Photoinduced Intermolecular [4+2] Cycloaddition Reaction for Construction of Benzobicyclo[2.2.2]octane Skeletons

Article abstract of DOI:10.1021/acs.joc.6b02547

A novel and efficient method for the synthesis of highly substituted benzobicyclo[2.2.2]octane skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.

Full text of DOI:10.1021/acs.joc.6b02547

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Article
Photo-induced Intermolecular [4+2] Cycloaddition Reaction
for Construction of Benzobicyclo[2.2.2]octane Skeletons
Qiang Liu, Junlei Wang, Dazhi Li, Chao Yang, and Wujiong Xia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02547 • Publication Date (Web): 05 Jan 2017
Downloaded from http://pubs.acs.org on January 6, 2017
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Photo-induced Intermolecular [4+2] Cycloaddition Reaction
for Construction of Benzobicyclo[2.2.2]octane Skeletons
Qiang Liu, Junlei Wang, Dazhi Li, Chao Yang,* and Wujiong Xia*
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School of Chemistry and Chemical Engineering, State Key Lab of Urban Water Resource and
Environment, Harbin Institute of Technology, Harbin 150080
*Eꢀmail: xyyang@hit.edu.cn
*Eꢀmail: xiawj@hit.edu.cn
ABSTRACT: A novel and efficient method for the synthesis of highly substituted
benzobicyclo[2.2.2]octane skeletons has been explored. Under UVꢀlight irradiation,
oꢀdivinylbenzenes underwent a pericyclic reaction to form the cyclic oꢀquinodimethane
intermediates which were subsequently reacted with olefins through [4+2] addition to construct
the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated
the synthetic potential application of this protocol.
INTRODUCTION
Photoꢀinduced organic reactions have played significant roles in green chemistry and total
synthesis, especially the construction of complex polycyclic compounds or highly functionalized
molecules, such as some bridgedꢀring compounds and natural products, which would be difficult
to access with the standard chemistry reactions in the ground state.1 Besides, photochemical
reaction often does not need activation reagents such as acids, bases, metals or enzymes, so it is an
economically and environmentally friendly way for many natural and unnatural products
synthesis.2
Benzobicyclo[2.2.2]octane derivatives compounds (Figure 1) are known to possess varieties of
biological activities.3 For example, benzobicyclo[2.2.2]octenals (Figure 1 A) was used as calcium
channel blockers in the treatment or prevention of angina pectoris, arrhythmias, and high blood
pressure.3 Additionally, due to its inherent stereochemistry, this skeleton is also a powerful
building block for other types of skeletons via cleavage of a carbonꢀcarbon bond.4 Therefore,
significant efforts have been made to access to benzobicyclo[2.2.2]octane skeletons. For instance,
Chittimalla’s group reported a twoꢀstep protocol to construct such a skeleton (Scheme 1a).5
Additionally, Nickelꢀcatalyzed intramolecular alkene insertion into cyclobutanones sequences
have been established by Murakami et al (Scheme 1b).6 Recently, Cramer and coꢀworkers used a
Rhꢀcatalyzed [4+2] cycloaddition to provide these bridgeꢀring compounds (Scheme 1c).7 In
addition, Lewis acid catalyzed intramolecular [3+3] reaction sequences have been developed by
Wang’s group (Scheme 1d)4. Despite of the above significant achievements, development of an
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efficient, transitionꢀmetalꢀfree, and stepꢀeconomical approach is still highly desirable. As part of
our continuing interest on the photochemical methodologies8, we herein disclose a simple way to
synthesize benzobicyclo[2.2.2]octane derivatives through photoꢀinduced [4+2] reactions from
substituted oꢀdivinylbenzenes with olefins (Scheme 1e).
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Figure 1. Products with bicyclo[2.2.2]octane skeletons and benzobicyclo[2.2.2]octane skeletons
Scheme 1. Approaches for the synthesis of benzobicyclo[2.2.2]octane skeletons
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RESULTS AND DISCUSSION
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Initially, our investigation was started from irradiation the mixture of substituted
oꢀdivinylbenzene 1a (Table 1) and Nꢀmethylmaleimide 2a in acetonitrile with 350 nm light at
room temperature. To our delight, the first attempt afforded the desired product 3aa in 74% yield
(Table 1, entry 1). Encouraged by this result, different types of light were tested (Table 1, entries
2ꢀ5). Pyrex works as a filter for a shorter wavelength of UV (~ < 280 nm), and it revealed that the
best wavelength is among 300ꢀ350 nm and the shorter wavelength (~ < 280 nm) is not suitable for
this reaction (Table 1, entries 1ꢀ4). So we choose 500W mediumꢀpressure mercury lamp with
Pyrex filter as the best light source. The reaction did not take place using blue LEDs (Table 1,
entry 5). On the basis of the optimal light source, a set of solvents were then examined, which
suggested MeCN was the ideal choice (Table 1, entries 6ꢀ12). Acetonitrile with water as solvent
also proceeded smoothly with a decreased yield (Table 1, entry 13). However, solvents, such as
benzene and THF were proved to be ineffective for this transformation (Table 1, entries 9, 12).
The best yield was obtained as 84% when the reaction was carried out under a N2 atmosphere
(Table 1, entry 14). This reaction is not air and moisture sensitive (Table 1, entries 13, 14), and it’s
most likely because this reaction mechanism (Scheme 3) might not be a free radical process.
Although oxygen does not have strong impact over the reaction (Table 1, entries 4, 14), we still
choose N2 atmosphere because oxygen can react with the carbonꢀcarbon double bond more or
less.9
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Table 1. Optimization of the reaction conditions a
Entry
1
Solvent
MeCN
Light Source
350 nm
Yield(%)b
74
2
3
MeCN
MeCN
MeCN
MeCN
Toluene
MeOH
DCM
300 nm
60
76
mercury lampc
4
mercury lamp with Pyrex
Blue LEDs
80
5
0
6
mercury lamp with Pyrex
mercury lamp with Pyrex
mercury lamp with Pyrex
mercury lamp with Pyrex
mercury lamp with Pyrex
45
7
53
8
62
9
Benzene
DMF
trace
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DMSO
THF
mercury lamp with Pyrex
mercury lamp with Pyrex
50
trace
6
7
8
9
13
14
MeCNd
MeCNe
mercury lamp with Pyrex
mercury lamp with Pyrex
65
84
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a
b
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), solvent (anhydrous, 10 mL), rt, under Air atmosphere.
Isolated yield. c 500 W medium pressure mercury lamp. d wet solvent. e N2 atmosphere
Having the optimized reaction conditions in hand, we subsequently investigated the scope
of this reaction, and the representative results were listed in Table 2. We first examined the
reaction of 1a with different olefins
2, which smoothly afforded the target products in good
to excellent yields (Table 2, 3aa 3ae). However, the general utility of the reaction sequence
ꢀ
was exemplified using maleic anhydride to give products 3af in 45% yield. This point
might be because maleic anhydride can form cyclobutane tetracarboxylic dianhydride10
through photodimerization or it is not a better dienophile compared with maleimides.
When 1a was changed into 1b, the reaction still worked well and the desired products
(
3ba
and electronꢀwithdrawing substituents (F, Cl) on the phenyl ring were suitable for this
reaction, leading to the corresponding products in moderate to good yields (3ca 3ga).
Furthermore, when R1 group and R2 group were
ꢀBu or ꢀPr groups, these reactions
worked smoothly to get the products (3ka
3la) in good yield. However, when R1 group
and R2 group are different, the product 3ha and its stereo isomer (ratio 1:1) were formed
(The possible process was depicted in Scheme 3, and II). Both the stereo isomers (3maa
3mab) were obtained when R1 and R2 were the large steric hindrance group, e.g.
ꢀBu,
ꢀ3bg) was also afforded in good yields. Both electronꢀdonating substituents (MeO, Me)
ꢀ
n
i
,
I
,
t
which was resulted from the isomerization of CꢀC double bond of the starting material due
to steric effects and the prolonged irradiation time (to see II and III in Scheme 3).
Similarly, the configuration of the reaction products (3na-3sa) are mainly the configuration
of compound 3mab when R1, R2 groups are the large steric hindrance groups. It is worth
noting that electronꢀwithdrawing substituents on the phenyl ring (3ga
, 3ua) were better
than electronꢀdonating substituents ones (3fa 3ta) for this reaction. The structure of these
,
products was assigned on the basis of 1D and 2D NMR, NOE and mass spectrometry
analysis. As a bonus, one of the products 3ad (Table 2) was suitable for Xꢀray
singleꢀcrystal structure analysis, allowing unambiguous determination of its structure and
relative configuration.11
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Table 2. Scope of the reaction
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R1OOC
COOR2
O
COOR1
COOR2
R3
hv
O
R3
+
X
MeCN, rt
X
1
2
3
O
O
MeOOC
3aa
R = Me
R = Et
4.0 h, 84%
MeOOC
COOMe
O
COOMe
O
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3ab 4.0 h, 76%
3ac 4.5 h, 75%
3ad 5.0 h, 64%
3ae 4.0 h, 68%
R = Bn
R = t-Bu
R = H
N
O
O
O
R
3af
5.0 h, 45%
MeOOC
EtOOC
3ba
5.5 h, 77%
R = Me
R = Et
COOMe
COOEt
O
3bb 6.0 h, 75%
3bc 6.5 h, 70%
3bd 7.0 h, 58%
3be 8.0 h, 78%
3bg 9.0 h, 60%
R
O
R = Bn
R = t-Bu
R = H
N
N
O
R
O
3ca
3da
R = Me
R = Cl
5.0 h, 64%
4.0 h, 70%
R = Ph
EtOOC
COOEt
R
O
3ad =
N
O
R = Cl
R = OMe 3fa 4.5 h, 55%
R = F 3ga 5.5 h, 67%
n-BuOOC
3ea 5.0 h, 63%
MeOOC
COOEt
EtOOC
COOMe
O
COOn-Bu
O
O
N
N
O
N
O
3ka 5.0 h, 78%
O
3ha
5.0 h, 70% (1:1)
t-BuOOC
t-BuOOC
t-BuOOC
i-PrOOC
COOt-Bu
COOi-Pr
O
O
O
N
O
7.5 h, 64%
N
O
N
O
3la
3maa 9.0 h, 42%
3mab 9.0 h, 30%
3oa 10 h, 50%
ROOC
ROOC
3na
R =
O
9.5 h, 58%
3qa
11 h, 54%
3pa 11 h, 48%
3ra
11 h, 56%
CF3
F
N
O
3sa
9 h, 46%
OMe
EtOOC
EtOOC
COOEt
COOEt
O
F
F
O
O
O
N
N
O
O
3ta
4 h, 56%
3ua
7 h, 66%
a Reaction conditions:
1 (0.2 mmol), 2 (0.3 mmol), solvent (anhydrous, 10 mL), rt, under N2 atmosphere,
irradiated by a 500 W medium pressure mercury lamp with Pyrex filter, isolated yields are shown.
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Table 3. Scope of the substrates with aldehyde group a
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a Reaction conditions:
4 (0.2 mmol), 2 (0.3 mmol), solvent (anhydrous, 10 mL), rt, under N2 atmosphere,
irradiated by a 500 W medium pressure mercury lamp with Pyrex filter, isolated yields are shown.
We envisioned that if the ester group of substrates was changed to aldehyde group, these
photocycloaddition reactions would still work. So we decided to examine the substrates
with aldehyde group
4 (Table 3). We found that less reaction time was needed, and this
might be because these substrates containing aldehyde group is more easily excited to form
excited state molecular. The yields were obtained from good to excellent (Table 3). Similar
to 3ha, the products (Table 3, 5aa
likely due to the proposed reaction mechanism (Scheme 3,
examine the substrate with two aldehyde groups 4c for this photocycloaddition reactions,
and we get the products in good yield without isomers (5ca 5cb). Whereafter, to broaden
ꢀ
5ah) are the mixture of isomers with a ratio of 1:1,
I
and II). Moreover, we
,
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the generality of this photocycloaddition reaction we turned to our attention to investigate
substrates containing acetyl group, benzoyl group and cyano group (Table 4). The reaction
still underwent smoothly with good yields (7aa-7ae) and a decreased yield (7baꢀ7bh)
probably due to the benzoyl group which is a large steric hindrance group and might cause
other side reactions, e.g. Norrish type I/II reactions.12 Then, we chose
3,3'ꢀ(1,2ꢀphenylene)diacrylonitrile 6d as a substrate containing cyano group to examine
this reaction and the result was satisfactory (Table 4, 7da). Other substrates containing both
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carbonyl group and ester group (6c
,
6f) or propanoyl group (6e) also were tested, giving
the corresponding products (7ca 7fa
,
, 7ea) in good yield.
Table 4. Scope of substrates containing acetyl group, benzoyl group and cyano groupa
R1
R2
O
R1
R2
hv
+
O
X
MeCN, rt
X
O
2
6
7
O
O
O
O
O
O
O
Ph
Ph
Me
Ph
Ph
Me
O
O
O
R
N
O
N
O
R
O
O
7bf
5.0 h, 50%
7ba
R = Me
4.0 h, 60%
7aa
R = Me
R = Et
R = H
4.0 h, 80% b
4.0 h, 82% b
4.5 h, 74% b
R = Et 7bb 5.0 h, 55%
7ab
7ae
5.0 h, 49% b
7be
R = H
Ph
O
NC
O
CN
O
COOEt
Ph
Ph
O
COOMe
O
N
N
COOMe
O
O
7da 5.0 h, 78% b
7bh
5.0 h, 48%
7ca
6.0 h, 52%
O
O
O
O
EtO
Et
Me
Et
O
O
NMe
5.0 h, 75%b
NMe
O
O
7ea 5.0 h, 70%b
7fa
a
Reaction conditions: 6 (0.2 mmol), 2 (0.3 mmol), solvent (anhydrous, 10 mL), rt, under N2
atmosphere, irradiated by a 500 W medium pressure mercury lamp with Pyrex filter, isolated
yields are shown. b Reaction conditions: 6 (1.0 mmol), 2 (1.5 mmol), solvent (anhydrous, 50 mL),
rt, under N2 atmosphere, irradiated by a 500 W medium pressure mercury lamp with Pyrex filter,
isolated yields are shown.
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To study the proposed mechanism, some brief survey of literature are listed in Scheme 2.
Although the study by Laarhoven13 on the photochemistry of stilbeneꢀlike compound [Scheme 2,
Equation (1)] shows that transformation involve a freeꢀradical process to get such
benzobicyclo[2.1.1]hexene photoproduct, the study by Marija ŠindlerꢀKulyk14 on the
photochemistry of stilbeneꢀlike compound with a novel substituted group [Scheme 2, Equation (2)]
did not detect such the benzobicclo[2.1.1]hexene photoproduct. This means that the substituted
groups on the stilbeneꢀlike compound have a significant impact on the photochemistry reaction of
these stilbeneꢀlike compound. This point also can be seen from the study of Irena Škorić15
[Scheme 2, Equation (3)]. To more important, the study of Irena Škorić is a key evidence for this
photoinduced intermolecular [4+2] cycloaddition. His research has shown that the reaction
mechanism of Equation (3) involves a sixꢀmembered ring closure followed by a sigmatropic 1,5ꢀH
shift to give photoproduct and the cyclic oꢀquinodimethane (oꢀQDM) is the key intermediate of
the photoreaction [Scheme 2, Equation (3)].
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To investigate this reaction mechanism and collect more information about this reaction
mechanism, several control experiments were carried out. In the first experiment this
photoinduced [4+2] reaction succeed to give the desired product 3aa in 55% yield in the presence
of the radical scavengers (2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀyl)oxidanyl (TEMPO) [Scheme 2,
Equation (5)], which indicated that this photoinduced reaction is not a radical pathway. Another
control experiment was conducted by adding 3 equiv of butylated hydroxytoluene (BHT) in the
reaction. The reaction was not prevented by BHT, and the product was obtained smoothly
[Scheme 2, Equation (6)]. This reaction also could not be suppressed by 1,1ꢀdiphenylethylene.
These experiments indicated this photoinduced reaction is not a radical pathway. We use 1b
without 2 as starting material and we found that the compound 8a and 8b were obtained in the
total yield 51% under the standard conditions [Scheme 2, Equation (8)], which were the products
of intramolecular photoinduced [4+2] reaction, but the reaction time became longer because there
was no dienophile 2 to trap the reactive intermediate cyclicꢀoꢀquinodimethane. This result is
different from the Ploder’ work.16 Besides, we did not found the intramolecular reaction products
[Scheme 2, Equation (7)], and more important all the experiments in Table 2 we also did not
found the intramolecular reaction products, and the time of this photoinduced intermolecular [4+2]
reaction is less than the time of intramolecular reaction. This result revealed that the reaction rate
of intermolecular reaction of 1b with 2a (k1) is larger than the reaction rate of intramolecular
reaction of 1b (k2) [Scheme 2, Equation (7), (8)] because there is dienophile (e.g. 2) which would
trap the reactive intermediate cyclic oꢀquinodimethane when the cyclic oꢀquinodimethane once
was generated from the substrates 1 under UV light in the system. In addition, it is noteworthy that
all the products are endoꢀtype compounds and this result is coincided with Freccero group’s work
[Scheme 2, Equation (4)].17 These results revealed that this photoinduced reaction maybe proceed
a key intermediate cyclic oꢀquinodimethane (cyclicꢀoꢀQDM), a highly reactive species,18 which
likely is formed via a conrotatory sixꢀmembered ring closure of substrates under UV light
according to WoodwordꢀHoffmann rules.19 Another two control experiment was conducted by
addition of cyclohexaꢀ1,3ꢀdiene and transꢀstilbene as a triplet quencher in the solution of 1a and
2a in acetonitrile, which did not depress the reaction. In addition, the oxygen, dissolved in the
acetonitrile under airꢀsaturated conditions (Table 1, entries 1ꢀ4), had no obvious effect on the
reaction. These experiments suggest that the reaction involves a singlet state.20
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Scheme 2. Previous work and control experiments
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On the basis of the above experimental results and some literatures (Scheme 2), a most
plausible mechanism pathway was proposed and depicted in Scheme 3. Under UV light irradiation,
the substrate 1 underwent a pericyclic reaction which is a conrotatory sixꢀmembered ring closure
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according to WoodwordꢀHoffmann rules19 to form cyclicꢀoꢀQDM intermediate which was then
trapped by an olefin through the DielsꢀAlder reaction. According to WoodwordꢀHoffmann rules19,
the starting material, trans,transꢀsubstrate 1 should form the transꢀoꢀQDM intermediate under
irradiation (Scheme 3), which could be trapped by olefins from the up or down side to form the
final products I and II with or without isomers. In addition, carbonꢀcarbon double bond could
undergo photochemical cis/transꢀisomerization reactions under UV light, thus trans,transꢀsubstrate
1 could be transformed to cis,transꢀ1 during the reaction if prolonged reaction time was involved.
Then the cisꢀoꢀQDM intermediate was formed from cis,transꢀ1 which was trapped by olefins from
down face to form the single product III (Scheme 3) due to the steric effects.
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Scheme 3. Possible reaction pathway
During our investigation, several gramꢀscale reactions were carried out under standard reaction
conditions and the desired products were obtained in good yield (Scheme 4). The results might
suggest its potential application in natural products synthesis as well as screening of
compound libraries for further chemical biology study.
CONCLUSION
In summary, we have established a facile oneꢀpot procedure for the synthesis of substituted
benzobicyclo[2.2.2]octane skeletons via photoinduced [4+2] reactions of substituted
oꢀdivinylbenzenes with olefins under mild condition. The method is an efficient,
transitionꢀmetalꢀfree, and stepꢀeconomical approach for the rapid construction of these
bridgedꢀring compounds. In addition, the gram scale reactions demonstrated the synthetically
potential applications.
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Scheme 4. Reactions of 1 at gram scale
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R1OOC
COOR1
O
COOR1
hv
+
O
X
CH3CN, r.t.
COOR1
X
O
O
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1 (1.0 g)
3
MeOOC
MeOOC
MeOOC
COOMe
COOMe
O
COOMe
O
O
N
N
N
O
3ab (1.10 g, 73%)
3ac (1.20 g, 68%)
Bn
3aa (1.19 g, 82%)
O
Et
O
Me
EtOOC
EtOOC
COOEt
COOEt
O
O
NH
N
3bb (1.05 g, 72%)
3be (1.06 g, 78%)
O
O
Et
EXPERIMENTAL SECTION
General Information All reactions were carried out with dry solvents using anhydrous conditions
unless otherwise stated. Reagents were purchased at the highest commercial quality and used
without further purification, unless otherwise stated. Reactions were monitored by GCꢀMS or thin
layer chromatography (TLC) carried out on 0.20ꢀ0.25 mm silica gel plates using UV light as the
visualizing agent and phosphomolybdic acid as developing agents. Silica gel was used for flash
column chromatography. Highꢀresolution mass spectra (HRMS) were recorded on a QꢀTOF (ESI)
mass spectrometer. Lowꢀresolution Mass spectra were obtained from GCꢀMS system.
General Procedure for Syntheses of Starting Materials.
General Procedure for Syntheses of Compound 1a-1g, 1k-1s
Corresponding alcohol (5.0 mmol) was dissolved in dry CH2Cl2 (25 mL) and pyridine (7.5
mmol) was added. Reaction mixture was cooled to 0°C and 2ꢀbromoacetyl bromide (5.5 mmol)
was added dropwise. Reaction mixture was stirred for 45 minutes at 0oC and then was quenched
by addition of water (25 mL). The resulting layers were separated and the aqueous layer was
extracted with EtOAc (25×3 mL). The combined organic layers were washed sequentially with
saturated aqueous CuSO4 (25 mL), water (25 mL), brine (25 mL), dried over Na2SO4, and
concentrated in vacuo evaporated to give the appropriate bromoalkyl acetates compound as a
colorless oil that was used in the next step without further purification.21 A solution of the
appropriate bromoalkyl acetates compound (5 mmol) in toluene (25 mL) was added dropwise over
10 min to a solution of triphenylphosphine (5 mmol) in toluene (25 mL). The reaction mixture was
stirred at room temperature for 18 h, and the resulting phosphonium salt was filtered and
ovenꢀdried. The phosphonium salt was obtained in quantitative yield, and was used without
further purification.22 NaOH (0.12 g, 30 mmol) dissolved in water (5 mL) was added to a
suspension of the phosphonium salt (20.0 mmol) in H2O (60 mL) and CH2Cl2 (60 mL). The
mixture was stirred vigorously at room temperature for 1 h and then transferred to a separating
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funnel. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (20×3
mL). The combined organic layers were dried (Na2SO4) and concentrated to give the
corresponding stabilized phosphonium ylides , which was used without further purification.22 To a
solution of corresponding oꢀphthalaldehyde (1 mmol) in THF (15 mL) was added the
corresponding esterꢀstabilized phosphonium ylide (2.4 mmol). The mixture was stirred at room
temperature for 12 h, and concentrated in vacuo. Purification of the residue by column
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chromatography (EtOAc:hexane, 1:4) afforded the compound 1 22
.
General Procedure for Syntheses of Compound 4
To a solution of the compound 1 (3 mmol) in dry THF (20 mL) at −78 °C was added
DIBALꢀH (6.2 mL of a 1.0 M solution in toluene, 6.2 mmol) slowly. After stirring for 1 h, the
reaction mixture was allowed to return to 0 °C. Four hours later, the reaction was quenched with
methanol (3 mL). Then 20 mL aqueous solution of 0.5 M HCl was added. One hour later, the
layers were separated and the aqueous layer was extracted with EtOAc (20×3 mL). The combined
organic extracts were washed with brine, dried over Na2SO4, and concentrated. Purification of the
crude product by chromatography on silica gel ( EtOAc/hexane, 1/3 ) gave the appropriate alcohol
as a clear oil.23 To a solution of oxalyl chloride (2.4 mmol) in dry CH2Cl2 (10 mL) cooled at
−78 °C was added dropwise a solution of dimethylsulfoxide (DMSO 2.3 mmol ) in CH2Cl2 (10
mL). After 5 min, a solution of the appropriate alcohol (2 mmol) in CH2Cl2 (10 mL) was added.
The reaction mixture was then stirred for 15 min at −78 °C and triethylamine (10 mmol) was
added in one portion. After 10 min at −78 °C, the mixture was allowed to warm to room
temperature and diluted with CH2Cl2 (40 mL). The organic layer was successively washed with a
saturated aqueous solution of NH4Cl (20 mL) and brine (20 mL). The combined organic extracts
were dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by flash
chromatography on silica gel (petroleum ether/EtOAc: 9/1) afforded the aldehyde 4 as solid.
The Syntheses of Substrate 4c.
To a solution of the compound 1b (10 mmol) in dry THF (200 mL) at −78 °C was added
DIBALꢀH (62 mL of a 1.0 M solution in toluene, 62 mmol) slowly. After stirring for 1 h, the
reaction mixture was allowed to return to 0 °C. 24 hours later, the reaction was quenched with
methanol (30 mL). Then 200 mL aqueous solution of 0.5 M HCl was added. One hour later, the
layers were separated and the aqueous layer was extracted with EtOAc (200×3 mL). The
combined organic extracts were washed with brine, dried over Na2SO4, and concentrated.
Purification of the crude product by chromatography on silica gel ( EtOAc/hexane, 2:1 ) gave the
Diol as white solid. The diol (0.5 g) in dichloromethane (250 mL) was stirred with activated
manganese dioxide (5g) at ambient temperature for 24 h. The mixture was filtered through Celite,
and the solid was washed well with dichoromethane. Evaporation of the solvent and purification
by flash chromatography on silica gel (petroleum ether/EtOAc: 10/1) gave the dialdehyde 4c.24
General Procedure for Syntheses of Compound 6
To
a solution of oꢀphthalaldehyde (5.0 mmol) in THF (60 mL) was added
1ꢀ(triphenylphosphoranylidene)propanꢀ2ꢀone (12.5 mmol). The mixture was stirred at room
temperature for 16 h and concentrated in vacuo. Purification of the residue by column
chromatography (petroleum ether/EtOAc: 9/1) afforded the compound 6a.22 To a solution of
oꢀphthalaldehyde
(5.0
mmol)
in
THF
(60
mL)
was
added
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1ꢀphenylꢀ2ꢀ(triphenylphosphoranylidene)ethanone (12.5 mmol). The mixture was stirred at room
temperature for 16 h and concentrated in vacuo. Purification of the residue by column
chromatography (petroleum ether/EtOAc: 9/1) afforded the compound 6b.22
The Syntheses of Substrates 1h and 6c.
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To a solution of oꢀphthalaldehyde (2.0 mmol) in THF (15 mL) at room temperature was added a
solution of ethyl 2ꢀ(triphenylphosphoranylidene)acetate (2.0 mmol) in THF (10 mL) dropwise
over 30 min, and the mixture was stirred at 60 °C for 18 h. Purification of the residue by column
chromatography afforded the compound (E)ꢀethyl 3ꢀ(2ꢀformylphenyl)acrylate. Then, to a solution
of (E)ꢀethyl 3ꢀ(2ꢀformylphenyl)acrylate (1.0 mmol) in THF (5mL) at room temperature was added
a solution of methyl 2ꢀ(triphenylphosphoranylidene)acetate (1.0 mmol) in THF (10 mL) dropwise
over 30 min, and the mixture was stirred at 60 °C for 18 h. Purification of the residue by column
chromatography (10% EtOAc/hexane ꢀ 30% EtOAc/hexane) gave compound 1h as an white solid
(45%). To a solution of (E)ꢀethyl 3ꢀ(2ꢀformylphenyl)acrylate (1.0 mmol) in THF (5 mL) at room
temperature was added a solution of 1ꢀphenylꢀ2ꢀ(triphenylphosphoranylidene)ethanone (1.0 mmol)
in THF (10 mL) dropwise over 30 min, and the mixture was stirred at 60 °C for 18 h. Purification
of the residue by column chromatography (10% EtOAc/hexane→30% EtOAc/hexane) gave
compound 6c as yellow oil.
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The Syntheses of Substrate 6d.
A solution of the 2ꢀbromoacetonitrile (25 mmol) in toluene (100 mL) was added dropwise over 10
min to a solution of triphenylphosphine (25 mmol) in toluene (50 mL). The reaction mixture was
stirred at room temperature for 18 h, and the resulting phosphonium salt was filtered and
ovenꢀdried. The phosphonium salt was obtained in quantitative yield, and was used without
further purification. NaOH (0.12 g, 30 mmol ) dissolved in water ( 5 mL ) was added to a
suspension of the phosphonium salt (20.0 mmol) in H2O (60 mL) and CH2Cl2 (60 mL). The
mixture was stirred vigorously at room temperature for 1 h and then transferred to a separating
funnel. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (20×3
mL). The combined organic layers were dried (Na2SO4) and concentrated to give the
corresponding stabilized phosphonium ylides, which was used without further purification.25 To a
solution of corresponding oꢀphthalaldehyde (1 mmol) in THF (15 mL) was added the
corresponding esterꢀstabilized phosphonium ylide (2.4 mmol). The mixture was stirred at room
temperature for 12 h, and concentrated in vacuo. Purification of the residue by column
chromatography (EtOAc:hexane, 1:4) afforded the compound 6d.
The Syntheses of Substrate 1t and 1u.
Using Heck Reactions. To a suspension of Pd(OAc)2 (90 mg, 0.4 mmol), nꢀBu4NCl (1.14g, 5
mmol), K2CO3 (3.45g, 25 mmol), and LiCl (212mg, 5mmol) in DMF (25 mL) was added
1,2ꢀdibromoꢀ4,5ꢀdifluorobenzene or 5,6ꢀdibromobenzo[d][1,3]dioxole (5 mmol) and ethyl acrylate
o
(25 mmol). The mixture was stirred at 100 C for 18 h, cooled to room temperature, diluted with
Et2O (25 mL), and washed with water (50 mL). The aqueous layer was extracted with Et2O (50
mL x 2), and the combined organic layers were washed with brine (100 mL), dried (MgSO4), and
concentrated. Purification of the residue by column chromatography gave the compound 1t and
1u.22
1
(E)ꢀ3ꢀ[2ꢀ{(E)ꢀ2ꢀMethoxycarbonylvinyl}phenyl]acrylic acid methyl ester (1a).22 White solid. H
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NMR (400 MHz, CDCl3) δ 8.04 (d, J = 15.8 Hz, 2H), 7.57 (dd, J = 5.7, 3.5 Hz, 2H), 7.40 (dd, J =
5.8, 3.4 Hz, 2H), 6.36 (d, J = 15.8 Hz, 2H), 3.83 (s, 6H). 13C NMR (150 MHz, CDCl3) δ 166.8,
141.5, 134.2, 130.1, 127.6, 121.4, 51.8. LRMS (EI): 246[M+], 231, 215, 199, 186, 171, 155, 143,
128, 115, 102, 92, 77. HRMS (ESI): calcd for C14H15O4, [M+H] +, 247.0970; found, 247.0976.
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(E)ꢀ3ꢀ[2ꢀ{(E)ꢀ2ꢀEthoxycarbonylvinyl}phenyl]acrylic acid ethyl ester (1b).22 White solid. 1H NMR
(400 MHz, CDCl3) δ 8.04 (d, J = 15.8 Hz, 2H), 7.65 – 7.52 (m, 2H), 7.46 – 7.35 (m, 2H), 6.35 (d,
J = 15.8 Hz, 2H), 4.29 (q, J = 7.1 Hz, 4H), 1.35 (t, J = 7.1 Hz, 6H).13C NMR (100 MHz, CDCl3) δ
166.4, 141.3, 134.3, 130.00, 127.6, 122.00, 60.7, 14.3. HRMS (ESI): calcd for C16H19O4, [M+H] +,
275.1283; found, 275.1281.
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(2E,2'E)ꢀdimethyl 3,3'ꢀ(4ꢀmethylꢀ1,2ꢀphenylene)diacrylate (1c). White solid. 1H NMR (400 MHz,
CDCl3) δ 7.99 (d, J = 15.8, 1H), 7.97 (d, J = 15.8, 1H), 7.58 (dd, J = 8.7, 5.7 Hz, 1H), 7.26 (dd, J
= 9.5, 2.6 Hz, 1H), 7.12 (td, J = 8.3, 2.6 Hz, 1H), 6.34 (d, 15.8 Hz, 1H), 6.32 (d, 15.8 Hz, 1H) 3.85
(s, 3H), 3.84 (s, 3H), 2.38 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.0, 166.9, 141.6, 141.3,
140.4, 134.2, 131.4, 131.1, 128.2, 127.5, 121.2, 120.4, 52.9, 52.8, 21.4. LRMS (EI): 260[M+], 245,
229, 213, 200, 185, 169, 155, 142, 129, 115, 99, 77. HRMS (ESI): calcd for C15H17O4, [M+H] +,
261.1127; found, 261.1128.
(2E,2'E)ꢀdimethyl 3,3'ꢀ(4ꢀchloroꢀ1,2ꢀphenylene)diacrylate (1d).26 White solid. 1H NMR (400 MHz,
CDCl3) δ 7.99 (d, J = 15.8, 1H), 7.98 (d, J = 15.8, 1H), 7.58 (dd, J = 8.7, 5.7 Hz, 1H), 7.26 (dd, J
= 9.5, 2.6 Hz, 1H), 7.12 (td, J = 8.3, 2.6 Hz, 1H), 6.34 (d, J = 15.8 Hz, 1H), 6.32 (d, J = 15.8 Hz,
1H), 3.85 (s, 3H), 3.84 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 166.6, 166.5, 140.2, 140.1, 136.2,
135.8, 132.6, 130.1, 128.9, 127.5, 122.6, 121.8, 52.1, 52.. LRMS (EI): 280[M+], 249, 228, 189,
+
162, 142, 126, 109, 81, 59. HRMS (ESI): calcd for C14H14ClO4, [M+H] , 281.0581; found,
281.0582.
1
(2E,2'E)ꢀdiethyl 3,3'ꢀ(4ꢀchloroꢀ1,2ꢀphenylene)diacrylate (1e). White solid. H NMR (400 MHz,
CDCl3) δ 7.94 (dd, J = 15.8, 1.8 Hz, 2H), 7.52 (dd, J = 13.5, 5.2 Hz, 2H), 7.41 – 7.25 (m, 1H),
6.34 (dd, J = 15.8, 8.2 Hz, 2H), 4.29 (qd, J = 7.1, 1.9 Hz, 4H), 1.35 (td, J = 7.1, 1.0 Hz, 6H). 13
C
NMR (150 MHz, CDCl3) δ 166.2, 166.0, 140.0, 139.9, 136.0, 135.8, 132.6, 130.0, 128.9, 127.5,
123.1, 122.3, 60.9, 60.8, 14.3. LRMS (EI): 308[M+], 295, 281, 263, 251, 234, 219, 207, 189, 177,
163, 149, 127, 115, 101, 89. HRMS (ESI): calcd for C16H18ClO4, [M+H] +, 309.0894; found,
309.0895.
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(2E,2'E)ꢀdiethyl 3,3'ꢀ(4ꢀmethoxyꢀ1,2ꢀphenylene)diacrylate (1f). White solid. H NMR (400 MHz,
CDCl3) δ 8.06 (d, J = 15.8 Hz, 1H), 8.00 (d, J = 15.8 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.06 (d, J
= 2.6 Hz, 1H), 6.96 (dd, J = 8.7, 2.6 Hz, 1H), 6.35 (d, J = 15.8 Hz, 1H), 6.29 (d, J = 15.7 Hz, 1H),
4.30 (p, J = 7.2 Hz, 4H), 3.86 (s, 3H), 1.35 (td, J = 7.1, 5.1 Hz, 6H). 13C NMR (150 MHz, CDCl3)
δ 166.8, 166.4, 160.9, 141.3, 140.7, 136.0, 129.1, 126.9, 122.2, 119.4, 116.5, 111.9, 60.8, 60.6,
55.5, 14.4, 14.3. HRMS (ESI): calcd for C17H21O5, [M+H] +, 305.1389; found, 305.1387.
1
(2E,2'E)ꢀdiethylꢀ3,3'ꢀ(4ꢀfluoroꢀ1,2ꢀphenylene)diacrylate (1g). White solid. H NMR (400 MHz,
CDCl3) δ 7.97 (dd, J = 15.8, 5.4 Hz, 2H), 7.57 (dd, J = 8.7, 5.7 Hz, 1H), 7.37 – 7.22 (m, 1H), 7.10
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(td, J = 8.3, 2.6 Hz, 1H), 6.32 (dd, J = 17.9, 15.8 Hz, 2H), 4.29 (qd, J = 7.1, 3.3 Hz, 4H), 1.35 (td,
J = 7.1, 1.9 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 166.3, 166.1, 163.4 (d, J = 251.3 Hz), 140.0
(d, J = 5.8 Hz), 136.4 (d, J = 7.8 Hz), 130.5 (d, J = 3.1 Hz), 129.7 (d, J = 8.7 Hz), 123.0, 121.7,
117.3 (d, J = 22.0 Hz), 114.0 (d, J = 22.5 Hz), 60.9, 60.8, 14.3, 14.3. HRMS (ESI): calcd for
C16H18FO4, [M+H]+, 293.1189; found, 293.1194..
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1
(E)ꢀethyl 3ꢀ(2ꢀ((E)ꢀ3ꢀmethoxyꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1h).27 White solid. H NMR
(400 MHz, CDCl3) δ 8.04 (dd, J = 15.8, 3.8 Hz, 2H), 7.57 (dd, J = 5.8, 3.4 Hz, 2H), 7.49 – 7.34
(m, 2H), 6.35 (dd, J = 15.8, 2.0 Hz, 2H), 4.29 (q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 1.35 (t, J = 7.1 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ 166.9, 166.4, 141.5, 141.3, 134.4, 134.2, 130.1, 130.0, 127.6,
127.6, 122.0, 121.5, 60.8, 51.9, 14.3. HRMS (ESI): calcd for C15H17O4, [M+H] +, 261.1127; found,
261.1128.
1
(E)ꢀbutyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxoꢀ3ꢀbutoxypropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1k).28 Colorless oil. H NMR
(400 MHz, CDCl3) δ 8.03 (d, J = 15.8 Hz, 2H), 7.57 (dd, J = 5.8, 3.4 Hz, 2H), 7.39 (dd, J = 5.8,
3.4 Hz, 2H), 6.35 (d, J = 15.8 Hz, 2H), 4.23 (t, J = 6.7 Hz, 4H), 1.75 – 1.66 (m, 4H), 1.51 – 1.38
(m, 4H), 0.97 (t, J = 7.4 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 166.5, 141.3, 134.3, 130.0, 127.7,
121.9, 64.6, 30.7, 19.2, 13.8. LRMS (EI): 330[M+], 315, 301, 274, 257, 242, 228, 214, 200, 172,
155, 101, 83, 57. HRMS (ESI): calcd for C20H27O4, [M+H] +, 331.1909; found, 331.1907.
1
(E)ꢀisopropylꢀ3ꢀ(2ꢀ((E)ꢀ3ꢀisopropoxyꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1l). Colorless oil. H
NMR (400 MHz, CDCl3) δ 8.02 (d, J = 15.8 Hz, 2H), 7.56 (dd, J = 5.7, 3.5 Hz, 2H), 7.38 (dd, J =
5.8, 3.3 Hz, 2H), 6.33 (d, J = 15.8 Hz, 2H), 5.24 – 5.03 (m, 2H), 1.33 (d, J = 6.3 Hz, 12H). 13C
NMR (150 MHz, CDCl3) δ 166.0, 141.0, 134.3, 129.9, 127.6, 122.5, 68.1, 22.0. LRMS (EI):
302[M+], 281, 260, 243, 231, 214, 200, 184, 172, 157, 144, 129, 115, 102, 89. HRMS (ESI): calcd
for C18H23O4, [M+H] +, 303.1596; found, 303.1592.
(E)ꢀ3ꢀ[2ꢀ{(E)ꢀ2ꢀtertꢀButoxycarbonylvinyl}ꢀphenyl]acrylic acid tertbutyl ester (1m).29 White solid.
1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 15.8 Hz, 2H), 7.55 (dd, J = 5.7, 3.5 Hz, 2H), 7.36 (dd,
J = 5.8, 3.3 Hz, 2H), 6.27 (d, J = 15.8 Hz, 2H), 1.54 (s, 18H). 13C NMR (150 MHz, CDCl3) δ
165.8, 140.4, 134.4, 129.7, 127.6, 123.6, 80.8, 28.2. LRMS (EI): 330[M+], 274, 257, 239, 218,
200, 172, 155, 129, 115, 92, 77. HRMS (ESI): calcd for C20H27O4, [M+H] +, 331.1909; found,
331.1918.
(E)ꢀcyclobutyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxoꢀ3ꢀcyclobutoxypropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1n). Colorless oil.
1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 15.8 Hz, 2H), 7.57 (dd, J = 5.6, 3.5 Hz, 2H), 7.39 (dd,
J = 5.8, 3.4 Hz, 2H), 6.33 (d, J = 15.8 Hz, 2H), 5.13 (p, J = 7.5 Hz, 2H), 2.49 – 2.37 (m, 4H), 2.24
– 2.07 (m, 4H), 1.84 (q, J = 10.3 Hz, 2H), 1.68 (qd, J = 10.4, 5.2 Hz, 2H).13C NMR (150 MHz,
CDCl3) δ 165.8, 141.3, 134.3, 130.0, 127.6, 121.9, 69.1, 30.4, 13.6. LRMS (EI): 326[M+], 227,
157, 128, 55. HRMS (ESI): calcd for C20H23O4, [M+H] +, 327.1596; found, 327.1594.
(E)ꢀcyclopentyl 3ꢀ(2ꢀ((E)ꢀ3ꢀ(cyclopentyloxy)ꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1o). Colorless
oil. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 15.8 Hz, 2H), 7.58 (dd, J = 5.7, 3.5 Hz, 2H), 7.48 –
7.34 (m, 2H), 6.34 (d, J = 15.8 Hz, 2H), 5.33 (td, J = 5.9, 3.0 Hz, 2H), 1.97 (m, 4H), 1.88 – 1.72
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(m, 8H), 1.72 – 1.58 (m, 4H). 13C NMR (150 MHz, CDCl3) δ 166.2, 141.0, 134.3, 129.9, 127.7,
122.4, 77.4, 32.8, 23.8. LRMS (EI): 354[M+], 201, 173, 129, 69. HRMS (ESI): calcd for
C22H27O4, [M+H] +, 355.1909; found, 355.1906.
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(E)ꢀcyclohexyl 3ꢀ(2ꢀ((E)ꢀ3ꢀ(cyclohexyloxy)ꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (1p). Colorless
oil. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 15.8 Hz, 2H), 7.57 (m, 2H), 7.38 (m, 2H), 6.34 (d,
J = 15.8 Hz, 2H), 5.01 – 4.78 (m, 2H), 2.00 – 1.87 (m, 2H), 1.82 – 1.74 (m, 4H), 1.61 – 1.37 (m,
10H), 1.35 – 1.25 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 165.9, 141.0, 134.3, 129.9, 127.6 ,
122.4, 73.0, 31.7, 25.4, 23.8. LRMS (EI): 382[M+], 367, 354, 327, 315, 300, 282, 267, 255, 237,
218, 200, 184, 172, 157, 128, 115. HRMS (ESI): calcd for C24H31O4, [M+H] +, 383.2222; found,
383.2221.
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(E)ꢀ4ꢀfluorobenzylꢀ3ꢀ(2ꢀ((E)ꢀ3ꢀ(4ꢀfluorobenzyloxy)ꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate(1q)
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White solid. H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 15.8 Hz, 2H), 7.58 (dt, J = 7.1, 3.6 Hz,
2H), 7.42 (dt, J = 5.5, 4.4 Hz, 6H), 7.09 (t, J = 8.6 Hz, 4H), 6.40 (d, J = 15.8 Hz, 2H), 5.25 (s, 4H).
13C NMR (150 MHz, CDCl3) δ 166.1, 162.7 (d, J = 246.8 Hz), 141.9, 134.2, 131.8 (d, J = 3.2 Hz),
130.4 (d, J = 7.9 Hz), 130.2, 127.7, 121.4, 115.6 (d, J = 21.8 Hz), 65.8. LRMS (EI): 434[M+], 201,
157, 109, 83.HRMS (ESI): calcd for C26H21O4F2, [M+H] +, 435.1408; found, 435.1413.
(E)ꢀ4ꢀ(trifluoromethyl)benzylꢀ3ꢀ(2ꢀ((E)ꢀ3ꢀ(4ꢀ(trifluoromethyl)benzyloxy)ꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)ph
enyl)acrylate (1r). White solid. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 15.8 Hz, 2H), 7.64 (d, J
= 8.2 Hz, 4H), 7.59 (dd, J = 5.7, 3.5 Hz, 2H), 7.53 (d, J = 8.1 Hz, 4H), 7.42 (dd, J = 5.8, 3.3 Hz,
2H), 6.41 (d, J = 15.8 Hz, 2H), 5.32 (s, 4H). 13C NMR (150 MHz, CDCl3) δ 166.0, 142.3, 139.9,
134.1, 130.4 (q, J = 32.2 Hz), 130.4, 128.2, 127.8, 125.6 (q, J = 3.8 Hz), 124.0 (q, J = 272.2 Hz),
121.1, 65.6. LRMS (EI): 534[M+], 335, 198, 159, 109. HRMS (ESI): calcd for C28H21O4F6, [M+H]
+, 535.1344; found, 535.1349.
(E)ꢀ4ꢀmethoxybenzyl 3ꢀ(2ꢀ((E)ꢀ3ꢀ((4ꢀmethoxybenzyl)oxy)ꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate
(1s). Colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 15.8 Hz, 2H), 7.53 (dd, J = 5.7, 3.5
Hz, 2H), 7.36 (m, 6H), 7.01 – 6.82 (m, 4H), 6.36 (d, J = 15.8 Hz, 2H), 5.20 (s, 4H), 3.81 (s, 6H).
13C NMR (150 MHz, CDCl3) δ 166.2, 159.7, 141.7, 134.2, 130.2, 130.1, 128.0, 127.6, 121.7,
114.0, 66.3, 55.3. HRMS (ESI): calcd for C28H27O6, [M+H] +, 459.1802; found, 459.1809.
(2E,2'E)ꢀdiethyl 3,3'ꢀ(benzo[d][1,3]dioxoleꢀ5,6ꢀdiyl)diacrylate (1t). Yellow solid. 1H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 15.7 Hz, 2H), 7.03 (s, 2H), 6.24 (d, J = 15.7 Hz, 2H), 6.04 (s, 2H), 4.27 (q,
J = 7.1 Hz, 4H), 1.34 (t, J = 7.1 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 166.6, 149.7, 140.4, 129.4,
120.1, 106.4, 102.0, 60.7, 14.3. HRMS (ESI): calcd for C17H19O6, [M+H] +, 319.1176; found,
319.1175.
(2E,2'E)ꢀdiethyl 3,3'ꢀ(4,5ꢀdifluoroꢀ1,2ꢀphenylene)diacrylate (1u). White solid. 1H NMR (400 MHz,
CDCl3) δ 7.91 (d, J = 15.8 Hz, 2H), 7.38 (t, J = 9.4 Hz, 2H), 6.29 (d, J = 15.8 Hz, 2H), 4.29 (q, J =
7.1 Hz, 4H), 1.35 (t, J = 7.1 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 165.9, 151.13 (dd, J = 255.7,
15.0 Hz), 138.9, 131.4 (d, J = 4.8 Hz), 122.8, 116.23 (dd, J = 13.3, 5.6 Hz), 60.9, 14.3. HRMS
(ESI): calcd for C16H17O4F2, [M+H] +, 311.1089; found, 311.1095.
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(E)ꢀMethyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxopropꢀ1ꢀenyl)phenyl)acrylate (4a).30 Yellow solid. 1H NMR (400 MHz,
CDCl3) δ 9.80 (d, J = 7.6 Hz, 1H), 8.09 (d, J = 15.8 Hz, 1H), 7.90 (d, J = 15.8 Hz, 1H), 7.72 –
7.58 (m, 2H), 7.55 – 7.43 (m, 2H), 6.69 (dd, J = 15.8, 7.7 Hz, 1H), 6.41 (d, J = 15.8 Hz, 1H), 3.86
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 193.5, 166.8, 148.8, 141.0, 134.5, 133.5, 131.4, 131.0,
130.3, 127.9, 127.7, 122.1, 52.0. LRMS (EI): 216[M+], 201, 184, 157, 143, 128, 115, 102, 89.
HRMS (ESI): calcd for C13H13O3, [M+H] +, 217.0865; found, 217.0866.
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(E)ꢀethyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxopropꢀ1ꢀenyl)phenyl)acrylate (4b).31 Yellow solid. H NMR (400 MHz,
CDCl3) δ 9.78 (d, J = 7.7 Hz, 1H), 8.06 (d, J = 15.8 Hz, 1H), 7.88 (d, J = 15.8 Hz, 1H), 7.69 –
7.57 (m, 2H), 7.55 – 7.38 (m, 2H), 6.67 (dd, J = 15.8, 7.7 Hz, 1H), 6.39 (d, J = 15.8 Hz, 1H), 4.30
(q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 193.4, 166.3, 148.8,
140.7, 134.7, 133.5, 131.4, 131.0, 130.2, 127.9, 127.6, 122.6, 60.9, 14.3.
1,2ꢀBis(2ꢀformylethenyl)benzene (4c). 1H NMR (400 MHz, CDCl3) δ 9.80 (d, J = 7.5 Hz, 2H), 7.88
(d, J = 15.8 Hz, 2H), 7.66 (dt, J = 7.2, 3.6 Hz, 2H), 7.59 – 7.34 (m, 2H), 6.69 (dd, J = 15.8, 7.5 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ 193.0, 148.1, 133.8, 132.1, 131.1, 128.1. HRMS (ESI): calcd for
C12H11O2, [M+H] +, 187.0754; found, 187.0752.
(3E,3'E)ꢀ4,4'ꢀ(1,2ꢀphenylene)bis(butꢀ3ꢀenꢀ2ꢀone) (6a).22 White solid. H NMR (400 MHz, CDCl3)
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δ 7.87 (d, J = 16.0 Hz, 2H), 7.60 (dd, J = 5.7, 3.5 Hz, 2H), 7.43 (dd, J = 5.8, 3.3 Hz, 2H), 6.64 (d,
J = 16.0 Hz, 2H), 2.41 (s, 6H). 13C NMR (150 MHz, CDCl3) δ 197.9, 139.8, 134.6, 130.4, 130.3,
127.8, 28.1.
(2E,2'E)ꢀ3,3'ꢀ(1,2ꢀphenylene)bis(1ꢀphenylpropꢀ2ꢀenꢀ1ꢀone) (6b).22 Yellow solid. H NMR (400
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MHz, CDCl3) δ 8.19 (d, J = 15.6 Hz, 2H), 8.03 (d, J = 7.6 Hz, 4H), 7.72 (dd, J = 5.5, 3.5 Hz, 2H),
7.59 (t, J = 7.3 Hz, 2H), 7.55 – 7.46 (m, 4H), 7.43 (d, J = 15.6 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ 190.1, 141.8, 137.9, 135.4, 133.0, 130.2, 128.7, 128.6, 128.2, 126.1.
(E)ꢀethyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxoꢀ3ꢀphenylpropꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (6c). Yellow oil. 1H NMR (400
MHz, CDCl3) δ 8.19 – 7.97 (m, 4H), 7.74 – 7.67 (m, 1H), 7.60 (t, J = 4.6 Hz, 2H), 7.51 (t, J = 7.5
Hz, 2H), 7.47 – 7.40 (m, 3H), 6.37 (d, J = 15.8 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 190.0, 166.4, 141.5, 141.5, 138.0, 134.9, 133.0, 130.2,
129.9, 128.8, 128.7, 128.6, 128.0, 127.8, 125.9, 122.1, 60.7, 14.3. HRMS (ESI): calcd for
C20H19O3, [M+H] +, 307.1334; found, 307.1332.
3,3'ꢀ(1,2ꢀphenylene)diacrylonitrile (6d). White solid. 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.39 (m,
6H), 6.14 – 5.50 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 147.0, 146.7, 132.9, 131.3, 131.2, 130.8,
129.0, 127.2, 126.8, 117.3, 100.9, 100.4. HRMS (ESI): calcd for C12H9N2, [M+H] +, 181.0766;
found, 181.0768.
(1E,1'E)ꢀ1,1'ꢀ(1,2ꢀphenylene)bis(pentꢀ1ꢀenꢀ3ꢀone) (6e). 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J =
16.0 Hz, 2H), 7.59 (dd, J = 5.7, 3.5 Hz, 2H), 7.41 (dd, J = 5.8, 3.3 Hz, 2H), 6.65 (d, J = 16.0 Hz, 2H),
2.72 (q, J = 7.3 Hz, 4H), 1.19 (t, J = 7.3 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 200.4, 138.7, 134.7,
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130.1, 129.4, 127.7, 34.5, 8.1. HRMS (ESI): calcd for C16H19O2, [M+H] +, 243.1380; found,
243.1387.
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(E)ꢀethyl 3ꢀ(2ꢀ((E)ꢀ3ꢀoxobutꢀ1ꢀenꢀ1ꢀyl)phenyl)acrylate (6f). 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J =
15.8 Hz, 1H), 7.87 (d, J = 16.1 Hz, 1H), 7.70 – 7.52 (m, 2H), 7.52 – 7.33 (m, 2H), 6.62 (d, J = 16.1 Hz,
1H), 6.36 (dd, J = 15.8, 0.8 Hz, 1H), 4.29 (qd, J = 7.1, 0.7 Hz, 2H), 2.41 (d, J = 0.8 Hz, 3H), 1.35 (td, J
= 7.1, 0.7 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 192.7, 161.1, 135.9, 134.6, 129.2, 128.9, 125.1,
124.9, 124.8, 122.4, 122.3, 116.8, 55.4, 22.5, 9.0. HRMS (ESI): calcd for C15H17O3, [M+H] +,
2245.1172; found, 245.1177.
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General Procedures for Preparation of Products 3, 5, and 7.
3: In a silica tube, 1 (0.2 mmol) and 2 (0.3 mmol) were added to anhydrous MeCN (10 mL), and
were charged with N2 three times. The mixture was allowed to expose to 500W medium
pressure mercury lamp with Pyrex filter for 4ꢀ15h (monitored by TLC). After the substrate 1 was
consumed, the solvent was removed under vacuo, and the residue was purified by column
chromatography (10% EtOAc/hexaneꢀ50% EtOAc/hexane) to give the product.
5: In a silica tube, 4 (0.2 mmol) and 2 (0.3 mmol) were added to anhydrous MeCN (10 mL), and
were charged with N2 three times. The mixture was allowed to expose to 500W medium
pressure mercury lamp with Pyrex filter for 2ꢀ4 h (monitored by TLC). After the substrate 4 was
consumed, the solvent was removed under vacuo, and the residue was purified by column
chromatography (10% EtOAc/hexaneꢀ50% EtOAc/hexane) to give the product.
7: In a silica tube, 6 (0.2 mmol) and 2 (0.3 mmol) were added to anhydrous MeCN (10 mL), and
were charged with N2 three times. The mixture was allowed to expose to 500W medium
pressure mercury lamp with Pyrex filter for 4 h (monitored by TLC). After the substrate 6 was
consumed, the solvent was removed under vacuo, and the residue was purified by column
chromatography (10% EtOAc/hexaneꢀ50% EtOAc/hexane) to give the product.
gram scale reactions : In a silica tube, 1a/1b ( 1.0g ) and 2 ( 1.5 equiv. ) were added to anhydrous
MeCN (100 mL) and charged with N2 three times. The mixture was allowed to expose to 500W
medium pressure mercury lamp with Pyrex filter for 12ꢀ16 h (monitored by TLC). After the
substrate 1a/1b was consumed, the solvent was removed under vacuo, and the residue was
purified by column chromatography (10% EtOAc/hexaneꢀ50% EtOAc/hexane) to give the
product.
Compound 3aa: Colorless oil. 60 mg. Yield 84%. 1H NMR (400 MHz, CDCl3) δ 7.26 – 7.14 (m,
3H), 7.14 – 6.99 (m, 1H), 4.06 (t, J = 2.7 Hz, 1H), 3.93 (t, J = 3.0 Hz, 1H), 3.82 (s, 3H), 3.59 (s,
3H), 3.47 (dd, J = 5.5, 2.2 Hz, 1H), 3.23 (dd, J = 8.5, 3.2 Hz, 1H), 3.19 (dd, J = 5.5, 2.9 Hz, 1H),
3.11 (dd, J = 8.5, 3.2 Hz, 1H), 2.47 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 177.4, 176.9, 173.3,
172.2, 136.3, 134.6, 128.2, 128.2, 126.1, 125.2, 52.8, 52.4, 44.6, 44.4, 43.9, 40.7, 38.8, 38.5, 24.3.
LRMS (EI): 357[M+], 325, 286, 187, 153, 128. HRMS (ESI): calcd for C19H20O6N, [M+H] +,
358.1285; found, 358.1294.
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Compound 3ab: White solid. 56 mg. Yield 76%. mp 110ꢀ111 C. 1H NMR (400 MHz, CDCl3) δ
7.26 – 7.00 (m, 4H), 4.07 (s, 1H), 3.94 (t, J = 2.8 Hz, 1H), 3.83 (s, 3H), 3.60 (s, 3H), 3.48 (dd, J =
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5.4, 1.9 Hz, 1H), 3.22 – 3.16 (m, 2H), 3.09 (dt, J = 9.8, 5.0 Hz, 3H), 0.35 (t, J = 7.2 Hz, 3H). 13
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NMR (150 MHz, CDCl3) δ 177.2, 176.8, 173.3, 172.3, 136.5, 134.8, 128.1, 128.1, 126.2, 125.3,
52.8, 52.4, 44.6, 44.4, 43.6, 40.4, 38.9, 38.6, 33.1, 11.9. LRMS (EI): 371[M+], 329, 186, 128.
HRMS (ESI): calcd for C20H22O6N, [M+H] +, 372.1442; found, 372.1451.
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Compound 3ac: White solid. 65 mg. Yield 75%. mp 189ꢀ190 oC. H NMR (400 MHz, CDCl3) δ
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7.25 – 7.01 (m, 7H), 6.57 (d, J = 7.1 Hz, 2H), 4.27 (s, 2H), 4.09 (t, J = 2.7 Hz, 1H), 3.96 (t, J = 3.0
Hz, 1H), 3.83 (s, 3H), 3.60 (s, 3H), 3.49 (dd, J = 5.4, 2.2 Hz, 1H), 3.26 (dd, J = 8.6, 3.2 Hz, 1H),
3.18 (dd, J = 5.4, 2.9 Hz, 1H), 3.15 (dd, J = 8.7, 3.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ
177.0, 176.6, 173.3, 172.2, 136.3, 134.8, 134.5, 128.4, 128.3, 128.3, 127.4, 127.2, 126.2, 125.2,
52.9, 52.5, 44.8, 44.7, 43.8, 42.0, 40.6, 38.7, 38.5. LRMS (EI): 433[M+], 401, 369, 186, 155, 128,
91. HRMS (ESI): calcd for C25H24O6N, [M+H] +, 434.1598; found, 434.1612.
Compound 3ad: White solid. 51 mg. Yield 64%. mp 138ꢀ139 oC. 1H NMR (400 MHz, CDCl3) δ
7.25 – 7.07 (m, 4H), 4.01 (t, 1H), 3.89 (t, J = 3.1 Hz, 1H), 3.82 (s, 3H), 3.60 (s, 3H), 3.46 (dd, J =
5.5, 2.3 Hz, 1H), 3.18 (dd, J = 5.5, 2.9 Hz, 1H), 3.06 (dd, J = 8.8, 3.3 Hz, 1H), 2.94 (dd, J = 8.8,
3.3 Hz, 1H), 1.08 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 178.5, 178.1, 173.3, 172.4, 136.8, 135.1,
128.0, 127.9, 126.3, 125.3, 58.1, 52.8, 52.4, 44.6, 44.4, 43.3, 40.2, 39.2, 38.9, 27.7. HRMS (ESI):
calcd for C22H25O6NNa, [M+Na] +, 422.1574; found, 422.1581.
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Compound 3ae: White solid. 47 mg. Yield 68%. mp 169ꢀ170 oC. H NMR (400 MHz, CDCl3) δ
7.67 (s, 1H), 7.29 – 7.02 (m, 4H), 4.06 (t, J = 2.7 Hz, 1H), 3.93 (t, J = 3.0 Hz, 1H), 3.83 (s, 3H),
3.62 (s, 3H), 3.45 (dd, J = 5.4, 2.2 Hz, 1H), 3.27 (dd, J = 8.7, 3.2 Hz, 1H), 3.20 (dd, J = 5.4, 2.9
Hz, 1H), 3.16 (dd, J = 8.7, 3.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 177.4, 176.8, 173.3, 172.2,
136.4, 134.6, 128.4, 126.3, 125.4, 52.9, 52.5, 45.1, 44.5, 44.4, 41.9, 38.6, 38.3. LRMS (EI):
343[M+], 311, 252, 18, 155, 128. HRMS (ESI): calcd for C18H17O6NNa, [M+Na] +, 366.0948;
found, 366.0959.
Compound 3af: Colorless oil. 31 mg. Yield 45%. 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.06 (m,
4H), 4.11 (t, J = 2.7 Hz, 1H), 3.97 (t, J = 3.0 Hz, 1H), 3.82 (s, 3H), 3.61 (s, 3H), 3.55 – 3.49 (m,
1H), 3.47 – 3.39 (m, 2H), 3.21 (dd, J = 5.4, 2.9 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 173.0,
171.7, 171.4, 170.9, 135.9, 134.0, 129.0, 126.5, 125.5, 53.0, 52.7, 44.6, 44.2, 44.1, 41.6, 38.5, 38.3.
HRMS (ESI): calcd for C18H16O7Na, [M+Na] +, 367.0788; found, 367.0794.
Compound 3ba: White solid. 56 mg. Yield 77%. mp 163ꢀ164 oC. 1H NMR (400 MHz, CDCl3) δ
7.28 – 7.15 (m, 3H), 7.14 – 7.03 (m, 1H), 4.34 – 4.17 (m, 2H), 4.12 – 3.98 (m, 3H), 3.94 (t, J = 3.1
Hz, 1H), 3.46 (dd, J = 5.4, 2.4 Hz, 1H), 3.24 (dd, J = 8.5, 3.2 Hz, 1H), 3.20 (dd, J = 5.4, 2.9 Hz,
1H), 3.12 (dd, J = 8.5, 3.3 Hz, 1H), 2.48 (d, J = 4.1 Hz, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.19 (t, J =
7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.5, 177.1, 172.9, 171.8, 136.5, 134.6, 128.2, 128.1,
126.1, 125.2, 61.8, 61.3, 44.6, 44.4, 43.9, 40.7, 38.8, 38.7, 24.3, 14.3, 14.2. HRMS (ESI): calcd
for C21H24O6N, [M+H] +, 386.1598; found, 386.1604.
Compound 3bb: Colorless oil. 60 mg. Yield 75%. 1H NMR (400 MHz, CDCl3) δ 7.17 – 7.10 (m,
3H), 7.06 (d, J = 6.0 Hz, 1H), 4.27 – 4.16 (m, 2H), 4.05 – 3.93 (m, 3H), 3.88 (s, 1H), 3.46 – 3.37
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(m, 1H), 3.15 (dd, J = 7.8, 3.2 Hz, 2H), 3.04 (dd, J = 12.9, 7.6 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H),
1.13 (t, J = 7.1 Hz, 3H), 0.29 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.2, 176.8,
172.8, 171.8, 136.6, 134.8, 128.0, 127.9, 126.1, 125.3, 61.7, 61.2, 44.5, 44.3, 43.6, 40.4, 38.8, 38.8,
33.0, 14.2, 14.1, 11.9. HRMS (ESI): calcd for C22H26O6N, [M+H] +, 400.1755; found, 400.1763.
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Compound 3bc: White solid. 60 mg. Yield 70%. H NMR (400 MHz, CDCl3) δ 7.23 – 6.88 (m,
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7H), 6.56 (d, J = 7.3 Hz, 2H), 4.30 – 4.19 (m, 4H), 4.09 – 3.97 (m, 3H), 3.94 (t, J = 3.0 Hz, 1H),
3.45 (dd, J = 5.3, 2.2 Hz, 1H), 3.25 (dd, J = 8.6, 3.1 Hz, 1H), 3.16 (dd, J = 5.3, 3.0 Hz, 1H), 3.13
(dd, J = 8.7, 3.2 Hz, 1H), 1.35 (t, J = 7.2 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 177.1, 176.7, 172.9, 171.8, 136.4, 134.8, 134.6, 128.4, 128.3, 128.2, 127.4, 127.2, 126.1,
125.2, 61.8, 61.3, 44.8, 44.6, 43.8, 42.0, 40.7, 38.7, 38.6, 14.3, 14.2. LRMS (EI): 461[M+], 373,
186, 155, 128. HRMS (ESI): calcd for C27H28O6N, [M+H] +, 462.1911; found, 462.1909.
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Compound 3bd: White solid. 50 mg. Yield 58%. H NMR (400 MHz, CDCl3) 7.26 – 6.82 (m,
4H), 4.26 (q, J = 7.1 Hz, 2H), 4.13 – 3.94 (m, 3H), 3.89 (t, J = 3.1 Hz, 1H), 3.44 (dd, J = 5.3, 2.3
Hz, 1H), 3.18 (dd, J = 5.3, 2.9 Hz, 1H), 3.07 (dd, J = 8.8, 3.3 Hz, 1H), 2.94 (dd, J = 8.8, 3.4 Hz,
1H), 1.35 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H), 1.08 (s, 9H). 13C NMR (150 MHz, CDCl3) δ
178.6, 178.2, 172.9, 172.0, 136.9, 135.1, 127.9, 127.8, 126.2, 125.4, 61.7, 61.2, 58.0, 44.6, 44.3,
43.3, 40.2, 39.2, 39.1, 27.7, 14.3, 14.2. HRMS (ESI): calcd for C24H29O6NNa, [M+H]+, 450.1887;
found, 450.1894.
Compound 3be: White solid. 58 mg. Yield 78%. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.27
– 7.13 (m, 3H), 7.13 – 6.99 (m, 1H), 4.24 (dtt, J = 10.8, 7.2, 3.6 Hz, 2H), 4.11 – 3.94 (m, 3H),
3.88 (t, J = 3.0 Hz, 1H), 3.39 (dd, J = 5.3, 2.3 Hz, 1H), 3.22 (dd, J = 8.6, 3.2 Hz, 1H), 3.15 (dd, J
= 5.3, 2.9 Hz, 1H), 3.10 (dd, J = 8.6, 3.3 Hz, 1H), 1.33 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 178.0, 177.5, 172.9, 171.7, 136.5, 134.6, 128.2, 128.1, 126.2,
125.3, 61.8, 61.3, 45.0, 44.5, 44.4, 41.8, 38.5, 38.5, 14.2, 14.1. HRMS (ESI): calcd for C20H22O6N,
[M+H] +, 372.1442; found, 372.1448.
Compound 3bg: Colorless oil. 54 mg. Yield 60%. 1H NMR (600 MHz, CDCl3) δ 7.36 – 7.23 (m,
6H), 7.19 (d, J = 6.5 Hz, 1H), 6.46 (dd, J = 6.7, 2.9 Hz, 2H), 4.37 – 4.24 (m, 2H), 4.18 (t, J = 2.7
Hz, 1H), 4.13 – 4.04 (m, 2H), 4.04 – 4.01 (m, 1H), 3.52 (dd, J = 5.3, 2.3 Hz, 1H), 3.42 (dd, J = 8.5,
3.3 Hz, 1H), 3.31 (dd, J = 8.5, 3.3 Hz, 1H), 3.27 (dd, J = 5.3, 2.9 Hz, 1H), 1.38 (t, J = 7.1 Hz, 3H),
1.21 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 176.7, 176.3, 172.9, 171.8, 136.7, 134.9,
131.3, 129.1, 128.8, 128.3, 128.2, 126.4, 126.4, 125.5, 61.9, 61.4, 44.5, 44.4, 44.0, 40.9, 39.1, 39.1,
14.3, 14.2. HRMS (ESI): calcd for C26H26O6N, [M+H] +, 448.1755; found, 448.1760.
Compound 3ca: Colorless oil. 47 mg. Yield 64%. 1H NMR (600 MHz, CDCl3) δ 7.14 – 6.70 (m,
3H), 4.02 (dt, J = 9.9, 2.6 Hz, 1H), 3.89 (dt, J = 10.0, 2.9 Hz, 1H), 3.82 (s, 3H), 3.60 (d, J = 7.2 Hz,
3H), 3.45 (d, J = 5.4 Hz, 1H), 3.22 (dd, J = 8.5, 3.2 Hz, 1H), 3.19 – 3.14 (m, 1H), 3.10 (dt, J = 8.3,
3.0 Hz, 1H), 2.50 (d, J = 3.1 Hz, 3H), 2.27 (d, J = 6.8 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ
177.5, 177.0, 173.3, 172.3, 137.9, 134.4, 133.3, 128.8, 125.8, 124.9, 52.8, 52.4, 44.7, 44.5, 44.0,
40.7, 38.5, 38.2, 24.3, 21.3. HRMS (ESI): calcd for C20H21O6NNa, [M+Na] +, 394.1261; found,
394.1267.
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Compound 3da: Colorless oil. 55 mg. Yield 70%. 1H NMR (400 MHz, CDCl3) δ 7.25 – 7.01 (m,
3H), 4.15 – 4.01 (m, 1H), 3.98 – 3.89 (m, 1H), 3.83 (s, 3H), 3.62 (d, J = 9.9 Hz, 3H), 3.55 – 3.40
(m, 1H), 3.23 (dd, J = 8.5, 2.9 Hz, 1H), 3.16 (dd, J = 5.2, 2.7 Hz, 1H), 3.11 (dd, J = 8.5, 3.0 Hz,
1H), 2.54 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 177.1, 176.6, 172.9, 172.0, 136.5, 134.9, 133.9,
128.4, 126.5, 126.4, 53.0, 52.6, 44.5, 44.3, 43.6, 40.4, 38.5, 38.1, 24.5. HRMS (ESI): calcd for
C19H19O6NCl, [M+H] +, 392.0895; found, 392.0893.
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Compound 3ea: Colorless oil. 53 mg. Yield 63%. 1H NMR (600 MHz, CDCl3) δ 7.24 – 7.03 (m,
3H), 4.41 – 4.19 (m, 2H), 4.17 – 3.97 (m, 3H), 3.93 (dt, J = 13.4, 3.0 Hz, 1H), 3.45 (dt, J = 5.3,
2.7 Hz, 1H), 3.24 (dd, J = 8.5, 2.5 Hz, 1H), 3.18 – 3.14 (m, 1H), 3.12 (dd, J = 8.4, 2.8 Hz, 1H),
2.55 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.20 (dd, J = 15.8, 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3)
δ 177.1, 176.7, 172.5, 171.5, 136.5, 135.0, 133.9, 128.4, 127.4, 126.5, 62.0, 61.5, 44.5, 44.3, 43.6,
40.5, 38.6, 38.2, 24.5, 14.3, 14.2. HRMS (ESI): calcd for C21H23O6NCl, [M+H] +, 420.1208; found,
420.1202.
Compound 3fa: Colorless oil. 46 mg. Yield 55%. 1H NMR (400 MHz, CDCl3) δ 7.04 (d, 8.2 Hz,
1H), 6.76 – 6.63 (m, 2H), 4.30 – 4.20 (m, 2H), 4.09 – 3.97 (m, 3H), 3.88 (t, J = 2.8 Hz, 1H), 3.77
– 3.71 (m, 3H), 3.47 – 3.37 (m, 1H), 3.31 – 3.14 (m, 2H), 3.12 – 3.05 (m, 1H), 2.52 (s, 3H), 1.34 (t,
J = 7.1 Hz, 3H), 1.19 (td, J = 7.1, 3.3 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.6, 177.0, 173.0,
171.7, 159.3, 135.9, 128.4, 126.2, 113.3, 112.0, 61.7, 61.3, 55.2, 45.0, 44.4, 43.8, 41.0, 39.0, 38.1,
24.4, 14.25, 14.22. 1H NMR (400 MHz, CDCl3) δ 7.04 (d, 8.2 Hz, 1H), 6.76 – 6.63 (m, 2H), 4.30
– 4.20 (m, 2H), 4.09 – 3.97 (m, 3H), 3.88 (t, J = 2.8 Hz, 1H), 3.77 – 3.71 (m, 3H), 3.47 – 3.37 (m,
1H), 3.31 – 3.14 (m, 2H), 3.12 – 3.05 (m, 1H), 2.52 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.19 (td, J =
7.1, 3.3 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.4, 177.2, 172.9, 171.9, 159.4, 137.7, 127.0,
126.4, 113.5, 110.9, 61.8, 61.3, 55.2, 44.8, 44.5, 44.1, 40.7, 39.1, 38.1, 24.4, 14.25, 14.20. HRMS
(ESI): calcd for C22H26O7N, [M+H] +, 416.1704; found, 416.1714.
Compound 3ga: Colorless oil. 54 mg. Yield 67%. 1H NMR (400 MHz, CDCl3) δ 7.22 – 7.03 (m,
1H), 6.96 – 6.79 (m, 2H), 4.37 – 4.18 (m, 2H), 4.11 – 4.01 (m, 3H), 3.94 (dd, J = 7.6, 3.2 Hz, 1H),
3.45 (td, J = 5.7, 2.4 Hz, 1H), 3.24 (ddd, J = 8.5, 3.0, 1.9 Hz, 1H), 3.17 (ddd, J = 8.1, 5.4, 2.9 Hz,
1H), 3.11 (ddd, J = 8.4, 4.9, 3.4 Hz, 1H), 2.53 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.23 – 1.16 (m,
3H).
13C NMR (150 MHz, CDCl3) δ 177.2, 176.7, 172.6, 171.6, 162.2 (d, J = 247.2 Hz), 136.8 (d, J =
7.8 Hz), 132.2, 126.8 (d, J = 8.6 Hz), 115.0 (d, J = 9.0 Hz), 113.6 (d, J = 22.3 Hz), 61.9, 61.4, 44.7,
44.2, 43.6, 40.7, 38.1, 24.4, 14.2. 1H NMR (400 MHz, CDCl3) δ 7.22 – 7.03 (m, 1H), 6.96 – 6.79
(m, 2H), 4.37 – 4.18 (m, 2H), 4.11 – 4.01 (m, 3H), 3.94 (dd, J = 7.6, 3.2 Hz, 1H), 3.45 (td, J = 5.7,
2.4 Hz, 1H), 3.24 (ddd, J = 8.5, 3.0, 1.9 Hz, 1H), 3.17 (ddd, J = 8.1, 5.4, 2.9 Hz, 1H), 3.11 (ddd, J
= 8.4, 4.9, 3.4 Hz, 1H), 2.53 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.23 – 1.16 (m, 3H). 13C NMR (150
MHz, CDCl3) δ 177.1, 176.9, 172.7, 171.6, 162.3 (d, J = 246.8 Hz), 138.5 (d, J = 8.3 Hz), 130.4,
127.7 (d, J = 8.6 Hz), 114.9 (d, J = 9.2 Hz), 112.8 (d, J = 22.8 Hz), 61.9, 61.5, 44.4, 44.3, 43.8,
40.7, 38.8, 24.4, 14.2. HRMS (ESI): calcd for C21H23O6NF, [M+H] +, 404.1504; found, 404.1511.
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4H), 4.27 (qd, J = 7.1, 2.2 Hz, 1H), 4.13 – 3.98 (m, 2H), 3.93 (dd, J = 6.0, 3.0 Hz, 1H), 3.82 (s,
3H), 3.46 (ddd, J = 15.7, 5.4, 2.3 Hz, 1H), 3.29 – 3.15 (m, 2H), 3.14 – 3.05 (m, 1H), 2.48 (s, 3H),
1.19 (t, J = 7.1 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 177.5, 177.0, 172.8, 171.7, 136.4, 134.5,
128.2, 128.2, 126.1, 125.2, 61.4, 52.4, 44.7, 44.4, 43.9, 40.7, 38.7, 38.6, 24.3, 14.2. 1H NMR (400
MHz, CDCl3) δ 7.26 – 6.96 (m, 4H), 4.27 (qd, J = 7.1, 2.2 Hz, 1H), 4.13 – 3.97 (m, 2H), 3.93 (dd,
J = 6.0, 3.0 Hz, 1H), 3.60 (s, 3H), 3.46 (ddd, J = 15.7, 5.4, 2.3 Hz, 1H), 3.28 – 3.15 (m, 2H), 3.15
– 3.03 (m, 1H), 2.48 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.4, 177.0,
173.4, 172.3, 136.4, 134.7, 128.2, 128.1, 126.1, 125.2, 61.9, 52.8, 44.5, 44.4, 43.9, 40.7, 38.8, 38.7,
24.3, 14.3. HRMS (ESI): calcd for C20H22O6N, [M+H] +, 372.1442; found, 372.1450.
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Compound 3ka: White solid. 69 mg. Yield 78%. H NMR (400 MHz, CDCl3) δ 7.25 – 7.15 (m,
3H), 7.14 – 6.94 (m, 1H), 4.29 – 4.16 (m, 2H), 4.10 – 4.05 (m, 1H), 4.02 – 3.94 (m, 2H), 3.92 (t, J
= 3.0 Hz, 1H), 3.46 (dd, J = 5.4, 2.3 Hz, 1H), 3.24 (dd, J = 8.5, 3.2 Hz, 1H), 3.19 (dd, J = 5.4, 2.9
Hz, 1H), 3.12 (dd, J = 8.5, 3.3 Hz, 1H), 2.48 (s, 3H), 1.71 (dt, J = 14.6, 6.8 Hz, 2H), 1.53 (tt, J =
10.3, 5.2 Hz, 2H), 1.43 (dt, J = 14.6, 7.5 Hz, 2H), 1.33 (dt, J = 15.1, 7.5 Hz, 2H), 0.98 (t, J = 7.4
Hz, 3H), 0.90 (t, J = 7.3 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.4, 177.1, 173.0, 171.9, 136.5,
134.6, 128.2, 128.1, 126.1, 125.2, 65.7, 65.2, 44.7, 44.6, 44.0, 40.8, 38.8, 38.7, 30.6, 30.6, 24.3,
+
19.2, 19.1, 13.8, 13.7. HRMS (ESI): calcd for C25H31O6NNa, [M+Na] , 464.2044; found,
464.2049.
Compound 3maa: Colorless oil. 37 mg. Yield 42%. 1H NMR (400 MHz, CDCl3) δ 7.21 – 7.14 (m,
3H), 7.09 (dd, J = 5.6, 2.0 Hz, 1H), 3.99 (t, J = 2.8 Hz, 1H), 3.88 (t, J = 3.1 Hz, 1H), 3.33 (dd, J =
5.1, 2.4 Hz, 1H), 3.21 (dd, J = 8.5, 3.2 Hz, 1H), 3.10 – 3.04 (m, 2H), 2.48 (s, 3H), 1.54 (s, 9H),
1.33 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 177.6, 177.4, 172.3, 171.1, 136.7, 134.8, 128.1, 127.8,
126.0, 125.2, 81.9, 81.4, 45.1, 44.9, 43.9, 40.8, 39.2, 38.9, 28.1, 28.0, 24.3. HRMS (ESI): calcd
for C25H31O6NNa, [M+Na] +, 464.2044; found, 464.2053.
Compound 3mab: White solid. 26 mg. Yield 30%. mp 141ꢀ143 oC. 1H NMR (400 MHz, CDCl3)
δ 7.20 (dt, J = 7.3, 3.7 Hz, 2H), 7.17 – 7.11 (m, 2H), 3.89 (s, 2H), 3.14 (s, 2H), 3.11 (s, 2H), 2.48
(s, 3H), 1.33 (s, 18H) 13C NMR (150 MHz, CDCl3) δ 177.1, 169.8, 134.8, 127.8, 126.3, 81.0, 45.8,
+
44.3, 38.9, 28.0, 24.3. HRMS (ESI): calcd for C25H31O6NNa, [M+Na] , 464.2044; found,
464.2052.
Compound 3la: Colorless oil. 53 mg. Yield 64%. 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.15 (m,
3H), 7.13 – 7.07 (m, 1H), 5.22 – 4.99 (m, 1H), 4.87 (hept, J = 6.2 Hz, 1H), 4.06 (t, J = 2.8 Hz, 1H),
3.93 (t, J = 3.1 Hz, 1H), 3.43 (dd, J = 5.3, 2.4 Hz, 1H), 3.24 (dd, J = 8.5, 3.2 Hz, 1H), 3.18 (dd, J
= 5.3, 3.0 Hz, 1H), 3.10 (dd, J = 8.5, 3.3 Hz, 1H), 2.50 (s, 3H), 1.36 (d, J = 6.2 Hz, 3H), 1.33 (d, J
= 6.3 Hz, 3H), 1.19 (d, J = 6.3 Hz, 3H), 1.14 (d, J = 6.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ
177.5, 177.2, 172.5, 171.3, 136.6, 134.6, 128.2, 128.0, 126.1, 125.2, 69.4, 68.8, 44.6, 44.5, 43.9,
40.8, 38.9, 38.8, 24.3, 21.9, 21.8, 21.7. HRMS (ESI): calcd for C23H28O6N, [M+H] +, 414.1911;
found, 414.1907.
Compound 3na: Colorless oil. 51 mg. Yield 58%. 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.07 (m,
4H), 4.74 (p, J = 7.3 Hz, 2H), 4.05 – 3.80 (m, 2H), 3.24 (s, 2H), 3.13 (s, 2H), 2.50 (s, 3H), 2.26 –
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2.10 (m, 4H), 1.97 – 1.80 (m, 4H), 1.76 – 1.65 (m, 2H), 1.59 – 1.41 (m, 2H). 13C NMR (150 MHz,
CDCl3) δ 176.9, 170.0, 134.7, 127.9, 126.4, 69.1, 45.0, 44.1, 38.6, 30.1, 29.9, 24.3, 13.5. HRMS
(ESI): calcd for C25H27O6NNa, [M+Na] +, 460.1731; found, 460.1735.
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Compound 3oa: Colorless oil. 46 mg. Yield 50%. 1H NMR (600 MHz, CDCl3) δ 7.16 – 7.11 (m,
2H), 7.11 – 6.92 (m, 2H), 5.11 – 4.77 (m, 2H), 3.83 (s, 2H), 3.16 (s, 2H), 3.06 (s, 2H), 2.42 (s, 3H),
1.78 – 1.29 (m, 16H). 13C NMR (150 MHz, CDCl3) δ 175.9, 169.4, 133.7, 126.9, 125.2, 76.8, 44.3,
43.2, 37.6, 31.6, 31.2, 23.3, 22.7, 22.6. HRMS (ESI): calcd for C27H31O6NNa, [M+Na] +, 488.2044;
found, 488.2045.
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Compound 3pa: Colorless oil. 49 mg. Yield 48%. 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.13 (m,
4H), 4.63 – 4.47 (m, 2H), 3.93 (s, 2H), 3.25 (s, 2H), 3.14 (s, 2H), 2.50 (s, 3H), 1.67 (dd, J = 12.3,
7.4 Hz, 8H), 1.49 (d, J = 9.8 Hz, 2H), 1.27 (dd, J = 9.0, 3.3 Hz, 10H). 13C NMR (150 MHz, CDCl3)
δ 177.0, 170.2, 134.7, 127.9, 126.3, 73.3, 45.3, 44.2, 38.8, 31.5, 31.4, 25.3, 24.3, 23.7, 23.7.
HRMS (ESI): calcd for C29H35O6NNa, [M+Na] +, 516.2357; found, 516.2359.
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Compound 3qa: Colorless oil. 59 mg. Yield 54%. H NMR (400 MHz, CDCl3) δ 7.14 (ddd, J =
14.0, 7.0, 4.3 Hz, 6H), 7.00 (dt, J = 14.5, 6.0 Hz, 6H), 4.87 (d, J = 12.1 Hz, 2H), 4.69 (d, J = 12.1
Hz, 2H), 3.91 (s, 2H), 3.32 (s, 2H), 3.12 (s, 2H), 2.47 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
176.6, 170.6, 162.7 (d, J = 247.3 Hz), 134.4, 131.1 (d, J = 2.9 Hz), 130.6 (d, J = 8.1 Hz), 128.9,
126.3, 115.4 (d, J = 21.7 Hz), 66.0, 45.1, 44.4, 38.6, 24.4. HRMS (ESI): calcd for C31H26O6NF2,
[M+H] +, 546.1723; found, 546.1736.
Compound 3ra: Colorless oil. 72 mg. Yield 56%. 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.1
Hz, 4H), 7.23 (d, J = 8.1 Hz, 4H), 7.16 (dd, J = 5.4, 3.2 Hz, 2H), 7.01 (dd, J = 5.4, 3.3 Hz, 2H),
4.93 (d, J = 12.7 Hz, 2H), 4.77 (d, J = 12.7 Hz, 2H), 3.94 (s, 2H), 3.38 (s, 2H), 3.15 (s, 2H), 2.48
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 176.5, 170.5, 139.1, 134.3, 130.6 (q, J = 32.4 Hz), 128.5,
128.2, 126.3, 125.4 (q, J = 3.6 Hz), 123.9 (q, J = 272.0 Hz), 65.8, 45.1, 44.0, 38.6, 24.4. HRMS
(ESI): calcd for C33H26O6NF6, [M+H] +, 646.1659; found, 646.1669.
Compound 3sa: Colorless oil. 50 mg. Yield 46%. 1H NMR (600 MHz, CDCl3) δ 7.21 – 7.12 (m,
2H), 7.08 (d, J = 8.0 Hz, 4H), 7.06 – 6.96 (m, 2H), 6.83 (d, J = 8.1 Hz, 4H), 4.86 (d, J = 11.9 Hz,
2H), 4.66 (d, J = 11.9 Hz, 2H), 3.90 (s, 2H), 3.80 (s, 6H), 3.28 (s, 2H), 3.09 (s, 2H), 2.47 (s, 3H).
13C NMR (150 MHz, CDCl3) δ 176.7, 170.7, 159.7, 134.4, 130.4, 128.0, 127.5, 126.3, 113.8, 66.5,
+
55.3, 45.1, 44.0, 38.5, 24.3. HRMS (ESI): calcd for C33H32O8N, [M+H] , 570.2122; found,
570.2127.
Compound 3ta: Colorless oil. 48 mg. Yield 56%. 1H NMR (400 MHz, CDCl3) δ 6.70 (s, 1H), 6.61
(s, 1H), 5.90 (dd, J = 2.5, 1.4 Hz, 2H), 4.31 – 4.21 (m, 2H), 4.12 – 4.01 (m, 2H), 4.00 (t, J = 2.8 Hz,
1H), 3.86 (t, J = 3.1 Hz, 1H), 3.40 (dd, J = 5.3, 2.4 Hz, 1H), 3.19 (dd, J = 8.4, 3.2 Hz, 1H), 3.15 (dd, J
= 5.3, 3.0 Hz, 1H), 3.06 (dd, J = 8.4, 3.2 Hz, 1H), 2.59 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1
Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 177.4, 177.0, 172.8, 171.8, 147.2, 147.1, 129.8, 127.8, 107.2,
106.5, 100.9, 61.8, 61.3, 44.7, 44.6, 43.9, 40.7, 38.87 , 38.84, 24.5, 14.27, 14.24. HRMS (ESI): calcd
for C22H24O8N, [M+H] +, 430.1496; found, 430.1492.
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Compound 3ua: Colorless oil. 56 mg. Yield 66%. 1H NMR (600 MHz, CDCl3) δ 7.06 (dd, J = 9.2,
7.6 Hz, 1H), 6.98 (dd, J = 9.1, 7.7 Hz, 1H), 4.34 – 4.20 (m, 2H), 4.13 – 4.00 (m, 3H), 3.92 (t, J =
3.0 Hz, 1H), 3.45 (dd, J = 5.3, 2.3 Hz, 1H), 3.24 (dd, J = 8.5, 3.2 Hz, 1H), 3.14 (dd, J = 5.3, 3.0
Hz, 1H), 3.11 (dd, J = 8.5, 3.3 Hz, 1H), 2.58 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ 176.9, 176.5, 172.3, 171.4, 150.02 (dd, J = 253.5, 17.0 Hz),
149.90 (dd, J = 254.2, 17.7 Hz), 132.94 (dd, J = 5.8, 3.9 Hz), 131.25 (dd, J = 6.0, 4.1 Hz), 115.65
(d, J = 17.9 Hz), 114.89 (d, J = 17.8 Hz), 62.0, 61.6, 44.4, 44.2, 43.5, 40.4, 38.2, 24.6, 14.23,
14.19. HRMS (ESI): calcd for C21H22O6NF2, [M+H] +, 422.1410; found, 422.1401.
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Compound 5aa: White solid. 56 mg. Yield 86%. 1H NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 7.34
– 7.04 (m, 4H), 4.12 (dd, J = 7.0, 2.9 Hz, 1H), 4.09 (t, J = 2.9 Hz, 1H), 3.61 (s, 3H), 3.51 (dd, J =
5.6, 2.2 Hz, 1H), 3.28 (dd, J = 5.6, 2.7 Hz, 1H), 3.20 (dd, J = 8.2, 3.2 Hz, 1H), 2.93 (dd, J = 8.5,
3.2 Hz, 1H), 2.49 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 199.7, 177.1, 176.7, 172.1, 136.1, 133.9,
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128.5, 128.3, 125.8, 125.0, 52.6, 52.4, 44.1, 41.4, 40.5, 38.6, 36.1, 24.4. H NMR (400 MHz,
CDCl3) δ 9.51 (s, 1H), 7.46 – 6.84 (m, 4H), 4.12 (dd, J = 7.0, 2.9 Hz, 1H), 3.99 (t, J = 3.0 Hz, 1H),
3.83 (s, 3H), 3.51 (dd, J = 5.6, 2.2 Hz, 1H), 3.31 (dd, J = 8.5, 3.2 Hz, 1H), 3.22 (dd, J = 4.9, 3.1
Hz, 1H), 3.12 (dd, J = 8.5, 3.2 Hz, 1H), 2.50 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 198.7, 177.2,
176.8, 173.0, 136.5, 135.2, 128.3, 128.3, 126.4, 125.3, 52.9, 51.7, 43.8, 41.6, 40.6, 38.6, 36.8, 24.4.
HRMS (ESI): calcd for C18H18O5N, [M+H] +, 328.1179; found, 328.1192.
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Compound 5ag: Colorless oil. 56 mg. Yield 72%. H NMR (400 MHz, CDCl3) δ 9.51 (s, 1H),
7.82 – 6.90 (m, 7H), 6.69 – 6.22 (m, 2H), 4.25 – 4.16 (m, 1H), 4.06 (t, J = 3.0 Hz, 1H), 3.82 (s,
3H), 3.46 (dd, J = 3.6, 1.8 Hz, 1H), 3.37 (dd, J = 8.6, 3.2 Hz, 1H), 3.28 (dd, J = 5.4, 2.9 Hz, 1H),
3.24 (dd, J = 8.6, 3.3 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 198.8, 176.5, 176.1, 173.0, 136.8,
134.2, 131.2, 129.1, 128.6, 128.5, 128.5, 126.4, 126.1, 125.3, 53.0, 51.6, 44.2, 41.5, 40.7, 39.0,
37.1. 1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 7.48 – 7.04 (m, 7H), 6.48 – 6.42 (m, 2H), 4.29 –
4.16 (m, 1H), 4.15 (t, J = 2.9 Hz, 1H), 3.61 (s, 3H), 3.55 (dd, J = 5.7, 2.2 Hz, 1H), 3.45 (dd, J =
7.6, 2.6 Hz, 1H), 3.31 (dd, J = 5.7, 2.6 Hz, 1H), 3.08 (dd, J = 8.6, 3.3 Hz, 1H). 13C NMR (150
MHz, CDCl3) δ 199.8, 176.4, 176.0, 172.2, 136.4, 135.5, 131.2, 129.1, 128.9, 128.6, 128.4, 126.6,
126.4, 125.6, 52.6, 52.3, 43.9, 41.5, 40.5, 39.0, 36.4. LRMS (EI): 389[M+], 339, 279, 186, 128.
HRMS (ESI): calcd for C23H20O5N, [M+H] +, 390.1336; found, 390.1343.
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Compound 5ac: Colorless oil. 66 mg. Yield 82%. H NMR (400 MHz, CDCl3) δ 9.46 (s, 1H),
7.15 – 6.95 (m, 7H), 6.55 (dd, J = 7.1, 1.7 Hz, 2H), 4.25 (s, 2H), 4.10 (dt, J = 6.2, 2.7 Hz, 1H),
3.97 (t, J = 3.0 Hz, 1H), 3.80 (s, 3H), 3.39 (dd, J = 5.3, 2.2 Hz, 1H), 3.29 (dd, J = 8.7, 3.1 Hz, 1H),
3.17 (dd, J = 5.3, 2.9 Hz, 1H), 2.92 (dd, J = 8.7, 3.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ
198.8, 176.9, 176.5, 173.0, 136.5, 134.7, 133.8, 128.6, 128.4, 128.4, 127.4, 127.3, 125.8, 125.3,
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52.9, 51.9, 44.0, 42.0, 41.8, 40.4, 38.5, 36.7. H NMR (400 MHz, CDCl3) δ 9.91 (s, 1H), 7.18 –
6.94 (m, 7H), 6.55 (dd, J = 7.1, 1.7 Hz, 2H), 4.24 (s, 2H), 4.10 (dt, J = 6.2, 2.7 Hz, 1H), 4.07 (t, J
= 2.9 Hz, 1H), 3.58 (s, 3H), 3.48 (dd, J = 5.6, 2.2 Hz, 1H), 3.21 (dd, J = 6.0, 2.5 Hz, 1H), 3.20 (dd,
J = 5.1, 3.4 Hz, 1H), 2.92 (dd, J = 8.7, 3.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 199.8, 176.8,
176.4, 172.1, 136.1, 135.2, 134.7, 128.6, 128.4, 128.4, 127.4, 127.3, 126.4, 125.0, 52.6, 52.5, 43.7,
42.0, 41.3, 40.8, 38.5, 36.0. LRMS (EI): 403[M+], 389, 361, 175, 155, 128. HRMS (ESI): calcd
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Compound 5ba: Colorless oil. 46 mg. Yield 68%. H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H),
7.26 – 7.06 (m, 4H), 4.27 (q, J = 7.1 Hz, 1H), 4.15 – 3.91 (m, 3H), 3.48 (dd, J = 5.5, 2.2 Hz, 1H),
3.35 – 3.25 (m, 1H), 3.23 – 3.17 (m, 1H), 2.94 (dd, J = 8.5, 3.2 Hz, 1H), 2.48 (s, 3H), 1.20 (t, J =
7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 199.9, 177.2, 176.8, 171.6, 136.2, 135.2, 128.5, 128.2,
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126.3, 125.0, 61.5, 52.3, 43.8, 40.7, 40.6, 38.8, 36.0, 24.4, 14.2. H NMR (400 MHz, CDCl3) δ
9.50 (s, 1H), 7.25 – 7.00 (m, 4H), 4.27 (q, J = 7.1 Hz, 1H), 4.14 – 3.95 (m, 3H), 3.43 (dd, J = 5.3,
2.2 Hz, 1H), 3.32 – 3.27 (m, 1H), 3.23 – 3.17 (m, 1H), 3.12 (dd, J = 8.5, 3.2 Hz, 1H), 2.49 (s, 3H),
1.36 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 198.9, 177.3, 176.9, 172.6, 136.5, 134.0,
128.5, 128.3, 125.9, 125.3, 62.0, 51.6, 44.1, 41.7, 41.4, 38.7, 36.8, 24.4, 14.2. HRMS (ESI): calcd
for C19H20O5N, [M+H] +, 342.1336; found, 342.1329.
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Compound 5af: Colorless oil. 36 mg. Yield 58%. H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H),
7.42 – 7.06 (m, 4H), 4.16 (dd, J = 6.2, 3.4 Hz, 1H), 4.09 (t, J = 3.0 Hz, 1H), 3.62 (s, 3H), 3.59 (dd,
J = 9.5, 3.2 Hz, 1H), 3.44 (dd, J = 5.7, 2.3 Hz, 1H), 3.41 (dd, J = 9.5, 3.4 Hz, 1H), 3.29 (dd, J =
5.7, 2.6 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 197.8, 171.5, 170.9, 170.5, 135.6, 134.6, 129.1,
129.1, 126.2, 125.3, 52.8, 51.8, 44.5, 41.3, 40.4, 38.4, 35.9. 1H NMR (400 MHz, CDCl3) δ 9.49 (s,
1H), 7.42 – 7.06 (m, 4H), 4.16 (dd, J = 6.2, 3.4 Hz, 1H), 4.02 (t, J = 3.0 Hz, 1H), 3.83 (s, 3H),
3.54 (dd, J = 9.4, 3.2 Hz, 1H), 3.36 (dd, J = 5.4, 2.2 Hz, 1H), 3.26 (dd, J = 9.4, 3.3 Hz, 1H), 3.22
(dd, J = 5.4, 2.9 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 199.2, 172.7, 171.0, 170.7, 135.9, 133.3,
129.3, 129.1, 126.7, 125.6, 53.1, 51.2, 44.8, 42.2, 41.1, 38.3, 36.5. LRMS (EI): 314[M+], 244, 186,
155, 133, 113. HRMS (ESI): calcd for C17H15O6, [M+H] +, 315.0863; found, 315.0885.
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Compound 5ah: Colorless oil. 43 mg. Yield 60%. H NMR (400 MHz, CDCl3) δ 9.50 (s, 1H),
7.39 – 6.90 (m, 4H), 4.80 (ddd, J = 13.7, 12.5, 2.5 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.74 (s, 3H),
3.38 (dd, J = 5.0, 2.6 Hz, 1H), 3.22 (dd, J = 5.0, 2.5 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ
198.1, 172.2, 165.6, 165.1, 143.4, 141.6, 140.1, 137.6, 127.2, 127.0, 124.6, 124.0, 54.6, 52.6, 52.6,
52.5, 45.1, 44.4, 42.5. 1H NMR (400 MHz, CDCl3) δ 9.78 (s, 1H), 7.56 – 6.70 (m, 4H), 4.80 (ddd,
J = 13.7, 12.5, 2.5 Hz, 2H), 3.80 (s, 3H), 3.78 (s, 3H), 3.60 (s, 3H), 3.44 (dd, J = 5.0, 2.7 Hz, 1H),
3.26 (dd, J = 5.1, 2.4 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 198.5, 171.5, 165.3, 165.3, 143.4,
141.1, 139.9, 138.7, 127.0, 126.9, 125.1, 123.7, 55.7, 52.6, 52.6, 52.5, 44.8, 44.2, 42.7. LRMS
+
(EI): 358[M+], 186, 155, 128. HRMS (ESI): calcd for C19H19O7, [M+H] , 359.1125; found,
359.1133.
Compound 5ca: White solid. 48 mg. Yield 80%. 1H NMR (600 MHz, CDCl3) δ 9.95 (s, 1H), 9.53
(s, 1H), 7.26 – 7.19 (m, 3H), 7.14 (d, J = 6.9 Hz, 1H), 4.17 (s, 1H), 4.12 (s, 1H), 3.47 (dd, J = 5.2,
1.9 Hz, 1H), 3.30 (dd, J = 5.2, 2.6 Hz, 1H), 3.20 (dd, J = 8.5, 3.1 Hz, 1H), 2.99 (dd, J = 8.5, 3.1
Hz, 1H), 2.50 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 199.6, 198.6, 176.8, 176.5, 136.2, 134.4,
128.6, 128.4, 125.9, 125.1, 49.5, 47.8, 43.9, 41.2, 36.9, 36.0, 24.4. HRMS (ESI): calcd for
C17H16O4N, [M+H] +, 298.1074; found, 298.1084.
Compound 5cb: Colorless oil. 45 mg. Yield 72%.
1H NMR (600 MHz, CDCl3) δ 9.94 (s, 1H), 9.53 (s, 1H), 7.28 – 7.17 (m, 3H), 7.15 (d, J = 7.0 Hz,
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1H), 4.17 (s, 1H), 4.13 (s, 1H), 3.48 (dd, J = 5.2, 1.6 Hz, 1H), 3.30 (dd, J = 5.2, 2.5 Hz, 1H), 3.17
(dd, J = 8.4, 3.1 Hz, 1H), 3.10 (q, J = 7.2 Hz, 2H), 2.96 (dd, J = 8.4, 3.2 Hz, 1H), 0.35 (t, J = 7.2
Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 199.7, 198.8, 176.7, 176.4, 136.4, 134.6, 128.4, 128.3,
126.0, 125.2, 49.4, 47.8, 43.7, 41.0, 37.0, 36.2, 33.2, 11.9. HRMS (ESI): calcd for C18H18O4N,
[M+H] +, 312.1230; found, 312.1235.
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Compound 7aa: White solid. 260 mg. Yield 80%. mp 204ꢀ205 oC. 1H NMR (400 MHz, CDCl3) δ
7.26 – 7.13 (m, 3H), 7.12 – 6.88 (m, 1H), 4.09 – 3.97 (m, 1H), 3.90 (t, J = 2.9 Hz, 1H), 3.49 (dd, J
= 5.3, 2.1 Hz, 1H), 3.43 (dd, J = 5.3, 2.7 Hz, 1H), 3.26 (dd, J = 8.5, 3.2 Hz, 1H), 2.97 (dd, J = 8.5,
3.3 Hz, 1H), 2.48 (s, 3H), 2.40 (s, 3H), 2.21 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 207.6, 205.2,
177.4, 177.0, 136.5, 134.3, 128.4, 128.2, 125.8, 125.2, 50.9, 50.3, 44.3, 40.6, 38.8, 38.6, 29.3, 28.1,
24.3. HRMS (ESI): calcd for C19H20O4N, [M+H] +, 326.1392; found, 326.1396.
Compound 7ab: White solid. 278 mg. Yield 82%. mp 188ꢀ189 oC. 1H NMR (400 MHz, CDCl3)
δ 7.24 – 7.13 (m, 3H), 7.09 (d, J = 6.7 Hz, 1H), 4.19 – 3.99 (m, 1H), 3.90 (t, J = 2.9 Hz, 1H), 3.49
(dd, J = 5.3, 2.1 Hz, 1H), 3.43 (dd, J = 5.3, 2.7 Hz, 1H), 3.22 (dd, J = 8.4, 3.3 Hz, 1H), 3.10 (q, J =
7.2 Hz, 2H), 2.93 (dd, J = 8.4, 3.3 Hz, 1H), 2.40 (s, 3H), 2.22 (s, 3H), 0.35 (t, J = 7.2 Hz, 3H).13C
NMR (100 MHz, CDCl3) δ 207.6, 205.3, 177.2, 176.8, 136.7, 134.4, 128.2, 128.1, 125.9, 125.3,
50.8, 50.4, 44.0, 40.4, 38.9, 38.5, 33.2, 29.3, 28.1, 11.9. HRMS (ESI): calcd for C20H22O4N,
[M+H] +, 340.1549; found, 340.1548.
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Compound 7ae: White solid. 230 mg. Yield 74%. mp 201ꢀ202 C. 1H NMR (400 MHz, CDCl3) δ
7.53 (s, 1H), 7.28 – 7.16 (m, 3H), 7.15 – 6.92 (m, 1H), 4.17 – 3.95 (m, 1H), 3.87 (t, J = 2.9 Hz, 1H),
3.45 (dd, J = 5.3, 2.1 Hz, 1H), 3.41 (dd, J = 5.3, 2.6 Hz, 1H), 3.28 (dd, J = 8.7, 3.2 Hz, 1H), 3.01 (dd, J
= 8.7, 3.3 Hz, 1H), 2.38 (s, 3H), 2.20 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 207.7, 205.2, 177.3,
176.9, 136.5, 134.2, 128.5, 128.4, 125.9, 125.4, 50.8, 50.2, 45.4, 41.8, 38.6, 38.1, 29.4, 28.1. HRMS
(ESI): calcd for C18H18O4N, [M+H] +, 312.1230; found, 312.1228.
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Compound 7ba: White solid. 54 mg. Yield 60%. mp 98ꢀ100 oC. H NMR (400 MHz, CDCl3) δ
8.08 (d, J = 7.3 Hz, 2H), 7.90 (d, J = 7.3 Hz, 2H), 7.67 – 7.48 (m, 6H), 7.28 – 7.25 (m, 2H), 7.18
(td, J = 6.9, 2.4 Hz, 1H), 6.88 (d, J = 7.3 Hz, 1H), 4.66 (dd, J = 5.2, 1.9 Hz, 1H), 4.55 (dd, J = 5.2,
2.5 Hz, 1H), 4.06 – 3.97 (m, 1H), 3.91 (t, J = 2.8 Hz, 1H), 3.54 (dd, J = 8.4, 3.2 Hz, 1H), 3.18 (dd,
J = 8.4, 3.3 Hz, 1H), 2.46 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 199.9, 198.5, 177.7, 177.2,
136.4, 135.9, 135.6, 134.2, 134.1, 133.4, 129.1, 129.0, 128.8, 128.4, 128.3, 128.2, 126.2, 125.0,
46.0, 45.1, 44.3, 40.6, 40.3, 39.6, 24.3. HRMS (ESI): calcd for C29H23O4NNa, [M+Na] +, 472.1519;
found, 472.1526.
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Compound 7bb: White solid. 51 mg. Yield 55%. mp 167ꢀ168 oC. H NMR (400 MHz, CDCl3) δ
8.07 (d, J = 7.3 Hz, 2H), 7.95 – 7.84 (m, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H),
7.51 (dt, J = 15.4, 7.6 Hz, 4H), 7.25 (d, J = 4.2 Hz, 2H), 7.21 – 7.11 (m, 1H), 6.88 (d, J = 7.3 Hz,
1H), 4.65 (dd, J = 5.2, 2.0 Hz, 1H), 4.53 (dd, J = 5.2, 2.5 Hz, 1H), 4.00 – 3.94 (m, 1H), 3.89 (t, J =
2.9 Hz, 1H), 3.49 (dd, J = 8.3, 3.2 Hz, 1H), 3.13 (dd, J = 8.3, 3.3 Hz, 1H), 3.07 (q, J = 7.1 Hz, 2H),
0.31 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 199.9, 198.6, 177.5, 177.0, 136.5, 135.9,
135.6, 134.4, 134.1, 133.4, 129.1, 129.0, 128.8, 128.4, 128.2, 128.1, 126.4, 125.1, 45.9, 45.1, 44.0,
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40.4, 40.3, 39.8, 33.1, 11.9. HRMS (ESI): calcd for C30H25O4NNa, [M+Na] +, 486.1676; found,
486.1677
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Compound 7be: Colorless oil. 213 mg. Yield 49%.δ 8.06 (d, J = 7.4 Hz, 2H), 7.94 (s, 1H), 7.88 (d, J
= 7.3 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.56 – 7.43 (m, 4H), 7.32 – 7.24 (m,
2H), 7.19 (td, J = 7.1, 2.0 Hz, 1H), 6.87 (d, J = 7.3 Hz, 1H), 4.61 (dd, J = 5.1, 1.9 Hz, 1H), 4.51 (dd,
J = 5.2, 2.5 Hz, 1H), 4.00 – 3.90 (m, 1H), 3.86 (t, J = 2.9 Hz, 1H), 3.53 (dd, J = 8.6, 3.2 Hz, 1H),
3.18 (dd, J = 8.6, 3.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 199.9, 198.5, 177.8, 177.2, 136.4,
135.8, 135.5, 134.2, 134.1, 133.4, 129.1, 129.0, 128.8, 128.4, 128.4, 128.2, 126.4, 125.1, 45.9,
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+
45.4, 45.0, 41.7, 40.1, 39.4. HRMS (ESI): calcd for C28H22O4N, [M+H] , 436.1549; found,
436.1548.
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Compound 7bf: White solid. 44 mg. Yield 50%. mp 211ꢀ212 oC. H NMR (400 MHz, CDCl3) δ
8.07 (d, J = 7.4 Hz, 2H), 7.87 (d, J = 7.3 Hz, 2H), 7.60 (m, 5H), 7.42 – 7.18 (m, 4H), 6.97 (d, J =
7.3 Hz, 1H), 4.57 (qd, J = 5.2, 2.2 Hz, 2H), 4.17 – 3.99 (m, 1H), 3.94 (t, J = 2.8 Hz, 1H), 3.84 (dd,
J = 9.3, 3.3 Hz, 1H), 3.53 (dd, J = 9.4, 3.4 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 199.8, 197.8,
171.6, 171.1, 135.8, 135.6, 135.3, 134.4, 133.7, 133.6, 129.3, 129.1, 128.9, 128.8, 128.4, 126.6,
125.3, 45.8, 44.9, 44.5, 41.5, 40.0, 39.4. HRMS (ESI): calcd for C28H21O5, [M+H] +, 437.1384;
found, 437.1393.
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Compound 7bh: White solid. 46 mg. Yield 48%. mp 126ꢀ127 oC. H NMR (400 MHz, CDCl3) δ
7.97 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 7.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.58 – 7.48 (m, 3H),
7.44 (t, J = 7.4 Hz, 3H), 7.26 (t, J = 8.0 Hz, 1H), 7.14 (t, J = 7.4 Hz, 1H), 6.96 (d, J = 7.3 Hz, 1H),
4.73 (d, J = 1.7 Hz, 1H), 4.69 (d, J = 1.9 Hz, 1H), 4.44 (dd, J = 5.4, 2.0 Hz, 1H), 4.39 (dd, J = 5.3,
2.1 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 199.4, 196.8, 166.3, 165.3,
142.1, 142.0, 140.6, 137.3, 136.1, 135.8, 133.6, 133.5, 129.0, 128.8, 128.7, 128.6, 127.2, 126.6,
+
125.0, 123.5, 52.6, 52.4, 50.1, 49.3, 47.0, 45.7. HRMS (ESI): calcd for C30H25O6, [M+H] ,
481.1646; found, 481.1656.
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Compound 7ca: White solid. 43 mg. Yield 52%. H NMR (400 MHz, CDCl3) δ 7.98 – 7.79 (m,
2H), 7.64 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.24 (d, J = 3.5 Hz, 2H), 7.19 – 7.03 (m,
1H), 6.82 (d, J = 7.3 Hz, 1H), 4.40 (dd, J = 5.3, 2.1 Hz, 1H), 4.34 – 4.16 (m, 2H), 4.06 (t, J = 3.1
Hz, 1H), 3.95 – 3.77 (m, 1H), 3.53 (dd, J = 5.3, 2.9 Hz, 1H), 3.44 (dd, J = 8.5, 3.2 Hz, 1H), 3.26
(dd, J = 8.5, 3.3 Hz, 1H), 2.50 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ
197.8, 177.5, 177.0, 173.3, 136.2, 135.8, 133.7, 133.4, 129.0, 128.4, 128.4, 128.1, 126.0, 125.2,
61.8, 47.1, 44.4, 43.0, 41.1, 40.0, 38.9, 24.4, 14.3. HRMS (ESI): calcd for C25H24O5N, [M+H] +,
418.1649; found, 418.1659.
Compound 7da: White solid. 227 mg. Yield 78%. 1H NMR (400 MHz, DMSOꢀd6) δ 7.65 – 7.11 (m,
4H), 4.02 (s, 1H), 3.88 (s, 1H), 3.82 (s, 1H), 3.55 (s, 1H), 3.46 (s, 1H), 3.40 (s, 1H), 2.36 (s, 3H). 13C
NMR (100 MHz, DMSOꢀd6) δ 176.9, 176.6, 135.5, 134.0, 129.1, 129.1, 126.9, 126.3, 119.9, 119.7 ,
42.6, 40.2, 38.5, 38.0, 31.7, 31.1, 24.5. HRMS (ESI): calcd for C17H14O2N3, [M+H] +, 292.1086;
found, 292.1088.
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Compound 7ea: White solid. 247 mg. Yield 70%. 1H NMR (600 MHz, CDCl3) δ 7.29 – 7.13 (m,
3H), 7.07 (d, J = 7.0 Hz, 1H), 4.14 – 3.95 (m, 1H), 3.84 (t, J = 2.8 Hz, 1H), 3.47 (dd, J = 5.4, 1.8
Hz, 1H), 3.42 (dd, J = 5.4, 2.6 Hz, 1H), 3.26 (dd, J = 8.4, 3.2 Hz, 1H), 2.99 (dd, J = 8.4, 3.2 Hz,
1H), 2.94 – 2.75 (m, 1H), 2.62 (ddd, J = 13.8, 12.4, 5.1 Hz, 1H), 2.58 – 2.50 (m, 2H), 2.47 (s, 3H),
1.13 (t, J = 7.2 Hz, 3H), 0.98 (t, J = 7.3 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 210.6, 208.2,
177.5, 177.1, 136.6, 134.4, 128.2, 128.1, 125.7, 125.0, 50.3, 49.4, 44.4, 40.6, 38.7, 38.6, 35.3, 33.8,
24.2, 7.8, 7.7. HRMS (ESI): calcd for C21H24O4N, [M+H] +, 354.1700; found, 354.1706.
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Compound 7fa: White solid. 266 mg. Yield 75%. 1H NMR (400 MHz, CDCl3) δ 7.24 – 7.14 (m,
3H), 7.12 – 6.97 (m, 1H), 4.25 (qd, J = 7.1, 2.2 Hz, 2H), 4.03 – 4.00 (m, 1H), 3.96 (t, J = 3.1 Hz, 1H),
3.45 (dd, J = 5.4, 2.2 Hz, 1H), 3.33 – 3.24 (m, 2H), 3.14 (dd, J = 8.5, 3.3 Hz, 1H), 2.49 (s, 3H), 2.22 (s,
3H), 1.35 (t, J = 7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 204.7, 177.3, 177.1, 173.0, 136.4, 133.9,
128.4, 128.2, 125.7, 125.3, 61.8, 52.4, 44.4, 42.5, 41.0, 38.7, 38.6, 28.0, 24.3, 14.2. HRMS (ESI):
calcd for C20H22O5N, [M+H] +, 356.1492; found, 356.1494.
Compound 8a: White solid. 109 mg. Yield 40%. 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 6.9 Hz,
1H), 7.27 – 7.22 (m, 1H), 7.14 (td, J = 7.3, 1.4 Hz, 1H), 7.09 (d, J = 7.1 Hz, 1H), 5.26 (d, J = 6.1 Hz,
1H), 3.96 – 3.68 (m, 4H), 3.53 (dd, J = 6.1, 2.9 Hz, 1H), 2.78 (d, J = 8.4 Hz, 1H), 2.54 – 2.19 (m, 1H),
1.26 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 169.6, 133.1, 131.6,
128.4, 126.1, 125.1, 123.9, 94.5, 75.7, 65.7, 60.4, 43.8, 25.0, 19.5, 15.3, 13.8. HRMS (ESI): calcd for
C16H19O4, [M+H] +, 275.1283; found, 275.1276.
Compound 8b: Colorless oil. 27 mg. Yield 11%. 1H NMR (400 MHz, CDCl3) δ 7.34 – 7.24 (m,
2H), 7.23 – 7.11 (m, 2H), 5.27 (s, 1H), 4.26 (q, J = 7.1 Hz, 2H), 4.06 – 3.59 (m, 2H), 2.76 (d, J =
8.5 Hz, 1H), 2.40 (d, J = 8.5 Hz, 1H), 2.29 (s, 1H), 1.33 (t, J = 7.1 Hz, 3H), 1.28 (t, J = 7.1 Hz,
3H). 13C NMR (101 MHz, CDCl3) δ 171.9, 134.7, 132.0, 128.3, 126.4, 125.4, 122.4, 94.0, 77.5,
65.8, 61.2, 45.2, 26.2, 19.1, 15.4, 14.2. HRMS (ESI): calcd for C16H19O4, [M+H] +, 275.1283;
found, 275.1275.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1H and 13C NMR spectra, NOE spectra, and 2D spectra of starting materials and products (PDF).
Xꢀray crystal structure data for 3ad (CIF).
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: xyyang@hit.edu.cn
*Eꢀmail: xiawj@hit.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
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We are grateful for the financial supports from China NSFC (Nos. 2137205, 21472030 and 21672047),
SKLUWRE (No. 2015DX01) and the Fundamental Research Funds for the Central Universities (Grant No.
HIT.BRETIV.201310).
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