketones in good to high yields as shown in
3
,4
eq 1. Now, we report the detailed study on this reaction
Results and Discussion
A) Benzannulation Using Enynal Units and Carbonyl
Compounds. As we previously reported, the [4 + 2] cycload-
dition reaction of o-(alkynyl)benzaldehydes 1 with various kinds
of carbonyl compounds 2 proceeded smoothly in the presence
of gold catalyst, leading to naphthyl ketone derivatives 3 together
(
*
(
Corresponding author. Phone: +81-22-795-3898. Fax: +81-22-795-6784.
1) (a) Reppe, W.; Schweckendieck, W. J. Liebigs Ann. Chem. 1948,
60, 104. For references, see: (b) Vollhardt, K. P. C. Angew. Chem., Int.
5
Ed. Engl. 1984, 23, 539. (c) Mohler, D. L.; Vollhardt, K. P. C. In AdVances
in Strain in Organic Chemistry; Halton, B., Ed.; JAI Press: London, 1995;
Vol. 5, p 121.
1
0.1021/jo060597m CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/08/2006
J. Org. Chem. 2006, 71, 5249-5253
5249

Asao and Aikawa
TABLE 1. AuBr3-Catalyzed [4 + 2] Benzannulation between
o-(Alkynyl)benzaldehydes 1 and Carbonyl Compounds 2a
13% yield (eq 3). Probably, acetaldehyde would be produced
in situ by the retro-aldol condensation between 2h and a small
amount of water, which might exist in the media. Then, the
benzannulation between the resulting acetaldehyde and 1a would
take place to afford 3i. This result clearly shows that 2h can be
used as a masked acetaldehyde in the [4 + 2] benzannulation,
although the chemical yield of 3i was low.
entry
1
1
R
2
R1
R2 ratio (3:4)b
yield (%)c
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
2a Ph
2b CH3
2c C5H11
2d Pr
2e
2f
H
3a:4a
3b:4b
3c:4c
3d:4d
3e:4e
3f:4f
87:13
97:3
99:<1
80:20
82:18
91:9
90
87
81
81
56
45
45
71
d,e
2
H
H
H
3
f
i
4
5
g
-(CH2)4-
H CH3
f
6
7
8
2g BnO
H
H
3g:4g
3h:4h
99:<1
99:<1
d
Not only the benzaldehyde derivatives underwent benzan-
nulation; conjugated enyne aldehydes also underwent benzan-
nulation, leading to polysubstituted benzene derivatives regio-
selectively. For example, the reaction of 1c with phenylacetal-
dehyde 2a gave terphenyl derivative 3j and 4i in 42 and 6%,
respectively. When the reaction was carried out using propanal
1b C4H9 2b CH3
a
The reaction was performed using 1 (1 equiv) and 2 (1.2 equiv) in the
presence of AuBr3 (10 mol %) in 1,4-dioxane at 100 °C within 3 h unless
b
1
c
d
otherwise noted. Determined by H NMR. Combined isolated yield. Five
equivalents of 2b were used. The reaction was carried out at 80 °C. The
reaction was carried out in the presence of 30 mol % of AuBr3. The
reaction was carried out in the presence of 20 mol % of AuBr3.
e
f
g
2
b, 3k was obtained in 70% together with 4j in 12% yield (eq
4
).
with small amounts of decarbonylated products 4 in good to
4
,5
high yields, and the results are summarized in Table 1. The
reaction proceeded well even with the sterically bulky aldehyde,
such as 3-methylbutanal 2d, although an increased amount of
catalyst was needed (entry 4). In addition to aldehydes, ketones
were also usable as a 2π-system in the present reaction. When
1
a was treated with cyclohexanone 2e, the corresponding six-
membered annulated naphthalene 3e was obtained in a moderate
yield (entry 5). Analogously, the reaction of 1a with acetone
The reaction of 1 with acetal compounds 5, instead of
carbonyl compounds 2, also proceeded to give a variety of
aromatic compounds. Treatment of 1a with 1,1-dimethoxyoctane
2
f proceeded to give 3f, which is a regioisomer of 3b (entry 6).
Not only simple alkyl and aryl substituents can be introduced
to the naphthalene skeleton; an alkoxy group can also be
introduced to the naphthalene skeleton. The reaction of 1a with
benzyloxyacetaldehyde 2g gave 3g as a sole product (entry 7).
The benzannulation of 1b, having butyl group at the terminal
position of alkyne, with 2b gave 3h in 71% yield (entry 8). In
5
a in the presence of gold catalyst gave the corresponding
naphthalene derivative 3l in 27% yield. The chemical yield was
improved by addition of water (3 equiv), and 3l was obtained
in 68% yield together with 4k in 5% yield (eq 5). We also
examined the reaction of 1a and 1d with paraldehyde 5b. Even
without external addition of water, the corresponding products
i and 3m were obtained in 61 and 52% yields, respectively
eq 6). Furthermore, the reaction between 1c and 5b proceeded
smoothly to give benzophenone derivative 3n in 51% yield
together with a small amount of 4l (8%) (eq 7). These results
showed that 5b can work as an acetaldehyde source in the
[4 + 2] benzannulation as well as 2h.
1
every case, we did not detect the regioisomers of 3; R was
2
always at the C-3 position and R was always at the C-2
3
(
position.
Interestingly, when the reaction of 1a with crotonaldehyde
2
h was examined, naphthyl phenyl ketone 3i was obtained in
(2) For reviews, see: (a) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J.
Org. Chem. 2005, 4741. (b) Modern Arene Chemistry; Astruc, D., Ed.;
Wiley-VCH: Weinheim, 2002. (c) Saito, S.; Yamamoto, Y. Chem. ReV.
2000, 100, 2901. (d) Gevorgyan, V.; Yamamoto, Y. J. Organomet. Chem.
1999, 576, 232. (e) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996,
96, 49. (f) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259. (g)
Grotjahn, D. B. In ComprehensiVe Organometallic Chemistry II; Hegedus,
L. S., Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press:
Oxford, 1995; Vol. 12, p 741. (h) Schore, N. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 5, p 1129. (i) Schore, N. E. Chem ReV. 1988, 88, 1081.
(
3) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126,
458.
4) For reviews on the Au-catalyzed reactions, see: (a) Ma, S.; Yu, S.;
7
(
Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200. (b) Hashmi, A. S. K. Angew.
Chem., Int. Ed. 2005, 44, 6990. (c) Hoffmann-R o¨ der, A.; Krause, N. Org.
Biomol. Chem. 2005, 3, 387. (d) Arcadi, A.; Di Giuseppe, S. Curr. Org.
Chem. 2004, 8, 795. (e) Hashmi, A. S. K. Gold Bull. 2004, 37, 51. (f)
Hashmi, A. S. K. Gold Bull. 2003, 36, 3. (g) Dyker, G. Angew. Chem., Int.
Ed. 2000, 39, 4237.
(5) For gold-catalyzed benzannulation, see: (a) Hashmi, A. S. K.; Frost,
T. M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553. (b) Hashmi, A. S.
K.; Frost, T. M.; Bats, J. W. Org. Lett. 2001, 3, 3769. (c) Dankwardt, J. W.
Tetrahedron Lett. 2001, 42, 5809. (d) Hashmi, A. S. K.; Frost, T. M.; Bats,
J. W. Catal. Today 2002, 72, 19.
5250 J. Org. Chem., Vol. 71, No. 14, 2006

Lewis Acid-Catalyzed [4 + 2] Benzannulation
SCHEME 1. Plausible Reaction Mechanism of the [4 + 2] Benzannulation between 1 and 2
TABLE 2. Copper-Catalyzed Benzannulation between 1a and 2ba
2, followed by dehydration would generate the intermediate 9
ratio (3b:4b)b
yield (%)c
through 8. When the reaction is catalyzed by AuX3, the
subsequent bond rearrangement would afford the naphthyl
ketone derivatives 3 and regenerate AuX3. On the other hand,
in the Cu(NTf2)2-HA system, protonolysis of the C-Cu bond
entry
Lewis acid
additives
1
2
3
4
5
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(NTf2)2
Cu(NTf2)2
none
60:40
48:52
38:62
13:87
10:90
80
79
66
31
48
CF2HCO2H
CF3CO2H
none
-
of 9 by HA, followed by the attack of A to the carbon of RCO,
H2O
would produce 10, which would undergo the retro Diels-Alder
reaction to lead the formation of 4. It is worth mentioning that
when the AuX3-catalyzed reaction of 1a with 2b was carried
out in the presence of MS 3A under conditions similar to those
mentioned in Table 1, the chemical yield of 3b was dramatically
decreased and only trace amounts of 3b were obtained. Trace
amounts of water, which might exist in the reaction medium,
would play an important role for the keto-enol tautomerization
a
The reaction was performed using 1a (1 equiv) and 2b (5 equiv) in the
presence of Lewis acid (10 mol %) and additives (1 equiv) in (CH2Cl)2 at
b
1
c
1
00 °C within 2 h. Determined by H NMR. Combined NMR yield using
p-xylene as an internal standard.
We have reported that the AuX3-catalyzed benzannulation
between enynal unit 1 and alkynes gives aromatic compounds
in high yields. On the other hand, selective formation of the
decarbonylated products 4 over 3 was observed by changing
the catalyst from AuX3 to a combination of a catalytic amount
of Cu(OTf)2 and a stoichiometric amount of Brønsted acid.
Therefore, we were interested whether the similar decarbon-
ylation reaction would be possible in the present reaction. We
examined the reaction of 1a with 2b using the copper catalyst
in the presence of Brønsted acid under the several conditions,
and results are summarized in Table 2. When the reaction was
conducted in the presence of a catalytic amount of Cu(OTf)2
without Brønsted acid, 3b was obtained predominantly over 4b
in 80% yield as a combined yield of 3b and 4b (entry 1).
Optimization experiments revealed that the addition of Brønsted
acids, such as CF2HCO2H and CF3CO2H, increased the ratio
of 4b against 3b (entries 2 and 3). Finally, we found that the
best selectivity was obtained by using the Cu(NTf2)2-H2O
system and 4b was produced in 43% yield together with a small
amount of 3b (5%) (entry 5).
6
3
9,10
between 2b and 7. The reaction would probably not proceed
well without water due to the lack of the generation of enol
form 7.
6
b
In the normal electron demand-type Diels-Alder reaction
between diene systems and carbonyl compounds, it is well-
known that the carbon-oxygen double bond of carbonyl
compounds acts as a 2π-system with various 4π-systems as a
hetero-Diels-Alder reaction (type a in Scheme 2). However,
to the best of our knowledge, the present benzannulation is the
first example of the Lewis acid-catalyzed reverse electron
demand-type cycloaddition between a 4π-system and an enol
11
derived from an aldehyde and ketone (type b in Scheme 2).
SCHEME 2. Reaction Type of the Diels-Alder Reaction
between Diene Systems and Carbonyl Compounds
A plausible mechanism for the present benzannulation is
(
B) Benzannulation Using Enynal Units and Enol Ethers.
3,4,7,8
shown in Scheme 1.
The coordination of the triple bond
In addition to carbonyl compounds, enol ethers can be used for
the present benzannulation reaction.
â-methoxystyrene 11a using AuBr3 catalyst proceeded, and
naphthyl ketone product 3a was obtained in 42% yield. The
chemical yield of 3a was increased to 84% when the reaction
of 1 to Lewis acid (M: AuX3 or Cu(NTf2)2) enhances the
electrophilicity of the alkyne, and the subsequent nucleophilic
attack of the carbonyl oxygen to the electron-deficient alkyne
would form the ate complex 6. The reverse electron demand-
type Diels-Alder reaction of 6 with the enol 7, derived from
12-14
The reaction of 1a with
(
9) A protic catalyst, which is formed from AuBr3 in water, might
(
6) (a) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J.
promote the enolization process. See: Dyker, G.; Hildebrandt, D.; Liu, J.;
Merz, K. Angew. Chem., Int. Ed. 2003, 42, 4399.
(10) A theoretical study on keto-enol tautomerization was reported.
See: Lee, D.; Kim, C. K.; Lee, B.-S.; Lee, I.; Lee, B. C. J. Comput. Chem.
1997, 18, 56 and references therein.
(11) For example, see: Fringuelli, F.; Taticchi, A. The Diels-Alder
Reaction-Selected Practical Methods; Wiley: Chichester, 2002.
(12) Asao, N.; Kasahara, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2003,
42, 3504.
(13) Pt-catalyzed benzannulation using ortho-alkynyl benzoates and vinyl
ethers was reported. See: Kusama, H.; Funami, H.; Takaya, J.; Iwasawa,
N. Org. Lett. 2004, 6, 605.
Am. Chem. Soc. 2002, 124, 12650. (b) Asao, N.; Nogami, T.; Lee, S.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 10921.
(7) For acid-induced pyrylium salts syntheses by electrophilic cyclizations
of o-alkynyl(oxo)benzenes, see: (a) Tovar, J. D.; Swager, T. M. J. Org.
Chem. 1999, 64, 6499. (b) Barluenga, J.; V a´ zquez-Villa, H.; Ballesteros,
A.; Gonz a´ lez, J. M. J. Am. Chem. Soc. 2003, 125, 9028. (c) Zhu, J.; Germain,
A. R.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2004, 43, 1239.
(
8) Benzo[c]pyrylium salts are known to play a dien part in the Diels-
Alder reaction with ethyl vinyl ether and azomethines. See: Kuznetsov,
E.; Shcherbakova, I. V.; Balaban, A. T. AdV. Heterocycl. Chem. 1990, 50,
57.
1
J. Org. Chem, Vol. 71, No. 14, 2006 5251

Asao and Aikawa
was carried out using Cu(OTf)2 instead of AuBr3. The Cu(OTf)2-
catalyzed reaction of 1a with 11b also proceeded to give 3l in
a catalytic amount of Cu(OTf)2 in THF to give 13a in 53%
yield (eq 9). The Cu-catalyzed reaction between 12 and acetal
5a also gave benzannulation product 13b in 79% yield (eq 10).
As we mentioned earlier, the selective formation of decarbo-
nylated naphthalene 4b over 3b was attained by using the Cu-
5
6% yield (eq 8).
(
NTf2)2-H2O system. However, attempts to prepare decarbo-
nylated indole did not give any satisfactory results. For example,
when the reaction of 12 with 11a was examined using the Cu-
(
NTf2)2-H2O system, 13a was produced in 49% yield and the
desired decarbonylated indole product was obtained in less than
2
0% yield.
(C) Construction of Benzofused Heteroaromatic Com-
pounds. We next turned our attention to the construction of
benzofused heteroaromatic compounds by using the present
methodology. Although many synthetic methods of indole and
15
benzofuran skeletons are known, little attention has been paid
to the approach based on the construction of a benzene ring
1
6
onto a functionalized pyrrole and furan derivatives. During
our research project, Barluenga et al. reported that the iodonium-
mediated benzannulation reaction using 3-alkynylpyrrole-2-
carboxaldehydes with alkenes (or the corresponding enamines
or enol ethers) led to indole derivatives.17 Benzofuran and
benzothiophene derivatives were also prepared in the same way.
To develop the catalytic version, we examined the reaction of
1
2 with enol ether 11 in the presence of several kinds of
catalysts, and results are summarized in Table 3. The reaction
of 12 with â-methoxystyrene 11a in the presence of a catalytic
amount of Cu(OTf)2 gave 13a in 90% yield (entry 1). AuBr3
and AgNTf2 were also suitable catalysts (entries 2 and 3).
Although the reaction proceeded even with a catalytic amount
of TfOH, the chemical yield was low (entry 4). The reaction of
We also examined the benzofuran synthesis using furan
derivatives 14. As we expected, the reaction of 14 with
propionaldehyde 2b proceeded in the presence of AuBr3 or Cu-
OTf)2 catalyst to give the corresponding product 15a in 58 and
7% yields, respectively (eq 11). The AuBr3-catalyzed reaction
of 14 with â-methoxystyrene 11a also gave 15b in 50% yield
eq 12).
(
6
1
2 with other enol ethers, such as 1-methoxy-1-octene 11b,
(
butoxyethene 11c, and 1-methoxycyclohexene 11d, proceeded
to give the corresponding products 13b-d in good to high yields
(entries 5-7).
TABLE 3. Lewis Acid-Catalyzed Indole Synthesisa
entry
11
R1
Ph
Ph
Ph
Ph
C6H13
H
R2
R3
catalyst
13
yield (%)b
1
2
3
4
5
6
7
11a
11a
11a
11a
11b
11c
11d
H
H
H
H
H
H
Me
Me
Me
Me
Me
C4H9
Me
Cu(OTf)2
AuBr3
AgNTf2
TfOH
AuBr3
AuBr3
13a
13a
13a
13a
13b
13c
13d
90
70
88
15
97
83
64
Conclusion
-(CH2)4-
Cu(OTf)2
We are now in a position to synthesize functionalized
aromatic compounds from enynals and carbonyl compounds in
good to high yields. The reaction most probably proceeds
through the reverse electron demand-type Diels-Alder reaction
between the pyrylium intermediate and enol 2π-system, derived
from carbonyl compounds. The scope of the reaction was
extended to the synthesis of benzofused heteroaromatic com-
pounds. Further studies to elucidate the precise mechanism of
a
The reaction was performed using 11 and 12 in the presence of Lewis
b
acid (10 mol %) in THF at 100 °C within 3 h. Isolated yield.
Not only enol ether 11 can be used as a 2π-system for the
indole synthesis; aldehyde 2 can also be used. For instance, the
reaction of 12 with 2a proceeded smoothly in the presence of
(14) Enol ethers, including furan derivatives, are known to behave as
2
π-systems. For example, see: (a) Chen, C.-H.; Rao, P. D.; Liao, C.-C. J.
Am. Chem. Soc. 1998, 120, 13254. (b) Avalos, M.; Babiano, R.; Cabello,
N.; Cintas, P.; Hursthouse, M. B.; Jim e´ nez, J. L.; Light, M. E.; Palacios, J.
C. J. Org. Chem. 2003, 68, 7193.
(16) For recent examples, see: (a) Katritzky, A. R.; Ledoux, S.; Nair,
S. K. J. Org. Chem. 2003, 68, 5728 and references therein. (b) Tsuchimoto,
T.; Matsubayashi, H.; Kaneko, M.; Shirakawa, E.; Kawakami, Y. Angew.
Chem., Int. Ed. 2005, 44, 1336. (c) Zhang, Y.; Candelaria, D.; Herndon, J.
W. Tetrahedron Lett. 2005, 46, 2211.
(15) For reviews, see, for instance: (a) Gilchrist, T. L. J. Chem. Soc.,
Perkin Trans. 1 1999, 2848. (b) Gribble, G. W. J. Chem. Soc., Perkin Trans.
1
1
2000, 1045. (c) Br a¨ se, S.; Gil, C.; Knepper, K. Bioorg. Med. Chem. 2002,
0, 2415. (d) Cacchi, S.; Fabrizi, G. Chem. ReV. 2005, 105, 2873.
(17) Barluenga, J.; V a´ zquez-Villa, H.; Ballesteros, A.; Gonz a´ lez, J. M.
AdV. Synth. Catal. 2005, 347, 526.
5252 J. Org. Chem., Vol. 71, No. 14, 2006

Lewis Acid-Catalyzed [4 + 2] Benzannulation
this reaction and to extend the scope of synthetic utility are in
progress in our laboratory.
°C for 1 h and then cooled to room temperature. The reaction
mixture was passed through a silica gel pad using AcOEt, and the
resulting crude product was purified by column chromatography
(
silica gel, hexane/AcOEt ) 8/1 as eluent); 13a was obtained as a
Experimental Section
white solid (101 mg, 0.23 mmol) in 90% yield.
Benzannulation between o-(Alkynyl)benzaldehydes (1) and
Carbonyl Compounds (2). The preparation of 3c is representative.
Benzannulation between 3-Phenylethynyl-furan-2-carbalde-
hyde (14) and Carbonyl Compounds (2). The preparation of 15a
To a suspension of AuBr
3
(22 mg, 10 mol %) in 1,4-dioxane (2
is representative. To a solution of Cu(OTf) (9 mg, 10 mol %) and
2
mL) were added 1a (103 mg, 0.5 mmol) and 2c (0.084 mL, 0.6
mmol) at room temperature under Ar atmosphere. The resulting
homogeneous solution was stirred at 100 °C for 3 h and then cooled
to room temperature. The reaction mixture was passed through a
silica gel pad using ether, and the resulting crude product was
purified by column chromatography (silica gel, hexane/AcOEt )
14 (49 mg, 0.25 mmol) in THF (2 mL) was added 2b (0.09 mL,
1.25 mmol) at room temperature under Ar atmosphere. The resulting
homogeneous solution was stirred at 100 °C for 3 h and then cooled
to room temperature. The reaction mixture was passed through a
silica gel pad using AcOEt, and the resulting crude product was
purified by column chromatography (silica gel, hexane/AcOEt )
20/1 as eluent); 15a was obtained as a yellow oil (40 mg, 0.17
mmol) in 67% yield.
2
5/1 as eluent); 3c was obtained as a pale yellow liquid (122 mg,
.41 mmol) in 81% yield.
0
Benzannulation between 3-Phenylethynyl-1-(toluene-4-sulfo-
nyl)-1H-pyrrole-2-carbaldehyde (12) and Enol Ethers (11). The
preparation of 13a is representative. To a solution of Cu(OTf) (9
mg, 10 mol %) and 12 (87 mg, 0.25 mmol) in THF (2 mL) was
added 11a (0.05 mL, 0.38 mmol) at room temperature under Ar
atmosphere. The resulting homogeneous solution was stirred at 100
Supporting Information Available: Spectroscopic and analyti-
cal data for 3a-n, 13a-d, and 15a-b (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
2
JO060597M
J. Org. Chem, Vol. 71, No. 14, 2006 5253