Palladium(II)-catalyzed aerobic intramolecular allylic C[sbnd]H activation for the synthesis of indolines

Article abstract of DOI:10.1016/j.tet.2017.02.040

A method for the preparation of indolines via palladium-catalyzed aerobic intramolecular allylic C[sbnd]H activation was developed. Oxygen was successfully used as oxidant with catalytic amount of 1,4-benzoquinone. 16 examples were reported, the majority of substrates gave moderate to good yields.

Full text of DOI:10.1016/j.tet.2017.02.040

Accepted Manuscript
Palladium(II)-catalyzed aerobic intramolecular allylic C-H activation for the synthesis
of indolines
Changrui Xu, Zhengxing Wu, Jianzhong Chen, Fang Xie, Wanbin Zhang
PII:
S0040-4020(17)30179-5
10.1016/j.tet.2017.02.040
TET 28481
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 January 2017
Revised Date: 17 February 2017
Accepted Date: 20 February 2017
Please cite this article as: Xu C, Wu Z, Chen J, Xie F, Zhang W, Palladium(II)-catalyzed aerobic
intramolecular allylic C-H activation for the synthesis of indolines, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.02.040.
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Palladium(II)-catalyzed aerobic intramolecular
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Changrui Xu, Zhengxing Wu, Jianzhong Chen, Fang Xie, and Wanbin Zhang

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Palladium(II)-catalyzed aerobic intramolecular
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Changrui Xu, Zhengxing Wu, Jianzhong Chen, Fang Xie, and Wanbin Zhang

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Tetrahedron
journal homepage: www.elsevier.com
Palladium(II)-catalyzed aerobic intramolecular allylic C-H activation for the
synthesis of indolines
Changrui Xua, Zhengxing Wua, Jianzhong Chena, Fang Xiea, *, and Wanbin Zhanga, *
aSchool of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A method for the preparation of indolines via palladium-catalyzed aerobic intramolecular allylic
C-H activation was developed. Oxygen was successfully used as oxidant with catalytic amount
of 1,4-benzoquinone. 16 examples were reported, the majority of substrates gave moderate to
good yields.
Available online
2017 Elsevier Ltd. All rights reserved
.
Keywords:
allylic
C-H activation
palladium
indolines
intramolecular
1. Introduction
Indolines, as important structural motifs, are present in many
natural molecules, pharmaceuticals and synthetic intermediates,1
such as indapamide,1a a dopamine D2/D4 receptor antagonist,1c an
intermediate used in the synthesis of perindopril,1g and the
antitumor agent SAR-260301 (Figure 1).1h In recent decades,
Figure 1 Selected examples of indolines.
Scheme 1 Pd-catalyzed reactions for the synthesis of
indolines.
numerous protocols have been developed for the synthesis of
indolines, including many metal-free2 and metal-catalyzed3
strategies. Palladium, one of the most commonly used metals for
catalytic reactions, has been applied to the construction of
indolines.3g-s In recent years, C-H activation has become a
popular research topic,4 and palladium-catalyzed aromatic C-H
activation has also been used for the synthesis of indolines.3n,q
Additionally, palladium-catalyzed Wacker oxidation3g,j,p and
allylic substitution3k are all efficient methods for the synthesis of
indolines (Scheme 1). On the other hand, palladium-catalyzed
allylic C-H activations have been investigated for the
construction of carbon-carbon and carbon-heteroatom bonds.5-8
Trost,5e,f Beak5g,h and Larock5j were some of the early pioneers in
Wanbin Zhang. Tel.: +86-021-5474-3265; fax: +86-021-5474-3265; e-mail:
wanbin@sjtu.edu.cn
Fang Xie. Tel.: +86-021-5474-3265; fax: +86-021-5474-3265; e-mail:
xiefang@sjtu.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
this field. Recently, White,6 Liu,7 Shi5m and Gong8 investigated
BQ was able to improve the product yield to 54% (entry 10). The
palladium-catalyzed allylic C-H oxidations. So far, despite
successful examples for the synthesis of indolines, the
construction of indolines via palladium-catalyzed allylic C-H
activation has not been reported. In continuation of our research
concerning the palladium-catalyzed cyclization of olefins,9 we
herein develop a mild palladium-catalyzed allylic C-H activation
for the synthesis of indolines, using oxygen as a terminal oxidant.
quantity of BQ was varied (entries 13-17), with 0.2 equiv BQ
showing the best result with a yield of 79% (entry 14). A series
of other additives were also screened but all failed to provide
higher yields (entries 18-21). In addition, we explored the effect
of temperature; increasing or reducing the temperature both led to
a reduction in yields (entries 22, 23).
With the optimized reaction conditions in hand (Table 1, entry
14), a wide range of substrates 1 were surveyed to explore
substrate scope (Table 2). N-methanesulfonyl protected 1b gave
the corresponding product with a yield of 54%. A series of N-
tosyl substrates with different substituent groups were
investigated (1c-1p). For Me-substituted substrates, the yields of
3-, 4-, and 5-substituted compounds (1c, 1d, and 1e, respectively)
were better than that of a 6-substituted substrate (1f). For
substrates bearing an OMe group, substitution at the 4-position
(1g) provided better reactivity than substitution at the 6-postion
(1h). The electronic character of the substituents had little impact
on the reaction, with substrates bearing electron-withdrawing
groups (R2 = Cl, F) providing the corresponding products with
similar activity to that of substrates bearing electron-donating
groups (R2 = Me, OMe). These results indicated that the effect of
steric bulk on the aryl ring appeared to be significant on the
yields. For the substrate 1p with naphthalene ring, the reaction
performed moderate reactivity.
2. Results and discussion
Table 1 Exploration of reaction conditionsa
entry
1
co-oxidant (equiv)
solvent
DMA
DMF
yield (%)b
44
-
2
-
25
3
-
DMSO
MeCN
CH2Cl2
THF
0
4
-
trace
trace
trace
28
5
-
6
-
Table 2 Scope of substratesa
7
-
AcOH
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
8c
9d
-
0
3
6
3
6
Pd(OAc)2 (10 mol%)
BQ (0.2 equiv)
4
4
R2
5
R2
5
-
23
DMA, 40 oC, 12 h
O2 (sealed tube)
NHR1
N
R1
10
11
12
13
14
15
16
17
18e
19f
20g
21h
22i
23j
BQ (1.0)
Cu(OAc)2 (1.0)
PhI(OAc)2 (1.0)
BQ (0.1)
BQ (0.2)
BQ (0.3)
BQ (0.5)
BQ (2.0)
BQ (0.2)
BQ (0.2)
BQ (0.2)
BQ (0.2)
BQ (0.2)
BQ (0.2)
54
1
2
48
Me
0
Me
55
N
N
N
N
Ms
Ts
Ts
Ts
2c, 81%
79
2b
2d
, 76%
2a
, 54%
, 79%
70
MeO
69
N
N
N
N
Ts
Ts
Me
Ts
41
Ts
OMe
Me
b
b
2e
2g
2h
, 33%
, 62%
2f
, 62%
, 51%
42
Cl
F
6
Cl
N
41
N
N
N
Cl
F
Ts
Ts
Ts
Ts
Cl
2l
32
b
2i, 80%
2j, 71%
2k
2o
, 67%
, 53%
70
F
56
N
N
N
N
Ts
Ts
, 65%
Ts
Ts
a Reaction conditions: unless otherwise noted, 1a (0.1 mmol), Pd(OAc)2 (10
2m
, 77%
2p
2n, 74%
, 62%
b
c
mol%), solvent (1 mL), under O2 at 40 °C for 12 h. Isolated yield.
Pd(CH3CN)2Cl2 was used. d Pd(OCOCF3)2 was uesd. e NaOAc (1.0 equiv) was
a Reaction conditions: unless otherwise noted, 1 (0.1 mmol), Pd(OAc)2 (10
mol%), DMA (1 mL), under O2 at 40 °C for 12 h. b Pd(OAc)2 (20 mol%) at
60 °C.
f
g
h
added. NaBr (1.0 equiv) was added. Cs2CO3 (1.0 equiv) was added.
i
j
pyridine (0.15 equiv) was added. At 30 °C. At 50 °C. DMA = N,N-
dimethylacetamide, DMF = N,N-dimethylformamide, DMSO = dimethyl
sulfoxide, THF = tetrahydrofuran, BQ = 1,4-benzoquinone.
Product 2a could be transformed to valuable biologically
active compounds in just a few simple steps. Chiral resolution of
the indoline 2a gave (S)-2a, which upon treatment with
Na/naphthalene in THF generated the intermediate (S)-3a in 89%
yield. Compound (S)-3a could be subsequently transformed to
(S)-4a, a dopamine D2/D4 receptor antagonist, following a
reported procedure (Scheme 2, a).1c In addition, oxidation of the
product 2a with RuCl3 and NaIO4 in CCl4/MeCN/H2O gave
compound 5a in 56% yield. 5a could be converted to 6a, an
intermediate used for the synthesis of an analogue of
camptothecin T-2513, which has shown potent antitumor activity
(Scheme 2, b).10
Initially, experiments were carried out with N-tosyl protected
compound 1a in the presence of 10 mol% Pd(OAc)2 under
oxygen using different solvents at 40 °C (Table 1, entries 1-7).
To our delight, the desired product 2a was obtained in 44% yield
when using DMA as the solvent (entry 1). Product 2a was also
obtained in DMF and AcOH but with lower yields (entries 2, 7).
Different Pd(II) catalysts were then screened, Pd(CH3CN)2Cl2
and Pd(OCOCF3)2 both gave lower yields of product compared to
Pd(OAc)2 (entries 8, 9). Co-oxidants were also investigated to
optimize the reaction (entries 10-12). We found that 1.0 equiv

3
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Scheme 3 Control experiments.
Scheme 2 Further transformations.
Several control experiments were carried out to determine the
mechanism of the reaction (Scheme 3). Considering the difficulty
encountered when preparing the π-allyl Pd(II) species using
substrate 1a, we chose compound 7 and allylpalladium acetate
dimer 8 for the intermolecular reaction using our catalytic system
(Scheme 3, a).7a The corresponding product 9 was obtained in 25%
yield. To the best of our knowledge, intramolecular reactions
proceed more readily than intermolecular variants. Thus, we
speculated that the formation of the π-allyl Pd(II) species occurs
via an allylic C-H activation in our catalytic system. Additionally,
there is a possibility that substrate 1a undergoes isomerization
and cyclization to yield the product 2a. We therefore prepared the
compounds (Z)-10 and (E)-10 bearing internal olefins and
employed them in our catalytic system (Scheme 3, b and c).
Product 2a was obtained in 74% yield and 48% yield,
respectively, from (Z)-10 and (E)-10. According to literature
reports concerning palladium-catalyzed alkene isomerization, the
E isomer is favored.11 However, the yield of 2a from (E)-10 is
much lower than that under standard reaction conditions,
indicating that isomerization and cyclization of substrate 1a is
possible, but not the primary pathway for the synthesis of
indoline 2a from substrate 1a. Furthermore, the formation of
compound 10 was not observed in our original catalytic reaction,
further indicating that the possibility of the isomerization and
cyclization of substrate 1a is extremely low.
Scheme 4 Proposed mechanism.
3. Conclusions
In summary, we have developed a novel method for the
synthesis of indolines using a mild palladium(II)-catalyzed allylic
C-H activation. A series of substrates were amenable to the
reaction conditions, affording the corresponding products in
moderate to good yields. Additionally, the indoline products
could be further transformationed to valuable products.
4. Experimental section
4.1. General
The
solvent
N,N-dimethylformamide
(DMF),
N,N-
dimethylacetamide (DMA) and dimethyl sulfoxide (DMSO) were
distilled over dehydrating reagents. All new compounds were
characterized on the basis of 1H NMR and 13C NMR
spectroscopic data, melting point data, IR data and HRMS data.
1H NMR and 13C NMR chemical shifts were reported in ppm
using TMS as an internal standard. Optical rotations were
measured with a SPSI SGW-1 polarimeter. All ee values were
determined by HPLC using a Daicel Chiralcel AD-H column
with n-hexane/i-PrOH as an eluent. IR was measured with
PerkinElmer Spectrum 100 FT-IR Spectrometer. HRMS was
performed on a Waters Micromass Q-TOF Premier Mass
Spectrometer.
According to known research concerning palladium-catalyzed
C-H activation and our experimental results, the most probable
mechanism has been proposed (Scheme 4). Initially, Pd(II)
species I is likely generated from substrate 1a and Pd(OAc)2.
Pd(II) species I undergoes an allylic C-H activation to form π-
allyl Pd complex II. Complex II then undergoes nucleophilic
attack to give the product 2a and Pd(0). The Pd(II) catalyst is
regenerated via the oxidation of Pd(0) to continue the catalytic
cycle.
4.2. General procedure for the synthesis of Indolines 2
(exclusive of 2f, 2h and 2l)

4
Tetrahedron
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Substrate 1 (0.10 mmol), Pd(OAc)2 (2.2 mg, 0.10 equiv), BQ
= 17.0 Hz, 1H), 5.19 (d, J = 10.2 Hz, 1H), 4.83-4.69 (m, 1H),
2.99 (dd, J = 16.7, 10.2 Hz, 1H), 2.74 (dd, J = 16.7, 3.6 Hz, 1H),
2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 144.3, 142.8, 137.3,
135.1, 130.8, 129.8, 129.6, 129.3, 127.1, 124.4, 116.2, 114.7,
63.6, 34.5, 21.6; HRMS(ESI) calcd for C17H17ClNO2S
[M+H]+334.0669, found 334.0668; IR (KBr, v/cm−1): 3430, 2924,
1595, 1451, 1354, 1246, 1166, 1090, 989, 782, 665, 579.
4.2.8. 5-Chloro-1-tosyl-2-vinylindoline (2j).3p A white solid (23.7
mg, 71% yield); mp = 75-77 °C; 1H NMR (400 MHz, CDCl3) δ
7.58 (dd, J = 8.2, 5.5 Hz, 3H), 7.22-7.17 (m, 3H), 7.01 (s, 1H),
5.97-5.79 (m, 1H), 5.38 (d, J = 17.0 Hz, 1H), 5.17 (d, J = 10.4 Hz,
1H), 4.80-4.65 (m, 1H), 2.90 (dd, J = 16.1, 9.7 Hz, 1H), 2.62 (dd,
J = 16.2, 2.7 Hz, 1H), 2.37 (s, 3H).
(2.2 mg, 0.20 equiv) and the solvent DMA (1 mL) were added in
a 25 mL sealed tube, then the tube was degassed and replaced by
O2. Then the sealed tube was stirred at 40 °C for 12 h. The
mixture was purified by column chromatography using
petroleum ether/EtOAc = 10/1 as eluent to give the product 2.
4.2.1. 1-Tosyl-2-vinylindoline (2a).3p A white solid (23.6 mg, 79%
yield); mp = 98-100 °C; 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J
= 8.1 Hz, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.20 (dd, J = 17.1, 8.4
Hz, 3H), 7.07-6.98 (m, 2H), 5.91 (ddd, J = 16.7, 10.2, 6.1 Hz,
1H), 5.39 (d, J = 17.0 Hz, 1H), 5.15 (d, J = 10.2 Hz, 1H), 4.78-
4.69 (m, 1H), 2.94 (dd, J = 16.0, 9.7 Hz, 1H), 2.64 (dd, J = 16.1,
3.2 Hz, 1H), 2.36 (s, 3H).
4.2.2. 1-(Methylsulfonyl)-2-vinylindoline (2b).3f A white solid
(12.0 mg, 54% yield); mp = 72-74 °C; H NMR (400 MHz,
CDCl3) δ 7.38 (d, J = 8.0 Hz, 1H), 7.20 (dd, J = 12.3, 4.7 Hz, 2H),
7.06-7.02 (m, 1H), 5.91 (ddd, J = 17.3, 10.2, 7.3 Hz, 1H), 5.40 (d,
J = 17.0 Hz, 1H), 5.20 (d, J = 10.2 Hz, 1H), 4.93-4.82 (m, 1H),
3.50 (dd, J = 16.1, 9.8 Hz, 1H), 2.93–2.79 (m, 4H).
4.2.9. 6-Chloro-1-tosyl-2-vinylindoline (2k). A white solid (22.4
mg, 67% yield); mp = 86-88 °C; 1H NMR (400 MHz, CDCl3) δ
7.64 (dd, J = 20.1, 4.9 Hz, 3H), 7.20 (dd, J = 17.5, 8.2 Hz, 2H),
7.03–6.92 (m, 2H), 5.88 (ddd, J = 16.7, 10.3, 6.2 Hz, 1H), 5.37 (d,
J = 17.0 Hz, 1H), 5.17 (d, J = 10.3 Hz, 1H), 4.80-4.66 (m, 1H),
2.93 (dd, J = 16.1, 9.8 Hz, 1H), 2.62 (dd, J = 16.1, 3.3 Hz, 1H),
2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 144.2, 142.7, 137.2,
135.1, 133.5, 129.8, 129.6, 127.1, 125.8, 124.5, 116.9, 116.1,
64.4, 34.6, 21.6; HRMS(ESI) calcd for C17H17ClNO2S
[M+H]+334.0669, found 334.0657; IR (KBr, v/cm−1): 3431, 2922,
1640, 1598, 1477, 1342, 1159, 1090, 972, 863, 669, 587.
1
4.2.3. 4-Methyl-1-tosyl-2-vinylindoline (2c). A white solid (25.4
mg, 81% yield); mp = 114-116 °C; 1H NMR (400 MHz, CDCl3)
δ 7.60 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.0 Hz, 1H), 7.23-7.07 (m,
3H), 6.83 (d, J = 7.4 Hz, 1H), 5.93 (ddd, J = 16.7, 10.2, 6.3 Hz,
1H), 5.39 (d, J = 17.0 Hz, 1H), 5.16 (d, J = 10.3 Hz, 1H), 4.83-
4.70 (m, 1H), 2.88 (dd, J = 16.0, 9.9 Hz, 1H), 2.59 (dd, J = 16.0,
3.4 Hz, 1H), 2.36 (s, 3H), 2.11 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.8, 141.1, 138.0, 135.4, 134.6, 129.8, 129.6, 127.9,
127.2, 125.4, 115.6, 114.0, 63.7, 34.0, 21.6, 18.7; HRMS(ESI)
calcd for C18H19NNaO2S [M+Na]+336.1034, found 336.1019; IR
(KBr, v/cm−1): 3426, 2921, 1643, 1594, 1461, 1353, 1245, 1167,
1092, 929, 669, 578.
4.2.4. 5-Methyl-1-tosyl-2-vinylindoline (2d).3p A white solid (23.8
mg, 76% yield); mp = 96-98 °C; 1H NMR (400 MHz, CDCl3) δ
7.55 (t, J = 8.8 Hz, 3H), 7.17 (d, J = 8.1 Hz, 2H), 7.01 (d, J = 8.2
Hz, 1H), 6.84 (s, 1H), 5.95-5.80 (m, 1H), 5.38 (d, J = 17.0 Hz,
1H), 5.14 (d, J = 10.2 Hz, 1H), 4.75-4.63 (m, 1H), 2.86 (dd, J =
15.8, 9.8 Hz, 1H), 2.57 (dd, J = 15.9, 2.9 Hz, 1H), 2.36 (s, 3H),
2.27 (s, 3H).
4.2.10. 4-Fluoro-1-tosyl-2-vinylindoline (2m). A white solid
1
(24.4 mg, 77% yield); mp = 107-109 °C; H NMR (400 MHz,
CDCl3) δ 7.60 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.1 Hz, 1H), 7.24-
7.15 (m, 3H), 6.74-6.70 (m, 1H), 5.98-5.85 (m, 1H), 5.40 (d, J =
17.0 Hz, 1H), 5.19 (d, J = 10.3 Hz, 1H), 4.84-4.72 (m, 1H), 2.94
(dd, J = 16.2, 9.8 Hz, 1H), 2.73 (dd, J = 16.3, 3.4 Hz, 1H), 2.38 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 159.1 (d, J = 245 Hz), 144.2,
144.0 (d, J = 8 Hz), 137.2, 135.1, 129.7, 129.6 (d, J = 8 Hz),
127.1, 117.6 (d, J = 22 Hz), 116.1, 112.5 (d, J = 3 Hz), 111.3 (d,
J = 20 Hz), 64.4, 31.3, 21.6; HRMS(ESI) calcd for C17H17FNO2S
[M+H]+318.0964, found 318.0965; IR (KBr, v/cm−1): 3427, 3088,
2925, 1623, 1599, 1461, 1351, 1241, 1165, 1070, 936, 785, 671,
579.
4.2.11. 5-Fluoro-1-tosyl-2-vinylindoline (2n). A white solid (23.5
mg, 74% yield); mp = 86-88 °C; 1H NMR (400 MHz, CDCl3) δ
7.71-7.44 (m, 3H), 7.19 (d, J = 8.5 Hz, 2H), 6.94-6.89 (m, 1H),
6.74 (dd, J = 7.4, 2.0 Hz, 1H), 5.95-5.78 (m, 1H), 5.39 (d, J =
17.0 Hz, 1H), 5.17 (d, J = 10.2 Hz, 1H), 4.80-4.67 (m, 1H), 2.84
(dd, J = 16.7, 9.2 Hz, 1H), 2.58 (dd, J = 16.2, 2.9 Hz, 1H), 2.37 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 160.1 (d, J = 242 Hz), 144.1,
137.4 (d, J = 2 Hz), 137.1, 134.9, 133.7(d, J = 9 Hz), 129.7,
127.1, 118.4 (d, J = 9 Hz), 116.0, 114.5 (d, J = 23 Hz), 112.3 (d,
J = 23 Hz), 64.1, 34.9 (d, J = 2 Hz), 21.6; HRMS(ESI) calcd for
C17H17FNO2S [M+H]+318.0964, found 318.0975; IR (KBr,
v/cm−1): 3422, 3079, 2926, 1596, 1480, 1347, 1246, 1168, 1086,
929, 813, 681, 599.
4.2.5. 6-Methyl-1-tosyl-2-vinylindoline (2e). A white solid (19.4
1
mg, 62% yield); mp = 78-80 °C; H NMR (400 MHz, CDCl3) δ
7.61-7.44 (m, 3H), 7.18 (d, J = 8.1 Hz, 2H), 6.87 (dd, J = 35.3,
7.4 Hz, 2H), 5.89 (ddd, J = 17.0, 8.2, 4.0 Hz, 1H), 5.37 (d, J =
17.0 Hz, 1H), 5.14 (d, J = 10.2 Hz, 1H), 4.76-4.66 (m, 1H), 2.87
(dd, J = 15.8, 9.3 Hz, 1H), 2.57 (dd, J = 14.9, 3.2 Hz, 1H), 2.36 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 143.8, 141.5, 137.8, 137.6,
135.5, 129.6, 128.3, 127.1, 125.4, 124.6, 117.6, 115.7, 64.1, 34.6,
21.6,
21.6;
HRMS(ESI)
calcd
for
C18H19NNaO2S
[M+Na]+336.1034, found 336.1019; IR (KBr, v/cm−1): 3431,
2918, 1643, 1597, 1495, 1365, 1246, 1184, 1156, 1092, 933, 810,
660, 579.
4.2.12. 6-Fluoro-1-tosyl-2-vinylindoline (2o). A white solid (20.6
mg, 65% yield); mp = 83-85 °C; 1H NMR (400 MHz, CDCl3) δ
7.62 (d, J = 8.4 Hz, 2H), 7.39 (dd, J = 9.9, 2.4 Hz, 1H), 7.22 (dd,
J = 8.6, 0.6 Hz, 2H), 7.01-6.91 (m, 1H), 6.76-6.65 (m, 1H), 5.91
(ddd, J = 16.8, 10.2, 6.3 Hz, 1H), 5.37 (d, J = 17.0 Hz, 1H), 5.17
(d, J = 10.3 Hz, 1H), 4.81-4.71 (m, 1H), 2.94 (dd, J = 15.8, 9.7
Hz, 1H), 2.62 (dd, J = 15.8, 3.5 Hz, 1H), 2.38 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 162.6 (d, J = 242 Hz), 144.2, 142.8 (d, J =
12 Hz), 137.3, 135.2, 129.7, 127.1, 126.3 (d, J = 3 Hz), 125.6 (d,
J = 9 Hz), 116.0, 111.0 (d, J = 23 Hz), 104.6 (d, J = 28 Hz), 64.8,
34.4, 21.6; HRMS(ESI) calcd for C17H17FNO2S [M+H]+318.0964,
4.2.6. 5-Methoxy-1-tosyl-2-vinylindoline (2g).3p A white solid
(20.4 mg, 62% yield); mp = 101-103 °C; H NMR (400 MHz,
CDCl3) δ 7.55 (dd, J = 23.4, 8.5 Hz, 3H), 7.17 (d, J = 8.0 Hz, 2H),
6.75 (dd, J = 8.7, 2.4 Hz, 1H), 6.64-6.53 (m, 1H), 5.96-5.78 (m,
1H), 5.39 (d, J = 17.0 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 4.76-
4.59 (m, 1H), 3.75 (s, 3H), 2.77 (dd, J = 16.1, 9.4 Hz, 1H), 2.53
(dd, J = 16.1, 2.6 Hz, 1H), 2.36 (s, 3H).
1
4.2.7. 4-Chloro-1-tosyl-2-vinylindoline (2i). A white solid (26.7
mg, 80% yield); mp = 91-93 °C; 1H NMR (400 MHz, CDCl3) δ
7.58 (dd, J = 20.9, 8.2 Hz, 3H), 7.25-7.13 (m, 3H), 6.99 (dd, J =
8.1, 0.7 Hz, 1H), 5.92 (ddd, J = 16.6, 10.2, 6.2 Hz, 1H), 5.40 (d, J

5
found 318.0971; IR (KBr, v/cm−1): 3433, 3084, 2924, 1610, 1598,
1494, 1340, 1266, 1167, 1092, 985, 814, 664, 587.
saturated NaCl, dried over anhydrous Na2SO4. The mixture was
ACCEPTED MANUSCRIPT
concentrated in vacuo and purified by column chromatography
using petroleum ether/EtOAc = 10/1 as eluent to give the product
(S)-3a.12
4.2.13. 1-Tosyl-2-vinyl-2,3-dihydro-1H-benzo[f]indole (2p). A
1
pale yellow solid (21.6 mg, 62% yield); mp = 117-119 °C; H
NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H),
7.68-7.64 (m, 3H), 7.52-7.32 (m, 3H), 7.15 (d, J = 7.2 Hz, 2H),
6.02-5.81 (m, 1H), 5.41 (d, J = 16.6 Hz, 1H), 5.16 (d, J = 10.8 Hz,
1H), 4.93-4.79 (m, 1H), 3.11 (dd, J = 15.9, 9.0 Hz, 1H), 2.82 (d,
J = 16.4 Hz, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
144.0, 139.7, 137.4, 135.6, 133.6, 131.6, 131.2, 129.7, 127.9,
127.3, 127.1, 126.0, 124.90, 123.8, 116.0, 113.0, 64.2, 34.7, 21.5;
HRMS(ESI) calcd for C21H19NNaO2S [M+Na]+372.1034, found
372.1034; IR (KBr, v/cm−1): 3434, 2974, 1633, 1458, 1354, 1267,
1163, 1087, 1040, 952, 881, 754, 670, 584.
(S)-2-Vinylindoline ((S)-3a).1c
A
white solid (12.9 mg,
20
89%, >99% ee), [α]D = 0.02 (c = 0.14 in CHCl3) HPLC
(Chiralcel AD-H, n-hexane/i-PrOH = 98.5:1.5, UV = 254 nm,
flow rate = 0.8 mL / min) tR1 = 19.162 min (major). 1H NMR
(400 MHz, CDCl3) δ 7.08-6.99 (m, 2H), 6.72-6.61 (m, 1H), 6.62
(d, J = 7.8 Hz, 1H), 6.00 (ddd, J = 17.3, 10.1, 7.4 Hz, 1H), 5.27-
5.17 (m, 1H), 5.10-5.07 (m, 1H), 4.37-4.31 (m, 1H), 3.21 (dd, J =
15.5, 8.9 Hz, 1H), 2.82 (dd, J = 15.5, 8.0 Hz, 1H).
4.5. Further transformations (b)
2a (60.0 mg, 0.20 mmol) and RuCl3 (4.1 mg, 0.10 equiv) was
4.3. General procedure for the synthesis of Indolines 2f, 2h
and 2l
added to
7
mL of mixed solvent (MeCN/CCl4/H2O
2mL/2mL/3mL) in a 25 mL round-bottom flask and the mixutre
was stirred at room temperature for 0.5 h. NaIO4 (342 mg, 8.0
equiv) was then added in one portion and the resulting mixture
was stirred for 12 h. Fianlly, the mixture was evaporated and
purified by column chromatography (PE:EA=3:1) to give pure
product 5a.13
1-Tosylindoline-2-carboxylic acid (5a).14 A white solid (35.5
mg, 56% yield); mp = 158-160 °С; 1H NMR (400 MHz, CDCl3)
δ 7.64-7.59 (m, 3H), 7.25-7.20 (m, 3H), 7.06-7.00 (m, 2H), 4.76
(dd, J = 7.5, 3.0 Hz, 1H), 3.24-3.09 (m, 2H), 2.36 (s, 3H).
Substrate 1 (0.10 mmol), Pd(OAc)2 (4.4 mg, 0.20 equiv), BQ
(2.2 mg, 0.20 equiv) and the solvent DMA (1 mL) were added in
a 25 mL sealed tube, then the tube was degassed and replaced by
O2. Then the sealed tube was stirred at 60 °C for 12 h. The
mixture was purified by column chromatography using
petroleum ether/EtOAc = 10/1 as eluent to give the product 2.
4.3.1. 7-Methyl-1-tosyl-2-vinylindoline (2f).3p A white solid (16.0
1
mg, 51% yield); mp = 110-112 °C; H NMR (400 MHz, CDCl3)
δ 7.38 (d, J = 8.3 Hz, 2H), 7.19-6.99 (m, 4H), 6.85 (d, J = 7.2 Hz,
1H), 5.69 (ddd, J = 16.9, 10.3, 4.9 Hz, 1H), 5.33 (d, J = 17.0 Hz,
1H), 5.05 (d, J = 10.3 Hz, 1H), 4.83-4.74 (m, 1H), 2.59 (s, 3H),
2.38 (s, 3H), 2.30–2.18 (m, 2H).
4.6. General procedure for the synthesis of 7
A solution of 4-toluene sulfonyl chloride (2.29 g, 1.2 equiv)
and pyridine (1 mL, 1.3 equiv) in 20 mL CH2Cl2 was added
slowly to the solution of aniline (0.93g, 0.01 mol) in 20 mL
CH2Cl2. The mixture was stirred overnight at room temperature.
Then 15 mL diluted HCl solution was added to the reaction
mixture, the organic layer was separated using separating funnel.
Subequently, the aqueous phase was extracted with 15 mL
CH2Cl2 three times, the combined organic layers were washed
separately with saturated NaHCO3 (20 mL) and saturated NaCl
(20 mL) three times. The organic layer was dried over Na2SO4,
filtered and evaporated under reduced pressure. The residue was
purified by column chromatography using petroleum
ether/EtOAc = 1/1 to give the product 7.15
4.3.2. 7-Methoxy-1-tosyl-2-vinylindoline (2h). A white solid
(10.9 mg, 33% yield); mp = 105-107 °C; 1H NMR (400 MHz,
CDCl3) δ 7.65 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.06-
7.02 (m, 1H), 6.75 (dd, J = 22.5, 7.9 Hz, 2H), 5.80 (ddd, J = 16.6,
10.2, 6.4 Hz, 1H), 5.32 (d, J = 17.0 Hz, 1H), 5.22-5.18 (m, 1H),
5.08 (d, J = 10.3 Hz, 1H), 3.74 (s, 3H), 2.99 (dd, J = 16.3, 8.9 Hz,
1H), 2.50 (d, J = 15.6 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 151.4, 143.2, 137.5, 136.9, 136.1, 130.2, 129.1, 127.3,
126.9, 117.4, 115.9, 111.9, 65.2, 55.7, 35.4, 21.6; HRMS(ESI)
calcd for C18H19NNaO3S [M+Na]+352.0983, found 352.0990; IR
(KBr, v/cm−1): 3388, 2975, 1603, 1489, 1358, 1277, 1167, 1082,
934, 781, 671, 539.
4.3.3. 7-Chloro-1-tosyl-2-vinylindoline (2l).3f A white solid (17.7
mg, 53% yield); mp = 112-114 °C; 1H NMR (400 MHz, CDCl3)
δ 7.60 (d, J = 8.3 Hz, 2H), 7.28-7.21 (m, 3H), 7.11-6.95 (m, 2H),
5.75-5.62 (m, 1H), 5.32 (d, J = 16.9 Hz, 1H), 5.05 (d, J = 10.3 Hz,
1H), 5.00-4.87 (m, 1H), 2.73 (dd, J = 15.8, 8.1 Hz, 1H), 2.44-
2.36 (m, 4H).
4-Methyl-N-phenylbenzenesulfonamide (7).15 A white solid
1
(2.10 g, 85% yield); H NMR (400 MHz, CDCl3) δ 7.66 (d, J =
8.3 Hz, 2H), 7.25-7.21 (m, 4H), 7.11-7.06 (m, 3H), 6.92 (s, 1H),
2.37 (s, 3H).
4.7. General procedure for the synthesis of 9
Substrate 7 (30.0 mg, 2.0 equiv), allylpalladium acetate dimer
8 (preparation according to the literature,7a allylpalladium
chloride dimer (22.0 mg, 0.06 mmol) and AgOAc (20.0 mg, 2
equiv) were poured into CHCl3, stirred overnight, filtered and
evaporated), BQ (26.0 mg, 4 equiv) and the solvent DMA (1 mL)
were added in a 25 mL sealed tube, then the tube was degassed
and replaced by O2. Then the sealed tube was stirred at 40 °C for
12 h. The mixture was purified by column chromatography using
petroleum ether/EtOAc = 10/1 as eluent to give the product 9.
N-Allyl-4-methyl-N-phenylbenzenesulfonamide (9).16 A white
solid (8.3 mg, 25% yield); 1H NMR (400 MHz, CDCl3) δ 7.49 (d,
J = 8.3 Hz, 2H), 7.29-7.24 (m, 5H), 7.05-7.03 (m, 2H), 5.81-5.66
(m, 1H), 5.14-4.98 (m, 2H), 4.17 (d, J = 6.3 Hz, 2H), 2.43 (s, 3H).
4.4. Further transformations (a)
Chiral resolution (conditions: Shimadzu preparative liquid
chromatography LC-8A, EnantioPak AD 5um 250*4.6 mm, n-
hexane/i-PrOH = 95.5:4.5, UV = 254 nm, flow rate = 8 mL / min,
tR1 = 26.816 min and tR2 = 36.792 min) of the indoline 2a (90.0
mg, 0.30 mmol) gave (S)-2a (41.0 mg, >99% ee) with 46% yield.
[α]D20 = 0.38 (c = 0.50 in CHCl3). HPLC (Chiralcel AD-H, n-
hexane/i-PrOH = 97.5:2.5, UV = 254 nm, flow rate = 0.8 mL /
min) tR1 = 19.998 min (minor) and tR2 = 31.017 min (major). Then
2 mL sodium naphthalide (sliced Na (0.18 g, 7.80 mmol) was
added to THF (15 mL) dissolving naphthalene (1.00 g, 7.80
mmol), the mixture was stirred at room temperature till the
solution turned navy-blue color) was transferred to (S)-2a (30.0
mg, 0.10 mmol) in THF (2 mL), and the mixture was stirred at
room temperature for 2 h. The reaction was quenched by the
addition of saturated NaCl. The organic phase was washed with
4.8. Conversion of (Z)-10 to 2a

6
Tetrahedron
ACCEPTED MANUSCRIPT
4. For selected reviews: (a) Miura, M.; Satoh, T. Top. Organomet.
Compound (Z)-10 (30.1 mg, 0.10 mmol), Pd(OAc)2 (2.2 mg,
Chem. 2005, 14, 55; (b) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel,
N.; Yu, J.-Q. Chem. Soc. Rev. 2009, 38, 3242; (c) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624; (d)
McMurray, L.; O’Hara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011,
40, 1885; (e) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res.
2012, 45, 936; (f) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev. 2012, 41,
5588; (g) Guo, X.-X.; Gu, D.-W.; Wu, Z.; Zhang, W. Chem. Rev.
2015, 115, 1622; (h) Yang, G.; Butt, N.; Zhang, W. Chin. J. Cata.
2016, 37, 98; (i) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu,
J.-Q. Chem. Rev. 2016, DOI: 10.1021/acs.chemrev.6b00622.
5. For selected reviews: (a) Liu, G.; Wu, Y. Top. Curr. Chem. 2010,
292, 195; (b) Engelin, C. J.; Fristrup, P. Molecules 2011, 16, 951;
(c) Liron, F.; Oble, J.; Lorion, M. M.; Poli, G. Eur. J. Org. Chem.
2014, 2014, 5863; (d) Tang, H.; Huo, X.; Meng, Q.; Zhang, W.
Acta Chimica Sinica 2016, 74, 219. For selected papers: (e) Trost,
B. M.; Strege, P. E.; Weber, L.; Fullerton, T. J.; Dietsche, T. J. J.
Am. Chem. Soc. 1978, 100, 3407; (f) Trost, B. M.; Metzner, P. J.
J. Am. Chem. Soc. 1980, 102, 3572; (g) Chrisope, D. R.; Beak, P.
J. Am. Chem. Soc. 1986, 108, 334; (h) Chrisope, D. R.; Beak, P.;
Saunders, W. H. J. Am. Chem. Soc. 1988, 110, 230; (i) van der
Schaaf, P. A.; Sutter, J.-P.; Grellier, M.; van Mier, G. P. M.; Spek,
A. L.; van Koten, G.; Pfeffer, M. J. Am. Chem. Soc. 1994, 116,
5134; (j) Larock, R. C.; Hightower, T. R.; Hasvold, L. A.;
Peterson, K. P. J. Org. Chem. 1996, 61, 3584; (k) Trost, B. M.;
Toste, F. D. J. Am. Chem. Soc. 1998, 120, 9074; (l) Beccalli, E.
M.; Broggini, G.; Paladino, G.; Penoni, A.; Zoni, C. J. Org. Chem.
2004, 69, 5627; (m) Lin, S.; Song, C.-X.; Cai, G.-X.; Wang, W.-
H.; Shi, Z.-J. J. Am. Chem. Soc. 2008, 130, 12901; (n) Wang, B.;
Du, H.; Shi, Y. Angew. Chem. Int. Ed. 2008, 47, 8224; (o)
Campbell, A. N.; White, P. B.; Guzei, I. A.; Stahl, S. S. J. Am.
Chem. Soc. 2010, 132, 15116; (p) Borelli,T.; Brenna, S.; Broggini,
G.; Oble, J.; Polib, G. Adv. Synth. Catal. 2016, DOI:
10.1002/adsc.201600813.
6. (a) Chen, M. S.; Prabagaran, N.; Labenz, N. A.; White, M. C. J.
Am. Chem. Soc. 2005, 127, 6970; (b) Delcamp, J. H.; White, M.
C. J. Am. Chem. Soc. 2006, 128, 15076; (c) Reed, S. A.; White,
M. C. J. Am. Chem. Soc. 2008, 130, 3316; (d) Strambeanu, I. I.;
White, M. C. J. Am. Chem. Soc. 2013, 135, 12032; (e) Ammann, S.
E.; Rice, G. T.; White, M. C. J. Am. Chem. Soc. 2014, 136, 10834;
(f) Ammann, S. E.; Liu, W.; White, M. C. Angew. Chem. Int. Ed.
2016, 55, 9571.
7. (a) Liu, G.; Yin, G.; Wu, L. Angew. Chem. Int. Ed. 2008, 47,
4733; (b) Wu, L.; Qiu, S.; Liu, G. Org. Lett. 2009, 11, 2707; (c)
Yin, G.; Wu, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 11978.
8. (a) Wang, P.-S.; Lin, H.-C.; Zhai, Y.-J.; Han, Z.-Y.; Gong, L.-Z.
Angew. Chem. Int. Ed. 2014, 53, 12218; (b) Wang, P.-S.; Liu, P.;
Zhai, Y.-J.; Lin, H.-C.; Han, Z.-Y.; Gong, L.-Z. J. Am. Chem. Soc.
2015, 137, 12732.
0.10 equiv), BQ (2.2 mg, 0.20 equiv) and the solvent DMA (1
mL) were added in a 25 mL sealed tube, then the tube was
degassed and replaced by O2. Then the sealed tube was stirred at
40 °C for 12 h. The mixture was purified by column
chromatography using petroleum ether/EtOAc = 10/1 as eluent to
give the product 2a (22.2 mg, 74% yield).
4.9. Conversion of (E)-10 to 2a
Compound (E)-10 (30.1 mg, 0.10 mmol), Pd(OAc)2 (2.2 mg,
0.10 equiv), BQ (2.2 mg, 0.20 equiv) and the solvent DMA (1
mL) were added in a 25 mL sealed tube, then the tube was
degassed and replaced by O2. Then the sealed tube was stirred at
40 °C for 12 h. The mixture was purified by column
chromatography using petroleum ether/EtOAc = 10/1 as eluent to
give the product 2a (14.4 mg, 48% yield).
Acknowledgments
This work was partially supported by the National Natural
Science Foundation of China (no. 21402117, and 21572129). We
thank the Instrumental Analysis Center of Shanghai Jiao Tong
University (SJTU) for analysis and characterization.
References and notes
1. (a) Furman, B. L.; Razark, T. B. A. J. Pharm. Pharmacol. 1981,
33, 735; (b) Adachi, S.; Koike, K.; Takayanagi, I. Pharmacology
1996, 53, 250; (c) Zhao, H.; He, X.; Thurkauf, A.; Hoffman, D.;
Kieltyka, A.; Brodbeck, R.; Primus, R.; Wasley, J. W. F. Bioorg.
Med. Chem. Lett. 2002, 12, 3111; (d) Williams, N. S.; Burgett, A.
W. G.; Atkins, A. S.; Wang, X.; Harran, P. G.; McKnight, S. L.
Proc. Natl. Acad. Sci. USA 2007, 104, 2074; (e) Siengalewicz, P.;
Gaich, T.; Mulzer, J. Angew. Chem. Int. Ed. 2008, 47, 8170; (f)
Lachia, M.; Moody, C. J. Nat. Prod. Rep. 2008, 25, 227; (g) Iida,
A.; Kyuuko, Y. PCT Int. Appl. 2009, WO 2009099140 A1
20090813; (h) Touge, T.; Arai, T. J. Am. Chem. Soc. 2016, 138,
11299; (i) Shifrin, H.; Moradov, D.; Bejar, C.; Schorer-Apelbaum,
D.; Weinstock, M. Pharmacol. Rep. 2016, 68, 1312; (j) Li, G.; Xie,
X.; Zu, L. Angew. Chem. Int. Ed. 2016, 55, 10483; (k) Loach, R.
P.; Fenton, O. S.; Movassaghi, M. J. Am. Chem. Soc. 2016, 138,
1057.
2. (a) Bennett, G. M.; Hafez, M. M. J. Chem. Soc. 1941, 287; (b) Xu,
F.; Simmons, B.; Reamer, R. A.; Corley, E.; Murry, J.; Tschaen,
D. J. Org. Chem. 2008, 73, 312; (c) Rueping, M.; Brinkmann, C.;
Antonchick, A. P.; Atodiresei, I. Org. Lett. 2010, 12, 4604; (d)
Yang, X.; Liu, W.; Li, L.; Wei, W.; Li, C.-J. Chem. Eur. J. 2016,
22, 15252.
9. (a) Wang, F.; Zhang, Y. J.; Wei, H.; Zhang, J.; Zhang, W.
Tetrahedron Lett. 2007, 48, 4083; (b) Wang, F.; Zhang, Y. J.;
Yang, G.; Zhang, W. Tetrahedron Lett. 2007, 48, 4179; (c) Zhang,
Y. J.; Wang, F.; Zhang, W. J. Org. Chem. 2007, 72, 9208; (d)
Wang, F.; Yang, G.; Zhang, Y. J.; Zhang, W. Tetrahedron 2008,
64, 9413; (e) Jiang, F.; Wu, Z.; Zhang, W. Tetrahedron 2011, 67,
1501; (f) Yang, G.; Zhang, W. Org. Lett. 2012, 14, 268; (g) Liu,
Q.; Wen, K.; Zhang, Z.; Wu, Z.; Zhang, Y. J.; Zhang, W.
Tetrahedron 2012, 68, 5209; (h) Yang, G.; Shen, C.; Zhang, W.
Angew. Chem. Int. Ed. 2012, 51, 9141; (i) Wang, X.; Wu, Z.; Zhu,
X.; Ye, C.; Jiang, F.; Zhang, W. Chin. J. Chem. 2013, 31, 132; (j)
Yang, Z.; Xia, C.; Liu, D.; Liu, Y.; Sugiya, M.; Imamoto, T.;
Zhang, W. Org. Biomol. Chem. 2015, 13, 2694; (k) Kou, X.; Li,
Y.; Wu, L.; Zhang, X.; Yang, G.; Zhang, W. Org. Lett. 2015, 17,
5566.
3. Cu: (a) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 7421; (b) Zabawa, T. P.; Kasi, D.; Chemler, S. R.
J. Am. Chem. Soc. 2005, 127, 11250; (c) Takamatsu, K.; Hirano,
K.; Satoh, T.; Miura, M. J. Org. Chem. 2015, 80, 3242; (d) F. Pan,
B. Wu, Z.-J. Shi, Chem. Eur. J. 2016, 22, 6487; Rh: (e) Thalji, R.
K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2001, 123, 9692; Hg: (f) Yamamoto, H.; Ho, E.; Namba, K.;
Imagawa, H.; Nishizawa, M. Chem. Eur. J. 2010, 16, 11271; Pd:
(g) Fix, S. R.; Brice, J. L.; Stahl, S. S. Angew. Chem. Int. Ed.
2002, 41, 164; (h) Lira, R.; Wolfe, J. P. J. Am. Chem. Soc. 2004,
126, 13906; (i) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am.
Chem. Soc. 2005, 127, 7690; (j) Rogers, M. M.; Wendlandt, J. E.;
Guzei, I. A.; Stahl, S. S. Org. Lett. 2006, 8, 2257; (k) Hara, O.;
Koshizawa, T.; Makino, K.; Kunimune, I.; Namiki, A.; Hamada,
Y. Tetrahedron 2007, 63, 6170; (l) Houlden, C. E.; Bailey, C. D.;
Gair Ford, J.; Gagne, M. R.; Lloyd-Jones, G. C.; Booker-Milburn,
K. I. J. Am. Chem. Soc. 2008, 130, 10066; (m) Watanabe, T.;
Oishi, S.; Fujii, N.; Ohno, H. Org. Lett., 2008, 10, 1759; (n) Mei,
T.-S.; Wang, X.; Yu, J.-Q.; J. Am. Chem. Soc. 2009, 131, 10806;
(o) Thansandote, P.; Lautens, M. Chem. Eur. J. 2009, 15, 5874;
(p) Jiang, F.; Wu, Z.; Zhang, W. Tetrahedron Lett. 2010, 51, 5124;
(q) He, G.; Lu, C.; Zhao, Y.; Nack, W. A.; Chen, G. Org. Lett.
2012, 14, 2944; (r) Venning, A. R. O.; Bohan, P. T.; Alexanian, E.
J. J. Am. Chem. Soc. 2015, 137, 3731; (s) Chen, S.-S.; Meng, J.;
Li, Y.-H.; Han, Z.-Y. J. Org. Chem. 2016, 81, 9402.
10. Watanabe, T.; Tsuboi, Y.; Nomura, S. Chem. Asian J. 2013, 8,
630.
11. (a) Sharma, S. K.; Srivastava, V. K.; Pandya, P. H.; Jasra, R. V.
Catal. Commun. 2005, 6, 205; (b) Vasseur, A.; Bruffaerts, J.;
Marek, I. Nature Chem. 2016, 8, 209.
12. Zhu, H.; Chen, P.; Liu, G. J. Am. Chem. Soc. 2014, 136, 1766.
13. Yang, D.; Wang, H.; Sun, Z.-N.; Chung, N.-W.; Shen, J.-G. J. Am.
Chem. Soc. 2006, 128, 6004.
14. Vakarov, S. A.; Gruzdev, D. A.; Chulakov, E. N.; Sadretdinova,
L. Sh.; Ezhikova, M. A.; Kodess, M. I.; Levit, G. L.; Krasnov, V.
P. Chem. Heterocycl. Compd. 2014, 50, 838.
15. Alp, C.; Özsoy, Ş.; Alp, N. A.; Erdem, D.; Gültekin, M. S.;
Küfrevioğlu, Ö. İ.; Şentürk, M. ; C. Supuran, T. J. Enzyme. Inhib.
Med. Chem. 2012, 27, 818.
16. Suna, G.-J.; Wang, Y.; K, Q. Synthesis 2015, 47, 2931.

7
Supplementary Material
Supplementary data
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associated
(experimental
and
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1
characterization data. Copies of the H and 13C NMR spectra of
the products produced in this study) with this article can be
found, in the online version, at http://