Cycloaddition Reaction of Vinylphenylfurans and Dimethyl Acetylenedicarboxylate to [8 + 2] Isomers via Tandem [4 + 2]/Diradical Alkene-Alkene Coupling/[1,3]-H Shift Reactions: Experimental Exploration and DFT Understanding of Reaction Mechanisms

Article abstract of DOI:10.1021/acs.joc.6b00792

An experimental test of designed [8 + 2] reaction of vinylphenylfuran and dimethyl acetylenedicarboxylate (DMAD) has been carried out, showing that the reaction gave unexpected addition products under different conditions. When the reaction was conducted under thermal conditions in toluene, expoxyphenanthrene, which was named as a [8 + 2] isomer, was generated. The scope of this reaction has been investigated in the present study. In addition, experiments and DFT calculations have been conducted to investigate how the reaction between vinylphenylfuran and DMAD took place. Surprisingly, the reaction did not involve the expected [8 + 2] intermediate, o-quinodimethane. Instead, the reaction starts from intermolecular Diels-Alder reactions between DMAD and the furan moiety of vinylphenylfuran, followed by unexpected intramolecular alkene-alkene coupling. This step generates a diradical species, which then undergoes [1,3]-H shift to give the experimentally observed expoxyphenanthrene. DFT calculations revealed that, the [8 + 2] cycloadduct cannot be obtained because the [1,5]-H shift process from the [1,5]-vinyl shift intermediate is disfavored kinetically compared to the [1,3]-H shift to the [8 + 2] isomer.

Full text of DOI:10.1021/acs.joc.6b00792

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Article
Cycloaddition Reaction of Vinylphenylfurans and Dimethyl
Acetylenedicarboxylate to [8+2] Isomers via Tandem [4+2]/Diradical
Alkene-Alkene Coupling/[1,3]-H Shift Reactions: Experimental
Exploration and DFT Understanding of Reaction Mechanism
Kai Chen, Feng Wu, Lijuan Ye, Ziyou Tian, Zhi-Xiang Yu, and Shifa Zhu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00792 • Publication Date (Web): 19 Aug 2016
Downloaded from http://pubs.acs.org on August 23, 2016
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Cycloaddition Reaction of Vinylphenylfurans and Dimethyl
Acetylenedicarboxylate to [8+2] Isomers via Tandem [4+2]/Diradical
Alkene-Alkene Coupling/[1,3]-H Shift Reactions: Experimental
Exploration and DFT Understanding of Reaction Mechanism
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†
,#
†,#
†
‡
‡
†
Kai Chen, Feng Wu, Lijuan Ye, Ziyou Tian, ZhiꢀXiang Yu, * Shifa Zhu *
†
Key Laboratory of Functional Molecular Engineering of Guangdong Province,
School of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510640, People’s Republic of China;
‡
College of Chemistry, Peking University, Beijing 100871,
People’s Republic of China
#
These two authors contributed equally to this work.
CO Me
2
DMAD
CO Me
2
CO Me
O
CO2Me
O
2
toluene, △
O
H
H
[8+2] isomer (observed)
[8+2] cycloadduct (anticipated)
[1,5]-H shift
(
kinetically
[4+2] DMAD
[
1,3]-H shift
disfavored)
H
alkene-alkene
coupling
H
CO Me
2
C-C cleavage
CO Me
2
CO Me
2
CO Me
2
CO Me
CO Me
O
2
2
O
O
rate-determining
step
[
4+2] cycloadduct
isolated intermediate)
diradical
intermediate
[1,5]-vinyl shift
intermediate
(
ABSTRACT: An experimental test of designed [8+2] reaction of vinylphenylfuran
and dimethyl acetylenedicarboxylate (DMAD) has been carried out, showing that the
reaction gave unexpected addition products under different conditions. When the
reaction was conducted under thermal conditions in toluene, expoxyphenanthrene,
which was named as a [8+2] isomer, was generated. The scope of this reaction has
been investigated in the present study. In addition, experiments and DFT calculations
have been conducted to investigate how the reaction between vinylphenylfuran and
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DMAD took place. Surprisingly, the reaction did not involve the expected [8+2]
intermediate, oꢀquinodimethane. Instead, the reaction starts from intermolecular
DielsꢀAlder reaction between DMAD and the furan moiety of vinylphenylfuran,
followed by unexpected intramolecular alkeneꢀalkene coupling. This step generates a
diradical species, which then undergoes [1,3]ꢀH shift to give the experimentally
observed expoxyphenanthrene. DFT calculations revealed that, the [8+2] cycloadduct
cannot be obtained because [1,5]ꢀH shift process from the [1,5]ꢀvinyl shift
intermediate is disfavored kinetically compared to the [1,3]ꢀH shift to the [8+2]
isomer.
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1
. INTRODUCTION
The [8+2]ꢀcycloaddition reaction can provide a straightꢀforward approach for the
1
synthesis of 10ꢀmembered ring compounds. However, before 2003, all reported [8+2]
reactions were limited to using geometrically constrained tetraenes as the 8π
1
b
2
3
components (such as heptafulvenes, tropones, and indolizines ), in which carbons
and 8 are rigidly held in close proximity. In 2003, Herndon and coꢀworkers reported
1
the first successful [8+2]ꢀcycloaddition reaction between conformationally flexible
tetraene (dienylisobenzofurans) and tetraenophile [dimethyl acetylenedicarboxylate
(DMAD)], as shown in Scheme 1a, which provided an incredibly simple entry into
4
furanꢀbridged tenꢀmembered rings. In their following study, it was found that simple
furandienes could also be excellent tetraene substrates for [8+2] reaction with DMAD
5
(
Scheme 1b). These [8+2] cycloadditions provide a potentially powerful method to
6
synthesize skeleton of a variety of biologically active coralꢀderived natural products.
Scheme 1. Cycloadditions of dienylfurans and DMAD reported by Herndon and
4
,5
coꢀworkers
R1
O
R2
R2
CO Me
R1
2
[8+2]
+
(a)
O
CO
CO
2
Me
MeO C
CO Me
2
2
R1
R2
R2
R1
2
Me
[
8+2]
(b)
+
O
O
CO Me
2
MeO C
2
CO Me
2
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Computational organic chemistry has become an important tool to facilitate
7
mechanistic understanding of chemical reactions. In 2007, Yu and coꢀworkers carried
out density functional theory (DFT) calculations to investigate the mechanism of the
8
[8+2] cycloaddition shown in Scheme 1a. It was suggested that the concerted [8+2]
pathway (Scheme 2, pathway A) was not favored because the two terminal carbons of
the tetraenes are far away from each other and this geometry did not allow
simultaneous frontier orbital overlap between HOMO of tetraenes and LUMO of
dienophiles. In contrast, these reactions were proposed to proceed through a stepwise
pathway, which starts from DielsꢀAlder [4+2] cycloaddition, followed by a [1,5]ꢀvinyl
shift to afford the observed [8+2] product (Scheme 2, pathway C). When there is an
electronꢀdonating group (such as a methoxy group) in the dienyl moiety of
dienylisobenzofurans, a stepwise reaction pathway involving formation of a
zwitterionic or diradical intermediate becomes very competitive (Scheme 2, pathway
B), especially in solution, due to the stabilization effect of electronꢀdonating group to
the transition state, which contains positive charge on its tetraene moiety. These
theoretical studies helped chemists to understand the mechanisms of these [8+2]
cycloadditions, and provided insights and guides for the future design of new [8+2]
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cycloaddition reactions and other higher order [m+n] cycloadditions as well.
Scheme 2. Three pathways for dienylisobenzofuranꢀalkyne [8+2] cycloaddition
8
proposed by Yu and coꢀworkers
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oꢀQuinodimethane (oꢀQDM), a transient and highly reactive species, has attracted
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much attention of both theoretical and synthetic chemists over the past four decades.
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As part of our continuing efforts to develop oꢀQDM chemistry, together with our
interests to develop new [8+2] reactions, we envisioned that vinylphenylfuran (1a)
can act as 8e tetraene and reacts with DMAD to generate oꢀQDM III, via [4+2]/vinyl
shift process (Scheme 3). Intermediate III here was also labeled as a [1,5]ꢀvinyl shift
intermediate. The vinyl shift could also occur in a stepwise fashion via diradical
intermediate II, which was formed by coupling the two alkene parts in intermediate I,
followed by CꢀC bond cleavage to give intermediate III. Intermediate III is regarded
as an [8+2] cycloadduct, but we thought direct [8+2] is not allowed geometrically, as
found previously in Herndon’s system. We then envisioned that, III is not stable and
can undergo [1,5]ꢀH shift to give IV as the final product. We expected that this
transformation from III to IV should be easy due to the restoration of aromaticity in
this process. But to our surprise, we did not obtain product IV when we carried out
the designed reaction (see Scheme 3 and later on the results and discussion part).
Instead, we obtained product 3aa, which was named as the [8+2] isomer, and its
retroꢀDielsꢀAlder reaction product (not shown in Scheme 3 and will be discussed later
on the results and discussion part). We then hypothesized that IV, generated through
[4+2]/[1,5]ꢀvinyl and H shifts, underwent [1,7]ꢀH shift to give V. Then V underwent
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e cyclization to furnish product 3aa (pathway I). Here we report our discovery of the
synthesis of 3aa, the computational and experimental exploration of whether 3aa is
generated via the pathway I described in Scheme 3, and the reason about why the
expected [8+2] cycloadduct IV was not observed.
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Scheme 3. Design and experimental finding of the [8+2] reaction between enylfuran
and DMAD
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2
. RESULTS AND DISCUSSION
2.1 Reaction of Vinylphenylfurans and DMAD
Initial efforts were made to systematically investigate various reaction conditions
1
2
for the designed [8+2] reaction of vinylphenylfuran 1a and DMAD 2a. Following
4,8
the conditions reported in previous work, the reaction was conducted in anhydrous
toluene at 85 ºC for 12 hours. In this case, product 3aa, which was named as a [8+2]
isomer, and its retroꢀDielsꢀAlder product 4aa were obtained in only 14% yield, as
1
determined by H NMR spectroscopy (Table 1, entry 1). The combined yield of 3aa
and 4aa could be enhanced to 65% when the reaction was conducted at 110 ºC for 24
hours (entry 2). Marginal improvement of the reaction yield was observed when the
reaction temperature was raised to 120 °C (entry 3). The reaction yields cannot be
substantially improved by using other solvents (see SI for detail). Interestingly, it was
found that the reaction in water gave different results from those in toluene (see later
discussion). The reaction yield was further improved to 86% when 1.5 equivalents
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DMAD was applied (entry 4). The structure of 3aa was confirmed by Xꢀray
diffraction analysis (see SI), where the two ester groups are in cisꢀposition, and the
bridge oxygen is in transꢀposition to the ester groups. The vicinal proton coupling
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constant of the bridgehead CH to CHCO Me in 3aa is about 4.2 Hz, which is also
consistent with the dihedral angle of these two protons in the crystal structure
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according to the Karplus equation.
[a]
Table 1. Optimization of reaction conditions
[
c]
yield(%)
[b]
entry 2a (eq) temp. (°C)
time (h)
total
3aa
4aa
[
d]
[d]
[d]
1
2
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4
1.0
1.0
1.0
1.5
85
12
24
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3
110
120
120
65
77
38
43
45
27
34
41
86
[
a] Unless otherwise noted, the reaction was carried out using sealed tubes in toluene under N . [b] The
2
1
oil bath temperature. [c] Isolated yield. [d] Yield determined by H NMR spectroscopy.
With the optimized reaction conditions (Table 1, entry 4) in hand, the substrate
scope was then examined. When diethyl acetylenedicarboxylate (DEAD, 2b) was
used as the 2π component, the desired products 3ab and 4ab could be produced in 45%
and 41%, respectively (Table 2, entry 2). For substituents in phenyl moiety of 1,
electronꢀdonating group (ꢀMe or ꢀOMe) was more favorable than
3
electronꢀwithdrawing group (ꢀF or ꢀCF ) (Table 2, entries 3ꢀ6). Such reactivity
difference may be attributed to the fact that the electronꢀrich tetraenes 1 have higher
HOMO energies than electronꢀpoor ones. Similar electronic effects and reactivity
trends had also been observed in the [8+2] of dienylisobenzofurans with dienophiles
4
,5,8
reported previously by Yu and Herndon.
Substituents in the alkene moiety of 1 was
2
explored as well. And a methyl group at R could be tolerated, affording the desired
products 3fa and 4fa in yields of 26% and 39%, respectively. But an
2
electronꢀwithdrawing group (ꢀCO
2
Me) at R or internal alkene was ineffective for this
transformation, as neither 3 nor 4 was obtained experimentally.
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[a]
Table 2. Substrate scope of the reaction of vinylphenylfuran and alkyne in toluene
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[
b]
yield (%)
entry
1
2
total
3
4
1
2
3
4
1
2
1a (R , R , R = H)
2a (R = Me) 86
45 (3aa)
41 (4aa)
1
2
3
4
1a (R , R , R = H)
2b (R = Et)
86
45 (3ab) 41 (4ab)
52 (3ba) 35 (4ba)
1
2
3
4
3
1b (R = 5ꢀMe; R , R = H)
2a (R = Me) 87
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4
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8
9
1c (R = 4ꢀOMe; R , R = H) 2a (R = Me) 88
52 (3ca)
36 (4ca)
1
2
3
4
1d (R = 4ꢀCF ; R , R = H)
2a (R = Me) 63
33 (3da) 30 (4da)
3
1
2
3
4
1e (R = 4ꢀF; R , R = H)
2a (R = Me) 71
43 (3ea)
28 (4ea)
1
3
2
4
1f (R , R = H; R = Me)
2a (R = Me) 65
26 (3fa)
39 (4fa)
1
3
2
4
1g (R , R = H; R = CO
2
Me) 2a (R = Me)
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1
2
3
4
1h (R , R = H; R = Me)
2a (R = Me)
[
2
a] The reaction was carried out using sealed tubes in toluene under N for 24 h. The molar ratio of 1/2
= 1:1.5. The oil bath temperature was set at 120 °C. [b] Yield of isolated product.
As mentioned above, when the reaction was conducted in water at 120 °C for 24
hours, four different products 5, 6, 7, and 8 were isolated. Compounds 5 and 6 were
two diastereomers, which should come from the nucleophilic ringꢀopening of 3 by
14
water (6aa was confirmed by Xꢀray diffraction analysis, see SI). Product 7 was
generated possibly from a decarboxylative aromatization of 3. Intermolecular
DielsꢀAlder reaction of compounds 4 with 1, followed by ringꢀopening led to the
generation of product 8. In all cases, 5 and its diastereomers 6 were the major
products (Table 3).
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[
a]
Table 3. Reaction of vinylphenylfuran and alkyne in water
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[
b]
entry
1
1
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6
7
8
yield
1a (R = H)
5aa (22%) 6aa (24%) 7aa (14%)
8aa (5%)
65%
2
3
4
1b (R = 5ꢀMe) 5ba (46%) 6ba (28%)
1d (R = 4ꢀCF3) 5da (29%) 6da (8%)
1e (R = 4ꢀF) 5ea (15%) 6ea (21%)
7ba (7%)
7da (8%)
7ea (13%)
8ba (4%)
8da (ꢀ)
85%
45%
62%
8ea (13%)
[a] The reaction was carried out using sealed tubes in water for 24 h under N
:1. The oil bath temperature was set at 120 °C. [b] Yield of isolated product.
2
. The molar ratio of 1/2 =
1
To further understand the water mediated process, a control reaction was then
conducted (Scheme 4). When the aqueous solution of 3aa or 4aa was refluxed for 24
hours, a mixture of 5aa and 6aa was produced in about 1:1 ratio. This control
experiment showed clearly that 5aa and 6aa came from the nucleophilic ringꢀopening
of 3 by water.
Scheme 4. The control reaction.
2 3
When catalytic amount of Lewis acid, such as ZnCl or FeCl , was used as catalyst
for this transformation in toluene, a different distribution of products was observed.
Taking the ZnCl ꢀcatalyzed system as an example, in additional to products 7 and 8,
2
which were found in the water reaction system, another product 4ꢀphenylphenol
derivative 9 was observed (Table 4). The product distributions were sensitive to the
electronic properties of tetraenes 1. For example, the reaction of vinylphenylfuran 1a
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with DMAD gave products 7aa, 8aa, and 9aa in 7%, 45%, and 30% yields,
respectively (Table 4, entry 1). Vinylphenylfurans with electronꢀdonating groups
(Table 4, entries 2ꢀ3) performed much better than those with electronꢀwithdrawing
groups (Table 3, entries 4ꢀ5). Interestingly, 4ꢀphenylphenol derivative 9ca was
obtained in quantitative yield when electronꢀrich substrate 1c was applied (Table 4,
entry 3). While for electronꢀdeficient substrate 1d, only 7da and 8da were detected
(Table 4, entry 4).
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[
a]
Table 4. Reaction of vinylphenylfuran and alkyne in toluene with zinc catalyst
[b]
entry
1
7
8
9
yield
1
2
3
4
5
1a (R = H)
1b (R = 5ꢀMe)
1c (R = 4ꢀOMe)
7aa (7%)
7ba (31%)
7ca (ꢀꢀ)
8aa (45%)
9aa (30%)
82%
81%
100%
38%
73%
8ba (16%) 9ba (34%)
8ca (ꢀꢀ) 9ca (100%)
8da (21%) 9da (ꢀꢀ)
8ea (39%) 9ea (28%)
1d (R = 4ꢀCF
1e (R = 4ꢀF)
3
)
7da (17%)
7ea (6%)
[
a] The reaction was carried out using sealed tubes in toluene for 24 h using 5 mol% ZnCl
2 2
under N .
The molar ratio of 1/2 = 1:1. The oil bath temperature was set at 120 °C. [b] Yield of isolated product.
2
.2 Understanding the Mechanism from Experimental Observations and DFT
Calculations
In this part, we will report our understanding of the reaction mechanism for the
thermal reaction of 1a and 2a using DFT calculations and experiments.
Experimental Study. We proposed pathway I for the formation of the final
8
,15
product 3aa in Scheme 3. It was expected that the [4+2] cycloadduct I should be a
stable and isolable intermediate if milder reaction conditions were applied. With this
hypothesis, we then carried out the reaction of vinylphenylfuran and DMAD in
toluene at 85 °C (not the original 120 °C ) for 4 hours. To our delight, the expected
[
4+2] cycloadduct I was successfully obtained (Scheme 5). This [4+2] cycloadduct I
can be further converted into 3aa in 80% yield at 85 ºC for additional heating of 4
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hours. It was found that 3aa and 4aa could be converted into each other at 120 °C in
toluene (the ratio of 3aa to 4aa was close to 1:1), implying that 4aa or 3aa could be
formed from its counterpart through DielsꢀAlder or retroꢀDielsꢀAlder reaction
16
(Scheme 5).
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Scheme 5. Interconversion of products in toluene
1
[a] The yield of I:3aa:4aa = 6%:8%:2%, The molar ratio was determined by H NMR spectroscopy.
Pathway I. Based on these experimental observations, DFT calculations were
then performed to help understanding the reaction mechanism. As shown in Figure 1,
the [4+2] via TS1 (with activation enthalpy of 16.5 kcal/mol) is easy and exothermic
(by 6.1 kcal/mol). This step is concerted but asynchronous, as evidenced by the large
difference between the two forming CꢀC bond distances in transition structure TS1
(2.81 vs. 1.86 Å, Figure 2). To our surprise, we found that the [1,5]ꢀvinyl shift is
stepwise. The first step is to form the C8ꢀC9 bond via a diradical transition state TS2.
2
The resulting intermediate II is a diradical species with a computed <S > of 1.03, and
the spin densities are mostly distributed on atoms C7 (0.87) and C10 (ꢀ0.74) (see
Supporting Information), both of which could be stabilized by the conjugated phenyl
group and ester group, respectively. Then the C4ꢀC9 bond breaks via TS3 to give
intermediate III, the vinyl shift product from I. The forming bond in TS2 is about
1.96 Å in length, and the breaking bond in TS3 is about 2.19 Å. We can locate a
closedꢀshell oneꢀstep concerted vinyl shift transition state, which is very similar to
TS3, but its wavefunction is not stable and such a transition state is an artificial one.
The difficult step of the stepwise [1,5]ꢀvinyl shift is the CꢀC bond formation step with
an activation enthalpy of 24.7 kcal/mol, and this step is endothermic. The CꢀC bond
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Figure 1. Computed potential energy surfaces for pathways I and II at the (U)B3LYP/6ꢀ31+G(d) level in toluene.
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TS1
TS2
II
TS3
III
TS4
IV
TS5
TS6
Figure 2. Optimized geometries of key transition states and intermediates. Bond
distances in Å.
breaking step in the [1,5]ꢀvinyl shift requires an activation enthalpy of 9.7 kcal/mol
and this step is exothermic.
The followed [1,5]ꢀH shift converting oꢀQDM III to IV via TS4 in pathway I is
not easy with an activation enthalpy of 31.1 kcal/mol. The distances of the forming
and breaking CꢀH bonds in TS4 are 1.37 and 1.43 Å, respectively. This step is an
exothermic process since IV is more stable than III by 2.7 kcal/mol.
We proposed that IV could be converted to V via [1,7]ꢀH shift process (Figure
17
3
), followed by 6eꢀelectrocyclization to give the experimentally observed product
3
aa. [1,7]ꢀH shifts are usually allowed antarafacially. In the present system, such a
transition state is not possible in geometry as the rotation of single bonds is restricted
18
due to the ring constrain. A suprafacial [1,7]ꢀH shift is also forbidden here,
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according to the WoodwardꢀHoffmann rules. As shown in Figure 3, the orbital
coefficients in 1 and 7 positions are out of phase in the SOMO orbital of X.
CO Me
CO Me
2
CO Me
2
2
antarafacial
X
geometrically
disallowed
suprafacial
X
orbital symmetry
forbidden
CO Me
CO Me
2
2
CO Me
O
2
O
O
H
H
H
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V
IV
V'
(a)
4
3
5
6
CO Me
2
7
2
CO Me
2
1
O
X
(b)
Figure 3. (a) Antarafacial or suprafacial [1,7]ꢀH shift from IV to V (or V’); (b) The
SOMO of X.
We can rule out pathway I due to the nonꢀexistence of [1,7]ꢀH shift. Actually we
can further exclude this pathway by the second reason, that formation of intermediate
IV is not favored kinetically than the pathway II involving a direct [1,3]ꢀH shift to
convert II to 3aa, which will be discussed in the latter of this paper.
Before closing our discussion of pathway I, we want to mention two other possible
pathways converting intermediate III to 3aa. One is the possible [1,3]ꢀH shift from
III. This is not allowed because in SOMO of X (Figure 3(b)), the orbitals at 5 and 7
are out of phase. All efforts to locate such a transition state failed. A waterꢀassistedꢀH
20
transfer pathway was considered as well (Scheme 6). Yu and coworkers have
demonstrated experimentally and computationally that water or other proton source
such as methanol can act as an efficient protonꢀtransfer catalyst in [1,2] and [1,3]ꢀH
21
transfers. we speculated that a trace amount of water, which exists in the reagent or
solvent, could catalyze [1,5]ꢀH shift to convert III to VI. The desired product 3aa
could then be accessed through 6πꢀelectrocyclization (from VI) or
enolization/6πꢀelectrocyclization (from V). However, this waterꢀassisted pathway was
not supported by DFT calculations and experiments, because the conversion from III
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to VI is very difficult, requiring an activation enthalpy about 40.2 kcal/mol (see
Supporting Information for details), and no H/D exchange was observed, when the
2
reaction was conducted in toluene with 10 equiv. of D O.
Scheme 6. A proposed waterꢀassisted pathway for the generation of 3aa.
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Pathway II. After the above mechanistic studies, we envisioned that maybe the
o
ꢀQDM intermediate III did not exist. We further hypothesized that intermediate II
underwent a [1,3]ꢀH shift directly converting II to product 3aa (pathway II, Scheme
22
7
). The [1,3]ꢀH shift can be regarded as a hydrogen radical shift and this step is very
facile with an activation enthalpy of 14.0 kcal/mol (Figure 1). The distances of the
forming and breaking CꢀH bonds in TS5 are 1.66 and 1.29 Å (Figure 2), respectively.
This [1,3]ꢀH shift is irreversible because this step is exothermic by 42.1 kcal/mol.
This explains why intermediate I could only be observed after a short time and at a
low temperature. The final step of the studied reaction is the retroꢀDꢀA reaction,
converting 3aa to the final product with an activation enthalpy of 27.8 kcal/mol
(Figure 1). The lengths of two forming carbonꢀcarbon bonds, C1ꢀC10 and C4ꢀC9 in
transition state TS6 are 2.28 and 2.04 Å, respectively (Figure 2).
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Scheme 7. Pathway II for the generation of 3aa.
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The potential energy surface of pathway II showed that the rateꢀdetermining step
is the formation of intermediate II. That is why at lower temperature we can obtain
the [4+2] cycloadduct I. Calculation results here indicate that the overall activation
free energy in pathway II is 37.1 kcal/mol in solution. Since there is overestimation of
entropy here for the twoꢀmolecule to oneꢀmolecule (1a + DMAD to II and then to
3
aa), the actual activation should be lower than this value by several kcal/mol. This is
consistent with the experimental reaction conditions (refluxing in toluene at 120 °C
for 24 hours).
Comparison of pathways I and II indicated that the stepwise vinyl shift to give III
is easy, but the [1,5]ꢀH shift to form IV in pathway I is difficult than the [1,3]ꢀH shift
from II to 3aa. TS5 is higher in energy than TS3 by 4.3 kcal/mol. This could explain
why the originally proposed [8+2] cycloadduct IV was not generated.
To further investigate the direct [1,3]ꢀhydrogen migration mechanism in pathway
II, an isotopicꢀlabeling experiment was then carried out to track whether the hydrogen
at C10 of the product 3aa come from the hydrogen at C8 of the starting material 1a
(Scheme 8). Selective isotopic labeled 1a (70% D) at the C8 was reacted with
nonlabeled DMAD, affording the product 3aa with 70% D at C10 (See SI for detail).
Such results are perfectly consistent with the direct intramolecular H shift from C8 to
C10. Therefore, based on theoretical and experimental studies, the reaction of
vinylphenylfuran and DMAD is suggested to take place through an intramolecular
DielsꢀAlder reaction, followed by a diradical alkeneꢀalkene coupling. Then a [1,3]ꢀH
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shift converts diradical intermediate II to polycyclic product 3aa, which then
undergoes retra-DielsꢀAlder to furnish final product 4aa. A key diradical intermediate
II via the alkeneꢀalkene coupling but not the [8+2] cycloaddition compound, oꢀQDM
III is supported by our DFT mechanistic studies. Further exploration of this system is
also underway in our group.
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Scheme 8. Deuterium labeling study of the [1,3]ꢀHꢀshift
3
. CONCLUSIONS
In conclusion, an experimental and theoretical study was carried out to investigate a
designed [8+2] reaction of vinylphenylfuran 1 and dimethyl acetylenedicarboxylate
DMAD, 2a) and its derivatives. The reactions occured efficiently under three
(
different conditions, giving rise to different products. When the reaction was
conducted in refluxing toluene, an unexpected expoxyphenanthrene derivative 3 ([8+2]
isomer product) and its retroꢀDielsꢀAlder product 4 were generated. The scope of this
reaction has been investigated in the present study. Experimental and DFT
calculations have been conducted to investigate how the reaction between
vinylphenylfuran and DMAD took place. The reaction was proposed through an
intermolecular DielsꢀAlder reaction between DMAD 2a and the furan moiety of
vinylphenylfuran 1a, followed by an unexpected intramolecular alkeneꢀalkene
coupling reaction. A diradical species was generated in this process, which then
underwent intramolecular [1,3]ꢀH shift to give the experimentally observed
expoxyphenanthrene 3aa. Product 3aa can be transformed to 4aa via
retroꢀDielsꢀAlder reaction. The mechanistic study ruled out the originally proposed
ꢀQDM intermediate from [4+2]/[1,5]ꢀvinyl shift step (Scheme 3, pathway I). The
a
o
expected [8+2] cycloadduct IV (pathway I) was not generated because the [1,5]ꢀH
shift from III is disfavored than the [1,3]ꢀH shift process in pathway II. These
theoretical studies, especially the finding of intramolecular alkeneꢀalkene coupling
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process via diradical intermediate and the [1,3]ꢀH shift mechanisms may provide
useful insights and guides for understanding of other [m+n] cycloadditions.
4
. EXPERIMENTAL SECTION
General information. Unless otherwise noted, all reactions were carried out under
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nitrogen atmosphere in Schlenk tube, and solvents were purified by standard methods.
1
13
19
H, C, and F NMR spectra were recorded on 400 MHz, 100 MHz, and 376 MHz
1
13
NMR spectrometers, respectively. H NMR and C NMR chemical shifts were
19
determined relative to internal standard TMS at δ 0.0, and F NMR chemical shifts
were determined relative to CFCl as external standard. Chemical shifts (δ) are
reported in ppm, and coupling constants ( ) are in Hertz (Hz). The following
3
J
abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, br = broad. The mass analyzer type used for the
HRMS is Fourier transform ion cyclotron resonance mass spectrometry (FTꢀICRꢀMS).
All reagents were purchased from commercial sources, unless specified otherwise, or
prepared as described in the literature.
Synthesis of vinylphenylfuran
Under a nitrogen atmosphere at 0 ºC, nꢀBuLi (1.2 mL, 2.5 M) was dropped into a
3 3
solution of CH PPh Br (1.1249 g, 3.140 mmol) in THF (10 mL) in a 50 mL Schlenk
tube, and was stirred for 30 min before being treated with 2ꢀbromoꢀbenzaldehyde
(464.7 mg, 2.512 mmol) dropwise. The resulting solution was stirred at room
3 4
temperature for 10 h, and then filtered through a Celite pad. The filtrate and Pd(PPh )
(87.1mg, 0.0754 mmol) was added into a 50 mL schlenk tube, and stirred for 10 min
at room temperature. Then 2ꢀfuranboronic acid (309.2 mg, 2.763 mmol, dissolved in 2
2 3
mL ethanol) and Na CO (532.6 mg, 5.024 mmol, in 2 mL water) were added into the
mixture in sequence. The mixture was heated under reflux for 16 h. After completion
of the reaction, the system was filtered, then the solvent was concentrated, and the
4
residue was extracted with 10 mL ether three times, dried over MgSO , and
evaporated under reduced pressure to afford 2ꢀ(2ꢀvinylphenyl)furan 1a (307 mg, 72%),
which was purified by column chromatography over silica gel eluting with petroleum
ether.
General procedure for reaction in toluene
Under a nitrogen atmosphere, 1a (25.5 mg, 0.15 mmol) and DMAD 2a (32.0 mg,
0.225 mmol) was injected into 1 mL toluene in 25 mL Schlenk tube. The system was
kept at 120 °C for 24 h. After completion of the reaction, the solvent was concentrated,
and purified by column chromatography over silica gel eluting with petroleum
ether/EtOAc (5:1) to afford the desired product 3aa and 4aa.
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General procedure for reaction in water
Under a nitrogen atmosphere, 1a (25.5 mg, 0.15 mmol) and DMAD 2a (32.0 mg,
0
.225 mmol) was injected into 1 mL water in 25 mL Schlenk tube. The system was
kept at 120 °C for 24 h. After completion of the reaction, the reaction mixture was
extracted with 3 mL acetic ether three times, dried over MgSO , and evaporated under
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reduced pressure. The residue was purified by column chromatography over silica gel
eluting with petroleum ether/EtOAc (10:1 to 5:1 to 2:1) to afford the desired product
5aa, 6aa, 7aa and 8aa.
General procedure for reaction in ZnCl
Under a nitrogen atmosphere, 1a (25.5 mg, 0.15 mmol) and DMAD 2a (32.0 mg,
.225 mmol) was injected into 1 mL toluene (with ZnCl 1.0 mg, 5 mol%) in 25 mL
2
/toluene
0
2
Schlenk tube. The system was kept at 120 °C for 24 h. After completion of the
reaction, the solvent was concentrated, and purified by column chromatography over
silica gel eluting with petroleum ether/EtOAc (5:1 to 3:1) to afford the desired product
7
aa, 8aa and 9aa.
2ꢀ(2ꢀVinylphenyl)furan (1a). Colorless oil, R
f
= 0.9 (petroleum ether), yield (307 mg,
= 7.5, 1.6 Hz, 1H), 7.49–7.43 (m,
= 17.4, 11.0 Hz, 1H), 6.43 (dt, = 3.3,
= 10.9, 1.3 Hz, 1H). C NMR
1
7
2%). H NMR (400 MHz, CDCl
3
) δ 7.57 (dd,
J
2
H), 7.24 (dd,
J
= 7.3, 1.5 Hz, 2H), 7.01 (dd,
J
J
13
2.6 Hz, 2H), 5.61 (dd,
100 MHz, CDCl
15.7, 111.4, 109.9. IR (thin film) νmax (cm ) 1767, 1688, 1627, 1402, 1216, 1194,
J
= 17.4, 1.3 Hz, 1H), 5.24 (dd,
J
(
3
) δ 152.8, 142.3, 136.5, 135.7, 129.3, 127.8, 127.8, 127.5, 127.1,
ꢀ1
1
+
1091, 1091, 1009, 763. HRMS (EI) mass calcd for C12H10O ([M] ): 170.0732; found
1
70.0728.
2
ꢀ(5ꢀMethylꢀ2ꢀvinylphenyl)furan (1b). Colorless oil, R = 0.9 (petroleum ether), yield
f
1
(400 mg, 75%). H NMR (400 MHz, CDCl
3
) δ 7.44–7.40 (m, 1H), 7.36 (d,
= 17.5, 11.0 Hz, 1H), 6.40 (td,
= 17.4, 1.3 Hz, 1H), 5.18 (dd, J = 10.9, 1.3 Hz, 1H), 2.29 (s, 3H).
J
= 7.8 Hz,
2
H), 7.02 (d,
J
= 8.2 Hz, 1H), 6.97 (dd,
J
J = 3.4, 2.2
Hz, 2H), 5.55 (dd,
J
1
3
C NMR (100 MHz, CDCl
3
) δ 152.9, 142.1, 137.5, 136.2, 132.9, 129.1, 128.7, 128.0,
ꢀ1
1
26.9, 114.8, 111.4, 109.7, 21.2. IR (thin film)
ν
max (cm ) 2921, 1769, 1687, 1608,
+
1
495, 1401, 1040, 977, 823, 652. HRMS (EI) mass calcd for C H O ([M] ):
13
12
184.0888; found 184.0887.
2
ꢀ(4ꢀMethoxyꢀ2ꢀvinylphenyl)furan (1c). Colorless oil, R
f
= 0.9 (petroleum ether), yield
= 8.6 Hz, 1H), 7.51 (dd, J =
1
(
494 mg, 70%). H NMR (400 MHz, CDCl
3
) δ 7.58 (d,
J
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1.8, 0.7 Hz, 1H), 7.14–7.04 (m, 2H), 6.92 (dd,
J
= 8.6, 2.6 Hz, 1H), 6.50 (dd, J = 3.3,
1
.8 Hz, 1H), 6.43 (dd,
J
= 3.3, 0.6 Hz, 1H), 5.71 (dd,
J
= 17.4, 1.3 Hz, 1H), 5.35 (dd,
J
13
=
10.9, 1.3 Hz, 1H), 3.89 (s, 3H). C NMR (100 MHz, CDCl
3
) δ 159.2, 152.8, 141.7,
137.1, 136.3, 129.1, 122.6, 115.7, 113.7, 111.7, 111.3, 108.6, 55.4. IR (thin film)
ν
max
ꢀ1
(
cm ) 2961, 2911, 2836, 1676, 1602, 1563, 1485, 1463, 1419, 1233. HRMS (EI) mass
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
calcd for C13
H
12
O
2
([M] ): 200.0837; found 200.0838.
f
2ꢀ(4ꢀ(Trifluoromethyl)ꢀ2ꢀvinylphenyl)furan (1d). Colorless oil, R = 0.9 (petroleum
1
ether), yield (170 mg, 34%)
.59 (d,
6.56 (dd,
.
H NMR (400 MHz, CDCl
= 17.4, 11.0 Hz, 1H), 6.67 (d,
= 2.9, 1.8 Hz, 1H), 5.78 (d, = 17.4 Hz, 1H), 5.46 (d,
) δ 151.3, 143.0, 135.9, 135.6, 132.1, 129.5 (q,
3
) δ 7.80 (d,
J
= 10.9 Hz, 2H),
7
J
= 5.2 Hz, 2H), 7.12 (dd,
J
J = 3.3 Hz, 1H),
J
J
J = 11.0 Hz, 1H).
1
3
C NMR (100 MHz, CDCl
3
JCꢀF = 32.4
Hz), 127.4, 124.3 (dd,
J
CꢀF = 9.7, 3.8 Hz), 124.2(d,
J
CꢀF = 273.1 Hz), 117.3, 111.7,
1
9
ꢀ1
111.5. F NMR (376 MHz, CDCl ) δ ꢀ62.60. IR (thin film) νmax (cm ) 2960, 2919,
3
2
9 3
849, 1401, 1330, 1270, 1167, 1040, 1012, 975. HRMS (EI) mass calcd for C13H F O
+
(
[M] ): 238.0605; found 238.0604.
2ꢀ(4ꢀFluoroꢀ2ꢀvinylphenyl)furan (1e). Colorless oil, R = 0.9 (petroleum ether), yield
f
1
(412 mg, 63%)
.
H NMR (400 MHz, CDCl
3
) δ 7.62 (dd, J = 8.7, 5.8 Hz, 1H), 7.54 (d,
J
= 0.9 Hz, 1H), 7.27 (dd,
J
= 10.2, 2.8 Hz, 1H), 7.10–7.01 (m, 2H), 6.54–6.46 (m,
13
2H), 5.72 (d, J = 17.4 Hz, 1H), 5.39 (d, J = 10.9 Hz, 1H). C NMR (100 MHz, CDCl )
3
δ 162.3(d,
JCꢀF = 247.2 Hz), 151.9, 142.2, 137.8(d, JCꢀF = 7.8 Hz), 135.4, 129.6(d, J
CꢀF
=
8.4 Hz), 125.7(d,
J
CꢀF = 3.1 Hz), 116.7, 114.8(d,
J
CꢀF = 21.9 Hz), 113.3(d,
J
CꢀF = 22.2
1
9
ꢀ1
Hz), 111.4, 109.6. F NMR (376 MHz, CDCl ) δ ꢀ114.18. IR (thin film) νmax (cm )
3
2
967, 2923, 2852, 1400, 1331, 1278, 1161, 1043, 1021, 964. HRMS (EI) mass calcd
+
for C12
H
9
FO ([M] ): 188.0637; found 188.0638.
2
ꢀ(2ꢀ(propꢀ1ꢀenꢀ2ꢀyl)phenyl)furan (1f).
Colorless oil, R
f
= 0.9 (petroleum ether), yield
= 7.5 Hz, 1H), 7.45 (s, 1H),
= 7.4 Hz, 1H), 7.26 – 7.16 (m, 2H), 6.66 (s, 1H), 6.42 (d, = 1.1 Hz, 1H),
.16 (s, 1H), 5.00 (s, 1H), 1.92 (s, 3H). C NMR (101 MHz, CDCl ) δ 152.9, 147.4,
1
(734 mg, 80%). H NMR (400 MHz, CDCl ) δ 7.67 (d,
J
3
7
5
1
.29 (t,
J
J
13
3
41.7, 141.6, 129.5, 128.3, 127.5, 127.2, 126.9, 115.1, 111.5, 108.5, 23.4. IR (thin film)
ꢀ1
νmax (cm ) 3060, 3020, 2924, 2860, 1724, 1487, 1441, 1013, 895, 729, 675. HRMS
+
(
EI) mass calcd for C H O ([M] ): 184.0888; Found 184.0894.
13
12
methyl 2ꢀ(2ꢀ(furanꢀ2ꢀyl)phenyl)acrylate (1g). Brown oil, R = 0.6 (petroleum
f
1
ether:EtOAc= 10:1), yield (620 mg, 75%). H NMR( 400 MHz, CDCl ) δ 7.68 (d,
J =
3
7.8 Hz, 1H), 7.41 (s, 1H), 7.38 (t, J = 7.4 Hz, 1H), 7.27 (m, 2H), 6.47 (s, 1H), 6.47 (s,
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2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
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4
4
4
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5
5
5
5
5
5
5
5
5
6
1
3
1H), 6.40 (s, 1H), 5.81 (s, 1H), 3.51 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 167.2,
1
53.2, 142.9, 142.1, 134.5, 130.9, 129.9, 128.5, 128.0, 127.6, 126.6, 111.5, 108.3,
ꢀ1
52.1. IR (thin film)
ν
max (cm ) 3122, 3066, 2926, 2846, 2188, 1638, 1599, 1506, 1290,
+
1
255, 1016, 832, 752, 542. HRMS (ESI) mass calcd for C14
51.0679; Found 251.0674.
H
12
O
3
Na ([M+Na] ):
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
E/Z) 2ꢀ(2ꢀ(propꢀ1ꢀenꢀ1ꢀyl)phenyl)furan (1h). Colorless oil, R
f
= 0.9 (petroleum ether),
1
yield (300 mg, 86%, E/Z = 2:3). H NMR( 400 MHz, CDCl
3
) δ 7.78( Z, d, = 7.6 Hz,
J
1
H), 7.64 – 7.59 (E, m, 1H), 7.49 (E, s, 1H), 7.46 (E, s , 1H), 7.44(Z, m, 1H ), 7.33 –
.19 (Z, m, 3H), 7.33 – 7.19 (E, m, 2H), 6.72( E, d, = 15.6 Hz, 1H), 6.63 (Z, d,
= 11.4 Hz, 1H), 6.48 (E, s, 2H), 6.45 – 6.43 (Z, m, 1H), 6.12
= 13.4, 6.6 Hz, 1H), 5.85(Z, dq, = 13.9, 7.0 Hz, 1H), 1.89 (E, d, = 6.6 Hz,
= 7.0 Hz, 3H). C NMR (101 MHz, CDCl ) δ 153.1, 152.8, 142.0,
41.8, 135.8, 134.0, 130.5, 130.4, 130.3, 129.6, 128.8, 127.7, 127.5, 127.2, 127.0,
26.9, 126.8, 126.8, 126.5, 111.4, 111.3, 109.8, 109.6, 18.7, 14.3. IR (thin film)
7
J
J =
3.1 Hz, 1H), 6.56 (Z, d,
E, dq,
3H), 1.77 (Z, d,
J
(
J
J
J
1
3
J
3
1
1
ν
max
ꢀ1
(
cm ) 3200, 3060, 3020, 2923, 2860, 1487, 1441, 1277, 1014, 968, 756, 730, 594.
+
HRMS (EI) mass calcd for C13
H
12O ([M] ): 184.0888; Found 184.0887.
Dimethyl 1ꢀ(2ꢀvinylphenyl)ꢀ7ꢀoxabicyclo[2.2.1]heptaꢀ2,5ꢀdieneꢀ2,3ꢀdicarboxylate (I).
1
Yellow oil, R
f
= 0.45 (petroleum ether:EtOAc = 5:1), yield (7 mg, 6%). H NMR (400
MHz, CDCl ) δ 7.54 (d,
J
= 5.3 Hz, 1H), 7.51 (d,
= 17.2, 10.9 Hz, 1H), 5.76 (d, = 1.9 Hz, 1H), 5.57 (dd,
H), 5.21 (dd, = 10.9, 1.2 Hz, 1H), 3.74 (s, 3H), 3.53 (s, 3H). C NMR (100 MHz,
J
= 7.6 Hz, 2H), 7.32–7.22 (m, 3H),
3
7
.05 (dd,
J
J
J
= 17.2, 1.2 Hz,
13
1
J
CDCl ) δ 164.6, 162.7, 158.4, 149.5, 144.6, 137.5, 135.3, 130.6, 129.4, 128.1, 127.7,
3
ꢀ1
1
1
3
27.0, 116.4, 98.1, 83.8, 52.4, 52.2. IR (thin film)
ν
max (cm ) 2951, 2925, 2851, 1721,
+
637, 1435, 1269, 1168, 763. HRMS (ESI) mass calcd for C18
35.0890; found 335.0895.
H
16
O
5
Na ([M+Na] ):
Dimethyl 2,10aꢀdihydroꢀ1Hꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate (3aa).
Yellow solid (m.p. 93ꢀ96 ºC), R
f
= 0.3 (petroleum ether:EtOAc = 5:1), yield (21 mg,
) δ 7.48 (d, = 7.2 Hz, 1H), 7.33–7.22 (m, 2H),
= 5.7 Hz, 1H), 6.71 (dd, = 5.6, 1.2 Hz, 1H), 6.48
= 9.6 Hz, 1H), 4.95 (dd, = 4.1, 1.3 Hz, 1H), 3.65 (s,
= 4.2 Hz, 1H). C NMR (100 MHz, CDCl ) δ 171.2,
70.3, 137.4, 137.3, 132.5, 130.1, 129.9, 128.9, 128.6, 128.5, 127.8, 127.0, 89.5, 77.9,
1
4
5%). H NMR (400 MHz, CDCl
3
J
7.14 (d,
d, = 9.6 Hz, 1H), 6.04 (d,
3H), 3.41 (s, 3H), 3.38 (d,
J
= 7.1 Hz, 1H), 6.77 (d,
J
J
(
J
J
J
13
J
3
1
5
1
ꢀ
1
9.9, 56.3, 52.2, 52.0. IR (thin film)
ν
max (cm ) 3001, 2952, 2845, 1739, 1644, 1435,
+
245, 1169, 1097. HRMS (MALDI) mass calcd for C18
H
16
O
5
Na ([M+Na] ): 335.0890;
found 335.0897.
Dimethyl 2ꢀ((Z)ꢀ2ꢀ(furanꢀ2ꢀyl)styryl)maleate (4aa). Yellow solid (m.p. 109 ºC), R =
f
1
0.5 (petroleum ether:EtOAc = 5:1), yield (19 mg, 41%). H NMR (400 MHz, CDCl ) δ
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7.79 (d,
J
= 7.8 Hz, 1H), 7.53 (s, 1H), 7.41 – 7.36 (m, 1H), 7.28 – 7.22 (m, 2H), 6.99
(d,
J
= 11.8 Hz, 1H), 6.67 (d,
J
= 3.2 Hz, 1H), 6.51 (dd,
J
1
= 3.0, 1.7 Hz, 1H), 6.32 (d,
3
J
= 11.8 Hz, 1H), 6.02 (s, 1H), 3.72 (s, 3H), 3.26 (s, 3H). C NMR (100 MHz, CDCl
3
)
δ 167.0, 165.2, 152.1, 145.0, 142.4, 139.0, 131.9, 130.9, 129.5, 128.5, 126.6, 126.0,
ꢀ1
1
1
25.9, 122.8, 111.7, 110.5, 51.9, 51.9. IR (thin film) νmax (cm ) 2953, 2921, 2850,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
734, 1649, 1437, 1265, 1204, 736. HRMS (MALDI) mass calcd for C18
H
16
O
5
Na
+
([M+Na] ): 335.0890; found 335.0902.
Dimethylꢀ2,3ꢀdihydroxyꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10aꢀ(1H)ꢀdicarboxylate
(5aa). Yellow solid (m.p. 115 ºC), R
f
= 0.2 (petroleum ether:EtOAc = 2:1), yield (24
) δ 7.54 (d, = 5.3 Hz, 1H), 7.51 (d, = 7.6 Hz,
= 17.2, 10.9 Hz, 1H), 5.76 (d, = 1.9 Hz, 1H),
= 17.2, 1.2 Hz, 1H), 5.21 (dd, = 10.9, 1.2 Hz, 1H), 3.74 (s, 3H), 3.53 (s,
H). C NMR (100 MHz, CDCl ) δ 172.4, 171.3, 138.5, 132.6, 131.8, 129.1, 128.5,
28.4, 127.6, 126.5, 125.1, 66.8, 65.2, 52.9, 52.4, 52.1, 49.1. IR (thin film)
1
mg, 22%). H NMR (400 MHz, CDCl
3
J
J
2H), 7.32–7.22 (m, 2H), 7.05 (dd,
J
J
5
3
1
2
.57 (dd,
J
J
13
3
ꢀ1
ν
max (cm )
953, 2922, 2852, 1734, 1436, 1264, 1229, 1086, 737. HRMS (MALDI) mass calcd
+
for C18
H
18
O
6
Na ([M+Na] ): 353.0996; found 353.1002.
Dimethylꢀ2,3ꢀdihydroxyꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10aꢀ(1H)ꢀdicarboxylate
(6aa). White solid (m.p. 225 ºC), R
f
= 0.3 (petroleum ether:EtOAc = 2:1), yield (26
1
mg, 24%). H NMR (400 MHz, DMSO) δ 7.43–7.36 (m, 1H), 7.28–7.20 (m, 2H),
7
.16–7.07 (m, 1H), 6.56 (d,
2H), 4.11 (s, 2H), 3.67 (s, 3H), 3.48 (s, 3H), 2.87 (q,
MHz, DMSO) δ 171.4, 170.7, 132.6, 132.3, 132.0, 131.3, 129.0, 128.4, 128.3, 126.8,
J
= 9.6 Hz, 1H), 6.01–5.93 (m, 2H), 5.38 (d,
J
= 4.7 Hz,
13
J
= 4.3 Hz, 1H). C NMR (100
ꢀ1
1
26.4, 124.5, 71.3, 70.4, 54.8, 52.4, 51.8, 50.8. IR (thin film) νmax (cm ) 2952, 2844,
1
730, 1650, 1433, 1265, 1169, 1121, 740. HRMS (MALDI) mass calcd for
+
C H O Na ([M+Na] ): 353.0996; found 353.1002.
18
18
6
23
Methyl phenanthreneꢀ1ꢀcarboxylate (7aa). Yellow solid (m.p. 95 ºC), R = 0.8
f
1
(petroleum ether: EtOAc = 5:1), yield (10 mg, 14%),. H NMR (400 MHz, CDCl ) δ
3
8
.84 (d,
J
= 8.4 Hz, 1H), 8.70 (d,
J
= 9.4 Hz, 1H), 8.62 (d,
J
= 8.2 Hz, 1H), 8.14 (dd,
J
= 7.4, 1.0 Hz, 1H), 7.87–7.83 (m, 1H), 7.80 (d,
J = 9.4 Hz, 1H), 7.63–7.54 (m, 3H),
13
3
1
.96 (s, 3H). C NMR (100 MHz, CDCl
3
) δ 168.5, 131.6, 130.9, 130.6, 130.0, 129.8,
28.8, 128.5, 128.2, 127.1, 127.1, 126.9, 125.3, 123.7, 122.8, 52.3.
(Z)ꢀDimethylꢀ2ꢀ(2ꢀ(furanꢀ2ꢀyl)styryl)ꢀ4,5ꢀdihydroxyꢀ2'ꢀvinylꢀ2,3,4,5ꢀtetrahydroꢀ[1,1'ꢀ
biphenyl]ꢀ2,3ꢀdicarboxylate (8aa). Brown oil, R
f
= 0.4 (petroleum ether:EtOAc = 3:1),
) δ 7.49–7.46 (m, 1H), 7.42–7.39 (m,
= 7.1, 5.6 Hz, 2H), 7.13 (dd, = 14.6, 6.7
= 13.9, 7.3 Hz, 1H), 6.49 (d, = 9.6 Hz, 1H), 6.37
= 7.9, 6.7 Hz, 2H), 6.07 (d, = 5.3 Hz, 1H), 5.53 (d,
1
yield (34 mg, 45%). H NMR (400 MHz, CDCl
3
1H), 7.36 (d,
Hz, 2H), 7.00 (s, 1H), 6.96 (dd,
(d, = 3.2 Hz, 1H), 6.20 (dd,
J
= 7.0 Hz, 1H), 7.20 (dd,
J
J
J
J
J
J
J
J
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2
2
2
2
2
2
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
= 17.4 Hz, 1H), 5.15 (d,
J
= 11.0 Hz, 1H), 4.75 (dd,
J
= 11.4, 6.4 Hz, 1H), 4.12 (t,
J
=
13
5
.8 Hz, 1H), 3.69 (s, 3H), 3.51 (s, 3H), 3.20 (d,
J
= 11.4 Hz, 1H), 2.39 (s, 1H). C
3
NMR (100 MHz, CDCl ) δ 172.4, 172.0, 153.3, 151.5, 136.5, 135.6, 135.5, 133.4,
1
1
2
31.7, 129.0, 128.9, 128.6, 128.3, 127.7, 127.7, 127.7, 127.3, 127.2, 126.5, 126.1,
ꢀ
1
24.9, 115.8, 111.8, 110.6, 66.4, 52.9, 52.3, 52.0, 50.9, 41.0. IR (thin film) νmax (cm )
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
952, 2850, 1734, 1436, 1256, 1229, 1204, 763, 737. HRMS (MALDI) mass calcd for
+
C
30
H
26
O
6
Na ([M+NaꢀH
2
O] ): 505.1622; found 505.1627.
Dimethyl 4ꢀhydroxyꢀ2'ꢀvinylꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (9aa). Yellow oil, R
f
1
=0.6 (petroleum ether:EtOAc = 5:1), yield (14 mg, 30%) . H NMR (400 MHz, CDCl
3
)
δ 10.93 (s, 1H), 7.54 (d,
8.6 Hz, 1H), 7.16 (dd,
.6 Hz, 1H), 6.38 (dd,
dd, = 11.0, 1.0 Hz, 1H), 3.84 (s, 3H), 3.42 (s, 3H). C NMR (100 MHz, CDCl
69.4, 168.4, 160.9, 137.6, 137.1, 136.7, 135.1, 135.0, 130.3, 128.2, 127.0, 125.0,
J
= 7.8 Hz, 1H), 7.26 (dd,
= 7.4, 1.1 Hz, 1H), 7.07 (dd,
= 17.5, 11.0 Hz, 1H), 5.57 (dd,
J
= 11.1, 4.1 Hz, 1H), 7.22 (d,
J
=
J
J = 7.6, 1.0 Hz, 1H), 7.01 (d,
J
=
8
J
J
= 17.5, 1.0 Hz, 1H), 5.07
) δ
13
(
J
3
1
ꢀ1
118.6, 114.9, 109.0, 53.0, 51.9. IR (thin film) νmax (cm ) 2952, 2919, 2850, 1738,
1
678, 1462, 1442, 1246, 1215. HRMS (MALDI) mass calcd for C18
H
16
O
5
Na
+
([M+Na] ): 335.0890; found 335.0894.
Diethyl
2,10aꢀdihydroꢀ1Hꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate
(3ab).
= 0.3 (petroleum ether:EtOAc = 5:1), yield (14 mg, 45%). H NMR
) δ 7.58 (d, = 7.2 Hz, 1H), 7.36 (dt, = 19.6, 7.3 Hz, 2H), 7.23 (d,
= 7.1 Hz, 1H), 6.88 (d, = 5.6 Hz, 1H), 6.79 (d, = 5.6 Hz, 1H), 6.57 (d, = 9.6 Hz,
H), 6.15 (d, = 9.6 Hz, 1H), 5.04 (d, = 3.4 Hz, 1H), 4.26–4.12 (m, 2H), 4.05 – 3.87
= 4.0 Hz, 1H), 1.33 (t, = 7.1 Hz, 3H), 1.07 (t, = 7.1 Hz, 3H).
1
Yellow oil, R
f
(400 MHz, CDCl
3
J
J
J
1
J
J
J
J
J
(
m, 2H), 3.46 (d,
J
J
J
1
3
C NMR (100 MHz, CDCl ) δ 170.7, 169.8, 137.3, 137.2, 132.6, 130.3, 129.8, 129.4,
3
1
28.5, 128.4, 127.7, 126.7, 89.5, 78.1, 61.0, 60.9, 60.0, 56.5, 14.2, 13.7. IR (thin film)
ꢀ1
νmax (cm ) 2982, 2820, 2851, 1730, 1649, 1257, 1197, 1091, 741. HRMS (MALDI)
+
mass calcd for C H O Na ([M+Na] ): 363.1203; found 363.1212.
20
20
5
Diethyl 2ꢀ((Z)ꢀ2ꢀ(furanꢀ2ꢀyl)styryl)maleate (4ab). Yellow solid (m.p. 90 ºC), R = 0.5
f
1
(petroleum ether:EtOAc = 5:1), yield (12 mg, 41%). H NMR (400 MHz, CDCl ) δ
3
7
1
J
.54 (d,
7.2, 10.9 Hz, 1H), 5.76 (d,
= 10.9, 1.2 Hz, 1H), 3.74 (s, 3H), 3.53 (s, 3H). C NMR (100 MHz, CDCl
64.8, 152.1, 144.8, 142.3, 138.6, 132.0, 131.1, 129.5, 128.5, 126.6, 126.2, 125.7,
J
= 5.3 Hz, 1H), 7.51 (d,
J
= 7.6 Hz, 2H), 7.32–7.22 (m, 3H), 7.05 (dd,
= 17.2, 1.2 Hz, 1H), 5.21 (dd,
) δ 166.6,
J =
J
= 1.9 Hz, 1H), 5.57 (dd,
J
13
3
1
1
1
ꢀ1
23.4, 111.7, 110.6, 61.3, 60.8, 14.1, 13.4. IR (thin film) νmax (cm ) 2982, 2934, 1787,
730, 1650, 1465, 1394, 1261, 1191. HRMS (MALDI) mass calcd for C20
H
21
O
5
+
([M+H] ): 341.1384; found 341.1377.
Dimethyl 6ꢀmethylꢀ2,10aꢀdihydroꢀ1Hꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate
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(3ba). Yellow solid (m.p. 105 ºC), R
f
= 0.3 (petroleum ether:EtOAc = 5:1), yield (28
mg, 52%). H NMR (400 MHz, CDCl ) δ 7.29 (s, 1H), 7.10 (d, = 7.7 Hz, 1H), 7.03
(d, = 7.7 Hz, 1H), 6.77 (d, = 5.7 Hz, 1H), 6.70 (dd, = 5.7, 1.7 Hz, 1H), 6.45 (d,
9.6 Hz, 1H), 5.97 (d, = 9.6 Hz, 1H), 4.94 (dd, = 4.3, 1.7 Hz, 1H), 3.65 (s, 3H),
.41 (s, 3H), 3.37 (d, = 4.3 Hz, 1H), 2.30 (s, 3H). C NMR (100 MHz, CDCl
71.3, 170.5, 138.5, 137.4, 137.3, 130.4, 129.9, 129.8, 129.4, 127.8, 127.7, 126.8,
1
3
J
J
J
J
J
=
J
J
1
3
3
1
8
1
J
3
) δ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ1
9.6, 77.9, 59.9, 56.4, 52.2, 52.0, 21.4. IR (thin film) νmax (cm ) 2952, 2921, 2851,
738, 1436, 1355, 1245, 1169, 735. HRMS (MALDI) mass calcd for C19
H
18
5
O Na
+
([M+Na] ): 349.1047; found 349.1051.
Dimethyl 2ꢀ((Z)ꢀ2ꢀ(furanꢀ2ꢀyl)ꢀ4ꢀmethylstyryl)maleate (4ba). Yellow solid (m.p. 85
1
ºC), R
CDCl
.6 Hz, 1H), 6.85 (d,
Hz, 1H), 6.21–6.16 (m, 1H), 5.92 (s, 1H), 3.62 (s, 3H), 3.19 (s, 3H), 2.31 (s, 3H). C
NMR (100 MHz, CDCl ) δ 167.1, 165.3, 152.2, 145.2, 142.2, 139.0, 138.4, 130.9,
29.3, 129.3, 127.4, 126.5, 125.6, 122.5, 111.7, 110.4, 51.9, 21.3. IR (thin film)
f
= 0.5 (petroleum ether:EtOAc = 5:1), yield (9 mg, 35%). H NMR (400 MHz,
3
) δ 7.51 (s, 1H), 7.42 (d,
J
= 1.2 Hz, 1H), 7.07 (d,
J
= 7.8 Hz, 1H), 6.96 (d,
J =
7
J
= 11.7 Hz, 1H), 6.55 (d,
J
= 3.3 Hz, 1H), 6.40 (dd, J
= 3.3, 1.8
13
3
1
ν
max
ꢀ1
(cm ) 2953, 2921, 2850, 1735, 1647, 1436, 1264, 1202, 1169, 736. HRMS (MALDI)
+
mass calcd for C19
H
19
O
5
([M+H] ): 327.1227; found 327.1237.
Dimethyl
2,3ꢀdihydroxyꢀ6ꢀmethylꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10aꢀ(1H)ꢀ
dicarboxylate (5ba). Yellow solid (m.p. 165 ºC), R
f
= 0.2 (petroleum ether:EtOAc =
) δ 7.09 (d, = 7.7 Hz, 1H),
= 9.6 Hz, 1H), 6.28 (d, = 4.8 Hz, 1H), 6.18 (d,
9.6 Hz, 1H), 4.56–4.42 (m, 2H), 3.84 (s, 3H), 3.59 (s, 3H), 3.16 (dt, = 5.3, 2.1 Hz,
1
2:1), yield (25 mg, 46%). H NMR (400 MHz, CDCl
3
J
6
.96 (d,
J
= 7.6 Hz, 1H), 6.51 (d,
J
J
J
=
J
13
1
1
H), 2.35 (s, 3H). C NMR (100 MHz, CDCl ) δ 172.4, 171.4, 138.8, 138.2, 132.5,
3
29.8, 129.3, 127.4, 127.4, 126.4, 126.1, 125.8, 66.9, 65.2, 52.8, 52.3, 52.1, 49.2, 21.4.
ꢀ
1
IR (thin film) νmax (cm ) 2953, 2918, 2850, 1733, 1639, 1436, 1232, 1086, 736.
+
HRMS (MALDI) mass calcd for C H O Na ([M+Na] ): 367.1152; found 367.1153.
1
9
20
6
Dimethyl
2,3ꢀdihydroxyꢀ6ꢀmethylꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10aꢀ(1H)ꢀ
dicarboxylate (6ba). White solid (m.p. 175 ºC), R = 0.3 (petroleum ether:EtOAc =
f
1
2
:1), yield (16 mg, 28%). H NMR (400 MHz, CDCl
3
) δ 7.32 (s, 1H), 7.07 (d,
= 9.6 Hz, 1H), 6.25 (d, = 9.5 Hz, 1H),
= 7.5 Hz, 2H), 3.85 (s, 3H), 3.59 (s, 3H), 3.06 (d, = 11.0 Hz,
) δ 172.1,
71.6, 138.3, 135.5, 132.4, 129.5, 129.1, 128.8, 127.7, 127.4, 126.4, 125.8, 72.1, 71.8,
J = 7.0
Hz, 1H), 6.96 (d,
J
= 7.6 Hz, 1H), 6.51 (d,
.09 (s, 1H), 4.40 (d,
H), 2.97 (s, 1H), 2.58 (s, 1H), 2.35 (s, 3H). C NMR (100 MHz, CDCl
J
J
6
1
1
5
J
J
13
3
ꢀ1
3.9, 53.0, 52.4, 51.7, 21.4. IR (thin film)
ν
max (cm ) 2953, 2920, 2851, 1734, 1650,
+
1436, 1262, 1069, 736. HRMS (MALDI) mass calcd for C19
67.1152; found 367.1149.
H
20
O
6
Na ([M+Na] ):
3
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2
2
2
2
2
2
2
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3
3
3
3
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3
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5
5
5
5
5
5
6
Methyl 6ꢀmethylphenanthreneꢀ1ꢀcarboxylate (7ba). White solid (m.p. 90 ºC), R
f
= 0.8
) δ
= 7.4, 1.1
= 8.2, 7.6 Hz, 1H), 7.43–7.36 (m,
H), 3.95 (s, 3H), 2.56 (s, 3H). C NMR (100 MHz, CDCl ) δ 168.5, 136.7, 130.7,
30.7, 130.1, 129.7, 129.6, 128.8, 128.6, 128.4, 128.2, 127.1, 125.0, 122.7, 122.5,
1
(petroleum ether:EtOAc = 5:1), yield (7 mg, 31%). H NMR (400 MHz, CDCl
3
8.83 (d,
J
= 8.4 Hz, 1H), 8.61 (d,
J = 9.3 Hz, 1H), 8.41 (s, 1H), 8.11 (dd, J
Hz, 1H), 7.75 (dd,
J
= 8.6, 6.4 Hz, 2H), 7.57 (dd,
J
13
1
1
5
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ꢀ1
2.3, 22.2. IR (thin film)
ν
max (cm ) 2949, 2917, 2849, 1712, 1631, 1254, 1121, 749.
+
HRMS (EI) mass calcd for C17
H
14
O
2
(M ): 250.0994; found 250.0995.
(Z)ꢀDimethyl
2ꢀ(2ꢀ(furanꢀ2ꢀyl)ꢀ5ꢀmethylstyryl)ꢀ4,5ꢀdihydroxyꢀ5'ꢀmethylꢀ2'ꢀvinylꢀ
2
,3,4,5ꢀtetrahydroꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (8ba). Yellow oil, R
f
= 0.4
) δ
= 9.5
= 9.5 Hz, 1H),
= 11.0 Hz, 1H), 4.89–
= 5.8 Hz, 1H), 3.80 (s, 3H), 3.62 (s, 3H), 3.29 (d, = 11.4 Hz,
= 6.6 Hz, 1H), 2.37 (s, 3H), 2.35 (s, 3H). C NMR (101 MHz, CDCl
1
(petroleum ether:EtOAc = 3:1), yield (54 mg, 16%). H NMR (400 MHz, CDCl
3
7
.42 (d,
J
= 8.9 Hz, 2H), 7.29 (d,
= 2.9 Hz, 1H), 6.28 (d,
= 5.3 Hz, 1H), 5.60 (d, = 17.4 Hz, 1H), 5.21 (d,
.77 (m, 1H), 4.22 (t,
H), 2.40 (d,
J
= 6.0 Hz, 2H), 7.19–6.88 (m, 4H), 6.57 (d,
J
Hz, 1H), 6.46 (d,
J
J
= 3.0 Hz, 1H), 6.25 (d,
J
6
4
1
.18 (d,
J
J
J
J
J
13
J
3
)
δ 172.4, 172.1, 153.4, 151.3, 138.1, 137.4, 136.2, 135.8, 133.3, 132.8, 129.3, 129.1,
128.7, 128.6, 128.0, 127.8, 127.5, 127.1, 126.4, 125.8, 125.6, 115.0, 111.8, 110.4, 66.5,
ꢀ1
5
2.8, 52.3, 52.0, 50.9, 41.0, 21.4, 21.1. IR (thin film)
ν
max (cm ) 2952, 2921, 2851,
1732, 1633, 1455, 1321, 908, 735. HRMS (MALDI) mass calcd for C32
H
30
6
O Na
+
([M+NaꢀH
2
O] ): 533.1935; found 533.1944.
Dimethyl
4ꢀhydroxyꢀ5'ꢀmethylꢀ2'ꢀvinylꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate
(9ba).
1
Yellow oil, R = 0.6 (petroleum ether:EtOAc = 5:1), yield (30 mg, 34%). H NMR
f
(
400 MHz, CDCl ) δ 10.91 (s, 1H), 7.44 (d,
J
= 8.0 Hz, 1H), 7.20 (d,
= 8.6 Hz, 1H), 6.89 (s, 1H), 6.34 (dd,
= 17.5 Hz, 1H), 5.00 (d, = 11.0 Hz, 1H), 3.84 (s, 3H), 3.43
s, 3H), 2.26 (s, 3H). C NMR (100 MHz, CDCl ) δ 169.4, 168.4, 160.9, 137.6, 137.0,
J
= 3.9 Hz, 1H),
3
7
.07 (d,
J
= 7.9 Hz, 1H), 7.00 (d,
J
J
= 17.5,
11.0 Hz, 1H), 5.52 (d,
J
J
13
(
3
136.8, 135.0, 134.8, 133.9, 130.9, 130.5, 129.0, 124.8, 118.6, 113.9, 109.0, 52.9, 51.9,
ꢀ1
2
1.0. IR (thin film) νmax (cm ) 2952, 2918, 2849, 1739, 1677, 1442, 1333, 1245, 1214.
+
HRMS (MALDI) mass calcd for C19
H
18
O
5
Na ([M+Na] ): 349.1052; found 349.1056.
Dimethyl 7ꢀmethoxyꢀ1,2ꢀdihydroꢀ10aHꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate
(
3ca). Yellow solid (m.p. 147 ºC), R
f
= 0.3 (petroleum ether:EtOAc = 5:1), yield (36
) δ 7.40 (d, = 8.4 Hz, 1H), 6.79–6.75 (m, 1H),
= 4.0, 2.0 Hz, 2H), 6.43 (d, = 9.7 Hz, 1H), 6.05
J = 4.3, 1.7 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.42 (s,
1
mg, 52%). H NMR (400 MHz, CDCl
3
J
6
.74 (d,
d, = 9.6 Hz, 1H), 4.93 (dd,
3H), 3.37 (d, = 4.3 Hz, 1H). C NMR (100 MHz, CDCl
37.5, 137.3, 133.9, 129.9, 129.7, 127.0, 122.4, 113.6, 113.3, 89.4, 77.8, 59.9, 56.3,
J
= 5.7 Hz, 1H), 6.69 (dd,
J
J
(
J
13
J
3
) δ 171.2, 170.3, 160.7,
1
ꢀ1
55.4, 52.2, 52.0. IR (thin film) νmax (cm ) 2953, 2918, 2847, 173, 1640, 1603, 1434,
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+
1267, 735. HRMS (MALDI) mass calcd for C19
65.1002.
18 6
H O Na ([M+Na] ): 365.1001; found
3
Dimethyl 2ꢀ((Z)ꢀ2ꢀ(furanꢀ2ꢀyl)ꢀ5ꢀmethoxystyryl)maleate (4ca). Yellow oil, R
f
= 0.5
) δ
1
(
petroleum ether:EtOAc = 5:1), yield (25 mg, 36%). H NMR (400 MHz, CDCl
3
7
.59 (d,
J
= 8.6 Hz, 1H), 7.39 (s, 1H), 6.86 (t,
= 11.8 Hz, 1H), 5.93 (s, 1H), 3.77 (s, 3H), 3.63 (s, 3H),
.21 (s, 3H). C NMR (101 MHz, CDCl ) δ 167.0, 165.2, 158.0, 152.1, 145.0, 141.8,
38.8, 133.2, 127.5, 126.1, 123.0, 122.5, 115.4, 115.1, 111.6, 108.9, 55.4, 51.9, 51.8.
J = 11.1 Hz, 2H), 6.72 (s, 1H), 6.42 (s,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
H), 6.38 (s, 1H), 6.22 (d,
J
13
3
3
1
ꢀ
1
IR (thin film)
ν
max (cm ) 2953, 2923, 1850, 1735, 1652, 1435, 1268, 1244, 735.
+
HRMS (MALDI) mass calcd for C19
H
18
O
6
Na ([M+Na] ): 365.1001; found 365.1004.
Dimethyl 4ꢀhydroxyꢀ4'ꢀmethoxyꢀ2'ꢀvinylꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (9ca)
.
1
Yellow oil, R
400 MHz, CDCl
.10 (d, = 2.4 Hz, 1H), 7.08 (d,
dd, = 17.5, 11.0 Hz, 1H), 5.65 (d,
s, 3H), 3.88 (s, 3H), 3.54 (s, 3H). C NMR (100 MHz, CDCl
f
= 0.6 (petroleum ether:EtOAc = 5:1), yield (86 mg, 100%). H NMR
) δ 11.02 (s, 1H), 7.28 (d, = 3.2 Hz, 1H), 7.15 (d, = 2.4 Hz, 1H),
= 2.6 Hz, 1H), 6.83 (dd, = 8.4, 2.5 Hz, 1H), 6.44
= 17.5 Hz, 1H), 5.17 (d, = 11.0 Hz, 1H), 3.93
) δ 169.4, 168.5, 160.9,
(
3
J
J
7
J
J
J
(
(
J
J
J
13
3
159.4, 138.1, 138.0, 135.4, 135.1, 131.5, 130.0, 129.8, 118.5, 115.0, 112.9, 109.9,
ꢀ1
1
08.9, 55.3, 52.9, 52.0. IR (thin film)
ν
max (cm ) 2953, 2840, 1739, 1677, 1600, 1462,
+
1218, 724. HRMS (MALDI) mass calcd for C19
65.1005.
H
18
O
6
Na ([M+Na] ): 365.1001; found
3
Dimethyl
7ꢀ(trifluoromethyl)ꢀ1,2ꢀdihydroꢀ10aHꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀ
dicarboxylate (3da). Yellow solid (m.p. 75 ºC), R = 0.3 (petroleum ether:EtOAc =
f
1
5
7
6
3
:1), yield (19 mg, 33%). H NMR (400 MHz, CDCl ) δ 7.60 (d,
J
= 7.9 Hz, 1H),
3
.51 (d,
.15 (d,
.38 (d,
J
J
J
= 8.0 Hz, 1H), 7.39 (s, 1H), 6.78–6.71 (m, 2H), 6.51 (d,
J = 9.7 Hz, 1H),
= 9.7 Hz, 1H), 4.97 (dd,
J
= 4.3, 0.9 Hz, 1H), 3.66 (s, 3H), 3.42 (s, 3H),
1
3
= 4.3 Hz, 1H). C NMR (100 MHz, CDCl ) δ 171.0, 170.0, 136.6, 133.8,
3
133.7, 133.4, 130.7, 129.2, 125.9, 125. 1 (dd,
J
CꢀF = 7.3, 3.4 Hz), 124.4
(q, JCꢀF = 3.7
1
9
Hz), 88.7, 78.1, 60.0, 56.0, 52.3, 52.1. F NMR (376 MHz, CDCl ) δ ꢀ62.98. IR (thin
3
ꢀ1
film)
ν
max (cm ) 2956, 2918, 2848, 1740, 1643, 1434, 1247, 1168, 1126. HRMS
+
(MALDI) mass calcd for C19
H
15
O
5
F
3
Na ([M+Na] ): 403.0769; found 403.0775.
Dimethyl 2ꢀ((Z)ꢀ2ꢀ(furanꢀ2ꢀyl)ꢀ5ꢀ(trifluoromethyl)styryl)maleate (4da). Yellow solid
1
(m.p. 85 ºC), R
f
= 0.5 (petroleum ether:EtOAc = 5:1), yield (17 mg, 30%). H NMR
(
400 MHz, CDCl
3
) δ 7.82 (d,
.3 Hz, 1H), 7.41 (s, 1H), 6.85 (d,
= 3.4, 1.8 Hz, 1H), 6.34–6.29 (m, 1H), 5.97 (s, 1H), 3.63 (s, 3H), 3.15 (s, 3H). C
) δ 166.8, 165.0, 150.7, 144.4, 143.3, 137.4, 132.6 d,
.2 Hz), 132.0, 128.3, 127.9 d, JCꢀF = 3.9 Hz), 127.4, 126.0, 125.2 q, JCꢀF = 3,.8 Hz),
J
= 8.2 Hz, 1H), 7.54 (d,
J
= 8.3 Hz, 1H), 7.47 (d,
J =
1
J
= 11.8 Hz, 1H), 6.72 (d,
J
= 3.4 Hz, 1H), 6.44 (dd,
13
J
NMR (100 MHz, CDCl
3
(
CꢀF
J =
1
(
(
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2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
9
123.8, 112.4, 112.1, 52.0, 51.9. F NMR (376 MHz, CDCl
3
) δ ꢀ62.58. IR (thin film)
ꢀ1
ν
max (cm ) 2956, 2850, 1736, 1650, 1436, 1330, 1169, 1127, 737. HRMS (MALDI)
+
15 5 3
mass calcd for C19H O F Na ([M+Na] ): 403.0769; found 403.0771.
Dimethyl 2,3ꢀdihydroxyꢀ7ꢀ(trifluoromethyl)ꢀ1,2,3,10aꢀtetrahydroꢀphenanthreneꢀ1,10aꢀ
(
1H)ꢀdicarboxylate (5da). Yellow solid (m.p. 148 ºC), R
f
= 0.2 (petroleum
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
ether:EtOAc = 5:1), yield (17 mg, 29%). H NMR (400 MHz, CDCl
3
) δ 7.46 (d,
J
=
8
.1 Hz, 1H), 7.39 (d,
J
= 8.0 Hz, 1H), 7.23 (s, 1H), 6.48 (d,
J
= 9.6 Hz, 1H), 6.30 (d,
J
=
9.7 Hz, 1H), 6.27 (d, J = 5.0 Hz, 1H), 4.50 – 4.33 (m, 2H), 3.77 (s, 3H), 3.50 (s, 3H),
1
3
3.11 (d,
J = 10.9 Hz, 1H), 3.04 (d, J = 5.4 Hz, 1H), 2.47 (s, 1H). C NMR (101 MHz,
CDCl
dd,
3
) δ 172.3, 170.8, 137.2, 136.0, 132.3, 130.9, 130.3, 128.6, 126.6, 125.5, 125.0
(
J
CꢀF = 7.9, 4.7 Hz), 123.2
(
d,
J
CꢀF = 5.0 Hz), 123.1, 122.5, 66.8, 65.0, 53.0, 52.5,
19
ꢀ1
5
2.0, 48.7. F NMR (376 MHz, CDCl ) δ ꢀ62.87. IR (thin film) νmax (cm ) 2956,
3
2917, 2850, 1725, 1643, 1433, 1330, 1116, 736. HRMS (MALDI) mass calcd for
+
C H O F Na ([M+Na] ): 421.0875; found 421.0859.
19
17
6 3
Dimethyl 2,3ꢀdihydroxyꢀ7ꢀ(trifluoromethyl)ꢀ1,2,3,10aꢀtetrahydroꢀphenanthreneꢀ1,10aꢀ
(
1H)ꢀdicarboxylate (6da). Yellow solid (m.p. 175 ºC), R
f
= 0.3 (petroleum
) δ 7.50 (d, = 8.0
= 9.6 Hz, 1H), 6.34 (d,
= 1.5 Hz, 1H), 4.35–4.28 (m, 2H), 3.77 (s, 3H), 3.50 (s, 3H),
1
ether:EtOAc = 2:1), yield (5 mg, 8%). H NMR (400 MHz, CDCl
3
J
Hz, 1H), 7.40 (d,
9.6 Hz, 1H), 6.08 (d,
.97 (d, = 10.9 Hz, 1H). C NMR (100 MHz, CDCl
131.0, 129.8, 129.2, 126.0, 124.3, 124.1
J
= 7.8 Hz, 1H), 7.23 (s, 1H), 6.48 (d,
J
J =
J
13
2
J
3
) δ 170.4, 170.1, 134.9, 133.1,
(
d, JCꢀF = 3.7 Hz), 122.2
(
dd, JCꢀF = 7.3, 3.5
) δ
19
Hz), 70.8, 70.7, 52.3, 52.1, 51.6, 50.6, 21.7, 13.1. F NMR (376 MHz, CDCl
3
ꢀ1
ꢀ62.84. IR (thin film)
ν
max (cm ) 3445, 2958, 2919, 2850, 1733, 1646, 1329, 1262,
+
1
121, 1082. HRMS (MALDI) mass calcd for C19
H
17
O
6
F
3
([M+Na] ): 421.0875;
found 421.0871.
Methyl 7ꢀ(trifluoromethyl)phenanthreneꢀ1ꢀcarboxylate (7da). White solid (m.p. 133
1
ºC), R = 0.8 (petroleum ether:EtOAc = 5:1), yield (8 mg, 17%). H NMR (400 MHz,
f
CDCl ) δ 8.82 (t,
J
= 9.1 Hz, 2H), 8.70 (d,
J
= 8.7 Hz, 1H), 8.24–8.17 (m, 1H), 8.12 (s,
3
1H), 7.83 (d,
J
13
= 9.4 Hz, 1H), 7.78 (dd,
J
= 8.7, 1.5 Hz, 1H), 7.65 (t, = 7.9 Hz, 1H),
J
3
.97 (s, 3H). C NMR (100 MHz, CDCl ) δ 168.1, 132.0, 131.3, 130.9, 130.8, 130.2,
3
128.5, 128.4, 127.4, 125.9, 125.8
(
d,
J
CꢀF = 4.2 Hz), 125.3, 123.8, 122.7 (dd, JCꢀF = 6.7,
19
ꢀ1
3
.3 Hz), 52.4. F NMR (376 MHz, CDCl
3
) δ ꢀ62.14. IR (thin film)
ν
max (cm ) 2955,
2923, 2850, 1715, 1644, 1267, 1151, 1117, 748. MS (EI) mass calcd for C17
H
11
O
2
F
3
+
(
M ): 304.0711; found 304.0710.
(
Z)ꢀDimethyl 2ꢀ(2ꢀ(furanꢀ2ꢀyl)ꢀ5ꢀ(trifluoromethyl)styryl)ꢀ4,5ꢀdihydroxyꢀ4'ꢀ(trifluoroꢀ
methyl)ꢀ2'ꢀvinylꢀ2,3,4,5ꢀtetrahydroꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (8da). Brown oil,
1
R
f
= 0.4 (petroleum ether:EtOAc = 3:1), yield (20 mg, 21%). H NMR (400 MHz,
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CDCl
.9 Hz, 1H), 7.26 (s, 1H), 6.96 (dd,
6.51 (d, = 3.3 Hz, 1H), 6.37 (d, = 9.6 Hz, 1H), 6.24 (d,
5.3 Hz, 1H), 5.61 (d, = 17.4 Hz, 1H), 5.26 (d, = 11.0 Hz, 1H), 4.75 (s, 1H), 4.15
t, = 5.8 Hz, 1H), 3.72 (s, 3H), 3.53 (s, 3H), 3.21 (d, = 11.4 Hz, 1H), 2.47 (s, 1H).
C NMR (100 MHz, CDCl ) δ 172.1, 171.3, 152.1, 152.0, 136.6, 135.8, 135.6, 134.6,
32.1, 131.7, 130.7, 130.5, 129.6, 129.3, 128.1, 127.3, 126.8, 125.4, 125.3, 125.0 d,
d, CꢀF = 3.8 Hz), 124.2 d, CꢀF = 3.8 Hz), 123.2, 122.7, 117.5,
) δ ꢀ62.65, ꢀ62.81.
3
) δ 7.63 (s, 1H), 7.59 (d,
J
= 8.3 Hz, 1H), 7.46 (t,
= 17.4, 11.0 Hz, 1H), 6.54 (d,
= 3.3 Hz, 1H), 6.16 (d,
J
= 9.3 Hz, 2H), 7.39 (d,
J =
7
J
J
= 9.6 Hz, 1H),
J
J
J
J
=
J
J
(
1
J
J
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
1
(
J
CꢀF = 3.7 Hz), 124.4
(
J
(
J
19
1
12.1, 66.2, 53.0, 52.4, 51.9, 50.5, 41.0. F NMR (376 MHz, CDCl
3
ꢀ1
IR (thin film)
ν
max (cm ) 3489, 2955, 2921, 2850, 1735, 1633, 1435, 1330, 1168, 1124.
+
HRMS (MALDI) mass calcd for C32
641.1372.
H
24
O
6
F
6
Na ([M+NaꢀH
2
O] ): 641.1369; found
Dimethyl
7ꢀfluoroꢀ2,10aꢀdihydroꢀ1Hꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate
1
(3ea). Yellow oil, R
f
= 0.3 (petroleum ether:EtOAc = 5:1), yield (36 mg, 43%). H
NMR (400 MHz, CDCl
3
) δ 7.46 (dd,
= 9.0, 2.5 Hz, 1H), 6.74 (d,
= 9.7 Hz, 1H), 6.10 (d, = 9.7 Hz, 1H), 4.94 (dd,
J
= 8.3, 5.6 Hz, 1H), 6.93 (td, = 8.4, 2.6 Hz,
J
1
1
3
1
1
H), 6.85 (dd,
J
J
= 5.7 Hz, 1H), 6.70 (dd, J = 5.7, 1.5 Hz,
H), 6.43 (d,
J
J
J
= 4.3, 1.5 Hz, 1H),
= 4.3 Hz, 1H). C NMR (100 MHz, CDCl ) δ
d, CꢀF = 8.6 Hz), 130.6,
CꢀF = 21.8 Hz), 114.6 d,
CꢀF = 21.3 Hz), 113.9, 100.0, 88.9, 77.9, 59.9, 56.1, 52.2. F NMR (376 MHz, CDCl
13
.65 (s, 3H), 3.42 (s, 3H), 3.37 (d,
J
3
1
71.0, 170.0, 163.6
26.13 d,
(
d,
J
CꢀF = 249.1 Hz), 137.5, 137.1, 134.8
(
J
(
JCꢀF = 2.2 Hz), 126.07
(
d, CꢀF = 3.1 Hz),114.9 d,
J
(
J
(
19
J
3
)
ꢀ1
δ ꢀ111.80. IR (thin film)
ν
max (cm ) 3455, 2953, 2920, 2847, 1739, 1641, 1612, 1434,
+
1
262, 737. HRMS (MALDI) mass calcd for C18
H
15
O
5
FNa ([M+Na] ): 353.0801;
found 353.0802.
Dimethyl 2ꢀ((Z)ꢀ5ꢀfluoroꢀ2ꢀ(furanꢀ2ꢀyl)styryl)maleate (4ea). Yellow oil, R
f
= 0.5
) δ
= 8.2, 2.3 Hz, 1H),
= 11.8 Hz, 1H), 6.51 (d, = 3.2 Hz, 1H),
1
(petroleum ether:EtOAc = 5:1), yield (23 mg, 28%). H NMR (400 MHz, CDCl
3
7.65 (dd, J = 8.7, 5.7 Hz, 1H), 7.41 (d, J = 1.1 Hz, 1H), 7.00 (td, J
6
6
3
.91 (dd,
J
= 9.3, 2.5 Hz, 1H), 6.81 (d,
= 3.4, 1.8 Hz, 1H), 6.24 (dd,
J
J
.40 (dd,
J
J
= 11.9, 0.9 Hz, 1H), 5.93 (s, 1H), 3.63 (s,
1
3
1
H), 3.28 (s, 3H). C NMR (100 MHz, CDCl
3
) δ 166.8, 165.1, 161.0
d, JCꢀF = 7.9 Hz), 127.9
CꢀF = 3.3 Hz), 123.4, 117.6 d, CꢀF = 22.7 Hz), 115.5
(
d,
J
CꢀF = 248.1
Hz), 151.2, 144.4, 142.3, 141.9, 137.3, 133.8
Hz), 126.7, 126.0 d,
(
(d, JCꢀF = 8.2
(
J
(
J
(
d,
CꢀF
J =
1
9
2
1.5 Hz), 111.7, 110.1, 52.0. F NMR (376 MHz, CDCl
3
) δ ꢀ114.81. IR (thin film)
ꢀ1
ν
max (cm ) 2953, 2922, 2849, 1738, 1609, 1502, 1436, 1265, 1201, 738. HRMS
+
(MALDI) mass calcd for C18
H
15
O
5
FNa ([M+Na] ): 353.0801; found 353.0795.
Dimethylꢀ7ꢀfluoroꢀ2,3ꢀdihydroxyꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10aꢀ(1H)ꢀdicar
boxylate (5ea). White solid (m.p. 280 ºC), R = 0.2 (petroleum ether:EtOAc = 2:1),
f
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
yield (13 mg, 15%). H NMR (400 MHz, CDCl
3
) δ 7.36–7.29 (m, 1H), 6.83 (t,
= 9.6 Hz, 1H),
= 11.3 Hz,
J = 8.4
Hz, 1H), 6.69 (d, = 8.7 Hz, 1H), 6.39 (d, = 9.6 Hz, 1H), 6.21 (d, J
J
J
6.12 (d,
J
= 4.0 Hz, 1H), 4.39 (s, 2H), 3.75 (s, 3H), 3.50 (s, 3H), 3.08 (d, J
13
1
2
H), 2.61 (s, 1H). C NMR (100 MHz, CDCl ) δ 172.3, 171.1, 163.4
(
d, JCꢀF = 248.7
3
Hz), 137.4, 133.8, 130.1, 128.7, 126.9, 126.4, 115.1, 114.9
(
d,
J
CꢀF = 21.4 Hz), 113.1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
19
(
d, JCꢀF = 22.5 Hz), 66.8, 65.1, 52.9, 52.3, 48.9. F NMR (376 MHz, CDCl ) δ
3
ꢀ1
ꢀ112.80. IR (thin film)
ν
max (cm ) 3508, 3448, 2954, 2917, 2849, 1733, 1400, 1260,
+
1
089, 735. HRMS (MALDI) mass calcd for C18
H
17
O
6
FNa ([M+Na] ): 371.0901;
found 371.0909.
Dimethyl
7ꢀfluoroꢀ2,3ꢀdihydroxyꢀ1,2,3,10aꢀtetrahydrophenanthreneꢀ1,10a
-
(1H)ꢀ
dicarboxylate (6ea).
W
hite solid (m.p. 237 ºC), R
f
= 0.3 (petroleum ether:EtOAc =
1
2
J
5
:1), yield (21 mg, 21%). H NMR (400 MHz, DMSO) δ 7.51–7.36 (m, 1H), 7.05 (dd,
= 12.4, 9.2 Hz, 2H), 6.57 (d,
J = 9.5 Hz, 1H), 6.04 (d, J = 9.5 Hz, 1H), 5.94 (s, 1H),
.41 (d,
J
= 3.9 Hz, 2H), 4.10 (s, 2H), 3.67 (s, 3H), 3.49 (s, 3H), 2.87 (d, J = 10.6 Hz,
13
1
1H). C NMR (100 MHz, DMSO) δ 171.3, 170.7, 162.1
(
d,
J
CꢀF = 245.5 Hz), 133.4,
19
1
31.7, 130.4, 128.6, 126.7, 126.1, 114.9, 112.8, 78.9, 71.2, 70.3, 54.5, 52.2, 50.8. F
ꢀ1
NMR (376 MHz, DMSO) δ ꢀ113.67. IR (thin film)
ν
max (cm ) 3484, 3453, 2849, 1637,
1
457, 1400, 1333, 11165, 740, 696. HRMS (MALDI) mass calcd for C18H O FNa
17 6
+
([M+Na] ): 371.0901; found 371.0908.
Methyl 7ꢀfluorophenanthreneꢀ1ꢀcarboxylate (7ea). Yellow solid (m.p. 115 ºC), R
f
=
1
0
8
7
.8 (petroleum ether:EtOAc = 5:1), yield (8 mg, 13%). H NMR (400 MHz, CDCl
.74 (dd, = 8.7, 4.5 Hz, 2H), 8.59 (dd, = 9.0, 5.3 Hz, 1H), 8.12 (d,
.72 (d, = 7.9 Hz, 1H), 7.46 (dd, = 9.1, 1.8 Hz, 1H), 7.38–
) δ 168.3, 161.6 (d,
3
) δ
J
J
J = 7.4 Hz, 1H),
J
= 9.4 Hz, 1H), 7.60 (t,
J
13
J
7
.29 (m, 1H), 3.96 (s, 3H). C NMR (100 MHz, CDCl
3
1
J
CꢀF=248.2 Hz), 133.1, 130.7, 130.0, 129.6, 128.4, 127.9, 126.9, 126.6, 125.7, 125.2,
19
1
15.9, 112.6, 112.4, 52.4. F NMR (376 MHz, CDCl
3
) δ ꢀ114.32. IR (thin film)
ν
max
ꢀ1
(cm ) 3447, 2987, 2918, 2849, 1715, 1649, 1458, 1265, 739, 705. MS (EI) mass calcd
+
for C16
H
11
O
2
F (M ): 254.0743; found 254.0742.
(
Z)ꢀDimethyl 4'ꢀfluoroꢀ2ꢀ(5ꢀfluoroꢀ2ꢀ(furanꢀ2ꢀyl)styryl)ꢀ4,5ꢀdihydroxyꢀ2'ꢀvinylꢀ2,3,4,5
ꢀ
tetrahydroꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (8ea). Yellow solid (m.p. 130 ºC), R
f
=
1
0
.4 (petroleum ether:EtOAc = 3:1), yield (52 mg, 39%). H NMR (400 MHz, CDCl
3
)
δ 7.43 (dd,
J
= 8.7, 5.8 Hz, 1H), 7.33 (dd,
= 8.5, 2.6 Hz, 1H), 6.71 (dd,
= 3.3 Hz, 1H), 6.28 (d, = 9.6 Hz, 1H), 6.19
= 5.3 Hz, 1H), 5.56 (d, = 17.4 Hz, 1H), 5.20 (d,
= 5.8 Hz, 1H), 3.71 (s, 3H), 3.52 (s, 3H),
J
= 8.5, 5.5 Hz, 1H), 7.12 (dd,
J = 10.0, 2.6
Hz, 1H), 6.98–6.87 (m, 2H), 6.82 (td,
J
J
= 8.9, 2.6 Hz,
1
H), 6.44 (d,
J
= 9.6 Hz, 1H), 6.32 (d,
J
J
(d,
J
= 3.2 Hz, 1H), 6.00 (d,
J
J
J =
1
1.5 Hz, 1H), 4.78 – 4.68 (m, 1H), 4.10 (t,
J
1
3
3.18 (d, = 11.4 Hz, 1H), 2.36 (d, = 6.2 Hz, 1H). C NMR (100 MHz, CDCl ) δ
J
J
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172.2, 171.6, 163.0
(d, JCꢀF = 248.0 Hz), 162.3 (d, JCꢀF = 248.3 Hz), 161.8, 161.1,
1
52.5, 151.4, 137.7, 137.5, 134.6, 133.5, 130.5, 129.4, 127.0, 126.6, 125.9, 125.4,
19
118.3, 116.8, 114.9, 113.3, 111.8, 110.2, 66.3, 52.9, 52.3, 52.0, 50.7, 40.9. F NMR
ꢀ1
(376 MHz, CDCl
3
) δ ꢀ113.62, ꢀ114.09. IR (thin film)
ν
max (cm ) 3520, 2954, 2849,
1737, 1607, 1575, 1486, 1437, 1262, 737. HRMS (MALDI) mass calcd for
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
C
30
H
24
O
6
F
2
Na ([M+NaꢀH
2
O] ): 541.1433; found 541.1435.
Dimethyl 4'ꢀfluoroꢀ4ꢀhydroxyꢀ2'ꢀvinylꢀ[1,1'ꢀbiphenyl]ꢀ2,3ꢀdicarboxylate (9ea). Yellow
1
oil, R
f
= 0.6 (petroleum ether:EtOAc = 5:1), yield (23 mg, 28%). H NMR (400 MHz,
CDCl ) δ 10.94 (s, 1H), 7.22 (dd,
J
= 10.2, 2.6 Hz, 1H), 7.18 (d,
J = 8.4 Hz, 1H), 7.05
3
(dd,
J
= 8.5, 5.9 Hz, 1H), 7.01 (d,
J
= 8.6 Hz, 1H), 6.87 (td, = 8.3, 2.6 Hz, 1H), 6.32
J
(ddd,
J
= 17.5, 11.0, 1.6 Hz, 1H), 5.57 (d,
J
= 17.4 Hz, 1H), 5.12 (d,
J
= 11.0 Hz, 1H),
13
1
3
.84 (s, 3H), 3.45 (s, 3H). C NMR (100 MHz, CDCl
3
) δ 169.3, 168.3, 162.5
(d,
J
CꢀF
= 282.1 Hz), 161.1, 139.0, 137.6, 135.4, 134.2, 133.0, 132.1, 129.2, 118.7, 116.1,
19
1
14.1, 111.5, 109.0, 53.0, 52.0. F NMR (376 MHz, CDCl
3
) δ ꢀ113.96. IR (thin film)
ꢀ1
ν
max (cm ) 3088, 2954, 2851, 1739, 1679, 1461, 1443, 1247, 1213, 728. HRMS
+
(MALDI) mass calcd for C18
H
15
O
5
FNa ([M+Na] ): 353.0801; found 353.0803.
Dimethyl 9ꢀmethylꢀ1,2ꢀdihydroꢀ10aHꢀ2,4aꢀepoxyphenanthreneꢀ1,10aꢀdicarboxylate
1
(
3fa). Yellow oil, R
NMR (400 MHz, CDCl
.88 (d, = 5.6 Hz, 1H), 6.78 (d,
1H), 3.75 (s, 1H), 3.49 (s, 1H), 3.48 (s, 1H), 2.17 (s, 1H). C NMR (101 MHz, CDCl
δ 171.3, 170.6, 137.7, 137.1, 134.1, 131.3, 130.3, 129.7, 128.7, 128.2, 126.2, 124.5,
f
= 0.3 (petroleum ether:EtOAc = 5:1), yield (28 mg, 26%). H
3
) δ 7.60 (d,
J
= 7.4 Hz, 1H), 7.43 (s, 1H), 7.39 – 7.34 (m, 1H),
6
J
J
= 5.7 Hz, 1H), 5.96 (s, 1H), 5.04 (d, = 4.1 Hz,
J
13
3
)
ꢀ1
89.4, 78.2, 59.9, 56.9, 52.1, 52.0, 19.8. IR (thin film)
ν
max (cm ) 2952, 2313, 1736,
Na
1
603, 1441, 1349, 1239, 1166, 928, 758. HRMS (ESI) mass calcd for C19H O
18 5
+
([M+Na] ): 349.1046; found 349.1055.
Dimethyl 2ꢀ((Z)ꢀ2ꢀ(2ꢀ(furanꢀ2ꢀyl)phenyl)propꢀ1ꢀenꢀ1ꢀyl)maleate (4fa). Yellow oil, R
f
1
=
0.5 (petroleum ether:EtOAc = 5:1), yield (27 mg, 39%). H NMR (400 MHz, CDCl )
3
δ 7.68 (d,
1H), 6.99 (s, 1H), 6.59 (d,
s, 1H), 3.57 (s, 1H), 3.07 (s, 1H), 1.97 (s, 1H). C NMR (101 MHz, CDCl ) δ 167.0,
J
= 7.8 Hz, 1H), 7.39 (s, 1H), 7.27 (t,
J
= 7.6 Hz, 1H), 7.18 (d,
J = 8.4 Hz,
J
= 2.7 Hz, 1H), 6.37 (d,
J
= 1.6 Hz, 1H), 6.11 (s, 1H), 5.71
13
(
3
165.5, 151.9, 149.8, 146.1, 142.1, 136.0, 129.9, 128.8, 128.1, 127.0, 126.3, 124.0,
ꢀ1
1
20.0, 111.8, 108.8, 100.0, 51.7, 27.3. IR (thin film) νmax (cm ) 3121, 2950, 2854,
1728, 1599, 1436, 1382, 1270, 1205, 1160, 812, 666. HRMS (ESI) mass calcd for
+
C
19
H
18
O
5
Na ([M+Na] ): 349.1046; found 349.1056.
2
4
Computational Details. Calculations were performed with Gaussian 09 program.
25
26
The hybrid B3LYP functional with the 6ꢀ31+G(d) basis set was applied for the
optimization of all stationary points in gas phase. Optimizations at different
ACS Paragon Plus Environment