Cu(OAc)2-Triggered Cascade Reaction of Malonate-Tethered Acyl Oximes with Indoles, Indole-2-alcohols, and Indole-2-carboxamides

Article abstract of DOI:10.1021/acs.orglett.9b00849

A Cu(OAc)₂-promoted cascade reaction of malonate-tetherd acyl oximes with indoles, indole-2-alcohols, or indole-2-carboxmides provides facile access to polysubstituted 3-pyrrolin-2-ones. The reaction features the generation of two adjacent elec

Full text of DOI:10.1021/acs.orglett.9b00849

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cu(OAc)2‑Triggered Cascade Reaction of Malonate-Tethered Acyl
Oximes with Indoles, Indole-2-alcohols, and Indole-2-carboxamides
Peng-Fei Mao, Li-Jin Zhou, An-Qi Zheng, Chun-Bao Miao,* and Hai-Tao Yang*
Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou
University, 1 Gehu Road, Changzhou, Jiangsu 213164, China
S
* Supporting Information
ABSTRACT: A Cu(OAc)2-promoted cascade reaction of
malonate-tetherd acyl oximes with indoles, indole-2-alcohols,
or indole-2-carboxmides provides facile access to polysubsti-
tuted 3-pyrrolin-2-ones. The reaction features the generation of
two adjacent electrophilic centers at the same time as cyclization
to lactam. The subsequent double addition with nucleophiles
followed by oxidation realizes the difunctionalization of the
imine sp2-carbon and the adjacent α-sp3-carbon.
Scheme 1. Main Reaction Types of Acyl Oximes
ximes are a class of important organic compounds widely
1
Oused in Beckmann rearrangement,
Semmler−Wolff
reaction,2 and Neber rearrangement3 owing to the relatively
low dissociation energy of the N−O bond. Introducing an acyl
group on the oxygen atom avoids the reaction from O−H
functionalization and makes the cleavage of N−O bond easier.
Acyl oximes have emerged as versatile building blocks for the
synthesis of structurally diverse N-heterocycles via N−O bond
cleavage and C−N bond formation catalyzed by transition
metals.4−12 In addition, acyl oximes can also act as internal
oxidants while participating in the reaction, avoiding the use of a
stoichiometric amount of external oxidant. A variety of the
synthetic transformations were developed in recent years. The
reaction types of acyl oximes are mainly as follows: (1) The
imine serves as the directing group in ortho-CAr−H activation
reaction, and a formal [4 + 2] product is produced (Scheme
1a).5 Zhao et al. has developed a highly para-selective CAr−H
difluoromethylation of acyl oximes.6 (2) A transition-metal-
catalyzed intramolecular Heck-type reaction through the
addition of an imine radical or imine−metal complex to the
tethered alkene group was followed by further elimination7 or
functionalization (Scheme 1b).8 (3) Radical coupling reaction at
the α-carbon of acyl oximes9 or [3 + n] reaction8f,10 generates
various coupling products or five/six-membered nitrogen-
containing heterocycles (Scheme 1c). (4) The iminyl radical
generated from acyl cyclobutanone/cyclopentanone oxime
triggered ring-opening C−C bond cleavage to form cyanoalkyl
radicals which were further functionalized in a series of radical
transformations (Scheme 1d).8f,11 Acyl oxime can also take part
in the intramolecular aromatic cyclization reaction via an iminyl
radical, iminyl cation, or imine−metal pathway.12 Recently, γ-
C(sp3)−H functionalization of oximes based on the 1,5-
hydrogen transfer of a generated iminyl radical was devel-
oped.11k,13 From the structural perspective of acyl oximes, most
of them are linked to an intramolecular alkene, arene unit or
have a cyclobutane/cyclopentane skeleton, whereas other types
of acyl oximes have rarely been investigated. In view of the above
points, we introduce a nucleophilic site on the α- carbon of acyl
oxime. In the presence of a transition-metal catalyst, an iminyl
radical or imine−metal intermediate can be generated, which
adds to the alkene or alkyne followed by cyclization to generate
the [4 + 2] product (Scheme 2a). The nucleophilic atom can be
carbon, nitrogen, and oxygen atom, which will lead to
structurally diverse products. In sharp contrast to the reported
[4 + 2] or [3 + 3] reaction of acyl oxime, the six-membered
heterocyclic products are mainly limited to pyridines.
Received: March 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00849
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choice. Using DMSO as the solvent, a considerable amount of
aminal product 4a was formed, whereas the reaction in CH3CN
only produced a trace amount of 4a. In the absence of base, the
reaction proceeded equally well to give a comparable yield of 3aa
(Table S1, entry 16). Using Cu(OTf)2, CuCl2, or Cu(ClO4)2
instead of Cu(OAc)2 generated only a trace of 3aa, and the
transformation of most of 1a into the ketone was observed.
Under open air conditions, neither 3aa nor 4a was generated.
Additionally, reducing the loading of Cu(OAc)2 to a catalytic
amount with a combination of external oxidant such as (t-
BuO)2, K2S2O8, or t-BuOOH was infeasible.
Scheme 2. Initial Design and the Primary Results
Based on the above optimization study, the generality of the
Cu(OAc)2-promoted reaction of acetyl oximes with indoles was
investigated (Scheme 3). A variety of acetyl oximes derived from
Scheme 3. Cu(OAc)2-Promoted Reaction of Indoles with
a
Acetyl Oximes 1
With this concept in mind, we prepared acetyl oxime 1a
bearing a malonate group because malonate is a good
nucleophile and is liable to generate free radicals oxidized by
transition metals. In a preliminary attempt, the reaction of 1a
with diphenylacetylene or 1,1-diphenylethylene catalyzed by
CuCl, CuI, or Pd(PPh3)4 in the presence of a base under a
nitrogen atmosphere was carried out. Disappointingly, no
anticipated [4 + 2] product was formed (Scheme 2b). When
it was treated with indole 2a under similar conditions (see
Supporting Information (SI), Table S1), no desired [4 + 2]
product was generated either. To our surprise, the formation of
3-pyrrolin-2-one product 3aa bearing two indole units along
with the aminal product 4a was observed. The formation of 3-
pyrrolin-2-ones from oximes and the difunctionalization of the
imine sp2-carbon and the adjacent α-sp3-carbon of acyl oximes
was unprecedented. An important point to note was that the
introduction of a malonate group on the α-carbon of acyl oximes
resulted in the emergence of a novel reaction mode of the acyl
oximes.
3-Pyrrolin-2-ones are important motifs occurring in many
natural products such as PI-090, myceliothermophins A−E,
oteromycin, amooramides A−L, salannolactams, and munronin
D,14 which display a broad range of biological activity as
anticancer, antimalarial, anti-HIV agents, ASK1, Mdm2
inhibitors, or nonpeptide CCK ligands.15 Therefore, the
development of new methods for their efficient synthesis with
structural diversity is still of high interest.
Inspired by the result, we further optimized the conditions for
the preparation of 3aa (see SI, Table S1). The formation of 3aa
indicated that an oxidative process was involved in this reaction.
Hence, Cu(OAc)2 was used instead of CuCl or CuBr, and the
amount of indole was increased to 2 equiv to optimize the
reaction condition. The reaction proceeded faster in CH3CN,
and the yield was improved significantly to 68%. However, a
small amount of indole 2a remained unreacted probably due to
the slight decomposition of 1a. Pleasingly, when the amount of
2a was decreased to 1.6 equiv, a full conversion of 1a and 2a was
observed, resulting in a further improvement of the yield of 3aa
to 86%. Solvent screening revealed that CH3CN was the best
a
Yield was calculated based on 2.
α-malonate-substituted ketones participated in the reaction with
different substituted indoles, affording the corresponding 3-
pyrrolin-2-ones. Various functional groups including bromo,
chloro, cyano, ester, and nitro groups as well as thiophene
heterocycles were well tolerated in the reaction. No electronic
effect was observed for the substituent on the phenyl ring. When
R1 was a methyl group, the desired product 3ha was obtained in
low yield. In addition, introducing a methyl group to the α-imine
carbon led to the formation of 1:1 adduct 3ia in 50% yield.
We reasoned that the formation of byproduct 4a might be
derived from the nucleophilic addition of water. Thus,
introducing a tethered nucleophilic site on the 2-position of
indole might lead to a cycloaddition reaction to generate various
polycyclic indole derivatives. It would be very interesting as
many polycyclic indoles have been reported to exhibit numerous
B
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biological activities.16 Accordingly, indole-2-methanol 5a and 2-
indoleformamide 7a were introduced in the reaction with 1a
(Scheme 4). The reaction of 1a with 5a in the presence of 2
Scheme 6. Cu(OAc)2-Promoted Reaction of Indole-2-
Carboxamides with Acetyl Oximes
Scheme 4. Reaction of 1a with 5a or 7a
equiv of Cu(OAc)2 proceeded rapidly at 80 °C, affording the
anticipated product 6aa in 80% yield within 1 h. However, the
reaction of 1a with 7a in the presence of 2 equiv of Cu(OAc)2
proceeded very slowly, and only a trace amount of the desired
product 8aa was formed after 2 h. We were pleased to find that
adding 2 equiv of K2CO3 as the base accelerated the reaction
remarkably, and the reaction was completed within 1 h to afford
63% yield of 8aa. It was noteworthy that the reaction of 1a with
5a or 7a showed excellent regioselectivity with indole-3-carbon
coupling with sp3-carbon and heteroatom attack on the imine
carbon.
To evaluate the generality of this process, various indole-2-
alcohols and indole-2-carboxamides were subjected to the
reaction with 1 (Schemes 5 and 6). For the indole-2-alcohols 5,
the substituent R2 on the phenyl ring had no influence on their
reactions with 1. All the primary, secondary, and tertiary alcohols
could react with 1a to give the corresponding products 6. When
an asymmetrical alcohol 5f (R3 = Me) was subjected to the
reaction with 1a, two diastereomeric products 6af-1 and 6af-2
were obtained with a ratio of 1.6:1. It was exciting that indole-2-
ethanol 5h was also tolerated in the reaction to give 6ah in 66%
yield. When R1 was an alkyl group, the product 6ha was formed
in 31% yield. The reaction of indole-2-carboxamides 7 with 1
proceeded well to give the corresponding products 8 in
moderate yields with either N-aryl or alkyl substitutions. The
reaction displayed a broad functional group tolerance such as
bromo, ester, amino, hydroxyl, allyl, and cyclopropyl as well as
thiophene heterocycle. Surprisingly, when R1 was changed from
an aryl to a methyl group, only the inverse addition product 8ha′
was obtained in 35% yield with the recovery of a lot of indole-2-
carboxamide 7h (37%). The structure of 8aj was also
unambiguously established by X-ray crystallography.
Scheme 5. Cu(OAc)2-Promoted Reaction of Indole-2-
alcohols 5 with Acetyl Oximes 1
a
To confirm the role of the malonate group, the reactions of
acetyl oximes 1j−1l with 2a were performed (Scheme 7). When
one of the two ester groups was replaced by hydrogen or methyl,
no reaction occurred. Extension of the distance between
malonate and imine carbon to two CH2 units also led to failure
of the reaction. These results illustrated that both the ester
groups and the distance to the imine carbon were crucial to the
reaction. During the reaction of 1a with indole 2a, no key
intermediate was detected, probably due to its rapid reaction
with 2a. For the self-reaction of 1a in the absence of 2a under
standard conditions, no key intermediate was generated and
most of the 1a was recovered after 3 h of stirring. A radical
capture experiment was also carried out under standard
a
Yield was calculated based on 5.
C
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of malonate, an intramolecular attack on Cu(III) may occur to
form 13, which undergoes β-hydride elimination to furnish 14. A
subsequent intramolecular attack on the ester group delivers the
key intermediate 2H-pyrrol-2-one 15. Distinctly, the indole also
has a synergetic cooperation in the generation of 14 or 15
because, in the absence of indole, most of 1a is recovered
without detection of any key intermediate for the self-reaction of
1a. Subsequently, double additions on the electron-deficient
CC and CN double bonds provide 16 and 17, which
undergo further oxidation by Cu(II) to afford 3 and 6/8,
respectively. It is also possible that the addition of indole to C
C double bonds of 14 occurs prior to the cyclization to form 15.
Finally, a preliminary biological activity test for the selected
nine representative compounds was performed to evaluate the
application against adenocarcinomic human alveolar basal
epithelial cells (A549) using final concentrations ranging from
0.01 to 100 μM (see the SI). Compounds 3ai and 3ga exhibited
a high degree of inhibition with more than 70% against A549 cell
growth at 10 μM concentration. These results showed that 3ai
and 3ga had an obvious cytotoxic activity, although it was a little
weaker in comparison with that of adriamycin as a classic
anticancer agent.
Scheme 7. Control Experiments
In summary, we have developed a novel reaction mode of acyl
oximes through installing a malonate group on the α-carbon,
thus providing a facile access to polysubstituted 3-pyrrolin-2-
ones through a Cu(OAc)2-promoted cascade reaction with
indoles, indole-2-alcohols, or indole-2-carboxmides. The high-
light of the method lies in the cyclization to lactam occurring at
the same time as the generation of two adjacent electrophilic
centers under mild conditions, which undergoes double addition
with two molecular indoles followed by oxidation. When the
indoles bear a nucleophilic site at the 2-position, a formal [n + 2]
(n = 4/5) reaction occurs to generate polycyclic indole
derivatives with high regioselectivity. The exploration of new
chemistry of the α-manolate-substituted acyl oximes is under-
way in our laboratory.
conditions with addition of BHT, AIBN, TEMPO, or galvinoxyl.
No obvious inhibition or sluggishness was observed, and no
radical capture intermediate was detected, which indicated that
the reaction might not proceed via a radical process (Scheme 7).
Based on the previously reported copper-catalyzed reaction of
acyl oximes8−10 and the above results, a plausible mechanism is
described in Scheme 8. Our studies indicate that Cu(I) rather
ASSOCIATED CONTENT
* Supporting Information
■
S
Scheme 8. Plausible Mechanism
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.9b00849.
1
Experimental procedures, characterization data, and H
NMR and 13C NMR spectra for all new products (PDF)
Accession Codes
CCDC 1887639 contains the supplementary crystallographic
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.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: estally@yahoo.com.
*E-mail: yht898@yahoo.com.
ORCID
than Cu(II) initiated the reaction because using Cu(OTf)2,
CuCl2, or Cu(ClO4)2 results in the failure of reaction, whereas
using CuCl or CuI gives the normal product. Cu(I) might be
formed in situ via reduction or disproportionation of Cu(OAc)2,
which has been reported in the literature.7d,17 The oxidative
addition of the in situ generated Cu(I) to the N−O bond
produced Cu(III) intermediate 12. Owing to the nucleophilicity
Chun-Bao Miao: 0000-0003-4666-2619
Hai-Tao Yang: 0000-0001-9803-5452
Notes
The authors declare no competing financial interest.
D
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Jiang, H. Chem. Commun. 2016, 52, 84. (l) Huang, H.; Cai, J.; Xie, H.;
Tan, J.; Li, F.; Deng, G.-J. Org. Lett. 2017, 19, 3743. (m) Huang, H.; Xu,
Z.; Ji, X.; Li, B.; Deng, G. Org. Lett. 2018, 20, 4917. (n) Wei, Y.;
Yoshikai, N. J. Am. Chem. Soc. 2013, 135, 3756. (o) Duan, J.; Cheng, Y.;
Li, R.; Li, P. Org. Chem. Front. 2016, 3, 1614. (p) Huang, H.; Cai, J.; Ji,
X.; Xiao, F.; Chen, Y.; Deng, G.-J. Angew. Chem., Int. Ed. 2016, 55, 307.
(q) Tan, W. W.; Ong, Y. J.; Yoshikai, N. Angew. Chem., Int. Ed. 2017, 56,
8240. (r) Bai, D.; Wang, X.; Zheng, G.; Li, X. Angew. Chem., Int. Ed.
2018, 57, 6633.
(11) (a) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122,
12049. (b) Zhao, B.; Shi, Z. Angew. Chem., Int. Ed. 2017, 56, 12727.
(c) Li, L.; Chen, H.; Mei, M.; Zhou, L. Chem. Commun. 2017, 53,
11544. (d) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Org. Lett. 2017,
19, 5908. (e) Yang, L.; Gao, P.; Duan, X.-H.; Gu, Y.-R.; Guo, L.-N. Org.
Lett. 2018, 20, 1034. (f) Zhao, J.-F.; Duan, X.-H.; Gu, Y.-R.; Gao, P.;
Guo, L.-N. Org. Lett. 2018, 20, 4614. (g) Yu, X.-Y.; Chen, J.-R.; Wang,
P.-Z.; Yang, M.-N.; Liang, D.; Xiao, W.-J. Angew. Chem., Int. Ed. 2018,
57, 738. (h) Yu, X.-Y.; Zhao, Q.-Q.; Chen, J.; Chen, J.-R.; Xiao, W.-J.
Angew. Chem., Int. Ed. 2018, 57, 15505. (i) Ai, W.; Liu, Y.; Wang, Q.; Lu,
Z.; Liu, Q. Org. Lett. 2018, 20, 409. (j) Dauncey, E. M.; Morcillo, S. P.;
Douglas, J. J.; Sheikh, N. S.; Leonori, D. Angew. Chem., Int. Ed. 2018, 57,
744. (k) Shen, X.; Zhao, J.-J.; Yu, S. Org. Lett. 2018, 20, 5523.
(l) Jackman, M. M.; Im, S.; Bohman, S. R.; Lo, C. C. L.; Garrity, A.;
Castle, S. L. Chem. - Eur. J. 2018, 24, 594.
ACKNOWLEDGMENTS
■
We are grateful for the financial support from Natural Science
Foundation of Jiangsu Province (BK20181462), the Jiangsu Key
Laboratory of Advanced Catalytic Materials and Technology
(BM2012110), and the Advanced Catalysis and Green
Manufacturing Collaborative Innovation Center.
REFERENCES
■
(1) (a) Mo, X.; Morgan, T. D. R.; Ang, H. T.; Hall, D. G. J. Am. Chem.
Soc. 2018, 140, 5264. (b) Kiely-Collins, H. J.; Sechi, I.; Brennan, P. E.;
McLaughlin, M. G. Chem. Commun. 2018, 54, 654.
(2) (a) Wolff, L. Justus Liebigs Ann. Chem. 1902, 322, 351. (b) Wang,
S.-K.; You, X.; Zhao, D.-Y.; Mou, N.-J.; Luo, Q.-L. Chem. - Eur. J. 2017,
23, 11757. (c) Hong, W. P.; Iosub, Q. V.; Stahl, S. S. J. Am. Chem. Soc.
2013, 135, 13664.
(3) (a) O’Brien, C. Chem. Rev. 1964, 64, 81. (b) Berkowitz, W. F. Org.
React. 2012, 78, 321.
(4) For reviews, see: (a) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Chem. Soc.
Rev. 2015, 44, 1155. (b) Walton, J. C. Acc. Chem. Res. 2014, 47, 1406.
(5) (a) Gerfaud, T.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed. 2009,
48, 572. (b) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 3676.
(c) Too, P. C.; Wang, Y.-F.; Chiba, S. Org. Lett. 2010, 12, 5688.
(d) Zhang, Z.-W.; Lin, A.; Yang, J. J. Org. Chem. 2014, 79, 7041.
(e) Chu, H.; Sun, S.; Yu, J.-T.; Cheng, J. Chem. Commun. 2015, 51,
13327. (f) Neely, J. M.; Rovis, T. J. Am. Chem. Soc. 2013, 135, 66.
(g) Neely, J. M.; Rovis, T. J. Am. Chem. Soc. 2014, 136, 2735. (h) Sun,
B.; Yoshino, T.; Kanai, M.; Matsunaga, S. Angew. Chem., Int. Ed. 2015,
54, 12968.
(12) (a) Jiang, H.; An, X.; Tong, K.; Zheng, T.; Zhang, Y.; Yu, S.
Angew. Chem., Int. Ed. 2015, 54, 4055. (b) Tan, Y.; Hartwig, J. F. J. Am.
Chem. Soc. 2010, 132, 3676. (c) Yang, T.-H.; Kuo, C.-W.; Kavala, V.;
Konala, A.; Huang, C.-Y.; Yao, C.-F. Chem. Commun. 2017, 53, 1676.
(d) Deb, I.; Yoshikai, N. Org. Lett. 2013, 15, 4254.
(13) (a) Shu, W.; Nevado, C. Angew. Chem., Int. Ed. 2017, 56, 1881.
(b) Li, Y.; Mao, R.; Wu, J. Org. Lett. 2017, 19, 4472. (c) Jiang, H.;
Studer, A. Angew. Chem., Int. Ed. 2018, 57, 1692.
(6) Yuan, C.; Zhu, L.; Zeng, R.; Lan, Y.; Zhao, Y. Angew. Chem., Int. Ed.
2018, 57, 1277−1281.
(7) (a) Tsutsui, H.; Narasaka, K. Chem. Lett. 1999, 28, 45. (b) Tsutsui,
H.; Kitamura, M.; Narasaka, K. Bull. Chem. Soc. Jpn. 2002, 75, 1451.
(c) Kitamura, M.; Chiba, S.; Saku, O.; Narasaka, K. Chem. Lett. 2002,
31, 606. (d) Faulkner, A.; Bower, J. F. Angew. Chem., Int. Ed. 2012, 51,
1675. (e) Faulkner, A.; Scott, J. S.; Bower, J. F. Chem. Commun. 2013,
49, 1521. (f) Race, N. J.; Bower, J. F. Org. Lett. 2013, 15, 4616.
(g) Faulkner, A.; Race, N. J.; Scott, J. S.; Bower, J. F. Chem. Sci. 2014, 5,
2416. (h) Race, N. J.; Faulkner, A.; Shaw, M. H.; Bower, J. F. Chem. Sci.
2016, 7, 1508. (i) Sakoda, K.; Mihara, J.; Ichikawa, J. Chem. Commun.
2005, 4684. (j) Ichikawa, J.; Nadano, R.; Ito, N. Chem. Commun. 2006,
4425. (k) Du, W.; Zhao, M.-N.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H.
Chem. Commun. 2014, 50, 7437.
(8) (a) Faulkner, A.; Scott, J. S.; Bower, J. F. J. Am. Chem. Soc. 2015,
137, 7224. (b) Chen, C.; Hou, L.; Cheng, M.; Su, J.; Tong, X. Angew.
Chem., Int. Ed. 2015, 54, 3092. (c) Bao, X.; Wang, Q.; Zhu, J. Angew.
Chem., Int. Ed. 2017, 56, 9577. (d) Su, H.; Li, W.; Xuan, Z.; Yu, W. Adv.
Synth. Catal. 2015, 357, 64. (e) Jiang, H.; Studer, A. Angew. Chem., Int.
Ed. 2017, 56, 12273. (f) Yang, H.-B.; Selander, N. Chem. - Eur. J. 2017,
23, 1779.
(9) (a) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu, W.; Jiang, H. Angew.
Chem., Int. Ed. 2014, 53, 4205. (b) Ke, J.; Tang, Y.; Yi, H.; Li, Y.; Cheng,
Y.; Liu, C.; Lei, A. Angew. Chem., Int. Ed. 2015, 54, 6604. (c) Zhu, C.;
Zhu, R.; Zeng, H.; Chen, F.; Liu, C.; Wu, W.; Jiang, H. Angew. Chem.,
Int. Ed. 2017, 56, 13324. (d) Zhu, Z.; Tang, X.; Li, J.; Li, X.; Wu, W.;
Deng, G.; Jiang, H. Chem. Commun. 2017, 53, 3228.
(10) For selected papers, see: (a) Ran, L.; Ren, Z.-H.; Wang, Y.-Y.;
Guan, Z.-H. Green Chem. 2014, 16, 112. (b) Jiang, S.-P.; Su, Y.-T.; Liu,
K.-Q.; Wu, Q.-H.; Wang, G.-W. Chem. Commun. 2015, 51, 6548.
(c) Tang, X.; Huang, L.; Yang, J.; Xu, Y.; Wu, W.; Jiang, H. Chem.
Commun. 2014, 50, 14793. (d) Wu, Q.; Zhang, Y.; Cui, S. Org. Lett.
2014, 16, 1350. (e) Zhu, Z.; Tang, X.; Li, J.; Li, X.; Wu, W.; Deng, G.;
Jiang, H. Org. Lett. 2017, 19, 1370. (f) Senadi, G. C.; Lu, T.-Y.;
Dhandabani, G. K.; Wang, J.-J. Org. Lett. 2017, 19, 1172. (g) Zhu, C.;
Zeng, H.; Chen, F.; Liu, C.; Zhu, R.; Wu, W.; Jiang, H. Org. Chem. Front.
2018, 5, 571. (h) Zhu, Z.; Tang, X.; Cen, J.; Li, J.; Wu, W.; Jiang, H.
Chem. Commun. 2018, 54, 3767. (i) Luo, B.; Weng, Z. Chem. Commun.
2018, 54, 10750. (j) Zhao, M.-N.; Ren, Z.-H.; Yu, L.; Wang, Y.-Y.;
Guan, Z.-H. Org. Lett. 2016, 18, 1194. (k) Zheng, M.; Chen, P.; Wu, W.;
(14) (a) Zhu, G.-Y.; Chen, G.; Liu, L.; Bai, L.-P.; Jiang, Z.-H. J. Nat.
Prod. 2014, 77, 983. (b) Nicolaou, K. C.; Shi, L.; Lu, M.; Pattanayak, M.
R.; Shah, A. A.; Ioannidou, H. A.; Lamani, M. Angew. Chem., Int. Ed.
2014, 53, 10970. (c) Mahida, A. K.; Kale, S. B.; Das, U. Eur. J. Org.
Chem. 2017, 2017, 6427 and references cited therein .
(15) (a) Surmiak, E.; Twarda-Clapa, A.; Zak, K. M.; Musielak, B.;
Tomala, M. D.; Kubica, K.; Grudnik, P.; Madej, M.; Jablonski, M.;
̈
Potempa, J.; Kalinowska-Tluscik, J.; Domling, A.; Dubin, G.; Holak, T.
A. ACS Chem. Biol. 2016, 11, 3310. (b) Kanishchev, O. S.; Lavoignat,
́
A.; Picot, S.; Medebielle, M.; Bouillon, J.-P. Bioorg. Med. Chem. Lett.
2013, 23, 6167. (c) Starosyla, S. A.; Volynets, G. P.; Lukashov, S. S.;
Gorbatiuk, O. B.; Golub, A. G.; Bdzhola, V. G.; Yarmoluk, S. M. Bioorg.
Med. Chem. 2015, 23, 2489. (d) Balaram, P. N.; Lattmann, P. Patent
Appl. US 2014005248 A1, 2014. (e) Della CA’, N.; Gabriele, B.;
Macchi, B.; Mastino, A.; Giofre, S. V.; Romeo, R.; Costa, M.; Queirolo,
M.; Mancuso, R. Patent Appl. WO2017149511 A1, 2017.
(16) (a) Maes, B. U. W. Heterocyclic Scaffolds II: Reactions and
Applications of Indoles. In Topics in Heterocyclic Chemistry; Gribble, G.
W., Ed.; Springer: Berlin, 2010; Vol. 26. (b) Zhang, M.-Z.; Chen, Q.;
Yang, G.-F. Eur. J. Med. Chem. 2015, 89, 421. (c) Pritchett, B. P.; Stoltz,
B. M. Nat. Prod. Rep. 2018, 35, 559.
(17) (a) King, A. E.; Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.;
Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 12068. (b) Wendlandt, A. E.;
Suess, A. M.; Stahl, S. S. Angew. Chem., Int. Ed. 2011, 50, 11062−11087.
(c) Guo, K.; Zhang, H.; Cao, S.; Gu, C.; Zhou, H.; Li, J.; Zhu, Y. Org.
Lett. 2018, 20, 2261.
E
DOI: 10.1021/acs.orglett.9b00849
Org. Lett. XXXX, XXX, XXX−XXX