Construction of C(sp2)?C(sp3) Bond between Quinoxalin-2(1H)-ones and N-Hydroxyphthalimide Esters via Photocatalytic Decarboxylative Coupling

Article abstract of DOI:10.1002/asia.201900904

A novel visible-light-driven decarboxylative coupling of alkyl N-hydroxyphthalimide esters (NHP esters) with quinoxalin-2(1H)-ones has been developed. This C(sp²)?C(sp³) bond-forming transformation exhibits excellent substrate generality with respect to both the coupling partners. Of note, a series of 3-primary alkyl-substituted quinoxalin-2(1H)-ones that were difficult to synthesize by previous methods could be obtained in moderate to excellent yields. Additionally, the mild conditions, easy availability of substrates, wide functional group tolerance and operational simplicity make this protocol practical in the synthesis of 3-alkylated quinoxalin-2(1H)-ones.

Full text of DOI:10.1002/asia.201900904

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Construction of C(sp2)-C(sp3) Bond between Quinoxalin-2(1H)-
ones and N-Hydroxyphthalimide Esters via Photocatalytic
Decarboxylative Coupling
Authors: Zhiyang Yan, Bin Sun, Xun Zhang, Xiaohui Zhuang, Jin Yang,
Weike Su, and Can Jin
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Asian J. 10.1002/asia.201900904
Link to VoR: http://dx.doi.org/10.1002/asia.201900904
A Journal of
A sister journal of Angewandte Chemie
and Chemistry – A European Journal

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
Construction of C(sp2)-C(sp3) Bond between Quinoxalin-2(1H)-
ones and N-Hydroxyphthalimide Esters via Photocatalytic
Decarboxylative Coupling
Zhiyang Yan,[a] Bin Sun,[a] Xun Zhang,[b] Xiaohui Zhuang,[b] Jin Yang,[b] Weike Su,[a, b] and Can Jin*,[b]
d).6d Wang’s group also achieved the oxyalkylation of
Abstract: A novel visible-light-driven decarboxylative coupling of
quinoxalin-2(1H)-ones via
a
visible-light-inducted cross-
alkyl N-hydroxyphthalimide esters (NHP esters) with quinoxalin-
2(1H)-ones has been developed. This C(sp2)-C(sp3) bond-forming
transformation exhibits excellent substrate generality with respect to
both the coupling partners, and of note, a series of 3-primary alkyl
substituted quinoxalin-2(1H)-ones that were difficult to synthesize
by previous methods could be obtained in moderate to excellent
yields. Additionally, the mild conditions, easy availability of
substrates, wide functional group tolerance and operational
simplicity make this protocol practically in synthesis of 3-alkylated
quinoxalin-2(1H)-ones.
dehydrogenative coupling reaction (scheme 1, reaction e).6e
However, these methods all require the participation of metal
catalyst or oxidant. Moreover, alkylation of quinoxalin-2(1H)-
ones with straight-chain-alkyl group such as n-propyl, isopropyl,
and tert-butyl groups is still a serious challenge.
Introduction
Figure 1. Representative biologically active of 3-alkyl quinoxalin-2(1H)-ones.
Construction of C(sp2)-C(sp3) bond is one of the most
important protocols to modify the structure of heterocyclic
compounds.1
Transition-metal
catalyzed
cross-coupling
reactions, such as Suzuki and Kumada couplings, are classical
methods for C(sp2)-C(sp3) bond formation.2 However,
prefunctionalization, multiple steps and low atomic economy
limited its further application. In recent years, direct C-H
functionalization has been considered as an efficient strategy to
construct C(sp2)-C(sp3) bond because this protocol can simplify
the reaction process and increase the atomic economy.3
However, this strategy still has several drawbacks. For example,
it usually requires the use of transition-metal catalysts, excess
amounts of oxidants and vigorous conditions, leading to high
toxicity and energy consumption. Therefore, developing green
and efficient methods for construction of C(sp2)-C(sp3) bonds is
still of great interest.
Quinoxalin-2(1H)-ones,
especially
the
3-alkylated
derivatives are widely existed in various pharmacologically
active compounds (Fig 1).4 The traditional method for synthesis
of 3-alkylated quinoxalin-2(1H)ones was realized via the
condensation between aryl-1,2-diamines and
a
suitable
partner.5 Recently, some progress has been made in the
synthesis of 3-alkylated quinoxalin-2(1H)-ones via direct C-H
functionalization (scheme 1).6 For example, Qu’s group
successively achieved the benzylation, oxyalkylation and
hydroxyalkylation of quinoxalin-2(1H)-ones (scheme 1, a-c).6a-c
Additionally, Yang and co-workers described an iron-catalyzed
direct C-H cyanoalkylation of quinoxalin-2(1H)-ones (scheme 1,
Scheme 1. Strategies for the synthesis of 3-alkylated quinoxalin-2(1H)-ones
Minisci reaction is a useful tool to accomplish the alkylation
of N-heteroarenes, in which a protonated N-heteroarene is
[a]
[b]
Dr. B. Sun, Z. Y. Yan, Prof. Dr. W. K. Su
Collaborative Innovation Center of Yangtze River Delta Region
Green Pharmaceuticals
Zhejiang University of Technology
Hangzhou 310014 (P. R. China)
X. Zhang, X. H. Zhuang, J. Yang, Prof. Dr. C. Jin, Prof. Dr. W. K. Su
College of Pharmaceutical Sciences
Zhejiang University of Technology
Hangzhou 310014 (P. R. China)
E-mail: jincan@zjut.edu.cn
attacked
by
an
alkyl
radical
generated
through
decarboxylation.7 Generally, decarboxylation of carboxylic acids
is widely used in organic synthesis.8 In recent years, alkyl N-
hydroxyphthalimide (NHP) esters was emerged as an efficient
decarboxylation alkylation reagent because it could be reduced
by photocatalyst, generating a variety of alkyl radicals via
elimination of CO2 and phthalimide.9 For example, the
regioselective alkylation of N-heteroarenes with alkyl NHP
esters under irradiation of blue LEDs was achieved by Shang
and Fu.10 We supposed that this process also could be applied
for the synthesis of 3-alkylated quinoxalin-2(1H)-ones. With our
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
ongoing interest on developing green and efficient methods for
direct C-H functionalization,11 herein, we report a metal and
oxidant free Minisci type reaction of quinoxalin-2(1H)one with
alkyl NHP esters via a photocatalytic system promoted by
visible light, leading to the synthesis of a variety of 3-alkylated
quinoxaline-2(1H)-ones in moderate to excellent yields.
as DCE, EtOAc, DCM, MeCN were screened but none of them
could give the desired product (Table 1, entries 8-11). In order
to explore the effect of light source, white LEDs were replaced
by blue LEDs or green LEDs, and the results revealed that the
yields of 3aa were both decreased (Table 1, entries 12, 13).
Furthermore, different acids such as TfOH, AcOH were
employed and both seem to be more negative than TFA, giving
3aa in 92% and 65% yields (Table 1, entries 14-15). It was also
observed that the yield of 3aa was sharply decreased to 11%,
when no additive was added (Table 1, entry 16). Contrast
experiments demonstrated that visible light and photocatalyst
were both essential for this decarboxylative coupling reaction
(Table 1, entries 17-18). Notably, only trace product 3aa was
obtained when this progress was carried out under air
atmosphere (Table 1, entries 19). After screening the reaction
conditions, it was concluded that this cross-coupling
transformation should be performed in the presence of Na2-
eosin Y (1 mol%) and TFA (0.5 equiv.) in DMSO with irradiation
of 3 W white LEDs under N2 atmosphere for 40 h.
Results and Discussion
To begin our study, N-methylquinoxalin-2(1H)-one 1a and
alkyl NHP esters 2a were chosen as model substrates to
optimize the reaction conditions. The reaction was initially
studied with fac-Ir(ppy)3 (1 mol%) as
a photocatalyst,
trifluoroacetic acid (TFA) as an additive, and irradiated with 3 W
white LEDs in DMSO under N2 atmosphere for 40 h.
Fortunately, the product 3aa was obtained in a yield of 61%
(Table 1, entry 1). When other photocatalysts such as
Ru(bpy)3Cl2, Na2-eosin Y, Rose Bengal, Methylene Blue and
Rhodamine B were examined, it was delighted to find that Na2-
eosin Y exhibited a better efficiency and gave 3aa in 97% yield
(Table 1, entries 2-6). It could not exhibit positive effect on the
yield of 3aa when the amount of Na2-eosin Y was increased to
3 mol% (Table 1, entry 7). Subsequently, other solvents such
Table 2. Substrate Scope of Quinoxalin-2(1H)-ones
Table 1. Optimization of the Reaction Conditions
3aa, 97%
3ba, 78%
3ca, 90%
3da, 92%
Entry
Photocatalyst
Solvent
Additive
Yield(%)
1
2
fac-Ir(ppy)3
Ru(bpy)3Cl2
Na2-Eosin Y
Rose Bengal
Methylene Blue
Rhodamine B
Na2-Eosin Y
Na2-Eosin Y
Na2-Eosin Y
Na2-Eosin Y
Na2-EosinY
Na2-Eosin Y
Na2-Eosin Y
Na2-Eosin Y
Na2-Eosin Y
Na2-Eosin Y
-
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DCE
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TfOH
AcOH
-
61
61
3
97
4
50
5
N. D.
N.D.
97
3ea, 72%
3ia, 78%
3fa, 82%
3ja, 92%
3ga, 63%
3ka, 80%
3ha, 80%
3la, 88%
6
7c
8
N. D.
N. D.
N. D.
N. D.
75
9
EtOAc
DCM
10
11
12d
13e
14
15
16
17
18f
19g
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
49
92
3ma, 83%
3qa, 90%
3na, 90%
3ra, 92%
3oa, 84%
3pa, 93%
65
11
TFA
TFA
TFA
N. D.
N. D.
trace
Na2-Eosin Y
Na2-Eosin Y
aReaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), catalyst (0.01 mmol),
additive (0.5 mmol), solvent (3.0 mL), rt, 3 W white lights, 40 h. bIsolated
yield base on 1a. cNa2-Eosin Y ( 0.03 mmol). d3 W Blue LEDs. e3 W Green
LEDs. fwithout light. gunder air. hN. D. = Not Detected
aAll reactions were performed with 1 (1.0 mmol), 2a (1.2 mmol), Na2-eosin Y
(0.01 mmol) and TFA (0.5 mmol) in DMSO (3.0 mL) at room temperature
with irradiation by white LEDs under N2 atmosphere for 40 h.
With the optimized conditions in hand, the scope of the
quinoxalin-2(1H)-ones was then investigated. As show in table
2, a series of N-alkylated quinoxalin-2(1H)-ones were examined,
and the results revealed that these substrates were all suitable
for this transformation, providing the corresponding products in
moderate to good yields (3aa-3fa). Initially, when the methyl
Na2-Eosin Y
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
group was changed into the n-octyl group, the corresponding
product 3ba could be obtained in satisfied yield. In addition,
primary alkyl with phenyl, ester or alkynyl group was also
tolerated in this reaction and gave the corresponding products
in moderate to good yields (3ca-3fa). Delightfully, the
quinoxalin-2(1H)-ones without N-substituted also displayed
good tolerance for this transformation and gave the product 3ga
in 63% yield. Subsequently, the quinoxalin-2(1H)-ones with
different substituents on the benzene ring were also
investigated under the optimized conditions, providing the
corresponding products 3ha-3ra in good to excellent yields. For
example, quinoxalin-2(1H)-ones bearing electron-donating
groups at 6-position of aromatic ring, such as methoxy and t-
butyl, provided corresponding products in 80% and 78% yields
(3ha, 3ia). Notably, substrates bearing electron-withdrawing
substituents such as fluoro, chloro, bromo at 6-position of
benzene ring showed excellent tolerance for this reaction, and
provided the corresponding products in good yields (3ja-3la).
Subsequently, quinoxalin-2(1H)-ones with substituents at 7-
positions were examined, and the corresponding product 3ma,
3na was obtained in 83% and 90% yields, respectively.
Remarkably, it was worth noting that quinoxalin-2(1H)-ones
bearing strong electron-withdrawing group (trifluoromethyl) at 7-
position, could also undergo this transformation smoothly, and
provided the target product 3oa in a yield of 84%. It was noted
that the disubstituted quinoxalin-2(1H)-ones containing two
electron-withdrawing groups (1p, 1q) or electron-donating
groups (1r) in the 6- and 7- positions, also could undergo this
decarboxylative coupling process well, and gave the
corresponding products in good yields (3pa-3ra).
types of alkyl (primary, secondary and tertiary) NHP esters
were found to be suitable for this reaction (3ab-3am). Initially,
primary alkyl NHP esters bearing n-propyl, 2-cyclopentyl-ethyl,
3-methyl-butyl, n-heptyl were tested and the corresponding
products were obtained in only moderate yields (3ab-3ae),
which mainly due to the lower reactivity of primary alkyl radical
compared with tertiary alkyl radicals. In addition, primary alkyl
group bearing additional benzyl, alkenyl or alkynyl group was
also well tolerated for this transformation, providing the desired
alkylated products 3af-3ai in 69-92% yields. However, no
methylated product was detected when methyl NHP ester was
applied to react with N-methylquinoxalin-2(1H)-one under
standard condition. Subsequently, the secondary alkyl NHP
esters were also explored, and the results showed that alkyl
NHP esters bearing isopropyl, cyclohexyl, pyridyl were all adapt
to this reaction and the desired products 3aj, 3ak, 3al were
obtained in 96%, 99% and 77% yields. Furthermore, adamantyl
NHP ester also survived in this procedure and gave the desired
product 3am in 75% yield.
To evaluate the potential synthetic utility of this
decarboxylative coupling reaction, the reaction between N-
methylquinoxalin-2(1H)-one 1a and t-butyl NHP esters 2a was
carried out on a gram-scale under the optimized conditions, and
gave the desired product 3aa in the yield of 87% (Scheme 2). In
addition, an aldose reductase inhibitor precursor 3sn was
obtained by this transformation in a yield of 73% (Scheme 3).
Ethyl 2-(2-oxoquinoxalin-1(2H)-yl)acetate 1s was coupled with
alkyl NHP ester 2n under the optimized standard conditions to
give the product 3sn, which could be used for synthesis of a
aldose reductase inhibitor after hydrolysis and acidification.
Table 3. Substrate Scope of Alkyl NHP Estersa
Scheme 2. Large-scale experiment
3ab, 71%
3ae, 49%
3ac, 73%
3af, 74%
3ad, 68%
3ag, 69%
3ah, 87%
3ai, 92%
3aj, 96%
Scheme 3. Application of the coupling strategy to the synthesis of the aldose
reductase inhibitor.
3ak, 99%
3al, 77%
3am, 75%
aAll reactions were performed with 1a (1.0 mmol), 2 (1.2 mmol), Na2-eosin
Y (0.01 mmol) and TFA (0.5 mmol) in DMSO (3.0 mL) at room temperature
with irradiation by white LEDs under N2 atmosphere for 40 h.
To unambiguously clarify this reaction mechanism, several
control experiments were conducted. As show in scheme 4,
when TEMPO (2,2,6,6-tetramethyl-1-piperidinyl-oxy) (3.0
equiv.) was added into the model reaction, the transformation
was completely suppressed, which might indicate that this
reaction proceeded via a radical process. To confirm the
formation of alkyl radical, another radical scavenger 1,1-
After the scope of quinoxalin-2(1H)-ones was explored, a
variety of alkyl NHP esters were then examined via the
decarboxylative coupling reaction with N-methylquinoxalin-
2(1H)-one 1a. The experimental results indicated that different
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
Scheme 5. Proposed mechanism
diphenylethylene (3.0 equiv.) was introduced into the coupling
reaction between N-methyl-quinoxalin-2(1H)-one 1a and aryl-
propyl NHP ester 2i. Expectedly, the adduct 4 of 3-phenylpropyl
radical and 1,1-diphenylethylene was isolated in a yield of 21%,
while the corresponding product 3ai was not observed.
Furthermore, the Stern-Volmer experiment demonstrated that
Na2-eosin Y* could be quenched by alkyl NHP esters rather
than quinoxalin-2(1H)-ones. Finally, the quantum yield (Φ) of
the reaction was estimated by chemical actinometry and a low
value was observed (Φ = 0.225) (for more details, see
Supporting Information).
Conclusions
In summary, we have developed a green and efficient
method for construction of C(sp2)-C(sp3) bonds via
decarboxylative coupling reaction between various quinoxalin-
2(1H)-ones and alkyl NHP esters. A wide scope of linear alkyl
NHP esters and a variety of quinoxalin-2(1H)-ones bearing
various functional groups were demonstrated to be suitable for
this transformation, providing a novel avenue to synthesize C-3
alkylated quinoxalin-2(1H)-ones. This protocol was featured by
its mild conditions, easy availability of substrates, wide
functional group tolerance and operational simplicity.
Experimental Section
General Information. Melting points were determined using a digital
melting point apparatus and uncorrected. 1H NMR spectra were
recorded at 400 MHz using TMS as internal standard, 13C NMR spectra
were recorded at 100 MHz using TMS as internal standard. 19F NMR
spectra were recorded at 376 MHz using TMS as internal standard. All
chemical shifts were reported as δ values (ppm) relative to TMS and
observed coupling constants ( J ) are given in Hertz (Hz). Mass spectra
were measured with a HRMS-ESI instrument. Cyclic voltammetry were
measured by CHI660E (Chenhua, China) electrochemical workstation.
Unless otherwise indicated, all reactions were carried out under N2
atmosphere at room temperature with magnetic stirring. Quinoxalin-
2(1H)-ones and N-acyloxyphthalimides were prepared according to
literatures. All reagents were purchased from commercial source and
without prior purification. Column chromatography was performed on
silica gel (200-300 mesh) and the elution was performed with
hexane/ethyl acetate.
Scheme 4. Control experiments
On the basis of control experiments and previous reports, a
plausible mechanism for this decarboxylative coupling reaction
was proposed in Scheme 4. Under visible light irradiation, the
photocatalyst Na2-eosin Y was turned into its excited form Na2-
eosin Y*. Through the comparision of the redox potential of
Na2-eosin Y (PC+/PC*: -1.44 V vs. SCE) and alkyl NHP esters
(-1.26 to -1.37 V vs. SCE),12 it could be concluded that Na2-
eosin Y* can be quenched by alkyl NHP ester 2a’ that was
protonated by TFA via a single-electron transfer (SET) process
to generate radical I and Na2-eosin Y+. After the elimination of
CO2 and phthalimide, radical I was change into tert-butyl radical
II. Subsequently, the radical II regioselectively attacked
quinoxalin-2(1H)-ones 1a to produce nitrogen radical III. After a
hydrogen transfer process, nitrogen radical III was turned into
carbon radical IV, which could be further oxidized by Na2-eosin
Y+ to provide carbocation V via another SET process. Finally,
General procedure for the synthesis of 1.13 Ethyl 2-oxoacetate (1.1
equiv.) was added to a suspension of o-arylenediamine (4 mmol, 1
equiv.) in ethanol (1 mol/L). The reaction mixture was stirred and heated
at reflux in an oil bath for 1 h, then at room temperature for 16 h. Upon
completion (as monitored by TLC), the precipitate was filtered and
washed with ethanol, then dried to give quinoxalinone. For alkylation,
the corresponding halogenoalkane (1.6 equiv.) was added to
a
suspension of quinoxalinone (1 equiv.) and potassium carbonate (1.2
equiv.) in DMF (16 mL). The mixture was stirred at room temperature for
16 h. Upon completion (as monitored by TLC), the reaction mixture was
washed with saturated solution of ammonium chloride (5 mL), ethyl
acetate (10 mL) and water (10 mL). The organic layer was separated
and the aqueous layer was extracted with ethyl acetate (2 × 10 mL). The
combined organic layers were dried with anhydrous Na2SO4, filtered and
concentrated under reduced pressure. The resulting organic residue
was purified by flash chromatography column over silica gel (SiO2) to
afford the desired substrate 1.
3aa was generated through
intermediate V.
a deprotonation process of
General procedure for the synthesis of 2.9c In a 50 mL round bottom
flask equipped with magnetic stir bar was added N-hydroxyphthalimide
(1.63 g, 10 mmol, 1.0 equiv), 4-dimethylaminopyridine (61mg, 0.5 mmol),
dicyclohexylcarbodiimide (2.47 g, 12 mmol, 1.2 equiv), CH2Cl2 (20 mL)
and carboxylic acid (12 mmol, 1.2 equiv). The mixture was stirred at
room temperature for 0.5-3 h, during which time the reaction mixture
became cloudy and a white solid precipitated from the solution. The
white solid was removed via vacuum filtration and the filtrate was
removed under reduced pressure. The crude product was purified by
chromatography on a silica gel column (0→20% ethyl acetate/hexane)
to afford the desired substrate 2.
General procedure for the synthesis of 3 (3aa as an example). To a
10 mL Schlenk-tube was charged with N-methylquinoxalin-2(1H)-one 1a
(160 mg, 1.0 mmol), N-(acyloxy)-phthalimide 2a (296 mg, 1.2 mmol),
Na2-eosin Y (7 mg, 0.01 mmol), DMSO (1.5 mL) and TFA (57 mg, 0.5
mmol). The tube was evacuated and backfilled with N2 for three times.
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
2015, 5, 89009-89014. g) J. Schwarz, B. König, Green Chem 2016,
18,4743-4749. h) A. F. Garrido-Castro, H. Choubane, M. Daaou, M. C.
Maestro, J. Alemän, Chem. Commun. 2017, 53, 7764-7767. i) X. Zhu,
Z. He, Q.-Y. Li, X.-J. Wang, RSC Adv. 2017, 7, 25171-25174. j) W.-M.
Cheng, R. Shang, M.-C. Fu, Y. Fu, Chem. Eur. J. 2017, 23, 2537-2541.
k) M.-C. Fu, R. Shang, B. Zhao, B. Wang, Y. Fu, Science. 2019, 363,
1429-1434.
The mixture was then irradiated by 3 W white LEDs for 40 h. The
reaction mixture was then quenched with water (20 mL) and extracted
with DCM (10 mL × 3). The organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The crude product was purified
by flash chromatography on silica gel column (ethyl acetate/hexane,
1:12) to afford 3aa as a white solid.
[10] a) W.-M. Cheng, R. Shang, Y. Fu, ACS Catal. 2017, 7, 907-911. b) W.-
M. Cheng, R. Shang, M.-C. Fu. Y. Fu, Chem.-Eur. J. 2017, 23, 2537-
2541.
Acknowledgements
[11] a) B. Sun, Y. Wang, D. Y. Li, C. Jin, W. K. Su, Org. Biomol. Chem. 201
8, 16, 2902-2909. b) B. Sun, S. Yin, X. H. Zhuang, C. Jin, W. K. Su,
Org. Biomol. Chem. 2018, 16, 6017-6024. c) B. Sun, Z. Y. Yan, C. Jin,
W. K. Su, Synlett. 2018, 29, 2432-2436. d) C. Jin, Z. Y. Yan, B. Sun, J.
Yang, Org. Lett. 2019, 21, 2064-2068. e) B. Sun, J. C. Deng, D. Y. Li,
C. Jin, W. K. Su, Tetrahedron Lett. 2018, 59, 4364-4369. f) C. Jin, X.
H. Zhuang, B. Sun, D. Y. Li, R. Zhu, Asian J. Org. Chem. 2019, DOI:
10.1002/ajoc.201900369. g) C. Jin, X. Zhang, B. Sun, Z. Y. Yan, T. W.
Xu, Synlett 2019, DOI: 10.1055/s-0037 -1611864.
This work was supported by the National Natural Science
Foundation of China (21606202). We are also grateful to the
College of Pharmaceutical Sciences, Zhejiang University of
Technology and Collaborative Innovation Center of Yangtze
River Delta Region Green Pharmaceuticals for the financial
help.
[12] K. Xu, Z.-M. Tan, H.-N. Zhang, J.-L. Liu, S. Zhang, Z.-Q. Wang, Chem.
Commun. 2017, 53, 10719−10722.
[13]
L. Sumunnee, C. Pimpasri, M. Noikham, S. Yotphan, Org. Biomol.
Chem. 2018, 16, 2697-2704.
Keywords: C(sp2)-C(sp3) • metal and oxidant free • quinoxalin-
2(1H)-ones • NHP esters • photoredox catalysis
[1]
[2]
a) M. A. J. Duncton, MedChemComm 2011, 2, 1135-1161. b) Y. T.
Zhao, W. J. Xia, Org. Biomol. Chem. 2019,17, 4951-4963.
a) J. S. Zhou, G. C. Fu, J. Am. Chem. Soc. 2004, 126, 1340-1341. b)
M. Nakamura, K. Matsuo, S. Ito, E. Nakamura, J. Am. Chem. Soc.
2004, 126, 3686-3687. c) O. Vechorkin, V. Proust, X. L. Hu, J. Am.
Chem. Soc. 2009, 131, 9756-9766. d) S. L. Wang, Q. Qian, H. G.
Gong, Org. Lett. 2012. 14, 3352-3355.
[3]
[4]
a) J. Yamaguchi, A. D. Yamaguchi, K. Itami, Angew. Chem. Int. Ed.
2012, 51, 8960-9009. b) Z. Chen, B. Wang, J. Zhang, W. Yu, Z. Liu, Y.
Zhang, Org. Chem. Front. 2015, 2, 1107-1295. c) A. P. Antonchick, L.
Burgmann, Angew. Chem. Int. Ed. 2013, 52, 3267-3271.
a) Y. Kobayashi, Y. Suzuki, T. Ogata, T. Kimachi, Y. Takemoto,
Tetrahedron Lett. 2014, 55, 3299-3301. b) J. Dudash, Y. Zhang, J. B.
Moore, R. Look, Y. Liang, M. P. Beavers, B. R. Conway, P. J.
Rybczynski, K. T. Demarest, Bioorg. Med. Chem. Lett. 2005, 15, 4790-
4793. c) S. N. Khattab, S. A. H. Abdel Moneim, A. A. Bekhit, A. M. EI
Massry, S. Y. Hassan, A. El-Faham, H. E. Ali Ahmed, A. Amer, Eur. J.
Med Chem. 2015, 93, 308-320. d) S. A. M. El-Hawash, N. S. Habib, M.
A. Kassem, Arch. Pharm. Chem. Life Sci. 2006, 339, 564-571. e) M. M.
Badran, K. A. M. Abouzid, M. H. M. Hussein, Arch. Pharm. Res. 2003,
26, 107-113. f) B. Wu, Y. Yang, X. Qin, S. Zhang, C. Jing, C. Zhu, B.
Ma, ChemMedChem 2013, 8, 1913-1917. g) R. E. TenBrink, W. B. Im,
V. H. Sethy, A. H. Tang, D. B. Carter, J. Med. Chem. 1994, 37, 758-
768. h) D. S. Lawrence, J. E. Copper, C. D. Smith, J. Med. Chem.
2001, 44, 594-601. i) R. Liu, Z. H. Huang, M. G. Murray, X. Y. Guo, G.
Liu, J. Med. Chem. 2011, 54, 5747-5768.
[5]
[6]
V. A. Mamedov, N. A. Zhukova, Progress in Heterocyclic Chemistry.
2012, 24, 55-88.
a) L. Q. Hu, J. W. Yuan, J. H. Fu, T. T. Zhang, L. L. Gao, Y. M. Xiao, P.
Mao, L. B. Qu, Eur. J. Org. Chem. 2018, 4113-4120. b) J. W. Yuan, J.
H. Fu, J. H. Yin, Z. H. Dong, Y. M. Xiao, P. Mao, L. B. Qu, Org. Chem.
Front. 2018, 5, 2820-2828. c) J. H. Fu, J. W. Yuan, Y. Zhang, Y. M.
Xiao, P. Mao, X. Q. Diao, L. B. Qu, Org. Chem. Front. 2018, 5, 3382-
3390. d) L. Yang, P. Gao, X.-H. Duan, Y.-R. Gu, L.-N. Guo, Org. Lett.
2018, 20, 1034-1017. e) W. Wei, L. L. Wang, H. L. Yue, P. L. Bao, W.
W. Liu, C. S. Hu, D. S. Yang, H. Wang, ACS Sustainable Chem. Eng.
2018, 6, 17252-17257.
[7]
[8]
a) F. Minisci, R. Bernardi, F. Bertini, R. Galli, M. Perchinummo,
Tetrahedron. 1971, 27, 3575-3579. b) F. Minisci, E. Vismara, F.
Fontana, Heterocycles. 1989, 28, 489-519.
a) R. Shang, D.-S. Ji, L. Chu, Y. Fu, L. Liu, Angew. Chem. Int. Ed.
2011, 50, 4470-4474. b) R. Shang, Z.-W. Yang, Y. Wang, S.-L. Zhang,
L. Liu, J. Am. Chem. Soc. 2010, 132, 14391-14393. c) R. Shang, Z.
Huang, L. Chu, Y. Fu, L. Liu, Org. Lett. 2011. 13, 4240-4243.
a) J.-C. Yang, J.-Y. Zhang, J.-J. Zhang, X.-H. Duan, L.-N. Guo, J. Org.
Chem. 2018, 83, 1598-1605. b) W. X. Sha, S. Y. Ni, J. L. Han, Y. Pan,
Org. Lett. 2017, 19, 5900-5903. c) G.-Z. Wang, R. Shang, Y. Fu, Org.
Lett. 2018, 20, 888-891. d) A. Tlahuext-Aca, R. A. Garza-Sanchez, M.
Schäfer, F. Glorius, Org. Lett. 2018, 20, 1546-1549. e) Z.-H. Xia, C.-L.
Zhang, Z.-H. Gao, S. Ye, Org. Lett. 2018, 20, 3496-3499. f) Q. Tang,
X. B. Liu, S. Liu, H. Q. Xie, W. Liu, J. G. Zeng, P. Cheng, RSC Adv.
[9]
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

10.1002/asia.201900904
Chemistry - An Asian Journal
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Zhiyang Yan, Bin Sun, Xun Zhang,
Xiaohui Zhuang, Jin Yang, Jiayang
Wang, and Can Jin*,
Page No. – Page No.
Construction of C(sp2)-C(sp3) Bond
between Quinoxalin-2(1H)-ones and
N-Hydroxyphthalimide Esters via
A metal and oxidant free decarboxylative coupling of quinoxalin-2(1H)-ones with
NHP esters via a photocatalytic system promoted by visible light has been
developed.
Photocatalytic
Coupling
Decarboxylative
[c]
[b]
Z. Yan, X. Zhang, X. Zhuang, J. Yang, J. Wang, Prof. Dr. C.
College of Pharmaceutical Sciences
Zhejiang University of Technology
Hangzhou 310014 (P. R. China)
E-mail: jincan@zjut.edu.cn
Dr. B. Sun
Collaborative Innovation Center of Yangtze River Delta Reg
Green Pharmaceuticals
Zhejiang University of Technology
Hangzhou 310014 (P. R. China)
Supporting information for this article is given via a link at th
the document.((Please delete this text if not appropriate))
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.