Asymmetric dearomatization of 2-nitrobenzofurans by organocatalyzed one-step Michael addition to access 3,3′-disubstituted oxindoles

Article abstract of DOI:10.1039/c9cc09939e

An efficient enantioselective dearomatization of 2-nitrobenzofurans was realized via an organocatalyzed one-step Michael addition process. This method provides a facile strategy to access a range of structurally diverse 3,3′-disubstituted oxindoles, which feature an intriguing combination of two privileged motifs including 3-pyrrolyl-substituted-oxindoles and 2,3-dihydrobenzofurans substructures, in excellent results.

Full text of DOI:10.1039/c9cc09939e

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DOI: 10.1039/C9CC09939E
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Received 00th January 20xx,
Accepted 00th January 20xx
Asymmetric dearomatization of 2-nitrobenzofurans by
organocatalyzed one-step Michael addition to access
DOI: 10.1039/x0xx00000x
3,3′-disubstituted oxindoles
www.rsc.org/
Zhen-Zhen Ge,a,d,§ Lei Yang,a,d,§ Yong You,b Zhen-Hua Wang,b Ke-Xin Xie,c Ming-Qiang Zhou,a Jian-
Qiang Zhao,b* and Wei-Cheng Yuana,b
*
An
efficient
enantioselective
dearomatization
of
2- these
asymmetric
reactions
undergo
a
tandem
nitrobenzofurans was realized via an organocatalyzed one-step dearomatization/annulation process for the formation of
Michael addition process. This method provides a facile strategy polycyclic structures, mainly relying on the first electrophilicity
to access
a range of structurally diverse 3,3′-disubstituted and the sequential nucleophilicity of electron-deficient
oxindoles, which are featured with an intriguing combination of nitroheteroarenes (Scheme 1, a).4-7 Despite the success of
two privileged motifs including 3-pyrrolyl-substituted-oxindoles these reactions, however, to the best of our knowledge, the
and 2,3-dihydrobenzofurans substructures, in excellent results.
involvement of electron-deficient nitroheteroarenes as
Michael acceptors just undergoing one-step dearomative
Michael addition has remained unexplored (Scheme 1, b). As
part of our continuing efforts on the research of the
Catalytic asymmetric dearomatization of simple planar
aromatic compounds has emerged as one of powerful and
reliable strategies for the construction of enantioenriched
there-dimensional molecules.1 Notably, the vast majority of
the reported asymmetric dearomative reactions are typically
focused on the application of the intrinsic nucleophilicity of
electron-rich arenes and heteroarenes.1,2 Actually, installing a
suitable electron-withdrawing substituent on the arenes and
heteroarenes can reverse them into electron-deficient
compounds thus serving as electrophiles for umpolung-like
reactions.3 In this context, creative reactions for the
construction of interesting cyclic compounds with innovative
structures would be expected by using electron-deficient
arenes and heteroarenes. Therefore, exploring new methods
to realize the asymmetric dearomatization of electron-
deficient aromatic compounds in organic synthesis remains in
high demand and has bright prospect.
asymmetric
dearomatization
of
electron-deficient
nitroheteroarenes,4,5b,5c,5e,5i,6b,6d,6e,7 we were intrigued by the
possibility of only one-step dearomative Michael addition to
electron-deficient
nitroheteroarenes
with
suitable
nucleophiles under
a
catalytic asymmetric control. If
successful, undoubtedly, the dearomative Michael addition
reaction will lead to the formation of chiral 2,3-disubstituted-
2,3-dihydrobenzo-heterocycle skeletons (Scheme 1, b), which
are ubiquitous structural units in a number of biologically
active compounds.8
Scheme 1 Outline of this work.
Nu
E
N
O2
Nu
E
*
NO2
(widely studied)
(a)
*
or
E
NO2
Nu
*
tandem dearomative
Michael-annulation process
*
X
X
Nu
E
X
: nucleophiles
: electrophiles
X = NPg, O, S
or
NO2
Nu
NO2
Electron-deficient nitroheteroarenes, such as 2- and 3-
Nu-
X
*
*
Nuor
(unexplored)
(b)
electron-deficient
nitroheteroarenes
NO2
one-step dearomative
Michael addition process
*
*
nitroindoles,4,5
2-nitrobenzofurans,6
2-
and
3-
X
X
nitrobenzothiophenes,5f,5o,6a,6e,7 have been used as C2
synthons for various enantioselective dearomative annulation
reactions in recent years. It is noteworthy that almost all of
N
N
*
O
*
organocatalysis
*
NO2
O
+
(this work) (c)
O
O NO2
N
R
N
R
the first enantioselective dearomatization of 2-nitrobenzofurans by one-step Michael addition
three contiguous stereocenters with excellent dr and high ee values
products containing two privileged motifs (3-pyrrolyl-oxindoles and 2,3-dihydrobenzofurans)
promising in medicinal application as potential biologically active candidates
a. National Engineering Research Center of Chiral Drugs, Chengdu Institute of
Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China.
b. Institute for Advanced Study, Chengdu University, Chengdu 610106, China.
E-mail: yuanwc@cioc.ac.cn; zhaojianqiang@cdu.edu.cn
3-Monosubstituted oxindoles have emerged as a type of
robust nucleophiles, and they can react with various
electrophiles via asymmetric catalysis to generate structurally
diverse 3,3'-disubstituted oxindoles,9 which are commonly
occurring structural motifs found in many natural products and
pharmaceuticals.10 Inspired by the elegant works in this field,
we chose to focus on the catalytic asymmetric dearomative
c. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041,
China
d. University of Chinese Academy of Sciences, Beijing, 100049, China
§
These authors contributed equally.
† Electronic Supplementary Information (ESI) available: Experimental procedures,
spectral data of new compounds, and crystallographic data. CCDC 1943699. For
ESI and crystallographic data in CIF or other electronic format. See DOI:
10.1039/x0xx00000x
Michael
addition
of
3-pyrrolyl-oxindoles11
to
2-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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nitrobenzofurans for constructing chiral 3,3'-disubstituted to 87% ee (Table 1, entry 4). And then, screeninVgiewofArstioclelvOennlintes
DOI: 10.1039/C9CC09939E
oxindoles, which are featured with an intriguing combination revealed that xylene was the best in the light of the chemical
of two privileged motifs including 3-pyrrolyl-substituted- yield, dr and ee values (Table 1, entry 7 vs entries 4-6 and 8-9).
oxindoles and 2,3-dihydrobenzofurans substructures (Scheme Afterwards, lowering the reaction temperature from room
o
1, c). Notably, this work represents the first example of temperature to 0 C resulted in slightly improved dr and ee
catalytic asymmetric dearomatizaiton of electron-deficient values (Table 1, entry 10). Ultimately, a set of excellent results
nitroheteroarenes only via one-step Michael addition process. (99% yield, 97:3 dr and 96% ee) could be obtained by further
o
Herein, we report our successful study on the reaction with a reducing the reaction temperature to -20 C (Table 1, entry
multiple hydrogen-bonding bifunctional-thiourea catalyst, 11).
affording optically enriched 3,3'-disubstituted oxindoles
Table 2. Substrate scope of 2-nitrobenzofurans and 3-pyrrolyl-
bearing three contiguous stereocenters including one
quaternary and two tertiary stereogenic centers (Scheme 1, c),
oxindolesa
R1
and on the further exploration for the potentially promising
application of the products in medicinal chemistry.
R1
N
R3
R3
N
O
D
(10 mol %)
xylene, -20 o
NO2
+
O
H
C
O
O
NO
2
N
R2
N
R2
Table 1. Optimization of reaction conditionsa
1
2
3
, R2 = Me, R3 = H;
, R2 = allyl, R3 = H;
, R2 = Me, R3 = 6-Cl;
, R2 = Et, R3 = H;
, R2 = Me, R3 = 5-F;
, R2 = Me, R3 =7-Cl;
, R2 = Bn, R3 = H
, R2 = Me, R3 =5-Cl
, R2 = Me, R3 = 5-Br
2a
2d
2g
2j
2b
2e
2h
2c
2f
N
N
2i
O
, R2 = Me, R3 =5-Me
A-D
(10 mol %)
NO2
O
+
H
O
O
N
NO2
solvent, r.t., time
N
Me
2a
entry
R1 (1)
2
time
(h)
3/yield
drc
ee
1a
Me
3a
(%)b
(%)d
CF3
CF3
S
CF3
S
O
N
N
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
5-F (1b)
7-F (1c)
5-Cl (1d)
5-Br (1e)
6-Br (1f)
7-Br (1g)
5-NO2 (1h)
5-Me (1i)
6-Me (1j)
5-OMe (1k)
5-But (1l)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
40
40
38
38
45
39
24
48
48
90
45
35
66
66
90
40
40
45
40
40
66
3b/92
3c/91
3d/99
3e/95
3f/99
3g/91
3h/99
3i/99
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
17:1
95
88
95
96
95
87
90
96
96
93
95
91
89
91
86
93
92
95
90
92
95
N
N
H
H
NH
N
NH
H
H
H
MeO
CF3
MeO
N
B
A
N
CF3
CF3
CF3
CF3
Bn
S
Bn
S
O
O
N
N
N
N
H
N
N
H
N
H
H
NH
NH
H
H
MeO
C
D
N
3j/99
3k/97
3l/99
entry
A-D
solvent
time (h) yield (%)b
drc
ee (%)c
1
2
3
4
5
6
7
8
9
A
B
C
toluene
toluene
toluene
toluene
CH2Cl2
CHCl3
xylene
mesitylene
MTBE
xylene
24
16
15
15
20
18
18
20
48
28
40
89
97
98
99
82
87
98
99
84
99
99
89:11
82:18
88:12
91:9
89:11
88:12
92:8
90:10
92:8
96:4
52
76
79
87
86
83
89
86
90
94
96
5,7-Br2 (1m) 2a
3m/92
3n/92
3o/89
3p/97
3q/98
3r/99
3s/98
3t/97
3u/95
3v/98
1a
1a
1a
1a
1a
1a
1a
1a
1a
2b
2c
2d
2e
2f
2g
2h
2i
D
D
D
D
D
D
D
D
13:1
10:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
10d
11e
xylene
97:3
2j
aUnless otherwise noted, the reactions were carried out with 1a (0.12 mmol), 2a
(0.1 mmol), and 10 mol % catalyst in 1.0 mL of solvent at room temperature.
bIsolated yields. cDetermined by chiral HPLC analysis. dRun at 0 oC. eRun at -20 oC.
MTBE = methyl tert-butyl ether.
aThe reactions were carried out with 1 (0.12 mmol), 2 (0.1 mmol), and 10 mol %
catalyst D in 1.0 mL of xylene at -20 oC for the specified time. bIsolated yields.
cDetermined by 1H NMR. dDetermined by chiral HPLC analysis.
Having identified the optimal reaction conditions, the
scope and limitation of the asymmetric dearomative Michael
addition was explored (Table 2). As for 2-nitrobenzofurans, the
first obvious scenario is that only one stereoisomer (>20:1 dr)
was formed among all the cases examined (Table 2, entries 1-
12). Diverse electron-withdrawing substituents, such as F-, Cl-,
Initially, the reaction of 2-nitrobenzofuran 1a and 3-
pyrrolyl-oxindole 2a in toluene at room temperature was
selected as the model reaction for optimizing conditions (Table
1). To our delight, with 10 mol % quinine-derived thiourea A as
the catalyst, the expected dearomative Michael addition
product 3a could be obtained in 89% yield with 89:11 dr, albeit Br-, and NO2-, regardless of their positions in the phenyl ring of
2-nitrobenzofurans, were well tolerated in the dearomative
Michael addition reaction with 2a, providing products 3b-h in
high to excellent yields with 87-96% ee values (entries 1-7).
Meanwhile, electron-donating groups, such as Me-, MeO- and
tBu-, were also compatible with the developed reaction
conditions, leading to the formation of 3i-l in 96-99% yields
with 93-96% ee (entries 8-11). Additionally, the reactivity and
stereoselectivity were hardly affected by the incorporation of
doubly substituents on the aromatic ring, just as 3m was
with 52% ee (Table 1, entry 1). The optimization was then
continued with some other multiple hydrogen-bonding
thiourea catalysts B-D. It was found that catalysts B and C
derived respectively from quinine with L-valine and L-
phenylalanine, could efficiently promote the dearomative
Michael addition reaction and furnish 3a in quantitative yield
with moderate dr and good ee (Table 1, entry 2-3). More
delightfully, catalyst D derived from cinchonidine and L-
phenylalanine could give 3a in 99% yield with 91:9 dr and high
2 | J. Name., 2012, 00, 1-3
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obtained in 92% yield with 91% ee (entry 12). On the other
hand, the nucleophiles 3-pyrrolyl-oxindole substrates were
further investigated (Table 2, entries 13-21). The ethyl, benzyl,
and allyl group in the N1-position are well tolerated, affording
3n-p in 89-97 yields with high to excellent dr and 86-91% ee
(entries 13-15). Substrates bearing electron-withdrawing
substituents such as F- and Br- at the C5-position of the 3-
pyrrolyl-oxindole were able to furnish their corresponding
products 3q and 3u in acceptable results (entries 16-17).
Nevertheless, chloric substituent at the C5, C6, and C7-
positions is well tolerated, generating products 3r-t in almost
quantitative yield with excellent dr and ee values (entries 18-
20). Additionally, electron-donating group such as methyl
group on the C5-position of oxindole skeleton had no effect on
the reactivity and stereoselectivity (entry 21). The absolute
and relative configuration of product 3d was determined to be
(C2S, C10S, C11R) by single crystal X-ray analysis.12,13
reaction of 1a and 2a was carried out on a gram scViaewleA,rtwiclheiOcnhlinies
23 times larger than the scale of the model reaction. As
DOI: 10.1039/C9CC09939E
showed in Scheme 3, under the standard conditions, 3a could
be smoothly obtained in almost quantitative yield and no any
loss in the dr and ee values, even with only 5 mol % catalyst
loading. This gram-scale experiment suggests that the
developed catalyst system has good scalability and the
potential value in organic synthesis.
Scheme 3 Gram-scale experiment.
N
N
O
D
(5 mol %)
NO2
+
xylene, -20 o
84 h
C
O
O
H
O
NO2
N
Me
N
Me
1a
3.6 mmol, 0.587 g
3a
2a
3.0 mmol, 0.636 g
1.12 g, 99% yield
>20:1 dr, 97% ee
With the successful generation of divers optically pure
3,3'-disubstituted oxindoles bearing chiral 2-nitro-2,3-
dihydrobenzofuran substructures (Table 2), we finally
attempted to identify the potential bioactivity of these
compounds. Some randomly selected compounds were
subjected to in vitro cytotoxicity test against different human
cancer cells, including K562 leukemia cells, A549 lung cancer
cells, and PC-3 prostate cancer cells.14 The preliminary results
revealed that all of the tested 12 compounds exhibited
cytotoxicity against the cell lines of K562, A549, and PC-3 with
IC50 values in the micromolar range (see Supporting
Information).15 Particularly, compound 3c, 3j, and 3k showed
impressive cytotoxicity to the K562 leukemia cells and A549
lung cancer cells with promising IC50 values (Scheme 4).
Meanwhile, to the PC-3 prostate cancer cells, compounds 3h,
3r, and 3v showed significant cytotoxicity with IC50 values in
the low micromolar range, even lower than that of
commercially available broad-spectrum anticancer drug
cisplatin as a positive control. These results suggest that this
type of 3,3'-disubstituted oxindole derivatives might be
promising in medicinal applications after further structural
modulation and biological investigations.
Scheme 2 Substrate scope of other 3-substituted oxindoles
with 2-nibenzofuran.a
R4
R4
O
D
(10 mol %)
O
+
NO2
xylene, -20 o
C
H
N
NO2
O
O
R5
4
N
R5
1a
5
EtO2C
nPr
Et
O
Me
O
O
O
H
O
H
O
H
O
H
O
NO2
NO2
NO2
NO2
N
N
N
N
CO2Me
5d, 12 h,70% yield
16:1 dr, 94% ee
CO2Me
, 12 h, 99% yield
13:1 drc, 95% eed
CO2Et
, 12 h,94% yield
10:1 dr, 94% ee
CO2Et
5c
, 12 h,95% yield
>20:1 dr, 94% ee
b
5a
5b
R
Bn
Ph
O
O
O
O
H
H
H
O
H
O
NO2
NO2
NO2
NO2
O
N
O
N
N
N
Me
CO2Me
Ac
CO2Et
5ee
5fe
5ge
R = OH, NHCHO, Br
n.r.
, 60 h, 82% yield
3:1 dr, 34% ee
, 72 h, 80% yield
10:1 dr, 71% ee
, 72 h, 50% yield
>20:1 dr, 0 ee
aUnless otherwise noted, the reactions were carried out with 1a (0.12
mmol), 4 (0.1 mmol), and 10 mol % catalyst D in 1.0 mL of xylene at -20 oC
for the specified time. bIsolated yields. cDetermined by 1H NMR.
dDetermined by chiral HPLC analysis. eRun for at rt.
Encouraged by the remarkable results of the above reactions,
we continued our attempt to investigate the dearomative Michael
addition reaction of 2-nitrobenzofuran 1a with other 3-
monosubstituted oxindoles (Scheme 2). Under the standard
reaction conditions, different substituents at C-3 position of 3-
monosubstituted oxindoles such as methyl, ethyl and propyl, were
found to be suitable for the transformation, generating products
5a-c in quantitative yields with excellent enantioselectivities. In
addition, ethyl ester substituted oxindole also could react with 1a,
providing dearomative Michael adduct 5d in 70% yield, with 16:1 dr
and 94% ee. As for 3-allyl oxindole and 3-benzyl oxindole, due to
their low reactivity, the reactions run at room temperature,
delivering the corresponding products 5e and 5f in good yields with
34% and 71% ee, respectively. In addition, 3-aryl oxindoles reacted
with 1a and provided the desired 5g in moderate yield with
excellent dr but in the racemate. Disappointedly 3-hetero-
substitution, such as 3-hydroxyoxindole, 3-formylaminooxindole
and 3-bromooxindole, was able to entirely inhibit the reaction with
1a.
Scheme 4 Biological activities evaluation
Me
MeO
F
N
N
O
O
N
O
H
O
H
O
H
O
NO2
NO2
NO2
N
N
N
Me
3k
Me
3c
Me
3j
IC50 = 13.04 M
IC50 = 10.36 M
IC50 9.04 M
IC50 = 14.78 M
IC50 = 12.04 M
to K562
to A549
IC50 = 10.14 M
=
O2N
Me
N
N
O
O Cl
NO2
N
O
H
O
H
O
H
O
NO2
NO2
N
N
N
Me
3v
Me
3h
Me
3r
IC50 = 8.52 M
IC50 = 12.80 M
IC50 = 9.33 M
to PC-3
In summary, an efficient asymmetric dearomatization of
2-nitrobenzofurans was accomplished by using chiral
a
multiple hydrogen-bonding thiourea as the catalyst only via
one-step Michael addition process. With the developed
protocol, a range of structurally diverse 3,3′-disubstituted
oxindoles, bearing three contiguous stereocenters including
In order to demonstrate the potential applicability of the
catalytic asymmetric dearomative Michael addition, the
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Liang H.-Y. Niu, D.-C. Wang, X.-H. Yang, G.-R. Qu and H.-M.
one quaternary and two tertiary stereogenic centers, could be
smoothly obtained in excellent results (up to 99% yield, >20:1
dr and 96% ee) under mild conditions. These products are
featured with an intriguing combination of two privileged
motifs including 3-pyrrolyl-substituted-oxindoles and 2,3-
dihydrobenzofurans substructures. This work represents the
first example of catalytic asymmetric dearomatizaiton of
electron-deficient nitroheteroarenes via a single reaction
View Article Online
Guo, Chem. Commun., 2019, 55, 553;D(dO)I:J1.0-Q.10. 3Z9h/aCo9,CYC.09Y9a3n9gE,
X.-J. Zhou, Y. You, Z.-H. Wang, M.-Q. Zhou, X.-M. Zhang, X.-Y.
Xu and W.-C. Yuan, Org. Lett., 2019, 21, 660; (e) X.-J. Zhou, J.-
Q. Zhao, X.-M. Chen, J.-R. Zhuo, Y.-P. Zhang, Y.-Z. Chen, X.-M.
Zhang, X.-Y. Xu and W.-C. Yuan, J. Org. Chem., 2019, 84,
4381; (f) X.-H. Yang, J.-P. Li, D.-C.Wang, M.-S. Xie, G.-R. Qu
and H.-M. Guo, Chem. Commun., 2019, 55, 9144.
7. D.-F. Yue, J.-Q. Zhao, Y.-Z. Chen, X.-M. Zhang, X.-Y. Xu and
W.-C. Yuan, Adv. Synth. Catal., 2018, 360, 1420.
8. For recent review, see: Z. Chen, M. Pitchakuntal and Y. Jia,
Nat. Prod. Rep., 2019, 36, 666.
process. Importantly,
a preliminary biological evaluation
indicated the products have moderate to good cytotoxicity in
vitro against different human cancer cells. Further exploration
on the catalytic asymmetric dearomatization of electron-
deficient heteroarenes for the construction of more
interesting molecules is currently underway.
We are grateful for financial support from the National
NSFC (21572223, 21871252, and 21901024), the National Key
R&D Program of China (2018YFC0807301-3), the Project of
Youth Science and Technology Innovation Team of Sichuan
Province (2016TD0027).
9. For selected reviews, see: (a) Y.-L. Liu and J. Zhou, Adv.
Synth. Catal., 2010, 352, 1381; (b) K. Shen, X. Liu, L. Lin and
X. Feng, Chem. Sci., 2012, 3, 327; (c) R. Rios, Chem. Soc. Rev.,
2012, 41, 1060; (d) R. Dalpozzo, G. Bartoli and G. Bencivenni,
Chem. Soc. Rev., 2012, 41, 7247; (e) L. Hong and R. Wang,
Adv. Synth. Catal., 2013, 355, 1023; (f) D. Cheng, Y. Ishihara,
B. Tan and C. F. Barbas III, ACS Catal., 2014, 4, 743; (g) J.-S.
Yu, F. Zhou, Y.-L. Liu and J. Zhou, Synlett, 2015, 26, 2491; (h) J.
Kaur, S. S. Chimni, S. Mahajan and A. Kumar, RSC Adv.,
2015,5, 52481; (i) G.-J. Mei and F. Shi, Chem. Commun. 2018,
54, 6607; (j) Y. C. Zhang, F. Jiang and F. Shi, Acc. Chem. Res.,
2019, 10.1021/acs.accounts.9b00549. For selected relevant
examples about the synthesis of chiral nitrogenous
heterocycles including oxindoles, see: (k) L.-J. Zhou, Y.-C.
Zhang, F. Jiang, G. He, J. Yan, H. Lu, S. Zhang and F. Shi, Adv.
Synth. Catal., 2016, 358, 3069; (l) W. Guo, Y. Liu and C. Li,
Org. Lett., 2017, 19, 1044; (m) C. Ma, J.-Y. Zhou, Y.-Z. Zhang,
G.-J. Mei and F. Shi, Angew. Chem. Int. Ed., 2018, 57, 5398.
10. (a) B. S. Jensen, CNS Drug Rev., 2002, 8, 353; (b) C. V.
Galliford and K. A. Scheidt, Angew. Chem., Int. Ed., 2007, 46,
8748; (c) J. J. Badillo, N. V. Hanhan and A. K. Franz, Curr.
Opin. Drug Discovery Dev., 2010, 13, 758; (d) G. S. Singh and
Z. Y. Desta, Chem. Rev., 2012, 112, 6104; (e) T. L. Pavlovska,
R. Redkin, V. V. Lipson and D. V. Atamanuk, Mol. Diversity,
2016, 20, 299.
Notes and references
1. For selected reviews on the catalytic asymmetric
dearomatization reactions, see: (a) C.-X. Zhuo, W. Zhang and
S.-L. You, Angew. Chem., Int. Ed., 2012, 51, 12662; (b) C.-X.
Zhuo, C. Zheng, S.-L. You, Acc. Chem. Res., 2014, 47, 2558; (c)
W.-T. Wu, L. Zhang and S.-L. You, Chem. Soc. Rev. 2016, 45,
1570; (e) W.-T. Wu, L. Zhang and S.-L. You, Acta Chim.
Sinica., 2017, 75, 419; (d) G. Huang and B. Yin, Adv. Synth.
Catal., 2019, 361, 405.
2. For selected recent examples, see: (a) Z.-P. Yang, C. Zheng, L.
Huang, C. Qian and S.-L. You, Angew. Chem. Int. Ed., 2017,
56, 1530; (b) L.-W. Feng, H. Ren, H. Xiong, P. Wang, L. Wang
and Y. Tang, Angew. Chem. Int. Ed., 2017, 56, 3055; (c) F.
Jiang, D. Zhao, X. Yang, F.-R. Yuan, G.-J. Mei and F. Shi, ACS
Catal., 2017, 7, 6984; (d) H.-F. Tu, C. Zheng, R.-Q. Xu, X.-J. Liu
and S.-L. You, Angew. Chem. Int. Ed., 2017, 56, 3237; (e) M.-
C. Zhang, D.-C. Wang, M.-S. Xie, G.-R. Qu, H.-M. Guo and S.-L.
You, Chem., 2019, 15, 156.
3. For selected examples, see: (a) I. Chataigner, S. R. Piettre,
Org. Lett., 2007, 9, 4159; (b) S. Lee, I. Chataigner, S. R.
Piettre, Angew. Chem. Int. Ed., 2011, 50, 472. (c) B. M. Trost,
V. Ehmke, B. M. O’Keefe and D. A. Bringley, J. Am. Chem.
Soc., 2014, 136, 8213.
4. J.-Q. Zhao, X.-J. Zhou, Y.-Z. Chen, X.-Y. Xu, X.-M. Zhang and
W.-C. Yuan, Adv. Synth. Catal., 2018, 360, 2482.
5. For selected examples see: (a) Awata, A.; Arai, T. Angew.
Chem. Int. Ed., 2014, 53, 10462; (b) J.-Q. Zhao, M.-Q. Zhou,
Z.-J. Wu, Z.-H. Wang, D.-F. Yue, X.-Y. Xu, X.-M. Zhang and W.-
C. Yuan, Org. Lett., 2015, 17, 2238; (c) J.-Q. Zhao, Z.-J. Wu,
M.-Q. Zhou, X.-Y. Xu, X.-M. Zhang and W.-C. Yuan, Org. Lett.,
2015, 17, 5020; (d) Y. Li, F. Tur, R. P. Nielsen, H. Jiang, F.
Jensen and K. A. Jørgensen, Angew. Chem. Int. Ed., 2016, 55,
1020; (e) D.-F. Yue, J.-Q. Zhao, X.-Z. Chen, Y. Zhou, X.-M.
Zhang, X. Y. Xu and W.-C. Yuan, Org. Lett., 2017, 19, 4508; (f)
Q. Cheng, F. Zhang, Y. Cai, Y.-L. Guo and S. L. You, Angew.
Chem. Int. Ed., 2018, 57, 2134; (g) H.-M. Wang, J.-Y. Zhang,
Y.-S. Tu and J.-L. Zhang, Angew. Chem. Int. Ed., 2019, 58,
5422; (h) K.-Z. Li, T. P. Gonçalves, K.-W. Huang and Y. Lu,
Angew. Chem. Int. Ed. 2019, 58, 5427; (i) X.-M. Chen, C.-W.
Lei, D.-F. Yue, J.-Q. Zhao, Z.-H. Wang, X.-M. Zhang, X.-Y. Xu
and W.-C. Yuan, Org. Lett., 2019, 21, 5452.
11. (a) B.-D. Cui, Y. You, J. -Q. Zhao, J. Zuo, Z. -J. Wu, X. -Y. Xu, X. -
M. Zhang and W. -C. Yuan, Chem. Commun., 2015, 51, 757;
(b) Y. You, Z.-J. Wu, J.-F. Chen, Z.-H. Wang, X.-Y. Xu, X.-M.
Zhang and W.-C. Yuan, J. Org. Chem., 2016, 81, 5759; (c) K.
Wang, L. Wang, X. Liu, D. Li, H. Zhu, P. Wang, Y. Liu, D. Yang
and R. Wang, Org. Lett., 2017, 19, 4351; (d) W.-T. Fan, N.-K.
Li, L. Xu, C. Qiao and X.-W. Wang, Org. Lett., 2017, 19, 6626;
(e) N.-K. Li, W.-T. Fan, J.-Q. Zhang, B.-B. Sun, J.-B. Chen and
X.-W. Wang, Chem. Commun., 2018, 54, 2260.
12. CCDC-1943699
(3d)
contains
the
supplementary
crystallographic data for this paper.
13. A possible activation mode to account for the
stereochemistry of the Michael addition process was
proposed, for the details see ESI.
14. (a) T. J. J. Mosmann, Immunol. Methods 1983, 65, 55; (b) M.
C. D. A. Alley, Scudiero, A. Monks, M. L. Hursey, M. J.
Czerwinski, D. L. Fine, B. J. Abbott, R. H. Shoemaker and M.
R. Boyd, Cancer Res. 1988, 48, 589.
15. For details on the biological activities evaluation, see ESI.
6. (a) Q. Cheng, H.-J. Zhang, W.-J. Yue and S.-L. You, Chem.,
2017, 3, 428; (b) J.-Q. Zhao, X.-J. Zhou, Y. Zhou, X.-Y. Xu, X.-
M. Zhang and W.-C. Yuan, Org. Lett. 2018, 20, 909; (c) L.
4 | J. Name., 2012, 00, 1-3
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