Sc(OTf)3-catalyzed synthesis of indoles and SnCl 4-mediated regioselective hydrochlorination of 5-(Arylamino)pent-3- yn-2-ones

Article abstract of DOI:10.1021/jo201514q

Highly substituted indole derivatives bearing alkyl and aryl moieties can be prepared by Sc(OTf)₃-catalyzed Friedel-Crafts alkenylation of 5-(arylamino)pent-3-yn-2-ones. In addition, a method for regioselective hydrochlorination of 5-(arylamino

Full text of DOI:10.1021/jo201514q

ARTICLE
pubs.acs.org/joc
Sc(OTf)3-Catalyzed Synthesis of Indoles and SnCl4-Mediated
Regioselective Hydrochlorination of 5-(Arylamino)pent-3-yn-2-ones
Fang Yang, Ke-Gong Ji, Shaukat Ali, and Yong-Min Liang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, and State Key Laboratory of Solid Lubrication,
Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, People’s Republic of China
S Supporting Information
b
ABSTRACT:
Highly substituted indole derivatives bearing alkyl and aryl moieties can be prepared by Sc(OTf)3-catalyzed FriedelꢀCrafts
alkenylation of 5-(arylamino)pent-3-yn-2-ones. In addition, a method for regioselective hydrochlorination of 5-(arylamino)pent-3-
yn-2-ones mediated by SnCl4 in moderate to good yields (up to 84%) has been developed. The resulting exclusive Z-selectivity of the
CꢀCl bond can be further exploited using cross CꢀN coupling reactions.
’ INTRODUCTION
’ RESULTS AND DISCUSSION
The indole skeleton is a ubiquitous bioactive heterocycle in
nature, especially in naturally occurring alkaloids. Indoles are
often used for the construction of many biologically active
compounds with diverse pharmacological properties,1 such as
Sumatriptan, ondansetron, and tadalafil.2 Their important
biological and pharmaceutical relevance has stimulated con-
siderable interest of synthetic chemists and has encouraged the
development of numerous synthetic strategies to prepare them.
The structural core of indoles can be synthesized by various
classical methods.3 However, the functional group tolerance
and the starting material availability often limit these syntheses.
In some cases, it remains difficult to prepare suitably substituted
indoles by standard indole-forming reactions. Thus, more
benign protocols for preparing indoles from readily available
and simple substrates still need to be actively persued. In recent
years, a range of synthetic approaches to indoles have been
reported,4 in most of which the formation of the NꢀC2,5
C2ꢀC3,6 or C3ꢀC3a7 bond is the key step. Lewis-acid-
catalyzed or mediated methods have also been proven to be
useful for preparing indoles.8 We envisioned that the treatment
of 5-(arylamino)pent-3-yn-2-ones 1 with Lewis acid would lead
to intramolecular FriedelꢀCrafts reaction,9 resulting in a
quinoline derivative. However, unexpectedly, the final data
revealed indole derivatives 2. Herein, we report a Sc(OTf)3-
catalyzed10 CꢀC bond formation for the synthesis of highly
substituted indole derivatives using 5-(arylamino)pent-3-yn-2-
ones as the substrates. Also, highly Z-selective CꢀCl bond
Our initial investigation was focused on finding a metal
triflate10a,b,12 catalyst to construct indole derivatives. Using 0.3
mmol of 4-((4-chlorophenyl)(methyl)amino)-1-phenylbut-2-yn-
1-one 1a and 5 mol % of Sc(OTf)3 in 1,2-dichloroethane (DCE)
at 60 °C, the desired product 2-(5-chloro-1-methyl-1H-indol-3-
yl)-1-phenylethanone 2a was formed in 35% yield after 24 h
(Table 1, entry1). Other triflate salts, such asBi(OTf)3, Hf(OTf)4,
In(OTf)3, Yb(OTf)3, Cu(OTf)2, and AgOTf, were also applied to
the reaction, but these catalysts were found to be inefficient
(entries 2ꢀ7). By increasing temperature to 85 °C, a 40% yield
of 2a was obtained (entry 8). With 10 mol % of Sc(OTf)3, a
moderate yield(51%) of 2awas obtained after24h at85 °C (entry
9). Other solvents were also tested in this reaction, but no superior
results were obtained (entries 11ꢀ13). Other Lewis acid catalysts,
such as TfOH, BF3 Et2O, SnCl4, TiCl4, AuCl3, FeCl3, and AlCl3,
3
were found to be inefficient to form indole derivatives. To our
surprise, when 10 mol % of SnCl4 was used as catalyst, a highly
Z-selective CꢀCl bond was constructed successfully. Then we
increased the amount of SnCl4 to 50 mol % (0.5 equiv), and a 60%
yield of (Z)-3-chloro-4-((4-chlorophenyl)(methyl)amino)-1-
phenylbut-2-en-1-one 3a was obtained after 5 h (Table 1, entry
18). Other MClx salts were also tested, but no better results were
obtained (entries 20ꢀ23).
To expand the scope of these divergent reactions of 5-
(arylamino)pent-3-yn-2-ones, we first examined various represen-
tative 5-(arylamino)pent-3-yn-2-ones 1aꢀs under indole-forming
11
formation was also achieved in the presence of SnCl4 as
Received: July 20, 2011
mediator.
Published: September 06, 2011
r
2011 American Chemical Society
8329
dx.doi.org/10.1021/jo201514q J. Org. Chem. 2011, 76, 8329–8335
|

The Journal of Organic Chemistry
ARTICLE
Table 1. Optimization of Conditions for the Transformation of 5-(Arylamino)pent-3-yn-2-ones 1a to Indole Derivatives 2a and
(Z)-4-Chloropent-3-en-2-ones 3a
yield (%)
entry
catalyst
solvent
DCE
temp (°C)
time (h)
2a
35
3a
1
2
Sc(OTf)3 (5 mol %)
Bi(OTf)3 (5 mol %)
Hf(OTf)4 (5 mol %)
In(OTf)3 (5 mol %)
Yb(OTf)3 (5 mol %)
Cu(OTf)2 (5 mol %)
AgOTf (5 mol %)
60
60
60
60
60
60
60
85
85
100
85
85
85
85
85
85
85
85
85
85
85
85
85
24
24
24
30
24
24
24
24
24
24
24
24
24
5
DCE
a
3
DCE
15
trace
10
a
4
DCE
5
DCE
6
DCE
7
DCE
a
8
Sc(OTf)3 (5 mol %)
Sc(OTf)3 (10 mol %)
Sc(OTf)3 (10 mol %)
Sc(OTf)3 (10 mol %)
Sc(OTf)3 (10 mol %)
Sc(OTf)3 (10 mol %)
HOTf (10 mol %)
DCE
40
51
43
a
9
DCE
10
11
12
13
14
15
16
17
18
19
20
21
22
23
DCE
CH3CN
1,4-dioxane
toluene
DCE
15
45
a
BF3 Et2O (10 mol %)
DCE
5
a
3
SnCl4 (10 mol %)
SnCl4 (30 mol %)
SnCl4 (50 mol %)
SnCl4 (100 mol %)
TiCl4 (50 mol %)
AuCl3 (50 mol %)
FeCl3 (50 mol %)
AlCl3 (50 mol %)
DCE
5
a
15
DCE
5
a
52
60
45
b
DCE
5
a
DCE
5
a
DCE
5
a
DCE
5
a
58
trace
20
DCE
5
a
DCE
5
a
a No desired product was observed. b Decomposed.
conditions, as depicted in Scheme 1. Thus, the cascade reaction
involving CꢀC bond formation of 5-(arylamino)pent-3-yn-2-ones
1aꢀsproceeded smoothly to provide corresponding products 2aꢀs
in moderate to good yields. When the R2 is a phenyl group, the
reaction works well with both electron-donating and electron-with-
drawing R1 groups (Scheme 1, 2aꢀ2i). Moderate yields of corre-
sponding products were obtained with little effect shown by R
groups to this transformation. Substrate 1j with an electron-with-
drawing aryl R2 group, such as 4-ClC6H4, and an electron-with-
drawing R1 group (4-Cl) can afford the desired product 2m in 63%
yield. The derivative 1m can also give the expected indole 2m in 81%
yield. Furthermore, to expand the scope of this reaction, we also
investigated a range of 5-(arylamino)pent-3-yn-2-ones 1nꢀq. Un-
der the optimized condition, several 1H-benzo[g]indole derivatives
2nꢀq can be prepared successfully in moderate yields. The
molecular structure of the representative product 2q was deter-
mined by X-ray crystallography (see Supporting Information).13 To
our delight, when 5-(arylamino)pent-3-yn-2-ones 1r,s were sub-
jected to this transformation, the corresponding 5,6-dihydro-4H-
pyrrolo[3,2,1-ij]quinoline derivatives 2r,s, which are important
intermediates in natural products, were separated in moderate yields.
After this, we examined the scope of CꢀCl bond formation of
5-(arylamino)pent-3-yn-2-ones. Under the optimized condition,
we also investigated a wide range of 5-(arylamino)pent-3-yn-2-
ones 1 with different substituents R, R1, and R2 in the presence of
0.5 equiv of SnCl4 at 85 °C in DCE. It was found that these
substrates were effectively converted into the corresponding (Z)-
4-chloropent-3-en-2-ones 3 in moderate to good yield with
exclusive Z-selectivity, as depicted in Table 2. The molecular
structure of the representative product 3l was determined by X-ray
crystallography (see Supporting Information).14 The reaction
tolerates the presence of different electron-donating and elec-
tron-withdrawing aryl groups. Fortunately, in all of the examples
studied, only exclusive Z-selective products were obtained.
A standard feature of this process is the fact that the (Z)-4-
chloropent-3-en-2-ones mediated by SnCl4 can be further elab-
orated by using various copper-catalyzed processes. For example,
the Ullmann coupling of (Z)-4-chloropent-3-en-2-ones 3l af-
forded the corresponding product 4l in moderate yield
(Scheme 2).
On the basis of the above observations, we propose the following
plausible mechanisms for Sc(OTf)3-catalyzed and SnCl4-mediated
8330
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335

The Journal of Organic Chemistry
ARTICLE
Scheme 1. Sc(OTf)3-Catalyzed CꢀC Bond Formation of 5-(Arylamino)pent-3-yn-2-ones 1 to Indole Derivatives 2a
a Conditions: 0.3 mmol of 1 with 10 mol % of Sc(OTf)3 in DCE (3.0 mL) at 85 °C. b For details, see the Supporting Information. c The reaction was
carried out in toluene at 85 °C.
Table 2. SnCl4-Mediated Regioselective formation of (Z)-4-Chloropent-3-en-2-ones 3 from 5-(Arylamino)pent-3-yn-2-ones 1a
a Conditions: 0.3 mmol of 1 with 0.5 equiv of SnCl4 in DCE (3.0 mL) at 85 °C.
cascade reactions (Scheme 3), which may involve the following
steps. (i) Coordination of the carbonyl moiety of 5-
(arylamino)pent-3-yn-2-ones 1 to Sc(OTf)3 catalyst gives the
complex A. (ii) The subsequent ortho-carbon atom of arylamine
as the nucleophile attacks the carbonꢀcarbon triple bond
and affords intermediate B. (iii) B on isomerization yields
8331
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335

The Journal of Organic Chemistry
ARTICLE
1-(indolin-3-ylidene)propan-2-one C and regenerates the cata-
lyst Sc(OTf)3. (iv) C undergoes the subsequent 1,3-H shift to
give indole derivatives 2. (v) SnCl4 eliminates a chloride anion to
give SnCl3, which coordinates with the carbonyl moiety of
5-(arylamino)pent-3-yn-2-ones 1 to give complex D.11a,b (vi)
The chlorine anion as nucleophile attacks the carbonꢀcarbon
triple bond and affords intermediate trichloro((3-chloropro-
pa-1,2-dien-1-yl)oxy)stannane E. (vii) E is hydrolyzed and
isomerization to give Z-selective products 3, during which the
diluted with ethyl ether (40 mL), washed with water and saturated brine,
dried over Na2SO4, and evaporated under reduced pressure. The residue
was purified by chromatography on silica gel to afford corresponding
2-(1H-indol-3-yl)ethanones 2aꢀ2s.
Characterization Data of 2aꢀs. 2-(5-Chloro-1-methyl-1H-in-
dol-3-yl)-1-phenylethanone 2a: yield 51%; dark red solid; mp
84ꢀ86 °C; 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.2 Hz, 2H),
7.57ꢀ7.53 (m, 2H), 7.47ꢀ7.43 (m, 2H), 7.19ꢀ7.14 (m, 2H), 7.01 (s,
1H), 4.34 (s, 2H), 3.70 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 197.4, 136.6, 135.3, 133.1, 129.2, 128.8, 128.6, 128.5, 125.1, 122.1,
118.4, 110.4, 106.9, 35.1, 32.9; IR (neat, cmꢀ1) 2923, 1724, 1683, 1477,
1451, 1211, 792, 690; HRMS (ESI) calcd for C17H14ClNO [M + H]+ =
284.0837, found 284.0841.
11c
steric effect plays a key role. Meanwhile, the SnCl4ꢀn(OH)n
can mediate the reaction again by eliminating a second
chloride anion.
2-(1-Methyl-1H-indol-3-yl)-1-phenylethanone 2b: yield 46%; dark
red oil; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 6.8 Hz, 2H), 7.59 (d,
J = 8.0 Hz, 1H), 7.51ꢀ7.47 (m, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.24ꢀ7.18
(m, 2H), 7.13ꢀ7.09 (m, 1H), 6.94 (s, 1H), 4.35 (s, 2H), 3.65 (s, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 197.8, 136.8, 136.6, 132.9, 128.5,
128.5, 127.8, 127.7, 121.7, 119.1, 118.8, 109.2, 107.1, 35.3, 32.6; IR
(neat, cmꢀ1) 2924, 1679, 1596, 1473, 1448, 1332, 1210, 742, 689;
HRMS (ESI) calcd for C17H15NO [M + H]+ = 250.1226, found
250.1228.
’ CONCLUSION
In summary, a Sc(OTf)3-catalyzed intramolecular Friedelꢀ
Crafts reaction for the synthesis of highly substituted indole
derivatives 2 from 5-(arylamino)pent-3-yn-2-ones 1 has been
realized. In addition, a SnCl4-mediated protocol for highly Z-
selective CꢀCl bond formation was also successfully developed.
The resulting CꢀCl bond can be further exploited using cross
CꢀN coupling reactions.
2-(4-Chloro-1-methyl-1H-indol-3-yl)-1-phenylethanone 2c0 Com-
pound with 2-(6-Chloro-1-methyl-1H-indol-3-yl)-1-phenylethanone
1
2c00 (1:1): yield 42%; dark red oil; H NMR (400 MHz, CDCl3) δ
’ EXPERIMENTAL SECTION
8.07 (d, J = 1.2 Hz, 2H), 8.03 (d, J = 8.0 Hz, 2H), 7.58ꢀ7.52 (m, 2H),
7.49 (s, 3H), 7.47ꢀ7.42 (m, 2H), 7.26 (d, J = 2.0 Hz, 1H), 7.18 (dd, J =
8.0 Hz, 0.8 Hz, 1H), 7.09ꢀ7.02 (m, 3H), 6.98 (s, 2H), 4.69 (s, 2H), 4.35
(s, 2H), 3.71 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 198.3, 197.5, 138.4, 137.3, 137.0, 136.6, 133.1, 132.9, 129.5, 128.6,
128.6, 128.5, 128.5, 128.4, 127.9, 126.4, 126.2, 124.4, 122.1, 120.1, 119.9,
General Procedure: Synthesis of Indole Derivatives
2aꢀ2s. To a solution of 5-(arylamino)pent-3-yn-2-ones 1 (0.20 mmol)
in DCE (3.0 mL) was added 9.8 mg (10 mol %) of Sc(OTf)3. The
resulting mixture was stirred at 85 °C. When the reaction was considered
complete as determined by TLC analysis, the reaction mixture was
119.8, 109.4, 108.2, 107.5, 107.5, 36.3, 35.2, 33.0, 32.8; IR (neat, cmꢀ1
)
Scheme 2. Cu-Catalyzed Ullmann Reaction of 3l to 4l
2926, 1687, 1600, 1476, 1452, 1331, 1212, 1067, 757, 691; HRMS (ESI)
calcd for C17H14ClNO [M + H]+ = 284.0837, found 284.0847.
2-(1,5-Dimethyl-1H-indol-3-yl)-1-phenylethanone 2d: yield 45%;
dark red oil; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 2H),
7.44 (d, J = 6.9 Hz, 1H), 7.38ꢀ7.31 (m, 3H), 7.09 (d, J = 8.1 Hz, 1H),
6.97 (d, J = 8.1 Hz, 1H), 6.86 (s, 1H), 4.29 (s, 2H), 3.62 (s, 3H), 2.38 (s,
3H); 13C NMR (75 MHz, CDCl3) δ ppm 197.9, 136.7, 135.3, 132.9,
128.6, 128.5, 128.4, 127.9, 123.4, 118.4, 109.0, 106.6, 35.5, 32.7, 21.5; IR
Scheme 3. Proposed Mechanism
8332
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335

The Journal of Organic Chemistry
ARTICLE
(neat, cmꢀ1) 2360, 1629, 1531, 1218, 768, 689; HRMS (ESI) calcd for
C18H17NO [M + H]+ = 264.1383, found 264.1389.
Hz, 2H), 7.57ꢀ7.54 (m, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.26ꢀ7.23 (m,
3H), 7.15ꢀ7.11 (m, 3H), 7.05ꢀ7.03 (m, 2H), 5.24 (s, 2H), 4.37 (s,
2H); 13C NMR (100 MHz, CDCl3) δ ppm 197.3, 137.0, 136.6, 134.9,
133.1, 129.2, 128.8, 128.7, 128.6, 128.5, 127.7, 126.7, 125.4, 122.3, 118.6,
110.9, 107.7, 50.2, 35.3; IR (neat, cmꢀ1) 2923, 1685, 1470, 1448, 1211,
772, 694; HRMS (ESI) calcd for C23H18ClNO [M + H]+ = 360.1150,
found 360.1153.
2-(1,7-Dimethyl-1H-indol-3-yl)-1-phenylethanone 2e: yield 30%;
dark red oil; 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.6 Hz, 2H),
7.52 (t, J = 7.6 Hz, 1H), 7.44ꢀ7.41 (m, 3H), 6.98 (t, J = 7.2 Hz, 1H), 6.90
(d, J = 7.2 Hz, 1H), 6.86 (s, 1H), 4.34 (s, 2H), 3.97 (s, 3H), 2.73 (s, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 197.9, 136.7, 135.6, 132.9, 129.4,
128.8, 128.6, 128.5, 124.4, 121.3, 119.5, 116.8, 107.0, 36.6, 35.3, 19.6; IR
(neat, cmꢀ1) 2922, 1670, 1382, 1069, 752, 689; HRMS (ESI) calcd for
C18H17NO [M + H]+ = 264.1383, found 264.1389.
2-(5-Methoxy-1-methyl-1H-indol-3-yl)-1-phenylethanone 2f: yield
37%; dark red oil; 1H NMR (400 MHz, CDCl3) δ 8.05ꢀ8.03 (m, 2H),
7.54ꢀ7.50 (m, 1H), 7.48 (s, 1H), 7.46ꢀ7.41 (m, 2H), 6.86 (s, 1H), 6.79
(dd, J = 8.4 Hz, 2.0 Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 4.34 (s, 2H), 3.86
(s, 3H), 3.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 197.8, 156.5,
137.6, 136.7, 132.9, 128.6, 128.5, 126.6, 122.2, 119.6, 109.1, 107.3, 92.9,
55.7, 35.5, 32.7; IR (neat, cmꢀ1) 2921, 1669, 1611, 1499, 1219, 1055,
772, 691; HRMS (ESI) calcd for C18H17 NO [M + H]+ = 280.1332,
found 280.1336.
2-(1-Benzyl-5-chloro-1H-indol-3-yl)-1-(4-chlorophenyl)ethanone
1
2m: yield 81%; dark red solid; mp 74ꢀ76 °C; H NMR (400 MHz,
CDCl3) δ 7.96 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 1.6 Hz, 1H), 7.41 (d, J =
8.8 Hz, 2H), 7.30ꢀ7.26 (m, 3H), 7.16ꢀ7.10 (m, 2H), 7.09 (s, 1H),
7.05ꢀ7.03 (m, 2H), 5.24 (s, 2H), 4.33 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 196.1, 139.5, 136.9, 135.0, 134.8, 129.9, 129.0, 128.9,
128.8, 128.7, 127.8, 126.7, 125.5, 122.4, 118.5, 110.9, 107.4, 50.2, 35.4;
IR (neat, cmꢀ1) 2923, 1689, 1588, 1470, 1204, 1092, 772, 733, 699;
HRMS (ESI) calcd for C23H17Cl2NO [M + H]+ = 394.0760, found
394.0766.
2-(1-Benzyl-1H-benzo[g]indol-3-yl)-1-phenylethanone 2n: yield
1
56%; dark red solid; mp 66ꢀ68 °C; H NMR (400 MHz, CDCl3) δ
2-(1Benzyl-1H-indol-3-yl)-1-phenylethanone 2g: yield 42%; dark
8.06 (d, J = 7.2 Hz, 2H), 8.01 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H),
7.72 (d, J = 8.4 Hz, 1H), 7.55ꢀ7.52 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H),
7.34ꢀ7.29 (m, 2H), 7.28ꢀ7.19 (m, 3H), 7.09 (s, 1H), 7.00 (d, J = 6.4
Hz, 2H), 5.70 (s, 2H), 4.48 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
ppm 197.8, 137.6, 136.7, 133.0, 131.4, 129.9, 129.1, 128.9, 128.6, 128.5,
128.1, 127.4, 125.9, 125.3, 125.2, 123.4, 122.6, 121.3, 120.9, 118.7, 109.1,
53.4, 35.5; IR (neat, cmꢀ1) 2089, 1637, 802, 745; HRMS (ESI) calcd for
C27H21NO [M + H]+ = 376.1690, found 376.1694.
1
red oil; H NMR (400 MHz, CDCl3) δ 8.06ꢀ8.04 (m, 2H), 7.63 (d,
J = 7.2 Hz, 1H), 7.55ꢀ7.51 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.24ꢀ7.21
(m, 3H), 7.19ꢀ7.11 (m, 3H), 7.08ꢀ7.05 (m, 3H), 5.26 (s, 2H), 4.41 (s,
2H); 13C NMR (100 MHz, CDCl3) δ ppm 197.8, 137.4, 136.7, 136.5,
132.9, 128.7, 128.6, 128.5, 128.0, 127.5, 127.3, 126.7, 122.0, 119.5, 119.0,
109.8, 108.1, 50.0, 35.6; IR (neat, cmꢀ1) 2923, 2360, 1678, 1601, 1449,
1174, 746, 695; HRMS (ESI) calcd for C23H19NO [M + H]+
326.1539, found 326.1543.
=
2-(1-Allyl-1H-benzo[g]indol-3-yl)-1-phenylethanone 2o: yield 40%;
dark red oil; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 1H),
8.06 (d, J = 7.2 Hz, 2H), 7.92 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H),
7.55ꢀ7.50 (m, 2H), 7.48ꢀ7.44 (m, 2H), 7.42ꢀ7.38 (m, 2H), 7.05 (s,
1H), 6.19ꢀ6.10 (m, 1H), 5.22 (d, J = 10.8 Hz, 1H), 5.11 (t, J = 2.4 Hz,
2H), 4.91 (d, J = 17.2 Hz, 1H), 4.46 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 197.8, 136.7, 133.6, 133.0, 131.4, 129.7, 129.2, 128.6,
128.5, 127.5, 125.2, 125.0, 123.4, 122.6, 121.1, 121.1, 118.7, 117.2, 108.9,
52.1, 35.5; IR (neat, cmꢀ1) 2922, 1681, 809, 747; HRMS (ESI) calcd for
C23H19NO [M + H]+ = 326.1539, found 326.1545.
1-Phenyl-2-(1-phenyl-1H-indol-3-yl)ethanone 2h: yield 39%; dark
red oil; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 7.2 Hz, 2H), 7.66 (d,
J = 7.6 Hz, 1H), 7.54 (t, J = 7.2 Hz, 2H), 7.47ꢀ7.43 (m, 6H), 7.33ꢀ7.30
(m, 2H), 7.25ꢀ7.17 (m, 2H), 4.46 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 197.5, 139.6, 136.6, 136.0, 133.1, 129.5, 128.8, 128.6,
128.5, 126.9, 126.3, 124.2, 122.7, 120.3, 119.2, 110.6, 110.0, 35.4; IR
(neat, cmꢀ1) 2921, 1683, 1596, 1500, 1455, 1210, 749, 695; HRMS
(ESI) calcd for C22H17 NO [M + H]+ = 312.1383, found 312.1389.
1-Phenyl-2-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)ethanone 2i: yield
1
35%; dark red oil; H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.6
2-(1-Methyl-1H-benzo[g]indol-3-yl)-1-phenylethanone 2p: yield
1
Hz, 2H), 7.61 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.6
Hz, 2H), 7.37 (d, J = 8.4 Hz, 1H), 7.25ꢀ7.23 (m, 1H), 7.16ꢀ7.14 (m,
2H), 4.81 (d, J = 2.0 Hz, 2H), 4.39 (s, 2H), 1.55 (s, 1H); 13C NMR (100
MHz, CDCl3) δ ppm 197.6, 136.7, 136.1, 133.0, 128.6, 128.6, 128.3,
126.3, 122.2, 119.8, 119.1, 109.4, 108.5, 77.7, 73.5, 35.7, 35.4; IR
(neat, cmꢀ1) 2922, 1681, 1598, 1466, 1337, 1211, 1181, 745, 689; HRMS
(ESI) calcd for C19H15NO [M + H]+ = 274.1226, found 274.1230.
2-(5-Chloro-1-methyl-1H-indol-3-yl)-1-(4-chlorophenyl)ethanone
45%; dark red oil; H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.4
Hz, 1H), 8.06 (d, J = 7.2 Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.8
Hz, 1H), 7.54ꢀ7.48 (m, 3H), 7.41 (q, J = 7.6 Hz, 3H), 6.97 (s, 1H), 4.43
(s, 2H), 4.19 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 197.8, 136.7,
133.0, 131.4, 130.2, 129.2, 128.6, 128.6, 128.1, 125.2, 124.8, 123.3, 120.8,
120.6, 118.7, 108.1, 38.3, 35.3; IR (neat, cmꢀ1) 2922, 2361, 2336, 1680,
1394, 1068, 689; HRMS (ESI) calcd for C21H17NO [M + H]+
300.1383, found 300.1377.
=
1
2-(1-Methyl-1H-benzo[g]indol-3-yl)-1-(p-tolyl)ethanone 2q: yield
2j: yield 63%; dark red solid; mp 190ꢀ192 °C; H NMR (400 MHz,
1
42%; yellow solid; mp 146ꢀ148 °C; H NMR (400 MHz, CDCl3) δ
CDCl3) δ 7.95 (d, J = 8.8 Hz, 2H), 7.52 (t, J = 0.8 Hz, 1H), 7.40 (d, J =
8.4 Hz, 2H), 7.19ꢀ7.16 (m, 2H), 6.99 (s, 1H), 4.29 (s, 2H), 3.70 (s,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 196.2, 139.5, 135.3, 134.8,
129.9, 129.2, 128.9, 128.7, 125.2, 122.1, 118.3, 110.4, 106.6, 35.2, 32.9;
IR (neat, cmꢀ1) 2922, 2361, 2336, 1679, 1091, 785, 671; HRMS (ESI)
calcd for C17H13Cl2NO [M + H]+ = 318.0447, found 318.0450.
2-(1-Benzyl-1H-indol-3-yl)-1-(4-chlorophenyl)ethanone 2k: yield
8.42 (d, J = 8.4 Hz, 1H), 7.97ꢀ7.92 (m, 3H), 7.68 (d, J = 8.8 Hz, 1H),
7.52ꢀ7.48 (m, 2H), 7.43ꢀ7.39 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 6.98
(s, 1H), 4.41 (s, 2H), 4.21 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 197.5, 143.7, 134.2, 131.4, 129.3, 129.2, 128.7, 128.1,
125.2, 124.9, 123.4, 123.3, 120.8, 120.6, 118.8, 108.4, 38.3, 35.3, 29.7,
21.6; IR (neat, cmꢀ1) 2922, 1677, 1605, 1397, 1284, 805, 748; HRMS
(ESI) calcd for C22H19NO [M + H]+ = 314.15393, found 314.1545.
2-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-1-phenylethanone
2r: yield 40%; dark red oil; 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J =
7.6 Hz, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 8.0 Hz, 3H), 7.03 (t, J =
7.6 Hz, 2H), 6.90 (d, J = 9.2 Hz, 1H), 4.39 (s, 2H), 4.09(t, J = 6.0 Hz,
2H), 2.96 (t, J = 6.0 Hz, 2H), 2.23ꢀ2.18 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 197.9, 136.7, 134.4, 132.9, 128.6, 128.5, 125.3, 125.1,
1
50%; dark red oil; H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.8
Hz, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.24 (s, 3H),
7.19ꢀ7.11 (m, 3H), 7.06ꢀ7.04 (m, 3H), 5.25 (s, 2H), 4.36 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ ppm 196.6, 139.3, 137.4, 136.6, 134.9,
130.0, 128.8, 128.7, 127.9, 127.6, 127.2, 126.7, 122.1, 119.6, 118.9, 109.9,
107.8, 50.0, 35.7; IR (neat, cmꢀ1) 2923, 2361, 1679, 1589, 1393, 1171,
1092, 741, 699; HRMS (ESI) calcd for C23H18ClNO [M + H]+
360.1150, found 360.1158.
=
121.7, 119.6, 118.6, 116.3, 107.2, 43.9, 35.8, 24.6, 22.8; IR (neat, cmꢀ1
)
2930, 1679, 1626, 1448, 1213, 752; HRMS (ESI) calcd for C19H17NO
2-(1-Benzyl-5-chloro-1H-indol-3-yl)-1-phenylethanone 2l: yield
73%; dark red oil; H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.6
[M + H]+ = 276.1383, found 276.1386.
1
8333
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335

The Journal of Organic Chemistry
ARTICLE
1-(4-Chlorophenyl)-2-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)
ethanone 2s: yield 30%; dark red solid; mp 77ꢀ79 °C; 1H NMR (400
MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 2H), 7.40ꢀ7.37 (m, 3H), 7.04 (t, J =
7.6 Hz, 1H), 6.98 (s, 1H), 6.91 (d, J = 6.8 Hz, 1H), 4.35 (s, 2H), 4.09 (t, J
= 5.6 Hz, 2H), 2.96 (t, J = 6.0 Hz, 2H), 2.23ꢀ2.16 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ ppm 196.7, 139.3, 135.0, 130.1, 128.8, 125.1,
125.0, 121.8, 119.7, 118.7, 116.2, 106.8, 44.0, 35.9, 29.7, 24.6, 22.8; IR
(neat, cmꢀ1) 2927, 1684, 1627, 1591, 1390, 1091, 750; HRMS (ESI)
calcd for C19H16 ClNO [M + H] = 310.0993, found 310.0999.
General Procedure: Synthesis of (Z)-4-Chloropent-3-en-2-
ones 3. To a solution of 5-(arylamino)pent-3-yn-2-ones 1(0.20 mmol) in
DCE (3.0 mL) was added SnCl4 (0.5 equiv). The resulting mixture was
stirred at 85 °C. When the reaction was considered complete as determined
by TLC analysis, the reaction mixture was diluted with ethyl ether (40 mL),
washed with water and saturated brine, dried over Na2SO4, and evaporated
under reduced pressure. The residue was purified by chromatography on
silica gel to afford corresponding (Z)-4-chloropent-3-en-2-ones 3.
Hz, 1H), 6.55 (d, J = 8.0 Hz, 1H), 4.15 (s, 2H), 3.44 (t, J = 6.0 Hz, 2H),
2.83 (t, J = 6.2 Hz, 2H), 2.07ꢀ2.01 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 189.9, 143.9, 142.0, 137.3, 133.3, 129.3, 128.6, 127.4,
122.5, 120.3, 117.2, 111.0, 59.4, 50.4, 27.9, 22.4; IR (neat, cmꢀ1) 2926,
1670, 1602, 1501, 1218, 748, 696; HRMS (ESI) calcd for C19H18ClNO
[M + H]+ = 312.1150, found 312.1156.
(Z)-3-Chloro-1-(4-chlorophenyl)-4-(3,4-dihydroquinolin-1(2H)-yl)but-
1
2-en-1-one 3s: yield 47%; orange solid; mp 78ꢀ80 °C; H NMR (300
MHz, CDCl3) δ 7.62, (d, J = 7.8 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.03 (t, J
= 7.8 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.84 (s, 1H), 6.62 (t, J = 7.2 Hz,
1H), 6.45(d, J= 8.4 Hz, 1H), 4.07 (s, 2H), 3.36 (t, J= 5.1 Hz, 2H), 2.75 (t, J
= 6.6 Hz, 2H), 1.95 (q, J = 5.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ
ppm 188.7, 143.8, 142.5, 139.8, 135.7, 130.0, 129.4, 129.0, 127.4, 122.6,
120.0, 117.3, 111.0, 59.4, 50.4, 27.9, 22.4; IR (neat, cmꢀ1) 2928, 2847,
1672, 1604, 1502, 1217, 1091, 853, 819, 748; HRMS (ESI) calcd for
C19H17Cl2NO [M + H]+ = 346.0760, found 346.0766.
(Z)-3-Chloro-4-((3,4-dimethylphenyl)(methyl)amino)-1-phenylbut-
2-en-1-one 3t: yield 72%; dark red oil; 1H NMR (400 MHz, CDCl3)
δ 7.79ꢀ7.77 (m, 2H), 7.55ꢀ7.50 (m, 1H), 7.39 (d, J = 8.0 Hz, 2H), 7.04
(d, J = 8.4 Hz, 1H), 6.92 (t, J = 1.2 Hz, 1H), 6.58 (d, J = 2.4 Hz, 1H), 6.53
(dd, J = 8.0 Hz, 2.8 Hz, 1H), 4.17 (d, J = 1.2 Hz, 2H), 3.08 (s, 3H), 2.26
(s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 189.8, 146.5,
142.5, 137.5, 137.3, 133.2, 130.4, 128.6, 128.6, 125.8, 120.6, 113.9, 109.9,
60.8, 38.9, 20.3, 18.6; IR (neat, cmꢀ1) 2920, 2361, 2336, 1671, 1615,
1511, 1219, 1018, 774, 695; HRMS (ESI) calcd for C19H20ClNO
[M + H]+ = 314.1306, found 314.1312.
Characterization Data of 4l. (Z)-4-(Benzyl(4-chlorophenyl)amino)-
3-(diethylamino)-1-phenylbut-2-en-1-one 4l: yield 65%; yellow solid; mp
104ꢀ106 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H),
7.44ꢀ7.38 (m, 3H), 7.23ꢀ7.19 (m, 2H), 7.18ꢀ7.15 (m, 5H), 6.82 (d, J=8.8
Hz, 2H), 5.77 (s, 1H), 4.89 (s, 2H), 4.60 (s, 2H), 3.22 (q, J = 7.2 Hz, 4H),
0.99 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ ppm 188.0, 159.4,
149.0, 142.7, 140.2, 130.6, 129.0, 128.2, 128.1, 127.3, 126.7, 126.6, 123.1,
115.6, 95.0, 54.7, 45.8, 44.4, 12.4; IR (neat, cmꢀ1) 2977, 2928, 1535, 1491,
1355, 1222, 759, 703; HRMS (ESI) calcd for C27H29ClN2O [M + H]+ =
433.2041, found 433.2047.
Characterization Data of 3aꢀ3t. (Z)-3-Chloro-4-((4-chlorophenyl)-
1
(methyl)amino)-1-phenylbut-2-en-1-one 3a: yield 60%; dark red oil; H
NMR (400 MHz, CDCl3) δ7.77ꢀ7.74(m,2H),7.57ꢀ7.52 (m, 1H), 7.42 (t,
J = 7.6 Hz, 2H), 7.25ꢀ7.23 (m, 2H), 6.84 (t, J = 1.6 Hz, 1H), 6.70ꢀ6.66 (m,
2H), 4.20 (d, J = 1.6 Hz, 2H), 3.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 189.5, 146.6, 141.6, 137.2, 133.4, 129.2, 128.7, 128.5, 122.7, 120.7, 113.3,
60.5, 39.1; IR (neat, cmꢀ1) 2917, 1670, 1598, 1501, 1217, 811, 764, 695;
HRMS (ESI) calcd for C17H15Cl2NO[M+H]+ = 320.0603, found 320.0608.
(Z)-3-Chloro-4-(methyl(p-tolyl)amino)-1-phenylbut-2-en-1-one 3d:
1
yield 42%; dark red oil; H NMR (300 MHz, CDCl3) δ 7.69 (d, J =
8.1 Hz, 2H), 7.46 (t, J = 7.2 Hz, 1H), 7.35ꢀ7.30 (m, 2H), 7.03 (d, J = 8.4
Hz, 2H), 6.84 (d, J = 1.2 Hz, 1H), 6.61 (d, J = 8.4 Hz, 2H), 4.11 (s, 2H),
3.02 (s, 3H), 2.23 (s, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 189.7,
146.0, 142.5, 133.3, 129.9, 129.6, 128.6, 128.5, 127.0, 120.5, 112.3, 60.8,
38.9, 20.2; IR (neat, cmꢀ1) 2922, 1669, 1616, 1518, 1449, 1258, 1219,
805, 756, 696; HRMS (ESI) calcd for C18H18ClNO [M + H]+
300.1150, found 300.1156.
=
(Z)-4-(Benzyl(phenyl)amino)-3-chloro-1-phenylbut-2-en-1-one 3g:
yield 68%; dark red oil; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.6
Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.2
Hz, 2H), 7.30ꢀ7.27 (m, 4H), 6.70 (s, 1H), 6.84ꢀ6.79 (m, 3H), 4.71 (s,
2H), 4.30 (s, 2H); 13C NMR (100 MHz, CDCl3) δ ppm 189.7, 147.6,
141.9, 137.6, 137.3, 133.3, 129.5, 128.8, 128.6, 127.3, 126.7, 120.9, 118.1,
112.6, 58.4, 54.4; IR (neat, cmꢀ1) 2360, 1641, 1502, 747, 694; HRMS
(ESI) calcd for C23H20ClNO [M + H]+ = 362.1306, found 362.1310.
(Z)-3-Chloro-1-(4-chlorophenyl)-4-((4-chlorophenyl)(methyl)amino)
but-2-en-1-one 3j: yield 84%; dark red oil; 1H NMR (400 MHz,
CDCl3) δ 7.67 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 7.24 (d,
J = 9.2 Hz), 7.12 (d, J = 8.8 Hz, 2H), 6.79 (s, 1H), 6.67 (d, J = 8.8 Hz,
2H), 4.19 (d, J = 1.6 Hz, 2H), 3.10 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 188.3, 146.6, 142.3, 139.9, 135.5, 129.9, 129.3, 129.0,
122.8, 120.3, 113.3, 60.5, 39.1; IR (neat, cmꢀ1) 2921, 2361, 2336, 1671,
1594, 1501, 1216, 1093, 813; HRMS (ESI) calcd for C17H14Cl3NO [M
+ H]+ = 354.0214, found 354.0220.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details, analytical
b
data for all new compounds, and X-ray crystallography data of 2p
and 3l in CIF format. This material is available free of charge via
the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: liangym@lzu.edu.cn.
’ ACKNOWLEDGMENT
We thank the NSF (NSF-21072080, NSF-20732002) for
financial support. We acknowledge National Basic Research
Program of China (973 program), 2010CB833203, and also
the support by the 111 Project.
(Z)-4-(Benzyl(4-chlorophenyl)amino)-3-chloro-1-phenylbut-2-en-1-
1
one 3l: yield 76%; yellow solid; mp 78ꢀ80 °C; H NMR (400 MHz,
CDCl3) δ 7.75 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 8.0
Hz, 2H), 7.37ꢀ7.33 (m, 2H), 7.28 (t, J = 7.2 Hz, 1H), 7.24ꢀ7.17 (m,
4H), 6.95 (s, 1H), 6.70 (d, J = 9.2 Hz, 2H), 4.67 (s, 2H), 4.28 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ ppm 189.5, 146.1, 141.5, 137.1, 137.0, 133.4,
129.3, 128.9, 128.7, 128.5, 127.4, 126.5, 123.0, 120.9, 113.7, 58.5, 54.5; IR
(neat, cmꢀ1) 2924, 1671, 1598, 1499, 1261, 1225, 811, 733, 697; HRMS
(ESI) calcd for C23H19Cl2NO [M + H]+ = 396.0916, found 396.0920.
(Z)-3-Chloro-4-(3,4-dihydroquinolin-1(2H)-yl)-1-phenylbut-2-en-1-
one 3r: yield 65%; yellow solid; mp 78ꢀ80 °C; 1H NMR (400 MHz,
CDCl3) δ 7.79 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.41 (t, J = 7.6
Hz, 2H), 7.11 (t, J = 7.6 Hz, 1H), 7.01 (t, J = 7.2 Hz, 2H), 6.69 (t, J = 7.6
’ REFERENCES
(1) (a) Baeyer, A. Justus Liebigs Ann. Chem. 1866, 140, 295. (b)
Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York,
1970. (c) Sundberg, R. J. Indoles; Academic Press: London, 1996. (d)
Brancale, A.; Silvestri, R. Med. Res. Rev. 2007, 27, 209. (e) Welsch, M. E.;
Snyder, S. A.; Stockwell, B. R. Curr. Opin. Chem. Biol. 2010, 14, 347.
(2) (a) Costall, B.; Gunning, S. J.; Naylor, R. J.; Tyers, M. B. Br. J.
Pharmacol. 1987, 91, 263. (b) Daugan, A. C.-M. Patent Application
8334
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335

The Journal of Organic Chemistry
ARTICLE
WO95/19978, 1995. (c) Doenicke, A.; Brand, J.; Perrin, V. L. Lancet
1988, 1, 1309.
(3) (a) Sundberg, R. J. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, UK, 1984; Vol. 4,
p 313. (b) Fischer, E.; Jourdan, F. Ber. Dtsch. Chem. Ges. 1883, 16, 2241.
(c) Fischer, E.; Jourdan, F. Ber. Dtsch. Chem. Ges. 1884, 17, 559. (d)
Robinson, B. Chem. Rev. 1969, 69, 227.
(4) (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873. (b)
Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875. (c) Saito, A.;
Kanno, A.; Hanzawa, Y. Angew. Chem., Int. Ed. 2007, 46, 3931. (d)
Opatz, T.; Ferenc, D. Org. Lett. 2006, 8, 4473. (e) Pei, T.; Chen, C.-Y.;
Dormer, P. G.; Davies, I. W. Angew. Chem., Int. Ed. 2008, 47, 4231. (f)
Okamoto, N.; Miwa, Y.; Minami, H.; Takeda, K.; Yanada, R. Angew.
Chem., Int. Ed. 2009, 48, 9693. (g) Haag, B. A.; Zhang, Z.-G.; Li, J.-S.;
Knochel, P. Angew. Chem., Int. Ed. 2010, 49, 9513. (h) Leogane, O.;
Lebel, H. Angew. Chem., Int. Ed. 2008, 47, 350. (i) Stuart, D. R.; Alsabeh,
P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 18326. (j)
Medeiros, M. R.; Schaus, S. E.; Porco, J. A., Jr. Org. Lett. 2011, 13, 4012.
(5) (a) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett
2000, 647. (b) Barluenga, J.; Trinicado, M.; Rubio, E.; Gonzꢀalez, J. M.
Angew. Chem., Int. Ed. 2003, 42, 2406. (c) Nakamura, I.; Yamagishi, U.;
Song, D.; Konta, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 2284.
(6) (a) Takeda, A.; Kamijo, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000,
122, 5662. (b) Kraus, G. A.; Guo, H.-T. J. Org. Chem. 2009, 74, 5337.
(7) (a) Chen, C. Y.; Lieberman, D. R.; Larsen, R. D.; Verhoeven,
T. R.; Reider, P. J. J. Org. Chem. 1997, 62, 2676. (b) Yagoubi, M.; Cruz,
A. C. F.; Nichols, P. L.; Elliott, R. L.; Willis, M. C. Angew. Chem., Int. Ed.
2010, 49, 7958.
(8) (a) Hiroya, K.; Itoh, S.; Sakamoto, T. J. Org. Chem. 2004,
69, 1126. (b) Kumar, M. P.; Liu, R.-S. J. Org. Chem. 2006, 71, 4951.
(c) Jana, S.; Clements, M. D.; Sharp, B. K.; Zheng, N. Org. Lett. 2010,
12, 3736.
(9) (a) Suꢀarez-Pantiga, S.; Palomas, D.; Rubio, E.; Gonzꢀalez, J. M.
Angew. Chem., Int. Ed. 2009, 48, 7857. (b) Fillion, E.; Fishlock, D. Org.
Lett. 2003, 5, 4653.
(10) (a) Yoon, M. Y.; Kim, J. H.; Choi, D. S.; Shin, U. S.; Lee, J. Y.;
Song, C. E. Adv. Synth. Catal. 2007, 349, 1725. (b) Song, C. E.; Jung,
D. U.; Choung, S. Y.; Roh, E. J.; Lee, S. G. Angew. Chem., Int. Ed. 2004,
43, 6183.
(11) (a) Dias, L. C.; Meira, P. R. R.; Ferreira, E. Org. Lett. 1999,
1, 1335. (b) Kitagawa, O.; Fujiwara, H.; Suzuki, T.; Taguchi, T.; Shiro,
M. J. Org. Chem. 2000, 65, 6819. (c) Zhang, Z.-G.; Zhang, Q.; Yan, Z.-H.;
Liu, Q. J. Org. Chem. 2007, 72, 9808.
(12) (a) Tsuchimoto, T.; Maeda, T.; Shirakawa, E.; Kawakami, Y.
Chem. Commun. 2000, 1573. (b) Komeyama, K.; Igawa, R.; Takaki, K.
Chem. Commun. 2010, 46, 1748.
(13) The molecular structure of the product 2p was determined by
means of X-ray crystallographic studies; for details, see the Supporting
Information.
(14) The molecular structure of the product 3l was determined by
means of X-ray crystallographic studies; for details, see the Supporting
Information.
8335
dx.doi.org/10.1021/jo201514q |J. Org. Chem. 2011, 76, 8329–8335