Metal cocatalyzed tandem alkynylative cyclization reaction of in situ formed N-iminoisoquinolinium ylides with bromoalkynes via C-H bond activation

Article abstract of DOI:10.1021/jo3013429

Silver triflate and copper(I) iodide cocatalyzed direct alkynylation and cyclization reaction of in situ formed N-iminoisoquinolinium ylides with bromoalkynes is described. The reaction proceeds efficiently through a combination of C-H activation and subs

Full text of DOI:10.1021/jo3013429

Article
pubs.acs.org/joc
Metal Cocatalyzed Tandem Alkynylative Cyclization Reaction of in
Situ Formed N‑Iminoisoquinolinium Ylides with Bromoalkynes via
C−H Bond Activation
Ping Huang,† Qin Yang,‡ Zhiyuan Chen,*,† Qiuping Ding,† Jingshi Xu,† and Yiyuan Peng*,†,‡
†Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical Engineering,
Jiangxi Normal University, Nanchang, Jiangxi 330022, People's Republic of China
‡Key Laboratory of Green Chemistry, Jangxi Province and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi
330022, People's Republic of China
S
* Supporting Information
ABSTRACT: Silver triflate and copper(I) iodide cocatalyzed
direct alkynylation and cyclization reaction of in situ formed
N-iminoisoquinolinium ylides with bromoalkynes is described.
The reaction proceeds efficiently through a combination of
C−H activation and subsequent tandem reaction in one pot,
leading to diverse H-pyrazolo[5,1-a]isoquinolines in good
yields under mild reaction conditions.
TC-PTP, and PTP1B. Therefore, a large collection of diverse
H-pyrazolo[5,1-a]isoquinolines is in great demand in the
discovery of lead compounds.
INTRODUCTION
■
Transition-metal-catalyzed C−H activation/functionalization
reactions have emerged as an attractive strategy for the
synthesis of interesting natural product like or pharmaceutical
compounds.1 The attraction to applying C−H direct
functionalization in complex molecule synthesis originates
from the notion that C−H bonds can be regarded as potential
synthetic equivalents of various active functional groups.
However, the principal challenge in the theme of C−H
activation that limits its synthetic application is its chemo- and
regioselectivity, especially for a C−H bond targeted over the
others that ubiquitously exist in a complex organic molecule. In
1993, Murai reported in a pioneering work that a pendant
heteroatom could function as a directing group to achieve
selectivity.2 Since then, many directing groups that contain
heteroatoms, such as −OH,3 −NH2,4 imine,5 −COOR,6
amide,7 heterocyclics,8 etc., have been well developed. Recently,
Charette described palladium-catalyzed direct alkenylation
reactions of N-iminopyridinium ylides to produce 2-substituted
pyrazolo[1,5-a]pyridines, through a combination of C−H
activation and a subsequent tandem reaction process in one
reaction vessel.9 Although N-activated pyridines have emerged
as versatile scaffolds whereby complex pyridine derivatives can
be prepared,9a the N-iminoisoquinolinium ylides, especially for
those in situ generated ylides used as directing groups for
further C−H activation transformations, still remain largely
unexplored.
The synthesis of H-pyrazolo[5,1-a]isoquinolines has been
developed by Wu and co-workers.10 They used silver triflate to
catalyze a tandem reaction of N′-(2-alkynylbenzylidene)-
hydrazide 1 with alkynes to produce H-pyrazolo[5,1-a]-
isoquinolines.10g The reaction was believed to occur through
the reactive intermediate N-iminoisoquinolinium ylide A, which
was produced via 6-endo cyclization of N′-(2-alkynylbenzyl-
idene)hydrazide 1 under the catalysis of silver salt, and
following nucleophilic addition of alkynes to the isoquinolinium
intermediate A afforded the corresponding H-pyrazolo[5,1-
a]isoquinolines 3 (Scheme 1). More recently, we have
described a silver triflate and palladium acetate cocatalyzed
tandem reaction of N′-(2-alkynylbenzylidene)hydrazide 1 with
Scheme 1
Recently, the construction of natural product like com-
pounds used in different biological assays has attracted much
attention. We noticed that the compounds with a H-
pyrazolo[5,1-a]isoquinoline core, which incorporates both
isoquinoline and pyrazolo[1,5-a]pyridine skeletons,10 showed
remarkable biological activity for the inhibition of CDC25B,
Received: July 4, 2012
Published: September 4, 2012
© 2012 American Chemical Society
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N-allyl ynamide to produce 2-amino-H-pyrazolo[5,1-a]iso-
elimination reaction would occur to furnish the 1-alkylisoquino-
line compound C. Finally, intramolecular 5-endo cyclization,
protonation, and aromatization reactions would occur, leading
to the functionalized H-pyrazolo[5,1-a]isoquinolines 3. Theo-
retically, the proposed synthetic route is feasible. The efficiency
of multicatalytic processes14 has been demonstrated in tandem
reactions. Usually, the combination of two or more catalysts in
a reaction is powerful for distinct chemical transformations.
Prompted by these results, we conceived that the combination
of bimetal catalysts such as those shown in Scheme 3 would
facilitate the reaction of N′-(2-alkynylbenzylidene)hydrazide 1
with haloalkyne 2 successfully.
quinolines (Scheme 2).11
Scheme 2
RESULTS AND DISCUSSION
■
The initial attempt was performed between the reaction of N′-
(2-alkynylbenzylidene)hydrazide 1a and 1-(2-bromoethynyl)-
benzene 2a. Since silver triflate was demonstrated to be the
most efficient catalyst for the 6-endo cyclization of N′-(2-
alkynylbenzylidene)hydrazide,10g the combinations of silver
triflate and other metal salts were investigated in the model
reaction (Table 1). At the outset, the reaction occurred in the
presence of DBU as the base in dichloroethane (DCE) at room
temperature. Only a trace amount of product was observed
when Pd(PPh3)2Cl2 or Au(PPh3)3Cl was employed as the
cocatalyst in the above reaction (Table 1, entries 1 and 2).
Gratifyingly, the desired product 3a could be isolated in 54%
yield when copper(I) iodide was used as catalyst in the
transformation (Table 1, entry 3). The structure of 3a was
identified by NMR and HRMS (the analogous structure of 3k
was identified unambiguously by X-ray diffraction analysis; see
the Supporting Information). Switching the copper catalyst to
CuBr, CuCl, Cu(OTf)2, or Cu(OAc)2, however, led to
production with lower yields (Table 1, entries 4−7). Next,
we examined the base effect of the reaction (Table 1, entries 8−
12). No better results were generated. Subsequently, different
solvents were screened (Table 1, entries 13−17), and the final
outcome could not be improved. Similar yields (53%) were
On the other hand, as a versatile and useful synthon,
haloalkyne has been widely applied in synthetic organic
chemistry.12 The reactivity of 1-haloalkynes has been
demonstrated recently. For example, Jiang and co-workers
reported an expedient synthesis of functionalized conjugated
enynes through a palladium-catalyzed bromoalkynylation of
alkynes.12f
Encouraged by the results and inspired by the work of
Charette,9 we conceived that haloalkyne might be a good
choice for the reaction development. We envisioned that in the
presence of a suitable transition-metal catalyst, the α-C−H
bond in the N-iminoisoquinolinium ylide intermediate A might
be selectively activated under the direction of an N-imino ylide
group (Scheme 3). Meanwhile, bromoalkyne would be
activated via oxidative addition under the metal catalyst
conditions, which resulted in attack of the in situ formed
isoquinolinium-2-yl amide A and subsequently proceeded
through a concerted metalation/deprotonation (CMD) proc-
ess9c,13 to form intermediate B. Also, the next reductive
Scheme 3. Generation of H-Pyrazolo[5,1-a]isoquinolines via the Reaction of N′-(2-Alkynylbenzylidene)hydrazide 1 with
Bromoalkyne 2
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moiety are of great importance in pharmaceuticals, since the
fluorinated compounds can significantly improve their proper-
ties such as solubility, bioavailability, and metabolic stability.15
Thus, reactions of fluoro-substituted N′-(2-alkynyl-
benzylidene)hydrazides 1f−i were explored. As expected, all
reactions involving 1f−i gave acceptable yields of the tricyclic
products under the standard conditions (entries 17−25).
Although a detailed mechanism has yet to be determined,10
we propose the following mechanism for this one-pot C−H
activation and subsequent tandem cyclization reaction, on the
basis of the above observations (Scheme 4). We believe that the
reaction first occurred through the reactive intermediate N-
iminoisoquinolinium ylides A10 and then proceeds by three
possible routes as depicted in Scheme 4: (1) direct
alkynylation,10i (2) dipolar cycloaddition,10j or (3) C−H
activation alkynykation. First, for the possible route 1, the
electron-deficient carbon, which was linked with a bromo atom
in the bromoalkyne, could not attack the C-1 position of the N-
iminoisoquinolinium ylide A to form B1, therefore ruling out
the possibility of direct alkynylation (1). Second, dipolar
cycloaddition of N-iminoisoquinolinium ylides A with
bromoalkyne may lead to the 2-bromo-H-pyrazolo[5,1-a]-
isoquinoline Br-3 instead of 3. Therefore, we think that the
reaction may involve oxidative addition of the copper(I)
catalyst to haloalkynes16 and then C−H activation alkynylation
of the N-iminoisoquinolinium ylide A to produce H-pyrazolo-
[5,1-a]isoquinoline 3 (route 3). Further exploration of the
mechanism is ongoing in our laboratory.
Table 1. Initial Studies for the Bimetal-Catalyzed Reaction of
N′-(2-Alkynylbenzylidene)hydrazide 1a with 1-(2-
Bromoethynyl)benzene 2a
a
entry
[M]
base
DBU
solvent
T (°C) yield (%)
1
Pd(PPh3)2Cl2
Au(PPh3)3Cl
CuI
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
dioxane
MeCN
toluene
DMF
DCE
DCE
DCE
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
50
70
90
trace
trace
54
45
31
38
42
5
2
DBU
DBU
3
4
CuBr
CuCl
Cu(OTf)2
Cu(OAc)2
CuI
DBU
5
DBU
6
DBU
7
DBU
8
K3PO4
Cs2CO3
DABCO
KOH
K2CO3
DBU
9
CuI
12
8
10
11
12
13
14
15
16
17
18
19
20
CuI
CuI
trace
9
CuI
CuI
45
30
28
43
12
53
62
53
CuI
DBU
CuI
DBU
CuI
DBU
CuI
DBU
CuI
DBU
CuI
DBU
CuI
DBU
CONCLUSION
a
■
Isolated yield based on N′-(2-alkynylbenzylidene) hydrazide 1a.
In summary, we have described a novel and efficient C−H
activation direct alkynylation reaction of in situ formed N-
iminoisoquinolinium ylide with bromoalkyne cocatalyzed by
silver triflate and copper(I) iodide under mild conditions, which
generates diverse H-pyrazolo[5,1-a]isoquinolines in good
yields. A wide substrate scope with good functional group
tolerance has been demonstrated. This method is an alternative
route for the preparation of H-pyrazolo[5,1-a]isoquinolines via
a C−H activation mechanism. Further library construction and
subsequent biological evaluation are in progress in our
laboratory.
obtained when the reaction was performed at 50 or 90 °C
(Table 1, entries 18 and 20). Interestingly, the reaction afforded
the corresponding H-pyrazolo[5,1-a]isoquinoline 3a in 62%
yield when it took place at 70 °C (Table 1, entry 19).
With this promising result in hand, we started to explore the
generality of this bimetal cocatalyzed reaction of N′-(2-
alkynylbenzylidene)hydrazide 1 with bromoalkyne 2 under
the conditions highlighted above (10 mol % of AgOTf, 10 mol
% of CuI, 3.0 equiv of DBU, DCE, 70 °C). The results are
summarized in Table 2. We found that all reactions proceeded
smoothly for the evaluation of various substituted N′-(2-
alkynylbenzylidene)hydrazides 1 and bromoalkynes 2. Not only
2-aryl-substituted bromoalkynes but also 2-alkyl-substituted
bromoalkynes were demonstrated to be good partners in the
transformation. For instance, N′-(2-alkynylbenzylidene)-
hydrazide 1a reacted with 1-(2-bromoethynyl)-4-methoxyben-
zene 2b, leading to the desired H-pyrazolo[5,1-a]isoquinoline
3b in 80% yield (Table 2, entry 2). When 1-(2-bromoethynyl)-
4-chlorobenzene 2c was used as a replacement, the
corresponding product 3c was afforded in 62% yield (Table
2, entry 3). The product was obtained with a slightly higher
yield when 1-bromohex-1-yne 2d or (2-bromoethynyl)-
cyclopropane 2e was employed in the reaction (Table 2,
entries 4 and 5). Reactions of N′-(2-alkynylbenzylidene)-
hydrazide 1b with various bromoalkynes were examined
subsequently, which furnished the desired products in good
yields (Table 2, entries 6−10). We further discovered that
reactions of N′-(2-alkynylbenzylidene)hydrazides 1 bearing
alkyl substituents at the R2 position provided good yields of the
targeted structures using the standard protocol (entries 11−
16). It is well-known that the molecules bearing a fluorine
EXPERIMENTAL SECTION
■
Typical Procedure for the Silver Triflate and Copper(I)
Iodide Cocatalyzed Reaction of N′-(2-Alkynylbenzylidene)-
hydrazide 1 with Bromoalkyne 2. A mixture of N′-(2-
alkynylbenzylidene)hydrazide 1 (0.20 mmol) and silver triflate (10
mol %) in anhydrous DCE (0.5 mL) was heated at 70 °C for 1 h. The
mixture was then cooled to room temperature. Copper(I) iodide (10
mol %) and a solution of DBU (0.6 mmol, 3.0 equiv) with
bromoalkyne 2 (0.3 mmol, 1.5 equiv) in DCE (2.0 mL) were added
subsequently. The mixture was stirred at 70 °C overnight. After
completion of the reaction as indicated by TLC, the solvent was
evaporated. The residue was diluted with EtOAc (10 mL), washed
with H2O (10 mL), and dried over anhydrous MgSO4. Evaporation of
the solvent followed by purification on silica gel provided the
corresponding product 3.
9-Methyl-2,5-diphenylpyrazolo[5,1-a]isoquinoline (3a). Com-
pound 3a was obtained as a white solid: mp 126−127 °C; yield
62%; 1H NMR (400 MHz, CDCl3) δ 2.53 (s, 3H), 6.99 (s, 1H), 7.31−
7.58 (m, 9H), 7.90 (s, 1H), 7.98−8.02 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 21.8, 94.5, 112.4, 123.2, 123.9, 126.3, 127.0, 128.0, 128.5,
129.0, 129.5, 129.6, 133.5, 133.8, 137.3, 137.5, 140.6, 152.0; HRMS
+
calcd for C24H18N2 [M + H]+ 335.1548, found 335.1532.
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Table 2. Silver Triflate and Copper(I) Iodide Cocatalyzed Reaction of N′-(2-Alkynylbenzylidene)hydrazide 1 with Bromoalkyne
2
a
Isolated yield based on N′-(2-alkynylbenzylidene)hydrazide 1.
Scheme 4. Plausible Mechanism for the Formation of H-Pyrazolo[5,1-a]isoquinolines via the Reaction of N′-(2-
Alkynylbenzylidene)hydrazide (1) with Bromoalkyne (2)
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2-(4-Methoxyphenyl)-9-methyl-5-phenylpyrazolo[5,1-a]iso-
quinoline (3b). Compound 3b was obtained as a white solid: mp
178−179 °C; yield 80%; 1H NMR (400 MHz, CDCl3) δ 2.56 (s, 3H),
3.85 (s, 3H), 6.96−7.00 (m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 7.48−7.56
(m, 4H), 7.61 (d, J = 8.0 Hz, 1H), 7.92−7.95 (m, 3H), 8.04 (d, J = 7.5
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.7, 55.2, 94.0, 112.0,
114.0, 123.2, 123.8, 126.2, 127.0, 127.6, 128.0, 129.0, 129.4, 129.6,
133.9, 137.2, 137.5, 140.5, 151.9, 159.7; HRMS calcd for C25H20N2O+
[M + H]+ 365.1654, found 365.1638.
2-Cyclopropyl-5-phenylpyrazolo[5,1-a]isoquinoline (3j). Com-
pound 3j was obtained as a white solid: mp 106−107 °C; yield
1
55%; H NMR (400 MHz, CDCl3) δ 0.86−0.87 (m, 2H), 1.01−1.03
(m, 2H), 2.15−2.18 (m, 1H), 6.67 (s, 1H), 6.95 (s, 1H), 7.46−7.51
(m, 5H), 7.69 (d, J = 7.8 Hz 1H), 7.94 (d, J = 7.8 Hz, 2H), 8.01 (d, J =
6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 9.0, 9.8, 93.2, 111.4,
123.3, 123.6, 127.0, 127.7, 128.2, 129.1, 129.3, 129.5, 133.9, 138.2,
+
140.1, 157.2; HRMS calcd for C20H16N2 [M + H]+ 285.1392, found
285.1367.
2-(4-Chlorophenyl)-9-methyl-5-phenylpyrazolo[5,1-a]iso-
quinoline (3c). Compound 3c was obtained as a light yellow solid: mp
164−165 °C; yield 62%; 1H NMR (400 MHz, CDCl3) δ 2.52 (s, 3H),
6.98 (s, 1H), 7.25 (s, 1H), 7.30−7.40 (m, 3H), 7.50−7.57 (m, 4H),
7.86−7.88 (m, 3H), 7.97 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.8, 94.5, 112.6, 123.2, 123.8, 127.0, 127.1, 127.5, 128.1,
128.7, 129.1, 129.5, 129.6, 132.0, 133.7, 133.8, 137.4, 140.7, 150.8;
5-Cyclopropyl-2-(4-methoxyphenyl)-9-methylpyrazolo[5,1-a]-
isoquinoline (3k). Compound 3k was obtained as a white solid: mp
1
161−162 °C; yield 58%; H NMR (400 MHz, CDCl3) δ 0.94−0.95
(m, 2H), 1.17−1.19 (m, 2H), 2.51 (s, 3H), 2.82−2.83 (m, 1H), 3.85
(s, 3H), 6.52 (s, 1H), 6.99 (d, J = 8.2 Hz, 2H), 7.22 (s, 1H), 7.28 (d, J
= 7.8 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.86 (s, 1H), 7.98 (d, J = 8.2
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 7.6, 11.2, 21.8, 55.4, 94.2,
105.7, 114.2, 123.3, 126.4, 126.7, 127.1, 127.8, 129.4, 134.1, 136.3,
140.1, 140.4, 152.0, 159.8; HRMS calcd for C22H20N2O+ [M + H]+
329.1654, found 329.1639.
+
HRMS calcd for C24H17ClN2 [M + H]+ 369.1159, found 369.1169.
2-Butyl-9-methyl-5-phenylpyrazolo[5,1-a]isoquinoline (3d).
Compound 3d was obtained as a light yellow solid: mp 112−113
1
°C; yield 73%; H NMR (400 MHz, CDCl3) δ 0.96 (t, J = 7.3 Hz,
2-(4-Chlorophenyl)-5-cyclopropyl-9-methylpyrazolo[5,1-a]-
3H), 1.40−1.47 (m, 2H), 1.72−1.78 (m, 2H), 2.50 (s, 3H), 2.84 (t, J =
7.8 Hz, 2H), 6.84 (s, 1H), 6.89 (s, 1H), 7.28 (d, J = 7.8 Hz, 1H),
7.43−7.48 (m, 3H), 7.54 (d, J = 8.2 Hz, 1H), 7.82 (s, 1H), 7.92 (d, J =
7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.9, 21.7, 22.6, 28.4,
31.9, 96.0, 111.5, 123.1, 123.7, 126.8, 126.9, 128.2, 128.9, 129.2, 129.4,
isoquinoline (3l). Compound 3l was obtained as a white solid: mp
1
129−130 °C; yield 58%; H NMR (400 MHz, CDCl3) δ 0.93−0.94
(m, 2H), 1.17−1.19 (m, 2H), 2.51 (s, 3H), 2.79−2.80 (m, 1H), 6.55
(s, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 0.48−7.49
(m, 2H), 7.85 (s, 1H), 7.97 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 7.4, 11.0, 21.7, 94.5, 106.2, 123.1, 126.4, 127.0, 127.6, 128.8,
129.4, 132.3, 133.7, 136.4, 140.1, 140.2, 150.8; HRMS calcd for
+
134.1, 136.9, 137.3, 139.8, 155.0; HRMS calcd for C22H22N2 [M +
H]+ 315.1861, found 315.1834.
+
C21H17ClN2 [M + H]+ 333.1159, found 333.1148.
2-Cyclopropyl-9-methyl-5-phenylpyrazolo[5,1-a]isoquinoline
(3e). Compound 3e was obtained as a white solid: mp 188−189 °C;
yield 65%; 1H NMR (400 MHz, CDCl3) δ 0.85−0.86 (m, 2H), 0.99−
1.02 (m, 2H), 2.14−2.17 (m, 1H), 2.50 (s, 3H), 6.63 (s, 1H), 6.89 (s,
1H), 7.29 (d, J = 8.2 Hz, 1H), 7.42−7.50 (m, 3H), 7.56 (d, J = 7.8 Hz,
1H), 7.80 (s, 1H), 7.93 (d, J = 6.9 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 9.0, 9.8, 21.7, 92.9, 111.4, 123.1, 123.6, 126.9, 127.0, 128.1,
128.9, 129.3, 129.4, 134.0, 137.0, 137.3, 140.0, 157.0; HRMS calcd for
5-Cyclopropyl-2-(4-methoxyphenyl)pyrazolo[5,1-a]isoquinoline
(3m). Compound 3m was obtained as a white solid: mp 108−109 °C;
yield 57%; 1H NMR (400 MHz, CDCl3) δ 0.95−0.96 (m, 2H), 1.18−
1.24 (m, 2H), 2.82−2.87 (m, 1H), 3.84 (s, 3H), 6.54 (s, 1H), 6.99 (d,
J = 8.2 Hz, 2H), 7.24 (s, 1H), 7.44−7.46 (m, 2H), 7.57 (d, J = 6.0 Hz,
1H), 7.98 (d, J = 8.7 Hz, 2H), 8.05 (d, J = 6.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 7.6, 11.1, 55.3, 94.2, 105.5, 114.1, 123.0, 123.4,
126.3, 126.4, 127.6, 127.7, 129.2, 140.1, 141.2, 152.0, 159.7; HRMS
calcd for C21H18N2O+ [M + H]+ 315.1497, found 315.1488.
+
C21H18N2 [M + H]+ 299.1548, found 299.1530.
2,5-Diphenylpyrazolo[5,1-a]isoquinoline (3f). Compound 3f was
obtained as a white solid: mp 142−143 °C; yield 67%; 1H NMR (400
MHz, CDCl3) δ 7.04 (s, 1H), 7.31−7.54 (m, 9H), 7.68−7.72 (m, 1H),
7.98−8.03 (m, 4H), 8.12 (d, J = 7.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 94.8, 112.4, 123.5, 123.9, 126.4, 127.2, 127.3, 127.9, 128.1,
128.6, 129.2, 129.6, 132.2, 133.4, 133.7, 138.4, 140.7, 152.2; HRMS
2-(4-Chlorophenyl)-5-cyclopropylpyrazolo[5,1-a]isoquinoline
(3n). Compound 3n was obtained as a white solid: mp 111−112 °C;
yield 55%; 1H NMR (400 MHz, CDCl3) δ 0.95−0.97 (m, 2H), 1.20−
1.22 (m, 2H), 2.80−2.83 (m, 1H), 6.58 (s, 1H), 7.27 (s, 1H), 7.41−
7.49 (m, 4H), 7.59−7.60 (m, 1H), 7.98 (d, J = 8.2 Hz, 2H), 8.05−8.06
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 7.6, 11.1, 29.7, 94.7, 106.2,
123.0, 123.4, 126.5, 127.6, 127.8, 128.8, 129.2, 132.2, 133.8, 140.2,
+
calcd for C23H16N2 [M + Na]+ 343.1211, found 343.1211.
2-(4-Methoxyphenyl)-5-phenylpyrazolo[5,1-a]isoquinoline (3g).
+
141.2, 160.0; HRMS calcd for C20H15ClN2 [M + H]+ 319.1002,
Compound 3g was obtained as a white solid: mp 130−131 °C;
1
yield 65%; H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H), 6.97 (d, J =
found 319.0995.
8.7 Hz, 2H), 7.04 (s, 1H), 7.31 (s, 1H), 7.51−7.55 (m, 5H), 7.72 (d, J
= 7.6 Hz, 1H), 7.94 (d, J = 8.3 Hz, 2H), 8.04 (d, J = 7.8 Hz, 2H), 8.12
(d, J = 7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.4, 94.4, 112.3,
114.1, 123.6, 124.0, 126.3, 127.1, 127.3, 127.8, 128.0, 128.3, 129.3,
129.4, 129.8, 133.9, 138.5, 140.8, 152.2, 159.9; HRMS calcd for
C24H18N2O+ [M + H]+ 351.1497, found 351.1489.
5-Butyl-2-(4-methoxyphenyl)pyrazolo[5,1-a]isoquinoline (3o).
Compound 3o was obtained as a white solid: mp 105−106 °C;
1
yield 68%; H NMR (400 MHz, CDCl3) δ 1.01 (t, J = 7.3 Hz, 3H),
1.49−1.55 (m, 2H), 1.86−1.92 (m, 2H), 3.20 (t, J = 7.8 Hz, 2H), 3.84
(s, 3H), 6.76 (s, 1H), 6.99 (d, J = 8.0 Hz, 2H), 7.21 (s, 1H), 7.45−7.48
(m, 2H), 7.61 (d, J = 6.8 Hz, 1H), 7.97 (d, J = 8.2 Hz, 2H), 8.04−8.05
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 22.5, 28.9, 30.5, 55.3,
94.0, 109.0, 114.1, 123.3, 123.4, 126.3, 126.4, 127.6, 129.3, 139.7,
140.0, 151.8, 160.0; HRMS calcd for C22H22ON2+ [M + H]+ 331.1810,
found 331.1815.
2-(4-Chlorophenyl)-5-phenylpyrazolo[5,1-a]isoquinoline (3h).
Compound 3h was obtained as a white solid: mp 149−150 °C.
yield 60%; 1H NMR (400 MHz, CDCl3) δ 7.03 (s, 1H), 7.29 (s, 1H),
7.36 (d, J = 8.2 Hz, 2H), 7.50−7.53 (m, 4H), 7.63−7.70 (m, 2H), 7.88
(d, J = 8.2 Hz, 2H), 7.98 (d, J = 6.9 Hz, 2H), 8.07 (d, J = 6.4 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 94.7, 112.7, 116.9, 123.4, 127.1, 127.2,
127.3, 127.6, 128.0, 128.1, 128.7, 129.2, 129.6, 133.4, 133.9, 138.2,
5-Butyl-2-(4-chlorophenyl)pyrazolo[5,1-a]isoquinoline (3p).
Compound 3p was obtained as a white solid: mp 97−98 °C; yield
1
63%; H NMR (400 MHz, CDCl3) δ 1.03 (t, J = 7.2 Hz, 3H), 1.51−
+
140.8, 151.0; HRMS calcd for C23H15ClN2 [M + Na]+ 377.0821,
1.58 (m, 2H), 1.88−1.95 (m, 2H), 3.21 (t, J = 7.5 Hz, 2H), 6.81 (s,
1H), 7.25 (s, 1H), 7.42 (d, J = 7.9 Hz, 2H), 7.49−7.51 (m, 2H), 7.63−
7.66 (m, 1H), 7.97 (d, J = 7.9 Hz, 2H), 8.05−8.07 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 14.0, 22.6, 28.9, 29.7, 30.5, 94.5, 109.6, 123.3,
123.4, 126.5, 127.5, 127.8, 128.8, 129.2, 132.2, 133.8, 139.6, 140.1,
found 377.0830.
2-Butyl-5-phenylpyrazolo[5,1-a]isoquinoline (3i). Compound 3i
1
was obtained as a light yellow solid: mp 115−116 °C; yield 70%; H
NMR (400 MHz, CDCl3) δ 0.96 (t, J = 7.3 Hz, 3H), 1.40−1.50 (m,
2H), 1.72−1.80 (m, 2H), 2.85 (t, J = 7.8 Hz, 2H), 6.87 (s, 1H), 6.93
(s, 1H), 7.44−7.49 (m, 5H), 7.66 (d, J = 7.3 Hz 1H), 7.93 (d, J = 6.4
Hz, 2H), 8.03 (d, J = 7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
13.9, 22.6, 28.4, 32.0, 96.3, 111.6, 123.3, 123.7, 127.0, 127.6, 128.2,
129.1, 129.2, 129.4, 134.0, 138.2, 140.0, 155.2; HRMS calcd for
+
150.8, HRMS calcd for C21H19ClN2 [M + H]+ 335.1315, found
335.1340.
9-Fluoro-2,5-diphenylpyrazolo[5,1-a]isoquinoline (3q). Com-
pound 3q was obtained as a white solid: mp 113−114 °C; yield
1
61%; H NMR (400 MHz, CDCl3) δ 6.93 (s, 1H), 7.22−7.27 (m,
+
C21H20N2 [M + H]+ 301.1705, found 301.1701.
2H), 7.30−7.42 (m, 4H), 7.51 (d, J = 6.4 Hz, 3H), 7.95−8.09 (m,
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Article
5H); 13C NMR (100 MHz, CDCl3) δ 94.5, 111.5, 111.8 (d, 2JCF = 21.8
Hz), 115.8 (d, 2JCF = 23.8 Hz), 120.5, 125.6 (d, 3JCF = 8.6 Hz), 126.4,
13C NMR (100 MHz, CDCl3) δ 7.7, 8.9, 9.8, 11.1, 92.9, 104.1, 110.9
2
2
3
(d, JCF = 21.9 Hz), 114.7 (d, JCF = 23.8 Hz), 119.4, 125.4 (d, JCF
=
3
9.5 Hz), 130.9, 139.2, 142.1, 157.4, 160.6 (d, 1JCF = 246.0 Hz); HRMS
128.3, 128.6, 129.4, 129.6, 130.8 (d, JCF = 8.6 Hz), 132.2, 133.1,
133.3, 139.4, 140.3, 152.5, 160.8 (d, 1JCF = 246.0 Hz); HRMS calcd for
+
calcd for C17H15FN2 [M + H]+ 267.1298, found 267.1273.
+
C23H15FN2 [M + H]+ 339.1298, found 339.1290.
5-Butyl-8-fluoro-2-(4-methoxyphenyl)pyrazolo[5,1-a]iso-
quinoline (3y). Compound 3y was obtained as a white solid: mp 150−
151 °C; yield 63%; 1H NMR (400 MHz, CDCl3) δ 1.01 (t, J = 7.3 Hz,
3H), 1.48−1.54 (m, 2H), 1.84−1.89 (m, 2H), 3.17 (t, J = 7.8 Hz, 2H),
3.84 (s, 3H), 6.66 (s, 1H), 6.98 (d, J = 8.2 Hz, 2H), 7.11 (s, 1H),
7.15−7.19 (m, 1H), 7.24 (d, J = 8.6 Hz, 1H), 7.93−7.96 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 13.9, 22.5, 28.9, 30.5, 55.3, 93.7, 108.2,
2-(4-Chlorophenyl)-9-fluoro-5-phenylpyrazolo[5,1-a]isoquinoline
(3r). Compound 3r was obtained as a light yellow solid: mp 188−189
1
°C; yield 65%; H NMR (400 MHz, CDCl3) δ 6.95 (s, 1H), 7.21−
7.26 (m, 2H), 7.31−7.38 (m, 3H), 7.51−7.52 (m, 3H), 7.86 (d, J = 8.2
Hz, 2H), 7.96 (d, J = 6.4 Hz, 2H), 8.03−8.08 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 94.4, 111.8, 112.0 (d, 2JCF = 23.8 Hz), 115.9 (d, 2JCF
=
3
2
2
23.8 Hz), 120.4, 125.6 (d, JCF = 8.6 Hz), 127.2, 127.6, 128.2, 128.7,
111.0 (d, JCF = 21.0 Hz), 114.1, 114.8 (d, JCF = 23.8 Hz), 119.9,
3
125.5 (d, 3JCF = 8.6 Hz), 126.2, 127.6, 130.9 (d, 3JCF = 9.5 Hz), 139.6,
129.5, 129.6, 131.7, 133.2 (d, JCF = 8.6 Hz), 134.0, 139.3, 140.4,
151.3, 160.8 (d, 1JCF = 246.0 Hz); HRMS calcd for C23H14ClFN2+ [M
1
140.8, 152.1, 159.8, 160.6 (d, JCF = 246.0 Hz), HRMS calcd for
+ H]+ 373.0908, found 373.0916.
C22H21FN2O+ [M + H]+ 349.1716, found 349.1691.
2-Butyl-9-fluoro-5-phenylpyrazolo[5,1-a]isoquinoline (3s). Com-
pound 3s was obtained as a white solid: mp 96−97 °C; yield 55%; 1H
NMR (400 MHz, CDCl3) δ 0.96 (t, J = 7.3 Hz, 3H), 1.40−1.47 (m,
2H), 1.71−1.77 (m, 2H), 2.83 (t, J = 7.3 Hz, 2H), 6.82 (s, 1H), 6.86
(s, 1H), 7.23 (t, J = 6.4 Hz, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.48−7.51
(m, 3H), 7.92 (d, J = 7.3 Hz, 2H), 8.00−8.05 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 13.9, 22.6, 28.4, 31.9, 96.1, 110.7, 111.6 (d, 2JCF =21.0
Hz), 115.5 (d, 2JCF = 23.8 Hz), 120.4, 125.6 (d, 3JCF = 9.5 Hz), 128.3,
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Figures giving H and 13C NMR spectra of all products and
CIF files giving crystallographic data for 3k. This material is
available free of charge via the Internet at http://pubs.acs.org.
3
AUTHOR INFORMATION
Corresponding Author
*E-mail: yiyuanpeng@yahoo.com; zchenjx@yahoo.cn
Notes
129.4, 130.8 (d, JCF = 8.6 Hz), 133.6, 139.3, 139.7, 155.6, 160.6 (d,
■
+
1JCF = 246.0 Hz); HRMS calcd for C21H19FN2 [M + H]+ 319.1611,
found 319.1584.
8-Fluoro-2,5-diphenylpyrazolo[5,1-a]isoquinoline (3t). Com-
pound 3t was obtained as a white solid: mp 121−122 °C; yield
The authors declare no competing financial interest.
1
54%; H NMR (400 MHz, CDCl3) δ 6.94 (s, 1H), 7.22−7.52 (m,
9H), 7.95−8.00 (m, 4H), 8.04−8.08 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 94.5, 111.5, 111.8 (d, 2JCF = 21.9 Hz), 115.8 (d, 2JCF = 23.8
Hz), 120.5, 125.7 (d, 3JCF = 8.6 Hz), 126.4, 127.2, 128.2, 128.3, 129.4,
129.6, 130.8 (d, 3JCF = 9.5 Hz), 133.2, 133.3, 139.4, 140.3, 152.5, 160.8
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(Nos. 20962010 and 21162012) and the Jiangxi Provincial
Department of Science and Technoloy (for Jiangxis Key
Laboratory of Green Chemistry) for their financial support.
■
1
+
(d, JCF = 246.9 Hz); HRMS calcd for C23H15FN2 [M + Na]+
̀
361.1117, found 361.1113.
5-Cyclopropyl-8-fluoro-2-phenylpyrazolo[5,1-a]isoquinoline (3u).
Compound 3u was obtained as a white solid: mp 118−119 °C; yield
REFERENCES
1
■
63%; H NMR (400 MHz, CDCl3) δ 0.96−0.97 (m, 2H), 1.21−1.28
(1) (a) Activation and Functionalization of C-H Bonds; Goldberg, K. I.,
Goldman, A. S., Eds.; American Chemical Society: Washington, DC,
2004; ACS Symposium Series 885. For selected recent reviews, see:
(b) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731.
(c) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826. (d) Kakiuchi,
F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. (e) Kakiuchi, F.
Top. Organomet. Chem. 2007, 24, 1. (f) Seregin, I. V.; Gevorgyan, V.
Chem. Soc. Rev. 2007, 36, 1173. (g) Park, Y.; Park, J.; Jun, C. Acc.
Chem. Res. 2008, 41, 222. (h) Lewis, J. C.; Bergman, R. G.; Ellman, J.
A. Acc. Chem. Res. 2008, 41, 1013. (i) Balcells, D.; Clot, E.; Eisenstein,
O. Chem. Rev. 2010, 110, 749. (j) Colby, D.; Bergman, R.; Ellman, J.
Chem. Rev. 2010, 110, 624. (k) Coperet, C. Chem. Rev. 2010, 110, 656.
́
(l) Conejero, S.; Paneque, M.; Poveda, M.; Santos, L.; Carmona, E.
Acc. Chem. Res. 2010, 43, 572 and references therein..
(2) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529.
(3) (a) Bedford, R.; Coles, S.; Hursthouse, M.; Limmert, M. Angew.
Chem., Int. Ed. 2003, 42, 112. (b) Bedford, R.; Limmert, M. J. Org.
Chem. 2003, 68, 8669.
(4) Jun, C.; Chung, K.; Hong, J. Org. Lett. 2001, 3, 785.
(5) (a) Jun, C.-H.; Hong, J.-B.; Kim, Y.-H.; Chung, K. Y. Angew.
Chem., Int. Ed. 2000, 39, 3440. (b) Thalji, R. K.; Ahrendt, K. A.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001, 123, 9692.
(c) Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. Org. Lett. 2003, 5,
1301. (d) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. J. Am.
Chem. Soc. 2006, 128, 202. (e) Thalji, R. K.; Ahrendt, K. A.; Bergman,
R. G.; Ellman, J. A. J. Org. Chem. 2005, 70, 6775. (f) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2006, 128, 5604.
(g) Parthasarathy, K.; Jeganmohan, M.; Cheng, C. Org. Lett. 2008, 10,
325.
(m, 2H), 2.85−2.87 (m, 1H), 6.47 (s, 1H), 7.17−7.24 (m, 3H), 7.36
(t, J = 6.8 Hz, 1H), 7.44−7.48 (m, 2H), 8.01−8.05 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 7.9, 11.1, 94.5, 105.0, 111.1 (d, 2JCF = 21.0 Hz),
114.9 (d, 2JCF = 23.8 Hz), 119.7, 125.5 (d, 3JCF = 8.6 Hz), 126.4, 128.2,
3
128.7, 130.9 (d, JCF = 9.5 Hz), 133.5, 139.7, 142.5, 152.4, 160.7 (d,
+
1JCF = 246.0 Hz); HRMS calcd for C20H15FN2 [M + H]+ 303.1298,
found 303.1312.
5-Cyclopropyl-8-fluoro-2-(4-methoxyphenyl)pyrazolo[5,1-a]-
isoquinoline (3v). Compound 3v was obtained as a white solid: mp
1
110−111 °C; yield 56%; H NMR (400 MHz, CDCl3) δ 0.95−0.96
(m, 2H), 1.19−1.21 (m, 2H), 2.84−2.86 (m, 1H), 3.85 (s, 3H), 6.43
(s, 1H), 6.98 (d, J = 7.4 Hz, 2H), 7.15−7.24 (m, 3H), 7.96 (d, J = 8.7
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 7.9, 11.1, 55.3, 94.0, 104.6,
2
2
111.0 (d, JCF = 21.9 Hz), 114.1, 114.8 (d, JCF = 23.8 Hz), 119.6,
125.5 (d, 3JCF = 9.5 Hz), 127.7, 130.9 (d, 3JCF = 9.5 Hz), 139.7, 142.5,
1
152.3, 159.8, 160.7, 163.1 (d, JCF = 246.0 Hz); HRMS calcd for
C21H17FN2O+ [M + H]+ 333.1403, found 333.1388.
2-(4-Chlorophenyl)-5-cyclopropyl-8-fluoropyrazolo[5,1-a]iso-
quinoline (3w). Compound 3w was obtained as a white solid: mp
1
172−173 °C; yield 63%; H NMR (400 MHz, CDCl3) δ 0.95−0.96
(m, 2H), 1.20−1.22 (m, 2H), 2.81−2.82 (m, 1H), 6.47 (s, 1H), 7.17−
7.23 (m, 3H), 7.41 (d, J = 8.2 Hz, 2H), 7.93−8.00 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 7.8, 11.0, 94.4, 105.3, 111.1 (d, 2JCF = 21.9 Hz),
115.0 (d, 2JCF = 23.8 Hz), 119.6, 125.5 (d, 3JCF = 9.5 Hz), 127.6, 128.8,
3
130.9 (d, JCF = 9.5 Hz), 132.0, 134.0, 139.8, 142.4, 151.2, 160.8 (d,
1JCF = 246.0 Hz); HRMS calcd for C20H14ClFN2+ [M + H]+ 337.0908,
found 337.0922.
2,5-Dicyclopropyl-8-fluoropyrazolo[5,1-a]isoquinoline (3x). Com-
pound 3x was obtained as a light yellow solid: mp 101−102 °C; yield
1
46%; H NMR (400 MHz, CDCl3) δ 0.89−0.92 (m, 4H), 1.06−1.08
(m, 2H), 1.18−1.20 (m, 2H), 2.20−2.23 (m, 1H), 2.72−2.76 (m, 1H),
6.41 (s, 1H), 6.57 (s, 1H), 7.14−7.22 (m, 2H), 7.92−7.95 (m, 1H);
(6) (a) Wang, D.; Engle, K.; Shi, B.; Yu, J. Science 2010, 327, 315.
(b) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362.
8097
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(c) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407. (d) Wang,
D.; Mei, T.; Yu, J. J. Am. Chem. Soc. 2008, 130, 17676. (e) Giri, R.; Yu,
J. J. Am. Chem. Soc. 2008, 130, 14082. (f) Zhang, Y.; Yu, J. J. Am. Chem.
Soc. 2009, 131, 14654. (g) Wang, H.; Glorius, F. Angew. Chem., Int. Ed.
2012, 51, 7318.
Ed. 2005, 44, 192. (d) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed.
2005, 44, 214. (e) Pihko, P. M. Angew. Chem., Int. Ed. 2006, 45, 544.
(16) (a) Hickmanl, A. J.; Sanfordl, M. S. Nature 2012, 484, 177.
(b) DeKorver, K. A.; Walton, M. C.; North, T. D.; Hsung, R. P. Org.
Lett. 2011, 3, 4862.
(7) (a) Wang, D.; Wasa, M.; Giri, R.; Yu, J. J. Am. Chem. Soc. 2008,
130, 7190. (b) Wan, X.; Ma, Z.; Li, B.; Zhang, K.; Cao, S.; Zhang, S.;
Shi, Z. J. Am. Chem. Soc. 2006, 128, 7416. (c) Yang, S.; Li, B.; Wan, X.;
Shi, Z. J. Am. Chem. Soc. 2007, 129, 6066.
(8) (a) Asaumi, T.; Matsuo, T.; Fukuyama, T.; Ie, Y.; Kakiuchi, F.;
Chatani, N. J. Org. Chem. 2004, 69, 4433. (b) Chatani, N.; Uemura, T.;
Asaumi, T.; Ie, Y.; Kakiuchi, F.; Murai, S. Can. J. Chem. 2005, 83, 755.
(c) Chen, X.; Hao, X.; Goodhue, C.; Yu, J. J. Am. Chem. Soc. 2006,
128, 6790. (d) Chen, X.; Goodhue, C.; Yu, J. J. Am. Chem. Soc. 2006,
128, 12634. (e) Lutz, A.; Andreas, A.; Born, R. B. Synlett 2007, 2833.
̈
(f) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Gouriaouen, C.; Maseras, F.;
Bruneau, C.; Dixneuf, P. J. Am. Chem. Soc. 2008, 130, 1156.
(g) Ackermann, L.; Vicente, R.; Althammer, A. Org. Lett. 2008, 10,
2299. (h) Ackermann, L; Mulzer, M. Org. Lett. 2008, 10, 5043.
(i) Guan, Z.; Ren, Z.; Spinella, S.; Yu, S.; Liang, Y.; Zhang, X. J. Am.
Chem. Soc. 2009, 131, 729.
(9) (a) Bull, J.; Mousseau, J.; Pelletier, G.; Charette, A. Chem. Rev.
2012, 112, 2642. (b) Mousseau, J.; Bull, J.; Ladd, C.; Fortier, A.;
Roman, D.; Charette, A. J. Org. Chem. 2011, 76, 8243. (c) Mousseau,
J.; Fortier, A.; Charette, A. Org. Lett. 2010, 12, 516.
(10) (a) Chen, Z.; Gao, L.; Ye, S.; Ding, Q.; Wu, J. Chem. Commun.
2012, 48, 3975. (b) Gao, L.; Ye, S.; Ding, Q.; Chen, Z.; Wu, J.
Tetrahedron 2012, 68, 2765. (c) Li, S.; Wu, J. Org. Lett. 2011, 13, 712.
(d) Li, S.; Luo, Y.; Wu, J. Org. Lett. 2011, 13, 4312. (e) Chen, Z.; Pan,
X.; Wu, J. Synlett 2011, 964. (f) Chen, Z.; Wu, J. Org. Lett. 2010, 12,
4856. (g) Ye, S.; Yang, X.; Wu, J. Chem. Commun. 2010, 46, 5238.
(h) Yu, X.; Ye, S.; Wu, J. Adv. Synth. Catal. 2010, 352, 2050. (i) Chen,
Z.; Yang, X.; Wu, J. Chem. Commun. 2009, 3469. (j) Chen, Z.; Ding,
Q.; Yu, X.; Wu, J. Adv. Synth. Catal. 2009, 351, 1692. (k) Chen, Z.; Su,
M.; Yu, X.; Wu, J. Org. Biomol. Chem. 2009, 7, 4641.
(11) Huang, P.; Chen, Z.; Yang, Q.; Peng, Y. Org. Lett. 2012, 14,
2790.
(12) For selected examples, see: (a) Seregin, I. V.; Ryabova, V.;
Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 7742. (b) Trofimov, A.;
Chernyak, N.; Gevorgyan, V. J. Am. Chem. Soc. 2008, 130, 13538.
(c) Tobisu, M.; Ano, Y.; Chatani, N. Org. Lett. 2009, 11, 3250.
(d) Matsuyama, N.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009,
11, 4156. (e) Morishita, T.; Yoshida, H.; Ohshita, J. Chem. Commun.
2010, 46, 640. (f) Li, Y.; Liu, X.; Jiang, H.; Feng, Z. Angew. Chem., Int.
Ed. 2010, 49, 3338. (g) Li, Y.; Liu, X.; Jiang, H.; Liu, B.; Chen, Z.;
Zhou, P. Angew. Chem., Int. Ed. 2011, 50, 6341. (h) Wada, T.; Iwasaki,
M.; Kondoh, A.; Yorimitsu, H.; Oshima, K. Chem. Eur. J. 2010, 16,
10671. (i) Yoshida, H.; Asatsu, Y.; Mimura, Y.; Ito, Y.; Ohshita, J.;
Takaki, K. Angew. Chem., Int. Ed. 2011, 50, 9676.
(13) (a) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc.
2008, 130, 10848. (b) Lafrance, M.; Rowley, C.; Woo, T.; Fagnou, K.
́
J. Am. Chem. Soc. 2006, 128, 8754. (c) Cardenas, D.; Martın-Matute,
́
B.; Echavarren, A. J. Am. Chem. Soc. 2006, 128, 5033.
(14) For selected recent reviews on cooperative catalysis, see:
(a) Ajamian, A.; Gleason, J. L. Angew. Chem., Int. Ed. 2004, 43, 3754.
(b) Lee, J. M.; Na, Y.; Han, H.; Chang, S. Chem. Soc. Rev. 2004, 33,
302. (c) Wasilke, J. C.; Brey, O. S. J.; Baker, R. T.; Bazan, G. C. Chem.
Rev. 2005, 105, 1001. (d) Enders, D.; Grondal, C.; Huttl, M. R. Angew.
Chem., Int. Ed. 2007, 46, 1570. (e) Chapman, C. J.; Frost, C. G.
Synthesis 2007, 1. (f) Walji, A. M.; MacMillan, D. W. C. Synlett 2007,
1477. (g) Wang, C.; Xi, Z. Chem. Soc. Rev. 2007, 36, 1395. (h) Shao,
Z.; Zhang, H. Chem. Soc. Rev. 2009, 38, 2745. (i) Zhong, C.; Shi, X.
Eur. J. Org. Chem. 2010, 2999.
(15) (a) Fluorine in Bioorganic Chemistry; Welch, J. T.,
Eswarakrishman, S., Eds.; Wiley: New York, 1991. (b) Organo¯uorine
Chemistry: Principles and Commercial Applications; Banks, R. E., Smart,
B. E., Tatlow, J. C., Eds.; Plenum Press: New York, 1994. For reviews
on fluorination of organic compounds, see: (c) Nyffeler, P. T.; Duron,
S. G.; Burkart, M. D.; Vincent, S. P.; Wong, C.-H. Angew. Chem., Int.
8098
dx.doi.org/10.1021/jo3013429 | J. Org. Chem. 2012, 77, 8092−8098