Cu-catalyzed direct amidation of aromatic C-H bonds: An access to arylamines

Article abstract of DOI:10.1021/jo5003592

A Cu-catalyzed aromatic C-H amidation with phthalimide under oxygen as a terminal oxidant without using additional additives has been achieved. This reaction has the broad substrate scope and shows moderate to good yields in most cases. This method is complementary to the previously reported metal-catalyzed C-H amination systems.

Full text of DOI:10.1021/jo5003592

Article
pubs.acs.org/joc
Cu-Catalyzed Direct Amidation of Aromatic C−H Bonds: An Access to
Arylamines
Hui Xu,†,‡ Xixue Qiao,† Shiping Yang,‡ and Zengming Shen*,†
†School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
‡The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai
Normal University, Shanghai 200234, China
S
* Supporting Information
ABSTRACT: A Cu-catalyzed aromatic C−H amidation with
phthalimide under oxygen as a terminal oxidant without using
additional additives has been achieved. This reaction has the
broad substrate scope and shows moderate to good yields in
most cases. This method is complementary to the previously
reported metal-catalyzed C−H amination systems.
directing groups using N-OTs phthalimide as amidating reagent
(eq 3).11 We wondered whether an inexpensive copper catalyst
and green and abundant molecular oxygen as a terminal oxidant
are feasible for the intermolecular amination of indoles and 2-
arylpyridines using phthalimide as the amine source (eq 4).
INTRODUCTION
■
The ubiquity of (hetero)arylamines in natural products,
pharmaceuticals, agrochemicals, and organic materials inspires
chemists to develop efficient synthetic methodologies for
constructing C−N bonds.1 Traditional approaches for the
synthesis of arylamines involve nitration of arenes, followed by
reduction.2 Using strongly acidic nitric acid and harsh
conditions in these systems have hampered their broad
applicability. Metal-catalyzed C−N cross-coupling reactions,
such as the Buchwald−Hartwig coupling, Cu-catalyzed Ullman
coupling, and Chan−Evans−Lam coupling, have been
developed as alternative protocols for C−N bond formation
and are a powerful tool for organic chemists.3 Despite these
advances, the requirement for prefunctionalization of arenes to
aryl (pseudo)halides or boronic acids as coupling partner is
inherently required.
Recently, the dehydrogenative cross-coupling of amines and
aromatic C−H moieties as coupling partners has emerged as a
straightforward pathway for the synthesis of (hetero)-
arylamines, which has been a complementary and potentially
more effective process for the formation of C−N bonds.4
However, most cases of metal-catalyzed C−H/N−H cross-
coupling reactions are limited to the use of expensive transition
metals, such as Pd,5 Rh,6 and Ru.7 The amine reagents used in
those amination reactions can be classified as amines, amides,
sulfonamides, N−O reagents, or N−X (X = halogen) reagents.4
Interestingly, phthalimide, which is a valuable ammonia
equivalent and used to synthesize primary amines, called the
Gabriel reaction,8 has recently captured much attention from
chemists. For example, Hartwig and co-workers documented a
Pd-catalyzed intermolecular C−H amination reaction of arenes
with phthalimide to form N-aryl phthalimides using 6 equiv of
PhI(OAc)2 as an oxidant (eq 1).9 Similar works reported by
Chang et al.10a and DeBoef et al.10b were performed in the
presence of PhI(OAc)2 (2.5−5 equiv) without adding any
metal species (eq 2). At the same time, Li et al. demonstrated a
Rh(III) and Ag cocatalyzed C−H amination of arenes bearing
Recently, much effort has been directed toward exploring
economical and environmentally friendly catalysts, which led to
various pioneering advances in Cu-mediated and Cu-catalyzed
direct C−H amination reactions.12 In this context, Yu and co-
workers first reported the stoichiometric Cu-mediated Ar−H
amination of 2-arylpyridines.13a Later, a similar work was
reported by the Chatani group.13b Several improved Cu-
catalyzed inter- and intramolecular versions were achieved by
Brasche and Buchwald,13c Li et al.,13d Su et al.,13e and John and
Received: February 14, 2014
Published: April 15, 2014
© 2014 American Chemical Society
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Nicholas.13f In addition, aminations of acidic C−H bonds of
heterocycles using catalytic Cu/ligand or stoichiometric Ag/
base systems were independently reported by Mori et al.,14a
Wang and Schreiber,14b Chang et al.,14c and others.14d−g More
recently, Daugulis et al.15a and Chen et al.,15b respectively,
documented Cu-catalyzed direct aminations of aromatic C−H
bonds using removable directing groups. However, in some
cases, the use of a stoichiometric amount of oxidant, such as
silver species, N−O oxides, and hypervalent iodine, is
inevitable. All of these pioneering studies inspired us to pursue
a simple Cu/O2 catalytic system for the sp2 C−H bond
amination. Herein, we document a Cu-catalyzed C−H
amidation of N-pyrimidyl(pyridyl) indoles and 2-arylpyridines
under oxygen using phthalimide as an aminating source (eq 4),
which is complementary to the previously reported metal-
catalyzed C−H amination systems.9−11,13−15
sp2 C−H amination process. The use of Cu(OAc)2, Cu(OTf)2,
and Cu(OPiv)2 also provided the desired amination product 3a
with a slightly decreased yield compared to CuOAc (Table 1,
entries 2−4). In contrast, CuCl, CuBr2, and CuCl2 showed no
reactivity for this transformation (Table 1, entries 5−8).
Notably, running reactions in the absence of a copper catalyst
or under a nitrogen atmosphere resulted in no aminated
products, indicating that both oxygen and the copper catalyst
are critical for amination (Table 1, entry 20). The screening of
solvents indicated that nonpolar solvents, including DCE,
anisole, o-dichlorobenzene, and chlorobenzene, efficiently
promoted this transformation, giving 62−81% yields. On the
contrary, performing reactions in polar solvents, such as DMF,
DMSO, CH3CN, 1,4-dioxane, and THF, resulted in nearly no
desired product (Table 1, entries 9−13). Finally, the mixed
solvent of toluene and o-dichlorobenzene (1:1) produced the
corresponding aminated product 3a in 86% yield (Table 1,
entry 18). By reducing the amount of catalyst from 20 to 10
mol %, a decreased yield (71%) was observed (Table 1, entry
19). Hence, the optimal conditions are CuOAc (20 mol %) and
phthalimide (1.2 equiv) under an O2 atmosphere at 150 °C in
toluene/o-dichlorobenzene (1:1).
RESULTS AND DISCUSSION
■
Encouraged by Yu et al.’s report,13a we began our study by
examining the reaction of N-pyrimidyl-substituted indole 1a
with phthalimide 2 in the presence of CuOAc (20 mol %)
under an oxygen atmosphere at 150 °C (Table 1, entry 1). To
our delight, the desired C−H aminated product 3a was
obtained in 60% yield with specific regioselectivity. The
coupling occurred exclusively at the 2-position of the indole.
A series of Cu salts examined during the optimization of
reaction conditions showed a significant role in promoting the
This protocol for CuOAc-catalyzed aromatic C−N coupling
via C−H activation is practical and efficient because green
molecular oxygen is used as oxidant, no additional additives are
needed, and the only byproduct is water. With these optimal
conditions in hand, we explored the scope and limitations of
this method, as shown in Table 2. A wide range of electron-rich
and electron-poor substituted indoles bearing a pyrimidine
directing group were first examined under the standard
Table 1. Cu-Catalyzed sp2 C−H Amination of N-Pyrimidyl
a
Indole
a b
,
Table 2. Amidation of N-Heteroarylindoles
b
entry [cat] (20 mol %)
solvent
T (h) yield (%)
1
2
CuOAc
Cu(OAc)2
Cu(OTf)2
Cu(OPiv)2
CuCl
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMF
48
48
52
72
48
48
48
48
70
70
70
70
70
60
60
60
60
60
60
37
3
49
4
40
5
trace
trace
trace
trace
trace
trace
trace
trace
trace
81
6
CuBr2
7
CuCl2
8
Cu(OH)2
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
9
10
11
12
13
14
15
16
17
18
DMSO
CH3CN
1,4-dioxane
THF
DCE
anisole
61
o-dichlorobenzene
chlorobenzene
56
62
toluene/o-dichlorobenzene
(1:1)
86
c
19
20
CuOAc
none
toluene/o-dichlorobenzene
(1:1)
60
60
71
0
toluene
a
a
Conditions: substrate 1a (0.3 mmol), phthalimide (0.36 mmol), cat.
Conditions: substrate (0.3 mmol), phthNH (0.36 mmol), CuOAc
b
c
(20 mol %), solvent (2 mL), O2 (1 atm), 150 °C. Isolated yield. 10
mol % CuOAc.
(20 mol %), O2 (1 atm), toluene/o-dichlorobenzene (1:1, 2 mL), 150
°C, 2−3 days. Isolated yield.
b
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ab
,
conditions. To our delight, electron-donating groups such as
Me or MeO, on either the indole ring or the pyrimidine
directing group, all provided the corresponding amination
products in moderate to good yields (57−77%). We reasoned
that electron-rich indole substrates are prone to proceeding
intermolecular polymization,16 and resulted in moderate yield
in MeO-substituted substrate 3d. Substrates with electron-
withdrawing groups, including 5-F (1e), 5-Cl (1f), 5-Br (1g),
and 5-CN (1h), which could be used as functional handles for
further transformations, were subjected to the Cu-catalyzed sp2
C−H amination reaction, efficiently giving the amination
products. The strongly electron-deficient NO2-substituted
indole 1i did not undergo amination under the standard
conditions. Besides the pyrimidine group as a directing group,
substrates with pyridine as a directing group also worked well
under the standard conditions (31−78% yields). Notably, the
aldehyde group (1o) was compatible in this system with 31%
yield. Some byproducts were observed possibly due to
decarbonylation, oxidation, or polymerization from 1o, but
because of the complexity of byproducts from 1o, structures
could not be determined yet. Unexpectedly, by switching the
directing group from pyridyl to carbonyl group, N-benzoyl
indole 1p gave the corresponding product 3p, albeit with a low
27% yield. Most of unreacted starting material 1p was
recovered. Other heterocycles, such as benzo[d]oxazole and
benzo[d]thiazole, were attempted, but no desired C−N
coupling product was obtained.
Table 3. Amidation of 2-Arylpyridine Derivatives
Encouraged by the success of a direct C−H amination
reaction of indole derivatives, various substituted 2-arylpyr-
idines were investigated to further extend the generality of this
approach. As shown in Table 3, either electron-rich or electron-
poor groups on the aryl ring gave the corresponding products
with moderate yields. We found that the efficiency of 2-
arylpyridines or 2-arylpyrimidines in this system was inferior to
that of N-substituted indoles. Starting materials did not
disappear completely after 3−4 days. For example, substrate
4a was subjected to the standard conditions to afford the
monoaminated 5a as a major product in 53% yield along with
19% of recovered 4a. By further prolonging the reaction time, a
trace amount of bisamination product could be observed.
Gratifyingly, electron-withdrawing F (4f), Cl (4g), CF3 (4h),
COOMe (4i), and CHO (4j) groups were all well-tolerated
under the standard conditions. It is worth noting that substrate
4e, containing an alkene group on the aryl ring, performed in
this case to provide the desired product 5e in 31% yield. In
addition, our efforts to apply the conditions optimized for 2-
pyrimidyl indole substrates to other types of substrates, such as
2-(naphthalen-2-yl)pyridine and benzo[h]quinoline, were
fruitful. Notably, benzo[h]quinoline 4s underwent amination
in almost quantitative yield (97%).
To test the scope and limitations of amines, the treatment of
N-pyridyl indole 1k with saccharin 2b under the standard
conditions was first carried out. As expected, saccharin 2b
worked well, giving the corresponding product 6a in 43% yield
(Table 4, entry 1). N-pyrimidyl indole 1a and 2-phenylpyridine
5a could also react with saccharin 2b (Table 4, entries 2−4).
To our surprise, benzamide 2c as an amine coupling partner
provided the desired C−N coupling product 6d, although with
a low 22% yield (Table 4, entry 5). We continued attempting
other amine reagents, such as 4-nitroaniline 2d and 2-amine
pyridine 2e, while no obvious corresponding products were
observed (Table 4, entries 5 and 6). Therefore, there is still a
a
Conditions: substrate (0.3 mmol), PhthNH (0.36 mmol), CuOAc
(20 mol %), toluene/o-dichlorobenzene (1:1, 2 mL), 3−4 days, O2 (1
atm), 150 °C. Isolated yield.
b
limitation in amine reagents, which are restricted to amides
with strong electron-withdrawing groups.
In order to gain an understanding of the mechanism of this
aromatic C−H amination, we performed some mechanistic
studies. First, radical inhibitors, such as TEMPO, BHT (2,6-di-
tert-butyl-4-methylphenol), and 1,4-dinitrobenzene, were added
to the reaction under standard conditions, and no significant
decrease in yield was observed (Scheme 1). This result suggests
that a radical pathway for the C−H amination reaction is
possibly unlikely. Next, we investigated the kinetic isotope
effect via intermolecular and intramolecular competition
experiments. The competition between substrate 4a and
deuterated substrate [D2]-4a under the standard conditions
revealed a primary isotope effect (KIE = 3.7, Scheme 2, eq 5).
An intramolecular competition experiment using substrate [D]-
4a was further measured, giving a KIE of 2.1 (Scheme 2, eq 6).
These experiments indicated that the C−H bond activation is a
rate-determining step in the Cu-catalyzed C−H amination
reaction.
On the basis of the above mechanistic studies and previous
findings,17 a tentative mechanism was proposed as shown in
Scheme 3. First, the in situ generation of the active Cu(II)
species occurs by oxidation with O2. The coordination of
pyrimidyl group in the substrate 1a to the copper(II) center is
followed by the disproportionative C−H activation reaction
with another Cu(II) species that produces the aryl-Cu(III)
intermediate 8 and a Cu(I) species.17 Subsequently, phthali-
mide coordinates to the aryl-Cu(III) center and the reductive
elimination of Cu(III) intermediate 9 takes place to provide the
corresponding aminated product 3a and a Cu(I) species, which
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ab c
, ,
Table 4. Scope and Limitation of Amines
a
Conditions: substrate (0.2 mmol), CuOAc (20 mol %), amine (0.2 mmol), toluene/o-dichlorobenzene (1:1, 2 mL), 2−3.5 days, O2 (1 atm), 150
b
c
°C. Isolated yield. Not determined.
advantage for this intermolecular transformation. This reaction
has the broad substrate scope and shows moderate to good
yields in most cases. Further exploration of the generality and
application of this approach is ongoing in our lab.
Scheme 1. Radical Inhibitor Experiments
EXPERIMENTAL SECTION
■
General. All experiments were carried out under an oxygen
atmosphere unless otherwise noted. Reactions were monitored using
thin-layer chromatography (TLC). Toluene was dried and distilled
before use according to the standard method.18 1H, 13C, and 19F NMR
spectra were obtained at 400, 100, and 400 MHz, respectively. NMR
spectra were run in a solution of deuterated chloroform (CDCl3) and
were reported in parts per million (ppm). Abbreviations for signal
multiplicity are as follows: s = singlet, d = doublet, t = triplet, q =
quartet, p = pentet, m = multiplet, dd = doublet of doublet, etc.
Coupling constants (J values) were calculated directly from NMR
spectra. High-resolution mass spectra (HRMS) were recorded using
electrospray ionization (ESI) techniques. Infrared spectra were
obtained using an FT-IR spectrometer.
would be oxidized by O2 under acidic conditions to regenerate
the Cu(II) species and water as a byproduct. Nevertheless, at
present, we cannot completely exclude a single electron transfer
(SET) pathway as proposed by Yu et al.13a
CONCLUSIONS
■
In conclusion, we have developed a simple and practical Cu-
catalyzed C−H amination of N-pyrimidyl(pyridyl) indoles and
2-arylpyridines using phthalimide as an aminating source. The
employment of inexpensive CuOAc as the catalyst and
molecular oxygen as the terminal oxidant is a significant
Preparation of Starting Materials 1 and 4. N-Substituted
indole derivatives (1a−1o) were prepared according to the literature
procedure.19 Pyridine derivatives (4a−4s) were prepared via Suzuki
coupling with the corresponding boronic acids and 2-bromopyridines
according to the reported procedure.20
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Scheme 2. KIE Experiments
1H), 7.27 (t, J = 8.0 Hz, 1H), 6.87 (s, 1H), 2.20 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.9, 158.3, 155.7, 135.8, 134.6, 132.5, 127.5,
126.6, 125.3, 124.8, 124.2, 123.7, 122.5, 121.3, 115.6, 108.8, 14.8; IR
(KBr) ν 3047, 2925 1727, 1452, 1433, 1344, 1562, 1601, 1232, 1082,
714 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for C21H15N4O2
[M + H]+ 355.1195, found: 355.1180.
Scheme 3. Proposed Mechanism for the Aromatic C−H
Bond Amination
2-(5-Methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3c). Yellow solid (72 mg, 71% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.28
(petroleum ether:EtOAc = 3:1, v:v); mp 216−217 °C; 1H NMR (400
MHz, CDCl3) δ 8.52 (d, J = 8.4 Hz, 1H), 8.43 (d, J = 4.8 Hz, 2H),
8.00−7.96 (m, 2H), 7.83−7.81 (m, 2H), 7.46 (s, 1H), 7.21 (dd, J =
8.8, 2.0 Hz, 1H), 6.94 (t, J = 4.4 Hz, 1H), 6.81 (s, 1H), 2.48 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 167.9, 158.2, 157.6, 134.6, 134.2,
132.6, 132.2, 127.8, 126.5, 125.3, 124.2, 121.1, 117.0, 115.8, 109.5,
21.6; IR (KBr) ν 2920, 1725,1425 1246 1100 718 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C21H15N4O2 [M + H]+ 355.1195, found:
355.1205.
2-(5-Methoxy-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3d). Yellow solid (63 mg, 57% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.39
(petroleum ether:EtOAc = 3:1, v:v); mp 230−231 °C; 1H NMR (400
MHz, CDCl3) δ 8.58 (d, J = 9.2 Hz, 1H), 8.41 (d, J = 4.8 Hz, 2H),
7.97 (dd, J = 5.4, 3.0 Hz, 2H), 7.82 (dd, J = 5.4, 3.0 Hz, 2H), 7.13 (d, J
= 2.4 Hz, 1H), 7.02 (dd, J = 9.2, 2.4 Hz, 1H), 6.93 (t, J = 4.8 Hz, 1H),
6.82 (s, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6,
157.9, 157.3, 155.7, 134.3, 132.3, 130.6, 128.1, 125.5, 123.9, 117.1,
116.7, 114.2, 109.4, 103.0, 55.7; IR (KBr) ν 2959, 2927, 2855, 1727,
1450, 1421, 1385, 1211, 1152, 1081, 810, 717 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C21H15N4O3 [M + H]+ 371.1144, found:
371.1127.
2-(5-Fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3e). Yellow solid (56 mg, 52% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.27
(petroleum ether:EtOAc = 3:1, v:v); mp 244 °C; 1H NMR (400 MHz,
CDCl3) δ 8.63 (dd, J = 9.2, 4.7 Hz, 1H), 8.45 (d, J = 4.8 Hz, 2H), 7.98
(dd, J = 5.6, 3.2 Hz, 2H), 7.83 (dd, J = 5.6, 3.2 Hz, 2H), 7.33 (dd, J =
8.8, 2.6 Hz, 1H), 7.13 (dt, J = 9.2, 2.6 Hz, 1H), 6.98 (t, J = 4.8 Hz,
1H), 6.86 (s, 1H); 19F NMR (400 MHz, CDCl3) δ −120.8; 13C NMR
(100 MHz, CDCl3) δ 106.2 (d, JC−F = 31 Hz), 109.1 (d, JC−F = 5.0
Hz), 112.8 (d, JC−F = 33 Hz), 117.1, 117.3, 124.0, 126.5, 128.0 (d, JC−F
= 14 Hz), 132.1, 132.2, 134.5, 157.1, 158.0, 159.1 (d, JC−F = 288 Hz),
167.5; IR (KBr) ν 2924, 2853, 1787, 1731, 1447, 1421, 1202, 1084,
807, 717 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for
C20H12N4O2F [M + H]+ 359.0944, found: 359.0928.
General Procedure for Cu-Catalyzed Direct Amidation of
Aromatic C−H Bonds. An oven-dried Schlenk tube equipped with a
magnetic stir bar was evacuated and backfilled with oxygen three times.
Under oxygen, CuOAc (0.06 mmol, 7.4 mg), indole derivatives (or 2-
arylpyridine derivatives) (0.3 mmol), and phthalimide (0.33 mmol,
48.5 mg) were dissolved in the mixed solvent of toluene and o-
dichlorobenzene (1:1, 2 mL) in the tube. The reaction mixture was
stirred at 150 °C for 2.5 days. Then, it was quenched with NaOH
solution (10%, 10 mL) and extracted with EtOAc (3 × 20 mL). The
combined organic layers were dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by column
chromatography to give the corresponding products.
2-(1-(Pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-dione (3a).
Yellow solid (88 mg, 86% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.43 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 232−233 °C; H NMR (400 MHz, CDCl3) δ
8.62 (d, J = 8.8 Hz, 1H), 8.45 (d, J = 4.8 Hz, 2H), 7.97 (dd, J = 5.4, 3.1
Hz, 2H), 7.82 (dd, J = 5.4, 3.1 Hz, 2H), 7.68 (d, J = 7.6, 1H), 7.41−
7.37 (m, 1H), 7.31−7.27 (m, 2H), 6.96 (t, J = 4.8 Hz, 1H), 6.70 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 167.9, 158.3, 157.6, 135.9,
134.7, 132.5, 127.6, 125.4, 125.0, 124.2, 122.8, 121.4, 117.3, 116.0,
109.6; IR (KBr) ν 2926, 2855, 1727, 1564, 1452, 1421, 1241, 1083,
753, 718, 709 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for
C20H13N4O2 [M + H] 341.1039, found: 341.1044.
2-(5-Chloro-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3f). Yellow solid (76 mg, 68% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.40
(petroleum ether:EtOAc = 3:1, v:v); mp 237−239 °C; 1H NMR (400
MHz, CDCl3) δ 8.59 (d, J = 9.2 Hz, 1H), 8.46 (d, J = 4.8, 2H), 7.97
(dd, J = 5.6, 3.2 Hz, 2H), 7.83 (dd, J = 5.6, 3.2 Hz, 2H), 7.65 (d, J =
2.4 Hz, 1H), 7.35 (dd, J = 8.8, 2.0 Hz, 1H), 7.00 (t, J = 9.6, 4.8 Hz,
1H), 6.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 167.4, 158.5,
2-(1-(5-Methylpyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-dione
(3b). Yellow solid (82 mg, 77% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.29
(petroleum ether:EtOAc = 3:1, v:v); mp 245−247 °C; 1H NMR (400
MHz, CDCl3) δ 8.56 (d, J = 8.4 Hz, 1H), 8.28 (s, 2H), 7.97−7.95 (m,
2H), 7.83−7.81 (m, 2H), 7.87 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 8.4 Hz,
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157.1, 134.5, 133.9, 132.2, 128.4, 128.1, 126.3, 124.9, 124.0, 120.4,
117.3, 117.1, 108.6; IR (KBr) ν 3121, 2926, 1725, 1442, 1423, 1386,
1100, 811, 721 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for
C20H12N4O2Cl [M + H]+ 375.0649, found: 375.0653.
1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.1, 155.2,
150.2, 149.4, 138.5, 134.4, 131.8, 130.4, 127.5, 125.5, 124.0, 121.6,
118.8, 114.0, 111.9, 104.8, 103.0, 55.8; IR (KBr) ν 2927, 1726, 1582,
1482, 1437, 1213, 1098, 1079, 789, 721, 709 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C22H16N3O3 [M + H]+ 370.1192, found:
370.1152.
2-(5-Bromo-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3g). Yellow solid (56 mg, 69% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.31
(petroleum ether:EtOAc = 3:1, v:v); mp 222 °C; 1H NMR (400 MHz,
CDCl3) δ 8.54 (d, J = 9.0 Hz, 1H), 8.46 (d, J = 4.8 Hz, 2H), 8.01−7.93
(m, 2H), 7.87−7.79 (m, 3H), 7.47 (dd, J = 9.0, 2.0 Hz, 1H), 7.00 (t, J
= 4.8 Hz, 1H), 6.83 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 167.4,
158.1, 157.1, 134.5, 134.3, 132.2, 129.0, 127.5, 126.3, 124.0, 123.5,
117.5, 117.3, 115.7, 108.5; IR (KBr) ν 3120, 2924, 1725, 1566, 1441,
1421, 1387, 1099, 811, 720 cm−1; HRMS (ESI+, QTOF) exact mass
calc’d for C20H12N4O2Br [M + H]+ 419.0144, found: 419.0147.
2-(1,3-Dioxoisoindolin-2-yl)-1-(pyrimidin-2-yl)-1H-indole-5-car-
bonitrile (3h). Yellow solid (34 mg, 31% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.33
(petroleum ether:EtOAc = 3:1, v:v); mp 271−272 °C; 1H NMR (400
MHz, CDCl3) δ 8.71 (d, J = 8.8 Hz, 1H), 8.51 (d, J = 4.8 Hz, 2H),
8.04 (s, 1H), 7.98 (dd, J = 5.6, 2.8 Hz, 2H), 7.85 (dd, J = 5.6, 3.2 Hz,
2H), 7.62 (dd, J = 8.8, 1.6 Hz, 1H), 7.08 (t, J = 4.8 Hz, 1H), 6.96 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 167.1, 158.3, 156.8, 137.3,
134.6, 132.1, 129.9, 127.5, 127.2, 126.1, 124.1, 119.8, 118.0, 116.7,
108.8, 105.9; IR (KBr) ν 2923, 2852, 2223, 1725, 1576, 1469, 1422,
1388, 1101, 1084, 822, 707 cm−1; HRMS (ESI+, QTOF) exact mass
calc’d for C21H12N5O2 [M + H]+ 366.0991, found: 366.0981.
2-(3-Methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)isoindoline-1,3-
dione (3j). Yellow solid (49 mg, 46% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.29
(petroleum ether:EtOAc = 3:1, v:v); mp 182−183 °C; 1H NMR (400
MHz, CDCl3) δ 8.68 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 4.8 Hz, 2H),
7.98 (dd, J = 5.6, 3.2 Hz, 2H), 7.84 (dd, J = 5.6, 3.2 Hz, 2H), 7.64 (d, J
= 8.0 Hz, 1H), 7.42 (dt, J = 7.2, 1.2 Hz, 1H), 7.32−7.28 (m, 1H), 6.90
(t, J = 4.8 Hz, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
167.7, 157.8, 157.4, 135.3, 134.3, 132.5, 128.5, 128.3, 124.9, 123.9,
122.2, 119.2, 117.6, 116.4, 115.9, 8.2; IR (KBr) ν 2923, 1726, 1562,
1459, 1426, 1369, 712 cm−1; HRMS (ESI+, QTOF) exact mass calc’d
for C21H15N4O2 [M + H]+ 355.1195, found: 355.1217.
2-(1,3-Dioxoisoindolin-2-yl)-1-(pyridin-2-yl)-1H-indole-5-carboni-
trile (3n). Yellow solid (57 mg, 52% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.22
(petroleum ether:EtOAc = 3:1, v:v); mp 223−225 °C; 1H NMR (400
MHz, CDCl3) δ 8.39−8.37 (m, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.91
(dd, J = 5.6, 3.2 Hz, 2H), 7.85 (dt, J = 7.6, 1.6 Hz, 1H), 7.81 (dd, J =
5.6, 3.2 Hz, 2H), 7.64 (d, J = 8.8 Hz, 1H), 7.54 (dd, J = 8.4, 1.6 Hz,
1H), 7.46 (d, J = 8.0 Hz, 1H), 7.25−7.23 (m, 1H), 6.91 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 166.8, 150.0, 149.3, 139.2, 137.1, 135.1,
131.7, 127.9, 127.1, 126.8, 124.4, 123.1, 120.3, 119.7, 112.3, 105.2,
104.9, 104.6; IR (KBr) ν 2924, 2351, 2218, 1734, 1471, 1583, 1398,
1366, 1082, 883, 802, 717 cm−1; HRMS (ESI+, QTOF) exact mass
calc’d for C22H13N4O2 [M + H]+ 365.1039, found: 365.1066.
2-(1,3-Dioxoisoindolin-2-yl)-1-(pyridin-2-yl)-1H-indole-5-carbal-
dehyde (3o). White solid (34 mg, 31% yield), purified by column
chromatography (petroleum ether:EtOAc = 3:1, v:v); Rf = 0.16
(petroleum ether:EtOAc = 3:1, v:v); mp 185 °C; 1H NMR (400 MHz,
CDCl3) δ 10.09 (s, 1H), 8.38−8.34 (m, 1H), 8.27 (d, J = 1.2 Hz, 1H),
7.92−7.79 (m, 6H), 7.66 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H),
7.21−7.26 (m, 1H), 6.99 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
192.4, 166.9, 149.9, 149.5, 139.1, 138.8, 134.9, 131.8, 131.2, 127.5,
126.9, 126.6, 124.4, 124.1, 122.9, 119.8, 111.9, 106.3; IR (KBr) ν 2927,
2814, 1732, 1683, 1588, 1477, 1392, 1348, 1303, 1104, 715 cm−1;
HRMS (ESI+, QTOF) m/z calc’d for C22H14N3O3 [M + H]+
368.1035, found: 368.1028.
2-(1-Benzoyl-1H-indol-2-yl)isoindoline-1,3-dione (3p). Yellow oil
(20 mg, 27% yield); purified by column chromatography (petroleum
ether:EtOAc = 8:1, v:v); Rf = 0.46 (petroleum ether:EtOAc = 3:1, v:v);
1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 3.2, 5.6 Hz, 2H), 7.71
(dd, J = 3.2, 5.6 Hz, 2H), 7.67−7.62 (m, 3H), 7.49−7.47 (m, 1H),
7.29−7.26 (m, 5H), 6.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
168.3, 166.5, 135.8, 134.6, 134.5, 132.3, 131.4, 129.3, 128.4, 127.4,
125.6, 125.1, 123.8, 123.3, 121.3, 114.8, 109.0; IR (KBr) ν 2923, 1727,
1683, 1451, 1379, 1324, 1079, 701; HRMS (ESI+, QTOF) exact mass
calc’d for C23H15N2O3 [M + H]+ 367.1083, found: 367.1079.
2-(2-(Pyridin-2-yl)phenyl)isoindoline-1,3-dione (5a).11 Yellow
solid (48 mg, 53% yield), purified by column chromatography
(petroleum ether:EtOAc = 3:1, v:v); Rf = 0.22 (petroleum ether:-
EtOAc = 3:1, v:v); mp 168 °C; 1H NMR (400 MHz, CDCl3) δ 8.29−
8.27 (m, 1H), 7.85 (dd, J = 5.6, 3.2 Hz, 2H), 7.73−7.70 (m, 3H), 7.65
(dt, J = 8.0, 2.0 Hz, 1H), 7.60−7.54 (m, 2H), 7.48 (d, J = 8.0 Hz, 1H),
7.44−7.38 (m, 1H), 7.08−7.04 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 167.9, 157.2, 149.5, 138.7, 136.9, 134.3, 132.3, 130.7, 130.3,
129.8, 129.7, 123.8, 123.0, 122.3; IR (KBr) ν 2925, 2854, 1713, 1469,
1426, 1382, 1116, 1099, 1084, 756, 720 cm−1; HRMS (ESI+, QTOF)
exact mass calc’d for C19H13N2O2 [M + H]+ 301.0977, found:
301.0979.
2-(1-(Pyridin-2-yl)-1H-indol-2-yl)isoindoline-1,3-dione (3k). Yel-
low solid (73 mg, 72% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.41 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 174−175 °C; H NMR (400 MHz, CDCl3) δ
8.30−8.28 (m, 1H), 7.91−7.88 (dd, J = 5.6, 3.2 Hz, 2H), 7.82−7.80
(m, 1H), 7.77 (dd, J = 5.6, 3.2 Hz, 2H), 7.74−7.72 (m, 1H), 7.60 (dd,
J = 8.4, 1.2 Hz, 1H), 7.53−7.51 (m, 1H), 7.32−7.24 (m, 2H), 7.15
(ddd, J = 7.6, 4.8, 1.2 Hz, 1H), 6.84 (d, J = 0.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 167.4, 150.3, 149.7, 138.8, 135.5, 134.8, 131.9,
127.2, 125.6, 124.2, 124.1, 122.1, 121.8, 121.8, 119.5, 111.2, 105.2; IR
(KBr) ν 3084, 2925, 1722, 1583, 1454, 1371, 736, 712, 883, 608 cm−1;
HRMS (ESI+, QTOF) exact mass calc’d for C21H14N3O2 [M + H]+
340.1086, found: 340.1068.
2-(5-Methyl-1-(pyridin-2-yl)-1H-indol-2-yl)isoindoline-1,3-dione
(3l). Yellow solid (72 mg, 68% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.41
2-(5-Methyl-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5b).11
Yellow solid (45 mg, 48% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.41 (petroleum ether:-
1
(petroleum ether:EtOAc = 3:1, v:v); mp 213-215 °C; H NMR (400
1
EtOAc = 3:1, v:v); mp 178−180 °C, H NMR (400 MHz, CDCl3) δ
MHz, CDCl3) δ 8.26−8.24 (m, 1H), 7.89 (dd, J = 5.6, 3.2 Hz, 2H),
7.79−7.74 (m, 3H), 7.50−7.46 (m, 3H), 7.12−7.10 (m, 2H), 6.74 (s,
1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4,150.5, 149.6,
138.7, 135.0, 134.7, 133.8, 132.0, 131.1, 125.6, 125.4, 124.4, 124.2,
121.9, 121.4, 119.2, 110.9, 21.7; IR (KBr) ν 2924, 1726, 1471, 1590,
1432, 1394, 1337, 1079, 721, 708 cm−1; HRMS (ESI+, QTOF) exact
mass calc’d for C22H16N3O2 [M + H]+ 354.1243, found: 354.1226.
2-(5-Methoxy-1-(pyridin-2-yl)-1H-indol-2-yl)isoindoline-1,3-dione
(3m). Yellow solid (86 mg, 78% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.27
(petroleum ether:EtOAc = 3:1, v:v); mp 199−200 °C; 1H NMR (400
MHz, CDCl3) δ 8.30−8.25 (m, 1H), 7.90 (dd, J = 5.6, 2.8 Hz, 2H),
7.82−7.74 (m, 3H), 7.51−7.47 (m, 2H), 7.16 (d, J = 2.4 Hz, 1H), 7.13
(ddd, J = 7.2, 4.8, 0.8 Hz, 1H), 6.95 (dd, J = 9.2, 2.8 Hz, 1H), 6.7 (s,
8.27−8.25 (m, 1H), 7.85 (dd, J = 5.6, 3.2 Hz, 2H), 7.73 (dd, J = 5.6,
3.2 Hz, 2H), 7.65−7.60 (m, 2H), 7.45 (d, J = 8.0 Hz, 1H), 7.40−7.37
(m, 1H), 7.22 (s, 1H), 7.04 (ddd, J = 7.6, 4.8, 1.2 Hz, 1H), 2.47 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 168.1, 157.1, 149.4, 140.0,
136.9, 135.8, 134.2, 132.4, 130.9, 130.7, 130.5, 129.6, 123.8, 122.9,
122.1, 22.2; IR (KBr) ν 3057, 2923, 1719, 1711, 1467, 1428, 1379,
1120, 880, 786, 715 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for
C20H15N2O2 [M + H]+ 315.1134, found: 315.1112.
2-(5-Methoxy-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5c).11
Yellow solid (48 mg, 48% yield), purified by column chromatography
(petroleum ether:EtOAc = 3:1, v:v); Rf = 0.22 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 157−158 °C, H NMR (400 MHz, CDCl3) δ
8.24−8.22 (m, 1H), 7.85 (dd, J = 5.6, 3.2 Hz, 2H), 7.73 (dd, J = 5.6,
4419
dx.doi.org/10.1021/jo5003592 | J. Org. Chem. 2014, 79, 4414−4422

The Journal of Organic Chemistry
Article
3.2 Hz, 2H), 7.67 (d, J = 8.8 Hz, 1H), 7.61 (dt, J = 7.6, 2 Hz, 1H), 7.42
(d, J = 8.0 Hz, 1H), 7.11 (dd, J = 8.8, 2.8 Hz, 1H), 7.04−7.00 (m, 1H),
6.93 (d, J = 2.8 Hz, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
167.6, 160.2, 156.6, 149.1, 136.5, 133.9, 132.0, 131.3, 130.8, 130.6,
123.5, 122.3, 121.5, 115.4, 55.5; IR (KBr) ν 3002, 1712, 1375, 1281,
1466, 1427, 1113, 875, 788, 716 cm−1; HRMS (ESI+, QTOF) exact
mass calc’d for C20H15N2O3 [M + H]+ 331.1083, found: 331.1070.
2-(5-(tert-Butyl)-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5d).
Yellow solid (62 mg, 58% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.45 (petroleum ether:-
Methyl 3-(1,3-Dioxoisoindolin-2-yl)-4-(pyridin-2-yl)benzoate (5i).
Yellow solid (42 mg, 39% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.35 (petroleum ether:-
EtOAc = 2:1, v:v); mp 184 °C, 1H NMR (400 MHz, CDCl3) δ 8.32−
8.31 (m, 1H), 8.24 (dd, J = 8.0, 1.6 Hz, 1H), 8.10 (d, J = 1.6 Hz, 1H),
7.87−7.85 (m, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.77−7.73 (m, 2H), 7.68
(dt, J = 7.6, 1.6 Hz, 1H), 7.54−7.49 (m, 1H), 7.12 (ddd, J = 7.6, 4.8,
1.2 Hz, 1H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6,
166.0, 156.2, 149.7, 142.8, 137.1, 134.4, 132.2, 131.8, 131.4, 130.9,
130.8, 130.2, 123.9, 123.2, 122.9, 52.7; IR (KBr) ν 3070, 2998, 2949,
1784, 1717, 1586, 1422, 1440, 1288, 1216, 1114, 765, 718 cm−1;
HRMS (ESI+, QTOF) exact mass calc’d for C21H15N2O4 [M + H]+
359.1032, found: 359.1002.
3-(1,3-Dioxoisoindolin-2-yl)-4-(pyridin-2-yl)benzaldehyde (5j).
Yellow solid (27 mg, 28% yield), purified by column chromatography
(petroleum ether:EtOAc = 3:1, v:v); Rf = 0.29 (petroleum ether:-
EtOAc = 2:1, v:v); mp 217 °C; 1H NMR (400 MHz, CDCl3) δ 10.11
(s, 1H), 8.32 (dd, J = 4.4, 0.8 Hz, 1H), 8.11−8.01 (m, 1H), 7.94−7.90
(m, 2H), 7.88−7.7.86 (m, 2H), 7.78−7.68 (m, 3H), 7.54 (d, J = 8.0
Hz, 1H), 7.16−7.13 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 190.9,
167.5, 156.0, 149.7, 144.1, 143.0, 137.2, 134.5, 132.1, 131.9, 131.6,
130.9, 130.3, 124.0, 123.3, 123.2; IR (KBr) ν 3070, 2818, 2724, 1715,
1695, 1465, 1385, 1111, 1084, 795, 716 cm−1; HRMS (ESI+, QTOF)
exact mass calc’d for C20H13N2O3 [M + H]+ 329.0926, found:
329.0924.
1
EtOAc = 3:1, v:v); mp 180−181 °C; H NMR (400 MHz, CDCl3) δ
8.28−8.27 (m, 1H), 7.85 (dd, J = 5.6, 3.2 Hz, 2H), 7.74 (dd, J = 5.6,
3.2 Hz, 2H), 7.68−7.58 (m, 3H), 7.46 (d, J = 8.0 Hz, 1H), 7.37 (d, J =
2.0 Hz, 1H), 7.09−7.02 (m, 1H), 1.39 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 168.1, 157.2, 153.1, 149.5, 136.8, 135.7, 134.2, 132.4, 130.3,
129.4, 127.4, 126.9, 123.8, 122.8, 122.1, 34.8, 31.2; IR (KBr) ν 3047,
2925, 1727, 1452, 1433, 1344, 1601, 1232, 1082, 887, 816, 741, 714
cm−1; HRMS (ESI+, QTOF) exact mass calc’d for C23H21N2O2 [M +
H]+ 357.1603, found: 357.1604.
2-(2-(Pyridin-2-yl)-5-vinylphenyl)isoindoline-1,3-dione (5e). Yel-
low solid (30 mg, 31% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.41 (petroleum ether:-
EtOAc = 2:1, v:v); mp 135 °C; 1H NMR (400 MHz, CDCl3) δ 8.27−
8.26 (m, 1H), 7.86 (dd, J = 5.6, 3.2 Hz, 2H), 7.74 (dd, J = 5.6, 3.2 Hz,
2H), 7.70 (d, J = 8.0 Hz, 1H), 7.66−7.59 (m, 2H), 7.47 (d, 8.0 Hz,
1H), 7.43 (d, J = 1.6 Hz, 1H), 7.06 (ddd, J = 7.6, 4.8, 1.2 Hz, 1H), 6.78
(dd, J = 17.6, 11.2 Hz, 1H), 5.85 (d, J = 17.6 Hz, 1H), 5.37 (d, J = 10.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.9, 156.8, 149.5, 139.3,
137.7, 136.9, 135.6, 134.3, 132.3, 130.8, 130.1, 128.2, 127.5, 123.8,
122.9, 122.3, 116.1; IR (KBr) ν 2927, 2308, 1717, 1466, 1424, 1377,
1116, 719, 715 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for
C21H15N2O2 [M + H]+ 327.1134, found: 327.1123.
2-(4-Methyl-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5k).11
Yellow solid (42 mg, 45% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.35 (petroleum ether:-
EtOAc = 3:1, v:v); mp 164 °C; 1H NMR (400 MHz, CDCl3) δ 8.32−
8.31 (m, 1H), 7.84 (dd, J = 5.2, 2.0 Hz, 2H), 7.72 (dd, J = 5.2, 2.0 Hz,
2H), 7.62 (dt, J = 7.6, 2.8 Hz, 1H), 7.55 (s, 1H), 7.47−7.42 (m, 1H),
7.38−7.35 (m, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.07 (ddd, J = 7.6, 4.8,
1.2 Hz, 1H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.8,
157.0, 149.3, 139.6, 138.3, 136.5, 133.9, 132.1, 131.2, 130.1, 129.7,
126.9, 123.5, 122.6, 122.0, 21.3; IR (KBr) ν 3077, 2925, 1726, 1588,
1471, 1429, 1380, 1105, 1084, 892, 826, 721 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C20H15N2O2 [M + H]+ 315.1134, found:
315.1133.
2-(4-Methoxy-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5l).
Yellow solid (49 mg, 50% yield), purified by column chromatography
(petroleum ether:EtOAc = 3:1, v:v); Rf = 0.24 (petroleum ether:-
EtOAc = 3:1, v:v); mp 170 °C; 1H NMR (400 MHz, CDCl3) δ 8.33−
8.31 (m, 1H), 7.84 (dd, J = 5.6, 3.2 Hz, 2H), 7.72 (dd, J = 5.6, 3.2 Hz,
2H), 7.63 (dt, J = 8.0, 2.0 Hz, 1H), 7.44 (dt, J = 8.0, 1.2 Hz, 1H), 7.31
(d, J = 8.4 Hz, 1H), 7.25 (d, J = 3.2 Hz, 1H), 7.10−7.07 (m, 2H),
3.91(s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.2, 160.4, 156.9,
149.5, 139.9, 136.9, 134.2, 132.3, 131.4, 123.8, 122.9, 122.5, 122.3,
116.0, 115.1, 55.9; IR (KBr) ν 3014, 2973, 2934, 1720, 1561, 1498,
1459, 1380, 1295, 1222, 1031, 796, 719 cm−1; HRMS (ESI+, QTOF)
exact mass calc’d for C20H15N2O3 [M + H]+ 331.1083, found:
331.1054.
2-(5-Fluoro-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5f).11
Yellow solid (49 mg, 51% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.27 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 196−197 °C; H NMR (400 MHz, CDCl3) δ
8.28−8.27 (m, 1H), 7.86 (dd, J = 5.6, 3.2 Hz, 2H), 7.76−7.70 (m,
3H), 7.65 (dt, J = 8.0, 2.0 Hz, 1H), 7.44 (dt, J = 7.6, 0.8 Hz, 1H),
7.31−7.26 (m, 1H), 7.17 (dd, J = 8.8, 2.4 Hz, 1H), 7.10−7.06 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 167.5, 164.0, 161.6, 156.4,
149.5, 137.1, 134.5, 132.2, 123.9, 122.9, 122.4, 117.9, 117.6, 116.9,
116.8; 19F NMR (400 MHz, CDCl3) δ −62.6; IR (KBr) ν 3069, 2925,
1720, 1468, 1424, 1374, 1269, 1115, 789, 718 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C19H12N2O2F [M + H]+ 319.0883,
found: 319.0903.
2-(5-Chloro-2-(pyridin-2-yl)phenyl)isoindoline-1,3-dione (5g).
Yellow solid (60 mg, 60% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.28 (petroleum ether:-
EtOAc = 3:1, v:v); mp 210 °C; 1H NMR (400 MHz, CDCl3) δ 8.28−
8.27 (m, 1H), 7.85 (dd, J = 5.2, 2.8 Hz, 2H), 7.75 (dd, J = 5.2, 2.8 Hz,
2H), 7.68−7.62 (m, 2H), 7.55 (dd, J = 8.4, 2.0 Hz, 1H), 7.49−7.43
(m, 2H), 7.10 (ddd, J = 7.6, 4.8, 1.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 167.2, 155.9, 149.3, 136.9, 136.8, 134.8, 134.1, 131.8, 131.4,
130.6, 130.2, 129.6, 123.6, 122.6, 122.3; IR (KBr) ν 3085, 1726, 1712,
1465, 1420, 1374, 1118, 1103, 1082, 717, 709 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C19H12N2O2Cl [M + H]+ 335.0587,
found: 335.0602.
2-(2-(Pyridin-2-yl)-5-(trifluoromethyl)phenyl)isoindoline-1,3-
dione (5h). Yellow solid (68 mg, 62% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.35
(petroleum ether:EtOAc = 3:1, v:v); mp 164 °C; 1H NMR (400 MHz,
CDCl3) δ 8.32−8.31 (m, 1H), 7.88−7.83 (m, 4H), 7.76 (dd, J = 5.2,
3.2 Hz, 2H), 7.72−7.68 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.14 (ddd, J
= 7.6, 4.8, 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.5, 155.9,
149.7, 142.1, 137.2, 134.5, 132.1, 131.6, 131.3, 130.5, 127.7, 126.6,
124.0, 123.7, 123.1, 123.1; 19F NMR (400 MHz, CDCl3) δ −111.4; IR
(KBr) ν 2922, 1722, 1371, 1321, 1115, 1079, 719, 874, 788 cm−1;
HRMS (ESI+, QTOF) exact mass calc’d for C20H12N2O2F3 [M + H]+
369.0851, found: 369.0820.
2-(2-(3-Methylpyridin-2-yl)phenyl)isoindoline-1,3-dione (5m).
Yellow solid (41 mg, 44% yield), purified by column chromatography
(petroleum ether:EtOAc = 5:1, v:v); Rf = 0.35 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 182 °C, H NMR (400 MHz, CDCl3) δ 8.17
(d, J = 4.0 Hz, 1H), 7.78 (dd, J = 5.6, 3.2 Hz, 2H), 7.68 (dd, J = 5.6,
3.2 Hz, 2H), 7.57−7.49 (m, 4H), 7.47−7.41 (m, 1H), 6.99 (dd, J =
7.6, 4.8 Hz, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4,
156.3, 146.6, 139.1, 138.5, 134.2, 132.2, 131.9, 130.7, 130.5, 129.9,
129.2, 128.9, 123.7, 122.5, 19.7; IR (KBr) ν 2923, 1710, 1461, 1446,
1381, 1121, 1083, 759, 721 cm−1; HRMS (ESI+, QTOF) exact mass
calc’d for C20H15N2O2 [M + H]+ 315.1134, found: 315.1117.
2-(5-(tert-Butyl)-2-(3-methylpyridin-2-yl)phenyl)isoindoline-1,3-
dione (5n). Yellow solid (60 mg, 54% yield), purified by column
chromatography (petroleum ether:EtOAc = 8:1, v:v); Rf = 0.48
(petroleum ether:EtOAc = 3:1, v:v); mp 203 °C; 1H NMR (400 MHz,
CDCl3) δ 8.16−8.15 (m, 1H), 7.78 (d, J = 5.2, 3.2 Hz, 2H), 7.67 (d, J
= 5.2, 3.2 Hz, 2H), 7.54 (dd, J = 8.4, 2.0 Hz, 1H), 7.49 (d, J = 8.0 Hz,
1H), 7.43 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 6.97 (dd, J =
7.6, 4.8 Hz, 1H), 2.35 (s, 3H), 1.39 (s, 9H); 13C NMR (100 MHz,
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CDCl3) δ 167.6, 156.4, 152.4, 146.6, 138.4, 136.1, 134.1, 132.2, 132.1,
130.3, 130.0, 126.8, 126.1, 123.6, 122.3, 35.0, 31.5; IR (KBr) ν 2965,
2868, 1715, 1423, 1373, 1360, 1122, 1086, 722 cm−1; HRMS (ESI+,
QTOF) exact mass calc’d for C24H23N2O2 [M + H]+ 371.1760, found:
371.1730.
2-(5-Methoxy-2-(3-methylpyridin-2-yl)phenyl)isoindoline-1,3-
dione (5o). Yellow solid (39 mg, 38% yield), purified by column
chromatography (petroleum ether:EtOAc = 5:1, v:v); Rf = 0.19
(petroleum ether:EtOAc = 3:1, v:v); mp 188 °C; 1H NMR (400 MHz,
CDCl3) δ 8.14 (dd, J = 4.8, 0.8 Hz, 1H), 7.78 (dd, J = 5.2, 3.2 Hz, 2H),
7.68 (dd, J = 5.2, 3.2 Hz, 2H), 7.50−7.47 (m, 1H), 7.42 (d, J = 8.8 Hz,
1H), 7.07 (dd, J = 8.8, 2.8 Hz, 1H), 6.97−6.93 (m, 2H), 3.88 (s, 3H),
2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 159.9, 156.2,
146.6, 138.4, 134.2, 132.3, 132.0, 131.5, 123.7, 122.2, 115.1, 114.9,
55.8, 19.8; IR (KBr) ν 3010, 2937, 1720, 1617, 1433, 1377, 1295,
1272, 1238, 1085, 716 cm−1; HRMS (ESI+, QTOF) exact mass calc’d
for C21H17N2O3 [M + H]+ 345.1239, found: 345.1236.
2-(2-(3-Methylpyridin-2-yl)-5-(trifluoromethyl)phenyl)isoindoline-
1,3-dione (5p). Yellow solid (85 mg, 75% yield), purified by column
chromatography (petroleum ether:EtOAc = 10:1, v:v); Rf = 0.51
(petroleum ether:EtOAc = 3:1, v:v); mp 159−160 °C; 1H NMR (400
MHz, CDCl3) δ 8.18 (dd, J = 4.4, 1.2 Hz, 1H), 7.80−7.78 (m, 3H),
7.74 (s, 1H), 7.71 (dd, J = 5.6, 3.2 Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H),
7.56−7.52 (m, 1H), 7.03 (dd, J = 7.6, 4.8 Hz, 1H), 2.34 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 166.9, 155.1, 146.9, 142.7, 138.8, 134.5,
132.3, 131.8, 131.6, 131.4, 131.3, 127.3, 125.8, 123.9, 123.1, 122.4,
19.5; 19F NMR (400 MHz, CDCl3) δ −62.6; IR (KBr) ν 3068, 2962,
1716, 1433, 1376, 1323, 1211, 1167, 1143; HRMS (ESI+, QTOF)
exact mass calc’d for C21H14N2O2F3 [M + H]+ 383.1007, found:
383.0979.
2-(5-Methyl-2-(pyrimidin-2-yl)phenyl)isoindoline-1,3-dione
(5q).11 Yellow solid (51 mg, 54% yield), purified by column
chromatography (petroleum ether:EtOAc = 8:1, v:v); Rf = 0.41
(petroleum ether:EtOAc = 3:1, v:v); mp 234 °C; 1H NMR (400 MHz,
CDCl3) δ 8.48 (d, J = 4.8 Hz, 2H), 8.34 (d, J = 8.0 Hz, 1H), 7.90 (dd,
J = 5.6, 3.2 Hz, 2H), 7.76 (dd, J = 5.6, 3.2 Hz, 2H) 7.42 (d, J = 8.0 Hz,
1H), 7.23 (s, 1H), 7.00 (t, J = 9.6, 4.8 Hz, 1H), 2.48 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 168.2, 164.0, 156.9, 141.6, 133.9, 132.5,
132.4, 131.5, 131.2, 130.40, 130.37, 123.5, 118.8, 21.2; IR (KBr) ν
2917, 1719, 1709, 1566, 1551, 1410, 1378, 1112, 1085, 805, 716 cm−1;
HRMS (ESI+, QTOF) exact mass calc’d for C19H14N3O2 [M + H]+
316.1086, found: 316.1066.
3H), 7.78−7.72 (m, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.0 Hz,
1H), 7.34 (t, J = 7.6 Hz, 1H), 7.27−7.19 (m, 2 H), 7.06 (s, 1 H); 13
C
NMR (100 MHz, CDCl3) δ 158.5, 149.8. 149.4, 138.4, 137.7, 136.2,
135.3, 134.4, 126.5, 126.4, 125.8, 124.6, 122.2, 121.7, 121.5, 120.6,
119.7, 111.6, 107.2; IR (KBr) ν 2926, 1745, 1590, 1470, 1453, 1331,
1348, 1187, 748, 584; HRMS (ESI+, QTOF) exact mass calc’d for
C20H14N3O3S [M + H]+ 376.0756, found: 376.0748.
2-(1-(Pyrimidin-2-yl)-1H-indol-2-yl)benzo[d]isothiazol-3(2H)-one
1,1-Dioxide (6b). Yellow solid (36 mg, 32% yield), purified by column
chromatography (petroleum ether:EtOAc = 3:1, v:v); Rf = 0.27
(petroleum ether:EtOAc = 3:1, v:v); mp 235−236 °C; 1H NMR (400
MHz, CDCl3) δ 8.58 (d, J = 8.4 Hz, 1H), 8.46 (d, J = 4.4 Hz, 2H),
8.19 (d, J = 6.8 Hz, 1H), 7.96−7.88 (m, 3H), 7.71 (d, J = 7.6 Hz, 1H),
7.43 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.14 (s, 1 H), 6.99 (t,
J = 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.4, 157.9, 157.0,
138.0, 136.3, 135.1, 134.4, 127.1, 126.9, 125.7, 125.5, 122.7, 121.5,
121.4, 120.5, 117.3, 115.7, 111.9; IR (KBr): ν 2976, 1751, 1443, 1424,
1347, 1186, 755; HRMS (ESI+, QTOF) exact mass calc’d for
C19H13N4O3S [M + H]+ 377.0708, found: 376.0708.
2-(2-(Pyridin-2-yl)phenyl)benzo[d]isothiazol-3(2H)-one 1,1-Diox-
ide (6c). Yellow solid (32 mg, 48% yelid), purified by column
chromatography (petroleum ether:EtOAc = 3:1, v:v); Rf = 0.22
(petroleum ether:EtOAc = 3:1, v:v); mp 188 °C; 1H NMR (400 MHz,
CDCl3) δ 8.46 (d, J = 4.4 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1 H), 7.89 (t, J
= 7.2 Hz, 1H), 7.85−7.79 (m, 3H), 7.67−7.58 (m, 5 H), 7.14−7.11
(m, 1 H); 13C NMR (100 MHz, CDCl3) δ 158.6, 156.2, 149.4, 140.9,
137.7, 136.3, 134.8, 134.2, 131.5, 131.0, 130.9, 129.8, 127.0, 125.9,
125.4, 122.9, 122.3, 121.1; IR (KBr) ν 3095, 1748, 1587, 1471, 1332,
1311, 1184, 759, 747, 732, 586; HRMS (ESI+, QTOF) exact mass
calc’d for C18H13N2O3S [M + H]+ 337.0647, found: 337.0638.
N-(2-(Pyridin-2-yl)phenyl)benzamide (6d). Yellow solid (12 mg,
22% yield); purified by column chromatography (petroleum ether:-
EtOAc = 1:1, v:v); Rf = 0.70 (petroleum ether:EtOAc = 3:1, v:v); mp
89 °C; 1H NMR (400 MHz, CDCl3) δ 13.30 (br, 1H), 8.79 (d, J = 8.4
Hz, 1H), 8.68 (d, J = 4.4 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 7.86−7.79
(m, 2 H), 7.73 (d, J = 7.6 Hz, 1H), 7.52−7.46 (m, 4H), 7.29 (t, J = 6.4
Hz, 1H), 7.29 (t, J = 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
165.5, 158.3, 147.3, 138.1, 137.9, 135.7, 131.5, 130.3, 128.8, 128.6,
127.4, 125.6, 123.6, 123.0, 122.0, 121.9; IR (KBr) ν 2960, 2927, 1666,
1589, 1475, 1439, 1323, 1262, 748, 669; HRMS (ESI+, QTOF) exact
mass calc’d for C18H15N2O [M + H]+ 275.1184, found: 275.1183.
KIE Experiment with [D]-4a as Substrate. Compounds [D]-4a and
[D2]-4a were synthesized according to the literature procedure.19
Under oxygen, CuOAc (0.04 mmol, 4.9 mg), [D]-4a (0.2 mmol, 31.2
mg), and phthalimide (0.24 mmol, 35.3 mg) were dissolved in toluene
and o-dichlorobenzene (1:1, 2 mL) in an oven-dried 25 mL Schlenk
tube. The mixture was stirred at 150 °C for 4 h. The reaction was then
stopped stirring, cooled down to room temperature, and poured into
NaOH solution (10%, 10 mL). It was extracted with EtOAc (3 × 20
mL). The combined organic layers were dried over Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by column
chromatography to give the corresponding products [D]-5a and 5a
2-(3-(Pyridin-2-yl)naphthalen-2-yl)isoindoline-1,3-dione (5r). Yel-
low solid (45 mg, 43% yield), purified by column chromatography
(petroleum ether:EtOAc = 8:1, v:v); Rf = 0.41 (petroleum ether:-
1
EtOAc = 3:1, v:v); mp 248−250 °C, H NMR (400 MHz, CDCl3) δ
8.27−8.26 (m, 1H), 8.19 (s, 1H), 7.98−7.95 (m, 3H), 7.87 (dd, J =
5.6, 3.2 Hz, 2H), 7.76 (dd, J = 5.6, 3.2 Hz, 2H), 7.69 (td, J = 7.6, 1.6
Hz, 1H), 7.63−7.57 (m, 3H), 7.10−7.07 (m,1H); 13C NMR (100
MHz, CDCl3) δ 168.2, 157.4, 149.4, 137.0, 136.0, 134.3, 133.6, 133.4,
132.4, 130.5, 130.0, 128.4, 128.2, 127.6, 127.4, 123.8, 123.3, 122.3; IR
(KBr) ν 3057, 2924, 1716, 1587, 1466, 1425, 1384, 1110, 869, 749,
711 cm−1; HRMS (ESI+, QTOF) exact mass calc’d for C23H15N2O2
[M + H]+ 351.1134, found: 351.1142.
2-(Benzo[h]quinolin-10-yl)isoindoline-1,3-dione (5s). Yellow solid
(94 mg, 97% yield), purified by column chromatography (petroleum
ether:EtOAc = 8:1, v:v); Rf = 0.46 (petroleum ether:EtOAc = 3:1, v:v);
mp 299−300 °C; 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 4.4, 1.6
Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H), 8.02 (dd, J = 5.6, 3.2 Hz, 2H), 7.89
(d, J = 8.8 Hz, 1H), 7.85−7.80 (m, 3H), 7.72−7.68 (m, 2H), 7.31 (dd,
J = 8.4, 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 169.3, 148.1,
145.5, 135.8, 133.7, 133.4, 131.1, 130.4, 129.2, 128.0, 127.8, 127.3,
127.1, 126.5, 123.5, 121.6; IR (KBr) ν 2925, 2854, 1727, 1399, 1382,
1117, 1086, 844, 726, 717 cm−1; HRMS (ESI+, QTOF) exact mass
calc’d for C21H13N2O2 [M + H]+ 325.0977, found: 325.0951.
2-(1-(Pyridin-2-yl)-1H-indol-2-yl)benzo[d]isothiazol-3(2H)-one
1,1-Dioxide (6a). Yellow solid (32 mg, 43% yield), purified by column
chromatography (petroleum ether:EtOAc = 3:1, v:v); Rf = 0.27
(petroleum ether:EtOAc = 3:1, v:v); mp 195 °C; 1H NMR (400 MHz,
CDCl3) δ 8.47−8.46 (m, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.94−7.82 (m,
1
(28% yield). The H NMR analysis showed that the ratio of 5a/[D]-
5a is 2.1.
KIE Experiment with [D2]-4a and 4a as Substrates. Under
oxygen, CuOAc (0.04 mmol, 4.9 mg), [D2]-4a (0.1 mmol, 15.7 mg),
4a (0.1 mmol, 15.5 mg), and phthalimide (0.24 mmol, 35.3 mg) were
dissolved in toluene and o-dichlorobenzene (1:1, 2 mL) in an oven-
dried 25 mL Schlenk tube. The mixture was stirred at 150 °C for 4 h.
The reaction was then stopped stirring, cooled down to room
temperature, and poured into NaOH solution (10%, 10 mL). It was
extracted with EtOAc (3 × 20 mL). The combined organic layers were
dried over Na2SO4, filtered, and concentrated in vacuo. The residue
was purified by column chromatography to give the corresponding
1
products [D]-5a and 5a (33% yield). The H NMR analysis showed
that the ratio of 5a/[D]-5a is 3.7.
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Article
(9) Shrestha, R.; Mukherjee, P.; Tan, Y.; Litman, Z. C.; Hartwig, J. F.
J. Am. Chem. Soc. 2013, 135, 8480.
(10) (a) Kim, H. J.; Kim, J.; Cho, S. H.; Chang, S. J. Am. Chem. Soc.
2011, 133, 16382. (b) Kantak, A. A.; Potavathri, S.; Barham, R. A.;
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(11) Yu, S.; Wan, B.; Li, X. Org. Lett. 2013, 15, 3706.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H NMR and 13C NMR spectra for all new products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(12) For reviews of Cu-catalyzed C−H activation, see: (a) Wend-
landt, A. E.; Suess, A. M.; Stahl, S. S. Angew. Chem., Int. Ed. 2011, 50,
11062. (b) Li, C.-J. Acc. Chem. Res. 2009, 42, 335. (c) Allen, S. E.;
Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013,
113, 6234. (d) Armstrong, A.; Collins, J. C. Angew. Chem., Int. Ed.
2010, 49, 2282 and references therein.
AUTHOR INFORMATION
Corresponding Author
*E-mail: shenzengming@sjtu.edu.cn.
Notes
■
(13) (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 6790. (b) Uemura, T.; Imoto, S.; Chatani, N. Chem.
Lett. 2006, 35, 842. (c) Brasche, G.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2008, 47, 1932. (d) Shuai, Q.; Deng, G.; Chua, Z.; Bohle, D. S.; Li,
C.-J. Adv. Synth. Catal. 2010, 352, 632. (e) Zhao, H.; Wang, M.; Su,
W.; Hong, M. Adv. Synth. Catal. 2010, 352, 1301. (f) John, A.;
Nicholas, K. M. J. Org. Chem. 2011, 76, 4158.
(14) (a) Monguchi, D.; Fujiwara, T.; Furukawa, H.; Mori, A. Org.
Lett. 2009, 11, 1607. (b) Wang, Q.; Schreiber, S. L. Org. Lett. 2009, 11,
5178. (c) Cho, S. H.; Kim, J. Y.; Lee, S. Y.; Chang, S. Angew. Chem.,
Int. Ed. 2009, 48, 9127. (d) Matsuda, N.; Hirano, K.; Satoh, T.; Miura,
M. Org. Lett. 2011, 13, 2860. (e) Zhou, W.; Liu, Y.; Yang, Y.; Deng, G.
Chem. Commun. 2012, 48, 10678. (f) Kawano, T.; Hirano, K.; Satoh,
T.; Miura, M. J. Am. Chem. Soc. 2010, 132, 6900. (g) Wang, H.; Wang,
Y.; Peng, C.; Zhang, J.; Zhu, Q. J. Am. Chem. Soc. 2010, 132, 13217.
(15) (a) Tran, L. D.; Roane, J.; Daugulis, O. Angew. Chem., Int. Ed.
2013, 52, 6043. (b) Li, Q.; Zhang, S.-Y.; He, G.; Ai, Z.; Nack, W. A.;
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(16) Bergman, J.; Eklund, N. Tetrahedron 1980, 36, 1445.
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(18) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 5th ed.; Pergamon Press: Oxford, U.K., 1988.
(19) Xu, S. G.; Huang, X. M.; Hong, X. H.; Xu, B. Org. Lett. 2012, 14,
4614.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Sciences
Foundation of China (21272001), the Shanghai Education
Committee (13ZZ014), and the program for Changjiang
Scholars and Innovative Research Team in University (No.
IRT1269). We appreciate Dr. P. K. Dornan (CIT) for helpful
suggestions.
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(6) For selected examples of Rh-catalyzed C−H amination, see:
(a) Ng, K.-H.; Zhou, Z.; Yu, W.-Y. Org. Lett. 2012, 14, 272.
(b) Grohmann, C.; Wang, H.; Glorius, F. Org. Lett. 2012, 14, 656.
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(7) For a recent review on ruthenium-catalyzed C−H amination, see:
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