Visible-Light-Triggered Decarboxylative Alkylation of 8-Acylaminoquinoline with N -Hydroxyphthalimide Ester

Article abstract of DOI:10.1055/s-0039-1691579

A facile protocol for visible-light-induced decarboxylative radical coupling of NHP esters with 8-aminoquinoline amides is reported, affording a highly efficient approach to synthesize a variety of 2-alkylated or 2,4-dialkylated 8-aminoquinoline derivativ

Full text of DOI:10.1055/s-0039-1691579

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2020, 31, A–F
letter
A
en
Synlett
B. Sun et al.
Letter
Visible-Light-Triggered Decarboxylative Alkylation of 8-Acylami-
noquinoline with N-Hydroxyphthalimide Ester
Bin Sunb,c
Deyu Lia,c
Xiaohui Zhuanga,c
Rui Zhua,c
Aertuke Aishad
Can Jin*a,b,c
O
O
O
O
O
Ir
visible light
R2
R1 NH
R1 NH
+
N
N
N
DMSO, TFA, r,t,
R2
O
alkyl source
3
2 examples R2 = 1°, 2°,and 3°
up to 85%
alkyl groups
Photocatalysis
Oxidant free
Decarboxylative coupling
Broad substrate scope
a
College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou 310014, P. R. of China
jincan@zjut.edu.cn
Collaborative Innovation Center of Yangtze River Delta Region
b
Green Pharmaceuticals, Zhejiang University of Technology,
Hangzhou 310014, P. R. of China
National Engineering Research Center for Process Develop-
c
ment of Active Pharmaceutical Ingredients, Zhejiang Universi-
ty of Technology, Hangzhou 310014, P. R. of China
The Development Laboratory Center of Research Institute of
d
Experiment and Detection of Xinjiang Oilfield Company,
Karamay 834000, P. R. of China
Received: 25.12.2019
Accepted after revision: 04.01.2020
Published online: 28.01.2019
ent positions (C2 or C4). This hypothesis has been demon-
strated by Xia’s group through the use of strong oxidizing
11
DOI: 10.1055/s-0039-1691579; Art ID: st-2019-l0693-l
conditions (combination of AgNO
3 2 2 8
and K S O ) (Scheme
1
b), affording a series of 2-cycloalkyl-8-aminoquinolines;
Abstract A facile protocol for visible-light-induced decarboxylative
radical coupling of NHP esters with 8-aminoquinoline amides is report-
ed, affording a highly efficient approach to synthesize a variety of 2-al-
kylated or 2,4-dialkylated 8-aminoquinoline derivatives. The reaction
proceeds smoothly without adding any ligand, and provides the corre-
sponding products containing a wide range of functional groups in
moderate to excellent yields. This reaction uses readily available starting
materials, and proceeds under mild conditions and with operational
simplicity.
Traditional Minisci reaction
RCOOH
AgNO3
(a)
(b)
H2SO4, (NH4)2S2O8
N
H
N
R
Previous work
O
Key words 8-aminoquinoline, visible light, C–H alkylation, decarbox-
ylation
O
.
Cu(OAc)2 H2O (10 mol%)
R1
2
R1 NH
NH
+ R COOH
AgNO3 (30 mol%)
K2S2O8 (2.0 equiv)
N
N
N
R2
ref 11
excess oxidants!!
As an important structural motif of heterocyclic mole-
cules in natural products, quinoline derivatives have been
O
Co(acac)2 (10 mol%)
Eosin Y (2 mol%)
O
1
R
NH
+
widely applied to pharmaceutical science. Particularly, 8-
O
R
NH
N
O
TBHP(4.0 equiv )
Cs2CO3 (2.0 equiv)
(c)
aminoquinolines exhibit several remarkable properties
32W CFL lamp
2
such as anti-Alzheimer and antimalarial activities. In addi-
ref 12
O
tion, 8-aminoquinoline amide was discovered as a biden-
tate directing group by Daugulis. Therefore, it is of great
Our work
R1 NH
3
N
O
N
O
O
O
importance to develop highly efficient methods for the
preparation of substituted 8-aminoquinoline derivatives.
The direct C–H functionalization of 8-aminoquinolines has
gained significant interest in organic synthesis, and many
O
R2
fac-Ir(ppy)3 (1 mol%)
TFA (0.5 equiv)
R2
R1 NH
+
R2 = tert-butyl
3W white LEDs
N
primary alkyl
R2
(d)
oxdiants
O
4
R1 NH
successful examples including C–H halogenation, alkyla-
tion, nitrification, esterification, phosphonation8 and
5
6
7
N
9
R2
R2 = secondary alkyl
carboxylation on the C5 position have been achieved. The
10
Minisci reaction, in which carboxylic acids serve as the al-
kyl source (Scheme 1a), was likely to be a feasible method
to lead to the alkylation of 8-aminoquinoline on the differ-
Scheme 1 Strategies for the synthesis of alkylated 8-aminoquinoline
derivatives
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
B. Sun et al.
Letter
however, primary alkyl acids did not participate in the re-
action. Recently, Ranu12 reported a cobalt-catalyzed selec-
tive remote C-4 alkylation of 8-aminoquinoline amides via
C–H activation with irradiation with a CFL lamp (Scheme
of a lack of effective methods for synthesis of chain alkylat-
ed 8-aminoquinoline derivatives.
As a part of our ongoing research on developing green
methods for C–H functionalization,15 herein, we described a
facile visible-light-induced photoredox alkylation between
8-aminoquinoline amides and alkyl NHP esters through a
radical type decarboxylative coupling process, affording an
oxidant-free method for the preparation of 2-alkyl and 2,4-
dialkyl 8-aminoquinoline amides under mild conditions
(Scheme 1d).
1c). Consequently, it is highly desirable to investigate both
mild and convenient methods for synthesizing alkylated,
especially primary-alkylated, 8-aminoquinoline derivatives,
which could further promote the application of 8-amino-
quinolines in new drug discovery and synthesis.
During the past decade, with the higher demand for de-
veloping green and sustainable chemistry, visible-light-in-
duced catalysis, which has the advantage of environment-
friendliness, mild conditions, and low-energy irradiation,
To explore and optimize the reaction conditions, N-
(quinolin-8-yl) benzamide (1a) and tert-butyl NHP ester
(2a) were chosen as the model substrates. Initially, photo-
catalysts such as Ru(bpy) Cl , fac-Ir(ppy)3, Eosin Y,
13
has received increasing attention. According to previous
3
2
14
reports, the alkyl N-hydroxyphthalimide (NHP) ester gen-
erated via condensation between NHPI and carboxylic acid,
was shown to be an effective alkyl source because it could
be easily reduced under photocatalytic conditions to donate
Rhodamine 6G, and Rose Bengal were selected as catalysts
to carry out the decarboxylative coupling reaction. Fortu-
nately, the 2-tert-butyl product 3aa was obtained, albeit in
a relatively low yield (21%), when the reaction was irradiat-
ed with 3 W blue LEDs for 12 hours at room temperature
under nitrogen atmosphere by employing fac-Ir(ppy)3 as
the photocatalyst and DMSO as the solvent (Table 1, entry
2), whereas none of the other screened photocatalysts cata-
a variety of alkyl radicals while releasing CO and phthalim-
2
ide. With this idea in mind, a visible-light-mediated radical
type decarboxylative alkylation of 8-aminoquinoline by
employing NHP esters was envisioned to solve the problem
Table 1 Optimization of the Reaction Conditionsa
O
O
O
O
O
photocatalyst (1 mol%)
additive (0.5 equiv)
Ph
N
+
N
Ph
N
H
H
visible light, solvent
N
N
O
1a
2a
3aa
Entry
Photocatalyst
Solvent
Additive
Yield (%)b
1
2
3
4
5
6
7
8
9
Ru(bpy)
3
Cl
2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
MeCN
DCE
–
trace
21
fac-Ir(ppy)
3
–
Eosin Y
–
N.D.
N.D.
trace
63
Rhodamine 6G
Rose Bengal
–
–
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
3
3
3
3
3
3
3
3
3
3
TFA
DIPEA
15
citric acid
TFA
trace
trace
N.D.
17
1
1
1
1
1
0
TFA
1
acetone
DMSO
DMSO
DMSO
DMSO
TFA
2c
3d
4e
TFA
81
TFA
39
TFA
N.D.
N.D.
1 f
5
TFA
a
Reaction conditions: a mixture of 1a (0.1 mmol), 2a (0.2 mmol), photocatalyst (1 mol%), additive (0.05 mmol), solvent (3 mL) was irradiated with CFL lamps
under nitrogen atmosphere at room temperature for 12 h.
b
Isolated yield.
White LEDs instead of blue LEDs.
Green LEDs instead of blue LEDs.
Without irradiation.
c
d
e
f
Without nitrogen atmosphere.
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

C
Synlett
B. Sun et al.
Letter
lyzed the reaction (entries 1–5). To further improve the
yield of target product 3aa, several additives were then ex-
amined. To our delight, the yield of 3aa increased to 63%
when the reaction was conducted in the presence of 0.5
equiv of TFA (entry 6). Other additives, such as DIPEA and
citric acid, did not give a satisfactory result (entries 7, 8).
Subsequently, a variety of other commonly used solvents
were also investigated for this transformation (entries 9–
O
O
O
O
fac-Ir(ppy)3 (1 mol%)
TFA (0.5 equiv)
O
R2
+
R1 NH
N
R1 NH
3
W white LEDs
DMSO
N
N
O
1
2a
3
O
3aa, R = H, 81%
3ba, R = 4-Me, 58%
3ca, R = 4- Bu, 36%
3da, R = 4-OMe, 56%
ea, R = 4-Cl, 80%
ka, R = Me, 72%
3la, R = nPr, 82%
3ma, R = Pr, 78%
3fa, R = 4-Br, 56%
ga, R = 4-F, 82%
3ha, R = 4-CF , 63%
3
N
H
R
t
3
N
3
3
ia, R = 3-Cl, 58%
ja, R = 3,5-diCF3, 53%
11). However, the experimental results revealed that the re-
3
action did not proceed well when carried out in MeCN,
DCM or acetone, and DMSO was still found to be the best
choice.
It was also pleasing to find that the yield of 3aa in-
creased sharply from 63 to 81% (Table 1, entry 12) when the
blue LEDs were replaced with white LEDs; only low yield
was obtained when green LEDs were employed as light
source (entry 13). The reaction failed to initiate without any
irradiation (entry 14). It is worth noting that the reaction
did not proceed without the protection of nitrogen (entry
O
3
3oa, R = 1-adamantyl, 52%
3pa, R = 2-furoyl, 54%
3qa, R = thiophen-2-yl, 80%
R
N
H
i
N
3
na, R = cyclohexyl, 67%
O
NH2
N
3ra, R = 5-Cl, 33%
3ta, 0%
N
H
R
3sa, R = 6-OMe, 52%
N
15). On the basis of the screening of the reaction conditions,
it was clear that this cross-coupling reaction should be per-
formed in the presence of fac-Ir(ppy) in DMSO with the ir-
Scheme 2 Substrate scope of 8-aminoquinolines and alkyl NHP esters.
3
Reagents and conditions: 1 (0.5 mmol), 2a (1 mmol), fac-Ir(ppy) (1
radiation of 3 W white LEDs at room temperature under ni-
trogen atmosphere (Table 1, entry 12).
3
mol%), TFA (0.25 mmol), DMSO (3 mL), with irradiation with white CFL
lamps in nitrogen atmosphere at room temperature for 12 h.
With the optimized conditions in hand, a series of 8-
aminoquinoline derivatives were then applied to this
2
3
C(sp )–C(sp ) bond formation to yield the corresponding al-
kylated 8-aminoquinoline derivatives via the decarboxyl-
ative coupling with tert-butyl NHP. As summarized in
Scheme 2, this method was found to be applicable to a wide
range of 8-aminoquinoline amides and afforded the desired
coupling products 3aa–sa in moderate to good yields. First-
ly, a series of 8-aminoquinoline amides bearing different
protecting groups on the amino moiety were studied for
this reaction. The results showed that the protecting groups
have no obvious influence on the reaction. Substrates con-
taining electron-donating groups (Me, tBu, OMe) or elec-
substituents on the quinoline ring were also studied. Both
5-Cl (3ra) and 6-OMe (3sa) derived products could be ob-
tained in moderate yields under the standard reaction con-
ditions. Unfortunately, when N-free protected 8-amino-
quinoline was subjected to the standard reaction condi-
tions, no corresponding product could be detected.
Subsequently, we continued to investigate the substrate
generality with a range of representative NHP esters via de-
carboxylative coupling with 1a under the standard condi-
tions. The results are summarized in Scheme 3. The prima-
ry alkyl NHP esters all showed good tolerance for this reac-
tion, affording the corresponding alkylated products 3ab–
ae in moderate yields.
Moreover, primary alkyl NHP esters with additional
hetero atoms such as oxygen (2f) or halogen (2g) were also
well tolerated for this transformation, and the desired prod-
ucts 3af–ah could be obtained in satisfactory yields. Sub-
strates with ester groups (2h) also exhibited good reactivi-
ty, providing the corresponding product 3ah in 65% yield.
When secondary aliphatic carboxylic NHP esters such as
isopropyl (2i), cyclopentyl (2j), cyclohexyl (2k) and N-Boc-
L-norvalinyl (2l) were employed to react with 1a, no C-2
monoalkylated product could be obtained. Instead, 2,4-
disubstituted products 3ai–al were isolated in good yields.
Similar results were found when 8-acetylaminoquinoline
1k was used under the reaction conditions (3ki, 3kj). We
tried to reduce the amount of NHP ester to 1 equivalent,
and products 3ki and 3kj were still obtained in lower
yields. Notably, neither 2-aryl-substituted N-(quinolin-8-
tron-withdrawing groups (Cl, Br, F, CF ) on the benzene ring
3
of 1 were all well tolerated and afforded the desired C2-tert-
butyl substituted products 3ba–ja in moderate to good
yields. By comparison of 3ea and 3ia, it also could be con-
cluded that the substrates with substituents at different po-
sitions of the benzene ring exhibited similar reactivity. Fur-
thermore, the substrate scope of this process with respect
to aliphatic amides was evaluated under the optimized re-
action conditions. The 8-aminoquinoline amides bearing
either noncyclic alkyl groups such as methyl- (3k), n-Pr-
(
3l) and i-Pr- (3m), or the cyclic alkyl group (cylcohexyl,
adamantyl) (3n, 3o), all exhibited excellent tolerance for
this transformation, providing the corresponding products
3ka–oa in yields of 52–82%.
Heterocyclic amides containing furan (3p) or thiophene
(
3q) moieties also showed good suitability and gave the de-
sired products in satisfactory yields. Moreover, to extend
the substrate scope, 8-aminoquinoline derivatives bearing
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

D
Synlett
B. Sun et al.
Letter
performed and the results indicated that Ir(ppy) * could be
quenched with alkyl NHP esters, suggesting that the reac-
tion might proceed through an oxidative quenching path-
way (for details, see the Supporting Information).
O
O
O
3
O
fac-Ir(ppy)3 (1 mol%)
TFA (0.5 equiv)
O
R3
Ph
NH
+
N
Ph
NH
3
W white LEDs
DMSO
N
N
O
R3
1a
2
3
O
O
standard
conditions
O
O
O
Ph
N
2a
Ph
N
N
O
+
+
Ph
N
H
H
TEMPO (3.0 equiv)
H
(1)
Ph
N
H
N
N
Ph
N
H
N
N
N
1
a
3
aa, N.D.
4
3
ad, 65%
detected by
HRMS
O
standard
conditions
O
3ab, 60%
3ac, 51%
Ph
N
H
+
2a
Ph
N
H
N
BHT (3.0 equiv)
N
(2)
(3)
O
O
O
Ph
N
Ph
N
H
Ph
N
H
1a
N
H
3aa, N.D.
N
N
O
standard
conditions
O
4
Br
O
Ph
N
+
2a
Ph
N
3
ae, 53%
3af, 78%
3ag, 68%
H
1
,1-diphenylethylene
H
N
N
(3.0 equiv)
O
O
O
Ph
N
1a
Ph
N
H
3aa, N.D.
H
N
Ph
N
H
N
N
Scheme 4 Control experiments
4
COOMe
3ah, 65%
3ai, 84%
3aj, 79%
O
O
O
Boc
N
Ph
N
Ph
N
N
H
H
H
H
N
N
N
Boc
N
H
3
ki, 81%, 38%a
3ak, 85%
3al, 80%
O
O
Scheme 5 Stern–Volmer experiments
O
Ph
Ph
N
N
H
Ph
N
H
N
N
H
N
Ph
According to the observations described above and to
a plausible mechanism for this decar-
boxylative coupling reaction is proposed in Scheme 6. First-
Ph
am, 0%
previous reports,1
5a,b
3
an, 0%
3
kj, 71% 30%a
3
ly, the photocatalyst fac-Ir(ppy) is irradiated to give its ac-
3
Scheme 3 Substrate scope of alkyl NHP esters. Reagents and condi-
*
tivated species Ir(ppy) , which can donate an electron to
3
tions: 1a (0.5 mmol), 2 (1 mmol), fac-Ir(ppy) (1 mol%), TFA (0.25
3
the protonated NHP esters 2a′ to form the radical A. After
elimination of phthalimide and carbon dioxide, radical A
could transform into the tert-butyl radical, which then un-
dergoes a regioselective addition to the TFA-protonated 1a
to generate the key intermediate B. A proton on the C2 posi-
tion of B is then removed by the phthalimide anion. The
deprotonated product gives Ir4 an electron in a SET step
and is transformed into the intermediate C. Finally, C is
transferred into the desired product 3aa by facile elimina-
tion of TFA.
In conclusion, we have succeeded in developing a novel
visible-light-induced C–H alkylation of 8-aminoquinolne
amides by employing alkyl NHP esters as the alkyl source,
preparing a variety of alkyl-substituted 8-aminoquinoline
derivatives.16 Remarkably, this transformation has been
shown to be compatible with a wide range of alkyl NHP es-
ters, and a variety of 8-aminoquinoline derivatives bearing
mmol), DMSO (3 mL), with irradiation with white CFL lamps in nitrogen
atmosphere at room temperature for 12 h. NHP ester (1 equiv) was used.
a
yl)benzamide product (3am) nor 2,4-disubstituted by-
product (3an) were found under the standard conditions.
Control experiments were carried out to gain insight
into the mechanism (Scheme 4). Firstly, the radical scaven-
ger 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was ap-
plied to the model reaction system and we found that this
decarboxylative coupling reaction was completely inhibited
+
(
Scheme 3, Eq. 1). Meanwhile, the adduct 4 of alkyl radical
and TEMPO was detected by HRMS. Similar results were ob-
tained when other radical scavengers 2,6-di-tert-butyl-4-
methylphenol (BHT) and 1,1-diphenylethylene were em-
ployed in the same reaction system (Scheme 3, Eq. 2 and 3).
Additionally, Stern–Volmer experiments (Scheme 5) were
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

E
Synlett
B. Sun et al.
Letter
O
O
O
O
O
standrad
conditions
Ph
N
N
+
Ph
N
H
H
N
N
O
CF3COO– TFA
O
1a
2a
3aa
Ph
N
H
HN
TFA
C
HNPhth
IrIII
NPhth–
CF3COO–
O
SET
hv
O
Ph
N
Photoredox
cycle
H
HN
IrIV
2a
NPhth–
Ph
N
TFA
CF3COO–
H
H
HN
IrIII
*
HNPhth
SET
B
O
O
N
O
N O
–
CO2
–
HNPhth
OH O
OH O
A
2a'
Scheme 6 Proposed mechanism
various functional groups also exhibited good tolerance for
this transformation. Mechanistic studies have revealed that
this decarboxylative coupling reaction proceeds through a
radical process.
(3) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005,
27, 13154.
1
(
4) (a) Chen, J. C.; Wang, T. Y.; Liu, Y. P.; Wang, T.; Lin, A. J.; Yao, H.
Q.; Xu, J. Y. Org. Chem. Front. 2017, 4, 622. (b) Motati, D. R.;
Uredi, D.; Watkins, E. B. Chem. Sci. 2018, 9, 1782. (c) Ma, B.; Lu,
F. L.; Yang, H. M.; Gu, X.; Li, Z.; Li, R.; Pei, H. Q.; Luo, D.; Zhang,
H.; Lei, A. W. Asian J. Org. Chem. 2019, 8, 1136.
Funding Information
(
(
(
5) (a) Mariappan, A.; Das, K. M.; Jeganmohan, M. Org. Biomol.
Chem. 2018, 16, 3419. (b) Chen, H.; Li, P. H.; Wang, M.; Wang, L.
Org. Lett. 2016, 18, 4794.
6) (a) Zhu, X. L.; Qiao, L.; Ye, P. P.; Ying, B. B.; Xu, J.; Shen, C.; Zhang,
P. F. RSC Adv. 2016, 6, 89979. (b) He, Y.; Zhao, N. N.; Qiu, L. Q.;
Zhang, X. Y.; Fan, X. S. Org. Lett. 2016, 18, 6054.
7) (a) Xia, C. C.; Wang, K.; Xu, J.; Shen, C.; Sun, D.; Li, H. S.; Wang, G.
D.; Zhang, P. F. Org. Biomol. Chem. 2017, 15, 531. (b) Xu, J.; Shen,
C.; Zhu, X. L.; Zhang, P. F.; Ajitha, M. J.; Huang, K. W.; An, Z. F.;
Liu, X. G. Chem. Asian J. 2016, 11, 882. (c) Thrimurtulu, N.; Dey,
A.; Pal, K.; Nair, A.; Kumar, S.; Volla, C. M. R. ChemistrySelect
2017, 2, 7251.
We thank the National Natural Science Foundation of China (Grant
No. 21606202) for financial support. We are also grateful to the Col-
lege of Pharmaceutical Sciences, Zhejiang University of Technology
and Collaborative Innovation Center of Yangtze River Delta Region
Green Pharmaceuticals for the financial help.
N
ati
o
n
a
l Natural S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(2
1
6
0
6
2
0
2)
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691579.
S
u
p
p
orti
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
(
8) (a) Qiao, H. J.; Sun, S. Y.; Zhang, Y.; Zhu, H. M.; Yu, X. M.; Yang, F.;
Wu, Y. S.; Li, Z. X.; Wu, Y. J. Org. Chem. Front. 2017, 4, 1981.
(b) Sun, M. M.; Sun, S. Y.; Qiao, H. J.; Yang, F.; Zhu, Y.; Kang, J. X.;
Wu, Y. S.; Wu, Y. J. Org. Chem. Front. 2016, 3, 1646.
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©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

F
Synlett
B. Sun et al.
Letter
(
14) (a) Candish, L.; Teders, M.; Glorius, F. J. Am. Chem. Soc. 2017,
39, 7440. (b) Schwarz, J.; Konig, B. Green Chem. 2016, 18, 4743.
c) Deng, W. L.; Feng, W. W.; Li, Y. J.; Bao, H. L. Org. Lett. 2018,
0, 4245. (d) Wang, X.; Han, Y. F.; Ouyang, X. H.; Li, J. H. Chem.
(16) Synthesis of 3; Typical Procedure for 3aa: A 10 mL Schlenk-
tube was charged with N-(quinolin-8-yl)benzamide (1a; 124
mg, 0.5 mmol), tert-butyl NHP ester 2a (247 mg, 1.0 mmol), fac-
Ir(ppy)3 (6 mg, 0.015 mmol), trifluoroacetic acid (29 mg, 0.25
mmol) and DMSO (3.0 mL). The tube was evacuated and back-
1
(
2
Commun. 2019, 55, 14637. (e) Guo, J. Y.; Zhang, Z. Y.; Guan, T.;
Mao, L. W.; Bao, Q.; Zhao, K.; Loh, T. P. Chem. Sci. 2019, 10, 8792.
15) (a) Jin, C.; Yan, Z. Y.; Sun, B.; Yang, J. Org. Lett. 2019, 21, 2064.
filled with N for three times. The mixture was then irradiated
2
(
with 3 W white CFL lamps and stirred for 12 hours at room tem-
perature. After the reaction finished, the reaction was quenched
with water (10 mL) and the mixture was extracted with DCM
(10 mL). The organic layer was dried over Na SO and concen-
(b) Yan, Z. Y.; Sun, B.; Zhang, X.; Zhuang, X. H.; Yang, J.; Su, W.
K.; Jin, C. Chem. Asian J. 2019, 14, 3344. (c) Sun, B.; Deng, J. C.; Li,
D. Y.; Jin, C.; Su, W. K. Tetrahedron Lett. 2018, 59, 4364. (d) Jin,
C.; Zhuang, X. H.; Sun, B.; Li, D. Y.; Zhu, R. Asian J. Org. Chem.
2
4
trated under reduced pressure. The crude product was purified
by flash chromatography on silica gel column (ethyl ace-
2019, 8, 1490. (e) Wang, J. Y.; Sun, B.; Zhang, L.; Xu, T. W.; Xie, Y.
Y.; Jin, C. Asian J. Org. Chem. 2019, 8, 1942. (f) Sun, B.; Yang, J.;
Zhang, L.; Shi, R. C.; Zhang, X.; Xu, T. W.; Zhuang, X. H.; Zhu, R.;
Yu, C. M.; Jin, C. Asian J. Org. Chem. 2019, 8, 2058. (g) Sun, B.; Yin,
S.; Zhuang, X. H.; Jin, C.; Su, W. K. Org. Biomol. Chem. 2018, 16,
tate/hexane, 1:200) to afford 3aa (123 mg, 81%) as a white solid;
1
mp 131.0–132.0 °C. H NMR (400 MHz, CDCl ):  = 11.04 (s,
3
1 H), 8.92 (d, J = 7.1 Hz, 1 H), 8.20–8.11 (m, 3 H), 7.68–7.48 (m,
13
6 H), 1.55 (s, 9 H). C NMR (101 MHz, CDCl ):  = 167.6, 156.3,
3
6
017. (h) Sun, B.; Wang, Y.; Li, D. Y.; Jin, C.; Su, W. K. Org. Biomol.
148.6, 144.4, 137.1, 136.5, 134.0, 126.6, 126.0, 121.3, 119.0,
116.3, 114.8, 112.4, 38.3, 30.1. HRMS: m/z [M + H] calcd for
+
Chem. 2018, 16, 2902. (i) Jin, C.; Zhu, R.; Sun, B.; Zhang, L.;
Zhuang, X. H. Asian J. Org. Chem. 2019, 8, 2213.
C20H21N O: 305.1648; found: 305.1638.
2
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–F