Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines

Article abstract of DOI:10.1021/acs.joc.5b01943

The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of indolines with disulfides and diselenides were developed. This protocol relies on the use of a removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance.

Full text of DOI:10.1021/acs.joc.5b01943

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Article
Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines
Wucheng Xie, Bin Li, and Baiquan Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01943 • Publication Date (Web): 19 Dec 2015
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Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines
Wucheng Xie,† Bin Li,† Baiquan Wang*,†,‡,§
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†State Key Laboratory of Elemento-Organic Chemistry, ‡Collaborative Innovation Center of
Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University,
Tianjin 300071, China
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§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
bqwang@nankai.edu.cn
ABSTRACT: The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of
indolines with disulfides and diselenides were developed. This protocol relies on the use of a
removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds
with ample substrate scope and broad functional group tolerance.
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Introduction
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Indole and Indoline scaffolds are ubiquitous structural motifs found in a multitude of
biologically active natural products and pharmaceutical compounds as well as organic dyes.1
In particular, 7-substituted indoles and indolines are particularly important as a result of their
ubiquitous presence in numerous biologically active compounds.2 Therefore, a method for a
general, rapid, and regioselective preparation of 7-substituted indoles and indolines would be
highly desirable.
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Transition-metal-catalyzed C−H bond functionalization has emerged as a powerful tool
due to its remarkable potential for step economy and environmental sustainability.3 Given the
significance of 7-substituted indolines, it would be highly desirable and attractive if we could
directly functionalize the C–H bond at the C-7 position of an indoline by using a
transition-metal-catalyzed C–H activation pathway. Recently, some examples of
transition-metal catalyzed chelation-assisted C7 C−H functionalization of indolines with
various coupling partners have been disclosed by several groups,4−11 e.g. arylation (Figure 1,
1.1a),4 alkenylation (Figure 1, 1.1b),5 alkynylation (Figure 1, 1.1c),6 amination (Figure 1,
1.1d),7 acylation (Figure 1, 1.1f),8 allylation (Figure 1, 1.1g),9 alkylation (Figure 1, 1.1h) of
indolines,10 and C−H functionalization/annulation to build 1,7-fused indolines (Figure 1,
1.1e).11 However, these approaches are generally limited to C–C bond and C–N bond
formation. To the best of our knowledge, there is no report on catalytic C-7 C−H thiolation or
selenation of indolines, although C−S and C−Se bonds represent an important linkage in
organic compounds and are widely found in biologically active natural products,
pharmaceuticals and functional materials.12 While numerous approaches to C−N or C−C bond
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formation through direct C−H functionalization have been reported in recent years, reports of
analogous C−S and C−Se bond formation through direct C−H thiolation and selenation by
transition metals remain scarce.13 Recently, Cu(II)-,14 Pd(II)-,15 Rh(III)-,16 and Ni(II)-17
catalyzed chelate-assisted direct chalcogenations of inert C−H bonds with disulfides and
diselenides have been reported by the groups of Yu, Daugulis, Nishihara, Kambe, Zhou and
Li, Lu, Shi, Zhang, and Qiu. Inspired by these pioneering studies and our interest in the
Rh(III)-catalyzed C−H bond functionalization,18 herein we report Rh(III)-catalyzed
C7-thiolation and selenation of indolines by using a readily available and easily removable
pyrimidyl group as a directing group (Figure 1.2).
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Figure 1. Transition-Metal-Catalyzed C7-Selective C−H Functionalization of Indolines
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Results and Discussions
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Our effort was initially focused on the direct thiolation of 1-(pyrimidin-2-yl)indoline (1a)
with diphenyl disulfide (2a) as a model reaction (Detail optimization studies of reaction see
SI). As shown in Table 1, treatment of 1a (0.3 mmol) with 2a (0.3 mmol, 1.0 equiv) in the
presence of [Cp*RhCl2]2 (5 mol %), AgOTf (20 mol %), and Ag2CO3 (1.0 equiv) in toluene at
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110
°C
for
12
h
under
air,
the
desired
thiolated
product
7-(phenylthio)-1-(pyrimidin-2-yl)indoline 3aa was isolated in 89% yield (entry 1). The
1
structure of 3aa was confirmed by its H and 13C NMR spectra and high-resolution mass
spectrometry. The reaction efficiency could be increased at higher temperature (130 °C),
affording 3aa in 95% yield (entry 2). Notably, when the reaction was carried out at 80 °C,
only trace amount of product was isolated (entry 3). Other representative solvents such as
t-AmOH and MeCN resulted in a significant decrease of yields (entries 4−5). Ag2CO3 played
an important role in the reaction. Decreasing the amount of Ag2CO3 to 50 mol % led to a
decrease in yield, and only 7% yield was obtained without Ag2CO3 (entries 6−7). The control
experiment suggested that AgOTf and [Cp*RhCl2]2 were indispensable for the catalytic
system (entries 8−9). Additionally, we also found that a related cationic Rh(III) catalyst
[Cp*Rh (MeCN)3](SbF6)2 alone was ineffective for this catalytic reaction (entry 10).
With the optimal conditions in hand, the substrate scope was examined with respect to
indolines (Table 2). The indolines bearing electron-donating or electron-withdrawing
substituents at C2, C3, C4, or C5 positions (3ba−ia) participated well in coupling, providing
the corresponding 7-substituted indolines in excellent yields. N-pyrimidinyl indolines
possessing halogen substituents at the C5 position were well-tolerated to afford the desired
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products (3fa−ha) in excellent yields, thus allowing for the possibility of further
transformations. Indoline with methyl moiety at the C4 position exhibited slightly decreased
reactivity (80%, 3da). Indoline with strong electron-withdrawing group NO2 at C5 position
afforded only 39% yield (3ja). It was found that substituents at C6 position would decreased
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Table 1. Optimization of Reaction Conditionsa
entry Ag2CO3 (eq.)
solvent
toluene
toluene
toluene
t-AmOH
MeCN
yields (%)
89%
95%
trace
37%
52%
83%
7%
temp (°C)
110
1
2
1
1
130
3
1
80
4
1
130
5
1
130
6
0.5
none
1
toluene
toluene
toluene
toluene
toluene
130
7
130
8b
9c
10bd
130
n.r.
1
130
n.r.
1
130
n.r.
aConditions: 1a (0.3 mmol), 2a (0.3 mmol), [Cp*RhCl2]2 (0.015 mmol,
5 mol %), AgOTf (0.06 mmol, 20 mol %), solvent (1.5 mL), heating
b
in an sealed tube, under air; isolated yields are shown. No AgOTf.
cNo [Cp*RhCl2]2. d[Cp*Rh(MeCN)3][SbF6]2 instead of [Cp*RhCl2]2.
the yields dramatically (3la, 3ma), probably due to the steric congestion neighboring the
reactive site. The substrate scope was further extended to disulfides. To our delight, various
diaryl disulfides showed good reactivities. Different substituents on the phenyl ring of diaryl
disulfides proceeded smoothly providing the corresponding products in 39−99% yields
(3ab−ag). Both of the strong electron-withdrawing (2c, 2d and 2g) and donating (2f)
substituents in the arene ring of diaryl disulfides decreased the yields. The molecular structure
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of 3ag was further confirmed by single-crystal X-ray diffraction analysis (Figure S1,
Supporting Information). Fortunately, the alkyl and benzyl disulfides were also compatible
with the conditions and afforded the corresponding thiolation products (3ah−aj), although in
low to moderate yields, thus allowing for high diversity in the synthesis of aryl thioethers.
Notably, the choice of the N-protecting group was found to be crucial for this reaction. Acetyl
(1n) or N, N-dimethylcarbamoyl (1o) directing group did not deliver the corresponding
product under the standard conditions.
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Table 2. Substrate Scope of Rh(III)-Catalyzed C7-Thiolation of Indolinesa
aConditions: 1 (0.3 mmol), 2 (0.3 mmol), [Cp*RhCl2]2 (5
mol %), AgOTf (20 mol %), Ag2CO3 (0.3 mmol), toluene
(1.5 mL), 130 °C, 12 h, under air; isolated yields are shown.
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The successful results of direct thiolation led us to examine the related direct selenation
of 1a with diphenyl diselenides. Under similar conditions optimized for direct thiolation, the
desired product 5aa was obtained in 81% yield after 24 h (Table 3). Consequently, we
explored the generality and limitations of this selenation protocol under optimized conditions.
The indolines with a methyl group at C2, C3, C4, or C5 positions were well tolerated, and the
corresponding products were isolated in good yields (5ba−ea). The slightly electron-deficient
(5fa−ha) and rich (5ea, 5ia) substrates were also selenylated under the standard conditions in
good yields. Especially, the indolines bearing a chloro or bromo functional group (5ga, 5ha)
were also compatible with this catalytic system, thus offering the opportunity for further
transformations. A relatively lower yield (30%) was obtained when a strong
electron-withdrawing group (NO2, 5ja) was introduced into the C5-position of indoline. To
demonstrate the scope of diselenide substrates, different readily synthesized diselenides were
applied as substrates to couple with 1a. Thus, symmetrical diselenides with a wide range of
valuable functional groups such as methoxy (4d), chloro (4b), and ester (4e) groups in the
arene ring of diaryl diselenides all reacted smoothly with good efficiency (5ab−ae).
In addition, the utility of this C7-thiolation reaction was further highlighted by its
successful conversion of indolines into indoles 6 in almost quantitative yield (Scheme 2, eq 1).
Moreover, the pyrimidyl group can be successfully removed by reaction with NaOEt in
DMSO at 100 °C for 4 h, affording 7-(phenylthio)-1H-indole 7 in 97% yield. Selective
oxidation of 3aa with m-CPBA furnished the sulfonyl indoline 8 in 54% yield (Scheme 1, eq
2).
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Table 3. Substrate Scope of Rh(III)-Catalyzed C7-Selenation of Indolinesa
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R1
R1
[Cp*RhCl2]2 5 mol %
AgOTf 20 mol %
N
N
RSeSeR
+
Ag2CO3 1.0 equiv
toluene, 130 oC, 24 h
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N
N
RSe
H
N
N
under air
1
5
4
N
N
N
N
N
N
N
N
PhSe
PhSe
PhSe
PhSe
N
N
N
N
5ca, 63%
R = 4-ClC6H4, 5ab, 79%c
5da, 68%
5ba,
5aa, 81%
57%
R = Me, 5ea, 69%
5fa,
R = Cl, 5ga, 58%
R = Br, 5ha, 58%
R = OMe,
R = NO2, 5ja, 30%
R
R = F,
58%
c
5ac,
R = 4-MeC6H4,
70%
N
N
R = 4-OMeC6H4, 5ad, 78%c
N
Se
c
N
5ae,
78%
R = 4-CO2EtC6H4,
PhSe
R
N
5ia,
61%
N
c
5af,
R = Bn,
25%
aConditions: 1 (0.3 mmol), 4 (0.3 mmol), [Cp*RhCl2]2 (5 mol %),
AgOTf (20 mol %), Ag2CO3 (0.3 mmol), toluene (1.5 mL), 130
°C, 24 h, under air; isolated yields are shown. c4 (0.45 mmol).
Scheme 1. Derivatization Reactions
To gain a mechanistic insight, H/D exchange experiments were performed (Scheme 2).
Significant H-D scrambling was observed at the C7 position of indoline 1a when toluene and
D2O were employed as a mixed solvent system (Scheme 2, eq 3). When the reaction was
performed in the presence of 2a, no deuterium incorporation of product 3aa was observed
except for significant deuteration (98% D) of recovered starting material (Scheme 2, eq 4).
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Together, these results indicated the reversibility of the C−H activation.
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Scheme 2. Deuterium Exchange Reactions
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Scheme 3. Mechanism Proposal
A proposed mechanistic pathway for the Rh(III)-catalyzed thiolation of indolines with
disulfide is depicted in Scheme 3.[16a] We hypothesize that a proposed catalytic cycle initiates
with the formation of the rhodacycle intermediate A via Rh(III)-catalyzed C−H activation.
Intermediate A can undergo nucleophilic substitution reaction with disulfide to afford the
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desired product 3aa and Rh(III) species B. Reaction of Rh(III) complex B with 1a forms the
rhodacycle intermediate C via C−H activation, which would undergo reductive elimination to
afford 3aa together with a rhodium(I) species. Finally, Rh(I) is oxidized to Rh(III) by external
oxidant Ag2CO3 to complete the catalytic cycle.
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Conclusion
In conclusion, we have disclosed a highly selective C7-thiolation and selenation of
indolines with disulfides and diselenides through Rh(III)-catalyzed C−H bond activation.
These transformations have been applied to a wide range of substrates, and typically proceed
with excellent levels of chemoselectivity as well as with high functional group tolerance.
Synthetic utility of the current approach was demonstrated by the successful access to C-7
thiolated indoles and the removal of a pyrimidyl group. Considering the valuable structure of
the products, we expect this regioselective thiolation and selenation reaction to gain broad
synthetic utility. Detailed mechanistic studies and synthetic applications are underway.
Experimental Section
General Information. All the reactions were carried out under argon atmosphere using
standard Schlenk technique. 1H NMR (400 MHz), 19F (376 M Hz), and 13C NMR (100 MHz)
were recorded on a NMR spectrometer with CDCl3 as solvent. Chemical shifts of 1H, 19F, and
13C NMR spectra are reported in parts per million (ppm). The residual solvent signals were
used as references and the chemical shifts converted to the TMS scale (CDCl3: δ H = 7.26
ppm, δ C = 77.00 ppm). All coupling constants (J values) were reported in Hertz (Hz).
Multiplicities are reported as follows: singlet (s), doublet (d), doublet of doublets (dd), triplet
(t), quartet (q), and multiplet (m). Column chromatography was performed on silica gel
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200−300 mesh. IR spectra were recorded as KBr disks on a FT-IR spectrometer.
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High-resolution mass spectrometry (HRMS) was done on a FTICR-mass spectrometer.
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.
[Cp*RhCl2]2 was prepared from RhCl3 xH2O following a literature procedure.19 The
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substrates disulfides and diselenides,20 and 1a−o6a were prepared according to the literatures.
Unless otherwise noted below, all other compounds have been reported in the literature or are
commercially available without any further purification.
General Procedure for the Preparation of 1-(Pyrimidin-2-yl)indolines 1.6a,21 To a
solution of an indole (5.0 mmol, 1.0 eq.) in AcOH (25 mL) at 0 °C was added NaBH3CN
(1.26 g, 20.0 mmol, 4.0 eq.) in portions. The reaction was allowed to stir at room temperature
until completion (typically 4 h). Water was then added and the reaction mixture was basified
with NaOH aqueous solution, extracted with EtOAc three times. The combined organic layers
were dried over MgSO4, filtered, and evaporated under reduced pressure to afford the
corresponding crude indoline.
The crude indoline and 2-chloropyrimidine (0.57g, 5.0 mmol, 1.0 eq.) was dissolved in a
mixture of EtOH (40 mL) and H2O (10 mL). Concentrated hydrochloric acid (1 mL) was
added to the mixture. Then the resulting solution was refluxed overnight. EtOH was then
removed under reduce pressure, and the aqueous phase was extracted twice with CH2Cl2. The
combined organic layers were dried over MgSO4, filtered, and evaporated under reduced
pressure. The purification was performed by flash column chromatography on silica gel with
petroleum ether/EtOAc (8:1−3:1).
General Procedure for Rh(III)-Catalyzed C7-Thiolation of Indolines. An oven-dried
reaction vessel was charged with [Cp*RhCl2]2 (9.3 mg, 0.015 mmol), AgOTf (15.4 mg, 0.06
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mmol), 1-(pyrimidin-2-yl)indoline (1a) (59.2 mg, 0.3 mmol), diphenyl disulfide (2a) (65.5
mg, 0.3 mmol), Ag2CO3 (82.7 mg, 0.3 mmol), and 1.5 mL of toluene under air. The vessel
was sealed and heated at 130 °C (oil bath) for 12 h. The resulting mixture was cooled to room
temperature, diluted with CH2Cl2 and transferred to a round bottom flask. Silica was added to
the flask and volatiles were evaporated under reduced pressure. The purification was
performed by column chromatography on silica gel with petroleum ether/EtOAc (8:1) to give
product 3aa (87.4 mg, 95%).
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7-(Phenylthio)-1-(pyrimidin-2-yl)indoline (3aa): white solid (87.4 mg, 95%); Mp
133−134 °C; 1H NMR (CDCl3, 400 MHz) δ 8.49 (d, J = 4.5 Hz, 2H), 7.41–7.09 (m, 7H), 6.96
(t, J = 7.5 Hz, 1H), 6.75 (t, J = 4.5 Hz, 1H), 4.51 (t, J = 7.8 Hz, 2H), 3.18 (t, J = 7.8 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ 160.6, 157.1, 143.7, 138.1, 134.6, 131.4, 131.0, 128.6, 126.4,
125.9, 124.1, 122.9, 112.7, 52.2, 29.5; IR (cm−1) ν 1576, 1552, 1455, 1426, 1382, 1278, 800,
770, 750, 694; HRMS (ESI) calcd for C18H16N3S [M+H]+ 306.1065, found 306.1062.
2-Methyl-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ba). white solid (90.0 mg, 94%);
mp 123−125 °C; 1H NMR (CDCl3, 400 MHz) δ 8.43 (d, J = 4.5 Hz, 2H), 7.23–7.10 (m, 7H),
6.93 (t, J = 7.5 Hz, 1H), 6.71 (t, J = 4.5 Hz, 1H), 5.04– 4.92 (m, 1H), 3.52 (dd, J = 15.4, 8.6
Hz, 1H), 2.58 (d, J = 15.5 Hz, 1H), 1.45 (d, J = 6.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ
160.3, 157.3, 142.8, 138.6, 133.5, 132.1, 130.9 128.7, 126.3, 126.2, 124.2, 123.8, 112.8, 59.7,
36.9, 21.4; IR (cm−1) ν 1576, 1551, 1462, 1435, 1222, 1056, 794, 765, 741, 686; HRMS (ESI)
calcd for C19H18N3S [M+H]+ 320.1221, found 320.1220.
3-Methyl-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ca): white solid (87.5 mg, 91%);
mp 123−125 °C; 1H NMR (CDCl3, 400 MHz) δ 8.41 (d, J = 4.7 Hz, 2H), 7.26 (d, J = 7.6 Hz,
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2H), 7.22–7.12 (m, 3H), 7.09 (d, J = 7.9 Hz, 1H), 7.04 (d, J = 7.2 Hz, 1H), 6.91 (t, J = 7.6 Hz,
1H), 6.67 (dd, J = 6.3, 3.1 Hz, 1H), 4.63 (t, J = 9.6 Hz, 1H), 3.99–3.91 (m, 1H), 3.44 (d, J =
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7.1 Hz, 1H), 1.30 (d, J = 6.8 Hz, 3H); C NMR (CDCl3, 100 MHz) δ 160.8, 157.2, 143.4,
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139.8, 138.0, 131.4, 131.1, 128.7, 126.5, 125.9, 124.3, 121.7, 112.7, 60.1, 36.2, 18.7; IR (cm−1)
ν 1576, 1552, 1423, 1279, 1054, 785, 749, 695; HRMS (ESI) calcd for C19H18N3S [M+H]+
320.1221, found 320.1222.
4-Methyl-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3da): white solid (76.5 mg, 80%);
mp 128−130 °C; 1H NMR (CDCl3, 400 MHz) δ 8.37 (d, J = 4.5 Hz, 2H), 7.21–7.11 (m, 4H),
7.10–7.01 (m, 2H), 6.73 (d, J = 8.0 Hz, 1H), 6.65 (t, J = 4.4 Hz, 1H), 4.41 (t, J = 7.8 Hz, 2H),
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3.00 (t, J = 7.7 Hz, 2H), 2.19 (s, 3H); C NMR (CDCl3, 100 MHz) δ 160.8, 157.1, 143.8,
138.9, 133.2, 132.8, 132.1, 130.3, 128.5, 126.0, 125.5, 122.2, 112.7, 52.0, 28.3, 18.4; IR (cm−1)
ν 1575, 1556, 1453, 1402, 1274, 1207, 1059, 797, 743, 693; HRMS (ESI) calcd for C19H18N3S
[M+H]+ 320.1221, found 320.1222.
5-Methyl-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ea): white solid (88.2 mg, 92%);
mp 137−139 °C; 1H NMR (CDCl3, 400 MHz) δ 8.37 (d, J = 4.7 Hz, 2H), 7.28–7.06 (m, 5H),
6.90 (d, J = 5.8 Hz, 2H), 6.63 (t, J = 4.7 Hz, 1H), 4.40 (t, J = 7.8 Hz, 2H), 3.04 (t, J = 7.8 Hz,
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3H), 2.15 (s, 3H); C NMR (CDCl3, 100 MHz) δ 160.8, 157.1, 141.8, 138.4, 134.8, 134.0
131.7, 130.6, 128.6, 126.2, 125.2, 124.1, 112.5, 52.3, 29.6, 20.7; IR (cm−1) ν 1575, 1552,
1458, 1402, 1274, 1208, 797, 748, 694; HRMS (ESI) calcd for C19H18N3S [M+H]+ 320.1221,
found 320.1221.
5-Fluoro-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3fa): white solid (87.0 mg, 90%);
mp 129−132 °C; 1H NMR (CDCl3, 400 MHz) δ 8.41 (d, J = 4.8 Hz, 2H), 7.35–7.27 (m, 2H),
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7.27–7.16 (m, 3H), 6.81–6.74 (m, 1H), 6.69 (dd, J = 11.4, 6.9 Hz, 2H), 4.45 (t, J = 7.8 Hz,
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2H), 3.07 (t, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 160.7, 159.4 (d, JC-F = 243.6 Hz)
157.3, 139.5, 136.7, 136.4 (d, JC-F = 8.9 Hz), 132.2, 129.0, 128.3 (d, JC-F = 8.4 Hz), 127.3,
116.4 (d, JC-F = 24.9 Hz), 112.7, 110.3 (d, JC-F = 24.1 Hz), 52.6, 29.8; 19F NMR (CDCl3, 376
MHz) δ −119.1; IR (cm−1) ν 1576, 1550, 1455, 1429, 1405, 1278, 1255, 1195, 864, 795, 748,
693; HRMS (ESI) calcd for C18H15FN3S [M+H]+ 324.0971, found 324.0972.
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5-Chloro-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ga): white solid (94.8 mg, 93%);
mp 146−148 °C; 1H NMR (CDCl3, 400 MHz) δ 8.41 (d, J = 4.7 Hz, 2H), 7.31–7.24 (m, 2H),
7.24–7.15 (m, 3H), 7.00 (d, J = 6.2 Hz, 1H), 6.70 (t, J = 4.7 Hz, 1H), 4.42 (t, J = 7.8 Hz, 2H),
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3.07 (t, J = 7.8 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.5, 157.2, 142.3, 136.9, 136.3,
131.7, 130.1, 128.9, 128.7, 127.8, 127.2, 123.0, 113.0, 52.4, 29.4; IR (cm−1) ν 1576, 1553,
1443, 1403, 1188, 1149, 853, 799, 760, 697; HRMS (ESI) calcd for C18H15ClN3S [M+H]+
340.0675, found 340.0675.
5-Bromo-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ha): white solid (111.8 mg, 97%);
mp 165−167 °C; 1H NMR (CDCl3, 400 MHz) δ 8.41 (d, J = 4.7 Hz, 2H), 7.30–7.13 (m, 7H),
6.71 (t, J = 4.7 Hz, 1H), 4.42 (t, J = 7.9 Hz, 2H), 3.08 (t, J = 7.8 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ 160.5, 157.3, 142.8, 136.9, 136.7, 133.0, 131.6, 129.0, 128.2, 127.1, 125.8, 116.2,
113.1, 52.3, 29.3; IR (cm−1) ν 1574, 1552, 1460, 1394, 1275, 1207, 1152, 794, 744, 691;
HRMS (ESI) calcd for C18H15BrN3S [M+H]+ 384.0170, found 384.0166.
5-Methoxy-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ia): white solid (89.1 mg, 89%);
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mp 95−97 °C; H NMR (CDCl3, 400 MHz) δ 8.36 (d, J = 4.7 Hz, 2H), 7.35–7.04 (m, 5H),
6.76–6.50 (m, 3H), 4.40 (t, J = 7.7 Hz, 2H), 3.56 (s, 3H), 3.03 (t, J = 7.7 Hz, 2H); 13C NMR
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(CDCl3, 100 MHz) δ 160.9, 157.2, 156.6, 137.6, 137.5, 136.1, 131.3, 128.7, 126.9, 126.6,
115.2, 112.3, 110.2, 55.5, 52.4, 30.0; IR (cm−1) ν 1577, 1550, 1461, 1407, 1277, 1194, 1116,
1040, 796, 748, 693; HRMS (ESI) calcd for C19H18N3OS [M+H]+ 336.1171, found 336.1171.
5-Nitro-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ja): yellow solid (41.4 mg, 39%); mp
162−164 °C; 1H NMR (CDCl3, 400 MHz) δ 8.52 (d, J = 4.8 Hz, 2H), 7.96 (d, J = 1.8 Hz, 1H),
7.90 (s, 1H), 7.27 (m, 5H), 6.87 (t, J = 4.8 Hz, 1H), 4.52 (t, J = 8.2 Hz, 2H), 3.24 (t, J = 8.2
Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 159.8, 157.5, 148.7, 143.8, 136.0, 135.4, 132.3,
129.3, 127.9, 127.7, 126.9, 118.0, 114.4, 52.8, 28.7; IR (cm−1) ν 1568, 1506, 1428, 1317,
1286, 1077, 802, 751, 695, 634; HRMS (ESI) calcd for C18H15N4O2S [M+H]+ 351.0916, found
351.0913.
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Methyl 7-(phenylthio)-1-(pyrimidin-2-yl)indoline-5-carboxylate (3ka): yellow solid (66.9
mg, 61%); mp 156−160 °C; 1H NMR (CDCl3, 400 MHz) δ 8.39 (s, 2H), 7.73 (d, J = 36.4 Hz,
2H), 7.13 (s, 5H), 6.72 (s, 1H), 4.39 (t, J = 7.4 Hz, 2H), 3.73 (s, 3H), 3.12 (t, J = 7.2 Hz, 2H).;
13C NMR (CDCl3, 100 MHz) δ 166.4, 160.2, 157.3, 147.9, 137.5, 134.8, 134.4, 130.9, 128.9,
126.8, 125.8, 125.1, 124.2, 113.7, 52.6, 51.9, 28.9; IR (cm−1) ν 1715, 1577, 1553, 1445, 1278,
1201, 1157, 908, 794, 769, 743, 689; HRMS (ESI) calcd for C20H18N3O2S [M+H]+ 364.1120,
found 364.1119.
6-Fluoro-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3la): white solid (38.7 mg, 40%); mp
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142−144 °C; H NMR (CDCl3, 400 MHz) δ 8.38 (d, J = 3.7 Hz, 2H), 7.20–7.05 (m, 6H),
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6.80–6.71 (m, 2H), 4.48 (t, J = 7.7 Hz, 2H), 3.12 (t, J = 7.7 Hz, 2H); C NMR (CDCl3, 100
MHz) δ 161.4 (d, JC-F = 122.5 Hz), 160.7, 160.5, 157.2, 147.2 (d, JC-F = 4.8 Hz), 137.5, 130.1
(d, JC-F = 2.6 Hz), 128.5, 127.9, 125.6, 124.7 (d, JC-F = 9.9 Hz), 113.4, 112.3 (d, JC-F = 22.2
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Hz), 110.7 (d, JC-F = 24.6 Hz), 53.3, 29.0; 19F NMR (CDCl3, 376 MHz) δ −107.9; IR (cm−1) ν
1577, 1551, 1458, 1431, 1379, 1230, 1186, 795, 754, 691; HRMS (ESI) calcd for C18H15FN3S
[M+H]+ 324.0971, found 324.0971.
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6-Chloro-7-(phenylthio)-1-(pyrimidin-2-yl)indoline (3ma): white solid (17.0 mg, 17%);
mp 176−178 °C; 1H NMR (CDCl3, 400 MHz) δ 8.37 (d, J = 4.8 Hz, 2H), 7.19–7.11 (m, 4H),
7.08 (d, J = 7.2 Hz, 1H), 6.96–6.91 (m, 2H), 6.75 (t, J = 4.8 Hz, 1H), 4.46 (t, J = 7.9 Hz, 2H),
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3.14 (t, J = 7.9 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.7, 157.2, 148.3, 137.6, 133.8,
128.5, 127.5, 125.6, 125.4, 125.1, 122.4, 113.4, 53.2, 29.4; IR (cm−1) ν 1571, 1551, 1426,
1106, 812, 741, 691; HRMS (ESI) calcd for C18H15ClN3S [M+H]+ 340.0675, found 340.0669.
1-(Pyrimidin-2-yl)-7-(p-tolylthio)indoline (3ab): white solid (95.2 mg, 99%); mp
121−123 °C; 1H NMR (CDCl3, 400 MHz) δ 8.43 (d, J = 4.7 Hz, 2H), 7.19 (d, J = 7.5 Hz, 2H),
7.03 (t, J = 9.4 Hz, 2H), 6.86 (d, J = 7.4 Hz, 3H), 6.69 (t, J = 4.7 Hz, 1H), 4.44 (t, J = 7.8 Hz,
2H), 3.11 (t, J = 7.8 Hz, 2H), 2.27 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 160.7, 157.3, 143.3,
136.8, 134.5, 134.2, 132.0, 130.7, 129.6, 127.0, 124.1, 122.5, 112.7, 52.3, 29.6, 21.0; IR (cm−1)
ν 1573, 1550, 1489, 1454, 1426, 799, 761, 723; HRMS (ESI) calcd for C19H18N3S [M+H]+
320.1221, found 320.1222.
7-(4-Fluorophenylthio)-1-(pyrimidin-2-yl)indoline (3ac): white solid (49.5 mg, 51%); mp
130−132 °C; 1H NMR (CDCl3, 400 MHz) δ 8.42 (d, J = 4.7 Hz, 2H), 7.24 (dd, J = 7.6, 5.3 Hz,
2H), 7.06 (d, J = 7.2 Hz, 1H), 6.97 (d, J = 7.9 Hz, 1H), 6.94–6.83 (m, 3H), 6.70 (t, J = 4.7 Hz,
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1H), 4.43 (t, J = 7.9 Hz, 2H), 3.11 (t, J = 7.8 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 162.0
(d, JC-F = 247.3 Hz), 160.8, 160.7, 157.4, 143.4, 134.7, 133.9 (d, JC-F = 7.8 Hz), 133.1 (d, JC-F
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= 3.3 Hz), 130.8, 126.7, 124.3, 122.9, 115.9 (d, JC-F = 21.8 Hz), 112.8, 52.3, 29.6; F NMR
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(CDCl3, 376 MHz) δ −114.8; IR (cm−1) ν 1575, 1551, 1485, 1452, 1423, 836, 797, 769, 728;
HRMS (ESI) calcd for C18H15FN3S [M+H]+ 324.0971, found 324.0969.
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7-(4-Chlorophenylthio)-1-(pyrimidin-2-yl)indoline (3ad): white solid (69.5 mg, 68%); mp
123−125 °C; 1H NMR (CDCl3, 400 MHz) δ 8.42 (d, J = 4.7 Hz, 2H), 7.17 (s, 4H), 7.09 (dd, J
= 17.1, 7.5 Hz, 2H), 6.91 (t, J = 7.6 Hz, 1H), 6.71 (t, J = 4.7 Hz, 1H), 4.45 (t, J = 7.9 Hz, 2H),
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3.13 (t, J = 7.8 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.6, 157.2, 144.0, 137.1, 134.8,
132.3, 132.1, 131.5, 128.8, 125.4, 124.3, 123.3, 112.8, 52.2, 29.5; IR (cm−1) ν 1574, 1549,
1456, 1429, 1382, 1087, 801, 775; HRMS (ESI) calcd for C18H15ClN3S [M+H]+ 340.0675,
found 340.0672.
7-(4-Bromophenylthio)-1-(pyrimidin-2-yl)indoline (3ae): white solid (102.2 mg, 89%);
mp 111−114 °C; 1H NMR (CDCl3, 400 MHz) δ 8.42 (d, J = 4.7 Hz, 2H), 7.31 (d, J = 8.4 Hz,
2H), 7.16–7.05 (m, 4H), 6.91 (t, J = 7.6 Hz, 1H), 6.72 (t, J = 4.7 Hz, 1H), 4.46 (t, J = 7.9 Hz,
2H), 3.14 (t, J = 7.9 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 160.7, 157.2, 144.1, 137.9,
134.8, 132.3, 131.7, 131.6, 125.2, 124.3, 123.4, 120.2, 112.9, 52.2, 29.5; IR (cm−1) ν 1574,
1549, 1456, 1430, 1381, 801, 774; HRMS (ESI) calcd for C18H15BrN3S [M+H]+ 384.0170,
found 384.0162.
7-(4-Methoxyphenylthio)-1-(pyrimidin-2-yl)indoline (3af): white solid (45.2 mg, 45%);
mp 117−119 °C; 1H NMR (CDCl3, 400 MHz) δ 8.47 (d, J = 4.7 Hz, 2H), 7.31 (d, J = 8.6 Hz,
2H), 7.03 (d, J = 7.1 Hz, 1H), 6.95 (d, J = 7.9 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.79 (d, J =
8.5 Hz, 2H), 6.71 (t, J = 4.7 Hz, 1H), 4.46 (t, J = 7.8 Hz, 2H), 3.77 (s, 3H), 3.12 (t, J = 7.8 Hz,
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2H); C NMR (CDCl3, 100 MHz) δ 160.7, 159.2, 157.3, 142.6, 134.7, 134.3, 129.9, 128.1,
127.8, 124.0, 122.1, 114.4, 112.6, 55.2, 52.3, 29.6; IR (cm−1) ν 1579, 1550, 1488, 1455, 1376,
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1291, 1243, 1168, 1033, 814, 787, 725; HRMS (ESI) calcd for C19H18N3OS [M+H]+ 336.1171,
found 336.1168.
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7-(2-Nitrophenylthio)-1-(pyrimidin-2-yl)indoline (3ag): yellow solid (41.1 mg, 39%); mp
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178−180 °C; 1H NMR (CDCl3, 400 MHz) δ 8.28 (d, J = 4.8 Hz, 2H), 8.06 (dd, J = 8.2, 1.2 Hz,
1H), 7.30 (m, 3H), 7.20–7.11 (m, 1H), 7.04 (t, J = 7.6 Hz, 1H), 6.98 (dd, J = 8.2, 0.9 Hz, 1H),
6.69 (t, J = 4.8 Hz, 1H), 4.42 (t, J = 7.9 Hz, 2H), 3.17 (t, J = 7.9 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ 160.3, 157.1, 146.6, 146.0, 139.6, 136.0, 135.0, 132.7, 129.8, 125.7, 125.1, 124.7,
124.7, 121.4, 113.4, 52.4, 29.5; IR (cm−1) ν 1576, 1552, 1510, 1455, 1427, 1344, 1303, 774,
733; HRMS (ESI) calcd for C18H15N4O2S [M+H]+ 351.0916, found 351.0912.
7-(Butylthio)-1-(pyrimidin-2-yl)indoline (3ah): white solid (37.1 mg, 43%); mp 76−78 °C;
1H NMR (CDCl3, 400 MHz) δ 8.36 (d, J = 4.7 Hz, 2H), 7.19 (d, J = 7.3 Hz, 1H), 6.96 (dd, J =
21.4, 7.3 Hz, 2H), 6.63 (t, J = 4.7 Hz, 1H), 4.35 (t, J = 7.8 Hz, 2H), 3.02 (t, J = 7.7 Hz, 2H),
2.82–2.71 (m, 2H), 1.47–1.36 (m, 2H), 1.27 (dd, J = 14.7, 7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz,
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3H); C NMR (CDCl3, 100 MHz) δ 160.7, 157.3, 143.5, 134.4, 128.3, 127.4, 124.1, 121.9,
112.6, 52.6, 35.0, 31.3, 29.7, 22.0, 13.6; IR (cm−1) ν 1577, 1550, 1461, 1434, 1385, 1276, 794,
769; HRMS (ESI) calcd for C16H20N3S [M+H]+ 286.1378, found 286.1371.
7-(Benzylthio)-1-(pyrimidin-2-yl)indoline (3ai): brown solid (36.8 mg, 38%); mp
158−159 °C; 1H NMR (CDCl3, 400 MHz) δ 8.42 (d, J = 4.8 Hz, 2H), 7.33 (d, J = 7.8 Hz, 1H),
7.27–7.22 (m, 4H), 7.22–7.17 (m, 1H), 7.08 (d, J = 6.7 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.68
(t, J = 4.8 Hz, 1H), 4.37 (t, J = 7.9 Hz, 2H), 4.03 (s, 2H), 3.08 (t, J = 7.9 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ 160.7, 157.3, 143.7, 137.7, 134.5, 129.2, 129.0, 128.2, 127.0, 126.9,
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124.1, 122.5, 112.6, 52.3, 40.6, 29.7; IR (cm−1) ν 1577, 1553, 1454, 1432, 1381, 796, 765,
702; HRMS (ESI) calcd for C19H18N3S [M+H]+ 320.1221, found 320.1217.
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88−90 °C; H NMR (CDCl3, 400 MHz) δ 8.43 (d, J = 4.7 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1H),
7.08 (d, J = 7.1 Hz, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.69 (t, J = 4.7 Hz, 1H), 4.41 (t, J = 7.8 Hz,
2H), 3.09 (t, J = 7.8 Hz, 3H), 1.83 (d, J = 8.3 Hz, 2H), 1.68 (d, J = 10.5 Hz, 2H), 1.56 (d, J =
10.6 Hz, 1H), 1.24–1.09 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ 161.0, 157.3, 144.8, 134.5,
130.0, 125.8, 124.0, 122.4, 112.7, 52.6, 47.3, 33.3, 29.8, 26.2, 25.8; IR (cm−1) ν 1575, 1549,
1450, 1423, 1377, 797, 773; HRMS (ESI) calcd for C18H22N3S [M+H]+ 312.1534, found
312.1533.
General Procedure for Rhodium(III)-Catalyzed C7-Selective Selenation of Indolines.
An oven-dried reaction vessel was charged with [Cp*RhCl2]2 (9.3 mg, 0.015 mmol), AgOTf
(15.4 mg, 0.06 mmol), 1-(pyrimidin-2-yl) indoline (1a; 59.2 mg, 0.3 mmol), diphenyl
diselenide (4a, 93.6 mg, 0.3 mmol, 1.0 eq.), Ag2CO3 (82.7 mg, 0.3 mmol), and 1.5 mL of
toluene (0.2 m) under air. The vessel was sealed and heated at 130 °C (oil bath) for 24 h. The
resulting mixture was cooled to room temperature, diluted with CH2Cl2 and transferred to a
round bottom flask. Silica was added to the flask and volatiles were evaporated under reduced
pressure. The purification was performed by flash column chromatography on silica gel with
petroleum ether/EtOAc (10:1) to give products 5aa (85.4 mg, 81%). 5ab−5ae were prepared
with 1.5 eq. diselenides.
7-(Phenylselanyl)-1-(pyrimidin-2-yl)indoline (5aa): brown solid (85.4 mg, 81%); mp
1
154−156 °C; H NMR (CDCl3, 400 MHz) δ 8.46 (d, J = 4.8 Hz, 2H), 7.53–7.45 (m, 2H),
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1H), 6.73 (t, J = 4.8 Hz, 1H), 4.49 (t, J = 8.0 Hz, 2H), 3.15 (t, J = 8.0 Hz, 2H); C NMR
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(CDCl3, 100 MHz) δ 160.6, 157.4, 144.0, 134.7, 134.2, 134.1, 132.2, 129.0, 127.2, 124.3,
122.9, 122.7, 112.7, 51.4, 29.5; IR (cm−1) ν 1573, 1550, 1455, 1427, 1378, 1278, 801, 789,
738, 690; HRMS (ESI) calcd for C18H16N3Se [M+H]+ 354.0509, found 354.0506.
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2-Methyl-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ba): brown solid (62.7 mg,
57%); mp 137−139 °C; 1H NMR (CDCl3, 400 MHz) δ 8.44 (d, J = 4.7 Hz, 2H), 7.52–7.39 (m,
2H), 7.26–7.14 (m, 4H), 7.09 (d, J = 7.2 Hz, 1H), 6.83 (t, J = 7.6 Hz, 1H), 6.71 (t, J = 4.7 Hz,
1H), 5.09–4.99 (m, 1H), 3.51 (dd, J = 15.5, 8.7 Hz, 1H), 2.60 (d, J = 15.6 Hz, 1H), 1.47 (d, J
= 6.5 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 160.3, 157.4, 142.8, 134.9, 133.9, 132.9, 132.5,
128.9, 127.0, 124.2, 123.5, 123.1, 112.7, 58.7, 36.8, 21.2; IR (cm−1) ν 1574, 1551, 1453, 1427,
1378, 1277, 1210, 803, 765; HRMS (ESI) calcd for C19H18N3Se [M+H]+ 368.0666, found
368.0663.
3-Methyl-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ca): brown solid (69.0 mg,
63%); mp 127−129 °C; 1H NMR (CDCl3, 400 MHz) δ 8.46 (d, J = 4.8 Hz, 2H), 7.49 (dd, J =
6.7, 2.6 Hz, 2H), 7.22 (dd, J = 7.2, 3.7 Hz, 3H), 7.13 (d, J = 7.9 Hz, 1H), 7.04 (d, J = 7.2 Hz,
1H), 6.85 (t, J = 7.6 Hz, 1H), 6.72 (t, J = 4.8 Hz, 1H), 4.68 (dd, J = 11.1, 8.4 Hz, 1H), 3.98
(dd, J = 11.2, 7.3 Hz, 1H), 3.46 (dd, J = 14.5, 7.2 Hz,1H), 1.33 (d, J = 6.8 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 160.8, 157.3, 143.7, 139.4, 134.5, 134.2, 132.2, 128.9, 127.2, 124.0,
122.7, 121.7, 112.6, 59.3, 36.3, 18.9.; IR (cm−1) ν 1574, 1551, 1441, 1424, 1279, 801, 781,
740, 691; HRMS (ESI) calcd for C19H18N3Se [M+H]+ 368.0666, found 368.0663.
4-Methyl-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5da): brown oil (76.0 mg, 69%);
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1H NMR (CDCl3, 400 MHz) δ 8.48 (d, J = 4.7 Hz, 2H), 7.53–7.45 (m, 2H), 7.26–7.20 (m,
3H), 7.12 (d, J = 8.0 Hz, 1H), 6.73 (dd, J = 11.8, 6.6 Hz, 1H), 4.52 (t, J = 8.0 Hz, 2H), 3.08 (t,
J = 7.9 Hz, 2H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 160.7, 157.3, 143.8, 135.0,
133.8, 133.6, 132.8, 132.4, 131.6, 129.0, 128.9, 128.8, 126.9, 125.5, 119.1, 112.6, 51.2, 28.2,
18.4; IR (cm−1) ν 1575, 1550, 1443, 1279, 1224, 794, 739, 692; HRMS (ESI) calcd for
C19H18N3Se [M+H]+ 368.0666, found 368.0664.
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5-Methyl-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ea): brown solid (76.5 mg,
70%); mp 160−161 °C; 1H NMR (CDCl3, 400 MHz) δ 8.44 (d, J = 4.7 Hz, 2H), 7.51–7.43 (m,
2H), 7.26–7.19 (m, 3H), 6.96 (s, 1H), 6.91 (s, 1H), 6.70 (t, J = 4.7 Hz, 1H), 4.47 (t, J = 7.9 Hz,
2H), 3.10 (t, J = 7.8 Hz, 2H), 2.15 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 160.8, 157.3, 142.0,
134.8, 134.3, 134.1, 133.8, 132.5, 128.9, 127.0, 124.0, 122.2, 112.4, 51.6, 29.6, 20.7; IR (cm−1)
ν 1579, 1547, 1459, 1433, 1402, 1374, 1276, 1221, 857, 796, 740, 690; HRMS (ESI) calcd for
C19H18N3Se [M+H]+ 368.0666, found 368.0659.
5-Fluoro-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5fa): brown solid (64.2 mg, 58%);
mp 132−135 °C; 1H NMR (CDCl3, 400 MHz) δ 8.48 (d, J = 4.7 Hz, 2H), 7.55 (d, J = 7.0 Hz,
2H), 7.29 (d, J = 5.9 Hz, 3H), 6.82 (d, J = 8.5 Hz, 2H), 6.75 (t, J = 4.7 Hz, 1H), 4.53 (t, J =
13
7.9 Hz, 2H), 3.14 (t, J = 7.8 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.6, 159.3 (d, JC-F
=
=
244.3 Hz), 157.4, 140.1, 135.9 (d, JC-F = 8.7 Hz), 134.7, 133.6, 129.2, 127.8, 124.4 (d, JC-F
7.6 Hz), 117.6 (d, JC-F = 24.8 Hz), 112.7, 110.3 (d, JC-F = 24.0 Hz), 51.7, 29.7; 19F NMR
(CDCl3, 376 MHz) δ −119.5; IR (cm−1) ν 1576, 1550, 1455, 1429, 1404, 1282, 865, 796, 738,
690; HRMS (ESI) calcd for C18H15FN3Se [M+H]+ 372.0415, found 372.0409.
5-Chloro-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ga): brown solid (67.5 mg,
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58%); mp 152−154 °C; 1H NMR (CDCl3, 400 MHz) δ 8.46 (d, J = 4.7 Hz, 2H), 7.57–7.44 (m,
2H), 7.27 (d, J = 4.2 Hz, 3H), 7.05 (d, J = 7.2 Hz, 2H), 6.75 (t, J = 4.7 Hz, 1H), 4.49 (t, J =
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8.0 Hz, 2H), 3.12 (t, J = 7.9 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.5, 157.4, 142.8,
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135.8, 134.4, 133.7, 131.1, 129.2, 128.9, 127.8, 124.2, 123.0, 113.0, 51.6, 29.4; IR (cm−1) ν
1576, 1552, 1447, 1401, 1278,1189, 1141, 858, 796, 750, 694; HRMS (ESI) calcd for
C18H15ClN3Se [M+H]+ 388.0120, found 388.0121.
5-Bromo-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ha): brown solid (74.6 mg,
58%); mp 153−156 °C; 1H NMR (CDCl3, 400 MHz) δ 8.45 (d, J = 4.8 Hz, 2H), 7.53–7.43 (m,
2H), 7.32–7.14 (m, 5H), 6.74 (t, J = 4.8 Hz, 1H), 4.46 (t, J = 8.0 Hz, 2H), 3.11 (t, J = 8.0 Hz,
13
2H); C NMR (CDCl3, 100 MHz) δ 160.5, 157.4, 143.3, 136.3, 134.3, 134.0, 133.8, 129.2,
127.7, 125.9, 124.6, 116.4, 113.0, 51.5, 29.3; IR (cm−1) ν 1577, 1551, 1444, 1398, 1277, 1186,
1135, 853, 796, 749, 693; HRMS (ESI) calcd for C18H15BrN3Se [M+H]+ 431.9615, found
431.9600.
5-Methoxy-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ia): brown solid (70.0 mg,
1
61%); mp 98−100 °C; H NMR (CDCl3, 400 MHz) δ 8.43 (d, J = 4.8 Hz, 2H), 7.52 (dd, J =
6.5, 2.9 Hz, 2H), 7.25–7.21 (m, 3H), 6.67 (dd, J = 8.7, 4.0 Hz, 3H), 4.47 (t, J = 7.9 Hz, 2H),
13
3.56 (s, 3H), 3.09 (t, J = 7.8 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.7, 157.3, 156.4,
137.8, 135.5, 134.3, 128.9, 127.3, 123.5, 116.1, 112.2, 109.9, 55.5, 51.5, 29.8; IR (cm−1) ν
1578, 1549, 1449, 1411, 1265, 1223, 1187, 1106, 1041, 846, 785, 747; HRMS (ESI) calcd for
C19H18N3OSe [M+H]+ 384.0615, found 384.0614.
5-Nitro-7-(phenylselanyl)-1-(pyrimidin-2-yl)indoline (5ja): yellow solid (35.4 mg, 30%);
mp 188−190 °C; 1H NMR (CDCl3, 400 MHz) δ 8.54 (d, J = 4.8 Hz, 2H), 8.03 (d, J = 2.1 Hz,
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1H), 7.93–7.87 (m, 1H), 7.51 (dd, J = 7.7, 1.6 Hz, 2H), 7.35–7.27 (m, 3H), 6.89 (t, J = 4.8 Hz,
1H), 4.55 (t, J = 8.3 Hz, 2H), 3.25 (t, J = 8.3 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 159.8,
157.6, 149.4, 143.6, 134.8, 133.0, 129.5, 128.7, 128.4, 122.7, 118.1, 114.3, 52.0, 28.5; IR
(cm−1) ν 1574, 1557, 1505, 1435, 1312, 1079, 993, 930, 891, 795, 752, 699, 626; HRMS (ESI)
calcd for C18H15N4O2Se [M+H]+ 399.0360, found 399.0346.
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7-(4-Chlorophenylselanyl)-1-(pyrimidin-2-yl)indoline (5ab): brown solid (92.2 mg, 79%);
mp 141−144 °C; 1H NMR (CDCl3, 400 MHz) δ 8.44 (d, J = 4.8 Hz, 2H), 7.39 (d, J = 8.4 Hz,
2H), 7.17 (d, J = 8.3 Hz, 2H), 7.13–7.06 (m, 1H), 6.82 (t, J = 7.6 Hz, 1H), 6.71 (t, J = 4.8 Hz,
1H), 4.48 (t, J = 8.0 Hz, 2H), 3.14 (t, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 160.5,
157.3, 144.1, 135.2, 134.2, 133.3, 133.2, 132.1, 129.0, 124.3, 123.1, 122.3, 112.7, 51.2, 29.3;
IR (cm−1) ν 1574, 1548, 1455, 1379, 1278, 1082, 1007, 799, 771, 722; HRMS (ESI) calcd for
C18H15ClN3Se [M+H]+ 388.0120, found 388.0110.
1-(Pyrimidin-2-yl)-7-(p-tolylselanyl)indoline (5ac): brown solid (76.8 mg, 70%); mp
120−122 °C; 1H NMR (CDCl3, 400 MHz) δ 8.46 (d, J = 4.8 Hz, 2H), 7.40 (d, J = 7.9 Hz, 2H),
7.13–7.02 (m, 4H), 6.80 (t, J = 7.6 Hz, 1H), 6.72 (t, J = 4.8 Hz, 1H), 4.48 (t, J = 8.0 Hz, 2H),
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3.14 (t, J = 7.9 Hz, 2H), 2.31 (s, 3H); C NMR (CDCl3, 100 MHz) δ 160.7, 157.4, 143.8,
137.3, 134.7, 134.1, 131.8, 130.7, 129.8, 124.2, 123.3, 122.7, 112.6, 51.4, 29.5, 21.1; IR (cm−1)
ν 1574, 1549, 1437, 1379, 1224, 1056, 793, 761, 732, 687; HRMS (ESI) calcd for C19H18N3Se
[M+H]+ 368.0666, found 368.0672.
7-(4-methoxyphenylselanyl)-1-(pyrimidin-2-yl)indoline (5ad): brown solid (88.9 mg,
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78%); mp 105−108 °C; H NMR (CDCl3, 400 MHz) δ 8.49 (d, J = 4.7 Hz, 2H), 7.50 (d, J =
8.5 Hz, 2H), 7.07 (t, J = 7.3 Hz, 2H), 6.82 (d, J = 8.2 Hz, 3H), 6.74 (t, J = 4.7 Hz, 1H), 4.50 (t,
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J = 8.0 Hz, 2H), 3.80 (s, 3H), 3.15 (t, J = 7.9 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 160.6,
159.4, 157.4, 143.4, 136.7, 133.9, 131.2, 124.3, 124.0, 123.8, 122.4, 114.6, 112.5, 55.1, 51.3,
29.4; IR (cm−1) ν 1574, 1550, 1485, 1450, 1377, 1280, 1244, 1176, 1027, 824, 793, 771;
HRMS (ESI) calcd for C19H18N3OSe [M+H]+ 384.0615, found 384.0619.
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Ethyl 4-(1-(pyrimidin-2-yl)indolin-7-ylselanyl)benzoate (5ae): brown solid (99.6 mg,
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78%); mp 125−127 °C; H NMR (CDCl3, 400 MHz) δ 8.42 (d, J = 4.8 Hz, 2H), 7.83 (d, J =
8.2 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 7.2 Hz, 1H), 6.84
(t, J = 7.6 Hz, 1H), 6.71 (t, J = 4.8 Hz, 1H), 4.47 (t, J = 8.0 Hz, 2H), 4.32 (q, J = 7.1 Hz, 2H),
3.14 (t, J = 7.9 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 166.2, 160.5,
157.2, 144.7, 142.4, 134.4, 132.9, 132.0, 129.8, 129.7, 128.5, 124.4, 123.6, 121.1, 112.8, 60.7,
51.2, 29.3, 14.2; IR (cm−1) ν 1703, 1577, 1551, 1458, 1390, 1272, 1170, 1102, 1014, 758;
HRMS (ESI) calcd for C21H20N3O2Se [M+H]+ 426.0721, found 426.0720.
7-(Benzylselanyl)-1-(pyrimidin-2-yl)indoline (5af): yellow solid (27.6 mg, 25%); mp
141−143 °C; 1H NMR (CDCl3, 400 MHz) δ 8.38 (d, J = 4.8 Hz, 2H), 7.45 (d, J = 7.8 Hz, 1H),
7.26 – 7.10 (m, 6H), 6.99 (t, J = 7.6 Hz, 1H), 6.66 (t, J = 4.8 Hz, 1H), 4.41 (t, J = 8.0 Hz, 2H),
13
4.01 (s, 2H), 3.12 (t, J = 7.9 Hz, 2H); C NMR (CDCl3, 100 MHz) δ 160.3, 157.3, 144.2,
138.5, 134.2, 130.8, 129.0, 128.4, 126.6, 124.2, 122.9, 112.5, 51.4, 33.4, 29.5; IR (cm−1) ν
1575, 1548, 1490, 1458, 1431, 1378, 1274, 796, 765, 695; HRMS (ESI) calcd for C19H18N3Se
[M+H]+ 368.0666, found 368.0668.
Derivatization reaction of 3aa (eq 1).6a To a solution of 3aa (91.5 mg, 0.3 mmol) in
1,4-dioxane (3 mL) was added DDQ (136.2 mg, 0.6 mmol). The mixture was stirred at 90 °C
for 12 h. After removal of solvent, the residue was absorbed to small amounts of silica. The
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product was purified by flash column chromatography with petroleum ether/EtOAc (8:1) to
give product 6 (89.3 mg, 98%).
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mg) in EtOH (0.4 mL) was added. The mixture was stirred at 100 °C for 4 h and then cooled,
and HCl (2 M) was added. The mixture was diluted with EtOAc and washed with brine. The
combined organic phase was dried (Na2SO4). After evaporation of the solvents under reduced
pressure, the crude product was purified on a silica gel column with petroleum ether/EtOAc
(4:1) to afford product 7 (52.5 mg, 97%).
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7-(Phenylthio)-1-(pyrimidin-2-yl)-1H-indole (6): white solid (89.3 mg, 99%); mp 62−64
°C; 1H NMR (CDCl3, 400 MHz) δ 8.68 (d, J = 4.8 Hz, 2H), 7.81 (d, J = 3.5 Hz, 1H), 7.57 (d,
J = 7.7 Hz, 1H), 7.28–7.23 (m, 1H), 7.14 (m, 7H), 6.75 (d, J = 3.5 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 158.0, 157.7, 137.7, 134.9, 132.1, 130.4, 129.9, 129.4, 128.7, 126.4, 122.7, 121.4,
120.3, 117.8, 106.7; IR (cm−1) ν 1567, 1426, 1192, 1134, 1063, 786, 744, 715, 689, 475;
HRMS (ESI) calcd for C18H14N3S [M+H]+ 304.0908, found 304.0909.
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8.39 (s, 1H), 7.76 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.24–7.18 (m, 3H), 7.14 (t, J =
13
7.2 Hz, 4H), 6.64 (d, J = 1.8 Hz, 1H); C NMR (CDCl3, 100 MHz) δ 137.4, 136.8, 129.1,
129.0, 128.3, 126.9, 125.6, 124.5, 122.3, 120.5, 113.1, 103.3; IR (cm−1) ν 3419, 1579, 1478,
1431, 1327, 1095, 1065, 791, 731, 691, 471; HRMS (ESI) calcd for C14H12NS [M+H]+
226.0690, found 226.0683.
Derivatization reaction of 3aa (eq 2).22 m-CPBA (≤77%) (67.3 mg, 0.39 mmol) was
added to a solution of 3aa (61.1 mg, 0.2 mmol) in CH2Cl2 (2 mL). The mixture was stirred
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under reflux for 18 hr and then quenched with aqueous NaHCO3. The aqueous layer was
extracted with CH2Cl2 and the combined organic extracts were dried with MgSO4, filtered,
and the solvent was removed in reduced pressure. The crude product was purified by column
chromatography with petroleum ether/EtOAc (2:1) to give 8 (36.3 mg, 54%) as a brown solid.
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1
Mp 218−221 °C; H NMR (CDCl3, 400 MHz) δ 8.00 (d, J = 4.8 Hz, 2H), 7.79 (dd, J = 5.3,
3.3 Hz, 2H), 7.64 (d, J = 8.1 Hz, 1H), 7.56–7.44 (m, 3H), 7.41 (dd, J = 7.3, 1.1 Hz, 1H),
7.12–7.04 (m, 1H), 6.67 (t, J = 4.8 Hz, 1H), 4.46 (t, J = 8.1 Hz, 2H), 3.13 (t, J = 8.0 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ 161.3, 157.1, 144.0, 142.4, 137.0, 131.9, 129.8, 129.3, 128.6,
128.1, 126.1, 123.0, 114.0, 52.6, 28.8; IR (cm−1) ν 1572, 1455, 1420, 1297, 11521127, 1075,
807, 762, 731, 689, 580, 478; HRMS (ESI) calcd for C18H16N3O2S [M+H]+ 338.0963, found
338.0965.
H/D exchange reaction without diphenyl disulfide (eq 3). An oven-dried reaction
vessel was charged with [Cp*RhCl2]2 (9.3 mg, 0.015 mmol), AgOTf (15.4 mg, 0.06 mmol),
1-(pyrimidin-2-yl)indoline (1a) (59.2 mg, 0.3 mmol), Ag2CO3 (82.7 mg, 0.3 mmol), toluene
(1.3 mL), and D2O (0.2 mL) under air. The vessel was sealed and heated at 130 °C (oil bath)
for 12 h. After removal of solvents, the residue was purified by flash column chromatography
on silica gel (eluent: EtOAc/petroleum ether = 1:20).
H/D exchange reaction in the presence of diphenyl disulfide (eq 4). An oven-dried
reaction vessel was charged with [Cp*RhCl2]2 (9.3 mg, 0.015 mmol), AgOTf (15.4 mg, 0.06
mmol), 1-(pyrimidin-2-yl)indoline (1a) (59.2 mg, 0.3 mmol), diphenyl disulfide (2a) (65.5
mg, 0.3 mmol), Ag2CO3 (82.7 mg, 0.3 mmol), toluene (1.3 mL) and D2O (0.2 mL) under air.
The vessel was sealed and heated at 130 °C (oil bath) for 1 h. After removal of solvents, the
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residue was purified by flash column chromatography on silica gel (eluent: EtOAc/petroleum
ether = 1:20).
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ASSOCIATED CONTENT
Supporting Information
Detail optimization studies of reaction, full spectroscopic data for all new compounds and CIF
files giving X-ray structural information for 3aj. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: bqwang@nankai.edu.cn (B. Wang).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China (Nos 21372122 and
21421062) for financial support.
REFERENCES
(1) For selected reviews, see: (a) Heterocyclic Chemistry, Joule, J. A.; Mills, K. Eds.;
Blackwell Science Ltd.: Oxford, 2000. (b) Boger, D. L.; Boyce, C. W.; Garbaccio, R. M.;
Goldberg, J. A. Chem. Rev. 1997, 97, 787. (c) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
Chem. Rev. 2003, 103, 893. (d) Kawasaki, T.; Higuchi, K. Nat. Prod. Rep. 2005, 22, 761. (e)
Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489.
(2) For selected examples, see (a) Owa, T.; Yokoi, A.; Yamazaki, K.; Yoshimatsu, K.;
27
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Page 28 of 32
1
2
3
4
5
Yamori, T.; Nagasu, T. J. Med. Chem. 2002, 45, 4913. (b) Mohan, R.; Banerjee, M.; Ray, A.;
6
7
8
9
Manna, T.; Wilson, L.; Owa, T.; Bhattacharyya, B.; Panda, D. Biochemistry 2006, 45, 5440. (c)
Ferandin, Y.; Bettayeb, K.; Kritsanida, M.; Lozach, O.; Polychronopoulos, P.; Magiatis, P.;
Skaltsounis, A.-L.; Meijer, L. J. Med. Chem. 2006, 49, 4638. (d) Dydio, P.; Zielinski, T.;
Jurczak, J. Chem. Commun. 2009, 4560. (e) Ozawa, Y.; Kusano, K.; Owa, T.; Yokoi, A.;
Asada, M.; Yoshimatsu, K. Cancer Chemother Pharmacol 2012, 69, 1353. (f) Burke, J. P.;
Bian, Z.; Shaw, S.; Zhao, B.; Goodwin, C. M.; Belmar, J.; Browning, C. F.; Vigil, D.; Friberg,
A.; Camper, D. V.; Rossanese, O. W.; Lee, T.; Olejniczak, E. T.; Fesik, S. W. J. Med. Chem.
2015, 58, 3794.
10
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12
13
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16
17
18
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21
22
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26
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41
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43
44
45
46
47
48
49
50
51
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53
54
55
56
57
58
59
60
(3) For selected recent reviews on C−H functionalization, see: (a) Rossi, R.; Bellina, F.;
Lessi, M.; Manzinia, C. Adv. Synth. Catal. 2014, 356, 17. (b) Kuhl, N.; Schröer, N.; Glorius,
F. Adv. Synth. Catal. 2014, 356, 1443. (c) Chen, Z.; Wang, B.; Zhang, J.; Yu W.; Liu, Z.;
Zhang Y. Org. Chem. Front. 2015, 2, 1107.
(4) (a) Jiao, L.-Y.; Smirnov, P.; Oestreich, M. Org. Lett. 2014, 16, 6020. (b) Jiao, L.;
Oestreich, M. Chem. Eur. J. 2013, 19, 10845. (c) Nishikata, T.; Abela, A. R.; Huang, S.;
Lipshutz, B. H. J. Am. Chem. Soc. 2010, 132, 4978. (d) Kalyani, D.; Deprez, N. R.; Desai, L.
V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330. (e) Shi, Z.; Li, B.; Wan, X.; Cheng, J.;
Fang, Z.; Cao, B.; Qin, C.; Wang, Y. Angew. Chem., Int. Ed. 2007, 46, 5554.
(5) (a) Urones, B.; Arrayás, R. G.; Carretero, J. C. Org. Lett. 2013, 15, 1120. (b) Jiao, L.;
Oestreich, M. Org. Lett. 2013, 15, 5374. (c) Song, Z.; Samanta, R.; Antonchick, A. P. Org.
Lett. 2013, 15, 5662. (d) Pan, S.; Wakaki, T.; Ryu, N.; Shibata, T. Chem. Asian J. 2014, 9,
1257. (e) Yang, D.; Mao, S.; Gao, Y.-R. Guo, D.-D.; Guo, S.-H.; Li, B.; Wang, Y.-Q. RSC
28
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2
3
4
5
6
7
Adv. 2015, 5, 23727. (f) Yang, X.-F.; Hu, X.-H.; Feng, C.; Loh, T.-P. Chem. Commun. 2015,
51, 2532.
8
9
(6) (a) Wu, Y.-X.; Yang, Y.-X.; Zhou, B.; Li, Y.-C. J. Org. Chem. 2015, 80, 1946. (b) Yang,
X.-F.; Hu, X.-H.; Feng, C.; Loh, T.-P. Chem. Commun. 2015, 51, 2532.
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53
54
55
56
57
58
59
60
(7) (a) Shin, K.; Chang, S. J. Org. Chem. 2014, 79, 12197. (b) Pan, C.; Abdukader, A.; Han,
J.; Cheng, Y.; Zhu, C. Chem. Eur. J. 2014, 20, 3606. (c) Hou, W.; Yang, Y.-X.; Ai, W.; Wu,
Y.-X.; Wang, X.; Zhou, B.; Li, Y.-C. Eur. J. Org. Chem. 2015, 395.
(8) (a) Kim, M.; Mishra, N. K.; Park, J.; Han, S.; Shin, Y.; Sharma, S.; Lee, Y.; Lee, E.-K.;
Kwak, J. H.; Kim, I. S. Chem. Commun. 2014, 50, 14249. (b) Shin, Y.; Sharma, S.; Mishra, N.
K. Han, S. Park, J.; Oh, H.; Ha, J.; Yoo, H. Jung, Y. H.; Kima, I. S. Adv. Synth. Catal. 2015,
357, 594. (c) Chan, C.-W.; Zhou, Z.; Yu, W.-Y. Adv. Synth. Catal. 2011, 353, 2999.
(9) (a) Park, J; Mishra, N. K.; Sharma, S.; Han, S.; Shin, Y.; Jeong, T.; Oh, J. S.; Kwak, J.
H.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2015, 80, 1818. (b) Sharma, S.; Shin, Y.; Mishra, N.
K.; Park, J.; Han, S.; Jeonga, T.; Oh, Y.; Lee, Y.; Choi, M.; Kim, I. S. Tetrahedron 2015, 71,
2435.
(10) (a) Pan, S.; Ryu, N.; Shibata, T. Adv. Synth. Catal. 2014, 356, 929. (b) Neufeldt, S. R.;
Seigerman, C. K.; Sanford, M. Org. Lett. 2013, 15, 2302. (c) Ai, W.; Yang, X.-Y.; Wu, Y.-X.;
Wang, X.; Li, Y.-C.; Yang, Y.-X.; Zhou, B. Chem. Eur. J. 2014, 20, 17653. (d) Premi, C.;
Dixit, A.; Jain, N. Org. Lett. 2015, 17, 2598.
(11) (a) Yi, C. S.; Yun, S. Y.; Guzei, I. A. J. Am. Chem. Soc. 2005, 127, 5782. (b) Yi, C. S.;
Yun, S. Y. J. Am. Chem. Soc. 2005, 127, 17000. (c) Wang, X.; Tang H.-Y., Feng, H.-J.; Li
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