Controllable synthesis of 3-chloro- and 3,3-dichloro-2-oxindoles via hypervalent iodine-mediated chlorooxidation

Article abstract of DOI:10.1039/c9ob01173k

An efficient and controllable protocol for the synthesis of 3-chloro- and 3,3-dichloro-2-oxindoles has been developed via hypervalent iodine-promoted chlorooxidation. By using two equivalents of 1-chloro-1,2-benziodoxol-3-(1H)-one, a wide range of indoles

Full text of DOI:10.1039/c9ob01173k

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: X. Jiang, L. Yang,
W. Yang, Y. Zhu, L. Fang and C. Yu, Org. Biomol. Chem., 2019, DOI: 10.1039/C9OB01173K.
Volume 15
Number 47
21 December 2017
Pages 9945-10124
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
Accepted Manuscripts are published online shortly after acceptance,
rsc.li/obc
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 1477-0520
PAPER
I . J. Dmochowski et al.
Oligonucleotide modifi cations enhance probe stability for
shall the Royal Society of Chemistry be held responsible for any errors
single cell transcriptome in vivo analysis (TIVA)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/obc

Please do not adjust margins
Page 1 of 5
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C9OB01173K
Journal Name
ARTICLE
Controllable Synthesis of 3-Choloro- and 3,3-Dicholoro-2-
oxindoles via Hypervalent Iodine Mediate Chlorooxidation
Received 00th January 20xx,
Accepted 00th January 20xx
Xinpeng Jiang, Liechao Yang, Wenlong Yang, Yu Zhu, Liyun Fang, Chuanming Yu*
An efficient and controllable protocol for the synthesis of 3-choloro- and 3,3-dicholoro-2-oxindoles has been developed via
hypervalent iodine promoted chlorooxidation. By using two equivalents of 1-chloro-1,2-benziodoxol-3-(1H)-one, a wide
range of indoles were transformed to 3-choloro-2-oxindoles in DMF/CF3CO2H/H2O at room temperature with good yields.
As far as we know, this is the first report on the selective C-2 oxidation and C-3 monochlorination of simple indoles. In
addition, three equivalents of same hypervalent iodine afforded 3,3-dicholoro-2-oxindoles in up to 99% yields under
optimized conditions (dioxane/H2O, 80 oC). The method features mild reaction conditions, widespread availability of the
substrates, and good functional group tolerance.
DOI: 10.1039/x0xx00000x
www.rsc.org/
knowledge, selective synthesis of 3-chlorooxindoles from
readily available indoles has been rarely explored. Limited
reports were concentrated on chlorooxidation of 3-substituted
Introduction
The 2-oxindole core is a widespread structural unit with
numerous applications in chemical and pharmaceutical
sciences.[1] In particular, 3-chlorooxindoles are important
O
O
O
O
NH
building
blocks
owing
to
its
dual
nature
(nucleophilic/electrophilic) of the C-3 position.[2] Encouraged
by this reactivity profile, 3-chlorooxindoles have been
successfully utilized to synthesize spirocyclic oxindole
scaffolds.[3] The 3,3-dichlorooxindole scaffolds, on the other
hand, were widely existed in a large number of biologically
active compounds,[4] with antidiabetic, anti-cancer and other
pharmacological activities (Figure 1).
R
CO2Me
ref. 3b
O
HN
O
Cl
R
R
O
ref. 3a
ref. 3c
O
O
N
N
H
H
N
Boc
ref. 3a
Over the past few decades, numerous chlorination methods
R1
R2
HO
have been developed to prepare 3,3-dichlorooxindoles from
[5, 4b]
isatins with various chlorine sources, including PCl5
,
O
[8]
SOCl2[6], ClSO3H[7], WCl5, and DCDMH.[9] Recently, Murphy
group reported 3-diazo-2-oxindoles[10] and isatin-3-
ptosylhydrazones[4c] could be transformed to 3,3-
dichlorooxindoles with PhICl2. Indole-2-carboxylic acids[11] and
indole-2,3-carboxylic acids[12] could also be converted to
corresponding dichlorooxindoles respectively. Despite the
N
H
Cl
Cl
O
O
S
Cl
Cl
O
Cl
N
O
N
OBn
N
H
O
impressive
progress
in
this
field,
regioselective
O
caspase inhibitor
anticancer reagent
dichlorooxidation of simple indoles has been less developed. In
2015, Finn group applied hypochlorite, acetic acid, and NaN3 to
generate gaseous ClN3 and then synthesize 3,3-dicholoro-2-
oxindoles (Scheme 1a).[13] Wu and co-workers developed
PhICl2 promoted selective dichlorooxidation of N-pyrimidine
protected indoles (Scheme 1b).[14] To the best of our
Ac
Cl
Cl
O
N
O
S
Cl
N
N
Cl
O
O
N
N
H
antidiabetic reagent
fungicide
Figure.1 Representative applications of 3-chlorooxindoles and 3,3-dichlorooxindoles.
a College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P.R.
China Fax: (+86)571-88320867, E-mail: ycm@zjut.edu.cn
†Electronic Supplementary Information (ESI) available.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 5
ARTICLE
Journal Name
indoles.[15] Recently, Rao and coworkers developed a novel gave 4a in 95% yield with no byproduct 3a observed (entries
View Article Online
strategy that using oxone and NaCl to convert indoles-3- 12 and 13). Moreover, other hypervaDleOnI:t10i.o10d3in9/eC,9OsuBc0h1173aKs
carboxaldehydes to 3-chlorooxindoles (Scheme 1c).[16] In phenyliodine(III) dichloride 2b was also investigated, but gave
pursuit of our efforts on building indole derivatives with inferior results (entries 14 and 15), which illustrated that 1-
[17]
special structures,
herein, we report a controllable C-2 chloro-1,2-benziodoxol-3-(1H)-one 2a possess higher reactivity
oxidation and C-3 mono-/di-chlorination of indoles with in this reaction system.[18]
hypervalent iodines (Scheme 1d).
With the optimal reaction conditions in hand, we examined
the scope of this reaction (Table 2). The reaction proceeded
smoothly to afford 3-chlorooxindoles in high yields with good
functional group compatibility. Halides (F, Cl, and Br) and
electron donating groups (Me and MeO) were tolerated at
different positions on indole aromatic ring, and gave
corresponding product 3-choloro-2-oxindoles in 61%–91%
yields (3a-3k). The tolerance of Cl/Br groups in this reaction
provides an opportunity for further functionalization.[19] The
substituent on nitrogen was then examined. Aliphatic groups,
such as methyl and isopropyl groups, on indole nitrogen were
tolerated under standard conditions, giving 3m-3n in 69% and
95% respectively. N-Benzyl substituted indole also gave 3o in
77% yield. However, 1H-indole gave 3l in lower yield (25%).
Next, the substrate scope of indoles in 3,3-dicholoro-2-
oxindoles formation were explored under optimized
Results and discussion
We tried the chlorooxidation of 4-chloro-1-ethyl-1H-indole 1a
with 1-chloro-1,2-benziodoxol-3-(1H)-one 2a in the first
instance. Considering the solubility of the starting materials,
acetone/H2O = 15:1 was initially tested, giving chlorooxidation
products 3a and 4a in 36% and 29% yield respectively (Table 1,
entry 1). Subsequently, a series of solvents were also screened
(entries 2-3). To our delight, CF3CO2H/H2O was beneficial to
the transformation (entry 3). We then screened a series of
mixed solvents to optimize this reaction (entries 4-6).
Interestingly, in DMF/TFA/H2O = 20/10/2, the yield of 3a
improved to 66% and 4a decreased to 7% (entry 6). Reducing
the amount of DMF afforded 3a in 89% yield with only 4% of
4a generated (entry 7). It’s worth to note that other acids,
such as formic acid and acetic acid, gave lower yields (entries
8-9). On the other hand, the yield of 4a enhanced to 53% in
dioxane: H2O = 15:1 (entry 10). Extending the reaction time to
30 min and increasing 2a to 3 equivalents improved the yield
of 4a to 64% (entry 11). Higher reaction temperature (80 °C)
o
conditions (3 eq of 2a in dioxane/H2O =15/1 at 80 C for 30
min) as illustrated in Table 2. Indoles bearing either an
electron-withdrawing group (F, Cl, Br, NO2, and CN) or an
electron-donating group (Me) on aromatic ring were
converted to the desired products in 77-99% yields (4a–4i). It
is worth noting that 1- ethyl-7-azaindol could also afford the
corresponding product 4j in 91% yield. Meanwhile, the reaction of
N-unsubstituted indoles with 2a under standard conditions
produced 4k-4o in 87-99% yields.
Previous work
:
Table 1. Optimization of the reaction conditionsa
Cl
Cl
Cl
Cl
ClN3
Cl
Cl
Cl
Cl
I
O
Cl
(a)
O
N
H
Solvent
T, t
MeO2C
N
MeO2C
O
O
+
H
N
N
N
Et
Et
Et
O
4a
1a
2a
3a
Cl
Cl
time
(min)
10
10
10
10
10
10
10
10
10
10
30
30
30
10
30
yield g
3a
R1
R1
(b)
Entry
solvent
T (oC)
O
N
PhICl2 (3 eq)
4a
29
36
39
29
13
7
N
1b
acetone:H2O
DMF:H2O
CF3CO2H:H2O
acetone:CF3CO2H:H2O
MeCN:CF3CO2H:H2O
DMF:CF3CO2H:H2O
DMF:CF3CO2H:H2O
DMF:HCO2H:H2O
DMF:AcOH:H2O
dioxane:H2O
dioxane:H2O
dioxane:H2O
dioxane:H2O
DMF:CF3CO2H:H2O
dioxane:H2O
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
36
23
33
39
54
66
89
70
16
11
9
N
N
N
N
2b
3b
4c
Cl
CHO
(c)
5c
Oxone (2 eq)
NaCl (2 eq)
R2
O
R2
6c
N
N
R1
R1
7d
4
8d
11
24
53
64
89
95
5
Cl
I
O
9d
This work
:
(2 eq)
Cl
10 b
11b,e
12b,e
13b,e
14d,f
15b,e,f
O
R2
O
rt
DMF/CF3CO2H/H2O
rt, 10 min
N
50
80
rt
8
0
66
20
R1
(d)
R2
Cl
I
O
N
R1
80
75
(3 eq)
Cl
Cl
a Reaction conditions: 1a (0.5 mmol), 2a (2.0 eq). Solvent (v/v = 15:1) Solvent
(v/v/v = 20:10:2). Solvent (v/v/v = 15:10:2). 2a (3.0 eq). phenyliodine(III)
dichloride 2b was used instead of 2a. Determined by H1 NMR spectroscopic
b
c
O
R2
O
d
e
f
dioxane/H2O,
80 oC, 30 min
N
g
R1
analysis.
Scheme 1
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 3 of 5
Organic & Biomolecular Chemistry
Journal Name
ARTICLE
Table 2. Synthesis of 3-chlorooxindoles via chlorooxidation of indoles.a,b
View Article Online
Cl
Cl
I
O
DOI: 10.1039/C9OB01173K
Cl
Dioxane, 80oC,
H2O, 30min
Cl
I
O
Cl
O
R2
R2
N
R1
4
DMF/CF3CO2H/H2O = 15/10/2
R2
N
R1
R2
O
+
N
O
N
rt, 10min
R1
1
R1
2a
(3 eq)
O
2a
3
(2 eq)
Br
1
R
Cl
Cl
Cl
Cl
Cl
Cl
Cl
R
Cl
Cl
Cl
Cl
O
N
Et
O
O
Cl
O
N
R
R
O
N
O
O
N
Et
N
Et
91%
Et
N
Et
N
4c
4d,
4e
4f
, R = NO2, 92%
Et
, 82%
Et
, 82%
4g
4h
4i
, R = F, 77%
, R = Br, 98%
, R = Me, 93%
4a
4b
, R = Cl, 95%
, R = Br, 99%
3a
, 89%
3b,
R = CN, 96%
, R = Cl, 93%
, R = Br, 93%
3c
3d
Cl
Cl
Cl
Cl
Br
Me
MeO
Cl
Cl
F
Cl
Cl
O
O
O
Cl
Cl
O
N
Et
N
N
N
F
O
O
Et
, 77%
Et
Et
, 67%
O
N
N
N
H
3f
3e
c
, 68%
N
H
3g
3h,
61%
Et
Cl
Cl
4j
, 91%
4l
,
R = Br, 99%
4k
Cl
, 90%
Cl
4m
, R = Me, 87%
O
O
N
O
O
Cl
Cl
Cl
Cl
Cl
Cl
N
Et
Cl
N
Me
Et
N
Br
H
Et
O
N
Bn
O
O
3i
, 65%
Cl
3j
, 71%
Cl
3k
, 79%
Cl
3l
, 25%
N
H
N
R
Me
, 94%
O
O
4q
, 94%
4n
4o
, R = F, 96%
, R = Br, 95%
4p
O
N
N
N
i-Pr
Me
Bn
, 77%
3n
, 95%
3m,
69%
3o
a
Reaction conditions: 1 (0.5 mmol), 2a (3.0 eq), solvent ：dioxane:H2O (3.0 mL:
0.2 mL), 80 oC, 30 min. b Isolated yields.
a
Reaction conditions: 1 (0.5 mmol), 2a (2.0 eq), solvent ：DMF: CF3CO2H: H2O
(1.5 mL: 1.0 mL: 0.2 mL), rt, 10 min. b Isolated yields. c 2a (2.1 eq) was used.
Based on the above experiments and previous reports, [20, 17c]
a possible mechanism was proposed (Scheme 3). Initially,
intermediate A was generated from the chlorophilic attack of
1m to hypervalent iodine 2a. The key intermediate 3-chloro-1-
methyl-1H-indole 5 was then formed via isomerization. Under
acidic conditions, trifluoroacetic acid (TFA) reacted with 5 to
form salt B, which might undergo 1,3-hydrogen transfer to
afford C. Water then attacked the C-2 position of C to produce
intermediate D, which could be oxidized by 2a to generate the
desired product 3m. On the other hand, in the absence of TFA,
5 reacted with another equivalent of hypervalent iodine 2a to
form E. Water attacked C-2 position of E to generate
intermediate F, which could easily be oxidized by the third
equivalent of 2a to afford 4p. Besides, intermediate H could
also undergo elimination to form 3m with insufficient
hypervalent iodine 2a (Scheme 2c).
Furthermore, N-methyl and benzyl substituted indoles
successfully generated 4p and 4q in 94% yields respectively.
To understand the mechanism of two reactions, the
following control experiments were performed (Scheme 2).
Firstly, the radical scavenger 2,6-di-tert-butyl-4-methylphenol
(BHT) was added to the two reactions respectively, giving the
ideal yield of 3m and 4p in slightly lower yields, which ruled
out the possibility of radical mechanism (Scheme 2a and
Scheme 2b). When 1m was treated with one equivalent of
hypervalent iodine 2a under standard conditions (Scheme 2c),
3-chloro-1-methyl-1H-indole 5 was isolated in 90% yield. We
speculated that this chlorination product could be an
intermediate of chlorooxidation. Indeed,
5
exhibited
comparable activity with the second equivalent of hypervalent
iodine 2a and gave desired product 3m in 82% yield, indicating
that 3-chloro-1-methyl-1H-indole is an intermediate (Scheme
2d). On the other hand, when the reaction of 1m and 2a (2.0
eq) were conducted in 1,4-dioxane at 80oC for 30 min, the
desired product 4p was isolated in only 30% yield, together
Conclusions
In summary, we have disclosed a novel hypervalent iodine
mediated chlorooxidation of indoles that could conduct
oxidation of C2 sites and mono-/di-chlorination of C3 sites of
indoles in one-step transformation. This method possessed
several advantages, including metal-free reaction conditions,
high selectivity, and mild reaction conditions with good
with 3-chloro-1-methyl-1H-indole
5
and 3-chloro-1-
methylindolin-2-one 3m in 17% and 27% yield respectively
(Scheme 2e). Since 5 could also transform to 4p in 90% yield,
we speculated that it also might be the intermediate (Scheme
2f). Furthermore, 3m was eliminated as a intermediate
because of its reaction with one equivalent of 2a resulted no
ideal product 4p (Scheme 2g).
Table 3. Synthesis of 3,3-dicholoro-2-oxindoles via chlorooxidation of indoles. a,b
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 5
ARTICLE
Journal Name
Scheme 2 Control experiments.
Scheme 3 Proposed mechanism.
View Article Online
DOI: 10.1039/C9OB01173K
Cl
1) Radical inhibiting experiment
2a
Cl
N
Cl
H
Cl
I
O
Cl
BHT (2 eq)
DMF/CF3CO2H/H2O
TFA
N
N
Me
Me
N
Me
(a)
CF3COO
H
Me
I
O
H
N
rt, 10 min
B
N
1m
A
5
Me
O
COO
Me
2a
3m
1m
2a
2 eq
I
69 %
Cl
Cl
I
BHT (2 eq)
1,4-dioxane/H2O
80 oC, 30 min
Cl
COO
Cl
Cl
Cl
Cl
Cl
O
OH2
(b)
H
O
Cl
N
Me
4p
Cl
OH
N
N
Me
O
N
N
Me
C
Me
O
O
N
Me
Me
CF3COO
2a
1m
4p
E
F
2a
3 eq
86 %
2) Intermediate capture experiment
H2O
HCl
O
Cl
I
O
Cl
TFA
OH
DMF/CF3CO2H/H2O
rt, 10 min
(c)
Cl
Cl
O
N
N
Me
O
Me
N
Me
N
Me
1m
5
2a
1 eq
2a
90%
D
3m
Cl
I
O
Cl
Cl
DMF/CF3CO2H/H2O
rt, 10 min
(d)
O
N
on silica gel (hexane:ethyl acetate = 20:1 to 10:1) to afford 3a
as a white solid (102 mg, 89%).
N
Me
O
Me
2a
1 eq
5
3m
82%
General procedure for the preparation of 4.
To the solution of 1,4-dioxane (3.0 mL) and H2O (0.2 mL) was
added 4-chloro-1-ethyl-1H-indole (92 mg, 0.5 mmol) and 1-
chloro-1,2-benziodoxol-3-(1H)-one (434 mg, 1.5 mmol)
successively. The reaction mixture was then stirred at 80 °C for
30min. After the completion of reaction, as indicated by TLC,
the reaction was then quenched by slow addition of saturated
NaHCO3 (aq., 15 mL)[21] and extracted with ethyl acetate (10
mL x 3). The combined organic phase was washed with brine
(10 mL), dried over Na2SO4, and evaporated under reduced
pressure. The residue was purified by flash chromatography on
silica gel (hexane:ethyl acetate = 30:1 to 20:1) to afford 4a as a
yellow solid (128 mg, 95%).
Cl
I
O
1,4-dioxane/H2O
80 oC, 30 min
4p
30%
3m
27%
5
17%
(e)
N
Me
O
2a
2 eq
1m
Cl
Cl
Cl
Cl
1,4-dioxane/H2O
80 oC, 30 min
I
O
(f)
O
N
N
Me
Me
O
p
4
90%
5
2a
2 eq
Cl
Cl
Cl
I
O
Cl
1,4-dioxane/H2O
80 oC, 30 min
O
O
(g)
N
N
Me
3m
Me
O
Conflicts of interest
There are no conflicts to declare.
p
4
2a
1 eq
Not observed
functional group tolerance. Further synthetic applications are
now ongoing in our laboratory.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (NSFC) (Grant Nos. 21506191 and
21676252).
Experimental
General procedure for the preparation of 3.
To the solution of DMF (1.5 mL) and TFA (1.0 mL) was added
H2O (0.2 mL). After the mixture cooled to room temperature,
4-chloro-1-ethyl-1H-indole (90 mg, 0.5 mmol) and 1-chloro-
1,2-benziodoxol-3-(1H)-one (282 mg, 1.0 mmol) were added
successively, and then stirred at room temperature for 10 min.
After the completion of reaction, as indicated by TLC, the
reaction was then quenched by slow addition of saturated
NaHCO3 (aq., 15 mL)[21] and extracted with ethyl acetate (10
mL x 3). The combined organic phase was washed with brine
(10 mL), dried over Na2SO4, and evaporated under reduced
pressure. The residue was purified by flash chromatography
Notes and references
[1] (a) M. Mohammadi, G. McMahon, L. Sun, C. Tang, P. Hirth, B. K.
Yeh, S. R. Hubbard, J. Schlessinger, Science . 1997, 276, 955-960; (b)
L. Sun, N. Tran, F. Tang, H. App, P. Hirth, G. McMahon, C. Tang, J.
Med. Chem. 1998, 41, 2588-2603; (c) M. Sassatelli, E. Debiton, B.
Aboab, M. Prudhomme, P. Moreau, Eur. J. Med. Chem. 2006, 41,
709-716; (d) C. V. Galliford, K. A. Scheidt, Angew. Chem. Int. Ed.
2007, 46, 8748-8758; (e) J. Xiao, W. Westbroek, O. Motabar, W. A.
Lea, X. Hu, A. Velayati, W. Zheng, N. Southall, A. M. Gustafson, E.
Goldin, E. Sidransky, K. Liu, A. Simeonov, R. J. Tamargo, A. Ribes, L.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 5 of 5
Organic & Biomolecular Chemistry
Journal Name
ARTICLE
Matalonga, M. Ferrer, J. J. Marugan, J. Med. Chem. 2012, 55, 7546- [20] (a) K. Kanamori, H. Kataoka, S. Matsugo, Eur. J. Inorg. Chem.
7559; (f) Q.-X. Liang, L. Liao, J. Luo, S. Pu, Y.-L. Wang, T. Chen, Asian. 2012, 4570-4573; (b) M. Wang, Y. Zhang, T. Wang, C. VWiewanAgrt,icDle.OXnulinee,
DOI: 10.1039/C9OB01173K
J. Chem. 2015, 27, 2959-2963.
J. Xiao, Org. Lett. 2016, 18, 1976-1979; (c) X. Liu, K. Tong, A. H.
[2] (a) M. Ošeka, A. Noole, S. Žari, M. Öeren, I. Järving, M. Lopp, T. Zhang, R. X. Tan, S. Yu, Org. Chem. Front 2017, 4, 1354-1357.
Kanger, Eur. J. Org. Chem. 2014, 3599-3606; (b) X.-L. Liu, J. Yue, S. [21] Following the recommendation from a reviewer, we applied
Chen, H.-H. Liu, K.-M. Yang, T.-T. Feng, Y. Zhou, Org. Chem. Front. saturated Na2S2O3 solution (0.5 mL) to quench potential remaining
2019, 6, 256-262.
oxidizing species after the addition of saturated NaHCO3 (aq., 15
[3] (a) A. Noole, M. Ošeka, T. Pehk, M. Öeren, I. Järving, M. R. J. mL) during workup and found that the yields of 3a and 4a did not
Elsegood, A. V. Malkov, M. Lopp, T. Kanger, Adv. Synth. Catal. 2013, change.
355, 829-835; (b) X.-L. Jiang, S.-J. Liu, Y.-Q. Gu, G.-J. Mei, F. Shi, Adv.
Synth. Catal. 2017, 359, 3341-3346; (c) Y. Kuang, B. Shen, L. Dai, Q.
Yao, X. Liu, L. Lin, X. Feng, Chem. Sci. 2018, 9, 688-692.
[4] (a) X. Dou, B. Zhou, W. Yao, F. Zhong, C. Jiang, Y. Lu, Org. Lett.
2013, 15, 4920-4923; (b) Y. He, C. Guo, B. Sun, J. Quinn, Y. Li, Chem.
Commun. 2015, 51, 8093-8096; (c) C. Hepples, G. K. Murphy,
Tetrahedron Lett. 2015, 56, 4971-4974.
[5] A. N. C. Lötter, R. Pathak, T. S. Sello, M. A. Fernandes, W. A. L.
van Otterlo, C. B. de Koning, Tetrahedron 2007, 63, 2263-2274.
[6] A. Smith, J. Thomson, A. Kyle, K. Gallagher, P. Lenden, C.
Concellón, L. Morrill, A. Miller, C. Joannesse, A. Slawin, Synthesis
2008, 2805-2818.
[7] Y. Jiang, T. V. Hansen, Bioorg. Med. Chem. Lett. 2011, 21, 1626-
1629.
[8] S. Dolci, F. Marchetti, G. Pampaloni, S. Zacchini, Dalton Trans.
2013, 42, 5635-5648.
[9] B. R. Buckley, B. Fernández D.-R, Tetrahedron Lett. 2013, 54,
843-846.
[10] G. K. Murphy, F. Z. Abbas, A. V. Poulton, Adv. Synth. Catal.
2014, 356, 2919-2923.
[11] (a) T. A. Foglia, D. Swern, J. Org. Chem. 1968, 33, 4440-4442;
(b) R. J. Bass, Tetrahedron 1971, 27, 3263-3270.
[12] (a) H. Hamamoto, H. Umemoto, M. Umemoto, C. Ohta, Y. Miki,
synlett 2010, 17, 2593–2596; (b) H. Hamamoto, Y. Miki, H.
Umemoto, M. Umemoto, C. Ohta, E. Fujita, A. Nakamura, T.
Maegawa, Y. Miki, Heterocycles 2015, 91, 561-572.
[13] R. A. Valiulin, S. Mamidyala, M. G. Finn, J. Org. Chem. 2015, 80,
2740-2755.
[14] D. Xu, W.-W. Sun, Y. Xie, J.-K. Liu, B. Liu, Y. Zhou, B. Wu, J. Org.
Chem. 2016, 81, 11081-11094.
[15] (a) J. S. Pilar López-Alvarado, Sonia Miranda, Carmen
Avendaño, J. Carlos Menéndez, synlett 2007, 18, 2792-2796 ; (b) P.
López-Alvarado, J. Steinhoff, S. Miranda, C. Avendaño, J. Carlos
Menéndez, Tetrahedron 2009, 65, 1660-1672; (c) H. Wang, D. Liu,
H. Chen, J. Li, D. Z. Wang, Tetrahedron 2015, 71, 7073-7076; (d) K.
Tong, X. Liu, Y. Zhang, S. Yu, Chem. Eur. J. 2016, 22, 15669-15673.
[16] V. Lakshmi Reddy, P. S. Prathima, V. J. Rao, R. Bikshapathi, New
J. Chem. 2018, 42, 20152-20155.
[17] (a) X. Jiang, J. Chen, W. Zhu, K. Cheng, Y. Liu, W.-K. Su, C. Yu, J.
Org. Chem. 2017, 82, 10665-10672; (b) X. Jiang, G. Li, C. Yu,
Tetrahedron Lett. 2018, 59, 1506-1510; (c) X. Jiang, C. Zheng, L. Lei,
K. Lin, C. Yu, Eur. J. Org. Chem. 2018, 1437-1442; (d) X. Jiang, B. Zhu,
K. Lin, G. Wang, W.-K. Su, C. Yu, Org. Biomol. Chem. 2019, 17, 2199-
2203; (e) X. Jiang, W. Zhu, L. Yang, Z. Zheng, C. Yu, Eur. J. Org. Chem.
2019, 2268-2274.
[18] In addition, we conducted the reaction of 1a and 2a (3.0 eq)
under standard conditions of ref. 14 (AcOH, 50 oC, 30 min) and
obtained product 4a in 60% yield.
[19] (a) S. Göring, J.-M. Taymans, V. Baekelandt, B. Schmidt, Bioorg.
Med. Chem. Lett. 2014, 24, 4630-4637; (b) Y.-G. Li, Wang, Zhen-Yu,
Zou, Ya-Ling, So, Chau-Ming, Kwong, Fuk-Yee, Qin, Hua-Li, Kantchev,
Eric Assen B, synlett 2017, 28, 499-503; (c) J. Wang, J. Zhao, H.
Gong, Chem. Commun. 2017, 53, 10180-10183.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins