Gold(I)-Initiated Cycloisomerization/Diels-Alder/Retro-Diels-Alder Cascade Strategy to Biaryls

Article abstract of DOI:10.1021/acs.joc.7b01561

A unique approach to biaryls was developed on the basis of propargyl vinyl ethers and dienophiles substrates via a gold(I)-initiated cycloisomerization/Diels-Alder/retro-Diels-Alder cascade reaction. The scope and mechanism of the reaction were investigated on the basis of a series of synthetic substrates, control experiments, and DFT calculations.

Full text of DOI:10.1021/acs.joc.7b01561

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Article
A Gold(I)-Initiated Cycloisomerization/Diels-Alder/
Retro- Diels-Alder Cascade Strategy to Biaryls
Shengfei Jin, Yujie Niu, Chengjun Liu, Lifeng Zhu, Yangming Li, Shanshan
Cui, Zhiling Xiong, Maosheng Cheng, Bin Lin, and Yongxiang Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01561 • Publication Date (Web): 04 Aug 2017
Downloaded from http://pubs.acs.org on August 4, 2017
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A Gold(I)-Initiated Cycloisomerization/Diels-Alder/Retro-
Diels-Alder Cascade Strategy to Biaryls
ǂ,♯
ǂ,ǁ,♯
ǂ,ǁ,♯
ǂ,ǁ,♯
ǂ,ǁ,♯
ǂ,♯
Shengfei Jin, Yujie Niu, Chengjun Liu, Lifeng Zhu, Yangming Li, Shanshan Cui, Zhiling
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Xiong, Maosheng Cheng, Bin Lin,∗ and Yongxiang Liu
ǂ,♯
ǂ,♯
ǂ,♯
∗
ǂ,ǁ,♯
ǂ Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang
110016, P. R. China.
ǁ Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China.
♯ Institute of Drug Research in Medicine Capital of China, Benxi 117000, P. R. China.
ABSTRACT: A unique approach to biaryls was developed based on propargyl vinyl ethers and dienophiles
substrates via a gold(I)-initiated cycloisomerization/Diels-Alder/retro-Diels-Alder cascade reaction. The scope
and mechanism of the reaction were investigated based on a series of synthetic substrates, control
experiments and DFT calculations.
Introduction
1
Biaryls are important scaffolds in a wide range of natural products, pharmaceutically active molecules, chiral
2
3
4
ligands, crown ethers and liquid crystals. Due to the increasing requirement for the efficient strategies to
5
constructing biaryl compounds, a number of methodologies have been developed, in which the transition
5
b,5f-5g5i
metal-catalyzed cross-coupling reactions were the predominant methods.
Moreover, a strategy to the
synthesis of biaryls by the construction of one aryl ring via transition metal-catalyzed [2+2+2] cycloaddition of
5
a,5c,5e
alkynes or Diels-Alder cycloaddition/aromatization also drew considerable attention.
Also, some
6
gold-catalyzed approaches to biaryls have been reported.
As our continued efforts on constructing structural diverse small molecules by gold-catalyzed
7
pathway-tunable reactions, an angle strain-controlled strategy of propargyl vinyl ether substrates to synthesize
furofuran and furopyran derivatives by altering the regioselectivity and disturbing intermediate formation has
7b
been developed. The existence of diene fragments in the furopyran derivatives inspired us to expand the
structural diversity of the methodology by introducing dienophiles in the cycloisomerization of the propargyl
vinyl ether to promote a cascade Diels-Alder reaction. To our delight, the cycloaddition between the furopyran
and dimethyl diacetylenedicarboxylate (DMAD) underwent smoothly to give the bridged-ring as expected by
following the gold-catalyzed cycloisomerization. Furthermore, the driving force to collapse into
thermodynamically stable aromatic ring from the strained bridged-ring by releasing formaldehyde caused a
sequential retro-Diels-Alder reaction to occur, leading to a biaryl product (Scheme 1). Examples describing the
8
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10
aromatization via the release of volatile small molecules such as carbon dioxide, alkene, sulfur dioxide and
1
1
aldehyde to form phenyl rings have been reported previously. In this study, by releasing formaldehyde via a
cycloisomerization/Diels-Alder/retro-Diels-Alder strategy, a novel gold-catalyzed cascade reaction to yield biaryl
compounds was developed.
Scheme 1. Strained-controlled Tandem Cyclization of Propargyl Vinyl Ether
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Results and Discussion
At the outset, substrate 1 was chosen as the model substrate for condition optimization. A variety of gold
catalysts (5 mol %) were first examined using toluene as the solvent and 120 °C as the initial temperature. Among
the gold catalysts screened, commercially available [bis-(trifluoromethanesulfonyl) imidate] (triphenylphosph-
1
2
ine) gold(I), (Ph
Ph PAuCl/AgOTf and (IPr)AuCl/AgNTf
lower activity (Table 1, entry 6). The possibility of the reaction catalyzed by trace amount of acid was excluded by
using HNTf as the catalyst (Table 1, entry 7). The optimal reaction time was identified to be 2 h by conducting
several experiments (Table 1, entries 8-9). The Diels-Alder reaction would not occur at lower reaction
3
PAuNTf
2
)
gave the best result. Other catalysts such as Ph
3
PAuCl, Ph
3 6
PAuCl/AgSbF
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were less reactive (Table 1, entries 1-5). AgNTf
2
was tested and showed
2
7
b
temperatures and only corresponding cycloisomerized product was isolated as we reported before (Table 1,
entries 10-11). A control experiment using conventional heating condition was performed to afford the product
with lower yields and longer reaction times (Table 1, entry 12). AuCl was also examined in the biaryl formation
3
reaction with an unsatisfactory yield (Table 1, entry 13). In the end, the optimal condition was determined as
stirring the reaction at 120 °C for 2 h in the solvent of toluene with Ph PAuNTf as the catalyst under the
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2
irradiation of microwave.
Table 1. Screening of Reaction Conditions
a, b
entry
catalyst
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
T (°C)
120
120
120
120
120
120
120
120
120
80
yield (%)
1
2
3
4
5
6
7
8
9
1
Ph
Ph
Ph
Ph
3
3
3
3
PAuNTf
2
68
5c
PAuCl
PAuCl/AgSbF
6
46
PAuCl/AgOTf
55
20c
(IPr)AuCl/AgNTf2
AgNTf
HNTf
2
30
0c
2
50d
69e
0f
Ph
Ph
Ph
Ph
Ph
3
3
3
3
3
PAuNTf
PAuNTf
PAuNTf
PAuNTf
PAuNTf
2
2
2
2
2
0
0f
11
toluene
toluene
toluene
80
40g
38
1
1
2
3
120
120
AuCl
3
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a
b
Isolated yield and the reaction time was 2 h; The reaction was performed under microwave irradiation;
c
d
e
f
IPr=1,3-bis(diisopropylphenyl) imidazol-2-ylidene], starting material 1 remained; Run for 1 h; Run for 3 h; Only the
g
cycloisomerized product was isolated; Reaction was conducted with the conventional heating.
With the optimal condition in hand, we explored the scope of the cascade reaction with a variety of aromatic
or heteroaromatic substituted propargyl vinyl ethers using DMAD as the dienophile. The substrates with para
electron-withdrawing substituted phenyl ring were first examined and the yields of the products were lower than
that of the substrate without substitutions (2a-2d). The substrates with ortho or meta-substituents phenyl rings
afforded the corresponding biaryls in 40-58% yields, which were also lower that of the substrate with no
substitutions (2e-2i). The substrates with multi-substituted phenyl rings afforded similar results (2j-2l). It was
worth mentioning that naphthalene and heterocycle-contained substrates showed good tolerance to the
reaction condition and provided acceptable yields (2m-2n).
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Scheme 2. Substrate Scopes of the Aryl Substitutions
Having successfully achieved the cascade transformation employing DMAD as the dienophile, we shifted our
attention to explore the regioselectivity of the cycloaddition by encompassing non-symmetrical dienophiles. We
anticipated that enone ether fragment existing in the furopyran intermediate derived from
Claisen-rearrangement/6-endo-trig cyclization could control the regioselectivity of the Diels-Alder cycloaddition
by raising the HOMO coefficient at C4 of the diene moiety to give the "ortho" product. In this light, a methyl
propiolate was used as the dienophile and the "ortho" product-derived biaryls as shown in Scheme 3 were
isolated as the single regioisomers (3a-3e). Next, 2-hexen-4-ynedioic acid dimethyl ester synthesized via the
dimerization of methyl propiolate was used as a dienophile in the biaryl synthesis reaction (3f-3h). The remote
vinyl ester had totally dictated the regioselectivity of the reaction, which was consistent with the results of the
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precedent research.
Scheme 3. Substrate Scopes of the Dienophiles
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Next, the scopes of the cyclic vinyl ethers in the cascade reaction were examined by several synthetic
propargyl vinyl ether substrates with similar angle strains as shown in Scheme 4. The substrates with the ketone
moiety afforded the biaryls with relative lower yields attributing to the electron deficient nature of the carbonyl
groups (4a-4c). The yields of the propargyl β-tetronic acid ether substrates were similar to those of the substrates
shown in Scheme 2 (4d-4f).
Scheme 4. Substrate Scopes of the Vinyl Ethers
0
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0
R
2
CO Me
5
mol % Ph3PAuNTf2, DMAD
MWI, toluene, 120 C, 2 h
R
O
CO2Me
O
X
O
4a-4f
X
1o-1t
CO2Me
CO2Me Cl
CO Me
Cl
2
CO Me
2
2
CO Me
2
CO Me
O
O
O
4a, 45%
CO2Me
CO2Me Cl
4b, 67%
4c, 37%
CO Me
CO2Me
CO2Me
Cl
2
2
CO Me
O
O
O
O
O
O
4d, 62%
4e, 61%
4f, 65%
To probe the detailed mechanism of the biaryl formation reaction, the furopyran intermediate 1b’ was isolated
7b
by following our previous procedure. Then the isolated intermediate was subjected to the standard condition
and the condition with the absence of gold catalyst. Both conditions could provide the biaryl product with similar
yields, which suggested that the reaction proceeded through the cycloaddition/fragmentation of furopyran and
DMAD leading to the biaryl and the gold catalyst was not essential to the aromatization stage of the reaction
(
Scheme 5).
Scheme 5. Control Experiments
Based on the experimental results and previous work, a proposed mechanism for this gold-initiated cascade
sequence is illustrated in Scheme 6a. Initially, under the activation of gold catalyst substrate 1d went through
,3-Claisen rearrangement to give allene intermediate followed by a 6-endo-trig cyclization to give furopyran
3
intermediate 1d’. In the presence of DMAD, a Diels-Alder reaction happened to deliver a highly congested
intermediate 2d-Int following the cycloisomerization. A tandem retro-Diels-Alder reaction occurred to provide
the biaryl product 2d with the fragmentation of formaldehyde, which to our knowledge was never reported
before. Attempts on the isolation of Diels-Alder cycloaddition product 2d under mild conditions failed owing to
the congested nature of the cycloaddition intermediate and the inherent driving force to generate aromatic
biaryl product by releasing formaldehyde. This result was also illustrated by density functional theory (DFT)
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4
calculations (B3LYP/6-31G) on the free energy of activation for the Diels-Alder cycloaddition (2d-TS1) and
6
d
retro-Diels-Alder reaction (2d-TS2) by following our previous protocol. The results are shown in Scheme 6b.
These computed barriers indicate that the Diels-Alder cycloaddition is the rate-determining step and the
retro-Diels-Alder reaction will proceed rather easily once the 2d-Int is formed, which is also consistent with our
experimental observations.
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Scheme 6. Proposed Mechanism and DFT Calculations (the energy unit: kcal/mol)
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Conclusion
In summary, we have demonstrated a facile, one-pot and straightforward approach toward a variety of
structurally diverse biaryls via a gold(I)-initiated cycloisomerization/Diels-Alder/retro-Diels-Alder cascade
reaction of propargyl vinyl ethers and readily available dienophiles. The detailed mechanism of this
transformation was probed by control experiments and DFT calculations. Further studies on the applications of
the synthesized biaryls are in progress in our laboratory.
Experimental Section
General Experimental Methods. Unless otherwise noted, reagents were obtained commercially and used
without further purification. Tetrahydrofuran was distilled from sodium under a nitrogen atmosphere.
Dichloroethane was distilled from calcium chloride under a nitrogen atmosphere. TLC analysis of reaction
mixtures was performed on Dynamicadsorbents silica gel F-254 TLC plates. Flash chromatography was carried out
on Zeoprep 60 (200-300 mesh) silica gel. Microwave reactions were performed with a Discover SP Microwave
Synthesizer in sealed reaction vessels. The temperature was monitored with an internal vertically focused IR
1
13
temperature sensor. H and C NMR spectra were recorded with Bruker Avance-III 600 spectrometers and
referenced to CDCl and DMSO-d . HR-ESI-MS was recorded on a Bruker micro-TOFQ-Q instrument. IR spectra
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were recorded on a Bruker IFS 55 spectrometer. Melting points were tested on Thomas Hoover capillary melting
point apparatus.
General Procedures for the Preparation of Propargylic Alcohols (A1-A15). To a stirring solution of alkyne (5
mmol) in THF (5 mL) was added dropwise n-BuLi (1.0 M in THF, 5.5 mL) at −78 °C. Paraformaldehyde (6 mmol,
1
80 mg) was added portionwise after 0.5 h. The solution was warmed to room temperature after 1.0 h. The
reaction was monitored by TLC till the consumption of the starting material; the reaction mixture was quenched
by addition of saturated aqueous ammonium chloride (20 mL) and extracted with ethyl acetate three times (20
2 4
mL). The combined organic layers were washed with brine, dried over anhydrous Na SO , and concentrated in
vacuo. The crude material was purified by a flash column chromatography on silica gel using petroleum
7b
ether/ethyl acetate as eluent to obtain the propargylic alcohols A2-A8, A15.
To a solution of aryl iodide (7.6 mmol), propargyl alcohol (555 mg, 10 mmol) and triethylamine (2 mL) in THF
(
20 mL) was added dichlorobis(triphenylphosphine) palladium(II) (155 mg, 0.2 mmol), followed by CuI (0.24 mmol,
5.4 mg). The reaction mixture was stirred at room temperature for 24 h. Water was added and the aqueous
solution was washed with EtOAc. The organic solutions were combined, dried over anhydrous MgSO , filtered
4
4
and concentrated. The crude material was purified by a flash column chromatography on silica gel using
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petroleum ether/ethyl acetate as eluent to obtain the propargylic alcohols A1, A9-A14. A9-A12 and A14 were
1
5
reported in previous work.
Isopropyl 4-(3-hydroxyprop-1-yn-1-yl)benzoate (A1). Purified by a flash column chromatography on silica gel
with petroleum ether/ethyl acetate (5:1) as an eluent to give the product A1 (1.7 g) with a yield of 80%; colorless
1
oil; H NMR (600 MHz, CDCl
3
) δ 8.08–7.87 (m, 2H), 7.51–7.41 (m, 2H), 5.24 (dt, J = 12.5, 6.2 Hz, 1H), 4.52 (d, J =
1
3
6
1
1
.1 Hz, 2H), 2.20–1.87 (m, 1H), 1.36 (d, J = 6.3 Hz, 6H); C NMR (150 MHz, CDCl
3
) δ 165.7, 131.6, 130.7, 129.5,
−1
27.1, 90.2, 85.1, 68.8, 51.7, 22.1; IR (thin film, cm ) 3399, 2985, 1711, 1605, 1405, 1376, 1346, 1289, 1177,
+
019, 857, 767; HRMS (ESI): m/z calcd. for C13
Methyl 2-chloro-5-(3-hydroxyprop-1-yn-1-yl)benzoate (A13). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product A13 (1.5 g) with a yield of 69%;
14 3
H O Na [M+Na] 241.0835, found 241.0843.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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7
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colorless oil; H NMR (600 MHz, CDCl ) δ 7.87 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 8.3, 2.1 Hz, 1H), 7.38 (d, J = 8.3 Hz,
1
3
1
1
1
H), 4.48 (d, J = 6.1 Hz, 2H), 3.92 (s, 3H), 2.08 (t, J = 6.2 Hz, 1H); C NMR (150 MHz, CDCl
3
) δ 165.5, 135.3, 134.7,
−1
34.0, 131.3, 130.2, 121.6, 89.4, 83.6, 52.7, 51.6; IR (thin film, cm ) 3490, 1705, 1475, 1440, 1309, 1254, 1232,
+
052, 1033, 835, 784; HRMS (ESI): m/z calcd. for C11
9 3
H O ClNa [M+Na] 247.0132, found 247.0129.
General Procedures for the Preparation of Propargyl γ-Butyrolactone-2-enol Ether (1, 1a-1n). A solution of
diisopropyl azodiformate (3 mmol, 606 mg) in dry THF was added dropwise to a solution of propargylic alcohol
A1-A15 (2 mmol), 3-hydroxy-2,5-dihydrofuran-2-one B (2 mmol, 200 mg) and triphenylphosphine (3 mmol, 787
mg) in THF at 0 °C for 15 min under a nitrogen atmosphere. The reaction was stirred at room temperature
overnight. The crude mixture was evaporated to dryness and purified by a flash column chromatography to
7b
afford the products 1, 1a-1n. 1a, 1b, 1e, 1g were reported in our previous work.
Isopropyl 4-(3-((2-oxo-2,5-dihydrofuran-3-yl)oxy)prop-1-yn-1-yl)benzoate (1). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1 (239 mg)
1
with a yield of 38%; white solid; Mp 100.7–102.1 °C; H NMR (600 MHz, CDCl
3
) δ 7.99 (d, J = 8.5 Hz, 2H), 7.48 (d, J
=
6
8.4 Hz, 2H), 6.40 (t, J = 2.1 Hz, 1H), 5.30–5.17 (m, 1H), 4.91 (s, 2H), 4.83 (d, J = 2.1 Hz, 2H), 1.36 (d, J = 6.3 Hz,
1
3
3
H); C NMR (150 MHz, CDCl ) δ 167.9, 165.4, 144.9, 131.8, 131.3, 129.6, 126.1, 115.3, 88.0, 84.3, 68.9, 67.7,
−1
59.2, 22.0; IR (thin film, cm ) 3425, 2920, 1765, 1707, 1650, 1454, 1274, 1134, 1104, 804, 762; HRMS (ESI): m/z
+
calcd. for C17
Methyl-4-(3-((2-oxo-2,5-dihydrofuran-3-yl)oxy)prop-1-yn-1-yl)benzoate (1c). Purified by
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1c (180
16 5
H O Na [M+Na] 323.0890, found 323.0883.
a
flash column
1
mg) with a yield of 33%; white solid; Mp 160.5–161.2 °C; H NMR (600 MHz, CDCl
3
) δ 7.99 (d, J = 8.3 Hz, 2H), 7.49
13
(d, J = 8.3 Hz, 2H), 6.40 (t, J = 2.0 Hz, 1H), 4.91 (s, 2H), 4.83 (d, J = 2.0 Hz, 2H), 3.92 (s, 3H); C NMR (150 MHz,
−
1
CDCl
431, 1783, 1763, 1715, 1650, 1431, 1136, 1045, 794; HRMS (ESI): m/z calcd. for C15
found 295.0585.
-((3-Phenylprop-2-yn-1-yl)oxy)furan-2(5H)-one (1d). Purified by a flash column chromatography on silica gel
with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1d (193 mg) with a yield of 45%; white
3
) δ 167.9, 166.4, 144.9, 131.8, 130.5, 129.7, 126.3, 115.3, 87.9, 84.5, 67.7, 59.1, 52.5; IR (thin film, cm )
+
3
12 5
H O Na [M+Na] 295.0577,
3
1
3
solid; Mp 98.2–99.6 °C; H NMR (600 MHz, CDCl ) δ 7.43 (dd, J = 8.1, 1.4 Hz, 2H), 7.38–7.29 (m, 3H), 6.41 (t, J =
1
3
2
1
1
.1 Hz, 1H), 4.89 (s, 2H), 4.81 (d, J = 2.1 Hz, 2H); C NMR (150 MHz, CDCl
3
) δ 168.1, 144.8, 131.9, 129.2, 128.5,
−1
21.7, 115.3, 88.7, 81.6, 67.7, 59.3; IR (thin film, cm ) 3429, 3091, 1766, 1649, 1491, 1445, 1396, 1332, 1256,
+
127, 1053, 818, 760, 691; HRMS (ESI): m/z calcd. for C13
-((3-(3-Chlorophenyl)prop-2-yn-1-yl)oxy)furan-2(5H)-one (1f). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1f (199 mg) with a yield of 40%;
10 3
H O Na [M+Na] 237.0522, found 237.0525.
3
1
3
white solid; Mp 92.0–93.9 °C; H NMR (600 MHz, CDCl ) δ 7.40 (t, J = 1.6 Hz, 1H), 7.36–7.29 (m, 1H), 7.25 (dd, J =
1
3
1
1
1
2
0.3, 5.3 Hz, 1H), 6.40 (t, J = 2.1 Hz, 1H), 4.88 (s, 2H), 4.82 (d, J = 2.1 Hz, 2H); C NMR (150 MHz, CDCl
3
) δ 167.9,
−1
44.8, 134.4, 131.7, 130.1, 129.8, 129.5, 123.4, 115.4, 87.2, 82.8, 67.7, 59.1; IR (thin film, cm ) 3432, 3115, 1762,
+
9 3
653, 1474, 1455, 1384, 1319, 1247, 1130, 1045, 801, 780, 678; HRMS (ESI): m/z calcd. for C13H O ClNa [M+Na]
71.0132, found 271.0148.
3-((3-(2-Chlorophenyl)prop-2-yn-1-yl)oxy)furan-2(5H)-one (1h). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 1h (194 mg) with a yield of
1
3
9%; white solid; Mp 69.3–93.9 °C; H NMR (600 MHz, CDCl
3
) δ 7.46 (dd, J = 7.7, 1.6 Hz, 1H), 7.38 (dd, J = 8.1, 1.0
Hz, 1H), 7.31–7.24 (m, 1H), 7.22 (td, J = 7.6, 1.2 Hz, 1H), 6.50 (t, J = 2.1 Hz, 1H), 4.94 (s, 2H), 4.81 (d, J = 2.1 Hz,
13
2
5
H); C NMR (150 MHz, CDCl
3
) δ 168.1, 144.6, 136.2, 133.7, 130.3, 129.4, 126.7, 121.7, 115.9, 86.7, 85.5, 67.7,
−1
9.1; IR (thin film, cm ) 3425, 1772, 1654, 1473, 1364, 1267, 1116, 1047, 999, 950, 801, 755; HRMS (ESI): m/z
+
calcd. for C13
Ethyl-2-(3-((2-oxo-2,5-dihydrofuran-3-yl)oxy)prop-1-yn-1-yl)benzoate (1i). Purified by
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1i (200 mg)
9 3
H O ClNa [M+Na] 271.0132, found 271.0124.
a
flash column
1
3
with a yield of 35%; yellow solid; Mp 65.5–66.7 °C; H NMR (600 MHz, CDCl ) δ 7.95 (dd, J = 7.8, 0.9 Hz, 1H), 7.61–
7.34 (m, 3H), 6.59 (t, J = 2.1 Hz, 1H), 4.95 (s, 2H), 4.83 (d, J = 2.1 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz,
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2
3
4
5
6
7
8
9
1
3
3H); C NMR (150 MHz, CDCl
3
) δ 168.2, 165.8, 144.7, 134.6, 132.5, 131.9, 130.5, 128.9, 122.3, 116.2, 87.4, 86.6,
−1
67.8, 61.4, 59.4, 14.4; IR (thin film, cm ) 3428, 2920, 1770, 1721, 1653, 1253, 1118, 1049, 759; HRMS (ESI): m/z
+
calcd. for C16
-((3-(2-Chloro-4-methylphenyl)prop-2-yn-1-yl)oxy)furan-2(5H)-one (1j). Purified by
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1j (210 mg)
14 5
H O Na [M+Na] 309.0733, found 309.0736.
3
a
flash column
1
with a yield of 40%; yellow solid; Mp 65.1–66.3 °C; H NMR (600 MHz, CDCl
3
) δ 7.40 (d, J = 1.4 Hz, 1H), 7.21 (dd, J
=
7.8, 1.5 Hz, 1H), 7.17 (d, J = 7.9 Hz, 1H), 6.39 (t, J = 2.1 Hz, 1H), 4.87 (s, 2H), 4.82 (d, J = 2.1 Hz, 2H), 2.36 (s, 3H);
1
3
3
C NMR (150 MHz, CDCl ) δ 168.0, 144.8, 137.7, 134.4, 132.1, 131.0, 130.1, 120.7, 115.3, 87.4, 82.1, 67.7, 59.2,
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
2
0.2; IR (thin film, cm ) 3426, 1765, 1649, 1365, 1121, 1108, 1047, 955, 813; HRMS (ESI): m/z calcd. for
+
C
14
H
11
O
3
ClNa [M+Na] 285.0289, found 285.0283.
-((3-(3,4-Dichlorophenyl)prop-2-yn-1-yl)oxy)furan-2(5H)-one (1k). Purified by a flash column chromatography
on silica gel with petroleum ether/ethyl acetate (10:1) as an eluent to give the product 1k (238 mg) with a yield of
3
1
4
7
2%; white solid; Mp 106.1–107.5 °C; H NMR (600 MHz, CDCl
3
) δ 7.53 (d, J = 1.8 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H),
1
3
.27 (dd, J = 7.7, 2.3 Hz, 1H), 6.38 (t, J = 2.0 Hz, 1H), 4.89 (s, 2H), 4.84 (d, J = 2.0 Hz, 2H); C NMR (150 MHz,
−1
CDCl
3
) δ 167.8, 145.0, 133.9, 133.6, 132.9, 131.1, 130.7, 121.7, 115.3, 86.4, 83.6, 67.7, 59.1; IR (thin film, cm )
3
431, 2925, 1775, 1748, 1654, 1461, 1367, 1328, 1264, 1141, 1044, 1008, 959, 884, 804; HRMS (ESI): m/z calcd.
-
7 3 2
for C13H O Cl [M-H] 280.9777, found 280.9778.
Methyl-2-chloro-5-(3-((2-oxo-2,5-dihydrofuran-3-yl)oxy)prop-1-yn-1-yl)benzoate (1l). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (10:1) as an eluent to give the product 1l (184
1
mg) with a yield of 30%; white solid; Mp 109.3–110.5 °C; H NMR (600 MHz, CDCl
3
) δ 7.89 (d, J = 2.0 Hz, 1H), 7.43
13
(
dd, J = 17.8, 5.2 Hz, 2H), 6.38 (t, J = 2.1 Hz, 1H), 4.88 (s, 2H), 4.83 (d, J = 2.1 Hz, 2H), 3.93 (s, 3H); C NMR (150
3
MHz, CDCl ) δ 167.9, 165.3, 144.9, 135.4, 134.8, 134.7, 131.5, 130.5, 120.6, 115.3, 86.6, 83.6, 67.7, 59.1, 52.8; IR
−1
(
thin film, cm ) 3426, 2922, 1766, 1724, 1650, 1471, 1427, 1392, 1303, 1231, 1117, 1049, 826; HRMS (ESI): m/z
-
10 5
calcd. for C15H O Cl [M-H] 305.0222, found 305.0223.
3
-((3-(Naphthalen-1-yl)prop-2-yn-1-yl)oxy)furan-2(5H)-one (1m). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (10:1) as an eluent to give the product 1m (236 mg) with a yield of
1
45%; yellow solid; Mp 102.3–103.5 °C; H NMR (600 MHz, CDCl
3
) δ 8.23 (d, J = 8.3 Hz, 1H), 7.86 (dd, J = 8.0, 3.3
Hz, 2H), 7.71–7.63 (m, 1H), 7.61–7.50 (m, 2H), 7.43 (dd, J = 8.1, 7.3 Hz, 1H), 6.47 (t, J = 2.1 Hz, 1H), 5.04 (s, 2H),
1
3
4.82 (d, J = 2.1 Hz, 2H); C NMR (150 MHz, CDCl
3
) δ 168.1, 144.9, 133.3, 133.2, 131.1, 129.7, 128.5, 127.2, 126.7,
−1
125.8, 125.2, 119.4, 115.5, 87.0, 86.4, 67.7, 59.5; IR (thin film, cm ) 3396, 2920, 1768, 1652, 1397, 1326, 1250,
+
12 3
1118, 1049, 979, 801, 775; HRMS (ESI): m/z calcd. for C17H O Na [M+Na] 287.0679, found 287.0682.
General Procedures for the Preparation of Propargyl Vinyl Ether (1o-1t). A solution of diisopropyl
azodiformate (3 mmol, 606 mg) in dry THF was added dropwise to a solution of propargylic alcohol A5-A7 (2
mmol), C (2 mmol) and triphenylphosphine (3 mmol, 787 mg) in THF at 0 °C for 15 min under a nitrogen
atmosphere. The reaction was stirred at room temperature overnight. The crude mixture was evaporated to
dryness and purified by a flash column chromatography to afford the products 1o-1t.
3
-(3-Phenylprop-2-ynyloxy)cyclopent-2-enone (1o). Purified by a flash column chromatography on silica gel
with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1o (191 mg) with a yield of 45%; white
1
6
solid; Mp 71.7–73.2 °C; H NMR (600 MHz, DMSO-d ) δ 7.48 (d, J = 6.4 Hz, 2H), 7.43 (dd, J = 11.6, 7.1 Hz, 2H), 5.51
1
3
(
s, 1H), 5.09 (s, 2H), 2.65–2.61 (m, 2H), 2.36–2.32 (m, 2H); C NMR (150 MHz, DMSO-d
6
) δ 179.2, 172.9, 156.2,
−1
1
1
2
31.7, 129.5, 128.9, 121.0, 89.8, 88.1, 82.5, 67.9, 67.5, 60.7, 22.0; IR (thin film, cm ) 3426, 2979, 2922, 1677,
+
13 2
589, 1436, 1339, 1240, 1113, 1008, 955, 696, 543; HRMS (ESI): m/z: calcd. for C14H O [M+H] 213.0916, found
13.0915.
3
-(3-(4-Chlorophenyl)prop-2-ynyloxy)cyclopent-2-enone (1p). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1p (444 mg) with a yield of
1
9
5
1
1
2
0%; white solid; Mp 84.4–85.7 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.51 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 8.7 Hz, 2H),
13
.51 (s, 1H), 5.08 (s, 2H), 2.64–2.60 (m, 2H), 2.36–2.32 (m, 2H); C NMR (150 MHz, DMSO-d ) δ 204.4, 188.8,
34.2, 133.4, 129.0, 120.0, 105.6 , 86.3, 84.2, 59.7, 34.1, 27.8; IR (thin film, cm ) 3429, 2980, 2924, 1739,
6
−1
+
12 2
711,1593, 1467, 1339, 1237, 832, 723, 544; HRMS (ESI): m/z calcd. for C14H O Cl [M+H] 247.0526, found
47.0531.
3
-(3-(3-Chlorophenyl)prop-2-ynyloxy)cyclopent-2-enone (1q). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1q (439 mg) with a yield of
1
8
7
9%; white solid; Mp 82.9–84.5 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.56 (s, 1H), 7.52 (dt, J = 7.4, 1.9 Hz, 1H),
13
.47–7.42 (m, 2H), 5.52 (s, 1H), 5.09 (s, 2H), 2.64–2.61 (m, 2H), 2.37–2.33 (m, 2H); C NMR (150 MHz, DMSO-d
6
−1
)
δ 204.4, 188.8, 133.4, 131.0, 130.7, 130.4, 129.6, 123.1, 105.7, 85.9, 84.5, 59.6, 34.1, 27.8; IR (thin film, cm )
+
2
3425, 2924, 2853, 1590, 1384, 1111, 961, 791, 618; HRMS (ESI): m/z calcd. for C14H12ClO [M+H] 247.0526, found
247.0529.
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8
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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
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4
4
4
5
5
5
5
5
5
5
5
5
5
6
4-(3-Phenylprop-2-ynyloxy)furan-2(5H)-one (1r). Purified by a flash column chromatography on silica gel with
petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1e (343 mg) with a yield of 80%; white solid;
1
Mp 96.9–97.6 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.50 (dd, J = 8.0, 1.5 Hz, 2H), 7.43 (dt, J = 14.1, 6.1 Hz, 2H), 5.51
) δ 179.2, 172.9, 131.7, 129.5, 128.9, 121.0, 89.8, 88.1, 82.5,
7.5, 60.7; IR (thin film, cm ) 3424, 2926, 2854, 1775, 1744, 1628, 1489, 1443, 1362, 1313, 1234, 1151, 1044.8,
1
3
(
s, 1H), 5.17 (s, 2H); C NMR (150 MHz, DMSO-d
6
−1
6
9
+
54, 884, 768, 695; HRMS (ESI): m/z calcd. for C13
-(3-(4-Chlorophenyl)prop-2-ynyloxy)furan-2(5H)-one (1s). Purified by a flash column chromatography on silica
gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1s (448 mg) with a yield of 90%;
11 3
H O [M+H] 215.0708, found 215.0711.
4
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
white solid; Mp 91.7–93.5 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.53 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 5.51
s, 1H), 5.17 (s, 2H), 4.82 (s, 2H); C NMR (150 MHz, DMSO-d ) δ 179.1, 172.9, 134.3, 133.5, 129.1, 119.9, 89.9,
6.9, 83.6, 67.4, 60.6; IR (thin film, cm ) 3286, 3250, 2980, 2944, 1745, 1689, 1526, 1456, 1385, 1361, 1259,
1
3
(
6
−1
8
1
+
110, 1050, 953, 799, 638; HRMS (ESI): m/z calcd. for C13
-(3-(3-Chlorophenyl)prop-2-ynyloxy)furan-2(5H)-one (1t). Purified by a flash column chromatography on silica
gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 1t (249 mg) with a yield of 50%;
3
H10ClO [M+H] 249.0318, found 249.0323.
4
1
6
white solid; Mp 70.1–72.0 °C; H NMR (600 MHz, DMSO-d ) δ 7.58 (s, 1H), 7.52 (d, J = 7.7 Hz, 1H), 7.45 (dt, J =
13
1
1
1
C
6
5.4, 7.6 Hz, 2H), 5.53 (s, 1H), 5.18 (s, 2H), 4.82 (s, 2H); C NMR (150 MHz, DMSO-d ) δ 179.1, 172.8, 133.4,
−1
31.1, 130.7, 130.4, 129.6, 122.9, 90.0, 86.5, 83.8, 67.4, 60.5; IR (thin film, cm ) 3426, 3100, 2923, 1780, 1746,
626, 1472, 1444, 1357, 1318, 1244, 1156, 1044, 958, 885, 828, 787, 714, 682; HRMS (ESI): m/z calcd. for
+
13
H
10ClO
3
[M+H] 249.0318, found 249.0322.
General Procedures for the Preparation of Biaryl Derivatives (2, 2a-2n). To a solution of the substrates 1,
a-1n (0.05 mmol) and Ph PAuNTf (0.0025 mmol, 2 mg) in dry toluene was added dimethyl diacetylenedicar-
1
3
2
boxylate (0.015 mmol, 2 mg) under a nitrogen atmosphere. The reaction mixture was reacted under the
irradiation of microwave at 120 °C for 2 h. The solvent was removed in vacuo and the residue was purified by a
flash column chromatography to afford the products 2, 2a-2n.
Dimethyl-7-(4-(isopropoxycarbonyl)phenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the
1
product 2 (14 mg) with a yield of 68%; white solid; Mp 162.3–163.5 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.38 (s,
1H), 8.09 (d, J = 8.3 Hz, 2H), 7.83 (d, J = 8.3 Hz, 2H), 5.70 (s, 2H), 5.25–5.10 (m, 1H), 3.92 (d, J = 5.6 Hz, 6H), 1.35
1
3
(d, J = 6.2 Hz, 7H); C NMR (150 MHz, DMSO-d
6
) δ 167.8, 165.5, 164.7, 164.1, 149.8, 134.0, 136.4, 134.5, 132.2,
−1
130.6, 129.9, 128.4, 128.1, 123.6, 69.9, 68.5, 53.2, 52.9, 21.6; IR (thin film, cm ) 3434, 2923, 1775, 1742, 1383,
+
21 8
1275, 1133, 1101, 1017, 798, 710; HRMS (ESI): m/z calcd. for C22H O [M+H] 413.1230, found 413.1248.
Dimethyl-7-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2a). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2a (10 mg)
1
with a yield of 60%; white solid; Mp 185.0–186.3 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.31 (s, 1H), 7.74 (dd, J = 8.8,
) δ 167.9,
65.6, 164.2, 162.6 (d, J = 247.1 Hz), 149.5, 136.5, 134.4, 132.1 (d, J = 3.1 Hz), 131.7, 130.3 (d, J = 8.5 Hz), 128.0,
13
5
1
1
8
.3 Hz, 2H), 7.40 (t, J = 8.8 Hz, 2H), 5.69 (s, 2H), 3.91 (d, J = 4.9 Hz, 6H); C NMR (150 MHz, DMSO-d
6
−1
23.4, 116.3 (d, J = 21.7 Hz), 69.9, 53.1, 52.8; IR (thin film, cm ) 3446, 1767, 1738, 1783, 1286, 1258, 1134, 978,
-
46, 795, 620; HRMS (ESI): m/z calcd. for C18
Dimethyl-7-(4-chlorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2b). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2b (11 mg)
12 6
H O F [M-H] 343.0623, found 343.0630.
1
with a yield of 62%; white solid; Mp 191.2–193.0 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.33 (s, 1H), 7.71 (d, J = 8.4
13
Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 5.69 (s, 2H), 3.91 (d, J = 6.0 Hz, 6H); C NMR (150 MHz, DMSO-d ) δ 167.9, 165.6,
6
−1
1
3
3
64.1, 149.6, 136.2, 134.5, 134.4, 134.1, 131.9, 129.9, 129.3, 128.1, 123.4, 69.9, 53.1, 52.8; IR (thin film, cm )
-
12 6
427, 1772, 1743, 1723, 1256, 1220, 1135, 1092, 1012, 979, 797; HRMS (ESI): m/z calcd. for C18H O Cl [M-H]
59.0327, found 359.0329.
Dimethyl-7-(4-(methoxycarbonyl)phenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2c). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the
1
product 2c (12 mg) with a yield of 62%; white solid; Mp 159.9–161.1 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.38 (s,
6
H), 8.11 (d, J = 8.3 Hz, 2H), 7.84 (d, J = 8.3 Hz, 2H), 5.71 (s, 2H), 4.00–3.79 (m, 9H); C NMR (150 MHz, DMSO-d )
13
1
δ 167.8, 165.8, 165.5, 164.1, 149.8, 140.1, 136.3, 134.6, 132.2, 130.0, 128.5, 128.1, 123.6, 69.9, 53.1, 52.9, 52.4;
−1
IR (thin film, cm ) 3447, 2922, 1771, 1734, 1437, 1288, 1220, 1138, 801, 769, 709; HRMS (ESI): m/z calcd. for
-
C
20
H
15
O
8
[M-H] 383.0772, found 383.0773.
Dimethyl-3-oxo-7-phenyl-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2d). Purified by
a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 2d (11 mg)
1
with a yield of 70%; white solid; Mp 177.6–178.9 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.32 (s, 1H), 7.67 (d, J = 7.4
1
3
Hz, 2H), 7.59–7.41 (m, 3H), 5.70 (s, 2H), 3.91 (d, J = 6.9 Hz, 6H); C NMR (150 MHz, DMSO-d ) δ 168.0, 165.7,
6
−1
164.2, 149.5, 137.5, 135.6, 134.4, 131.6, 129.3, 129.2, 128.0, 127.9, 123.4, 70.0, 53.1, 52.8; IR (thin film, cm )
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-
13 6
3425, 1768, 1745, 1384, 1282, 1255, 1217, 1129, 1004, 706; HRMS (ESI): m/z calcd. for C18H O [M-H] 325.0717,
found 325.0719.
Dimethyl-7-(3-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2e). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2e (10 mg)
1
with a yield of 55%; white solid; Mp 189.2–190.7 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.35 (s, 1H), 7.67–7.55 (m,
1
3
2
H), 7.54–7.43 (m, 1H), 7.36 (td, J = 8.3, 2.0 Hz, 1H), 5.72 (s, 2H), 3.91 (d, J = 5.5 Hz, 6H); C NMR (150 MHz,
6
DMSO-d ) δ 167.9, 165.5, 164.1, 162.5 (d, J = 244.9 Hz), 149.7, 137.9 (d, J = 8.0 Hz), 136.2 (d, J = 2.2 Hz), 134.7,
1
5
32.1, 131.4 (d, J = 8.5 Hz), 128.1, 124.3 (d, J = 2.7 Hz), 123.4, 116.0 (d, J = 21.0 Hz), 115.0 (d, J = 22.6 Hz), 69.9,
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
3.1, 52.9; IR (thin film, cm ) 3432, 1768, 1720, 1432, 1383, 1294, 1258, 1206, 1013, 792; HRMS (ESI): m/z calcd.
+
14 6
for C18H O F [M+H] 345.0768, found 345.0777.
Dimethyl-7-(3-chlorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2f). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2f (10 mg)
1
with a yield of 55%; white solid; Mp 192.9–194.3 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.34 (s, 1H), 7.78 (s, 1H),
) δ 167.9, 165.5, 164.1,
49.7, 137.7, 136.0, 134.7, 134.0, 132.1, 131.1, 129.1, 128.1, 127.8, 126.8, 123.4, 69.8, 53.1, 52.9; IR (thin film,
1
3
7
1
.69–7.54 (m, 3H), 5.71 (s, 2H), 3.91 (d, J = 6.1 Hz, 6H); C NMR (150 MHz, DMSO-d
6
−1
cm ) 3432, 1771, 1744, 1724, 1429, 1286, 1253, 1218, 1154, 1086, 975, 796; HRMS (ESI): m/z calcd. for
-
C
18
H
12
O
6
Cl [M-H] 359.0327, found 359.0330.
Dimethyl-3-oxo-7-(m-tolyl)-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2g). Purified by
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2g (7 mg)
a
flash column
1
6
with a yield of 40%; white solid; Mp 169.3–170.7 °C; H NMR (600 MHz, DMSO-d ) δ 8.31 (s, 1H), 7.54–7.39 (m,
13
3
1
5
H), 7.33 (d, J = 6.9 Hz, 1H), 5.70 (s, 2H), 3.91 (d, J = 4.2 Hz, 6H), 2.41 (s, 3H); C NMR (150 MHz, DMSO-d
6
) δ
68.0, 165.7, 164.2, 149.5, 138.8, 137.6, 135.6, 134.3, 131.5, 129.8, 129.2, 128.5, 128.0, 125.0, 123.4, 70.0, 53.1,
−1
2.8; IR (thin film, cm ) 3433, 1769, 1751, 1429, 1384, 1263, 1205, 1084, 1017, 798, 713; HRMS (ESI): m/z calcd.
-
15 6
for C19H O [M-H] 339.0874, found 339.0875.
Dimethyl-7-(2-chlorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2h). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 2h (10 mg)
1
with a yield of 58%; white solid; Mp 186.2–187.1 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.24 (s, 1H), 7.68 (dd, J = 7.9,
1.1 Hz, 1H), 7.59 (dd, J = 7.4, 1.8 Hz, 1H), 7.54 (dd, J = 7.8, 1.9 Hz, 1H), 7.52 (dd, J = 7.4, 1.3 Hz, 1H), 5.42 (s, 2H),
1
3
3.93 (s, 3H), 3.89 (s, 3H); C NMR (150 MHz, DMSO-d
6
) δ 167.8, 165.5, 164.0, 150.7, 136.2, 135.0, 134.0, 132.4,
−1
131.4, 131.1, 130.9, 130.1, 127.9, 127.5, 123.2, 69.5, 53.2, 52.9; IR (thin film, cm ) 3429, 1769, 1752, 1723, 1278,
-
12 6
1262, 1214, 1157, 1133, 1055, 974; HRMS (ESI): m/z calcd. for C18H O Cl [M-H] 359.0327, found 359.0329.
Dimethyl-7-(2-(ethoxycarbonyl)phenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2i). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (6:1) as an eluent to give the
1
product 2i (9 mg) with a yield of 47%; white solid; Mp 129.2–130.1 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.04 (d, J =
8
2
1
.0 Hz, 1H), 7.74 (d, J = 7.5 Hz, 1H), 7.67 (d, J = 7.7 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 5.30 (s, 2H), 4.05 (q, J = 7.1 Hz,
1
3
H), 3.92 (s, 3H), 3.87 (s, 3H), 0.96 (t, J = 7.1 Hz, 3H); C NMR (150 MHz, DMSO-d
6
) δ 167.9, 165.9, 165.6, 164.1,
50.2, 138.0, 136.1, 134.8, 132.7, 131.8, 130.6, 130.4, 129.4, 127.6, 122.4, 69.3, 60.9, 53.1, 52.9; IR (thin film,
−
1
-
cm ) 3440, 1772, 1722, 1435, 1333, 1284, 1152, 1133, 1071, 800; HRMS (ESI): m/z calcd. for C21
97.0928, found 397.0931.
Dimethyl-7-(3-chloro-4-methylphenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2j). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the
17 8
H O [M-H]
3
1
6
product 2j (9 mg) with a yield of 47%; white solid; Mp 132.3–133.9 °C; H NMR (600 MHz, DMSO-d ) δ 8.32 (s,
1
3
1
H), 7.75 (d, J = 1.5 Hz, 1H), 7.64–7.41 (m, 2H), 5.70 (s, 2H), 3.91 (d, J = 4.1 Hz, 6H), 2.41 (s, 3H); C NMR (150
MHz, DMSO-d ) δ 167.9, 165.6, 164.2, 149.6, 136.6, 136.0, 135.1, 134.5, 134.2, 132.0, 131.9, 128.1, 126.7, 123.4,
9.9, 53.1, 52.9, 19.4; IR (thin film, cm ) 3434, 2922, 1768, 1725, 1432, 1253, 1218, 1134, 981, 796; HRMS (ESI):
6
−1
6
-
14 6
m/z calcd. for C19H O Cl [M-H] 373.0484, found 373.0485.
Dimethyl-7-(3,4-dichlorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2k). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 2k
1
(
9 mg) with a yield of 45%; white solid; Mp 167.4–169.1 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.36 (s, 1H), 7.99 (d, J
13
=
2.1 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.67 (dd, J = 8.3, 2.2 Hz, 1H), 5.70 (s, 2H), 3.91 (d, J = 4.9 Hz, 6H); C NMR
(
150 MHz, DMSO-d ) δ 167.8, 165.5, 164.1, 149.8, 136.2, 135.1, 134.8, 132.3, 132.1, 132.1, 131.3, 130.0, 128.4,
6
−1
1
28.1, 123.4, 69.8, 53.1, 52.9; IR (thin film, cm ) 3433, 1780, 1739, 1432, 1282, 1267, 1128, 1082, 1011; HRMS
-
(
ESI): m/z calcd. for C18
Dimethyl-7-(4-chloro-3-(methoxycarbonyl)phenyl)-3-oxo-1,3-dihydroiso-benzofuran-4,5-dicarboxylate
Purified by a flash column chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to
11 6 2
H O Cl [M-H] 392.9938, found 392.9939.
(2l).
) δ
1
give the product 2l (14 mg) with a yield of 66%; white solid; Mp 184.6–186.1 °C; H NMR (600 MHz, DMSO-d
8.36 (s, 1H), 8.05 (d, J = 2.3 Hz, 1H), 7.87 (dd, J = 8.4, 2.4 Hz, 1H), 7.76 (d, J = 8.3 Hz, 1H), 5.69 (s, 2H), 3.99–3.84
6
1
3
6
(m, 9H); C NMR (150 MHz, DMSO-d ) δ 167.8, 165.5, 165.2, 164.1, 149.8, 135.3, 134.8, 134.6, 132.4, 132.24,
ACS Paragon Plus Environment

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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
132.21, 131.5, 131.2, 130.3, 128.1, 123.4, 69.8, 53.1, 52.9, 52.8; IR (thin film, cm ) 3446, 1779, 1733, 1630, 1383,
-
14 8
1292, 1244, 1216, 1089, 1014; HRMS (ESI): m/z calcd. for C20H O Cl [M-H] 417.0382, found 417.0384.
Dimethyl-7-(naphthalen-1-yl)-3-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2m). Purified by a column
chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 2m (12
1
mg) with a yield of 63%; white solid; Mp 177.8–179.2 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.26 (s, 1H), 8.16–7.97
(
m, 2H), 7.75–7.56 (m, 4H), 7.52 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 5.43 (d, J = 13.8 Hz, 1H), 5.14 (d, J = 14.2 Hz, 1H),
1
3
3
1
3
.96 (s, 3H), 3.87 (s, 3H); C NMR (150 MHz, DMSO-d
6
) δ 168.1, 165.7, 164.2, 151.2, 136.3, 136.3, 133.4, 133.00,
−1
32.03, 130.1, 129.4, 128.6, 127.6, 127.2, 127.2, 126.5, 125.6, 124.7, 123.5, 69.6, 53.1, 52.9; IR (thin film, 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
+
15 6
431, 1779, 1745, 1582, 1442, 1262, 1154, 971, 802, 777; HRMS (ESI): m/z calcd. for C22H O [M-H] 375.0874,
found 375.0874.
Dimethyl-3-oxo-7-(1-tosyl-1H-pyrrol-2-yl)-1,3-dihydroisobenzofuran-4,5-dicarboxylate (2n). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (6:1) as an eluent to give the product 2n
1
(
(
16 mg) with a yield of 68%; white solid; Mp 188.2–189.7 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.00 (s, 1H), 7.68
dd, J = 3.3, 1.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 6.66 (dd, J = 3.3, 1.6 Hz, 1H), 6.54 (t, J = 3.4
13
6
Hz, 1H), 5.11 (s, 2H), 3.94 (s, 3H), 3.90 (s, 3H), 2.35 (s, 3H); C NMR (150 MHz, DMSO-d ) δ 167.6, 165.4, 163.9,
1
2
51.3, 145.9, 137.3, 134.2, 132.5, 130.2, 127.9, 127.7, 126.7, 126.7, 126.4, 122.8, 118.6, 113.8, 69.4, 53.2, 52.9,
−1
1.0; IR (thin film, cm ) 3446, 2954, 2922, 1778, 1731, 1594, 1434, 1369, 1282, 1150, 669, 590, 541; HRMS (ESI):
-
m/z calcd. for C23
H
18NO
8
S [M-H] 468.0758, found 468.0762.
General Procedures for the Preparation of Biaryls (3a-3h). To a solution of the substrates 1,1b,1c,1j,1l,1m
0.05 mmol) in anhydrous toluene Ph PAuNTf (0. 0025 mmol, 2 mg) was added under a nitrogen atmosphere.
(
3
2
Then the dienophiles (0.015 mmol) were added. The reaction mixture was irradiated under microwave at 120 °C
for 2 h. The solvent was removed in vacuo and the residue was purified by a flash column chromatography to
afford the products 3a-3h.
Methyl-7-(4-chlorophenyl)-3-oxo-1,3-dihydroisobenzofuran-4-carboxylate (3a). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 3a (6 mg)
1
with a yield of 40%; white solid; Mp 165.0–166.2 °C; H NMR (600 MHz, DMSO-d
6
1
) δ 7.94 (d, J = 7.7 Hz, 1H), 7.85
3
(s, 1H), 7.68 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 5.60 (s, 2H), 3.90 (s, 3H); C NMR (150 MHz, DMSO-d
6
) δ
−
1
168.0, 166.2, 145.9, 137.2, 135.3, 133.8, 133.6, 130.2, 129.9, 129.2, 129.0, 122.9, 69.4, 52.7; IR (thin film, cm )
-
10 4
3495, 2921, 1767, 1725, 1432, 1283, 1199, 1055, 1002, 833, 758; HRMS (ESI): m/z calcd. for C16H O Cl [M-H]
301.0273, found 301.0273.
Methyl-7-(4-(methoxycarbonyl)phenyl)-3-oxo-1,3-dihydroisobenzofuran-4-carboxylate (3b). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (8:1) as an eluent to give the product 3b
1
(
7 mg) with a yield of 45%; white solid; Mp 150.3–151.6 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.21–8.05 (m, 2H),
1
3
8
.01 (d, J = 7.7 Hz, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.84–7.71 (m, 2H), 5.63 (s, 2H), 3.90 (d, J = 4.4 Hz, 6H); C NMR
(
150 MHz, DMSO-d ) δ 168.0, 166.1, 165.8, 146.1, 141.0, 137.2, 133.8, 130.6, 129.9, 129.7, 129.0, 128.4, 122.9,
6
−1
6
9.4, 52.7, 52.4; IR (thin film, cm ) 3436, 2923, 1767, 1741, 1713, 1292, 1116, 1052, 756; HRMS (ESI): m/z calcd.
-
13 6
for C18H O [M-H] 325.0717, found 325.0720.
Methyl-7-(4-(isopropoxycarbonyl)phenyl)-3-oxo-1,3-dihydroisobenzofuran-4-carboxylate (3c). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the
1
product 3c (7 mg) with a yield of 39%; white solid; Mp 142.7–143.5 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.08 (d, J =
8
3
1
1
.3 Hz, 2H), 7.99 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.80 (d, J = 8.3 Hz, 2H), 5.62 (s, 2H), 5.24–5.09 (m, 1H),
1
3
.91 (s, 3H), 1.35 (d, J = 6.2 Hz, 6H); C NMR (150 MHz, DMSO-d
6
) δ 168.0, 166.1, 164.8, 146.1, 140.9, 137.3,
−1
33.8, 130.5, 130.3, 129.8, 129.0, 128.4, 122.9, 69.4, 68.4, 52.7, 21.6; IR (thin film, cm ) 3434, 1772, 1713, 1628,
-
384, 1278, 1116, 757; HRMS (ESI): m/z calcd. for C20
Methyl-7-(3-chloro-4-methylphenyl)-3-oxo-1,3-dihydroisobenzofuran-4-carboxylate (3d). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 3d
17 6
H O [M-H] 353.1030, found 353.1032.
1
(
6
8 mg) with a yield of 50%; white solid; Mp 186.8–187.9 °C; H NMR (600 MHz, DMSO-d ) δ 7.95 (d, J = 7.7 Hz,
13
1
H), 7.83 (d, J = 7.7 Hz, 1H), 7.71 (s, 1H), 7.52 (s, 2H), 5.62 (s, 2H), 3.90 (s, 3H), 2.40 (s, 3H); C NMR (150 MHz,
6
DMSO-d ) δ 168.1, 166.1, 146.0, 137.0, 136.3, 135.9, 134.1, 133.7, 131.9, 130.1, 129.0, 128.1, 126.7, 122.8, 69.4,
−1
5
2.7, 19.4; IR (thin film, cm ) 3426, 2922, 1765, 1726, 1638, 1383, 1297, 1135, 1019; HRMS (ESI): m/z calcd. for
-
C
17
H
12
O
4
Cl [M-H] 315.0429, found 315.0431.
Methyl-7-(naphthalen-1-yl)-3-oxo-1,3-dihydroisobenzofuran-4-carboxylate (3e). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (7:1) as an eluent to give the product 3e (9 mg)
1
with a yield of 55%; white solid; Mp 150.9–152.5 °C; H NMR (600 MHz, DMSO-d
6
) δ 8.06 (dd, J = 11.7, 4.3 Hz,
2
H), 7.88 (dd, J = 29.0, 7.6 Hz, 2H), 7.66–7.62 (m, 1H), 7.62–7.57 (m, 3H), 7.52 (dd, J = 6.9, 1.5 Hz, 1H), 5.34 (d, J =
1
3
6
13.0 Hz, 1H), 5.03 (d, J = 11.6 Hz, 1H), 3.94 (s, 3H); C NMR (150 MHz, DMSO-d ) δ 168.2, 166.2, 147.5, 137.4,
135.5, 133.9, 133.4, 130.2, 129.1, 128.7, 128.6, 127.1, 126.9, 126.4, 125.6, 124.8, 122.8, 69.0, 52.7; IR (thin film,
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8
9
−
1
-
13 4
cm ) 3437, 1754, 1721, 1638, 1384, 1295, 1141, 1078, 1035, 778; HRMS (ESI): m/z calcd. for C20H O [M-H]
317.0819, found 317.0820.
Methyl-(E)-7-(4-(isopropoxycarbonyl)phenyl)-4-(3-methoxy-3-oxoprop-1-en-1-yl)-3-oxo-1,3-dihydroisobenzofur
an-5-carboxylate (3f). Purified by a flash column chromatography on silica gel with petroleum ether/ethyl acetate
1
(
(
(
10:1) as an eluent to give the product 3f (10 mg) with a yield of 44%; white solid; Mp 167.3–168.9 °C; H NMR
600 MHz, DMSO-d ) δ 8.25 (d, J = 16.3 Hz, 1H), 8.22 (s, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 6.25
d, J = 16.3 Hz, 1H), 5.61 (s, 2H), 5.28–5.08 (m, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 1.35 (d, J = 6.3 Hz, 6H); C NMR (150
) δ 168.8, 166.5, 165.6, 164.7, 148.7, 140.2, 137.3, 135.3, 134.14, 134.11, 132.2, 130.4, 129.8,
6
1
3
MHz, DMSO-d
6
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
1
1
28.4, 125.4, 124.1, 68.7, 68.5, 52.9, 51.9, 21.6; IR (thin film, cm ) 3423, 1772, 1715, 1647, 1434, 1277, 1144,
-
103, 976, 809, 707; HRMS (ESI): m/z calcd. for C24
21 8
H O [M-H] 437.1241, found 437.1243.
Methyl-(E)-7-(3-chlorophenyl)-4-(3-methoxy-3-oxoprop-1-en-1-yl)-3-oxo-1,3-dihydroisobenzofuran-5-carboxylat
e (3g). Purified by a flash column chromatography on silica gel with petroleum ether/ethyl acetate (9:1) as an
1
eluent to give the product 3g (11 mg) with a yield of 55%; white solid; Mp 161.6–163.3 °C; H NMR (600 MHz,
6
DMSO-d ) δ 8.25 (d, J = 16.3 Hz, 1H), 8.19 (s, 1H), 7.75 (d, J = 0.8 Hz, 1H), 7.62 (dd, J = 3.8, 2.1 Hz, 1H), 7.57 (dd, J
13
=
1
1
6
3.8, 1.4 Hz, 2H), 6.25 (d, J = 16.3 Hz, 1H), 5.62 (s, 2H), 3.87 (s, 3H), 3.77 (s, 3H); C NMR (150 MHz, DMSO-d ) δ
68.8, 166.5, 165.6, 148.7, 137.9, 137.3, 135.0, 134.3, 134.0, 133.9, 132.2, 131.1, 128.9, 127.7, 126.7, 125.4,
−1
24.0, 68.6, 52.9, 51.9; IR (thin film, cm ) 3438, 1770, 1723, 1632, 1384, 1276, 1115, 1034, 618; HRMS (ESI): m/z
-
calcd. for C20
H
14
O
6
Cl [M-H] 385.0484, found 385.0486.
Methyl-(E)-7-(4-chloro-3-(methoxycarbonyl)phenyl)-4-(3-methoxy-3-oxoprop-1-en-1-yl)-3-oxo-1,3-dihydroisobe
nzofuran-5-carboxylate (3h). Purified by a flash column chromatography on silica gel with petroleum ether/ethyl
1
acetate (7:1) as an eluent to give the product 3h (11 mg) with a yield of 48%; white solid; Mp 129.3–130.5 °C; H
6
NMR (600 MHz, DMSO-d ) δ 8.25 (d, J = 16.3 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J = 2.3 Hz, 1H), 7.90–7.82 (m, 1H), 7.75
1
3
(
d, J = 8.4 Hz, 1H), 6.25 (d, J = 16.3 Hz, 1H), 5.61 (s, 2H), 3.90 (s, 3H), 3.87 (s, 3H), 3.77 (s, 3H); C NMR (150 MHz,
6
DMSO-d ) δ 168.8, 166.5, 165.6, 165.2, 148.8, 137.2, 135.0, 134.2, 134.2, 134.1, 132.3, 132.2, 131.5, 131.2, 130.3,
−
1
1
25.4, 124.0, 109.5, 68.6, 52.9, 52.8, 51.9; IR (thin film, cm ) 3435, 2922, 1761, 1734, 1431, 1383, 1245, 1140,
-
16 8
1045; HRMS (ESI): m/z calcd. for C22H O Cl [M-H] 443.0539, found 443.0541.
General Procedures for the Preparation of Biaryl Derivatives (4a-4f). To a solution of the substrates 1o-1t
(0.05 mmol) in dry toluene, Ph PAuNTf (0. 0025 mmol, 2 mg) was added under a nitrogen atmosphere. Then
3
2
DMAD (0.015 mmol, 2 mg) were added into the mixture. The reaction mixture was reacted under the irradiation
of microwave at 120 °C for 2 h. The solvent was removed in vacuo and the residue was purified by a flash column
chromatography to afford the products 4a-4f.
Dimethyl 1-oxo-7-phenyl-2,3-dihydro-1H-indene-4,5-dicarboxylate (4a). Purified by
a
flash column
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4a (7 mg)
1
6
with a yield of 45%; yellow solid; Mp 146.3–147.8 °C; H NMR (600 MHz, DMSO-d ) δ 7.64 (s, 1H), 7.47 (dd, J =
1
3
6
.6, 3.0 Hz, 2H), 7.45–7.42 (m, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.18–3.15 (m, 2H), 2.72–2.68 (m, 2H); C NMR (150
6
MHz, DMSO-d ) δ 204.0, 166.5, 166.2, 154.9, 142.3, 136.3, 135.6, 134.1, 129.8, 129.6, 129.3, 128.5, 127.9, 53.1,
−1
5
6
2.9, 36.5, 24.3; IR (thin film, cm ) 3426, 2923, 2853, 1773, 1715, 1441, 1383, 1331, 1289, 1160, 1066, 986, 781,
+
18; HRMS (ESI): m/z calcd. for C19
Dimethyl 7-(4-chlorophenyl)-1-oxo-2,3-dihydro-1H-indene-4,5-dicarboxylate (4b). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4b (12
17 5
H O [M+H] 325.1076, found 325.1083.
1
mg) with a yield of 67%; yellow solid; Mp 89.1–90.1 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.65 (s, 1H), 7.50 (s, 4H),
.89 (s, 3H), 3.87 (s, 3H), 3.18–3.14 (m, 2H), 2.72–2.68 (m, 2H); C NMR (150 MHz, DMSO-d ) δ 204.1, 166.5,
66.1, 154.9, 140.8, 135.7, 135.0, 134.2, 133.4, 131.2, 129.9, 129.7, 127.9, 53.1, 52.8, 36.5, 24.3; IR (thin film,
1
3
3
1
6
−1
cm ) 3425, 2953, 2854, 1722, 1436, 1384, 1293, 1225, 1126, 1110, 1069, 979, 840, 798, 726; HRMS (ESI): m/z
+
5
calcd. for C19H16ClO [M+H] 359.0686, found 359.0697.
Dimethyl 7-(3-chlorophenyl)-1-oxo-2,3-dihydro-1H-indene-4,5-dicarboxylate (4c). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4c (7 mg)
1
with a yield of 37%; yellow solid; Mp 90.3–91.7 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.67 (s, 1H), 7.55 (t, J = 1.7 Hz,
1
H), 7.51–7.49 (m, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.42 (dt, J = 7.5, 1.4 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 3.19–3.13
13
(
m, 2H), 2.74–2.67 (m, 2H); C NMR (150 MHz, DMSO-d
6
) δ 204.0, 166.4, 166.0, 154.8, 140.4, 138.2, 135.7,
−1
1
1
34.1, 132.4, 130.1, 129.8, 129.1, 128.3, 128.0, 53.1, 52.8, 36.5, 24.3; IR (thin film, cm ) 3422, 2924, 2853, 1718,
+
5
591, 1562, 1465, 1442, 1312, 1123, 1048, 961, 849, 783; HRMS (ESI): m/z calcd. for C19H16ClO [M+H] 359.0686,
found 359.0689.
Dimethyl 1-oxo-7-phenyl-1,3-dihydroisobenzofuran-4,5-dicarboxylate (4d). Purified by
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4d (10
a
flash column
1
mg) with a yield of 62%; light yellow solid; Mp 102.8–104.2 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.74 (s, 1H), 7.59
13
(dd, J = 6.5, 3.0 Hz, 2H), 7.50–7.47 (m, 3H), 5.57 (s, 2H), 3.90 (s, 3H), 3.88 (s, 3H); C NMR (150 MHz, DMSO-d ) δ
6
168.1, 167.3, 164.3, 149.7, 145.2, 138.4, 134.7, 130.2, 129.7, 129.1, 128.1, 123.9, 122.2, 69.4, 53.2, 53.1; IR (thin
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2
2
2
2
2
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3
3
3
3
3
3
3
3
3
3
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4
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−
1
film, cm ) 3286, 3251, 2981, 2854, 1737, 1689, 1526, 1459, 1384, 1259, 1179, 1110, 1051, 927, 794, 593; HRMS
+
15 6
(ESI): m/z calcd. for C18H O [M+H] 327.0869, found 327.0874.
Dimethyl 7-(4-chlorophenyl)-1-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (4e). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4e (11
1
mg) with a yield of 61%; white solid; Mp 134.5–135.8 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.76 (s, 1H), 7.62 (d, J =
) δ 168.1,
67.2, 164.3, 149.7, 143.7, 138.4, 134.2, 133.4, 131.6, 130.1, 128.1, 124.0, 122.5, 69.5, 53.16, 53.12; IR (thin film,
1
3
8
1
.5 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H), 5.57 (s, 2H), 3.90 (s, 3H), 3.88 (s, 3H); C NMR (150 MHz, DMSO-d
6
−1
cm ) 3425, 2954, 2854, 1722, 1436, 1384, 1293, 1225, 1110, 1069, 979, 840, 798, 726, 692; HRMS (ESI): m/z:
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
+
6
calcd for C18H14ClO [M+H] 361.0479, found 361.0485.
Dimethyl 7-(3-chlorophenyl)-1-oxo-1,3-dihydroisobenzofuran-4,5-dicarboxylate (4f). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give the product 4f (12
1
mg) with a yield of 65%; white solid; Mp 169.9–171.6 °C; H NMR (600 MHz, DMSO-d
6
) δ 7.80 (s, 1H), 7.70 (t, J =
1
3
1
.7 Hz, 1H), 7.57–7.54 (m, 2H), 7.52 (d, J = 7.6 Hz, 1H), 5.57 (s, 2H), 3.90 (s, 3H), 3.88 (s, 3H); C NMR (150 MHz,
6
DMSO-d ) δ 168.0, 167.1, 164.2, 149.5, 143.2, 138.4, 136.6, 132.6, 130.2, 129.9, 129.4, 128.9, 128.3, 124.2, 122.8,
−1
6
9.4, 53.1; IR (thin film, cm ) 3426, 2923, 2853, 1773, 1715, 1441, 1383, 1331, 1289, 1150, 1066, 986, 780, 618;
+
6
HRMS (ESI): m/z calcd. for C18H14ClO [M+H] 361.0479, found 361.0459.
Associate Content
1
13
The Supporting Information is available free of charge on the ACS Publications website. H and C NMR spectra
for all compounds and computational details for proposed mechanism (PDF)
Author Information
Corresponding Author
Email: randybinlin@gmail.com, yongxiang.liu@syphu.edu.cn.
ORCID
Shengfei Jin: 0000-0001-9349-7332
Yongxiang Liu: 0000-0003-0364-0137
Notes
The authors declare no competing financial interest.
Acknowledgments
We thank the program for innovative research team of the Ministry of Education and the program for Liaoning
innovative research team in university.
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