Rhodium(III)-Catalyzed Oxidative Annulation of 4-Aminoquinolines and Acrylate through Two Consecutive C(sp2)-H Activations

Article abstract of DOI:10.1021/acs.orglett.0c00630

The C-H annulation of the five-position of quinolines and acrylates to afford heterocycles is an active field of research in organic synthesis. Herein the annulation of 4-aminoquinolines with acrylates through two consecutive C-H activations catalyzed by

Full text of DOI:10.1021/acs.orglett.0c00630

pubs.acs.org/OrgLett
Letter
Rhodium(III)-Catalyzed Oxidative Annulation of 4‑Aminoquinolines
2
and Acrylate through Two Consecutive C(sp )−H Activations
§
§
§
Jian Liu, Yi Gao, Yehua Zhu, Junru Zhu, Chao Wang, Xiyan Rui, Kundi Yang, Dongjuan Si,
Jiamin Lin, Dandan Yuan, Hongmei Wen, and Wei Li*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c00630
Read Online
ACCESS
Metrics & More
Article Recommendations
*
sı Supporting Information
ABSTRACT: The C−H annulation of the five-position of
quinolines and acrylates to afford heterocycles is an active field
of research in organic synthesis. Herein the annulation of 4-
aminoquinolines with acrylates through two consecutive C−H
activations catalyzed by Rh(III) is described. The reaction
proceeds with high atom efficiency under mild reaction conditions,
and this protocol will provide appealing strategies for the synthesis
of fused quinoline heterocycles.
uinoline scaffolds are widely found in many pharmaco-
Scheme 1. Transition-Metal-Catalyzed C−H
Functionalization
Q
logically molecules, natural products, catalysts, and
1
,2
functional materials. Indeed, 4-aminoquinoline fragments
exist in a tremendous number of approved drugs and active
natural products such as neratinib, bosutinib, and so on
3
(
Figure 1a). At the C2, C3, C4, and C8 positions of the
quinoline substrates, quinoline as a building block has a broad
4
−6
prospect for structural functionalization.
The C5-modified
quinolines have been one of the essential heterocycles in
organic synthesis and medicinal chemistry owing to their
7
diverse biological activities and unique properties (Figure 1b).
However, it should be noted that there are few examples of
quinoline functionalization at the C5 position. Furthermore,
most of the reactions in the C5 position of quinoline often
need severe conditions owing to its less favorable electronic
8
factors. Therefore, the development of efficient, general, and
reliable methods for chemical modification, especially
annulation on the five-position of quinoline, has been
considered to be a great challenge in the organic chemistry
9
community.
Received: February 17, 2020
Figure 1. (a) Representative drugs containing 4-aminoquinoline
moieties. (b) Representative compounds modified on the five-
position of quinoline ring.
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c00630
A
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Screening the Reaction Conditions
b
entry
catalyst (mol %)
[Cp*RhCl ] (5)
oxidant (equiv)
solvent
yield (%)
1
2
3
4
5
6
7
8
9
Cu(OAc) (4)
DMF
DMF
DMF
DMF
DMF
DMF
MeOH
DCE
DMA
toluene
NMP
DMSO
i-PrOH
54
2
2
2
[Cp*RhCl ] (5)
AgSbF (4)
trace
2
2
6
c
[Cp*RhCl ] (5)
CuI (4)
ND
2
2
[Cp*RhCl ] (5)
AgOAc (4)
AgOTf (4)
Ag PO (4)
trace
2
2
c
[Cp*RhCl ] (5)
ND
2
2
[Cp*RhCl ] (5)
trace
5
7
2
2
3
4
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
[Cp*RhCl ] (5)
Cu(OAc) (4)
32
14
19
11
ND
ND
2
2
2
10
11
12
13
14
15
16
17
18
19
20
21
22
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
c
[Cp*RhCl ] (5)
Cu(OAc) (4)
2
2
2
c
[Cp*RhCl ] (5)
Cu(OAc) (4)
H O
2
2
2
2
[Cp*RhCl ] (5)
Cu(OAc) (3)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
70
81
85
ND
ND
ND
ND
ND
2
2
2
d
d
d
d
d
d
d
[Cp*RhCl ] (5)
Cu(OAc) (3)
2
2
2
[Cp*RhCl ] (2.5)
Cu(OAc) (3)
2
2
2
c
[RuCl (p-cymene)] (2.5)
Cu(OAc) (3)
2
2
2
c
Pd(OAc) (2.5)
Cu(OAc) (3)
2
2
c
Ni(COD) (2.5)
Cu(OAc) (3)
2
2
c
[Cp*RhCl ] (2.5)
2
2
c
Cu(OAc) (3)
2
a
Reaction conditions: 4-aminoquinolines 1a (0.34 mmol), ethyl acrylate 2a (0.50 mmol), catalyst, oxidant, and solvent (5 mL); reactions run in a
b
c
d
sealed tube at 120 °C under a nitrogen atmosphere for 12 h. Isolated yields. Desired product was not detected. Reaction was carried out under
an O atmosphere.
2
Over the past two decades, the transition-metal-catalyzed
carbon−hydrogen (C−H) functionalization via the directing
group has gained much attention, and these methods are still
being widely applied for the construction of carbon−carbon
value-added molecules with olefins, which would be of great
significance.
In recent years, the research on the C−H functionalization
of quinoline substrates has focused mainly on the C2, C3, C4,
4c,5e
and C8 positions rather than C5.
Considering the five-
(
C−C) and carbon−heteroatom (C−X) bonds in medicinal
10,11
position functionalization of quinoline, the C5 annulation-
modified compounds may possess particularly good biological
activity, and thus it is necessary to develop an effective method
for the C−H annulation of the five-position of quinoline to
construct a heterocycle. As far as we know, reactions of the
five-position of quinolines and acrylates to synthesize
annulated products via Rh(III)-catalyzed C−H activation
reaction have not been reported. Herein we first report the
synthesis of the annulated five-position of 4-aminoquinolines
and acrylates through two consecutive C−H activations
catalyzed by Rh(III) (Scheme 1b). Furthermore, in this
transformation, four hydrogen atoms are efficiently removed,
and this also demonstrates good atom efficiency.
chemistry, organic synthesis, and materials science.
In
particular, the rhodium(III)-catalyzed C−H functionalization
of alkynes or alkenes has been proven to be one of the more
effective strategies for the synthesis of complex molecules other
12
than other transition metals. Among these studies, the
participation of alkynes is often required in the one-step
annulation reaction, and acrylates are utilized for alkenylation
modification. Nevertheless, there is limited literature about
intermolecular C−H annulation reactions with acrylates. This
is because if this cyclization takes place, then two consecutive
C−H activations occur, which requires higher activation
energy and makes the reaction more difficult. In 2016,
Wang’s group demonstrated Rh(III)-catalyzed carbocyclization
reactions with alkynes and alkenes with a broad range of
We initiated our study by exploring reaction conditions for
the envisioned two consecutive C−H activations of 4-
aminoquinolines 1a with ethyl acrylate 2a. (See the Supporting
Information for details.) Quinoline (1a, 0.34 mmol) was
treated with ethyl acrylate (2a, 0.50 mmol) in the presence of a
catalytic amount of [Cp*RhCl ] (5 mol %) and Cu(OAc)
1
3a
substrates and high yields.
Then, in 2019, Qin and
coworkers reported the Rh(III)-catalyzed coupling reactions
of olefins and picolinamides and completed the application of
13b
this method in the structural modification of sorafenib.
2
2
2
Additionally, Xia’s group developed a reaction for the C−H
alkenylation and annulation of O-methylketoxime with
styrenes via palladium catalysis to synthesize benzothienopyr-
(
4.0 equiv) as an oxidant and DMF (5 mL) as a solvent at 120
°C under a nitrogen atmosphere for 12 h. To our delight, the
reaction furnished the desired annulated product 3a in a 54%
isolated yield (Table 1, entry 1). Later, to improve the
1
3c
idines and benzofuropyridines (Scheme 1a).
In these
studies, the directing group can also be transformed into
reactivity, other oxidants such as AgSbF , CuI, AgOAc, AgOTf,
6
B
https://dx.doi.org/10.1021/acs.orglett.0c00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
,
a b
Scheme 2. Substrate Scope of Quinoline
Scheme 4. Gram-Scale Synthesis of 3e
Scheme 5. Control Experiments
a
Reaction conditions: 4-aminoquinoline (0.34 mmol), acrylate (0.50
mmol), [Cp*RhCl ] (2.5 mol %), Cu(OAc) (1.02 mmol), and
2
2
2
solvent (5 mL); reaction run in a sealed tube at 120 °C under an
b
oxygen atmosphere for 12 h. Isolated yields.
,
a b
Scheme 3. Substrate Scope of Acrylate
a
an obvious effect on the yield of the reaction, and the effect of
different solvents was examined (entries 7−14). In general,
when switching to the other solvents, the C−H activation
reaction did not improve, and in some case it provided no
product. DMF was still the best solvent. Gratifyingly, after
screening the ratio of oxidant and catalyst, the reaction
proceeded smoothly, and the desired product yield was
Reaction conditions: 4-aminoquinolines (0.34 mmol), acrylate (0.50
mmol), [Cp*RhCl ] (2.5 mol %), Cu(OAc) (1.02 mmol), and
2
2
2
solvent (5 mL); reactions run in a sealed tube at 120 °C under an
b
oxygen atmosphere for 12 h. Isolated yields.
and Ag PO were investigated separately (entries 2−6).
Finally, only when we used Cu(OAc) as an oxidant was the
3
4
2
desired product afforded. Thus the choice of Cu(OAc) as the
promoted. The optimized ratios of Cu(OAc) and Rh(III)
2
2
oxidant was essential for the cyclization process, owing to the
fact that Cu(OAc)2 furnished the acetate source for the
were 3.0 and 2.5 mol % (entry 15 vs 1, 16 vs 17).
Subsequently, it was noteworthy that an 85% yield was
attained for 3a when the reaction was carried out under an
14
rhodium deprotonation metalation pathway. The solvent has
C
https://dx.doi.org/10.1021/acs.orglett.0c00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Scheme 6. Plausible Mechanism
various acrylates 2a−g and the same 4-aminoquinoline 1a
proceeded smoothly to provide the annulated product 3a, 3e,
and 4a−e with yields ranging from 41 to 95%. Interestingly,
with the rise of the electron-donating ability of the ester group,
the yield of this reaction was also enhanced. Consequently, the
highest yield of the desired product 4b could reach 95%
through two consecutive activation reactions of n-butyl acrylate
and 4-aminoquinoline 1a. However, the large t-butyl-
substituted substrate provided the desired product 4c in only
57% yield, which also revealed that the steric effects of the
acrylate substrates had a great influence on the annulation
reaction.
To further verify the synthetic utility of this reaction, a gram-
scale synthesis of 3e was carried out under the standard
reaction conditions (Scheme 4). Interestingly, 0.927 g of
desired product 3e was obtained in 60.2% yield when the
reaction was performed on a 4.05 mmol scale. The yield was
comparable to that obtained in the small-scale experiment.
To provide insight into the mechanism of these two
rhodium-catalyzed consecutive C−H activations, a series of
control experiments were designed and performed. Once the N
atom on sulfonamide was methylated and thus could not act as
a directing group, the transformation did not work. When the
hydrogen atom on acrylate alkenyl was substituted by methyl,
the reaction also did not occur. It was proved that the oxidative
annulation reaction was a C−H activation process (Scheme
oxygen atmosphere instead of nitrogen (entry 17). In addition,
whereas we explored using different transition-metal catalysts,
such as palladium, ruthenium, and nickel, together with the
same oxidant, surprisingly, the oxidative annulation reaction
did not occur (entries 18−20). Finally, several control
experiments were conducted to prove that each component
of the scheme was critical to the reaction efficiency (entries 21
and 22). After the extensive screening of different parameters,
optimized conditions for these two consecutive C−H reaction
were established: quinoline (1.0 equiv), ethyl acrylate (1.5
equiv), rhodium (2.5 mol %), and Cu(OAc) (3.0 equiv) in
2
DMF at 120 °C under an oxygen atmosphere for 12 h.
With the optimized conditions in hand, we then tested the
versatility and scope of two consecutive rhodium(III)-
catalyzed C−H activations with the structural diversity of
various 4-aminoquinolines by assessing the substitution effect
on the quinoline framework. As shown in Scheme 2, electron-
donating substituents generally have excellent tolerance,
providing the desired products 3c−k bearing mono-methyl
5
a). In addition, the influence of substituents on the
intermolecular competition revealed that the electron-donating
group reacts more readily than the electron-withdrawing group
(
Scheme 5b). Then, the mechanistic study was further
explored. When the starting material reacted in deuterium
solvent for 2 h, 90% deuterium product was obtained (Scheme
5
c). It was thereby proved that the C−H activation reaction
(3c−e), dimethyl (3f,g), ethyl (3h), and methoxy (3i−k) in
was reversible. Furthermore, the kinetic isotope effect of
deuterium was investigated by the intermolecular competitive
reaction between 1a and 1a-d. As a result, the kinetic isotope
effect (k /k ) was 2.2, indicating that the cleavage of the
moderate to good yield of 61−71%. Interestingly, the
significant influence of the same substituents at different
positions on this transformation was observed. For example,
ortho-methyl (3c: 68%), ortho-methoxy (3i: 71%) gave better
yields than the corresponding meta-methyl (3d: 61%), meta-
methoxy (3j: 65%) and para-methyl (3e: 64%), para-methoxy
H
D
aromatic C−H bond in 1a was the rate-determining step
15
(
Scheme 5d).
On the basis of the results of these experiments and the
(
2
3k: 68%). As for the dimethyl-substituted compounds, the
,4-dimethyl substrate was likewise converted with higher
efficiency, and the desired product 3f was obtained in a higher
1% yield compared with the 62% yield of the 3,5-dimethyl-
reported transition-metal-catalyzed C−H bond functionaliza-
16
tion reactions, a plausible mechanism was proposed for the
present C−H activation reaction (Scheme 6). First, the
7
cationic rhodium catalyst [Cp*Rh(OAc) ] was formed by
2
substituted compound 3g. Meanwhile, as for the electron-
withdrawing groups, a relatively lower yield was observed in
the reaction of the substrate bearing chlorine and fluorine at
different positions (3l: 40%, 3m: 24%, 3n: 36%; 3o: 18%, 3p:
the reaction of the catalyst [Cp*RhCl ] and the oxidant
2
2
Cu(OAc) . The second step is likely to generate a five-
2
2
membered intermediate B through a C(sp )−H activation
process, which would subsequently involve the coordination
and insertion of acrylate. As a result, a seven-membered
metallacycle intermediate C was generated. After β-H
elimination, the intermediate D was obtained in the absence
0
%, 3q: <5%). In particular, a strong electron-withdrawing
nitro group resulted in oxidative annulation reaction difficulty,
and no desired products 3r−t were found. The bromine
substituents (3u−w) were also not tolerated for this reaction.
They mainly contributed to the removal of bromine atoms
during the reaction process. Similarly, when the seven-position
of the quinoline scaffold was replaced by an electron-rich
methoxy group (3x: 70%), a better yield was obtained
compared with that of the corresponding electron-deficient
chlorine groups (3y: 60%). Therefore, whether this C−H
activation reaction could take place depended on the electronic
effects of the aromatic rings.
of Cu(OAc) , while the first C−H activation was finished.
2
Meanwhile, Cp*Rh(I) was oxidized to Cp*Rh(OAc) and
2
participated in the next catalytic cycle. Similarly, the
coordination amino of intermediate D to Cp*Rh(OAc)2
followed by metalation afforded an intermediate E. Coor-
dinative insertion into the double bond of intermediate E
afforded a seven-membered metallacycle F. This intermediate
F might undergo a reductive elimination to afford the desired
product G. Finally, the second C−H activation was completed,
Subsequently, the impact of different substituted acrylate
substrates on this Rh-catalyzed oxidative annulation reaction
was also investigated (Scheme 3). In general, the cyclization of
and the remaining active Cu(OAc) was regenerated under an
2
oxygen atmosphere.
D
https://dx.doi.org/10.1021/acs.orglett.0c00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
In summary, we have reported here an unprecedented
synthesis of the annulated five-position of 4-aminoquinolines
and acrylate that furnishes heterocycles through two
consecutive C−H activations catalyzed by rhodium(III). A
wide variety of functional groups can be successfully
incorporated into these heterocycles. The reaction proceeds
with high atom efficiency, mild reaction conditions, and
experimental simplicity, rendering the methodology highly
useful for the synthesis of five-position-fused quinoline
heterocycles. A plausible mechanism has been proposed, and
more details of the mechanism are being explored. In our
laboratory, further optimization of reaction conditions to
achieve a broader scope is ongoing.
Foundation of Jiangsu (no. BK20161050), and the Post-
graduate Research & Practice Innovation Program of Jiangsu
Province (no. SJKY19_1467).
REFERENCES
■
(
1) (a) Romero, E. A.; Chen, G.; Gembicky, M.; Jazzar, R.; Yu, J.-Q.;
Bertrand, G. J. Am. Chem. Soc. 2019, 141, 16726. (b) Yang, Y. F.;
Chen, G.; Hong, X.; Yu, J. Q.; Houk, K. N. J. Am. Chem. Soc. 2017,
139, 8514. (c) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223.
(
(
d) Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2002, 124, 4233.
e) Hughes, G.; Bryce, M. R. J. Mater. Chem. 2005, 15, 94.
(
2) (a) Wang, H. W.; Lu, Y.; Zhang, B.; He, J.; Xu, H. J.; Kang, Y. S.;
Sun, W. Y.; Yu, J. Q. Angew. Chem., Int. Ed. 2017, 56, 7449.
b) Ashok, P.; Ganguly, S.; Murugesan, S. Drug Discovery Today 2014,
19, 1781. (c) Saito, M.; Nakajima, M.; Hashimoto, S. Chem. Commun.
000, 19, 1851.
3) (a) Singh, H.; Walker, A. J.; Amiri-Kordestani, L.; Cheng, J.;
(
ASSOCIATED CONTENT
sı Supporting Information
■
2
(
*
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00630.
Tang, S.; Balcazar, P.; Barnett-Ringgold, K.; Palmby, T. R.; Cao, X.;
Zheng, N.; Liu, Q.; Yu, J.; Pierce, W. F.; Daniels, S. R.; Sridhara, R.;
Ibrahim, A.; Kluetz, P. G.; Blumenthal, G. M.; Beaver, J. A.; Pazdur, R.
Clin. Cancer Res. 2018, 24, 3486. (b) Rossari, F.; Minutolo, F.;
Orciuolo, E. J. Hematol. Oncol. 2018, 11, 84. (c) Martin, M.; Holmes,
F. A.; Ejlertsen, B.; Delaloge, S.; Moy, B.; Iwata, H.; von Minckwitz;
Chia, S.; Mansi, J.; Barrios, C. H.; et al. Lancet Oncol. 2017, 18, 1688.
Experimental procedures and spectroscopic data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
(
5
d) Vitaku, E.; Smith, D. T.; Njardarson, J.T. J. J. Med. Chem. 2014,
7, 10257.
4) (a) Iwai, T.; Sawamura, M. ACS Catal. 2015, 5, 5031. (b) Du, B.
N.; Qian, P.; Wang, Y.; Mei, H. B.; Han, J. L.; Pan, Y. Org. Lett. 2016,
8, 4144. (c) Bering, L.; Antonchick, A. P. Org. Lett. 2015, 17, 3134.
Wei Li − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China; Email: liwaii@126.com
(
Authors
1
Jian Liu − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China; orcid.org/0000-0001-
(5) (a) Zhu, L. Z.; Sheng, X. H.; Li, Y.; Lu, D.; Qiu, R. H.; Kambe,
N. Org. Lett. 2019, 21, 6785. (b) Degorce, S. L.; Barlaam, B.;
Cadogan, E.; Dishington, A.; Ducray, R.; Glossop, S. C.; Hassall, L.
A.; Lach, F.; Lau, A.; McGuire, T. M.; Nowak, T.; Ouvry, G.; Pike, K.
G.; Thomason, A. G. J. Med. Chem. 2016, 59, 6281. (c) Sun, K.; Lv, Y.
H.; Wang, L. J.; Sun, J. J.; Liu, L. L.; Jia, M. Y.; Liu, X.; Li, Z. D.;
Wang, X. Org. Lett. 2015, 17, 4408. (d) Ribelles, P.; Ramos, M. T.;
Menendez, J. C. Org. Lett. 2012, 14, 1402. (e) Kumar, S.; Pradhan, S.;
Roy, S.; De, P. B.; Punniyamurthy, T. J. Org. Chem. 2019, 84, 10481.
9
482-9036
Yi Gao − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China
Yehua Zhu − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China
Junru Zhu − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China
Chao Wang − School of Pharmacy, Nanjing University of
Chinese Medicine, Nanjing 210023, China
(6) (a) Chen, X. P.; Cui, X. L.; Wu, Y. J. Org. Lett. 2016, 18, 3722.
(b) Kim, J.; Kim, S.; Kim, D.; Chang, S. J. Org. Chem. 2019, 84,
13150. (c) Sharma, R.; Kumar, R.; Sharma, U. J. Org. Chem. 2019, 84,
2786. (d) Sharma, U.; Park, Y.; Chang, S. J. Org. Chem. 2014, 79,
9899.
Xiyan Rui − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China
Kundi Yang − Department of Chemistry and Biochemistry,
Miami University, Oxford, Ohio 45056, United States
Dongjuan Si − School of Pharmacy, Nanjing University of
Chinese Medicine, Nanjing 210023, China
Jiamin Lin − School of Pharmacy, Nanjing University of Chinese
Medicine, Nanjing 210023, China
Dandan Yuan − School of Pharmacy, Nanjing University of
Chinese Medicine, Nanjing 210023, China
Hongmei Wen − School of Pharmacy, Nanjing University of
Chinese Medicine, Nanjing 210023, China
(7) (a) Chekerov, R.; Hilpert, F.; Mahner, S.; El-Balat, A.; Harter, P.;
De Gregorio, N.; Fridrich, C.; Markmann, S.; Potenberg, J.; Lorenz,
R.; et al. Lancet Oncol. 2018, 19, 1247. (b) Centelles, M. N.; Wright,
M.; So, P. W.; Amrahli, M.; Xu, X. Y.; Stebbing, J.; Miller, A. D.;
Gedroyc, W.; Thanou, M. J. Controlled Release 2018, 280, 87.
(c) Hawkins, D. S.; Chi, Y.-Y.; Anderson, J. R.; Tian, J.; Arndt, C.
A.S.; Bomgaars, L.; Donaldson, S. S.; Hayes-Jordan, A.; Mascarenhas,
L.; McCarville, M. B.; et al. J. Clin. Oncol. 2018, 36, 2770. (d) Naro,
Y.; Ankenbruck, N.; Thomas, M.; Tivon, Y.; Connelly, C. M.;
Gardner, L.; Deiters, A. J. Med. Chem. 2018, 61, 5900.
(e) Vandekerckhove, S.; Van Herreweghe, S.; Willems, J.; Danneels,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00630
B.; Desmet, T.; de Kock, C.; Smith, P. J.; Chibale, K.; D'hooghe, M.
Eur. J. Med. Chem. 2015, 92, 91. (f) Rech, J. C.; Bhattacharya, A.;
Branstetter, B. J.; Love, C. J.; Leenaerts, J. E.; Cooymans, L. P.;
Eckert, W. A.; Ao, H.; Wang, Q.; Chaplan, S. R.; Wickenden, A. D.;
Lebsack, A. D.; Breitenbucher, J. G. Bioorg. Med. Chem. Lett. 2016, 26,
Author Contributions
§J.L., Y.G., and Y.Z. contributed equally.
Notes
4
781. (g) Yu, H. B.; Yang, F.; Sun, F.; Li, J.; Jiao, W. H.; Gan, J. H.;
Hu, W. Z.; Lin, H. W. Mar. Drugs 2014, 12, 6003.
8) (a) Zhang, Z. P.; Tanaka, K.; Yu, J. Q. Nature 2017, 543, 538.
b) Suess, A. M.; Ertem, M. Z.; Cramer, C. J.; Stahl, S. S. J. Am. Chem.
(
The authors declare no competing financial interest.
(
Soc. 2013, 135, 9797. (c) Zhu, L.; Qiu, R.; Cao, X.; Xiao, S.; Xu, X.;
Au, C. T.; Yin, S. F. Org. Lett. 2015, 17, 5528. (d) Cong, X.; Zeng, X.
Org. Lett. 2014, 16, 3716. (e) Stephens, D. E.; Larionov, O. V.
Tetrahedron 2015, 71, 8683.
ACKNOWLEDGMENTS
We gratefully acknowledge the National Science Foundation of
China (nos. 81573304 and 81703342), the Natural Science
■
E
https://dx.doi.org/10.1021/acs.orglett.0c00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(
9) (a) Ge, S. Z.; Chaładaj, W.; Hartwig, J. F. J. Am. Chem. Soc.
2014, 136, 4149. (b) Friis, S. D.; Pirnot, M. T.; Dupuis, L. N.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2017, 56, 7242. (c) Wang, Y.;
Chen, C.; Peng, J.; Li, M. Angew. Chem., Int. Ed. 2013, 52, 5323.
(
(
d) Rousseaux, S.; Liegault, B.; Fagnou, K. Chem. Sci. 2012, 3, 244.
e) Kulkarni, A.; Torok, B. Green Chem. 2010, 12, 875. (f) Li, L.;
Jones, W. D. J. Am. Chem. Soc. 2007, 129, 10707. (g) Gao, Y.; Yang,
F.; Sun, F.; Liu, L.; Liu, B.; Wang, S.-P.; Cheng, C.-W.; Liao, H.; Lin,
H.-W. Org. Lett. 2019, 21, 1430. (h) Heredia, D. A.; Larghi, E. L.;
Kaufman, T. S. Eur. J. Org. Chem. 2016, 2016, 1397. (i) Liao, G.;
Song, H.; Yin, X. S.; Shi, B. F. Chem. Commun. 2017, 53, 7824.
(
10) (a) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J. Q. Chem.
Rev. 2017, 117, 8754. (b) Park, Y.; Kim, Y.; Chang, S. Chem. Rev.
017, 117, 9247. (c) Gensch, T.; Hopkinson, M. N.; Glorius, F.;
2
Wencel-Delord, J. Chem. Soc. Rev. 2016, 45, 2900. (d) Chen, Z.;
Wang, B.; Zhang, j.; Yu, W.; Liu, Z.; Zhang, Y. Org. Chem. Front.
2
015, 2, 1107. (e) Girard, S. A.; Knauber, T.; Li, C. J. Angew. Chem.,
Int. Ed. 2014, 53, 74. (f) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011,
1
2
11, 1215. (g) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev.
007, 107, 174. (h) Zhang, Q.; Shi, B. F. Chin. J. Chem. 2019, 37, 647.
(
i) Rao, W. H.; Shi, B. F. Org. Chem. Front. 2016, 3, 1028.
11) (a) Shang, R.; Ilies, L.; Nakamura, E. Chem. Rev. 2017, 117,
086. (b) Zhang, M.; Zhang, Y.; Jie, X.; Zhao, H.; Li, G.; Su, W. Org.
(
9
Chem. Front. 2014, 1, 843. (c) Rouquet, G.; Chatani, N. Angew.
Chem., Int. Ed. 2013, 52, 11726. (d) Engle, K. M.; Mei, T. S.; Wasa,
M.; Yu, J. Q. Acc. Chem. Res. 2012, 45, 788. (e) Neufeldt, S. R.;
Sanford, M. S. Acc. Chem. Res. 2012, 45, 936. (f) Sun, C. L.; Li, B. J.;
Shi, Z. J. Chem. Rev. 2011, 111, 1293. (g) Chen, X.; Engle, K. M.;
Wang, D. H.; Yu, J. Q. Angew. Chem. 2009, 121, 5196. (h) Zhou, J.;
Li, X.; Liao, G.; Shi, B. F. Chin. J. Chem. 2018, 36, 1143. (i) Qian, Z.
C.; Zhou, J.; Li, B.; Hu, F.; Shi, B. F. Org. Biomol. Chem. 2014, 12,
3
594. (j) Zhou, J.; Li, B.; Hu, F.; Shi, B. F. Org. Lett. 2013, 15, 3460.
k) Wei, X. H.; Wang, F.; Song, G. Y.; Du, Z. Y.; Li, X. W. Org.
Biomol. Chem. 2012, 10, 5521.
12) (a) Martinez, A. M.; Rodriguez, N.; Gom
(
(
ez Arrayas, R.;
́ ́
Carretero, J. C. Chem. Commun. 2014, 50, 6105. (b) Cai, S.; Chen, C.;
Shao, P.; Xi, C. Org. Lett. 2014, 16, 3142. (c) Zhou, J.; Li, B.; Qian,
Z.-C.; Shi, B.-F. Adv. Synth. Catal. 2014, 356, 1038. (d) Presset, M.;
Oehlrich, D.; Rombouts, F.; Molander, G. A. Org. Lett. 2013, 15,
1
(
1
528. (e) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651.
f) Kuhl, N.; Schroder, N.; Glorius, F. Adv. Synth. Catal. 2014, 356,
443. (g) Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007. (h) Ye, B.;
̈
Cramer, N. Acc. Chem. Res. 2015, 48, 1308.
13) (a) Zhou, T.; Wang, Y. W.; Li, B.; Wang, B. Q. Org. Lett. 2016,
8, 5066. (b) Li, C.; Qin, H. L. Org. Lett. 2019, 21, 4495. (c) Fu, X.
P.; Yang, J. Y.; Deng, K. Z.; Shao, L. Y.; Xia, C. C.; Ji, Y. F. Org. Lett.
019, 21, 3505.
14) (a) Ackermann, L. Chem. Rev. 2011, 111, 1315. (b) Cai, S. J.;
(
1
2
(
Chen, C.; Shao, P.; Xi, C. J. Org. Lett. 2014, 16, 3142. (c) Wang, X.
Y.; Qiu, X.; Wei, J. L.; Liu, J. Z.; Song, S.; Wang, W.; Jiao, N. Org. Lett.
2
(
5
1
018, 20, 2632.
15) (a) Li, M. B.; Grape, E. S.; Backvall, J. E. ACS Catal. 2019, 9,
184. (b) Wu, X. Y.; Fan, J. J.; Fu, C. L.; Ma, S. M. Chem. Sci. 2019,
0, 6316. (c) Li, H.; Zhang, S.; Feng, X. J.; Yu, X. Q.; Yamamoto, Y.;
Bao, M. Org. Lett. 2019, 21, 8563.
16) (a) Park, S. H.; Kim, J. Y.; Chang, S. Org. Lett. 2011, 13, 2372.
b) Wang, X. G.; Zhang, J.; Chen, D.; Wang, B.; Yang, X. F.; Ma, Y.
(
(
M.; Szostak, M. Org. Lett. 2019, 21 (17), 7038. (c) Dutta, U.; Maiti,
S.; Pimparkar, S.; Maiti, S.; Gahan, L. R.; Krenske, E. H.; Lupton, D.
W.; Maiti, D. Chem. Sci. 2019, 10, 7426.
F
https://dx.doi.org/10.1021/acs.orglett.0c00630
Org. Lett. XXXX, XXX, XXX−XXX