A copper/O2-mediated direct sp3 C-H/N-H cross-dehydrogen coupling reaction of acylated amines and: N -aryl glycine esters

Article abstract of DOI:10.1039/c8ob00176f

A copper salt-catalyzed cross-dehydrogenative coupling reaction between N-aryl glycine esters and acylated amines has been developed. The reaction proceeded effectively under an oxygen atmosphere without the use of peroxide agents. This simple protocol al

Full text of DOI:10.1039/c8ob00176f

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Copper/O2-mediated direct sp3 C-H/N-H cross-dehydrogen
coupling reaction of acylated amines and N-aryl glycine esters†
Received 00th January 20xx,
Accepted 00th January 20xx
Bin Sun,a Yao Wangb, Deyu Lib, Can Jin,*a,b and Weike Su*a,b
A copper salt-catalyzed cross-dehydrogenative coupling reaction between N-aryl glycine esters and acylated amines has
been devleloped. The reaction proceeded effectively under an oxygen atmosphere without the use of peroxide agents.
This simple protocol allows for the preparation of a series of new compounds in a moderate to excellent yield via the CDC
reaction of a wide range of N-aryl glycine derivatives with acylated amines, which are of great interest in the field of
medicinal chemistry. A plausible mechanism involing the forming of iminium ion intermediate, followed by coupling with
acylated amines was proposed after some control experiments were conducted.
DOI: 10.1039/x0xx00000x
www.rsc.org/
realized by Huo and co-authors.6 Very recently, Tang’s group
reported a novel CuCl/air-mediated oxidative cross coupling of
imidazoheterocycles with glycine esters.7c To the best of our
Introduction
In the past decades, the use of only C-H bonds to undergo the
oxidative coupling reaction to form C-C or C-X bonds has
become a new method due to it being atom economical and
environmentally friendly.1 Meanwhile, α-amino acids are the
key structural motifs of many natural products,
pharmaceuticals and biological molecules.2 For these reasons,
much attention has been paid to the direct cross coupling of α-
C(sp3)−H bonds adjacent to carbonyl group with different
nucleophiles for the synthesis of various α-substituted α-
amino acid derivatives. These reactions were mostly catalyzed
by iron or copper salts in combination with stoichiometric
chemical oxidants such as TBHP,3 DTBP,4 DDQ.5 For example, Li
and co-workers reported the first CDC reaction between N-
substituted glycine derivatives and alkynes under the catalysis
of copper salts.3a Subsequently, Huang’s group developed a
facile approach to N-aryl amino acid derivatives that involves
the coupling of N-aryl glycine esters with ketones under the
catalysis of copper salt.3b Hu et. al. developed another simple
method for functionalizing of glycine esters with ketones by
FeCl3 in the presence of DDQ.5
knowledge, the formation of C-C bonds via cross-dehydrogen
coupling of α-amino acid derivatives and other nucleophiles
has been reported largely. However, functionlizations of
C(sp3)-H bond leading to C-N formation has rarely been
researched. Huang’s group presented an efficient method for
C-N oxidative cross-coupling reaction via direct C(sp3)-H bond
functionalization of α-amino acid compounds with amines
using copper salts as catalyst.8 However, this transformation
could only furnish the product of 2-amino-2-iminocarbonyl and
2-amino-2-oxocarbonyl compounds, rather than the expected
diaminocarbonyl compounds [Scheme 1, eqn(1,2)], in which
the skeleton of glycine could not be maintained. Herein, we
describe a mild and efficient CDC reaction between N-aryl
glycine esters and various acylated amines for the synthesis of
α-amino α-amide acid esters with an excellent regioselectivity
in the presence of copper salts [Scheme 1, eqn(3)].
Pr evious work(Huang's group)
R1
O
H
N
N
R1
Cu(OAc)2, Et3N
CH2Cl2, air, r.t.
R2
R2
(1)
(2)
+
+
N
H
N
The use of oxygen rather than stoichiometric chemical
oxidants applied in oxidative cross-coupling of glycine
derivatives has gained significant progress in the past few
years.6-7 In 2014, an unprecedented aerobic auto-oxidative
cross-coupling reaction of glycine derivatives with indoles
without using any metal catalyst and chemical oxidant was
O
O
N
H
N
R1
R2
Cu(OAc)2, BPO
R2
O
DMSO, O2, 110 o
C
N
H
O
O
This work
O
H
O
N
R2
H
N
R2
CuCl/O2
O
O
O
R1
(3)
R1
+
H
N
CH3CN, 50 o
C
N
H
Scheme 1 The C-N bond formation via oxidative cross-coupling
of α-amino acids derivatives with amines or acylated amines
.
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the yield to some extent, e.g. 45% with CuCl (1 mmol %) or 71%
with CuCl (10 mmol%) (Table 1, entry ). Subsequently,
Results and discussion
7, 8
Our research focused on N-aryl glycine ester that is a more
challenging substrate compared with glycine amides due to its
structure containing a highly reactive ester carbonyl group
which may cause competitive reaction. To begin our study, we
chose N-aryl glycine ester 1a and phthalimide 2a as a model
reaction to explore and optimize the cross-dehydrogen
reaction between them. The reaction was initially studied with
O2 as an oxidant without any catalyst. However, no desired C-
N bond formation product was detected after heating at 40 oC
in CH3CN for 24 h. When CuBr (5%) was used as the catalyst,
product 3aa was successfully obtained in 58% yield (Table 1,
several other solvents including THF, DCE, toluene and acetone
were examined and CH3CN was still found to be the best
choice. The optimization experiment also indicated that raising
the temperature to 50 oC was beneficial to this coupling
reaction, giving a better yield of desired product (81%)(Table 1,
entry 13). However, it will exhibit negative effect on this
reaction when the temperature was elevated over 50 oC. Next,
a series of oxidants such as TBHP, DTBP, K2S2O8 and PhI(OAc)2
were examined with 5 mol% of CuCl in CH3CN at 40 oC. Among
these oxidants, only TBHP and DTBP worked, but were much
less effective than O2, while other oxidants inhibited this
reaction (Table 1, entry 15-18). The yield dropped slightly
when the reaction was performed under air atmosphere
(Table 1, entry 19).
On the basis of the screening of the reaction conditions, it
can be concluded that the optimized reaction should be
performed under the catalysis of 5 mol% CuCl at 50 oC in
CH3CN using oxygen as an oxidant. Under the optimized
conditions, different sets of experiments were carried out to
investigate the scope and limitations of this reaction. This
method was found to be applicable to a wide range of N-aryl
entry 2). We were pleased to find that this C-N bond formation
displayed an excellent regioselectivity and expected by-
product of phthalimide substitution 3aa’ was not observed.
Encouraged by this result, other copper catalysts such as CuI,
Cu(OTf)2, Cu(OAc)2 and CuCl were also investigated. The
experiment indicated that among these copper salts, CuCl
displayed the highest catalytic activity for this transformation
(Table 1, entry 6). The reaction with 5 mol% of CuCl proceeded
well under O2, giving product 3aa in 78% yield. Unexpectedly,
when Cu(OAc)2 was employed, substrate 1a was transformed
into ethyl 2-oxo-2-(p-methylphenylamino) acetate rather than
glycine esters 1a
reaction with phthalimide 2a smoothly, affording the desired
coupling products 3aa 3ta in the yield of 43-86% (Table 2).
-t which were able to undergo the CDC
product 3aa (Table 1, entry 5). Screening revealed that either
increasing or decreasing amount of CuCl led to a decrease in
-
Table 1. Screening of optimal reaction conditionsa
Initially, N-aryl glycine esters with a substituent (for example,
methyl, fluoro, chloro, or bromo) on the benzene ring were
tested under the optimized conditions. Both chloro, bormo
and fluoro groups reduced the reactivity of N-phenyl glycine
esters, leading to a lower yield compared with methyl group
substrate. Furthermore, substituents at different positions of
the N-aryl group could affect the efficiency of the coupling
reaction. For example, substrates bearing a methyl group at
the para- or meta- position had a much higher reactivity than
ortho- position. The results also demonstrated that this CDC
reaction is not very sensitive to the groups which was
connected with carbonyl group, such as methoxy, ethoxy,
isopropoxy and butoxy.
O
H
N
O
N
O
O
O
O
Catalyst (5 mol%)
Oxidant
H
N
3aa
+
O
N
H
O
Slovent (5.0 mL)
40 oC, 24 h
O
H
N
O
N
1a
2a
O
3aa'
Entry
1
2
3
4
Catalyst
-
CuBr
CuI
Oxidant (equiv.) Solvent Yield (%)b
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
0
58
46
52
0
78
45
71
74
70
trace
62
81
66
49
40
0
After the scope of N-aryl glycine esters was examined, a
series of acylated amines 2a-2l were investigated in the CDC
reaction with various N-aryl glycine esters. Bromo or methyl
substituted phthalimide reacted smoothly as well as
phthalimide and afforded the desired product with satisfied
Cu(OTf)2
Cu(OAc)2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
5
6
7c
8d
9
yield (Table 2, 3bb, 3db, 3eb, 3ac). Next, a range of cyclic
imides that contain no phenyl moiety were researched.
Gratifyingly, this transformation showed excellent tolerance
for these aliphatic cyclic imides, such as succinimide,
10
11
12
13e
14f
15g
16
17
18
19
DCE
toluene
acetone
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
piperidine-2,6-dione,
maleimide,
1,2,3,6-
tetrahydrophthalimide, and provided the corresponding
coupling products in moderate to good yield. The result may
imply that the phenyl moiety in the cyclic imides substrate is
not indispensable for this transformation. However, saccharin
are not suitable for this CDC reaction and only trace of the
target product was observed (Table 2, 3ah). Apart from the
cyclic substrates mentioned above, straight chain acylated
amines or sulfamides were employed to react with the N-
phenyl glycine derivatives under standard conditions.
Disappointingly, only benzamide could react smoothly and
O2
TBHP (2.0)
DTBP(2.0)
K2S2O8 (2.0)
PhI(OAc)2 (2.0)
air
0
75
aConditions: Unless otherwise noted, all reactions were performed
with 1a (0.6 mmoL) , 2a (0.5 mmol), catalyst (5 mol%) and solvent
(5.0 mL) at 40 oC under O2 for 24 h. bIsolated yield based on 1a.
c
o
f
o
g
CuCl (1 mmol%). d CuCl (10 mmol%). e At 50 C. At 60 C. (70% in
afforded the desired product in a satisfied yield (Table 2, 3ai
3oi). Other acyclic substrates including p-toluenesulfonamide
,
water).
or other secondary imides either gave the yield at a trace level
2 | J. Name., 2012, 00, 1-3
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(Tabel 2, 3aj) or failed to produce desired product (Table 2,
3ak 3al).
,
Table 2. Scope of the CuCl-catalyzed aerobic CDC reactiona
3ah (trace)
3ai (62%)
3oi (49%)
R1=4-CH3, R2=-CH2CH3
3aa (81%)
3-CH3,
2-CH3,
-H,
-CH2CH3
-CH2CH3
-CH2CH3
-CH3
3ba (86%)
3ca (56%)
3da (78%)
3ea (80%)
3fa (82%)
3ga (52%)
3ha (76%)
3ia (86%)
3ja (83%)
3ka (51%)
3la (82%)
3ma(59%)
3na (52%)
3oa (46%)
3pa (49%)
3qa (43%)
3ra (62%)
3sa (58%)
3ta (62%)
4-CH3,
3-CH3,
2-CH3,
-H
-CH3
-CH3
3aj (trace)
3ak(N.D.)
1 (0.6 mmoL), 2 (0.5 mmol), CuCl (5 mol%) and
3al (N.D.)
aConditions:
CH3CN (5.0 mL) at 50 oC under O2 for 24 h.
-CH3
4-CH3,
3-CH3,
2-CH3,
-H,
-isopropyl
-isopropyl
-isopropyl
-isopropyl
R2=-CH2CH3
-CH2CH3
-CH2CH3
-CH3
To elucidate the mechanism, some control experiments
were carried out. Firstly, the reaction of 1a with phthalimide
2a in an nitrogen atmosphere furnished no product [Scheme 2,
(1)], indicating that molecular oxygen is definitely crucial for
the reaction. Subsequently, no desired product was observed
when a stoichiometric amount of radical-trapping reagent
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) was employed
in standard reaction conditions [Scheme 2, (2)]. At the same
time, we found that when 1.2 equivalent of the 2,6-di-tert-
butyl-4-methyphenol (BHT), a radical scavenger, was added
into the same reaction system, the yield of coupling product
decreased dramatically from 83% to 15% [Scheme 2, (3)].
These results suggested that the reaction may proceed via a
radical mechanism. Under standard conditions, N-aryl glycine
ester 1a was oxidized to ethyl 2-(4-methylphenylimino)
acetate 1a’ at a yield of 87%, which may indicate that
transformation of N-phenyl glycine esters into imino
intermediate was crucial to the coupling reaction. As we
expected, phthalimide 2a underwent a CDC reaction with 2-(4-
methylphenylimino) acetate to produce the desired product at
a yield of 85%.
R1=4-F,
4-Cl,
4-Br,
4-Cl,
4-Br,
4-Cl,
4-Br,
4-F,
-CH3
-isopropyl
-isopropyl
-t-butyl
3bb (72%)
O
3db (70%)
3eb (75%)
H
N
O
N
O
O
3ac (83%)
3rd (41%)
3ad (66%)
3ae (82%)
3bd (57%)
3re (61%)
O
H
N
O
O
N
O
3af (85%)
3ff (77%)
3rf (56%)
R1=4-CH3,
R2=-CH2CH3
-CH2CH3
-CH3
3ag (80%)
2-CH3,
4-CH3,
3-CH3,
4-Cl,
3cg (55%)
3eg (70%)
3jg (86%)
3ng (40%)
-isopropyl
-CH2CH3
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Scheme 2 Control experiments.
N-aryl glycine esters
protocols.9
1
were prepared according to reported
On the basis of control experimental results and previous
reports, a possible mechanism for this Cu-catalyzed aerobic General procedure for the CDC reactions between N-aryl
transformation was proposed in Scheme 3. Initially, a Cu(II) glycine esters derivatives 1 and acylated amines 2: N-aryl
peroxide radical generated by a combination of molecular glycine esters
oxygen with copper (I) might abstract an α-hydrogen atom of were dissolved in CH3CN, CuCl (0.025 mmol) was then added in
glycine ester 1a to form radical . Subsequently, a single one portion under stirring. The reactions were performed
electron transfer (SET) from to Cu(II) leads to cation
, which under an oxygen atmosphere (oxygen ballon) at 50 oC for 24 h.
could immediately tautomerize to iminium ion . Finally, Next, the reaction mixture was concentrated in vacuum, and
1 (0.6 mmol) and acylated amine 2 (0.5 mmol)
4
4
5
6
coupling iminium ion
desired product 3aa
6
with phthalimide 2a results in the the residues were purified by silica gel column
chromatography (n-hexane-EtOAc) to afford the desired
product 3.
.
o
3aa: yellow solid; yield 81% (137 mg); m.p. 113.8-116.5 C;
1H NMR (600 MHz, CDCl3): δ 7.87-7.84 (m, 2H), 7.75-7.72 (m,
2H), 7.01 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 7.8 Hz, 2H), 6.23 (s, 1H),
5.23 (br. s, 1H), 4.33 (q, J = 7.2 Hz, 2H), 2.22 (s, 3H), 1.28 (t, J =
7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 167.2, 141.6,
134.4, 131.7, 130.0, 128.8, 123.7, 114.0, 63.0, 60.4, 20.4, 14.1.
HRMS: C19H18N2NaO4 [M+Na]+; calculated: 361.1159, found:
361.1144.
o
3ba: yellow solid; yield 86% (145 mg); m.p. 115.1-117.2 C;
1H NMR (600 MHz, CDCl3): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m,
2H), 7.07 (t, J = 7.8 Hz, 1H), 6.66-6.60 (m, 3H), 6.21 (s, 1H), 5.27
(br. s, 1H), 4.30 (q, J = 7.2 Hz, 2H), 2.26 (s, 3H), 1.25 (t, J = 7.2
Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 167.2, 143.9, 139.4,
134.4, 131.7, 129.4, 123.7, 120.5, 114.7, 110.6, 63.0, 59.9, 21.6,
14.1. HRMS: C19H18N2NaO4 [M+Na]+; calculated: 361.1159,
found: 361.1141.
Scheme 3 A possible mechanism.
o
1
3ca: yellow solid; yield 56% (95 mg); m.p. 94.2-97.3 C; H
NMR (600 MHz, CDCl3): δ 7.85-7.84 (m, 2H), 7.73-7.72 (m, 2H),
7.10 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.2 Hz, 1H), 6.88 (d, J = 8.4
Hz, 1H), 6.72 (t, J = 7.2 Hz, 1H), 6.25 (s, 1H), 5.27 (br. s, 1H),
Conclusions
In summary, we have developed a novel CDC reaction between
N-aryl glycine esters 1 and acylated amines 2 with an excellent
4.32 (q, J = 7.2 Hz, 2H), 2.26 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H). 13
C
regioselectivity by copper catalysis using O2 as an oxidant. To
the best of our knowledge, no examples describe the C(sp3)-N
bond formation of N-aryl glycine derivatives as well as the
skeleton of glycine can be kept. The use of cheap and non-
toxic simple copper salts as catalyst and molecular oxygen as
the oxidant makes this transformation environmentally
friendly and practical. A variety of substituted N-aryl glycine
esters could be tolerated by this procedure which proceeds
smoothly and gives a moderate to excellent yield. Further
studies on the CDC reactions of secondary acyclic imides or
NMR (150 MHz, CDCl3) δ 167.5, 167.3, 142.1, 134.4, 131.7,
130.7, 127.3, 123.7, 123.3, 119.2, 110.9, 63.1, 59.9, 17.4, 14.1.
HRMS: C19H19N2O4 [M+H]+; calculated: 339.1339, found:
339.1339.
o
3da: yellow solid; yield 78% (126 mg); m.p. 112.6-114.6 C;
1H NMR (600 MHz, CDCl3): δ 7.89-7.86 (m, 2H), 7.77-7.74 (m,
2H), 7.23-7.20 (m, 2H), 6.85 (d, J = 7.8 Hz, 2H), 6.81 (t, J = 7.2
Hz, 1H), 6.24 (s, 1H), 5.31 (br. s, 1H), 4.33 (q, J = 7.2 Hz, 2H),
1.28 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5,
167.1, 143.9, 134.4, 131.7, 129.5, 123.7, 119.6, 113.7, 63.1,
59.9, 14.1. HRMS: C18H16N2NaO4 [M+Na]+; calculated:
347.1002, found: 347.0993.
amines with α–amino acids derivatives are in progress.
o
3ea: yellow solid; yield 80% (130 mg); m.p. 144.3-146.1 C;
Experimental
1H NMR (600 MHz, CDCl3): δ 7.88-7.84 (m, 2H), 7.76-7.73 (m,
2H), 7.02 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 8.4 Hz, 2H), 6.25 (s, 1H),
3.85 (s, 3H), 2.23 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.7,
167.5, 141.4, 134.4, 131.7, 130.0, 129.0, 123.7, 114.0, 60.2,
53.6, 20.4. HRMS: C18H17N2O4 [M+H]+; calculated: 325.1183,
found: 325.1183.
General experimental method
Melting points were determined using a digital melting point
apparatus and uncorrected. H NMR spectra were recorded at
1
500 and 600MHz using TMS as internal standard, 13C NMR
spectra were recorded at 125 and 150 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. All chemical 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 n-hexane/ethyl acetate.
o
3fa: yellow solid; yield 82% (133 mg); m.p. 108.4-111.3 C;
1H NMR (600 MHz, CDCl3): δ 7.87-7.84 (m, 2H), 7.73-7.71 (m,
2H), 7.07 (t, J = 7.8 Hz, 1H), 6.65-6.60 (m, 3H), 6.24 (s, 1H), 5.19
(br. s, 1H), 3.83 (s, 3H), 2.26 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 167.7, 167.5, 143.8, 139.4, 134.4, 131.7, 129.4, 123.7, 120.5,
114.8, 110.7, 59.8, 53.7, 21.6. HRMS: C18H17N2O4 [M+H]+;
calculated: 325.1183, found: 325.1169.
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3ga: yellow solid; yield 52% (84 mg); m.p. 116.0-118.9 oC; 1H 13C NMR (150 MHz, CDCl3) δ 167.4, 166.9, 142.6, 134.5, 131.6,
NMR (600 MHz, CDCl3): δ 7.86-7.84 (m, 2H), 7.74-7.72 (m, 2H), 129.4, 124.4, 123.8, 115.0, 63.2, 59.8, 14.1. HRMS:
7.11-7.06 (m, 2H), 6.87 (d, J = 7.8 Hz, 1H), 6.74-6.71 (m, 1H), C18H15ClN2NaO4 [M+Na]+; calculated: 381.0613, found:
6.28 (d, J = 8.4 Hz, 1H), 5.26 (d, J = 9.0 Hz, 1H), 3.85 (s, 3H), 381.0627.
2.26 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.9, 167.5, 142.0,
134.4, 131.7, 130.7, 127.3, 123.8, 123.4, 119.3, 110.9, 59.6,
53.7, 17.4. HRMS: C18H16N2NaO4 [M+Na]+; calculated:
347.1002, found: 347.1016.
o
1
3oa: yellow solid; yield 46% (92 mg); m.p. 99.6-102.4 C; H
NMR (600 MHz, CDCl3): δ 7.86-7.84 (m, 2H), 7.75-7.73 (m, 2H),
7.26 (d, J = 9.0 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H), 6.16 (d, J = 9.0
Hz, 1H), 5.40 (d, J = 8.4 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H), 1.26 (t,
o
3ha: yellow solid; yield 76% (118 mg); m.p. 117.2-119.8 C; J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.4, 166.9, 143.1,
1H NMR (600 MHz, CDCl3): δ 7.87-7.83 (m, 2H), 7.75-7.71 (m, 134.5, 132.2, 131.6, 123.8, 115.4, 111.5, 63.2, 59.7, 14.1.
2H), 7.20-7.18 (m, 2H), 6.83 (d, J = 8.4 Hz, 2H), 6.79 (t, J = 7.8 HRMS: C18H15BrN2NaO4 [M+Na]+; calculated: 425.0107, found:
Hz, 1H), 6.24 (s, 1H), 5.31 (br. s, 1H), 3.83 (s, 3H). 13C NMR (150 425.0125.
3pa: yellow solid; yield 49% (84 mg); m.p. 127.3-130.5 oC; 1H
MHz, CDCl3) δ 167.7, 167.5, 143.8, 134.5, 131.7, 129.5, 123.8,
119.6, 113.8, 59.7, 53.7. HRMS: C17H14N2NaO4 [M+Na]+;
calculated: 333.0846, found: 333.0852.
NMR (600 MHz, CDCl3): δ 7.87-7.85 (m, 2H), 7.76-7.74 (m, 2H),
7.13 (d, J = 8.4 Hz, 2H), 6.75 (d, J = 9.0 Hz, 2H), 6.17 (d, J = 8.4
o
3ia: yellow solid; yield 86% (151 mg); m.p. 106.3-109.1 C; Hz, 1H), 5.31 (d, J = 9.0 Hz, 1H), 3.84 (s, 3H). 13C NMR (150 MHz,
1H NMR (600 MHz, CDCl3): δ 7.84-7.83 (m, 2H), 7.72-7.71 (m, CDCl3) δ 167.4, 142.4, 134.6, 131.6, 129.4, 124.5, 123.9, 115.0,
2H), 6.99 (d, J = 7.8 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 6.15 (d, J = 59.7, 53.8. HRMS: C17H13ClN2NaO4 [M+Na]+; calculated:
9.0 Hz, 1H), 5.22-5.12 (m, 2H), 2,20 (s, 3H), 1.28 (d, J = 6.6 Hz, 367.0456, found: 367.0468.
3H), 1.19 (d, J = 6.0 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5,
3qa: yellow solid; yield 43% (83 mg); m.p. 155.9-158.8 oC; 1H
NMR (600 MHz, CDCl3): δ 7.78-7.76 (m, 2H), 7.67-7.65 (m, 2H),
7.19-7,17 (m, 2H), 6.62 (d, J = 9.0 Hz, 2H), 6.09 (s, 1H), 5.27 (br.
166.7, 141.6, 134.4, 131.7, 130.0, 128.8, 123.7, 114.0, 71.1,
60.5, 21.6, 21.5, 20.4. HRMS: C20H21N2O4 [M+H]+; calculated:
353.1496, found: 353.1479.
s, 1H), 3.75 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.4, 167.3,
3ja: yellow solid; yield 83% (146 mg); m.p. 117.0-120.3 C; 142.9, 134.6, 132.3, 131.6, 123.9, 115.5, 111.6, 59.5, 53.8.
o
1H NMR (600 MHz, CDCl3): δ 7.85-7.82 (m, 2H), 7.73-7.70 (m, HRMS: C17H13BrN2NaO4 [M+Na]+; calculated: 410.9951, found:
2H), 7.07 (t, J = 7.8 Hz, 1H), 6.66-6.64 (m, 2H), 6.60 (d, J = 7.2 410.9927.
o
3ra: yellow solid; yield 62% (115 mg); m.p. 127.0-129.7 C;
Hz, 1H), 6.17 (s, 1H), 5.25 (br. s, 1H), 5.18-5.12 (m, 1H), 2.26 (s,
3H), 1.28 (d, J = 6.0 Hz, 3H), 1.19 (d, J = 6.6 Hz, 3H). 13C NMR
1H NMR (600 MHz, CDCl3): δ 7.87-7.85 (m, 2H), 7.75-7.74 (m,
(150 MHz, CDCl3) δ 167.5, 166.7, 144.0, 139.4, 134.4, 131.7,
2H), 7.13 (d, J = 9.0 Hz, 2H), 6.76 (d, J = 9.0 Hz, 2H), 6.10 (s, 1H),
129.4, 123.7, 120.4, 114.7, 110.6, 71.1, 60.1, 21.6, 21.5. HRMS:
C20H20N2NaO4 [M+Na]+; calculated: 375.1315, found: 375.1324.
5.18-5.14 (m, 1H), 1.28 (d, J = 6.6 Hz, 3H), 1.19 (d, J = 6.0 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 166.4, 142.6, 134.5,
3ka: yellow solid; yield 51% (90 mg); m.p. 110.0-112.1 oC; 1H 131.6, 129.4, 124.3, 123.8, 115.0, 71.3, 59.8, 21.6, 21.5. HRMS:
NMR (600 MHz, CDCl3): δ 7.89-7.86 (m, 2H), 7.77-7.74 (m, 2H), C19H17ClN2NaO4 [M+Na]+; calculated: 395.0769, found:
7.14-7.11 (m, 1H), 7.09 (d, J = 7.2 Hz, 1H), 6.91 (d, J = 7.8 Hz, 395.0776.
o
1H), 6.76-6.73 (m, 1H), 6.23 (s, 1H), 5.29 (br. s, 1H), 5.22-5.16
3sa: yellow solid; yield 58% (120 mg); m.p. 125.8-128.9 C;
(m, 1H), 2,28(s, 3H), 1.31 (d, J = 6.0 Hz, 3H), 1.23 (d, J = 6.0 Hz, 1H NMR (600 MHz, CDCl3): δ 7.87-7.85 (m, 2H), 7.75-7.74 (m,
3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 166.8, 142.2, 134.4, 2H), 7.26 (d, J = 9.0 Hz, 2H), 6.71 (d, J = 9.0 Hz, 2H), 6.10 (s, 1H),
131.7, 130.6, 127.3, 123.7, 123.2, 119.1, 110.9, 71.2, 60.0, 21.6, 5.18-5.14 (m, 1H), 1.28 (d, J = 6.6 Hz, 3H), 1.19 (d, J = 6.0 Hz,
21.5, 17.4. HRMS: C20H20N2NaO4 [M+H]+; calculated: 375.1315, 3H). 13C NMR (150 MHz, CDCl3) δ 167.4, 166.3, 143.1, 134.5,
found: 375.1334.
132.2, 131.6, 123.8, 115.4, 111.4, 71.4, 59.8, 21.6, 21.5. HRMS:
C19H17BrN2NaO4 [M+Na]+; calculated: 439.0264, found:
439.0244.
o
3ta: yellow solid; yield 62% (115 mg); m.p. 144.3-147.1 C;
o
3la: yellow solid; yield 82% (139 mg); m.p. 118.0-120.2 C;
1H NMR (600 MHz, CDCl3): δ 7.87-7.84 (m, 2H), 7.75-7.72 (m,
2H), 7.20-7.18 (m, 2H), 6.83 (d, J = 7.8 Hz, 2H), 6.78 (t, J = 7.2
Hz, 1H), 6.17 (s, 1H), 5.19-5.13 (m, 1H), 1.28 (d, J = 6.0 Hz, 3H), 1H NMR (600 MHz, CDCl3): δ 7.89-7.88 (m, 2H), 7.77-7.76 (m,
1.19 (d, J = 6.6 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 2H), 6.92-6.88 (m, 2H), 6.79-6.77 (m, 2H), 6.04 (s, 1H), 1.47 (s,
166.6, 144.0, 134.4, 131.7, 129.5, 123.7, 119.5, 113.7, 71.2, 9H). 13C NMR (150 MHz, CDCl3) δ 167.6, 165.9, 156.9 (d, JC-F
=
60.0, 21.6. HRMS: C19H18N2NaO4 [M+Na]+; calculated: 235.7 Hz), 140.6, 134.4, 131.6, 123.7, 116.0 (d, JC-F = 22.5 Hz),
361.1159, found: 361.1162.
114.9 (d, JC-F = 7.5 Hz), 84.2, 61.0, 27.8. HRMS: C20H19FN2NaO4
[M+Na]+; calculated: 393.1221, found: 393.1232.
1
3bb: yellow glass; yield 72% (150 mg); H NMR (600 MHz,
3ma: yellow solid; yield 59% (101 mg); m.p. 92.2-95.0 C; 1H
NMR (600 MHz, CDCl3): δ 7.90-7.86 (m, 2H), 7.79-7.75 (m, 2H),
o
6.93-6.89 (m, 2H), 6.81-6.77 (m, 2H), 6.15 (s, 1H), 4.33 (q, J = CDCl3): δ 8.00 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.4 Hz,
7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 1H), 7.10 (t, J = 7.8 Hz, 1H), 6.66-6.63 (m, 3H), 6.21 (d, J = 9.0
167.5, 167.0, 157.0 (d, JC-F = 235.5 Hz), 140.2, 134.5, 131.6, Hz, 1H), 5.25 (d, J = 9.0 Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 2.28 (s,
123.8, 116.0 (d, JC-F = 22.4 Hz), 115.0 (d, JC-F = 7.5 Hz), 63.1, 3H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 166.9,
60.6, 14.1. HRMS: C18H15FN2NaO4 [M+Na]+; calculated: 166.7, 166.2, 143.8, 139.4, 137.4, 133.3, 130.2, 129.4, 127.1,
365.0908, found: 365.0911.
125.0, 120.6, 114.7, 110.6, 63.1, 60.2, 21.6, 14.1. HRMS:
C19H17BrN2NaO4 [M+Na]+; calculated: 439.0264, found:
439.0243.
o
3db: yellow solid; yield 70% (141 mg); m.p. 120.9-123.1 C;
3na: yellow solid; yield 52% (93 mg); m.p. 108.7-111.0 oC; 1H
NMR (600 MHz, CDCl3): δ 7.87-7.84 (m, 2H), 7.76-7.74 (m, 2H),
7.13 (d, J = 9.0 Hz, 2H), 6.75 (d, J = 9.0 Hz, 2H), 6.14 (s, 1H),
5.32 (br. s, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H). 1H NMR (600 MHz, CDCl3): δ 7.88 (s, 1H), 7.76 (d, J = 7.8 Hz,
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1H), 7.61 (d, J = 7.8 Hz, 1H), 7.10-7.08 (m, 2H), 6.72-6.68 (m, C15H15ClN2NaO4 [M+Na]+; calculated: 345.0613, found:
3H), 6.11 (d, J = 9.0 Hz, 1H), 5.23 (d, J = 9.0 Hz, 1H), 4.22 (q, J = 345.0601.
7.2 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ
164.8, 164.6, 164.0, 141.7, 135.4, 131.2, 128.1, 127.4, 127.3,
o
3af: yellow solid; yield 85% (145 mg); m.p. 103.8-106.0 C;
1H NMR (600 MHz, CDCl3): δ 7.00 (d, J = 8.4 Hz, 2H), 6.65 (d, J =
125.0, 123.0, 117.6, 111.6, 61.1, 58.0, 12.0. HRMS:
8.4 Hz, 2H), 5.99 (s, 1H), 5.80-5.74 (m, 2H), 4.33-4.22 (m, 2H),
3.09-3.04 (m, 2H), 2.58-2.52 (m, 2H), 2.25-2.19 (m, 5H), 1.28 (t,
C18H15BrN2NaO4 [M+Na]+; calculated: 425.0107, found:
425.0095.
J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 179.3, 179.2, 166.7,
o
3eb: yellow solid; yield 75% (151 mg); m.p. 142.2-144.1 C; 141.4, 129.9, 128.9, 127.7, 127.4, 114.3, 62.8, 61.0, 39.1, 38.9,
1H NMR (600 MHz, CDCl3): δ 7.98 (s, 1H), 7.87 (d, J = 7.8 Hz, 23.3, 23.2, 20.4, 14.1. HRMS: C19H22N2NaO4 [M+Na]+;
1H), 7.72 (d, J = 7.8 Hz, 1H), 7.01 (d, J = 8.4 Hz, 2H), 6.73 (d, J = calculated: 365.1472, found: 365.1486.
8.4 Hz, 2H), 6.22 (d, J = 9.6 Hz, 1H), 5.19 (d, J = 9.6 Hz, 1H), 3.85
3ff: yellow solid; yield 77% (126 mg); m.p. 120.6-122.9 oC; 1H
(s, 3H), 2.22 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.5, 166.7, NMR (600 MHz, CDCl3): δ 7.09-7.07 (m, 1H), 6.65 (d, J = 7.8 Hz,
166.2, 141.2, 137.4, 133.3, 130.2, 130.0, 129.4, 129.2, 127.1, 1H), 6.56-6.53 (m, 2H), 6.04 (s, 1H), 5.78-5.73 (m, 2H), 5.13 (br.
125.0, 114.0, 60.5, 53.7, 20.3. HRMS: C18H15BrN2NaO4 [M+Na]+; s, 1H), 3.81 (s, 3H), 3.10-3.06 (m, 2H), 2.55-2.52 (m, 2H), 2.28
calculated: 425.0107, found: 425.0090.
(s, 3H), 2.25-2.17 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 179.4,
179.2, 167.2, 143.7, 139.2, 129.3, 127.3, 127.2, 120.6, 115.1,
111.1, 60.6, 53.4, 39.2, 39.1, 23.4, 23.3, 21.5. HRMS:
C19H21ClN2NaO4 [M+Na]+; calculated: 351.1315, found:
351.1327.
o
1
3ac: yellow solid; yield 83% (146 mg); m.p. 46.8-49.0 C; H
NMR (500 MHz, CDCl3): δ 7.73 (d, J = 7.5 Hz,1H), 7.65 (s, 1H),
7.51 (d, J = 7.5 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.5
Hz, 2H), 6.19 (s, 1H), 5.20 (br. s, 1H), 4.31 (q, J = 7.0 Hz, 2H),
2.50 (s, 3H), 2.21 (s, 3H), 1.27 (t, J = 7.0 Hz, 3H). 13C NMR (125
MHz, CDCl3) δ 167.7, 167.6, 167.3, 145.8, 141.6, 134.9, 132.1,
129.9, 129.1, 128.8, 124.2, 123.6, 114.0, 62.9, 60.2, 22.0, 20.4,
14.1. HRMS: C18H15BrN2NaO4 [M+Na]+; calculated: 375.1315,
found: 375.1305.
3rf: yellow solid; yield 56% (105 mg); m.p. 128.7-131.0 oC;
1H NMR (600 MHz, CDCl3): δ 7.13 (d, J = 9.0 Hz, 2H), 6.66 (d, J =
9.0 Hz, 2H), 5.89 (d, J = 9.0 Hz, 1H), 5.81-5.76 (m, 2H), 5.22 (d, J
= 9.0 Hz, 1H), 5.14-5.08 (m, 1H), 3.11-3.04 (m, 2H), 2.59-2.53
(m, 2H), 2.26-2.18 (m, 2H), 1.27 (d, J = 6.0 Hz, 3H), 1.22 (d, J =
6.0 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 179.2, 179.1, 165.9,
142.5, 129.3, 127.5, 127.4, 124.3, 115.2, 71.1, 60.4, 39.1, 38.9,
23.3, 23.2, 21.6, 21.5. HRMS: C19H21ClN2NaO4 [M+Na]+;
calculated: 399.1082, found: 399.1088.
1
3ad: glass; yield 66% (100 mg); H NMR (600 MHz, CDCl3): δ
6.90 (d, J = 8.4 Hz, 2H), 6.60-6.58 (m, 3H), 4.96 (br. s, 1H), 4.20-
4.11 (m, 2H), 2.55 (t, J = 6.6 Hz, 4H), 2.15 (s, 3H), 1.83-1.80 (m,
2H), 1.18 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 172.6,
168.1, 142.3, 129.9, 128.6, 114.1, 62.4, 61.9, 32.5, 20.4, 16.9,
14.1. HRMS: C16H20N2NaO4 [M+Na]+; calculated: 327.1315,
found: 327.1328.
o
3ag: yellow solid; yield 80% (116 mg); m.p. 113.0-116.5 C;
1H NMR (600 MHz, CDCl3): δ 7.00 (d, J = 8.4 Hz, 2H), 6.67 (d, J =
8.4 Hz, 2H), 6.03 (s, 1H), 5.10 (br. s, 1H), 4.29 (q, J = 7.2 Hz, 2H),
2.72-2.65 (m, 4H), 2.23 (s, 3H), 1.29 (t, J = 7.2 Hz, 3H). 13C NMR
(150 MHz, CDCl3) δ 176.4, 166.8, 141.5, 130.0, 129.0, 113.9,
63.0, 61.0, 28.1, 20.4, 14.1. HRMS: C15H18N2NaO4 [M+Na]+;
calculated: 313.1159, found: 313.1149.
1
3bd: glass; yield 57% (87 mg); H NMR (600 MHz, CDCl3): δ
7.11-7.08 (m, 1H), 6.70 (s, 1H), 6.64 (d, J = 7.8 Hz, 1H), 6.62-
6.60 (m, 2H), 4.30-4.24 (m, 2H), 2.69-2.67 (m, 4H), 2.29 (s, 3H),
1.97-1.93 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 172.5, 168.0, 144.6, 139.3, 129.3, 120.2, 114.8, 110.7,
62.4, 61.5, 32.6, 21.6, 16.9, 14.1. HRMS: C16H20N2NaO4
[M+Na]+; calculated: 327.1315, found: 327.1317.
3rd: white solid; yield 41% (70 mg); m.p. 89.2-92.3 oC; 1H
NMR (600 MHz, CDCl3): δ 7.13 (d, J = 9.0 Hz, 2H), 6.70 (d, J =
9.0 Hz, 2H), 6.59 (d, J = 10.2 Hz, 1H), 5.16 (d, J = 10.2 Hz, 1H),
5.11-5.07 (m, 1H), 2.71-2.63 (m, 4H), 1.95-1.91 (m, 2H), 1.29 (d,
J = 6.0 Hz, 3H), 1.22 (d, J = 6.0 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 172.5, 167.1, 143.4, 129.3, 123.9, 115.1, 70.5, 61.6,
32.6, 21.7, 21.6, 16.9. HRMS: C16H19ClN2NaO4 [M+Na]+;
calculated: 361.0926, found: 361.0918.
3cg: yellow solid; yield 55% (80 mg); m.p. 132.9-134.8 oC; 1H
NMR (600 MHz, CDCl3): δ 7.12-7.07 (m, 2H), 6.78-6.74 (m, 2H),
6.09 (d, J = 7.8 Hz, 1H), 5.18 (d, J = 7.8 Hz, 1H), 4.34-4.26 (m,
2H), 2.75-2.65 (m, 4H), 2.22 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H). 13C
NMR (150 MHz, CDCl3) δ 176.3, 166.9, 142.1, 130.7, 127.3,
123.3, 119.3, 110.9, 63.1, 60.5, 28.1, 17.3, 14.1. HRMS:
C15H18N2NaO4 [M+Na]+; calculated: 313.1159, found: 313.1149.
3eg: yellow solid; yield 70% (97 mg); m.p. 144.4-147.1 oC; 1H
NMR (600 MHz, CDCl3): δ 6.92 (d, J = 7.2 Hz, 2H), 6.59 (d, J =
7.8 Hz, 2H), 5.97 (d, J = 10.2 Hz, 1H), 5.04 (d, J = 10.2 Hz, 1H),
3.74 (s, 3H), 2.64-2.54 (m, 4H), 2.15 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 176.5, 167.4, 141.4, 130.0, 129.0, 114.0, 60.8, 53.6,
28.1, 20.4. HRMS: C14H16N2NaO4 [M+Na]+; calculated:
299.1002, found: 299.0996.
o
3ae: yellow solid; yield 82% (118 mg); m.p. 141.0-142.3 C;
1H NMR (600 MHz, CDCl3): δ 7.02 (d, J = 8.4 Hz, 2H), 6.72-6.69
(m, 4H), 6.01 (s, 1H), 5.09 (br. s, 1H), 4.34-4.27 (m, 2H), 2.25 (s,
3H), 1.29 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 169.9,
167.0, 141.4, 134.4, 130.0, 129.0, 114.0, 63.0, 60.2, 20.4, 14.1.
HRMS: C15H16N2NaO4 [M+Na]+; calculated: 311.1002, found:
311.1010.
o
3jg: yellow solid; yield 86% (131 mg); m.p. 111.0-113.4 C;
1H NMR (600 MHz, CDCl3): δ 7.08 (t, J = 7.8 Hz, 1H), 6.63 (d, J =
7.2 Hz, 1H), 6.59-6.57 (m, 2H), 6.00 (s, 1H), 5.15-5.11 (m, 1H),
2.74-2.64 (m, 4H), 2.27 (s, 3H), 1.29 (d, J = 6.0 Hz, 3H), 1.24 (d,
J = 6.0 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 176.4, 166.2, 144.0,
139.4, 129.4, 120.4, 114.7, 110.6, 71.1, 60.7, 28.1, 21.7, 21.6,
21.5. HRMS: C16H20N2NaO4 [M+Na]+; calculated: 327.1315,
found: 327.1302.
3re: yellow solid; yield 61% (98 mg); m.p. 118.0-120.1 oC; 1H
NMR (600 MHz, CDCl3): δ 7.16 (d, J = 9.0 Hz, 2H), 6.74 (s, 2H),
6.71 (d, J = 9.0 Hz, 2H), 5.92 (d, J = 8.4 Hz, 1H), 5.21 (d, J = 9.0
Hz, 1H), 5.18-5.14 (m, 1H), 1.30 (d, J = 6.6 Hz, 3H), 1.24 (d, J =
6.0 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 169.7, 166.1, 142.5,
134.4, 129.4, 124.5, 115.0, 71.4, 59.8, 21.6, 21.5. HRMS:
3ng: yellow solid; yield 40% (62 mg); m.p. 150.5-152.9 oC; 1H
NMR (600 MHz, CDCl3): δ 7.17 (d, J = 9.0 Hz, 2H), 6.71 (d, J =
8.4 Hz, 2H), 6.00 (s, 1H), 5.26 (br. s, 1H), 4.31 (q, J = 7.2 Hz, 2H),
6 | J. Name., 2012, 00, 1-3
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2.80-2.70 (m, 4H), 1.31 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 176.3, 166.4, 142.5, 129.4, 124.5, 115.0, 63.2, 60.4,
28.1, 14.1. HRMS: C14H15ClN2NaO4 [M+Na]+; calculated:
333.0613, found: 333.0612.
4
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C. D. Huo, Y. Yuan, M. X. Wu, X. D. Jia, X. C. Wang, F. J. Chen
and J. Tang, Angew. Chem., Int. Ed., 2014, 53, 13544.
(a) C. D. Huo, C. Wang, M. X. Wu, X. D. Jia, H. S. Xie and Y.
Yuan, Adv. Synth. Catal., 2014, 356, 411. (b) Z. Q. Zhu, P. Bai
and Z. Z. Huang, Org. Lett., 2014, 16, 4881. (c) J. Jiao, J. R.
Zhang, Y. Y. Liao, L. Xu, M. L. Hu and R. Y. Tang, RSC. Adv.,
2017, 7, 30152. (d) R. Y. Tang, X. K. Guo, J. N. Xiang and J. H.
Li, J. Org. Chem., 2013, 78, 11163. (e) S. Q. Zhu and M.
Rueping, Chem. Commun., 2012, 48, 11960. (f) X. D. Jia, F. F.
5
6
7
o
1
3ai: yellow solid; yield 62% (97 mg); m.p. 139.2-141.9 C; H
NMR (600 MHz, CDCl3): δ 7.75 (d, J = 7.2 Hz, 2H), 7.52-7.49 (m,
1H), 7.42 (t, J = 7.8 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.72-6.68
(m, 3H), 6.09 (d, J = 7.8 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H), 2.23 (s,
3H), 1.32 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 170.0,
167.3, 141.7, 133.4, 132.0, 130.0, 128.9, 128.6, 127.1, 114.3,
62.6, 61.3, 20.4, 14.1. HRMS: C18H20N2NaO3 [M+Na]+;
calculated: 335.1366, found: 335.1369.
o
3oi: yellow solid; yield 49% (92 mg); m.p. 166.7-168.2 C; 1H
Peng, C. Qing, C. D. Huo and X. C. Wang, Org. Lett., 2012, 14
4030.
,
NMR (600 MHz, DMSO-d6): δ 9.32 (d, J = 7.2 Hz, 1H), 7.86 (d, J
= 7.8 Hz, 2H), 7.56-7.54 (m, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.25 (d,
J = 9.0 Hz, 2H), 6.80-6.78 (m, 2H), 6.51 (d, J =8.4 Hz, 1H), 5.79-
5.75 (m, 1H), 4.24-4.16 (m, 2H), 1.21 (t, J = 7.2 Hz, 3H). 13C
NMR (150 MHz, DMSO-d6) δ 169.2, 166.8, 145.6, 133.8, 132.2,
131.9, 128.8, 127.9, 115.6, 108.8, 61.9, 60.8, 14.5. HRMS:
C17H17BrN2NaO3 [M+Na]+; calculated: 399.0315, found:
399.0309.
8
9
X. X. Liu, Z. Y. Wu, Y. Q. He, X. Q. Zhou, T. Hu, C. W. Ma and
G. S. Huang, Adv. Synth. Catal., 2016, 358, 2385.
W. K. Anderson, D. Bhattacharjee and D. M. Houston, J. Med.
Chem., 1989, 32, 119.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (No. 21406200) and Collaborative Innovation Center of
Yangtze River Delta Region Green Pharmaceuticals for financial
help.
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