Copper-catalyzed regiodivergent 1,4-and 1,6-conjugate silyl addition to diendioates: Access to functionalized allylsilanes

Article abstract of DOI:10.1039/c9ob01086f

A copper-catalyzed regioselective 1,4-and 1,6-conjugate addition of a silyl reagent to diendioates was established. Various 1,4-and 1,6-protosilylation products were obtained in good yields and with high regioselectivity via tuning the ligands used in the reactions. This protocol has provided a simple and efficient method for the synthesis of multisubstituted functionalized allylsilanes.

Full text of DOI:10.1039/c9ob01086f

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DOI: 10.1039/C9OB01086F
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Copper-Catalyzed Regiodivergent 1,4- and 1,6-Conjugate Silyl
Addition to the Diendioates: Access to the Functionalized
Allylsilanes
Tanveer Ahmad,a Qi Li,a Sheng-Qi Qiu,a Jian-Lin Xu,a Yun-He Xu*,a and Teck-Peng Lohab
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Previous work:
A copper-catalyzed regioselective 1,4- and 1,6-conjugate
addition of silyl reagent to the diendioates was established.
Various 1,4- and 1,6-protosilylation products were obtained in
good yields and with high regioselectivity via tuning the
ligands used in the reactions. This protocol has provided a
simple and efficient method for the synthesis of
multisubstituted functionalized allylsilanes.
PhMe2Si-Bpin
[Cu]
O
R
O
R1
(1)
(2)
PhMe2Si
R1
R
R1 = H, Alkyl, aryl, alkoxy, alkylamino; R = aryl, alkyl
Hoveyda (2010), Cordova (2011), Santos (2012), Procter (2013), Kobayashi (2015)
PhMe2Si-Bpin
Me
O
Me
O
R
[Cu]
R1
PhMe2Si
R1
R
R1 = Alkyl, alkoxy, alkylthio; R= aryl, alkyl
Hoveyda (2012)
O
O
A regioselective conjugate addition to the diendioates with silyl
reagent is one of the most important C_Si bond forming
reactions for the synthesis of functionalized allylsilanes.1
Nevertheless, the improvement of practical and effective
procedures to the incorporation of silicon as a nucleophile at a
specific site in a substrate for the catalytic formation of C_Si
bonds is a highly desirable, owing to extensive applications in
the total synthesis of natural products, material chemistry and
pharmaceutical industry.2,3 In 1988, Hayashi elegantly
PhMe2Si-Bpin
[Cu]
SiMe2Ph
R
(3)
R
n
n
n = 1-3; R = aryl
Hoveyda (2010, 2012) Kobayashi (2015)
This work:
6
4
SiPhMe2
SiPhMe2
CO2R1
PhMe2Si-Bpin
[Cu]
PhMe2Si-Bpin
CO2R1
R1O2C
R
[Cu]
R
R
CO2R1
CO2R1
CO2R1
Scheme 1. Reported reactions of silyl addition to unsaturated
carbonyls compounds
developed a palladium-catalyzed 1,4-disilylation reaction of α,β-
4
unsaturated ketones with using disilane reagent
Suginome’s silylboron reagent
.
After that,
dimethylphenylsilyl
pinacolatoboronate (PhMe2Si-Bpin)5 has introduced a new
strategy for the silyl conjugate additions. Oestreich,5d,6
Hoveyda,7 Córdova,8a Procter,8 Santos9 and Kobayashi10 have
successfully established the 1,4-conjugate addition by using
Me2PhSi-B(pin) to synthesize the organosilicon compounds
(Scheme 1, eq. 1).11,5d On the other hand, Hoveyda7a,7c and
Kobayashi10a et al. have explored the asymmetric silyl 1,6-conjugate
addition to the cyclic α,β,γ,δ-unsaturated dienones and also a single
example of 1,6-conjugate addition to the acyclic α,β,γ,δ-unsaturated
dienones7c with the locked β-position (Scheme 1, eq. 2 and 3).
Despite the final products with allylsilane fragments having
been accessed in these protocols, there are still some problems
for an evaluation of substrate scope and reaction type which
demands more practical and efficient methodologies to expand
the diversity of the products related to functionalities.10,7a,7c To
the best of our knowledge, there is no study disclosed on
regiodivergent 1,4- and 1,6-silyl conjugate addition to the
α,β,γ,δ-unsaturated diendioates. The key challenge for silyl
conjugate addition is mainly control of regioselectivity. In
continuation of our interest in C-Si bond formation,12 herein, we
reported a copper-catalyzed highly regioselective 1,4- and 1,6-
protosilylation of Diethyl (E)-2-(3-phenylallylidene)malonate to
access 1,4- and 1,6-protosilylation of diendioates compounds
under mild reaction conditions.
We initially examined the reaction of diethyl-(E)-2-(3-
phenylallylidene)malonate 1a and Me2PhSi-B(pin) 2a as shown
in Chart 1. We first employed 10 mol% CuCN, 20 mol% LiOtBu in
acetonitrile at 30 °C for 24 h under argon atmosphere. The
a. Department of Chemistry, University of Science and Technology of China, Hefei,
China, 230026.
target
diethyl
(E)-2-(1-(dimethyl(phenyl)silyl)-3-
phenylallyl)malonate 3a as the major product with poor
regioselective ratio (r.r.) (3a:4a = 64:36) could be isolated in a
low yield (44%) (Chart 1, entry 1). Therefore, t-butyl-2,2′-
bipyridine (L1) as ligands with strong coordinating-ability were
introduced to this catalytic system, the yield was increased up
to 69% (Chart 1, entry 2).
b. Division of Chemistry and Biological Chemistry, School of Physical and
Mathematical Sciences, Nanyang Technological University, Singapore 637371.
E-Mail: xyh0709@ustc.edu.cn
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
This journal is © The Royal Society of Chemistry 2019
Org. Biomol. Chem.
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Chart 1. Optimization of reaction conditions for 1,4- and 1,6- experiments showed that both the copper catalysVtieawnAdrtiLc3lewOnelirnee
additiona,b
crucial to afford the target product with better result.
DOI: 10.1039/C9OB01086F
2a)
PhMe2Si-Bpin (
SiPhMe2
SiPhMe2
CO2Et
After finishing the optimization of the reaction conditions,
we next explored the generality of different ester groups
containing substrates in Chart 2. The substrates with different
ester groups (1a-1e) were tested to react with Me2PhSi-B(pin)
(2a) respectively, under the optimal reaction condition. It was
noted that the ethyl ester substrate (1a) was the best choice in
term of regioselectivity and yield (Chart 2).
CuCN (10 mol%)
base (X mol%)
CO2Et
CO2Et
CO2Et
+
CO2Et
CO2Et
ligands (X mol%)
4a
3a
solvent, 30 oC, 24 h
1a
entry
cat. (10 mol %) base (X mol %) ligand (X mol %)
-
solvent
r.r. (3a:4a)c
yield (%)d
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
LiOtBu (20)
LiOtBu (20)
LiOtBu (20)
LiOtBu (20)
Pyridine (20)
DIPEA (20)
TMP (20)
TMP (20)
TMP (20)
TMP (20)
TMP (20)
LiOtBu (10)
LiOtBu (10)
LiOtBu (10)
KOAC (10)
DIPEA (10)
Pyridine (10)
TMP (10)
TMP (10)
TMP (10)
-
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
nBuOH
THF
64:36
72:28
65:35
80:20
90:10
81:19
92:08
68:32
80:20
86:14
82:18
40:60
24:76
20:80
20:80
19:81
18:78
14:86
19:81
21:79
26:74
35:65
44(3a)
69(3a)
62(3a)
78(3a)
80(3a)
78(3a)
86(3a)
63(3a)
76(3a)
82(3a)
80(3a)
36(4a)
68(4a)
72(4a)
70(4a)
78(4a)
74(4a)
82(4a)
73(4a)
67(4a)
63(4a)
42(4a)
1
L1 (12)
L2 (12)
L3 (12)
L3 (12)
L3 (12)
2
3
4
5
6
Chart 2. Screening of different ester group for the 1,4-
L3
(12)
7
protosilylationa
L3 (12)
L3 (12)
L3 (12)
L3 (12)
-
8
2a)
PhMe2Si-Bpin (
SiPhMe2
SiPhMe2
CO2R1
9
CO2R1
CuCN (10 mol%)
L3 (12 mol%)
CO2R1
CO2R1
10
11
12
13
14
15
16
17
18
19
20
21
22
+
CO2R1
CO2R1
DCM
TMP (20 mol%)
4
3
1
MeCN, 30 oC, 24 h
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
Et3OH
,
R1 = Et
R1 = Me
R1 = iPr
,
R1 = Et, 86%d
( : = 92:8)
3a 4a
c
1a
3a
L4 (14)
L5 (14)
L5 (14)
L5 (14)
L5 (14)
L5 (14)
L5 (14)
L5 (14)
L5 (14)
-
,
,
,
R1 = Me, 82%d
(
:
= 90:10)
c
1b
1c
3b
3b 4b
,
R1
R1
R1
=
=
=
iPr, 78%d
(
c
3c
3c 4c
: = 87:13)
,
,
R1
R1
=
=
nBu
tBu
,
nBu, 80%d
tBu, 70%d
c
1d
3d
3e
3d 4d
( : = 88:12)
c
1e
3e 4e
: = 84:16)
,
(
Chart 3. Substrate scope for the 1,4-protosilylation of
nBuOH
CH3OH
CH3OH
diendioatesa
PhMe2Si-Bpin (2a)
SiPhMe2
CO2Et
SiPhMe2
CuCN (10 mol %)
L3 (12 mol %)
TMP (10)
CO2Et
CO2Et
CO2Et
+
O O
TMP (20 mol %)
CO2Et
CO2Et
MeCN, 30 oC, 24 h
H
tBu
tBu
P
3a
4a
1a 1v
-
P
BF4
PH
O
BF4
O
O
O
R
R
=
H, 3a, 86%d (3a:4a
=
=
(92:8)c R = 4-Cl, 3k, 88%d (3k:4k = 93:7)c
P
P
O
Cy
Cy Cy
L4
Cy
N
N
=
4-Me,
,
81%d
d
90:10)c
c
R = 4-Br, 3l, 82%d (3l:4l = 94:6)c
3f
3f:4f
(
SiPhMe2
CO2Et
L1
L2
L3
L5
3g
3g:4g
= 89:11)
R = 4-CN, 3m, 80%d (3m:4m = 88:12)c
R = 2-Me,
, 78%
(
aReaction was performed according to following conditions: the
mixture of 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv), CuCN (0.02
mmol, 0.1 equiv), L3 (0.024 mmol, 0.12 equiv), TMP (0.04 mmol,
0.2 equiv), and in MeCN (1 mL) under argon atmosphere (1 atm)
R = 4-OMe 3h, 79%d (3h:4h = 88:12)c R = 4-NO2, 3n, 71%d (3n:4n = 81:19)c
R
CO2Et
R = 2-OMe, , 74%
(
= 85:15)
c
R = 4-CF3, 3o, 78%d (3o:4o = 85:15)c
R = 4-Ph, 3p, 81%d (3p:4p = 90:10)c
d
c
3i
3i:4i
d
3j
R = 4-F, , 84%
3j:4j
= 92:8)
(
SiPhMe2
SiPhMe2
SiPhMe2
SiPhMe2
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
b
CO2Et
CO2Et
d
was stirred at 30 °C for 24 h (entries, 1-11). L5 (0.028 mmol,
d
d
d
3q
3q:4q
, 84%
3t
, 79%
3s
, 72%
3r
, 76%
c
0.14 equiv), TMP (0.02 mmol, 0.1 equiv), and in MeOH (1 mL)
under argon atmosphere (1 atm) (entries, 12-22).
cRegioselectivity ratio (r.r.) (3a:4a) was confirmed by the crude
1H NMR. dIsolated yields for 1,4- and 1,6-protosilylation adduct.
c
3t:4t
(
= 88:12)
(
= 91:9)
SiPhMe2
CO2Et
SiPhMe2
CO2Et
S
O
CO2Et
d
CO2Et
d
3u
3u:4u
, 80%
3v
, 79%
c
c
3v:4v
= 91:9)
(
= 90:10)
(
aReaction conditions: Unless otherwise specified, the reactions
were performed with 1 (0.2 mmol), 2a (0.3 mmol, 1.5 equiv),
CuCN (0.02 mmol, 0.1 equiv), L3 (0.024 mmol, 0.12 equiv), TMP
(0.04 mmol, 0.2 equiv), and Ar (1 atm) in MeCN (1 mL) at 30 °C
When tri-t-butylphosphonium tetrafluoroborate (L2) was used
in this system, the yield was slightly decreased to 62% (Chart 1,
entry 3). Pleasingly, when tricyclohexylphosphonium
tetrafluoroborate (L3) was applied in this reaction, the desired
product 3a could be obtained in good yield 78% and with an
improved r.r., (3a:4a = 80:20) (Chart 1, entry 4). The reaction
conditions were further optimized by different copper salts. It
was found that both Cu(I) and Cu(II) salts could catalyze this 1,4-
protosilylation reaction and afford the product 3a in moderate
to good yield under the basic condition (please see the details
in the Supporting Information). Considering the operation and
efficiency, copper(I) cyanide was chosen as a good catalyst.
After screening of different organic bases, the desired product
3a was obtained in a 86% yield in the presence of 20 mol%
2,2,6,6-tetramethylpiperidine (TMP) (Chart 1, entry 5-7).
Finally, extensive screening of solvents were performed, the
product 3a was obtained in moderate to good yield in MeOH,
nBuOH, THF, and DCM respectively (Chart 1, entry 8-11). It is
worth noting that acetonitrile was an effective solvent
comparing with other solvents (Chart 1, entry 7). The controlled
c
for 24 h. r.r., (3:4) was confirmed by the crude 1H NMR.
dIsolated yields.
Having determined the optimized reaction conditions, we
examined the substrate scope of the various diendioates with
Me2PhSi-B(pin) (2a), and the results were summarized in Chart
3. Notably, the steric and electronic effects of different
substituents on the phenyl ring were investigated. It was
observed that whatever the electron-withdrawing or the
electron-donating group substituted substrates all could afford
the desired products in high yields (Chart 3, 3f-3p). Various
functionalities such as halides (fluoro, chloro and bromo),
cyano, nitro, and trifluoromethyl were all well tolerated in this
reaction (3j-3o). Additionally, the naphthyl substituted
substrate also provided the corresponding product in good yield
(Chart 3, 3q). Moreover, the tert-butyl and dimethyl substituted
Org. Biomol. Chem.
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diendioates could furnish the desired products with solo Chart 5. Substrate scope for the 1,6-protosilylation of
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regioselectivity (3r and 3s). Finally, the substrates containing diendioatesb
DOI: 10.1039/C9OB01086F
2a)
PhMe2Si-Bpin (
heterocycles (thienyl and furyl) and cyclohexyl group were also
compatible to afford the desired product in good yield (Chart 3,
3t-3v).
CuCN (10 mol%)
L5 (14 mol%)
MeOH, 30 oC, 24 h
TMP (10 mol%)
SiPhMe2
SiPhMe2
CO2Et
CO2Et
CO2Et
+
CO2Et
CO2Et
1a-1v
CO2Et
4a
3a
82%d
(
:
=
86:14)c
d
c
4a
4a 3a
R
R
=
=
H,
,
4k
4k 3k
:
R = 4-Cl, , 70%
(
= 80:20)
In the course of screening the reaction conditions for the
synthesis of 1,4-protosilylation product 3a, the 1,6-
protosilylation product 4a was also observed (Chart 1). Because
it is another kind of functionalized allylsilane product, we tried
to optimize the reaction to improve its yield. When the bulky
phosphine ligands (L4) were used to this system, the r.r. value
was improved significantly (Chart 1, entry 13). Hence, we
assumed that increasing the steric hindrance around the copper
center could regulate the product’s regioselectivity. When the
more bulky tris(2,6-dimethoxyphenyl)phosphane (L5) was
added in this reaction, the target product 4a could be generated
with good regioselectivity (4a:3a = 80:20). (Chart 1, entry 14).
Subsequently, we tried different copper salts, bases, and
solvents. It was found that MeOH could furnish the 1,6-
protosilylation product in 82% isolated yield (Chart 1, entry 18).
The controlled experiments displayed that both the base and
ligand used in reaction were crucial to control the
regioselectivity of product (Chart 1, entries 21 and 22).
c
64%d
(
:
= 78:22)
SiPhMe2
4f
4-Me,
,
75%d
(
:
84:16)c
4f 3f
=
4l
4l 3l
R = 4-Br,
,
CO2Et
d
c
c
78%e
(
4g
4g 3g
:
R = 2-Me,
, 64%
(
= 75:25)
4m,
4m 3m
: = 87:13)
R = 4-CN,
R
e
c
CO2Et
d
c
4h
4h 3h
R = 4-OMe, , 76%
(
:
= 90:10)
4o
4o 3o
( : = 72:28)
R = 4-CF3, , 67%
e
d
c
4i
4i 3i
R = 2-OMe, , 70%
(
:
= 65:35)c
4p
R = 4-Ph, , 70%
4p 3p
( : = 84:16)
d
c
4j
R = 4-F, , 72%
4j 3j
:
(
= 85:15)
SiPhMe2
SiPhMe2
SiPhMe2
SiPhMe2
CO2Et
CO2Et
CO2Et
CO2Et
O
S
CO2Et
CO2Et
CO2Et
CO2Et
e
e
e
e
4q
, 80%
4t
4u,
4v
, 80%
, 79%
83%
c
c
c
c
4q 3q
:
(
= 81:19)
4t 3t
4u 3u
4v 3v
: = 60:40)
(
:
= 80:20)
(
:
= 60:40)
(
bReaction conditions: Unless otherwise specified, the reactions
were performed with 1 (0.2 mmol), 2a (0.3 mmol, 1.5 equiv),
CuCN (0.02 mmol, 0.1 equiv), L5 (0.028 mmol, 0.14 equiv), TMP
(0.02 mmol, 0.1 equiv), in MeOH (1 mL) under argon
atmosphere (1 atm) at 30 °C for 24 h. cr.r., (4:3) was confirmed
1
d
e
by the crude H NMR. Isolated yields. Isolated yield of the
mixture of 3 and 4.
Finally, the synthetic utilities of products (3a) were depicted
in Chart 6. Notably, the compound 3a was achieved by the gram
scaled synthesis in 79% isolated yield (1.46 g). When it was
reduced by DIBAL-H in DCM, the 1,3-diol product 5 was
obtained in good yield (70%).13a In addition, when the
compound 3a was treated with K2CO3 in DMF, the desilylation
product diethyl 2-cinnamylmalonate 6 was obtained in 65%
yield which was difficult to prepare by the traditional
method.13b The compound 3a was reacted with TBAT in THF and
using CO2 as electrophile to afford the tricarboxylate product 7
in 58 % yield.12d
Furthermore, different ester groups containing substrates
were also subjected to 1,6-protosilylation, and the results were
summarized in Chart 4. It was found that the ethyl containing
ester substrate 1a reacted efficiently in term of regioselectivity
and yield (Chart 4).
Under the developed reaction conditions, different α,β,γ,δ-
unsaturated diendioates with substituents on the phenyl ring
were examined. All performed well in this catalytic system to
give the corresponding products in moderate to good yield
(Chart 5, 4f-4P). It was observed that the steric effect of the
substituents on the phenyl ring would result a slightly decreased
r.r., of product (Chart 5, 4g and 4i). Similarly, the desired
products were obtained only in moderate yields and with
diminished r.r., values when the phenyl ring of the substrate
containing p-bromo or p-CF3 group (4l-4o). In addition, the
naphthyl and cyclohexyl group substituted substrates could
provide the corresponding products in good yields and
regioselectivities (Chart 5, 4q-4t). Finally, the thienyl and furyl
substituents were also compatible to give the desired products
in moderate yield (4u-4v). Unfortunately, in these two cases,
the regioselectivities of products were significantly decreased.
Chart 6. Transformation of 1,4-protosilylation product 3a.
SiPhMe2
DIBAL-H (4.0 equiv)
OH
5
DCM (0.2 M)
-78 °C to r.t, 12 h
OH
70%
SiPhMe2
CO2Et
CO2Et
K2CO3 (3 equiv)
DMF, 40 °C, 12 h
6
CO2Et
CO2Et
65%
3a
CO2Me
CO2Et
1) TBAT (1.1 equiv)
DMSO, 30 °C, CO2 ,16 h
79 %
7
2) CH3I (1.1 equiv)
CO2Et
58%
A plausible mechanistic pathway accounting for the Cu(I)-
catalyzed regioselective 1,4- and 1,6-conjugate addition was
proposed as depicted in Chart 7. In the presence of a copper
catalyst and base, a L-[Cu]-SiMe2Ph intermediate A would be
generated. Then, subsequent migratory insertion of the double
bond could furnish the intermediate ll or III selectively which
was probably controlled by ligand, solvent, and base utilized in
the reactions respectively. We proposed that the bulky ligand
mainly controlled the selectivity between 1,4- and 1,6-
conjugate addition. The more bulky ligand favor to the
formation of 1,6-conjugate addition product as shown in Chart
1 (entry 3 and 4, 13 and 14). Therefore, the more bulky L5 favors
Chart 4. Screening of different ester group for the 1,6-
protosilylation reactionb
2a)
PhMe2Si-Bpin (
SiPhMe2
SiPhMe2
CO2R1
CuCN (10 mol%)
L5 (14 mol%)
CO2R1
CO2R1
CO2R1
+
MeOH, 30 oC, 24 h
TMP (10 mol%)
CO2R1
CO2R1
4
3
1
R1 = Et
c
,
R1 = Et, 82%d
(
1a
,
4a
4a 3a
: = 86:14)
R1 = Me, 76%d
(
:
= 82:18)
,
R1 = Me
R1 = iPr
c
1b
1c
4b
4c
4b 3b
,
c
,
c 3c
:
,
R1 = iPr, 70%d (4
= 74:26)
,
,
R1
R1
=
=
nBu
tBu
c
1d
4d
4d 3d
:
,
,
R1
R1
=
=
nBu,72%d
tBu, 60%d
(
= 80:20)
c
1e
4e
4e 3e
:
(
= 70:30)
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Org. Biomol. Chem.
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Organic & Biomolecular Chemistry
Page 4 of 4
COMMUNICATION
Organic & Biomolecular Chemistry
Kako, T. Akasaka, K. Kobayashi, S. Nagase, J. Organomet.
the formation of 1,6-conjugate addition in Chart 6. On the other
hand, the less bulky L3 favors the formation of 1,4-conjugate
addition. After protonation, the desired products 3 and 4 would
be generated along with releasing the active copper catalyst for
the next catalytic cycle.
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Chart 7 Proposed mechanism
Cu/ L3 or L5
PhMe2Si-Bpin
Base
4
5
Base-Bpin
(L3 or L5)Cu-SiMe2Ph
1a
1a
A
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O
L3
Base-Bpin
O
O
PhMe2Si-Bpin
H-Base
R
OEt
OEt
Cu
OEt
PhMe2Si
PhMe2Si
Cu
O
III
OEt
H-Base
L5
R
-complex for
1,4-addition
II
-complex for
1,6-addition
Base-Cu(L3 or L5)
6
7
PhMe2Si
O
SiMe2Ph
O
O
R
OEt
OEt
R
OEt
OEt
O
3
4
Conclusions
In conclusion, we have established copper-catalyzed highly
regioselective 1,4- and 1,6-conjugate addition of silyl reagent to
the diendioates. The corresponding products were obtained in
moderate to good yields. The phosphine ligands proved to be
particularly efficient to obtain good regioselectivity of 1,4-
versus 1,6-conjugate addition to the diendioates. This work
provides a simple and general approach for the synthesis of
regioselective silylation products under mild reaction
conditions. Overall, the broad substrate scope can prove the
effective methodology for the regioselective formation of C-Si
bond.
8
9
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Conflicts of interest
“There are no conflicts to declare”.
Acknowledgments
We gratefully acknowledge the funding support of Anhui
Provincial Natural Science Foundation (1708085MB29), the
National Natural Science Foundation of China (21871240,
21672198), the Fundamental Research Funds for the Central
Universities (WK2060190082), and the State Key Program of
National Natural Science Foundation of China (21432009).
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Org. Biomol. Chem.
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