Route to pyrazolo[5,1-a]isoquinolines via a copper-catalyzed tandem reaction of 2-alkynylbromobenzene with pyrazole

Article abstract of DOI:10.1021/jo400523v

A copper-catalyzed tandem reaction of 2-alkynylbromobenzene and pyrazole is described that provides a facile route to pyrazolo[5,1-a]isoquinolines in good yields. During the reaction process, copper(I)-catalyzed hydroamination and C-H activation are involved.

Full text of DOI:10.1021/jo400523v

Note
pubs.acs.org/joc
Route to Pyrazolo[5,1‑a]isoquinolines via a Copper-Catalyzed
Tandem Reaction of 2‑Alkynylbromobenzene with Pyrazole
Xiaolin Pan,† Yong Luo,† and Jie Wu*,†,‡
†Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
S
* Supporting Information
ABSTRACT: A copper-catalyzed tandem reaction of 2-
alkynylbromobenzene and pyrazole is described that provides
a facile route to pyrazolo[5,1-a]isoquinolines in good yields.
During the reaction process, copper(I)-catalyzed hydro-
amination and C−H activation are involved.
Scheme 1. Possible Mechanism for the Proposed Synthetic
Route to Pyrazolo[5,1-a]isoquinolines via a Copper-
Catalyzed Tandem Reaction of 2-Alkynylbromobenzene
with Pyrazole
urrently, there is a great demand for access to natural
Cproduct-like compounds in the field of chemical biology
and drug discovery.1,2 Among the privileged scaffolds
constructed, continuous interest has been focused on pyrazolo-
[5,1-a]isoquinolines due to their promising biological activ-
ities.3,4 For instance, pyrazolo[5,1-a]isoquinoline derivatives
show activities for inhibition of CDC25B, TC-PTP, and
PTP1B.4b Additionally, in our preliminary biological evalua-
tions, several compounds were found to be active for inhibition
of cervical carcinoma. In our continuous efforts for the
generation of druglike small molecules, we are interested in
the construction of diverse pyrazolo[5,1-a]isoquinolines with
an expectation of finding more active compounds.
Tandem reaction is regarded as a powerful approach for the
formation of complex heterocycles.5 The advantages and
efficiency of tandem reaction have been well recognized.
Recently, we and others identified that 2-alkynylbromobenzene
was a useful building block for the generation of polycyclic
molecules.6,7 On the basis of this result, we conceived that
pyrazolo[5,1-a]isoquinoline would be produced via a transition-
metal-catalyzed tandem reaction of 2-alkynylbromobenzene
with pyrazole. The proposed synthetic route is described in
Scheme 1. We hypothesized that the reaction would proceed
through a transition-metal-catalyzed hydroamination and C−H
activation.8 The transformation seems feasible on the basis of
the previous results, since Verma and Larock reported the
generation of indolo- and pyrrolo[2,1-a]isoquinolines via a
copper(I)-catalyzed reaction of 2-alkynylbromobenzene with
indole or pyrrole.9 However, there are still some challenges for
this reaction between pyrazole and 2-alkynylbromobenzene.
For instance, the direct coupling of 2-alkynylbromobenzene 1
and pyrazole 2 would easily lead to the formation of C−N
bond10 which should be excluded in our protocol. Moreover,
C−H activation of pyrazole is usually catalyzed by the
palladium catalyst, with only two examples of copper catalyst
reported. For example, Daugulis and Xi reported the copper-
catalyzed arylation of arenes via C−H bond activation
independently.11 Compared with the palladium catalyst,
copper(I) salts obviously would be more attractive. We
envisioned that the transformation would be possible if the
copper(I) salt could serve as the catalyst for the subsequent C−
H activation as well. With these results in mind, we proposed
that a copper(I)-catalyzed hydroamination of 2-alkynylbromo-
benzene with pyrazole would occur to generate compound A.12
Subsequently, an oxidative addition of Cu(I) to aryl bromide A
would afford intermediate B, which would undergo intra-
molecular attack with the subsequent deprotonation of pyrazole
Received: March 23, 2013
© XXXX American Chemical Society
A
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Note
Table 1. Initial Studies for the Copper-Catalyzed Reaction of 2-Alkynylbromobenzene 1a with Pyrazole 2a
a
entry
[Cu]
ligand
base
solvent
yield (%)
1
CuOTf
Cu2O
CuCl
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L8
L9
L8
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
KOH
DMF
NR
trace
14
2
DMF
3
DMF
4
DMF
15
5
toluene
dioxane
NMP
NR
NR
NR
34
6
7
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
9
40
10
11
12
13
14
15
16
17
18
19
20
tBuONa
tBuOLi
NaH
33
34
28
KOH
43
KOH
39
KOH
30
KOH
41
KOH
45
KOH
45
KOH
51
KOH
46
b
21
KOH
65
b
22
KOH
40
a
b
Isolated yield based on pyrazole 2a. In the presence of 2,6-diethylaniline (10 mol %).
ring to produce intermediate C. Reductive elimination of
intermediate C would furnish the expected pyrazolo[5,1-
a]isoquinoline 3. Encouraged by the previous results as
mentioned above, we began to explore this copper-catalyzed
tandem reaction of 2-alkynylbromobenzene 1 and pyrazole 2.
For the model reaction, 2-alkynylbromobenzene 1a with
pyrazole 2a was adopted. The preliminary screening for the
reaction was performed in the presence of copper(I) catalyst
(10 mol %) at 110 °C (Table 1). Various copper sources were
screened first, but only a trace amount of product was observed
when the reaction occurred in the presence of L1 (20 mol %),
Cu2O, and t-BuOK in DMF at 110 °C (Table 1, entry 2). No
reaction took place when the copper salt was changed to
CuOTf (Table 1, entry 1). The reaction could proceed leading
to the desired product 3a in 14% yield catalyzed by copper(I)
chloride in the presence of ligand L1 and t-BuOK in DMF
(Table 1, entry 3). No reaction occurred in a control
experiment without the addition of ligand L1 (data not
shown in Table 1). A similar yield was obtained when the
catalyst was changed to copper(I) iodide (Table 1, entry 4).
The reaction could not proceed when the solvent was changed
to toluene, 1,4-dioxane, or NMP (Table 1, entries 5−7).
Interestingly, the yield was improved when the reaction was
performed in DMSO, giving rise to the corresponding product
3a in 34% yield (Table 1, entry 8). Subsequently, different
bases were examined, which identified that potassium
hydroxide was the best choice (40% yield, Table 1, entry 9).
With these results in hand, we next screened various ligands. To
our delight, the desired product 3a was obtained in 51% yield
when N-heterocyclic carbene L8 was employed in the reaction
as a ligand (Table 1, entry 19). However, other ligands (such as
X-Phos) were ineffective in this reaction. After careful
investigation, we found that the addition of 10 mol % of 2,6-
diethylaniline would increase the final outcome of the reaction,
which afforded compound 3a in 65% yield (Table 1, entry 21).
The yield was reduced to 40% without the addition of ligand L8
in the presence of 10 mol % of 2,6-diethylaniline (Table 1,
entry22). However, the role of 2,6-diethylaniline remains
uncertain. The presence of other anilines could not improve
the yield. The reaction became complex when the temperature
B
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Note
was lowered, while higher temperature could not enhance the
yield. Furthermore, other additive such as silver salts and other
amines could not improve the final outcome.
The reaction scope was then examined under the optimized
conditions (10 mol % of CuI, 10 mol % of ligand L8, 10 mol %
of 2,6-diethylaniline, 2.0 equiv of KOH, DMSO, 110 °C). The
results are summarized in Scheme 2 for the evaluation of
EXPERIMENTAL SECTION
■
General Experimental Procedure for the Copper-Catalyzed
Tandem Reaction of 2-Alkynylbromobenzene with Pyrazole.
2-Alkynylbromobenzene 1 (0.25 mmol) was added to a mixture of CuI
(10 mol %), NHC L8 (10 mol %), 2,6-diethylbenzeneamine (10 mol
%), pyrazole 2 (0.2 mmol), and KOH (2.0 equiv) in DMSO (2.0 mL)
under nitrogen atmosphere. The mixture was heated at 110 °C. After
consumption of the starting material as indicated by TLC, the reaction
mixture was cooled to room temperature. The solvent was diluted by
EtOAc (10 mL), washed with saturated brine (2 × 10 mL), and dried
by anhydrous Na2SO4. Evaporation of the solvent followed by
purification on silica gel (petroleum ether/ethyl acetate = 16:1)
provided the product 3.
Scheme 2. Copper-Catalyzed Tandem Reaction of 2-
a
Alkynylbromobenzenes 1 with Pyrazoles 2
5-Phenylpyrazolo[5,1-a]isoquinoline (3a).4a Yellow solid. Mp:
145.2−146.0 °C. Weight: 32.0 mg. Yield: 65%. H NMR (400 MHz,
1
CDCl3): δ 8.09 (d, J = 6.9 Hz, 1H), 7.99 (s, 1H), 7.87 (d, J = 6.9 Hz,
2H), 7.72−7.70 (m, 1H), 7.52−7.48 (m, 5H), 7.07−7.02 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ 140.7, 139.2, 138.3, 133.7, 129.3, 129.2,
128.8, 128.3, 127.8, 127.2, 127.0, 123.9, 123.4, 112.5, 97.7.
5-(p-Tolyl)pyrazolo[5,1-a]isoquinoline (3b). Yellow solid. Mp:
1
134.8−135.2 °C. Weight: 26.9 mg. Yield: 52%. H NMR (400 MHz,
CDCl3): δ 8.10−8.09 (m, 1H), 7.98 (s, 1H), 7.78−7.70 (m, 3H),
7.54−7.52 (m, 2H), 7.33 (d, J = 7.8 Hz, 2H), 7.07−7.01 (m, 2H), 2.43
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 140.7, 139.3, 138.6, 130.9,
129.3, 129.2, 129.0, 127.8, 127.1, 127.0, 125.9, 123.9, 123.5, 112.1,
97.7, 21.4. HRMS (ESI): calcd for C18H15N2 259.1230 (M + H+),
found 259.1247.
5-(4-Methoxyphenyl)pyrazolo[5,1-a]isoquinoline (3c). Yellow
1
solid. Mp: 138.5−139.2 °C. Weight: 28.1 mg. Yield: 51%. H NMR
(400 MHz, CDCl3): δ 8.08−8.07 (m, 1H), 7.99 (s, 1H), 7.83 (d, J =
8.2 Hz, 2H), 7.70−7.65 (m, 2H), 7.52−7.50 (m, 2H), 7.05−7.00 (m,
3H), 3.86 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.3, 140.7,
139.3, 138.2, 130.7, 129.2, 127.8, 127.0, 126.9, 126.1, 123.8, 123.4,
113.7, 111.8, 97.7, 29.6. HRMS (ESI): calcd for C18H15N2O 275.1179
(M + H+), found 275.1185.
5-(4-Chlorophenyl)pyrazolo[5,1-a]isoquinoline (3d). White sol-
1
id.Mp: 173.9−174.8 °C. Weight: 38.2 mg. Yield: 68%. H NMR (400
MHz, CDCl3): δ 8.10 (d, J = 7.3 Hz, 1H), 7.98 (s, 1H), 7.83 (d, J = 8.2
Hz, 2H), 7.73−7.71 (m, 1H), 7.58−7.48 (m, 4H), 7.08−7.01 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 140.8, 139.3, 137.2, 135.2, 132.1,
130.7, 128.9, 128.6, 128.0, 127.5, 127.1, 124.0, 123.5, 112.6, 97.9.
HRMS (ESI): calcd for C17H12ClN2 279.0684 (M + H+), found
279.0688.
a
Isolated yield based on pyrazole 2.
8-Chloro-5-phenylpyrazolo[5,1-a]isoquinoline (3e). White solid.
1
Mp: 114.3−115.1 °C. Weight: 36.3 mg. Yield: 65%. H NMR (400
MHz, CDCl3): δ 7.99−7.97 (m, 2H), 7.84 (d, J = 6.4 Hz, 2H), 7.66 (s,
1H), 7.52−7.45 (m, 4H), 7.02−7.82 (s, 1H), 6.9 (s, 1H). 13C NMR
(100 MHz, CDCl3): δ 141.1, 139.6, 138.7, 133.6, 133.4, 130.3, 129.5,
129.3, 128.4, 127.7, 126.2, 124.9, 122.3, 111.3, 98.1. HRMS (ESI):
calcd for C17H12ClN2 279.0684 (M + H+), found 279.0694.
5-(4-(tert-Butyl)phenyl)pyrazolo[5,1-a]isoquinoline (3f). Yellow
solid. Mp: 96.1−97.1 °C. Weight: 31.2 mg. Yield: 52%. 1H NMR
(400 MHz, CDCl3): δ 8.11−8.09 (m, 1H), 8.01 (s, 1H), 7.83 (d, J =
7.8 Hz, 2H), 7.72−7.70 (m, 1H), 7.56−7.52 (m, 4H), 7.07−7.03 (m,
2H), 1.38 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 152.3, 140.8,
139.3, 138.5, 130.9, 129.2, 129.1, 127.8, 127.1, 125.3, 123.9, 123.5,
112.3, 97.8, 37.8, 31.3 HRMS (ESI): calcd for C21H21N2 301.1699 (M
+ H+), found 301.1699.
various substituted 2-alkynylbromobenzenes 1 with pyrazoles 2.
These reactions proceeded well, leading to the corresponding
pyrazolo[5,1-a]isoquinolines 3 in good yields. A better result
was obtained when 2-alkynylbromobenzene 1 with an electron-
withdrawing aryl groups attached on the triple bond (R2
position) was employed in the reaction. Various substrates
with different substituents on the aromatic ring of 2-
alkynylbromobenzene 1 or attached on the pyrazole 2 worked
well under the standard conditions, giving rise to the desired
products in moderate to good yields. Unfortunately, only a
trace amount of the corresponding products were detected
when the terminal alkyne or alkyl-substituted alkynes (n-butyl
or cyclopropyl) were used as the substrates in the trans-
formation.
8-Chloro-5-(4-methoxyphenyl)pyrazolo[5,1-a]isoquinoline (3g).
1
Yellow solid. Mp: 134.5−135.0 °C. Weight: 34.7 mg. Yield: 56%. H
NMR (400 MHz, CDCl3): δ 7.98−7.96 (m, 2H), 7.81 (d, J = 8.7 Hz,
2H), 7.65 (m, 1H), 7.45−7.43 (m, 1H), 7.05−7.01 (m, 3H), 6.87 (s,
1H), 3.87 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.5, 141.0,
139.3, 138.7, 133.5, 130.7, 130.4, 127.4, 126.0, 125.7, 124.9, 122.1,
113.8, 110.6, 98.0, 29.6. HRMS (ESI): calcd for C18H14ClN2O
309.0789 (M + H+), found 309.0796.
In summary, we have described a copper-catalyzed tandem
reaction of 2-alkynylbromobenzene with pyrazole, providing a
facile route for the synthesis of pyrazolo[5,1-a]isoquinolines.
The reaction involves copper(I)-catalyzed hydroamination and
C−H activation during the process.
1-Methyl-5-phenylpyrazolo[5,1-a]isoquinoline (3h).4a White
1
solid. Mp: 130.5−131.4 °C. Weight: 23.4 mg. Yield: 45%. H NMR
(400 MHz, CDCl3): δ 8.27 (d, J = 7.8 Hz, 1H), 7.85−7.80 (m, 3H),
C
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Note
7.70 (d, J = 7.3 Hz, 1H), 7.57−7.46 (m, 5H), 6.95 (s, 1H), 2.65 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 142.0, 138.5, 135.1, 134.0,
129.4, 129.3, 129.1, 128.3, 127.1, 126.0, 125.6, 123.1, 112.3, 110.0,
11.8.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jie_wu@fudan.edu.cn.
2,5-Diphenylpyrazolo[5,1-a]isoquinoline (3i).13 Yellow solid. Mp:
Notes
1
140.8−141.5 °C. Weight: 51.4 mg. Yield: 80%. H NMR (400 MHz,
The authors declare no competing financial interest.
CDCl3): δ 8.09 (d, J = 6.8 Hz, 1H), 7.01−7.97 (m, 3H), 7.68−7.66
(m, 1H), 7.53−7.47 (m, 5H), 7.42−7.39 (m, 2H), 7.36−7.30 (m, 3H),
7.01 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 140.7, 138.3, 133.7,
133.3, 129.7, 129.5, 129.2, 128.6, 128.1, 127.9, 127.2, 126.4, 126.3,
123.9, 123.5, 123.3, 112.5, 94.7.
ACKNOWLEDGMENTS
■
Financial support from National Natural Science Foundation of
China (Nos. 21032007, 21172038) is gratefully acknowledged.
5-(4-Chlorophenyl)-2-phenylpyrazolo[5,1-a]isoquinoline (3j). Yel-
1
low solid. Mp: 159.8−160.2 °C. Weight: 58.8 mg. Yield: 83%. H
NMR (400 MHz, CDCl3): δ 7.98−7.91 (m, 3H), 7.85 (d, J = 7.3 Hz,
2H), 7.55 (d, J = 6.9 Hz, 1H), 7.44−7.45 (m, 6H), 7.31−7.27 (m,
1H), 7.23 (s, 1H), 6.86 (s, 1H). 13C NMR (100 MHz, CDCl3): δ
152.1, 140.5, 136.9, 134.9, 133.1, 132.0, 130.9, 130.7, 128.9, 128.5,
128.2, 127.8, 127.3, 126.3, 123.8, 123.4, 123.2, 112.4, 94.8. HRMS
(ESI): calcd for C23H16ClN2 355.0997 (M + H+), found: 355.0990.
9-Methyl-2,5-diphenylpyrazolo[5,1-a]isoquinoline (3k).3f Yellow
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solid. Mp: 125.8−126.5 °C. Weight: 40.9 mg. Yield: 61%. H NMR
(400 MHz, CDCl3): δ 8.02−7.98 (m, 3H), 7.91 (s, 1H), 7.58 (d, J =
7.8 Hz, 1H), 7.51−7.49 (m, 3H), 7.43−7.39 (m, 2H), 7.33−7.31 (m,
4H), 6.99 (s, 1H), 2.53 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
152.0, 140.5, 137.5, 137.3, 133.8, 133.4, 129.6, 129.5, 129.0, 128.5,
128.1, 127.0, 126.4, 126.2, 123.9, 123.3, 112.5, 94.5. HRMS (ESI):
calcd for C24H19N2 335.1543 (M + H+), found 335.1538.
2-(4-Methoxyphenyl)-5-phenylpyrazolo[5,1-a]isoquinoline (3l).3f
1
Yellow solid. Mp: 128.9−129.9 °C. Weight: 40.8 mg. Yield: 58%. H
NMR (400 MHz, CDCl3): δ 8.10 (d, J = 6.9 Hz, 1H), 8.02 (d, J = 6.9
Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 7.71−7.69 (m, 1H), 7.52−7.48 (m,
5H), 7.29 (s, 1H), 7.02 (s, 1H), 6.95 (d, J = 8.7 Hz, 2H), 3.83 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 159.8, 152.1, 140.7, 138.4, 133.8,
129.6, 129.3, 129.1, 128.1, 127.8, 127.6, 127.1, 126.2, 123.8, 123.5,
114.5, 112.2, 94.3, 29.7. HRMS (ESI): calcd for C24H19N2O 351.1492
(M + H+), found 351.1500.
2-(4-Methoxyphenyl)-5-(p-tolyl)pyrazolo[5,1-a]isoquinoline
(3m). Yellow solid. Mp: 120.4−121.0 °C. Weight: 37.1 mg. Yield: 51%.
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 6.9 Hz, 1H), 7.93−7.90
(m, 3H), 7.70−7.68 (m, 1H), 7.50−7.49 (m, 2H), 7.34−7.28 (m, 3H),
7.00−6.93 (m, 4H), 3.82 (s, 3H), 2.45 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 159.7, 152.0, 140.7, 139.1, 138.4, 130.9, 129.5, 129.4, 128.8,
127.8, 127.6, 127.0, 126.2, 123.7, 123.4, 118.3, 113.9, 111.8, 94.2, 29.7,
21.4. HRMS (ESI): calcd for C25H21N2O 365.1648 (M + H+), found
365.1630.
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isoquinoline (3n). Yellow solid. Mp: 143.4−144.2 °C. Weight: 46.4
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131, 2796.
1
mg. Yield: 60%. H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 7.3 Hz,
1H), 7.94−7.87 (m, 4H), 7.65 (d, J = 7.8 Hz, 1H), 7.51−7.45 (m,
4H), 7.24 (s, 1H), 6.95−6.93 (m, 3H), 3.81 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 159.7, 152.1, 140.7, 137.1, 135.0, 132.2, 130.9, 129.1,
128.3, 127.9, 127.6, 127.3, 127.2, 126.0, 123.9, 123.4, 114.1, 112.1,
94.3, 29.7. HRMS (ESI): calcd for C24H18ClN2O: 385.1102 (M + H+),
found 385.1099.
(8) (a) Nishino, M.; Hirano, K.; Tetsuya, S.; Miura, M. Angew. Chem.,
Int. Ed. 2013, 52, 4457. (b) Zhao, D.; Wang, W.; Yang, F.; Lan, J.;
Yang, L.; Gao, G.; You, J. Angew. Chem., Int. Ed. 2009, 48, 3296.
(c) Zou, L.; Mottweiler, J.; Priebbenow, D. L.; Wang, J.; Stubenrauch,
J. A.; Bolm, C. Chem.Eur. J. 2013, 19, 3302. (d) Nishino, M.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 6993.
(e) Hirano, K.; Miura, M. Chem. Commun. 2012, 48, 10704. (f) Qin,
X.; Feng, B.; Dong, J.; Li, X.; Xue, Y.; Lan, J.; You, J. J. Org. Chem.
2012, 77, 7677. (g) Mao, Z.; Wang, Z.; Xu, Z.; Huang, F.; Yu, Z.;
Wang, R. Org. Lett. 2012, 14, 3854. (h) Fan, S.; Chen, Z.; Zhang, X.
Org. Lett. 2012, 14, 4950.
8-Chloro-2-(4-methoxyphenyl)-5-phenylpyrazolo[5,1-a]-
isoquinoline (3o). Yellow solid. Mp: 163.6−164.4 °C. Weight: 35.3
1
mg. Yield: 46%. H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 8.00−
7.98 (m, 2H), 7.89 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 1H), 7.52−
7.50 (m, 3H), 7.46−7.43 (m, 1H), 7.25−7.24 (m, 1H), 6.96−6.94 (m,
3H), 3.83 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.9, 152.4,
139.7, 138.6, 133.5, 132.8, 129.6, 129.3, 128.6, 128.3, 128.2, 127.7,
125.9, 124.8, 122.9, 114.1, 111.3, 94.7, 29.7. HRMS (ESI): calcd for
C24H18ClN2O 385.1102 (M + H+), found 385.1085.
(9) Verma, A. K.; Kesharwani, T.; Singh, J.; Tandon, V.; Larock, R. C.
Angew. Chem., Int. Ed. 2009, 48, 1138.
ASSOCIATED CONTENT
■
(10) For selected examples, see: (a) Cristau, H.; Cellier, P. P.;
Spindler, J.; Taillefer, M. Eur. J. Org. Chem. 2004, 695. (b) Kumar, S.;
Ila, H.; Junjappa, H. J. Org. Chem. 2009, 74, 7046. (c) Monnier, F.;
Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 6954. (d) Meldal, M.;
Tornøe, W. C. Chem. Rev. 2008, 108, 2952.
S
* Supporting Information
1
Copies of H and 13C NMR spectra for the products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
D
dx.doi.org/10.1021/jo400523v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(11) (a) Do, H.; Khan, R. M. K.; Daugulis, O. J. Am. Chem. Soc. 2008,
130, 15185. (b) Liao, Q.; Zhang, L.; Li, S.; Xi, C. Org. Lett. 2011, 13,
228.
(12) (a) Verma, A. K.; Joshi, M.; Singh, V. P. Org. Lett. 2011, 13,
1630. (b) Joshi, M.; Tiwari, R.; Verma, A. K. Org. Lett. 2012, 14, 1106.
(c) Verma, A. K.; Jha, R. R.; Chaudhary, R.; Tiwari, R. K.; Reddy, K. S.
K.; Danodia, A. J. Org. Chem. 2012, 77, 8191. (d) Tsuchimoto, T.;
Aoki, K.; Wagatsuma, T.; Suzuki, Y. Eur. J. Org. Chem. 2008, 4035.
(13) Chen, Z.; Yang, X.; Wu, J. Chem. Commun. 2009, 23, 3469.
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dx.doi.org/10.1021/jo400523v | J. Org. Chem. XXXX, XXX, XXX−XXX