One-pot synthesis of indole-fused scaffolds via gold-catalyzed tandem annulation reactions of 1,2-bis(alkynyl)-2-en-1-ones with indoles

Article abstract of DOI:10.1021/jo2017668

The gold-catalyzed tandem cyclization of 1,2-bis(alkynyl)-2-en-1-ones with indoles offers an efficient and straightforward route to indole-fused polycyclic systems. The process is realized through a cascade carbonyl-yne cyclization/Friedel-Crafts/indole-yne cyclization sequence catalyzed by a single-pot catalyst of gold.

Full text of DOI:10.1021/jo2017668

NOTE
pubs.acs.org/joc
One-Pot Synthesis of Indole-Fused Scaffolds via Gold-Catalyzed
Tandem Annulation Reactions of 1,2-Bis(alkynyl)-2-en-1-ones with
Indoles
Xin Xie, Xiangwei Du, Yifeng Chen, and Yuanhong Liu*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Lu, Shanghai 200032, People’s Republic of China
S Supporting Information
b
ABSTRACT: The gold-catalyzed tandem cyclization of 1,2-bis(alkynyl)-2-en-1-
ones with indoles offers an efficient and straightforward route to indole-fused
polycyclic systems. The process is realized through a cascade carbonyl-yne
cyclization/FriedelÀCrafts/indole-yne cyclization sequence catalyzed by a
single-pot catalyst of gold.
used heterocyclic compounds containing indole rings are
present in many biologically active natural products as well
attack onto the metal-coordinated alkynes (Figure 1). Herein, we
report the utilization of gold as the catalyst for the cyclization of
bis(alkynyl)-2-en-1-ones with indoles, which offers a convenient,
general, and highly efficient approach to polycyclic indole-fused
scaffolds under extremely mild reaction conditions.
The initial cyclization study of (E)-4-benzylidene-1,6-diphe-
nylhexa-1,5-diyn-3-one 1a with 2 equiv of indole was performed;
to our delight, the desired polycyclic indole 3a could be obtained
F
as pharmaceutically important substances. For example, indole-
fused seven-membered carbocycles can be found in ambiguine,1a
ambiguine E isonitrile,1b silicone,1c,d caulersin,1eÀg antitumor
benzo[5,6]cyclohepta[b]-indoles,1h and anticancer agents of
oxophenylarcyriaflavins,1i etc.1 Thus, the concise methods for
the construction of polycyclic indole skeletons are highly attrac-
tive. Among various synthetic approaches for indole derivatives,
gold-catalyzed annulations of indole/ynes have been proven
versatile in terms of efficiency and wide scope of application.2
These include intramolecular cyclization of indoles with alkynes
leading to azepino[4,5-b]indoles and indoloazocines,2aÀc cyclo-
isomerization of N-propargylamides to β-carbolinones,2d,e 1,2-
indole migration,2f and cyclization of 2,3-disubstituted indoles to
tetracyclic indolines,2g etc. We have also developed straightfor-
ward syntheses of functionalized indole derivatives through gold-
catalyzed domino reactions of (Z)-enynols with indoles3a and
1,5-indole migration3b reactions, etc.3 From a practical point of
view, domino reactions are ideal strategies for building up com-
plex structures because multiple bond-forming and -cleaving
events could occur in one sequence, and there is no need to iso-
late the corresponding intermediates.4 Inspired by these studies
and our previous work of electrophilic cyclization of enynones5
and gold-catalyzed cascade reactions of 1,6-diyne-4-en-3-ols,6,7
we designed a new building block of 1,2-bis(alkynyl)-2-en-1-ones
in which one more alkyne unit is incorporated into the enynones.
We envisioned that indoles may induce double annulations of
these enynones because both of the indole C-2 and C-3 can react
with activated intermediates to form CÀC bonds, furnishing a
multiply substituted furan ring8 and a dihydrocyclohepta[b]-
indole framework in the same product via sequential nucleophilic
in an excellent yield of 92% using 5 mol % NaAuCl4 2H2O
3
(Table 1, entry 1). Obviously, the cascade cyclization occurs,
and the overall domino process entails one CÀO bond and a
2-fold CÀC bond formation.9 Interestingly, 3a exhibits a strong
yellow-green fluorescence in organic solvents. The use of AuCl3,
Ph3PAuNTf2, or gold-oxonium salt [(Ph3PAu)3O]BF4 also
provided good yields (82À90%) of 3a (Table 1, entries 2À4).
Decreasing the catalyst loading to 1 mol % resulted in the for-
mation of 3a and indole-substituted furan 2a in 52 and 30% yields,
respectively (Table 1, entry 5). AgOTf gave 2a in a low yield of
30%, together with several byproducts (Table 1, entry 7).
With the optimized reaction conditions in hand, we next
investigated the scope of the reaction with a variety of substituted
enynones using NaAuCl4 2H2O as catalyst, and the results are
3
presented in Table 2. The reaction proved to be quite general
with respect to substitution of R1ÀR3 because aryl or alkyl groups
were all suitable for these substituents, showing a broad diversity
of the products. The cyclizations of enynones 1 with different R2
and R3 groups were examined first (3aÀi). The reactions toler-
ated both electron-rich and electron-poor aryl substituents,
furnishing the corresponding indole derivatives 3bÀc and 3fÀh
Received: August 24, 2011
Published: September 22, 2011
r
2011 American Chemical Society
9175
dx.doi.org/10.1021/jo2017668 J. Org. Chem. 2011, 76, 9175–9181
|

The Journal of Organic Chemistry
NOTE
Table 2. Synthesis of Polycyclic Heterocycles through Cas-
cade Reactionsa
Figure 1. Strategy for metal-catalyzed cascade reaction for the synthesis
of indole-fused polycycles.
Table 1. Optimization Studies for the Cascade Reactions
yield
yield
entry
catalyst
solvent time (%) of 2aa (%) of 3aa
1
2
3
4
5
6
7
8c
5% NaAuCl4 2H2O
DCE
DCE
DCE
DCE
DCE
THF
DCE
DCE
1 h
1 h
1 h
1 h
6 h
3 h
5 h
8 h
92
89
82
90
52
b
3
5% AuCl3
5% Ph3PAuNTf2
2% [(Ph3PAu)3O]BF4
1% NaAuCl4 2H2O
30
30
3
5% Ph3PAuOTf
5% AgOTf
5% TfOH
a Isolated yields. b Several products were formed. c 1a was recovered in
30% yield, and some byproducts were formed.
in 56À90% yields. The functionalities of ÀCl, ÀOMe, and ÀCF3
were very compatible for this reaction. An alkenyl-substituent,
such as 1-cyclohexenyl group, as R2 produced 3d in 41% yield.
The reactions with the alkyl-substituted (either as R2 or R3)
alkynes were also satisfactory, leading to 3e and 3i in 64 and 73%
yields, respectively. In addition, alkyl substitution on the olefin
moiety was also well accommodated; for example, methyl-
substituted 3j and 3k could be isolated in 47 and 68% yields,
respectively.
a Isolated yields. b PPh3AuNTf2 (5 mol %) was used.
Next, we explored the cyclization reactions with various
substituted indoles. Gratifyingly, the reaction could be success-
fully extended to indole substrates bearing ÀBr, ÀMe, ÀMeO,
and ÀBnO functionalities, and high yields were realized for all
cases (Table 3, entries 1À4). 4-CO2Me-substituted indole afford-
ed a moderate yield of the desired 3p using 5 mol % of (PPh3)-
AuNTf2 as the catalyst (Table 3, entry 5). The structure of the
indole-fused carbocycle 3p has been verified by X-ray crystal-
lography (see Supporting Information), which clearly shows a
dihydrocyclohepta[b]indole skeleton. It is noted that the crystals
suitable for X-ray analysis should be prepared in the glovebox
(vide infra).
Interestingly, when enynone 1l bearing a siloxymethyl group
was employed, an indole-tethered polycycle 4 was formed in 74%
yield via the cleavage of the ÀOTBS group (Scheme 1, eq 1). The
outcome of this experiment may be rationalized by the sponta-
neous reaction of the initially formed product (3) with the second
molecule of indole via a carbocation intermediate generated by
gold-assisted ionization of the CÀO bond.10 On the other hand,
it was found when a solution of 3a in ethyl acetate was stirred in
air for 5 days, a photooxygenation reaction took place, and the
oxirane 5 was isolated in 50% yield as a single diastereomer
(Scheme 1, eq 2). The structure of 5 was confirmed by X-ray
analysis (see Supporting Information), which reveals that the
phenyl ring and the oxygen atom of the oxirane are in trans
orientation. This result indicates that 3a itself may act as a
photosensitizer to generate the singlet oxygen, which reacts with
the furan moiety to afford diacyl oxirane 5 via the rearrangement
of the unstable endoperoxide intermediate.11
The apparent formation of furan rings and indole-fused
carbocycles in the products 3 and the observation of indole-yne
2 led us to propose a plausible reaction mechanism as depicted
9176
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181

The Journal of Organic Chemistry
NOTE
Table 3. Formation of Various Indole-Fused Polycycles
Scheme 3
To gain insight into the reaction mechanism, we subjected the
indole-yne 2a to the cyclization conditions; however, only a 38%
yield of the desired product 3a was isolated after 8 h, and 2a was
recovered in 47% yield (Scheme 3). To our surprise, when 1
equiv of indole was used as an additive, the desired 3a was
obtained in 82% yield within 2 h. The results indicated that the
excess indole played an important role in the gold(III)-catalyzed
cyclization of 2a and also in the one-pot process. It has been
reported that the reaction of indole with a stoichiometric amount
entry
substrate
time
product
yield (%) of 3a
1
2
3
4
5
5-Br-indole
1 h
1 h
1 h
1 h
4 h
3l
83
6-Me-indole
3m
3n
3o
3p
82
5-MeO-indole
5-BnO-indole
4-COOMe-indole
83
85
25 (55)b
of NaAuCl4 2H2O might afford a C-3 aurated indole via electro-
a Isolated yields. b The yield in parentheses was obtained by using 5 mol
% of (PPh3)AuNTf2 for 1.5 h.
3
philic metalation.13 We postulate that this 3-indolylaurate species
may be the real catalyst in our reaction, which exhibits higher
catalytic activities and may be responsible for the above results.
We also found when Ph3PAuNTf2 was used as a catalyst, 3a
could be formed in 82% yield for 0.5 h from 2a without the
addition of any additive.
Scheme 1
In summary, we have developed a highly efficient gold-
catalyzed double cyclization of bis(alkynyl)-2-en-1-ones with indoles.
This methodology provides rapid access to heterocyclic systems
fused both with indole and furan rings with diverse substitution
patterns. It is anticipated that the new cascade reactions using
various nucleophiles would be exploited on the basis of these
findings.
’ EXPERIMENTAL SECTION
Synthesis of 1,2-Bis(alkynyl)-2-en-1-ones 1aÀg, 1i, and 1l.
Typical Procedure for the Synthesis of (E)-4-Benzylidene-1-(4-methoxy-
phenyl)-6- phenylhexa-1,5-diyn-3-one (1f). To a solution of 1-ethynyl-
4-methoxybenzene (0.79 g, 6 mmol) in THF (10 mL) was added n-BuLi
(2.3 mL, 5.5 mmol, 2.4 M solution in hexanes) at 0 °C. After the solution
was stirred at the same temperature for 0.5 h, (E)-2-benzylidene-4-
phenylbut-3-ynal14 (1.16 g, 5.0 mmol) was added, and then the solution
was warmed up to room temperature. After the starting material was
consumed, themixture was quenchedwith saturated ammonium chloride
solution, extracted with ethyl acetate, and dried over anhydrous Na2SO4.
The solvent was evaporated, and the residue was purified by flash
chromatography on silica gel to afford (E)-4-benzylidene-1-(4-methoxy-
phenyl)-6-phenylhexa-1,5-diyn-3-ol. This alcohol was used directly for
the next step.
Scheme 2
To a solution of the above alcohol in DMSO (10 mL) was added
2-iodoxybenzoic acid (IBX) (1.82 g, 6.5 mmol) at room temperature.
After the starting material was consumed, the mixture was quenched
by water, filtered, extracted with ethyl acetate, and dried over Na2SO4.
The solvent was evaporated in vacuo, and the residue was purified by
chromatography on silica gel (eluent: petroleum ether/ethyl acetate/
dichloromethane = 10:1:1) to afford compound 1f (1.34 g, 74%) as a
1
in Scheme 2. In the first step, the alkyne moiety is activated through
forming a π-complex with gold catalyst, which facilitates the
nucleophilic attack by the carbonyl oxygen. Thus, the subsequent
5-endo-dig cyclization occurs to form a cationic intermediate 7. The
intermolecular nucleophilic attack of indole on the carbocation
affords the furanyl gold 8. This is followed by indole/yne cyclization
to give gold species 10; protonation of the resulting carbonÀgold
bond delivers products 3 and regenerates the gold catalyst.12
yellow solid: H NMR (CDCl3, Me4Si, 400 MHz) δ 3.84 (s, 3H),
6.87À6.91 (m, 2H), 7.38À7.41 (m, 3H), 7.45À7.49 (m, 3H), 7.56À
7.61 (m, 4H), 8.11 (s, 1H), 8.15À8.17(m, 2H);13CNMR(CDCl3, Me4Si,
100.6 MHz) δ 55.4, 85.2, 87.0, 95.4, 100.2, 111.9, 114.4, 121.8, 122.8,
128.5, 128.7, 128.9, 130.9, 131.2, 131.7, 134.3, 135.2, 146.2, 161.7, 176.3.
HRMS (EI) for C26H18O2: calcd 362.1307, found 362.1312.
(E)-4-Benzylidene-1,6-diphenylhexa-1,5-diyn-3-one (1a). It was further
purified by recrystallization. Yield 84%. Light yellow solid: mp 129À130 °C;
9177
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181

The Journal of Organic Chemistry
NOTE
1H NMR (CDCl3, Me4Si, 400 MHz) δ 7.36À7.41 (m, 5H), 7.44À7.49
(m, 4H), 7.58À7.64 (m, 4H), 8.13 (s, 1H), 8.15À8.18(m, 2H);13CNMR
(CDCl3, Me4Si, 100.6 Hz) δ 85.0, 87.0, 94.1, 100.4, 120.1, 121.8, 122.7,
128.5, 128.6, 128.7, 129.0, 130.8, 131.0, 131.4, 131.7, 133.1, 134.2, 146.7,
176.3. HRMS (EI) for C25H16O: calcd 332.1201, found 332.1198.
(E)-4-Benzylidene-6-(4-methoxyphenyl)-1-phenylhexa-1,5-diyn-3-
one (1b). Yield 93%. Brown oil: 1H NMR (CDCl3, Me4Si, 400 MHz) δ
3.84 (s, 3H), 6.90À6.92 (m, 2H), 7.38À7.42 (m, 2H), 7.45À7.48 (m, 4H),
7.52À7.54 (m, 2H), 7.63À7.65 (m, 2H), 8.10 (s, 1H), 8.16À8.18 (m,
2H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 55.3, 83.9, 87.0, 94.0,
100.7, 114.1, 114.9, 120.2, 122.1, 128.6, 128.7, 130.7, 130.9, 131.2, 133.1,
135.3, 134.4, 146.0, 160.2, 176.6. HRMS (EI) for C26H18O2: calcd
362.1307, found 362.1312.
solution was warmed up to room temperature and stirred for 2 h. Then,
the mixture was quenched with saturated ammonium chloride solution,
extracted with ethyl acetate, and dried over anhydrous Na2SO4. The
solvent was evaporated, and the residue was purified by flash chromato-
graphy on silica gel to afford (E)-4-benzylidene-6-phenyl-1-(trimethylsilyl)-
hexa-1,5-diyn-3-ol. To a solution of the above alcohol in THF (20 mL)
was added TBAF (1.0 M in THF) at room temperature. The reaction
mixture was stirred until the starting material was consumed. Then, the
reaction was quenched by water, extracted with ethyl acetate, and dried
over Na2SO4. The solvent was evaporated in vacuo, and the residue was
purified by chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 5:1) to afford (E)-4-benzylidene-6-phenylhexa-1,5-diyn-3-ol
(1.4 g, 54% yield for two steps) as a yellow solid.
(E)-4-Benzylidene-6-(4-chlorophenyl)-1-phenylhexa-1,5-diyn-3-one
(1c). Yield 70%. Yellow oil: 1H NMR (CDCl3, Me4Si, 400 MHz) δ 7.31À
7.43 (m, 4H), 7.46À7.52 (m, 6H), 7.62À7.64 (m, 2H), 8.12À8.15 (m,
2H), 8.15 (s, 1H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 85.8, 86.8,
94.2, 99.1, 120.0, 121.2, 121.6, 128.65, 128.73, 128.8, 130.8, 130.9, 131.5,
132.9, 133.0, 134.1, 135.0, 147.3, 176.2. HRMS (EI) for C25H15ClO:
calcd 366.0811, found 366.0814.
(E)-4-Benzylidene-6-cyclohexenyl-1-phenylhexa-1,5-diyn-3-one (1d).
Yield 49%. Yellow oil: 1H NMR (CDCl3, Me4Si, 400 MHz) δ 1.62À1.74
(m, 4H), 2.17À2.22 (m, 2H), 2.28À2.31 (m, 2H), 6.31À6.35 (m, 1H),
7.38À7.50 (m, 6H), 7.63À7.66 (m, 2H), 8.03 (s, 1H), 8.10À8.13 (m,
2H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 21.4, 22.1, 25.8, 28.6,
82.4, 86.9, 93.8, 102.7, 120.2, 120.7, 122.1, 128.5, 128.6, 130.7, 130.8,
131.0, 133.0, 134.3, 137.0, 145.6, 176.6. HRMS (EI) for C25H20O: calcd
336.1514, found 336.1517.
(E)-4-Benzylidene-1-phenyldeca-1,5-diyn-3-one (1e). Yield 93%.
Yellow oil: 1H NMR (CDCl3, Me4Si, 400 MHz) δ 0.95 (t, J = 7.2 Hz,
3H), 1.50À1.55 (m, 2H), 1.64À1.69 (m, 2H), 2.59 (t, J = 7.2 Hz, 2H),
7.39À7.49 (m, 6H), 7.63À7.66 (m, 2H), 8.07 (s, 1H), 8.10À8.14 (m, 2H);
13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 13.6, 19.8, 22.0, 30.4, 75.5, 86.6,
93.7, 102.9, 120.2, 122.6, 128.5, 128.6, 130.6, 130.6, 131.1, 132.9, 134.2,
146.8, 177.2. HRMS (EI) for C23H20O: calcd 312.1514, found 312.1515.
(E)-4-Benzylidene-1-(4-chlorophenyl)-6-phenylhexa-1,5-diyn-3-one
(1g). It was further purified by recrystallization. Yield 62%. Light yellow
solid: mp 86À87 °C; 1H NMR (CDCl3, Me4Si, 400 MHz) δ 7.35À7.40
(m, 5H), 7.46À7.48 (m, 3H), 7.53À7.59 (m, 4H), 8.09 (s, 1H), 8.15À
8.17 (m, 2H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 85.0, 87.7, 92.7,
100.4, 118.6, 121.6, 122.7, 128.5, 128.7, 129.0, 129.1, 131.0, 131.5, 131.7,
134.1, 134.2, 137.2, 146.7, 176.1. HRMS (EI) for C25H15ClO: calcd
366.0811, found 366.0809.
(E)-3-Benzylidene-1-phenyldeca-1,5-diyn-4-one (1i). Yield 79%.
Yellow oil: 1H NMR (CDCl3, Me4Si, 300 MHz) δ 0.93 (t, J = 7.2 Hz,
3H), 1.43À1.55 (m, 2H), 1.59À1.68 (m, 2H), 2.49 (t, J = 6.9 Hz, 2H),
7.35À7.38 (m, 3H), 7.43À7.46 (m, 3H), 7.55À7.59 (m, 2H), 8.07 (s,
1H), 8.10À8.14 (m, 2H); 13C NMR (CDCl3, Me4Si, 75.5 MHz) δ 13.5,
18.9, 22.0, 29.7, 79.4, 84.7, 97.8, 100.3, 121.9, 122.8, 128.4, 128.6, 128.8,
130.8, 131.2, 131.6, 134.2, 147.0, 176.5. HRMS (EI) for C23H20O: calcd
312.1514, found 312.1513.
To a solution of (E)-4-benzylidene-6-phenylhexa-1,5-diyn-3-ol (0.52 g,
2.0 mmol) in triethylamine (8 mL) were added 1-iodo-4-(trifluoro-
methyl)benzene (0.65 g, 0.35 mL, 2.4 mmol), Pd(PPh3)2Cl2 (28 mg,
0.04 mmol), and CuI (19 mg, 0.1 mmol) at room temperature, and then
the mixture was stirred overnight. After the starting material was con-
sumed, the mixture was quenched with H2O, extracted with ethyl acetate,
and dried over anhydrous Na2SO4. The solvent was evaporated, and the
residue was purified by flash chromatography on silica gel (petroleum/
ethyl acetate = 5:1) to afford (E)-4-benzylidene-6-phenyl-1-(4-(trifluo-
romethyl)phenyl)hexa-1,5-diyn-3-ol (290 mg, 36% yield) as a brown oil.
To a solution of the above alcohol (290 mg, 0.72 mmol) in DMSO
(3 mL) was added IBX (0.26 g, 0.94 mmol) at room temperature. After
the starting material was consumed, the mixture was quenched by water,
filtered, extracted with ethyl acetate, and dried over Na2SO4. The solvent
was evaporated in vacuo, and the residue was purified by chromatogra-
phy on silica gel (eluent: petroleum ether/ethyl acetate = 15:1) to afford
compound 1h (0.16 g, 56%) as a yellow oil: 1H NMR (CDCl3, Me4Si,
400 MHz) δ 7.36À7.40 (m, 3H), 7.45À7.48 (m, 3H), 7.55À7.59 (m,
2H), 7.62À7.72 (m, 4H), 8.09 (s, 1H), 8.14À8.18 (m, 2H); 13C NMR
(CDCl3, Me4Si, 100.6 MHz) δ 84.8, 88.2, 91.5, 100.6, 121.4, 122.1,
122.6, 123.9, 125.5 (q, J = 3.5 Hz), 126.2 (q, J = 272.0 Hz), 128.5, 128.7,
129.1, 131.0, 131.55, 131.60, 132.1 (q, J = 32.9 Hz), 133.1, 134.0, 147.0,
175.9. HRMS (EI) for C26H15F3O: calcd 400.1075, found 400.1078.
Synthesis of (E)-1-Phenyl-4-(phenylethynyl)hex-4-en-1-
yn-3-one (1j). To a solution of phenylacetylene (0.56 g, 0.60 mL,
5.5 mmol) in THF (10 mL) was added n-BuLi (2.1 mL, 5.0 mmol, 2.4 M
solution in hexanes) at À78 °C. After the solution was stirred at the same
temperature for 1 h, (Z)-2-bromobut-2-enal (0.75 g, 5.0 mmol) was
added. The resulting solution was warmed up to room temperature
and stirred for 3 h. Then, the mixture was quenched with saturated
ammonium chloride solution, extracted with ethyl acetate, and dried
over anhydrous Na2SO4. The solvent was evaporated, and the residue
was purified by flash chromatography on silica gel (petroleum/ethyl
acetate= 5:1) toafford (Z)-4-bromo-1-phenylhex-4-en-1-yn-3-ol (1.04 g,
83%) as a yellow oil.
To a solution of (Z)-4-bromo-1-phenylhex-4-en-1-yn-3-ol (0.25 g,
1.0 mmol) in diethylamine (1.5 mL) and THF (1.5 mL) were added
phenylacetylene (0.15 g, 0.16 mL, 1.5 mmol), Pd(PPh3)2Cl2 (14 mg,
0.02 mmol), and CuI (9.5 mg, 0.05 mmol) at room temperature, and
then the mixture was stirred overnight. After the starting material was
consumed, the mixture was quenched with H2O, extracted with ethyl
acetate, and dried over anhydrous Na2SO4. The solvent was evaporated,
and the residue was purified by flash chromatography on silica gel
(petroleum/ethyl acetate = 8:1) to afford (E)-1-phenyl-4-(phenyl-
ethynyl)hex-4-en-1-yn-3-ol (200 mg, 74%) as a yellow oil.
(E)-4-Benzylidene-7-(tert-butyldimethylsilyloxy)-1-phenylhepta-1,
1
5-diyn-3-one (1l). Yield 58%. Brown oil: H NMR (CDCl3, Me4Si,
400 MHz) δ 0.17 (s, 6H), 0.94 (s, 9H), 4.68 (s, 2H), 7.40À7.48 (m, 6H),
7.65À7.67 (m, 2H), 8.12À8.14 (m, 3H); 13C NMR (CDCl3, Me4Si,
100.6 MHz) δ À5.2, 18.3, 25.8, 52.5, 79.5, 86.5, 94.0, 99.7, 120.1, 121.7,
128.65, 128.68, 130.8, 131.0, 131.5, 133.0, 133.9, 148.1, 176.6. HRMS
(EI) for C26H28O2Si: calcd 400.1859, found 400.1857.
Synthesis of (E)-4-Benzylidene-6-phenyl-1-(4-(trifluoro-
methyl)phenyl)hexa-1,5-diyn-3-one (1h). To a solution of ethynyl-
trimethylsilane (1.18 g, 12 mmol) in THF (20 mL) was added n-BuLi
(4.6 mL, 11 mmol, 2.4 M solution in hexanes) at À78 °C. After the
solution was stirred at the same temperature for 1 h, (E)-2-benzylidene-
4-phenylbut-3-ynal (2.32 g, 10 mmol) was added, and the resulting
To a solution of the above alcohol (0.2 g, 0.74 mmol) in DMSO
(3 mL) was added IBX (0.27 g, 0.96 mmol) at room temperature. After
the starting material was consumed, the mixture was quenched by water,
filtered, extracted with ethyl acetate, and dried over Na2SO4. The solvent
was evaporated in vacuo, and the residue was purified by chromatography
on silica gel (eluent: petroleum ether/ethyl acetate = 20:1) to afford
9178
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181

The Journal of Organic Chemistry
NOTE
compound 1j (0.10 g, 50%) as a yellow oil: 1H NMR (CDCl3, Me4Si,
400 MHz) δ 2.24 (d, J = 7.2 Hz, 3H), 7.32À7.39 (m, 5H), 7.42À7.47
(m, 1H), 7.53À7.55 (m, 2H), 7.58À7.62 (m, 3H); 13C NMR (CDCl3,
Me4Si, 100.6 MHz) δ 17.3, 81.9, 86.3, 93.2, 98.6, 120.0, 122.7, 128.1,
128.3, 128.60, 128.63, 130.7, 131.6, 132.9, 151.4, 175.5. HRMS (EI) for
C20H14O: calcd 270.1045, found 270.1042.
131.7, 136.1, 140.2, 145.3, 148.2, 154.7. HRMS (EI) for C33H23NO:
calcd 449.1780, found 449.1783.
3b. Yield 56% (silica gel was used instead of Al2O3). Yellow solid: 1H
NMR (CDCl3, Me4Si, 400 MHz) δ 3.76 (s, 3H), 5.83 (s, 1H), 6.63
(s, 1H), 6.84 (s, 1H), 6.88 (d, J = 8.8Hz, 2H), 7.05À7.19 (m, 6H), 7.34À
7.45 (m, 5H), 7.53À7.61 (m, 4H), 7.76 (d, J = 7.6 Hz, 1H), 7.78 (s, 1H);
13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.1, 55.2, 107.2, 110.6, 114.1,
115.8, 117.7, 118.3, 119.8, 123.2, 123.5, 125.3, 126.3, 126.9, 127.6, 128.1,
128.4, 128.8, 128.9, 129.8, 131.8, 136.2, 140.3, 145.4, 147.6, 154.9, 159.2.
HRMS (EI) for C34H25NO2: calcd 479.1885, found 479.1880.
3c. PPh3AuNTf2 (5 mol %) was used. Yield 75%. Yellow solid: mp
131À132 °C; 1H NMR (CDCl3, Me4Si, 400 MHz) δ 5.79 (s, 1H), 6.67
(s, 1H), 6.80 (s, 1H), 7.04À7.18 (m, 6H), 7.24À7.27 (m, 2H), 7.32À
7.44 (m, 5H), 7.49À7.53 (m, 4H), 7.73À7.75 (m, 1H), 7.75 (s, 1H);
13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.1, 109.1, 110.6, 115.9,
117.3, 118.3, 119.9, 123.3, 124.9, 126.4, 126.8, 127.52, 127.54, 128.2, 128.4,
128.76, 128.79, 128.82, 128.9, 130.9, 131.6, 133.1, 136.2, 140.1, 145.3, 148.4,
153.5. HRMS (EI) for C33H22ClNO: calcd 483.1390, found 483.1394.
Synthesis of (E)-1-(4-Methoxyphenyl)-4-(phenylethynyl)-
hex-4-en-1-yn-3-one (1k). To a solution of 1-ethynyl-4-methoxy-
benzene (0.79 g, 6 mmol) in THF (10 mL) was added n-BuLi (2.3 mL,
5.5 mmol, 2.4 M solution in hexanes) at À78 °C. After the solution was
stirred at the same temperature for 1 h, (Z)-2-bromobut-2-enal (0.75 g,
5.0 mmol) was added. The resulting solution was warmed up to room
temperature and stirred for 1 h. Then, the mixture was quenched with
saturated ammonium chloride solution, extracted with ethyl acetate, and
dried over anhydrous Na2SO4. The solvent was evaporated, and the resi-
due was purified by flash chromatography on silica gel to afford (Z)-4-
bromo-1-(4-methoxyphenyl)hex-4-en-1-yn-3-ol. To a solution of the
above product in diethylamine (10 mL) and THF (10 mL) were added
phenylacetylene (0.77 g, 0.83 mL, 7.5 mmol), Pd(PPh3)2Cl2 (70 mg,
0.1 mmol), and CuI (47.6 mg, 0.25 mmol) at room temperature, and
then the mixture was stirred overnight. After the starting material was
consumed, the mixture was quenched with H2O, extracted with ethyl
acetate, and dried over anhydrous Na2SO4. The solvent was evaporated,
and the residue was purified by flash chromatography on silica gel
(petroleum/ethyl acetate = 8:1) to afford (E)-1-(4-methoxyphenyl)-
4-(phenylethynyl)hex-4-en-1-yn-3-ol (0.60 g, 40% yield for two steps)
as a brown oil.
To a solution of the above alcohol (0.60 g, 2 mmol) in DMSO
(10 mL) was added IBX (0.73 g, 2.6 mmol) at room temperature. After
the starting material was consumed, the mixture was quenched by water,
filtered, extracted with ethyl acetate, and dried over Na2SO4. The solvent
was evaporated in vacuo, and the residue was purified by chromatogra-
phy on silica gel (eluent: petroleum ether/ethyl acetate = 15:1 to 10:1)
to afford compound 1k (0.45 g, 75%) as a yellow solid: mp 92À93 °C;
1H NMR (CDCl3, Me4Si, 400 MHz) δ 2.23 (d, J = 6.8 Hz, 3H), 3.84 (s,
3H), 6.88À6.91 (m, 2H), 7.34À7.36 (m, 3H), 7.53À7.61 (m, 5H); 13C
NMR (CDCl3, Me4Si, 100.6 MHz) δ 17.3, 55.3, 82.2, 86.3, 94.4, 98.4,
111.8, 114.3, 122.8, 128.1, 128.3, 128.6, 131.7, 135.0, 150.8, 161.6, 175.5.
HRMS (EI) for C21H16O2: calcd 300.1150, found 300.1151.
1
3d. Yield 41%. Yellow oil: H NMR (CDCl3, Me4Si, 400 MHz) δ
1.60À1.71 (m, 4H), 2.18À2.28 (m, 4H), 5.77 (s, 1H), 6.28 (s, 1H), 6.36
(t, J = 4.0 Hz, 1H), 6.78 (s, 1H), 7.06À7.19 (m, 6H), 7.31 (d, J = 7.6 Hz,
2H), 7.38À7.45 (m, 3H), 7.51À7.53 (m, 2H), 7.73À7.75 (m, 1H), 7.75
(s, 1H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 22.1, 22.3, 24.8, 25.3,
39.1, 107.4, 110.5, 115.9, 117.8, 118.3, 119.7, 123.1, 123.5, 126.2, 126.9,
127.0, 127.1, 127.6, 128.0, 128.3, 128.8, 128.9, 129.8, 131.8, 136.1, 140.3,
145.5, 147.1, 156.5. HRMS (EI) for C33H27NO: calcd 453.2093, found
453.2089.
3e. Yield 64%. Yellow solid: 1H NMR (CDCl3, Me4Si, 300 MHz) δ
0.90 (t, J = 7.5 Hz, 3H), 1.26À1.42 (m, 2H), 1.56À1.66 (m, 2H), 2.60 (t,
J = 7.5 Hz, 2H), 5.75 (s, 1H), 6.10 (s, 1H), 6.75 (s, 1H), 7.03À7.18 (m,
6H), 7.29À7.43 (m, 5H), 7.50À7.52 (m, 2H), 7.74 (m, 2H); 13C NMR
(CDCl3, Me4Si, 75.5 MHz) δ 13.8, 22.3, 28.0, 29.9, 39.0, 108.7, 110.5,
115.8, 118.0, 118.2, 119.6, 123.0, 126.1, 126.3, 126.8, 127.6, 128.0, 128.3,
128.8, 128.9, 129.0, 131.8, 136.1, 140.3, 145.6, 146.8, 158.4. HRMS (EI)
for C31H27NO: calcd 429.2093, found 429.2096.
3f. Yield 70% (silica gel was used instead of Al2O3). Light yellow
crystalline solid: mp 130À131 °C; 1H NMR (CDCl3, Me4Si, 400 MHz)
δ 3.81 (s, 3H), 5.82 (s, 1H), 6.76 (s, 1H), 6.80 (d, J = 0.4 Hz, 1H),
6.93À6.97 (m, 2H), 7.04À7.09 (m, 1H), 7.10À7.23 (m, 6H), 7.32À
7.35 (m, 4H), 7.44À7.47 (m, 2H), 7.65À7.67 (m, 2H), 7.76 (d, J =
7.6 Hz, 1H), 7.83 (s, 1H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ
39.0, 55.3, 108.7, 110.6, 114.2, 115.8, 116.8, 118.3, 119.8, 123.2, 123.7,
126.3, 126.9, 127.2, 127.5, 127.6, 128.4, 128.6, 130.0, 130.3, 130.4, 132.1,
132.5, 136.1, 145.3, 148.4, 154.5, 159.6. HRMS (MALDI/DHB) for
C34H26NO2 [M + H]+: calcd 480.1958, found 480.1955.
Typical Procedure for Gold-Catalyzed Tandem Annula-
tion Reactions of 1,2-Bis(alkynyl)-2-en-1-ones with Indoles.
All reactions were carried out on 0.2 or 0.3 mmol scale. To a solution of
NaAuCl4 2H2O (6 mg, 0.015 mmol) and indole (70.3 mg, 0.6 mmol) in
3
DCE (3 mL) was added (E)-4-benzylidene-1-(4-chlorophenyl)-6-phe-
nylhexa-1,5-diyn-3-one (1g) (110 mg, 0.3 mmol) at room temperature.
The reaction mixture was stirred until the reaction was complete as
monitored by thin-layer chromatography. The solvent was evaporated
under the reduced pressure, and the residue was purified by chroma-
tography on Al2O3 (eluent: n-hexane/ethyl acetate = 15:1) to afford the
indole-fused carbocycle 3g (130 mg, 90%) as a light yellow crystalline
solid: mp 146À147 °C; 1H NMR (CDCl3, Me4Si, 400 MHz) δ 5.81 (s,
1H), 6.74 (s, 1H), 6.78 (s, 1H), 7.04À7.08 (m, 1H), 7.10À7.23 (m, 6H),
1
3h. Yield 77%. Light yellow crystalline solid: mp 134À135 °C; H
NMR (CDCl3, Me4Si, 400 MHz) δ 5.81 (s, 1H), 6.73 (s, 1H), 6.82 (s,
1H), 7.06 (t, J = 7.2 Hz, 1H), 7.12À7.22 (m, 6H), 7.30À7.34 (m, 4H),
7.56 (d, J = 8.0 Hz, 2H), 7.63À7.66 (m, 4H), 7.76 (d, J = 7.2 Hz, 2H);
13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.0, 108.8, 110.7, 116.6,
118.3, 118.4, 120.1, 122.7, 123.6, 123.8, 125.4, 125.8 (q, J = 3.5 Hz),
126.4, 126.8, 127.5, 127.8, 128.35, 128.44, 128.7, 128.95, 129.01, 130.0
(q, J = 34.4 Hz), 130.2, 130.9, 136.3, 143.7, 145.0, 147.8, 155.2. HRMS
(EI) for C34H22F3NO: calcd 517.1653, found 517.1656.
7.29À7.41 (m, 8H), 7.64À7.68 (m, 3H), 7.75 (d, J = 7.2 Hz, 1H); 13
C
3i. Yield 73%. Yellow solid: 1H NMR (CDCl3, Me4Si, 300 MHz) δ
0.86 (d, J = 7.2 Hz, 3H), 1.23À1.35 (m, 2H), 1.45À1.61 (m, 2H), 2.39À
2.71 (m, 2H), 5.72 (s, 1H), 6.58 (s, 1H), 6.69 (s, 1H), 7.00À7.62
(m, 11H), 7.62À7.72 (m, 3H), 7.97 (s, 1H); 13C NMR (CDCl3, Me4Si,
75.5 MHz) δ 13.9, 22.1, 31.2, 35.1, 38.7, 108.5, 110.5, 115.5, 116.2,
118.4, 119.8, 123.0, 123.6, 126.1, 126.8, 127.3, 127.8, 128.2, 128.6, 129.2,
130.5, 132.7, 136.2, 145.2, 148.4, 153.8. HRMS (EI) for C31H27NO:
calcd 429.2093, found 429.2095.
NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.0, 108.7, 110.7, 116.3, 117.6,
118.4, 120.0, 123.4, 123.8, 126.4, 126.8, 127.6, 127.7, 127.8, 128.4, 128.7,
129.1, 129.2, 130.1, 130.3, 131.3, 134.1, 136.3, 136.5, 145.1, 148.0, 154.9.
HRMS (EI) for C33H22ClNO: calcd 483.1390, found 483.1385.
3a. Yield 92%. Yellow crystalline solid: mp 208À209 °C; 1H NMR
(CDCl3, Me4Si, 400 MHz) δ 5.83 (s, 1H), 6.75 (s, 1H), 6.84 (s, 1H),
7.04À7.22 (m, 7H), 7.31À7.45 (m, 7H), 7.52À7.54 (m, 2H), 7.65À
7.67 (m, 2H), 7.76À7.79 (m, 2H); 13C NMR (CDCl3, Me4Si, 75.5 MHz)
δ 39.1, 108.7, 110.6, 115.9, 117.6, 118.3, 119.8, 123.3, 123.8, 126.3, 126.9,
127.5, 127.56, 127.58, 128.2, 128.4, 128.7, 128.8, 128.9, 130.4, 130.5,
1
3j. Yield 47%. Yellow solid: mp 195À196 °C; H NMR (CDCl3,
Me4Si, 300 MHz) δ 1.40 (d, J = 6.9 Hz, 3H), 4.61 (q, J = 6.9 Hz, 1H),
9179
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181

The Journal of Organic Chemistry
NOTE
6.69 (s, 1H), 6.85 (s, 1H), 7.13À7.24 (m, 4H), 7.35À7.49 (m, 5H),
7.57À7.59 (m, 2H), 7.68À7.71 (m, 4H); 13C NMR (CDCl3, Me4Si,
75.5 MHz) δ 23.2, 27.9, 107.8, 110.6, 117.4, 118.0, 118.1, 119.5, 123.0,
123.7, 126.9, 127.4, 128.1, 128.7, 128.8, 128.9, 129.6, 130.5, 130.6, 130.9,
136.2, 140.3, 147.8, 154.6. HRMS (EI) for C28H21NO: calcd 387.1623,
found 387.1624.
Hz, 1H), 7.14À7.24 (m, 2H), 7.29À7.43 (m, 13H), 7.63 (d, J = 7.6 Hz,
2H), 7.92 (s, 1H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 40.0, 79.2,
97.2, 107.5, 111.1, 118.3, 119.5, 119.9, 122.1, 122.5, 123.3, 124.1, 126.5,
126.9, 127.8, 128.3, 128.40, 128.43, 128.5, 128.6, 130.1, 131.3, 133.6,
135.4, 136.6, 142.8, 154.1. HRMS (EI) for C33H23NO: calcd 449.1780,
found 449.1776.
1
1
3k. Yield 68%. Light yellow crystalline solid: mp 123À125 °C; H
4. 2.5 equiv of indole was used. Yield 74%. Yellow solid: H NMR
NMR (CDCl3, Me4Si, 300 MHz) δ 1.39 (d, J = 6.9 Hz, 3H), 3.82 (s,
3H), 4.59 (q, J = 6.9 Hz, 1H), 6.67 (s, 1H), 6.79 (s, 1H), 6.96 (d, J = 8.7
Hz, 2H), 7.13À7.24 (m, 4H), 7.35 (t, J = 7.5 Hz, 2H), 7.56 (d, J = 8.7 Hz,
2H), 7.67À7.75 (m, 4H); 13C NMR (CDCl3, Me4Si, 75.5 MHz) δ 23.1,
27.9, 55.3, 107.8, 110.6, 114.2, 116.6, 117.9, 118.0, 119.5, 122.9, 123.6,
126.9, 127.3, 128.6, 129.2, 130.0, 130.2, 130.6, 131.3, 132.7, 136.2, 147.9,
154.4, 159.5. HRMS (EI) for C29H23NO2: calcd 417.1729, found
417.1725.
(CDCl3, Me4Si, 400 MHz) δ 4.07 (s, 1H), 5.68 (s, 1H), 6.08 (s, 1H),
6.75 (s, 1H), 6.88 (d, J = 2.0 Hz, 1H), 7.03À7.18 (m, 9H), 7.24À7.27
(m, 3H), 7.36À7.42 (m, 3H), 7.46À7.49 (m, 2H), 7.53 (d, J = 11.6 Hz,
1H), 7.67À7.74 (m, 3H); 13C NMR (CDCl3, Me4Si, 75.5 MHz) δ 24.8,
39.0, 109.7, 110.5, 111.1, 111.7, 115.9, 118.0, 118.2, 119.1, 119.4, 119.7,
122.0, 122.6, 123.1, 126.2, 126.4, 126.9, 127.1, 127.5, 128.0, 128.3, 128.8,
128.9, 129.3, 131.8, 136.1, 136.2, 140.3, 145.5, 147.2, 156.7. HRMS (EI)
for C36H26N2O: calcd 502.2045, found 502.2044.
3l. Yield 83%. Orange crystalline solid: mp 150À151 °C; 1H NMR
(CDCl3, Me4Si, 400 MHz) δ 5.73 (s, 1H), 6.77 (s, 1H), 6.88 (s, 1H),
7.04À7.12 (m, 2H), 7.18À7.27 (m, 4H), 7.31À7.49 (m, 7H),
7.54À7.56 (m, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.82 (s, 1H), 7.86 (s,
1H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.0, 108.6, 112.1, 113.1,
115.2, 118.4, 120.8, 123.9, 126.0, 126.5, 126.8, 127.7, 127.8, 128.4, 128.5,
128.7, 128.8, 129.1, 129.4, 130.0, 130.3, 133.1, 134.7, 139.9, 144.9, 148.0,
155.1. HRMS (EI) for C33H22BrNO: calcd 527.0885, found 527.0886.
3m. Yield 82%. Yellow crystalline solid: mp 110À111 °C; 1H NMR
(CDCl3, Me4Si, 400 MHz) δ 2.37 (s, 3H), 5.80 (s, 1H), 6.73 (s, 1H),
6.80 (d, J = 0.8 Hz, 1H), 6.90 (s, 1H), 6.94 (dd, J = 0.8, 8.0 Hz, 1H),
7.03À7.07 (m, 1H), 7.10À7.20 (m, 3H), 7.29À7.42 (m, 7H),
7.50À7.52 (m, 2H), 7.61À7.66 (m, 4H); 13C NMR (CDCl3, Me4Si,
100.6 MHz) δ 21.8, 39.2, 108.7, 110.5, 115.9, 117.0, 118.0, 121.7, 123.7,
125.5, 126.2, 127.3, 127.7, 127.5, 128.1, 128.4, 128.6, 128.8, 128.9, 130.4,
130.7, 131.0, 133.3, 136.6, 140.3, 145.4, 148.3, 154.6. HRMS (EI) for
C34H25NO: calcd 463.1936, found 463.1939.
Synthesis of Oxirane 5. Compound 3a (90 mg, 0.2 mmol) was
dissolved in ethyl acetate (2 mL). The reaction mixture was stirred
for 5 days. During the process, a white solid precipitated. The mixture
was filtrated, and the precipitate was washed with ethyl acetate and
n-pentane. The solid was confirmed to be oxirane 5. Yield 50% (48 mg):
mp 248À249 °C; 1H NMR (d-DMSO, Me4Si, 400 MHz, δ = 2.5 ppm as
internal reference) δ 5.05 (s, 1H), 5.20 (s, 1H), 5.82 (s, 1H), 7.08À7.38
(m, 5H), 7.47À7.66 (m, 12H), 7.95 (d, J = 7.6 Hz, 2H), 10.89 (s, 1H);
13C NMR (DMSO-d6, Me4Si, 75 MHz, δ = 40.45 ppm as internal
reference) δ 44.5, 66.1, 72.4, 113.8, 119.2, 120.0, 121.2, 125.5, 126.5,
128.6, 129.0, 129.1, 129.5, 129.6, 129.8, 130.6, 131.5, 134.2, 136.8, 137.0,
137.8, 140.1, 148.7, 191.5, 192.4. HRMS (EI) for C33H23NO3: calcd
481.1678, found 481.1674.
’ ASSOCIATED CONTENT
S
Supporting Information. X-ray crystallography of com-
b
3n. Yield 83%. Yellow crystalline solid: mp 134À135 °C; 1H NMR
(CDCl3, Me4Si, 400 MHz) δ 3.82 (s, 3H), 5.77 (s, 1H), 6.76 (s, 1H),
6.80À6.83 (m, 2H), 7.00À7.19 (m, 2H), 7.15À7.21 (m, 4H),
7.29À7.41 (m, 7H), 7.50À7.52 (m, 2H), 7.64À7.67 (m, 3H); 13C
NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.1, 55.8, 99.9, 108.7, 111.4,
113.6, 115.6, 117.3, 123.7, 126.3, 126.8, 127.4, 127.5, 128.0, 128.1, 128.4,
128.6, 128.78, 128.84, 130.4, 130.7, 131.6, 132.6, 140.2, 145.3, 148.2,
154.2, 154.6. HRMS (EI) for C34H25NO2: calcd 479.1885, found
479.1882.
pounds 3p and 5 and spectroscopic characterization of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Fax: (+86) 021-64166128. E-mail: yhliu@mail.sioc.ac.cn.
3o. Yield 85%. Yellow crystalline solid: mp 119À120 °C; 1H NMR
(CDCl3, Me4Si, 400 MHz) δ 5.08 (s, 2H), 5.73 (s, 1H), 6.74 (s, 1H),
6.80 (d, J = 0.8 Hz, 1H), 6.89 (dd, J = 0.8, 8.8 Hz, 1H), 7.00 (d, J = 8.8 Hz,
1H), 7.04À7.08 (m, 1H), 7.13À7.21 (m, 3H), 7.24 (d, J = 1.6 Hz, 1H),
7.28À7.42 (m, 10H), 7.43À7.46 (m, 2H), 7.48À7.51 (m, 2H),
7.63À7.66 (m, 3H); 13C NMR (CDCl3, Me4Si, 100.6 MHz) δ 39.2,
70.8, 101.7, 108.7, 111.4, 114.3, 115.7, 117.3, 123.7, 126.3, 126.8, 127.4,
127.51, 127.54, 127.7, 127.9, 128.1, 128.4, 128.5, 128.6, 128.8, 128.9,
130.4, 130.6, 131.7, 132.5, 137.5, 140.2, 145.3, 148.3, 153.3, 154.6.
HRMS (EI) for C40H29NO2: calcd 555.2198, found 555.2200.
3p. PPh3AuNTf2 (5 mol %) was used. Yield 55%. Light yellow
crystalline solid: mp 139À140 °C; 1H NMR (CDCl3, Me4Si, 300 MHz)
δ 3.90 (s, 3H), 6.51 (s, 1H), 6.90 (s, 1H), 6.91 (s, 1H), 7.01À7.22 (m,
7H), 7.26À7.43 (m, 8H), 7.61 (d, J = 6.9 Hz, 1H), 7.68 (d, J = 8.1 Hz,
2H), 8.10 (s, 1H); 13C NMR (CDCl3, Me4Si, 75.5 MHz) δ 37.4, 52.2,
109.0, 114.7, 116.4, 118.7, 121.6, 123.6, 123.8, 124.0, 124.5, 125.7, 126.9,
127.5, 127.8, 128.1, 128.6, 128.7, 128.9, 129.2, 130.46, 130.49, 135.1,
137.2, 140.1, 144.6, 148.2, 155.0, 169.1. HRMS (MALDI/DHB) for
C35H26NO3 [M + H]+: calcd 508.1907, found 508.1915.
’ ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China
(Grants No. 20872163, 20732008, and 20821002), Chinese
Academy of Science, and the Major State Basic Research Devel-
opment Program (Grant No. 2011CB808700) for financial
support.
’ REFERENCES
(1) (a) Chandra, A.; Viswanathan, R.; Johnston, J. N. Org. Lett. 2007,
9, 5027. (b) Smitka, T. A.; Bonjouklian, F.; Doolin, L.; Jones, N. D.;
Deeter, J. B. J. Org. Chem. 1992, 57, 857. (c) Bennasar, M.-L.; Vidal, B.;
Bosch, J. Chem. Commun. 1996, 2755. (d) Clivio, P.; Richard, B.; Nuzillard,
J.; Zꢀeches-Hanrot, M. Phytochemistry 1995, 40, 987. (e) Wahlstr€om, N.;
Stenslandc, B.; Bergmana, J. Tetrahedron 2004, 60, 2147. (f) Su, J.; Zhu, Y.;
Zeng, L.; Xu, X. J. Nat. Prod. 1997, 60, 1043. (g) Fresneda, P. M.; Molina,
P.; Saez, M. A. Synlett 1999, 1651. (h) Joseph, B.; Alagille, D.; Mꢁerour, J.;
Lꢁeonce, S. Chem. Pharm. Bull. 2000, 48, 1872. (i) Bourderioux, A.;
Bꢁenꢁeteau, V.; Mꢁerour, J.; Baldeyrou, B.; Ballot, C.; Lansiaux, A.; Bailly,
C.; Guꢁevel, R. L.; Guillouzoc, C.; Routier, S. Org. Biomol. Chem. 2008,
6, 2108. (j) Vaswani, R. G.; Day, J. J.; Wood, J. L. Org. Lett. 2009, 11, 4532.
(2) (a) Ferrer, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006,
45, 1105. (b) Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem.—Eur.
2a. It was synthesized from 1a using 5 mol % AgOTf and 2.0 equiv of
indole in DCE. Yield 30% (silica gel was used instead of Al2O3). Light
yellow solid: 1H NMR (CDCl3, Me4Si, 400 MHz) δ 5.75 (s, 1H), 6.59
(s, 1H), 6.82 (d, J = 1.6 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 7.16 (t, J = 7.2
9180
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181

The Journal of Organic Chemistry
NOTE
J. 2007, 13, 1358. (c) Ferrer, C.; Escribano-Cuesta, A.; Echavarren, A. M.
Tetrahedron 2009, 65, 9015. (d) England, D. B.; Padwa, A. Org. Lett.
2008, 10, 3631. (e) Verniest, G.; England, D.; De Kimpe, N.; Padwa, A.
Tetrahedron 2010, 66, 1496. (f) Sanz, R.; Miguel, D.; Rodríguez, F.
Angew. Chem., Int. Ed. 2008, 47, 7354. (g) Liu, Y.; Xu, W.; Wang, X. Org.
Lett. 2010, 7, 1448. (h) Zhang, G.; Huang, X.; Li, G.; Zhang, L. J. Am.
Chem. Soc. 2008, 130, 1814. (i) Zhang, L. J. Am. Chem. Soc. 2005,
127, 16804. (j) Hirano, K.; Inaba, Y.; Takahashi, N.; Shimano, M.; Oishi,
S.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76, 1212.
(3) (a) Lu, Y.; Du, X.; Jia, X.; Liu, Y. Adv. Synth. Catal. 2009,
351, 1517. (b) Li, G.; Liu, Y. J. Org. Chem. 2010, 75, 3526. (c) Wang, L.;
Li, G.; Liu, Y. Org. Lett. 2011, 13, 3786.
(4) (a) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem.,
Int. Ed. 2006, 45, 7134. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(5) Liu, Y.; Zhou, S. Org. Lett. 2005, 7, 4609.
(6) Chen, Y.; Li, G.; Liu, Y. Adv. Synth. Catal. 2011, 353, 392.
(7) For related cascade reactions carried out in our group, see: (a)
Chen, Y.; Lu, Y.; Li, G.; Liu, Y. Org. Lett. 2009, 11, 3838. (b) Lu, Y.; Fu,
X.; Chen, H.; Du, X.; Jia, X.; Liu, Y. Adv. Synth. Catal. 2009, 351, 129. (c)
Li, G.; Liu, Y. J. Org. Chem. 2010, 75, 2903. (d) Yan, B.; Liu, Y. Org. Lett.
2007, 9, 4323.
(8) For AuCl3-catalyzed cyclization of 2-(1-alkynyl)-2-alken-1-ones
leading to substituted furans, see: Yao, T.; Zhang, X.; Larock, R. C. J. Am.
Chem. Soc. 2004, 126, 11164.
(9) A Pd-catalyzed oxidative cyclization of 1-diynyl-2-en-1-ones with
indoles over a reaction time of 17À36 h has been reported, see: Liu, R.;
Zhang, J. Adv. Synth. Catal. 2011, 353, 36.
(10) For the CÀO bond scission catalyzed by gold, see: (a) Guo, S.;
Song, F.; Liu, Y. Synlett 2007, 964. (b) Dubꢁe, P.; Toste, F. D. J. Am.
Chem. Soc. 2006, 128, 12062. (c) An, S. E.; Jeong, J.; Baskar, B.; Lee, J.;
Seo, J.; Rhee, Y. H. Chem.—Eur. J. 2009, 15, 11837.
(11) Onitsuka, S.; Nishino, H.; Kurosawa, K. Tetrahedron 2001, 57,
6003.
(12) Alternatively, intermediate 8 may attack the gold-coordinated
alkyne moiety directly before protonation.
(13) Arcadi, A.; Bianchi, G.; Chiarini, M.; D’Anniballe, G.; Marinelli,
F. Synlett 2004, 944.
(14) Chen, Y.; Liu, Y. J. Org. Chem. 2011, 76, 5274.
9181
dx.doi.org/10.1021/jo2017668 |J. Org. Chem. 2011, 76, 9175–9181