Access to 2-Aroylthienothiazoles via C-H/N-O Bond Functionalization of Oximes

Article abstract of DOI:10.1021/acs.orglett.9b03900

A novel strategy for the synthesis of 2-aroylthienothiazoles via C-H/N-O bond functionalization of ketoximes is developed. This reaction features excellent step- and atom-economy, as well as broad substrate scope. Various common ketoximes, even vinyl ketoximes, were efficiently converted to 2-aroylthienothiazoles. Preliminary mechanistic studies indicated that the radical process should be involved in this transformation. Moreover, the product exhibited good coordination with Cu(II), showing the potential application in the metal coordination field.

Full text of DOI:10.1021/acs.orglett.9b03900

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Access to 2‑Aroylthienothiazoles via C−H/N−O Bond
Functionalization of Oximes
Peiqi Zhou, Yubing Huang, Wanqing Wu,* Jiaming Zhou, Wentao Yu, and Huanfeng Jiang*
Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China
University of Technology, Guangzhou 510640, P. R. China
S
* Supporting Information
ABSTRACT: A novel strategy for the synthesis of 2-aroylthienothiazoles via C−H/N−O bond functionalization of ketoximes
is developed. This reaction features excellent step- and atom-economy, as well as broad substrate scope. Various common
ketoximes, even vinyl ketoximes, were efficiently converted to 2-aroylthienothiazoles. Preliminary mechanistic studies indicated
that the radical process should be involved in this transformation. Moreover, the product exhibited good coordination with
Cu(II), showing the potential application in the metal coordination field.
ximes are versatile and fascinating building blocks in
organic synthesis with the advantages of easy availability,
convenient storage, and high reactivity. With base or free
radical initiator added, the oximes could be converted into
various N−O bond-bearing compounds (Scheme 1, route I).1
(Scheme 1, route III−①),3 probably due to the competitive
O−H bond cleavage, making the single electron transfer (SET)
of the N−OH bond on oxime difficult. To date, the direct
employment of cyclobutanone oxime to form an iminyl radical
under photocatalysis developed by Chen has been the only
example.4 Therefore, the development of more types of
transformations of oximes is highly desirable. To the best of
our knowledge, the study of C−H functionalization of oxime
to incorporate both α-C(sp3) and β-C(sp2) into the final cyclic
product remains unexplored (Scheme 1, route III−②).
O
Scheme 1. Reaction Mode of Oximes
2-Aroylthiazoles are an important class of thiazole
derivatives existing in a myriad of clinical drugs and bioactive
molecules, such as anti-infectives, immune agents, cardiovas-
cular drugs, enzyme inhibitors, etc.5 Despite their good
synthetic utility, only one example is reported by Krayushkin
for the synthesis of 2-aroylthienothiazole through four steps
with the thiophene ring as the starting skeleton.6 Until now,
the polycyclization strategy for the preparation of 2-
aroylthienothiazoles would be a high atom- and step-economic
method, but still undeveloped. Herein, we reveal a multi-
component tandem cyclization to assemble the 2-aroylthieno-
thiazole framework, using readily available oximes, S8, and
aromatic ketones as substrates (Scheme 1, route III). This type
of annulation successfully achieves three Csp3−H and a single
Csp2−H bond cleavage in unactivated oximes. Also, this
method can be efficiently carried out in a metal-free manner
without external oxidant, which simplifies the experimental
protocol and improves the atom economy of the process.
In our initial studies, the reaction of acetophenone oxime
(1a), acetophenone (2b), and S8 was chosen as a model to
optimize the reaction conditions, and the results are
On the other hand, another common strategy to activate oxime
is based on O-functionalization, obtaining oxime esters with a
reactive N−O bond. Undergoing in situ imino intermediate
generation and the α-sp3 C−H bond activation process, oxime
esters efficiently construct various N-heterocycles (Scheme 1,
route II).2 Despite significant advances, the prefunctionaliza-
tion operation and harsh storage conditions of oxime esters
(usually below 10 °C) make this strategy relatively
uneconomical and inconvenient. In contrast, synthetic
methods that directly allow N−OH cleavage of oximes to
construct N-bearing heterocycles have been rarely achieved
Received: October 31, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03900
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
summarized in Table 1. The solvent was first screened,
including nonpolar solvents (toluene and DCE, Table 1,
Scheme 2. Substrate Scope of Acetophenones
a
Table 1. Optimization of Reaction Conditions
b
c
entry
solvent
toluene
DCE
base
additive
yield [%]
1
2
3
4
5
6
7
8
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
TBD
-
-
-
-
trace
n.d.
n.d.
18
41
26
22
11
15
78 (73)
33
1,4-dioxane
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
-
FeCl2
CuCl2
I2
NaI
-
-
-
-
9
10
11
12
13
MTBD
Li2CO3
tBuOLi
31
52
a
Reaction conditions: 1a (0.4 mmol), S8 (0.2 mmol), 2b (0.2 mmol),
base (1.0 equiv), and additive (20 mol %) in 1.0 mL of solvent at 120
b
°C under N2 for 26 h unless otherwise noted. MTBD = 7-methyl-
1,5,7-triazabicyclo[4.4.0]dec-5-ene. DBU = 1,8-diazabicyclo[5.4.0]-
c
undec-7-ene. TBD = 1,5,7-triazabicyclo[4.4.0]-dec-5-ene. 1H NMR
yield using nitromethane as an internal standard. The number in
parentheses is isolated yield.
a
Reaction conditions: 1a (0.6 mmol), S8 (0.3 mmol), 2 (0.3 mmol),
and TBD (1.0 equiv) in 1.5 mL of DMSO at 120 °C under N2 for 26
h unless otherwise noted.
entries 1 and 2) and polar solvents (DMSO, MeCN, and 1,4-
dioxane, Table 1, entries 3−5). DMSO was effective for this
transformation, providing the desired product in 41% yield.
Different additives were then examined. It was found that
CuCl2, FeCl2, NaI, and I2 had a negative effect on the reaction
(Table 1, entries 6−9). The effect of base was investigated
(Table 1, entries 10−13), and a lower yield was obtained when
tolerated many heteroarenes such as thiophene (3am), furan
(3an), and pyridine (3ao) and afforded the desired products in
moderate yields.
Next, we examined the substrate scope of aromatic oximes
bearing different substituents (Scheme 3). To our delight,
electron-withdrawing (fluoro, chloro) and electron-donating
(methyl, methoxy, and phenyl) groups at different positions of
the aromatic ring were tolerated, providing the desired
products in yields from 42% to 88%. Even sterically hindered
2-methyl, 2-methoxy, and 3,5-dimethyl oximes worked
efficiently in this reaction and converted to 3ga, 3ha, and
3ia in 88%, 73%, and 75% yields, respectively. Fused ring
oximes such as naphthalene and benzofuran oximes also
reacted smoothly, affording the larger conjugated fused rings
3ja and 3ka in moderate yields. However, heterocyclic
ketoximines, such as pyridine and thiophene oximes, failed to
obtain the corresponding product (3la, 3ma). Notably, vinyl
ketoximes were also well tolerated in this protocol and
converted to the linear heteroaromatic structures 3na and 3oa
in 77% and 52% yields. Moreover, the ionone oxime, derived
from naturally occurring molecules, could be transformed to
the desired product 3pa in 80% yield, indicating the potential
of this method in the elaboration of complex molecules.
Linear domino sequence reaction is an attractive research
topic, which, significantly, provides an efficient tool for
constructing complex molecules with simple raw materials.
Considering acetophenone is a synthetic precursor of oxime,
we envisioned that the present reaction protocol could be
readily extended to a four-component tandem cyclization.
Gratifyingly, a series of ketoximes reacted well under the
standard conditions, providing the expected 2-aroylthienothia-
t
using Li2CO3, BuOLi, DBU, or MTBD as base. TBD was
found to be the optimal choice, and the reaction gave 3ab in
78% NMR yield.
With the optimized conditions in hand, the substrate scope
of this protocol was explored. As presented in Scheme 2, the
reaction was compatible with different aromatic ketones
equipped with either electron-rich or electron-poor substitu-
ents. Thus, the substrates with a methyl, methoxy, or phenyl
group para to the acyl group converted to the corresponding 2-
aroylthienothiazoles 3ab, 3ac, and 3ad in 73%, 87%, and 76%
yields, respectively. The structure of 3aa was confirmed by
single-crystal X-ray diffraction analysis. Substrates with
electron-withdrawing groups, such as fluoro-, chloro-, and
methoxyformyl, were also well tolerated, obtaining 3ae, 3af,
and 3ag in 68%, 70%, and 56% yields. The compatibility of
halogen substituents provides a potential handle for further
synthetic transformations through cross-coupling techniques.
Delightfully, acetophenones bearing electron-rich or electron-
poor substituents such as methyl, methoxy, and halogen at
meta- or ortho-positions reacted well with oxime, giving the
corresponding products (3ah−3ak) in good yields. In addition,
this transformation could be successfully extended to multi-
substituted aromatic ketone, furnishing the corresponding
product 3al in 80% yield. The substrate scope regarding the
heteroarenes was next investigated. Gratifyingly, the reaction
B
DOI: 10.1021/acs.orglett.9b03900
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
was obtained in 79% isolated yield, which indicated the
practical value of this approach (Scheme 5).
Scheme 3. Substrate Scope of Different Oximes
Scheme 5. Gram-Scale Synthesis of 2-Aroylthienothiazoles
Due to their unique 1,4-diheteroatom structures, 2-
aroylthienothiazoles 3 should have important metal coordina-
tion properties. To our delight, the reaction of CuCl2 with 2-
aroylthienothiazole (3ca) afforded a copper(II) complex (Cu-
3ca) (Scheme 6). As shown by single-crystal X-ray analysis, the
Scheme 6. Coordination of 2-Aroylthienothiazole with
a
Copper
a
The crystal structure of Cu-3ca is drawn with 50% probability
ellipsoids.
N and O atoms of 3ca were coordinated with copper, which
indicated that 2-aroylthienothiazoles 3 could serve as an [N,
O] chelate ligand with potential applications in the metal ion
probe,7 bioinorganic chemistry,8 and metal-complex materials.9
To investigate the reaction mechanism, several control
experiments were conducted (Scheme 7). Initially, when the
a
Reaction conditions: 1 (0.6 mmol), S8 (0.3 mmol), 2a (0.3 mmol),
and TBD (1.0 equiv) in 1.5 mL of DMSO at 120 °C under N2 for 26
h unless otherwise noted.
zole products 3aa−3pp in modest yields (Scheme 4). Different
substituents such as methyl, methoxyl, and phenyl on the
Scheme 7. Control Experiments
a
Scheme 4. One-Step Synthesis of 2-Aroylthienothiazoles
a
Reaction conditions: 2 (0.6 mmol), S8 (0.3 mmol), NH2OH·HCl
(0.9 mmol), NaOAc (3.0 equiv), and TBD (1.0 equiv) in 1.5 mL of
a
1H NMR yield using nitromethane as an internal standard.
DMSO at 120 °C under N2 for 26 h unless otherwise noted.
radical scavenger TEMPO was added, the reaction system
became complex, and the yield of 3ab was decreased to 13%
yield (Scheme 7a), which indicated that a radical pathway
might be involved in this reaction. Next, we blended the
oximes and S8 under the standard conditions, and compound 4
was detected by GC-MS (Scheme 7b). Subsequently, when 5
was used as the substrate to react with 6, the target product
3aa was obtained in 81% yield, suggesting that 4 and 6 might
be the intermediates in the reaction (Scheme 7c).
aromatic ring of acetophenone were well tolerated in this
reaction. Notably, this process could efficiently afford sym-
metrically substituted 2-aroylthienothiazoles without prepara-
tion of the starting materials, which simplified the procedure
further.
To test the scalability of the present reaction, a gram-scale
reaction was carried out with 4 mmol of 4-methoxy
acetophenone (2c) as substrate, and the desired product 3ac
C
DOI: 10.1021/acs.orglett.9b03900
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Letter
Considering the S3•− can be generated by the reaction of S8
with base in polar solvent,10 the electron paramagnetic
resonance (EPR) experiment was carried out. Fortunately, an
EPR signal was observed when the mixture of S8 and TBD was
tested (Scheme 8). Therefore, we confirmed that a radical
process was involved in this transformation, and S3•− might be
the key intermediate.
which shows high atom- and step-economy for the synthesis of
N-heterocycles. Preliminary mechanistic studies suggest the
involvement of S3•−, and a radical mechanism for this reaction
is proposed. Moreover, 2-aroylthienothiazoles show good
coordination property with transition metal copper. Further
applications of the metal complex are currently underway in
our laboratory.
ASSOCIATED CONTENT
* Supporting Information
Scheme 8. EPR Studies of Interaction between S8 and Base
■
S
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b03900.
Experimental procedures, condition screening table,
characterization data, and copies of NMR spectra for
all products (PDF)
Accession Codes
CCDC 1921834−1921835 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Based on the above experimental results, a tentative
mechanism is proposed in Scheme 9. First, B is generated
AUTHOR INFORMATION
Corresponding Authors
■
Scheme 9. Proposed Mechanism
*E-mail: cewuwq@scut.edu.cn.
*E-mail: jianghf@scut.edu.cn.
ORCID
Yubing Huang: 0000-0002-3025-8366
Wanqing Wu: 0000-0001-5151-7788
Huanfeng Jiang: 0000-0002-4355-0294
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Ministry of Science and Technology of the
People’s Republic of China (2016YFA0602900), the National
Natural Science Foundation of China (21420102003), and the
Fundamental Research Funds for the Central Universities
(2019PY05) for financial support.
under oxidative conditions,11 where oxime or elemental sulfur
serves as internal oxidant. Meanwhile, S8 reacts with the base
REFERENCES
■
(1) (a) Hoskin, D. H.; Olofson, R. A. J. Org. Chem. 1982, 47, 5222.
(b) Zhu, M.-K.; Zhao, J.-F.; Loh, T.-P. J. Am. Chem. Soc. 2010, 132,
6284. (c) Jiang, D.; Peng, J.; Chen, Y. Org. Lett. 2008, 10, 1695.
(d) Tripathi, C. B.; Mukherjee, S. Angew. Chem., Int. Ed. 2013, 52,
8450. (e) Dong, K.-Y.; Qin, H.-T.; Bao, X.-X.; Liu, F.; Zhu, C. Org.
Lett. 2014, 16, 5266. (f) Peng, X.-X.; Deng, Y.-J.; Yang, X.-L.; Zhang,
L.; Yu, W.; Han, B. Org. Lett. 2014, 16, 4650. (g) Yang, X.-L.; Chen,
F.; Zhou, N.-N.; Yu, W.; Han, B. Org. Lett. 2014, 16, 6476. (h) Wang,
L.-J.; Chen, M.; Qi, L.; Xu, Z.; Li, W. Chem. Commun. 2017, 53, 2056.
(i) He, Y.-T.; Li, L.-H.; Yang, Y.-F.; Wang, Y.-Q.; Luo, J.-Y.; Liu, X.-
Y.; Liang, Y.-M. Chem. Commun. 2013, 49, 5687. (j) Zhang, X.-W.;
Xiao, Z.-F.; Wang, M.-M.; Zhuang, Y.-J.; Kang, Y.-B. Org. Biomol.
Chem. 2016, 14, 7275. (k) Chen, F.; Yang, X.-L.; Wu, Z.-W.; Han, B.
J. Org. Chem. 2016, 81, 3042. (l) Zhang, X.-W.; Xiao, Z.-F.; Zhuang,
Y.-J.; Wang, M.-M.; Kang, Y.-B. Adv. Synth. Catal. 2016, 358, 1942.
(m) Tripathi, C. B.; Mukherjee, S. Org. Lett. 2015, 17, 4424. (n) Wei,
Q.; Chen, J.-R.; Hu, X.-Q.; Yang, X.-C.; Lu, B.; Xiao, W.-J. Org. Lett.
2015, 17, 4464. (o) Kong, W.; Guo, Q.; Xu, Z.; Wang, G.; Jiang, X.;
Wang, R. Org. Lett. 2015, 17, 3686. (p) Yang, X.-L.; Long, Y.; Chen,
to provide S3•−, which has been confirmed by the EPR
•−
experiment. Interaction between oxime and S3
gives
iminosulfur radical intermediate C, followed by tautomeriza-
tion to form D.2p Next, intramolecular cyclization of D and
subsequent oxidative aromatization afford intermediate F,
which then undergoes Willgerodt−Kindler-type sulfuration of
the enamine moiety to generate intermediate G.12 Con-
densation annulation between B and G, followed by oxidative
aromatization, finally produces the desired product 3aa.
In summary, we have developed a novel approach for the
synthesis of 2-aroylthienothiazoles using aromatic ketones,
oximes, and S8. Inexpensive reagents, simple operations, broad
substrate scope, and good scalability make the transformation
attractive. In this protocol, oximes, instead of prefunctionalized
oxime esters, efficiently construct the N-heterocycles. This new
type of annulation involving three Csp3−H and a single Csp2−
H/N−OH cleavage in unactivated ketoximes is first reported,
D
DOI: 10.1021/acs.orglett.9b03900
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
F.; Han, B. Org. Chem. Front. 2016, 3, 184. (q) Triandafillidi, I.;
Kokotos, C. G. Org. Lett. 2017, 19, 106. (r) Zhang, W.; Su, Y.; Wang,
K.; Wu, L.; Chang, B.; Shi, Y.; Huang, D.; Hu, Y. Org. Lett. 2017, 19,
376.
Duboc, C.; Dolbecq, A. Inorg. Chem. 2012, 51, 7921. (b) Tommasino,
J.-B.; Renaud, F. N. R.; Luneau, D.; Pilet, G. Polyhedron 2011, 30,
1663. (c) Li, Y.; Luo, X.; Shao, Y.; Chen, L. J. Org. Chem. 2018, 83,
8768. (d) Feng, L.; Gao, M.; Tao, D.; Chen, Q.; Wang, H.; Dong, Z.;
Chen, M.; Liu, Z. Adv. Funct. Mater. 2016, 26, 2207.
(2) (a) Yang, H.; Pathipati, S. R.; Selander, N. ACS Catal. 2017, 7,
8441. (b) Ke, J.; Tang, Y.; Yi, H.; Li, Y.; Cheng, Y.; Liu, C.; Lei, A.
Angew. Chem., Int. Ed. 2015, 54, 6604. (c) Duan, J.; Cheng, Y.; Li, R.;
Li, P. Org. Chem. Front. 2016, 3, 1614. (d) Lin, X.; Stien, D.; Weinreb,
S. M. Org. Lett. 1999, 1, 637. (e) Too, P. C.; Wang, Y. F.; Chiba, S.
Org. Lett. 2010, 12, 5688. (f) Huang, H.; Cai, J.; Ji, X.; Xiao, F.; Chen,
Y.; Deng, G. Angew. Chem., Int. Ed. 2016, 55, 307. (g) Zhao, M.-N.;
Hui, R.-R.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H. Org. Lett. 2014, 16,
3082. (h) Huang, H.; Xu, Z.; Ji, X.; Li, B.; Deng, G. Org. Lett. 2018,
20, 4917. (i) Zhu, C.; Zhu, R.; Zeng, H.; Chen, F.; Liu, C.; Wu, W.;
Jiang, H. Angew. Chem., Int. Ed. 2017, 56, 13324. (j) Tan, W. W.;
Ong, Y. J.; Yoshikai, N. Angew. Chem., Int. Ed. 2017, 56, 8240.
(k) Zhou, P.; Huang, Y.; Wu, W.; Yu, W.; Li, J.; Zhu, Z.; Jiang, H.
Org. Biomol. Chem. 2019, 17, 3424. (l) Yang, H.; Selander, N. Chem. -
Eur. J. 2017, 23, 1779. (m) Zhao, B.; Liang, H.; Yang, J.; Yang, Z.;
Wei, Y. ACS Catal. 2017, 7, 5612. (n) Too, P. C.; Chua, S. H.; Wong,
S. H.; Chiba, S. J. Org. Chem. 2011, 76, 6159. (o) Tang, X.; Yang, J.;
Zhu, Z.; Zheng, M.; Wu, W.; Jiang, H. J. Org. Chem. 2016, 81, 11461.
(p) Huang, H.; Qu, Z.; Ji, X.; Deng, G. Org. Chem. Front. 2019, 6,
1146. (q) Wei, Y.; Yoshikai, N. J. Am. Chem. Soc. 2013, 135, 3756.
(r) Ramaraju, A.; Chouhan, N. K.; Ravi, O.; Sridhar, B.; Bathula, S. R.
Eur. J. Org. Chem. 2018, 2018, 2963. (s) Bai, D.; Wang, X.; Zheng, G.;
Li, X. Angew. Chem., Int. Ed. 2018, 57, 6633. (t) To, T. A.; Vo, Y. H.;
Nguyen, A. T.; Phan, A. N. Q.; Truong, T.; Phan, N. T. S. Org.
Biomol. Chem. 2018, 16, 5086. (u) Tang, X.; Wu, W.; Zeng, W.; Jiang,
H. Acc. Chem. Res. 2018, 51, 1092.
(9) (a) Fang, X.-Q.; Deng, Z.-P.; Huo, L.-H.; Wan, W.; Zhu, Z.-B.;
Zhao, H.; Gao, S. Inorg. Chem. 2011, 50, 12562. (b) Gorgas, N.;
̈
Stoger, B.; Veiros, L. F.; Kirchner, K. ACS Catal. 2016, 6, 2664.
(c) Kuriki, R.; Matsunaga, H.; Nakashima, T.; Wada, K.; Yamakata,
A.; Ishitani, O.; Maeda, K. J. Am. Chem. Soc. 2016, 138, 5159.
(d) Pardo, E.; Train, C.; Gontard, G.; Boubekeur, K.; Fabelo, O.; Liu,
H.; Dkhil, B.; Lloret, F.; Nakagawa, K.; Tokoro, H.; Ohkoshi, S.-i.;
Verdaguer, M. J. Am. Chem. Soc. 2011, 133, 15328. (e) Yuan, Y.-J.; Yu,
Z.-T.; Chen, D.-Q.; Zou, Z.-G. Chem. Soc. Rev. 2017, 46, 603.
(10) (a) Zhang, G.; Yi, H.; Chen, H.; Bian, C.; Liu, C.; Lei, A. Org.
Lett. 2014, 16, 6156. (b) Li, J. H.; Huang, Q.; Wang, S.-Y.; Ji, S. J. Org.
Lett. 2018, 20, 4704. (c) Gu, Z. Y.; Cao, J. J.; Wang, S. Y.; Ji, S. J.
Chem. Sci. 2016, 7, 4067. (d) Chivers, T. Nature 1974, 252, 32.
(11) (a) Xue, W.-J.; Guo, Y.-Q.; Gao, F.-F.; Li, H.-Z.; Wu, A.-X. Org.
Lett. 2013, 15, 890. (b) Zhao, P.; Wu, X.; Zhou, Y.; Geng, X.; Wang,
C.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2019, 21, 2708. (c) Mupparapu,
N.; Vishwakarma, R. A.; Ahmed, Q. N. Tetrahedron 2015, 71, 3417.
(d) Zhang, J.; Wu, X.; Gao, Q.; Geng, X.; Zhao, P.; Wu, Y.-D.; Wu, A.
Org. Lett. 2017, 19, 408.
(12) Priebbenow, D. L.; Bolm, C. Chem. Soc. Rev. 2013, 42, 7870.
(3) (a) Madabhushi, S.; Vangipuram, V. S.; Mallu, K. K. R.;
Chinthala, N.; Beeram, C. R. Adv. Synth. Catal. 2012, 354, 1413.
(b) Ngwerume, S.; Lewis, W.; Camp, J. E. J. Org. Chem. 2013, 78, 920.
(c) Kaewchangwat, N.; Sukato, R.; Vchirawongkwin, V.; Vilaivan, T.;
Sukwattanasinitt, M.; Wacharasindhu, S. Green Chem. 2015, 17, 460.
(d) Hu, W.; Li, J.; Xu, Y.; Li, J.; Wu, W.; Liu, H.; Jiang, H. Org. Lett.
2017, 19, 678. (e) Zhao, J.-Q.; Yue, D.-F.; Zhang, X.-M.; Xu, X.-Y.;
Yuan, W.-C. Org. Biomol. Chem. 2016, 14, 10946. (f) Konstantinova,
L. S.; Bol’shakov, O. I.; Obruchnikova, N. V.; Laborie, H.; Tanga, A.;
́
́
́
Sopena, V.; Lanneluc, I.; Picot, L.; Sable, S.; Thiery, V.; Rakitin, O. A.
Bioorg. Med. Chem. Lett. 2009, 19, 136.
(4) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Song, D.; Xiang, H.-Y.; Chen, X.-
Q.; Yang, H. Org. Lett. 2019, 21, 2658.
́
̂
(5) (a) Colombo, E.; Desilets, A.; Duchene, D.; Chagnon, F.;
Najmanovich, R.; Leduc, R.; Marsault, E. ACS Med. Chem. Lett. 2012,
3, 530. (b) Cha, J.; Debnath, T.; Lee, K.-G. Sci. Rep. 2019, 9, 5325.
(c) Erdmann, A.; Menon, Y.; Gros, C.; Masson, V.; Aussagues, Y.;
Fleury, L.; Ausseil, F.; Novosad, N.; Schambe, P.; Baltas, M.;
Arimondo, P. B. Future Med. Chem. 2016, 8, 373. (d) Dhameliya, T.
M.; Tiwari, R.; Banerjee, A.; Pancholia, S.; Sriram, D.; Panda, D.;
Chakraborti, A. K. Eur. J. Med. Chem. 2018, 155, 364. (e) Pancholia,
S.; Dhameliya, T. M.; Shah, P.; Jadhavar, P. S.; Sridevi, J. P.;
Yogeshwari, P.; Sriram, D.; Chakraborti, A. K. Eur. J. Med. Chem.
2016, 116, 187. (f) Seierstad, M.; Breitenbucher, J. G. J. Med. Chem.
2008, 51, 7327. (g) Otrubova, K.; Ezzili, C.; Boger, D. L. Bioorg. Med.
Chem. Lett. 2011, 21, 4674. (h) Tang, G.; Nikolovska-Coleska, Z.;
Qiu, S.; Yang, C.-Y.; Guo, J.; Wang, S. J. Med. Chem. 2008, 51, 717.
(i) Nguyen, T. B.; Pasturaud, K.; Ermolenko, L.; Al-Mourabit, A. Org.
Lett. 2015, 17, 2562. (j) Hong, H.; Li, Y.; Chen, L.; Li, B.; Zhu, Z.;
Chen, X.; Chen, L.; Huang, Y. J. Org. Chem. 2019, 84, 5980.
(k) Komiya, M.; Asano, S.; Koike, N.; Koga, E.; Igarashi, J.; Nakatani,
S.; Isobe, Y. Chem. Pharm. Bull. 2013, 61, 1094.
(6) Yarovenko, V. N.; Smirnova, N. G.; Bulgakova, V. N.; Zavarzin,
I. V.; Krayushkin, M. M. Russ. J. Org. Chem. 2003, 39, 1161.
(7) (a) Montagner, D.; Yap, S. Q.; Ang, W. H. Angew. Chem., Int. Ed.
2013, 52, 11785. (b) Zhang, P.; Hou, Y.; Zeng, J.; Li, Y.; Wang, Z.;
Zhu, R.; Ma, T.; Gao, M. Angew. Chem., Int. Ed. 2019, 58, 11088.
(8) (a) El Moll, H.; Zhu, W.; Oldfield, E.; Rodriguez-Albelo, L. M.;
Mialane, P.; Marrot, J.; Vila, N.; Mbomekalle, I. M.; Riviere, E.;
E
DOI: 10.1021/acs.orglett.9b03900
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