A Copper-Catalyzed Formal [3 + 2]-Cycloaddition for the Synthesis of All Different Aryl-Substituted Furans and Thiophenes

Article abstract of DOI:10.1021/acs.joc.5b01139

A highly efficient formal [3 + 2]-cycloaddition was established using a copper catalyst. The resulting dihydrofurans were subjected to oxidation followed by arylations to produce tetraarylfurans. In addition, the dihydrofuran can be converted to diaryldih

Full text of DOI:10.1021/acs.joc.5b01139

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Article
A copper catalyzed Formal [3+2]-Cycloaddition for the
Synthesis of All Different Aryl-Substituted Furan and Thiophene
Shingo Ishikawa, Yushi Noda, Masaru Wada, and Takashi Nishikata
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01139 • Publication Date (Web): 09 Jul 2015
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A copper catalyzed Formal [3+2]-Cycloaddition for the
Synthesis of All Different Aryl-Substituted Furan and
Thiophene
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Shingo Ishikawa, Yushi Noda, Masaru Wada and Takashi Nishikata*
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Graduate School of Science and Engineering, Yamaguchi University, 2ꢀ16ꢀ1 Tokiwadai, Ube,
Yamaguchi, 755ꢀ8611, Japan.
ABSTRACT: A highly efficient formal [3+2] cycloaddition was established using a copper
catalyst. The resulting dihydrofurans were subjected to oxidation followed by arylations
to produce tetraaryl furans. In addition, the dihydrofuran can be converted to diaryl
dihydrothiophene by using Lawesson’s reagent. This protocol will facilitate the
synthesis of all different aryl-substituted furan and thiophene.
INTRODUCTION
Multiply substituted furans are valuable molecules because various bioactive compounds contain furan
units1,2. Although numerous methods of synthesizing substituted furans have been developed3,4, synthetic
methods for accessing possible isomers of a furan are not currently well developed, because unlike thiophenes
and other heteroaromatics5, the regioselective substitution of a furan is very difficult. We herein report an
efficient synthetic protocol for preparing various arylꢀsubstituted furans 5 via the cycloaddition of styrene 1
followed by sequential arylations (Scheme 1).
Scheme 1. The synthesis of various aryl-substituted furans 5
Br
CO2Me
2
Ar"
Ar
Ar"
Ar
Ar"'
Ar'
CO2Me
CO2Me
[O]
O
Ar'
Ar
Ar
1
Ar'
Ar'
O
3
O
5
O
4
cycloaddition
arylation
arylation
The goal of our current protocol is to successfully achieve a formal [3+2] cycloaddition of styrenes 1 and
ketoesters 2 to produce dihydrofurans 36. Dihydrofurans or furan derivatives have been synthesized in the past
by reacting 1,3ꢀdicarbonyl compounds in the presence or absence of a large excess of metal salts7,8. Traditional
methods such as the Paal–Knorr synthesis9 are reliable for the synthesis of various furans and their related
rings. In addition, radical reactions are one of the most convenient protocols for the synthesis of dihydrofurans
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and furan derivatives. For example, Lei’s group recently reported on a methodology that employs iodine as a
catalyst for the synthesis of dihydrofurans and furans8a,b. Hajra’s group also synthesized furans from
βꢀnitrostyrenes or α,β−unsaturated carbonyl compounds8c,d. Flowers’ group successively obtained substituted
furans using Ce(IV)8e. Conversely, during the course of our research in atom transfer radical reactions10, we
discovered that a copper catalyst is extremely effective at promoting the formal [3+2] cycloaddition reaction of
styrene and 2ꢀbromoketoesters (Scheme 2). We hypothesize that this reaction undergoes a typical atomꢀtransfer
radical reaction via intermediate A (Scheme 3)11. Previous results demonstrated that the reaction starts with the
generation of alkyl radical species A from the reaction between Cu(I) and 210b. After the generation of A, the
addition of A to 1 gives radical intermediate B. Intermediate B can either react with a Cu(II) salt to produce
intermediate C or be oxidized by the Cu(II) species to produce intermediate C’ with the concomitant formation
of a Cu(I) species to complete the catalytic cycle. The generation of C or C’ is somewhat controversial in this
radical chemistry. Intermediate C or C’ undergoes intramolecular cyclization to give the desired product 3.
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Scheme 2. A formal [3+2] cycloaddition catalyzed by a copper salt.
Scheme 3. Proposed mechanism.
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RESULTS&DISCUSSION
In our initial experiments, 16% yield of dihydrofuran 3a was obtained when bromoketoester 2a was
employed for the reaction (Table 1 entry 1). During the reaction, 1a and 2a were consumed due to the
generation of the corresponding dehalogenated product and polymer. [Cu(Me2S)]Br slightly increased the yield
but other catalysts were not effective (entry 2). Addition of amine was crucial, and iꢀPr2NH gave 3a in 36%
yield. However, other amines, such as tꢀBuMeNH, CyMeNH, tꢀBuNH2, Et3N, iꢀPr2NEt, and pyridine, were not
effective (entry 3). We also tested the effects of ligands, temperature, and ammonium salts but higher yields
were not obtained (entries 4−6). Significant progress was obtained in the solvent screening. CH2Cl2 gave 33%
yield at 60 °C; surprisingly, the yield increased to 87% at 80 °C (entry 7). In this case, all starting materials
were consumed, and longer reaction time was not effective to obtain higher yield. Other solvents, such as
toluene, xylene, and CH2ClCH2Cl, were not effective. The combination of tris(2ꢀpyridylmethyl)amine
(TPMA), Bu4NNO2(TBAꢀNO2), CH2Cl2, and 80°C was crucial to obtain the highest yield. Contrary to our
previous works10, Cu(II) gave the best result among copper catalyst, such as CuI, CuBr, CuCl, and CuI·SMe2.
Generally, bromoesters 2 react with Cu(I) not Cu(II) to produce the corresponding alkyl radical species for the
atom transfer radical addition or polymerization12. To undergo current [3+2] cycloaddition, Cu(II) must be
reduced to Cu(I). But, in this reaction, any reductant, such as lowꢀvalent metals, Sn(II), glucose, hydrazine, and
ascorbic acid, were not used to generate active Cu(I) species from Cu(II) species. Weiss and coꢀworkers have
reported that excess amine can reduce Cu(II) to Cu(I)12. Therefore, iꢀPr2NH could act as a reductant. The effect
of Bu4NNO2 is not clear; however, it may be that the nitrite ion acts as a reducing agent to generate active Cu(I)
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species or it may increase the single electron transfer ability[12]
.
Table 1. Optimizations.
Cu/ligand
amine
O
C
O
CO2Me
OMe
C
Br
+
t-Bu
R
t-Bu
TBABr
R
O
R= -MeOC H
p
6
4
1a
2a
3a
amine
solvent
entry
Cu
CuI
ligand
yield of (%)
3a
1a
2a
3a
4a
16
21
36
35
35
33
87
33
none PMDETA toluene
none PMDETA toluene
[Cu(Me2S)]Br
[Cu(Me2S)]Br
[Cu(Me2S)]Br
none i-Pr2NH
TPMA i-Pr2NH
TPMA i-Pr2NH
TPMA i-Pr2NH
TPMA i-Pr2NH
TPMA i-Pr2NH
toluene
toluene
toluene
toluene
CH2Cl2
CH2Cl2
5a
[Cu(H2O)6](BF4)2
[Cu(H2O)6](BF4)2
[Cu(H2O)6](BF4)2
[Cu(H2O)6](BF4)2
6b,c
7b,c
8a,c
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All reactions were carried out in shield tubes for 20 h in toluene or CH2Cl2 with 10 mol% Cu salt, amine (1.5
equiv.), ligand (0 or 10 mol%), Bu4NBr(or ꢀNO2) (0 or 20 mol%), 1a (1 equiv.) and 2a (2.0 equiv.). Yields
were determined by 1HNMR. a Run at 60°C. b Run at 80°C. c Bu4NNO2 was used instead of Bu4NBr.
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We next examined the substrate scope in [3 + 2] cycloaddition under the optimized conditions shown in
Table 1 (Table 2). There are no reports on successful copperꢀcatalyzed [3 + 2] cycloadditions of styrenes and
2ꢀbromoketoesters to obtain diarylated dihydrofuranes 3; however, our copperꢀTPMA catalyst system realized
the reaction of styrenes and 2ꢀbromoketoesters to produce the corresponding [3 + 2] cycloadducts,
dihydrofurans 3, in moderate to good yields without isomers. 2ꢀBromoketoester derivatives 2 smoothly reacted
with pꢀmethoxystyrene 1a and gave the products 3b–3k. These results demonstrate the broad applicability of
our protocol. Ketoester 2 possessing an adamantyl group gave the corresponding furan derivatives 3b in 91%
yield, and aromatic ketoesters possessing electronꢀdonating or electronꢀwithdrawing groups also afforded the
products 3c, 3d, and 3e in good yields. Ketoesters 2 possessing orthoꢀsubstituted aryl groups leading to 3h and
3i resulted in 78 and 83% yields; however, 2 possessing a more hindered mesityl group and two tertꢀbutyl
groups gave 3j and 3k in 73% and 60% yields, respectively. The reaction with alphaꢀmethylstyrene resulted in
42% yield. The steric bulkiness of 2 tended to decrease the product yields.
Table 2. Regioselective [3+2] cycloadditions
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All reactions were carried out for 20 h at 80 °C in shield tubes with CH2Cl2 10 mol% [Cu(II)(H2O)6](BF4)2, iꢀPr2NH
(1.5 equiv), TPMA (10 mol%), Bu4NꢀNO2 (20 mol%), 2 (1 equiv.) and 4 (2.0 equiv.). Pure compounds 5 were
obtained by GPC and yields were determined by 1H NMR because of inseparable dehalogenated starting material 4
from 5. a (tris[2ꢀ(dimethylamino)ethyl]amine) (Me6TREN, 10 mol%) was added.
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Our next challenge is to develop the synthesis of diarylꢀsubstituted furans 6 from the reaction of 1 and 2. We
attempted to oxidize the crude product 3 with 2,3ꢀdichloroꢀ5,6ꢀdicyanoꢀpꢀbenzoquinone (DDQ) to produce 6.
However, the reaction did not proceed smoothly to completion, and inseparable side products were also
obtained after oxidation. Further reaction optimization conditions revealed that increases in the amount of 1 (or
2) and the reaction temperature (100°C at 4 bar) were very effective for efficiently obtaining the
[3+2]ꢀcycloaddition product 3 in 1 h. The resulting crude product 3 reacted smoothly with DDQ to give the
corresponding furan 6 in high yields. After the simple oxidation of the crude product 3 with DDQ, various
furans 6 with ether, amine, and halogen functional groups (6aꢀg) were obtained in good yields without any
isolation of 3. (Scheme 4).
Scheme 4. Diaryl furan 6 synthesis.
a Isolated yields for 2 steps. b 3 equiv of 1. c 3 equiv of 2 was used. d 2 equiv of 2 was used.
The third arylation of 6 to give 4 was examined via 3) bromination with NꢀBromosuccinimide (NBS) and 4)
Suzuki–Miyaura couplings (Scheme 5). Although the bromination of 3 occurred smoothly to give the
brominated furans (6Br-aꢀd), careful optimization of the following Suzuki–Miyaura couplings was required.
The Suzuki–Miyaura coupling of highly bulky substrates is not easy15. We examined various conditions that
included the modification of solvents, bases, and Pd catalysts such as Pd(OAc)2, PdCl2(PPh3)2, and
PdCl2(P(oꢀtolyl)3). We discovered that PdCl2(dppf) (or PdCl2(tꢀBu2PC6H4(pꢀNMe2))) and Na2CO3(aq) in DMF
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were the best conditions (see SI). These established conditions were suitable for couplings between brominated
furans 6Br and representative arylboronic acids such as pꢀCF3C6H4ꢀ, pꢀClC6H4ꢀ, Ph, and pꢀCH3C6H4B(OH)2.
Under optimized conditions, the trisubstituted furans that possess various aryl groups (4aꢀd) were obtained in
good to excellent yields. We also attempted to obtain direct furan C–H arylations, but no reaction was
observed.
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Finally, the fourth arylation to obtain the desired tetraarylfuran 5 was conducted using 6) Pdꢀcatalyzed
decarboxylative coupling after the 5) hydrolysis of 4 (Scheme 5). The ester groups on the furan rings in 4 were
smoothly hydrolyzed to give their corresponding carboxylic acids in high yields (4OH-aꢀd). Although there are
some reports on decarboxylative couplings, couplings with sterically hindered aromatic groups have not been
extensively investigated4c, 16. We further examined various reaction conditions with different solvents,
additives, and Pd catalysts such as Pd(OAc)2ꢀPCy3, PdCl2(tꢀBu2PC6H4(pꢀNMe2)), PdCl2(PPh3)2, and
PdCl2(DPEphos)2, (see SI). As a result, we developed an efficient decarboxylative coupling reaction of
hydrolyzed 4 with aryl iodides such as pꢀClC6H4ꢀ, pꢀCH3C6H4ꢀ, pꢀFC6H4ꢀ, and pꢀCF3C6H4I in the presence of
PdCl2(dppf) in mesitylene at 170°C. We demonstrated that the styrenes 1 were successfully converted into
various aryl substitutedꢀfurans 5cꢀ5d in a total of 6 steps (from styrene 1) with good yields.
Scheme 5. Tri- and tetraarylfurans
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aPdCl2(tꢀBu2PC6H4(pꢀNMe2)) was used. bPd(OAc)2/PCy3 was used.
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Our established protocol in this manuscript can be applied to the synthesis of a tetraarylated thiophene
(scheme 6). The [3+2] cycloaddition reaction of 1a and 2a and a subsequent sulfur–oxygen exchange reaction
with Lawesson’s reagent16 gave dihydrothiophene. The oxidation of dihydrothiophene with DDQ gave 7
without its regioisomer in a 48% yield after 3 steps. Triarylthiophene 8 was obtained after the bromination of 7
with NBS (95%) followed by Suzuki–Miyaura coupling (81%). The resulting product 8 was then subjected to
hydrolysis followed by decarboxylative coupling with pꢀCF3C6H4ꢀI to produce tetraarylthiophene 9 in a 66%
yield (2 steps).
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Scheme 6.
Tetraarylthiophene 9 synthesis
CONCLUSION
It is very difficult to selectively synthesize all of the various aryl-substituted furans. In this
manuscript, our current protocol for the synthesis of these compounds involves a 1) Cu-catalyzed
formal [3+2]-cycloaddition of styrenes 1 and bromoketoesters 2 to give diaryl-substituted
dihydrofurans 3, 2) DDQ oxidation of 3 to give diarylfurans 6, 3) bromination of 6 to give
brominated furans 6Br, 4) Suzuki–Miyaura coupling to give triarylfurans 4, 5) hydrolysis of 4 to
give carboxylic acids 4OH, and 6) decarboxylative couplings of 4OH to give the desired
tetraarylfurans 5. Our protocol enabled the efficient installation of four different aryl groups onto
the furan ring in 6 steps with perfect selectivities from widely available styrenes 1. In addition,
diaryl-substituted dihydrofurans 3 can easily be converted into dihydrothiophenes with
Lawesson’s reagent. After an oxygen–sulfur exchange, transformations that are similar to the
reactions shown above can be applied to dihydrothiophene to obtain tetraarylthiophene 9 in 7
steps. These short sequences constitute a new and convenient method for the synthesis of 5 and
9.
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EXPERIMENTAL SECTION
General Information
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All reactions were carried out under nitrogen (99.95%) atmosphere. For TLC analyses
precoated Kieselgel 60 F254 plates (0.25 mm thick) were used; for column chromatography
1
(40-63 µm) was used. Visualization was accomplished by UV light (254 nm), H and 13C
NMR spectra were obtained using a 500 MHz NMR spectrometer. Chemical shifts for 1H
NMR were described in parts per million (chloroform as an internal standard δ = 7.26) in
CDCl3, unless otherwise noted. Chemical shifts for 13C NMR were expressed in parts per
million in CDCl3 as an internal standard (δ = 77.16), unless otherwise noted. High resolution
mass analyses were obtained using a TOF-MS for ESI. Purification was performed by Gel
Permeation Chromatography (GPC) System (Detector UV 254 nm).
Typical Experimental Procedure for Synthesis of 3a-3u
Cu salt (0.05 mmol), TPMA (0.05 mmol), and tetrabutylammonium nitrite (0.1 mmol)
were sequentially added under air to a dram vial equipped with a stir bar and a screw
cap (or Biotage shield tube for microwave.). 1 (0.50 mmol), 2 (1.0 mmol), amine (0.75
mmol) and dried CH2Cl2 (2.0 mL) were added by syringe and the resulting mixture
vigorously stirred under nitrogen atmosphere (charged by general N2 (99.95%) gas
flow) for 20 h at the temperature shown in tables. After this time, the contents of the
flask were filtered through the plug of silica gel, and then concentrated by rotary
evaporation. The residue was purified by flash chromatography, eluting with
hexane/EtOAc to afford the product (3a-3u). Further purification was carried out by
using GPC.
Typical Experimental Procedure for Synthesis of 4a-4d
Pd cat. (5 mol%), bromide 6Br (1 equiv.), and boronic acid (2 equiv.) were added under
air to a dram vial equipped with a stir bar and a screw cap. DMF and 2M Na2CO3 aq. (2
mL/mmol, 4 equiv.) were added to the mixture under nitrogen atmosphere (charged by
o
general N2 (99.95%) gas flow) and the reaction mixture was stirred at 80 C for 12 h.
After this time, the contents of the flask were filtered through the plug of silica gel, and
then concentrated by rotary evaporation. The residue was purified by flash
chromatography, eluting with hexane/EtOAc and GPC (Gel Permeation
Chromatography) to afford the product (4a-4d).
Typical Experimental Procedure for Synthesis of 4OH-a-4OH-d
Ester (0.25 mmol, 1 equiv.) in 0.5 M NaOH aq. (2 eqiv. 4 mL/mmol) and Dioxane was
stirred at 100 oC for 12 hr. At this time, the mixture was acidified by conc. HCl aq. and
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extracted with EtOAc to afford the carboxylic acid (4OH-a-4OH-d).
Typical Experimental Procedure for Synthesis of 5a-5d
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Pd cat. (10 mol%), carboxylic acid 4OH (0.25 mmol, 1 equiv.), iodide (2 equiv.), Cs2CO3
(3 equiv.) MS4A (300 mg/mmol) were added under air to a dram vial equipped with a stir
bar and a screw cap. Mesitylene was added to the mixture under nitrogen atmosphere
(charged by general N2 (99.95%) gas flow) and the reaction mixture was stirred at 170
oC for 12 h. After this time, the contents of the flask were filtered through the plug of
silica gel, and then concentrated by rotary evaporation. The residue was purified by
flash chromatography, eluting with hexane/EtOAc and GPC (Gel Permeation
Chromatography) to afford the product (5a-5d).
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Typical Experimental Procedure for Synthesis of 6Br-a-6Br-g
Furan 6 (1 equiv.) and NBS (1.05 equiv.) and CH3CN were added to a dram vial
equipped with a stir bar and a screw cap and the resulting mixture was stirred at 50 oC
for 12 h. After this time, the contents of the flask were concentrated by rotary
evaporation. The residue was purified by flash chromatography, eluting with
hexane/EtOAc to afford the bromide (6Br-a-6Br-g)
.
Typical Experimental Procedure for Synthesis of 6a-6g
Cu salt (0.05 mmol) was added under air to a dram vial equipped with a stir bar and a
screw cap. 1 (1.50 mmol), 2 (0.50 mmol), amine (0.75 mmol), ligand (0.05 mmol) and
dried CH2Cl2 (2.0 mL) were added by syringe and the resulting mixture vigorously stirred
under nitrogen atmosphere (charged by general N2 (99.95%) gas flow) at 100 oC for 1 h
(The ratio of 1 and 2 was shown in each compound analysis). After this time, the
contents of the flask were filtered through the plug of silica gel, and then concentrated
by rotary evaporation. The residue dissolved in toluene was taken into a dram vial
equipped with a stir bar and a screw cap. DDQ (0.60 mmol) was added and the reaction
o
mixture was stirred at 110 C for 12 h. After this time, the contents of the flask were
concentrated by rotary evaporation. The residue was purified by flash chromatography,
eluting with hexane/EtOAc to afford the product 6.
Methyl 2-(tert-butyl)-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-carboxylate (3a).
Pale yellow oil (82%, 119mg), IR (neat) ν 2951, 1700, 1598, 1512, 1238, 1099 cm-1. 1H
NMR (500 MHz, CDCl3) δ: 1.35 (s, 9H), 2.91 (dd, J = 8.3 and 14.5 Hz, 1H), 3.33 (dd, J =
10.9 and 14.5 Hz, 1H), 3.67 (s, 3H), 3.80 (s, 3H), 5.45 (dd, J = 8.3 and 10.9 Hz, 1H),
6.90 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 27.7,
34.6, 40.1, 50.8, 55.4, 81.7, 99.1, 114.1, 127.0, 134.3, 159.5, 165.9, 177.4. HRESIMS
calcd. for C17H22O4Na (M+Na+): 313.1494; found 313.1490.
Methyl
2-(1-adamantanyl)-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-carboxylate
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(3b). Pale yellow oil (91%, 168mg), IR (neat) ν 2901, 2848, 1699, 1592, 1512, 1241,
1173, 1074, 1033 cm-1. 1H NMR (500 MHz, CDCl3) δ: 1.69-1.78 (m, 6H), 3.12 (brs, 3H),
2.12 (brs, 6H), 2.90 (dd, J = 8.4 and 14.6 Hz, 1H), 3.33 (dd, J = 10.9 and 14.6 Hz, 1H),
3.67 (s, 3H), 3.80 (s, 3H), 5.43 (dd, J = 8.4 and 10.9 Hz, 1H), 6.89 (d, J = 8.6 Hz, 1H),
7.24 (d, J = 8.6 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 28.5, 36.8, 37.1, 38.2, 40.1, 50.9,
55.4, 81.5, 99.1, 114.2, 127.1, 134.5, 159.6, 166.0, 177.4. HRESIMS calcd. for C23H29O4
(M+H+): 369.2066; found 369.2074.
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Methyl 2,5-bis(4-methoxyphenyl)-4,5-dihydrofuran-3-carboxylate (3c).
Pale yellow oil (84%, 143mg), IR (neat) ν 2947, 1694, 1680, 1606, 1511, 1242, 1175,
1081, 1032 cm-1. 1H NMR (500 MHz, CDCl3) δ: 3.10 (dd, J = 8.7 and 15.1 Hz, 1H), 3.47
(dd, J = 10.6 and 15.1 Hz, 1H), 3.67 (s, 3H), 3.78 (s, 3H), 3.81 (s, 3H), 5.62 (dd, J = 8.7
and 10.6 Hz, 1H), 6.88 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 7.32 (d, J = 8.7 Hz,
2H), 7.87 (d, J = 9.0 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 39.6, 51.1, 55.4, 55.4, 82.4,
100.4, 113.2, 114.2, 122.3, 127.5, 131.4, 133.8, 159.8, 161.5, 165.1, 166.1. HRESIMS
calcd. for C20H20O5Na (M+Na+): 363.1231; found 363.1208.
Methyl 5-(4-methoxyphenyl)-2-phenyl-4,5-dihydrofuran-3-carboxylate (3d). Pale
yellow oil (80%, 124mg), IR (neat) ν 2948, 1705, 1514, 1244, 1088 cm-1. 1H NMR (500
MHz, CDCl3) δ: 3.13 (dd, J = 8.7 and 15.2 Hz, 1H), 3.51 (dd, J = 10.7 and 15.2 Hz, 1H),
3.66 (s, 3H), 3.79 (s, 3H), 5.66 (dd, J = 8.7 and 10.7 Hz, 1H), 6.89 (d, J = 8.7 Hz, 2H),
7.33 (d, J = 8.7 Hz, 2H), 7.36-7.42 (m, 3H), 7.82 (dd, J = 1.7 and 8.4 Hz, 2H). 13C NMR
(125 MHz, CDCl3) δ: 39.7, 51.1, 55.4, 82.7, 101.8, 114.2, 127.5, 127.8, 129.5, 130.0,
130.6, 133.6, 159.8, 165.2, 165.8. HRESIMS calcd. for C19H18O4Na (M+Na+): 333.1103;
found 333.1097.
Methyl
2-(4-bromophenyl)-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-carboxylate(3e). Pale
yellow oil (99%, 193mg), IR (neat) ν 2946, 1700, 1610, 1512, 1238, 1081 cm-1. 1H NMR
(500 MHz, CDCl3) δ: 3.12 (dd, J = 8.7 and 15.3 Hz, 1H), 3.48 (dd, J = 10.7 and 15.3 Hz,
1H), 3.67 (s, 3H), 3.78 (s, 3H), 5.55 (dd, J = 8.7 and 10.7 Hz, 1H), 6.89 (d, J = 8.7 Hz,
2H), 7.31 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H). 13C NMR
(125 MHz, CDCl3) δ: 39.6, 51.2, 55.3, 82.7, 102.47, 114.2, 125.0, 127.4, 128.8, 131.0,
131.1, 133.3, 159.8, 163.8, 165.6. HRESIMS calcd. for C19H17O4BrNa (M+Na+):
411.0208; found 411.0210.
Methyl 5-(4-methoxyphenyl)-2-(thiophen-2-yl)-4,5-dihydrofuran-3-carboxylate (3f).
Pale yellow oil (77%, 122mg), IR (neat) ν 2946, 1691, 1597, 1511, 1239, 1174, 1072,
1030 cm-1. 1H NMR (500 MHz, CDCl3) δ: 3.10 (dd, J = 8.4 and 15.4 Hz, 1H), 3.49 (dd, J
= 10.5 and 15.4 Hz, 1H), 3.75 (s, 3H), 3.78 (s, 3H), 5.64 (dd, J = 8.4 and 10.5 Hz, 1H),
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6.88 (dd, J = 8.6 Hz, 2H), 7.09 (dd, J = 3.8 and 5.1 Hz, 1H), 7.30 (d, J = 8.6 Hz, 2H),
7.48 (d, J = 1.2 and 5.1 Hz, 1H), 8.22 (d, J = 3.7 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ:
39.8, 51.1, 55.3, 82.4, 100.0, 114.1, 127.2, 127.3, 130.4, 131.4, 132.5, 133.55, 158.67,
159.7, 165.7. HRESIMS calcd. for C17H16O4SNa (M+Na+): 339.0667; found 339.0671.
Methyl 5-(4-methoxyphenyl)-4,5-dihydro-[2,2'-bifuran]-3-carboxylate (3g). Pale
yellow oil (76%, 114mg), IR (neat) ν 2947, 1690, 1652, 1513, 1231, 1089, 1027 cm-1. 1H
NMR (500 MHz, CDCl3) δ: 3.11 (dd, J = 8.7 and 15.5 Hz, 1H), 3.45 (dd, J = 10.5 and
14.6 Hz, 1H), 3.73 (s, 3H), 3.78 (s, 3H), 5.67 (dd, J = 8.7 and 10.5 Hz, 1H), 6.51 (dd, J
= 1.8 and 3.5 Hz, 1H), 6.88 (d, J = 8.7 Hz, 2H), 7.32 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 1.2
Hz, 1H), 7.80 (d, J = 3.5 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ: 39.3, 51.3, 55.5, 83.3,
100.8, 112.1, 114.3, 114.3, 118.0, 127.7, 133.2, 144.4, 144.5, 154.7, 160.0, 165.3.
HRESIMS calcd. for C17H16O5Na (M+Na+): 323.0895; found 323.0900.
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Methyl 5-(4-methoxyphenyl)-2-(o-tolyl)-4,5-dihydrofuran-3-carboxylate (3h). Pale
yellow oil (78%, 127mg), IR (neat) ν 2947, 1685, 1636, 1513, 1436, 1235, 1077, 1030
cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.31 (s, 3H), 3.16 (dd, J = 8.9 and 15.0 Hz, 1H), 3.49
(dd, J = 10.7 and 15.0 Hz, 1H), 3.57 (s, 3H), 3.79 (s, 3H), 5.72 (dd, J = 8.9 and 10.7 Hz,
1H), 6.91 (d, J = 8.8 Hz, 2H), 7.18-7.21 (m, 2H), 7.28 (dt, J = 1.4 and 7.6 Hz, 1H), 7.33
(d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 19.7, 38.3,
51.1, 55.4, 83.8, 114.3, 125.3, 127.7, 129.6, 129.8, 130.2, 130.7, 133.4, 137.0, 159.9,
165.6, 166.6. HRESIMS calcd. for C20H20O4Na (M+Na+): 347.1259; found 347.1267.
Methyl 2-(2-bromophenyl)-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-
carboxylate (3i). Pale yellow oil (83%, 162mg), IR (neat) ν 2947, 1690, 1652, 1513,
1231, 1089, 1027 cm-1. 1H NMR (500 MHz, CDCl3) δ: 3.16 (dd, J = 9.2 and 15.2 Hz, 1H),
3.50 (dd, J = 10.7 and 15.2 Hz, 1H), 3.58 (s, 3H), 3.81 (s, 3H), 5.76 (dd, J = 9.2 and 10.7
Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 7.24 (m, 1H), 7.32 (dt, J = 0.9 and 7.5 Hz, 1H ), 7.39
(dd, J = 1.8 and 7.5 Hz, 1H), 7.41 (dd, J = 0.9 and 8.0 Hz, 2H), 7.61 (d, J = 0.9 and 8.7
Hz, 1H). 13C NMR (125 MHz, CDCl3) δ: 38.4, 51.2, 55.5, 84.6, 105.4, 114.3, 122.7,
127.1, 128.0, 131.0, 131.0, 132.9, 133.2, 160.0, 164.5, 165.3. HRESIMS calcd. for
C19H17O4BrNa (M+Na+): 411.0208; found 411.0217.
Methyl 2-mesityl-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-carboxylate (3j). Pale
yellow oil (73%, 129mg), IR (neat) ν 2948, 1685, 1637, 1513, 1436, 1230, 1076, 1031
cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.18 (s, 3H), 2.25 (s, 6H), 3.16 (dd, J = 9.4 and 14.8
Hz, 1H), 3.45 (dd, J = 10.7 and 14.8 Hz, 1H), 3.54 (s, 3H), 3.79 (s, 3H), 5.72 (dd, J = 9.4
and 10.7 Hz, 1H), 6.82 (s, 1H), 6.84 (s, 1H), 6.89 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz,
2H). 13C NMR (125 MHz, CDCl3) δ: 19.6, 21.3, 37.8, 51.0, 55.4, 83.8, 104.8, 114.2,
127.9, 127.94, 128.1, 128.1, 133.3, 136.2, 136.5, 138.8, 159.8, 165.5, 1664. HRESIMS
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calcd. for C22H24O4Na (M+Na+): 375.1572; found 375.1578.
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1-(2-(tert-Butyl)-5-(4-methoxyphenyl)-4,5-dihydrofuran-3-yl)-2,2-dimethylpropan-1
-one (3k). Pale yellow oil (60%, 95mg), IR (neat) ν 2959, 1514, 1248, 902 cm-1. 1H NMR
(500 MHz, CDCl3) δ: 1.14 (s, 9H), 1.18 (s, 9H), 2.98 (dd, J = 9.1 and 13.8 Hz, 1H), 3.33
(dd, J = 10.3 and 13.8 Hz, 1H), 3.79 (s, 3H), 5.38 (dd, J =9.1 and 10.3 Hz, 1H), 6.88 (d,
J = 8.7 Hz, 2H), 7.26 (d, J = 8.7 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 27.3, 28.4, 34.2,
43.2, 44.2, 55.4, 81.4, 108.0, 114.1, 127.0, 134.5, 159.5, 169.2, 209.4. HRESIMS calcd.
for C20H29O3 (M+H+): 317.2117; found 317.2109.
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Methyl 2-(tert-butyl)-5-(p-tolyl)-4,5-dihydrofuran-3-carboxylate (3l). Pale yellow oil
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(85%, 117mg), IR (neat) ν 2950, 1701, 1599, 1238, 1100 cm-1. H NMR (500 MHz,
CDCl3) δ: 1.36 (s, 9H), 2.34 (s, 3H), 2.91 (dd, J = 8.2 and 14.5 Hz, 1H), 3.34 (dd, J =
10.9 and 14.5 Hz, 1H), 3.66 (s, 3H), 5.47 (dd, J = 8.2 and 10.9 Hz, 1H), 7.16 (d, J = 8.2
Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 21.8, 27.7, 34.6, 40.1,
50.8, 81.7, 99.1, 125.5, 129.4, 137.8, 139.3, 165.8, 177.4. HRESIMS calcd. for
C17H22O3Na (M+Na+): 297.1467; found 297.1473.
Methyl 2-(tert-butyl)-5-(o-tolyl)-4,5-dihydrofuran-3-carboxylate (3m). Pale yellow oil
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(54%, 74mg), IR (neat) ν 2951, 1701, 1599, 1238, 1101 cm-1. H NMR (500 MHz,
CDCl3) δ: 1.41 (s, 9H), 2.31 (s, 3H), 2.79 (dd, J = 8.7 and 14.3 Hz, 1H), 3.40 (dd, J =
11.1 and 14.3 Hz, 1H), 3.67 (s, 3H), 5.68 (dd, J = 8.7 and 11.1 Hz, 1H), 7.17-7.24 (m,
3H), 7.30-7.32 (m, 1H). 13C NMR (125 MHz, CDCl3) δ: 19.2, 27.7, 34.7, 39.3, 50.8, 79.6,
99.0, 124.2, 126.2, 127.6, 130.6, 134.1, 140.2, 165.7, 177.4. HRESIMS calcd. for
C17H22O3Na (M+Na+): 297.1467; found 297.1465.
Methyl 2-(tert-butyl)-5-phenyl-4,5-dihydrofuran-3-carboxylate (3n). Pale yellow oil
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(56%, 73mg), IR (neat) ν 2951, 1701, 1599, 1238, 1100 cm-1. H NMR (500 MHz,
CDCl3) δ: 1.36 (s, 9H), 2.90 (dd, J = 8.2 and 14.5 Hz, 1H), 3.34 (dd, J = 11.0 and 14.5 Hz,
1H), 3.67 (s, 3H), 5.47 (dd, J = 8.2 and 11.0 Hz, 1H), 7.29-7.31 (m, 3H), 7.35-7.38 (m,
2H). 13C NMR (125 MHz, CDCl3) δ: 27.7, 34.7, 40.2, 50.9, 81.7, 125.4, 128.0, 128.8,
142.3, 165.8, 177.4. HRESIMS calcd. for C16H20O3Na (M+Na+): 283.1310; found
283.1315.
Methyl 2-(tert-butyl)-5-(4-fluorophenyl)-4,5-dihydrofuran-3-carboxylate (3o). Pale
yellow oil (62%, 86mg), IR (neat) ν 2952, 1701, 1601, 1509, 1238, 1101 cm-1. 1H NMR
(500 MHz, CDCl3) δ: 1.35 (s, 9H), 2.91 (dd, J = 8.3 and 14.5 Hz, 1H), 3.33 (dd, J = 10.9
and 14.5 Hz, 1H), 3.67 (s, 3H), 3.80 (s, 3H), 5.45 (dd, J = 8.3 and 10.9 Hz, 1H), 7.06 (t, J
= 8.7 Hz, 2H), 7.28 (dd, J = 5.2 and 8.7 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 27.7,
34.6, 40.2, 50.9, 81.4, 99.1, 115.7 (d, J = 21.5 Hz), 127.3 (d, J = 8.2 Hz), 138.1 (d, J =
3.2 Hz), 162.0 (d, J = 246.2 Hz), 165.7, 177.2. HRESIMS calcd. for C16H19O3FNa
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(M+Na+): 301.1216; found 301.1211.
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Methyl 2-(tert-butyl)-5-(4-chlorophenyl)-4,5-dihydrofuran-3-carboxylate (3p). Pale
yellow oil (82%, 121mg), IR (neat) ν 2950, 1701, 1601, 1238, 1100 cm-1. 1H NMR (500
MHz, CDCl3) δ: 1.35 (s, 9H), 2.87 (dd, J = 8.2 and 14.6 Hz, 1H), 3.35 (dd, J = 11.0 and
14.6 Hz, 1H), 3.67 (s, 3H), 5.47 (dd, J = 8.2 and 11.0 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H),
7.33 (d, J = 8.4 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 27.7, 34.6, 40.2, 50.9, 80.9,
99.23, 126.9, 128.9, 133.8, 140.8, 165.7, 177.2. HRESIMS calcd. for C16H19O3ClNa
(M+Na+): 317.0920; found 317.0927.
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Methyl 2-(tert-butyl)-5-(2-chlorophenyl)-4,5-dihydrofuran-3-carboxylate (3q). Pale
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yellow oil (51%, 75mg), IR (neat) ν 2951, 1702, 1606, 1239, 1101 cm-1. H NMR (500
MHz, CDCl3) δ: 1.40 (s, 9H), 2.76 (dd, J = 8.0 and 14.8 Hz, 1H), 3.53 (dd, J = 11.2 and
14.8 Hz, 1H), 3.65 (s, 3H), 5.79 (dd, J = 8.0 and 11.2 Hz, 1H), 7.23 (dt, J = 1.8 and 7.5
Hz, 1H), 7.28 (dt, J = 1.2 and 7.5 Hz, 1H), 7.35 (dt, J = 1.6 and 9.2 Hz, 2H),. 13C NMR
(125 MHz, CDCl3) δ: 27.8, 34.7, 39.6, 50.9, 78.8, 99.3, 125.8, 127.1, 128.9, 129.8, 131.3,
140.2, 165.7, 177.1. HRESIMS calcd. for C16H19O3ClNa (M+Na+): 317.0920; found
317.0914.
Methyl 5-(4-bromophenyl)-2-(tert-butyl)-4,5-dihydrofuran-3-carboxylate (3r). Pale
yellow oil (81%, 137mg), IR (neat) ν 2951, 1701, 1602, 1239, 1100 cm-1. 1H NMR (500
MHz, CDCl3) δ: 1.35 (s, 9H), 2.87 (dd, J = 8.1 and 14.5 Hz, 1H), 3.35 (dd, J = 10.0 and
14.5 Hz, 1H), 3.67 (s, 3H), 5.46 (dd, J = 8.1 and 10.0 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H),
7.49 (d, J = 8.4 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 27.7, 34.6, 40.1, 50.9, 80.9, 99.1,
121.8, 127.1, 131.8, 141.2, 165.5, 177.0. HRESIMS calcd. for C16H19O3BrNa (M+Na+):
361.0415; found 361.0420.
Methyl 2-(tert-butyl)-5-methyl-5-phenyl-4,5-dihydrofuran-3-carboxylate (3s). Pale
yellow oil (42%, 58mg), IR (neat) ν 2951, 1702, 1600, 11242, 1107, 1017 cm-1. 1H NMR
(500 MHz, CDCl3) δ: 1.34 (s, 9H), 3.04 (d, J = 4.3 Hz, 1H), 3.13 (d, J = 4.3 Hz, 1H), 3.61
(s, 3H), 7.20-7.24 (m, 1H), 7.32 (d, J = 4.8 Hz, 4H). 13C NMR (125 MHz, CDCl3) δ: 27.6,
29.5, 34.7, 46.1, 50.8, 86.8, 98.7, 124.3, 127.2, 128.5, 147.0, 165.9, 176.3. HRESIMS
calcd. for C17H22O3Na (M+Na+): 297.1467; found 297.1465.
Methyl 2-(4-methoxyphenyl)-5-(p-tolyl)-4-(4-(trifluoromethyl)phenyl)furan-3-
carboxylate (4a). White solid (97%, 113mg), Mp: 169 – 170 oC, IR (neat) ν 2952, 1717,
1615, 1500, 1331, 1116 cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.32 (s, 3H), 3.59 (s, 3H),
3.89 (s, 3H), 6.97 – 7.03 (m, 2H), 7.08 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H), 7.49
(d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H), 7.84 – 7.89 (m, 2H). 13C NMR (125 MHz,
CDCl3) δ: 21.3, 51.5, 55.4, 113.8, 114.8, 121.6, 122.4, 124.4 (q, J = 273.0 Hz), 125.4 (q,
J = 3.9 Hz), 126.0, 126.9, 129.3, 129.7 (d, J = 32.0 Hz), 129.8, 130.6, 137.6 (q, J = 1.0
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Hz), 138.2, 148.7, 155.6, 160.6, 164.6. HRESIMS calcd. for C27H22F3O4 (M+H+):
467.1470; found 467.1480.
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Methyl 4-(4-chlorophenyl)-5-(4-fluorophenyl)-2-(4-methoxyphenyl)furan-3-
carboxylate (4b). White solid (72%, 79mg), Mp: 120 – 121 oC, IR (neat) ν 2960, 1704,
1607, 1499, 1228, 829 cm-1. H NMR (500 MHz, CDCl3) δ: 3.60 (s, 3H), 3.88 (s, 3H),
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6.67 – 7.01 (m, 4H), 7.27 – 7.30 (m, 2H), 7.33 – 7.37 (m, 2H), 7.38 – 7.41 (m, 2H), 7.82
– 7.86 (m, 2H). 13C NMR (125 MHz, CDCl3) δ: 51.5, 55.4, 113.9, 115.0, 115.7 (d, J =
21.8 Hz), 122.1, 122.3, 126.2 (d, J = 3.1 Hz), 127.8 (d, J = 8.1 Hz), 128.9, 129.7, 131.5,
131.8, 133.8, 147.5, 155.7, 160.7, 162.4 (d, J = 248.6 Hz), 164.6. HRESIMS calcd. for
C25H18ClFNaO4 (M+Na+): 459.0775; found 459.0769.
Methyl 5-(4-chlorophenyl)-4-phenyl-2-(p-tolyl)furan-3-carboxylate (4c). Colorless
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oil (68%, 68mg), IR (neat) ν 2947, 1717, 1590, 1500, 820 cm-1. H NMR (500 MHz,
CDCl3) δ: 2.42 (s, 3H), 3.59 (s, 3H), 7.19 – 7.23 (m, 2H), 7.25 – 7.30 (m, 2H), 7.31 –
7.37 (m, 4 H), 7.39 – 7.44 (m, 3H), 7.77 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3)
δ: 21.6, 51.6, 116.2, 124.2, 126.0, 127.2, 128.0, 128.0, 128.7, 128.8, 129.3, 130.0,
133.0, 133.7, 139.7, 147.3, 155.3, 164.8. HRESIMS calcd. for C25H19ClNaO3 (M+Na+):
425.0920; found 425.0917.
Methyl 5-(4-methoxyphenyl)-2-phenyl-4-(p-tolyl)furan-3-carboxylate (4d). White
solid (75%, 75mg), Mp: 127 – 128 oC, IR (neat) ν 2951, 1720, 1606, 1492 cm-1. 1H NMR
(500 MHz, CDCl3) δ: 2.41 (s, 3H), 3.62 (s, 3H), 3.78 (s, 3H), 6.76 – 6.83 (m, 2H), 7.18 –
7.28 (m, 4H), 7.35 – 7.42 (m, 3H), 7.42 – 7.49 (m, 2H), 7.81 – 7.89 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ: 21.3, 51.5, 55.2, 113.8, 116.5, 122.1, 123.0, 127.4, 127.6, 128.3,
128.9, 129.2, 129.8, 130.0, 130.1, 137.2, 148.6, 153.7, 159.2, 165.0. HRESIMS calcd.
for C26H23O4 (M+H+): 399.1596; found 399.1596.
2-(4-Methoxyphenyl)-5-(p-tolyl)-4-(4-(trifluoromethyl)phenyl)furan-3-carboxylic
acid (4OH-a). White solid (92%, 104mg), IR (neat) ν 2917, 1674, 1609, 1498, 1440,
1328, 1112 cm-1. 1H NMR (500 MHz, DMSO-d6) δ: 1.51 (s, 3H), 3.08 (s, 3H), 6.30 – 6.34
(m, 2H), 6.39 (d, J = 8.2 Hz, 2H), 6.48 (d, J = 8.2 Hz, 2H), 6.81 (d, J = 8.1 Hz, 2H), 7.02
(d, J = 8.2 Hz, 2H), 7.09 – 7.14 (m, 2H). 13C NMR (125 MHz, DMSO-d6) δ: 20.8, 55.3,
114.0, 115.9, 121.4, 121.7, 124.4 (q, J = 273.7 Hz), 125.3 (q, J = 4.0 Hz), 125.8, 126.4,
128.1 (d, J = 31.5 Hz), 129.2, 129.4, 130.8, 137.5 (q, J = 1.9 Hz), 138.0, 147.8, 153.5,
160.1, 164.8. HRESIMS calcd. for C26H19F3NaO4 (M+Na+): 475.1133; found 475.1126.
4-(4-Chlorophenyl)-5-(4-fluorophenyl)-2-(4-methoxyphenyl)furan-3-carboxylic
acid (4OH-b). White solid (87%, 92mg), IR (neat) ν 3075, 1674, 1606, 1501, 1441, 833
cm-1. 1H NMR (500 MHz, DMSO-d6) δ: 3.08 (s, 3H), 6.29 – 6.33 (m, 2H), 6.41 – 6.46 (m,
2H), 6.59 – 6.67 (m, 4H), 6.71 – 6.75 (m, 2H), 7.09 – 7.13 (m, 2H). 13C NMR (125 MHz,
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DMSO-d6) δ: 55.3, 114.1, 115.9 (d, J = 21.9 Hz), 116.2, 121.7, 122.0, 126.0 (d, J = 3.0
Hz), 127.9 (d, J = 8.4 Hz), 128.7, 129.2, 131.7, 131.8, 132.6, 146.5, 153.5, 160.2, 161.8
(d, J = 246.3 Hz), 164.9. HRESIMS calcd. for C24H16ClFNaO4 (M+Na+): 445.0619; found
445.0621.
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5-(4-Chlorophenyl)-4-phenyl-2-(p-tolyl)furan-3-carboxylic acid (4OH-c). White solid
(73%, 71mg), IR (neat) ν 3219, 1681, 1613, 1480, 1445, 827 cm-1. 1H NMR (500 MHz,
DMSO-d6) δ: 1.53 (s, 3H), 6.46 – 6.63 (m, 11H), 6.95 (d, J = 8.1 Hz, 2H). 13C NMR (125
MHz, DMSO-d6) δ: 20.9, 117.7, 124.0, 126.5, 127.0, 127.2, 128.1, 128.4, 128.7, 128.8,
129.3, 129.7, 132.3, 132.7, 139.1, 146.3, 152.5, 165.1. HRESIMS calcd. for
C24H17ClNaO3 (M+Na+): 411.0764; found 411.0773.
5-(4-Methoxyphenyl)-2-phenyl-4-(p-tolyl)furan-3-carboxylic acid (4OH-d). White
1
solid (92%, 88mg), IR (neat) ν 2918, 1687, 1606, 1487 cm-1. H NMR (500 MHz,
DMSO-d6) δ: 1.51 (s, 3H), 2.89 (s, 3H), 6.01 – 6.10 (m, 2H), 6.35 – 6.41 (m, 4H), 6.47 –
6.52 (m, 2H), 6.56 – 6.62 (m, 1H), 6.62 – 6.69 (m, 2H), 7.01 (d, J = 7.4 Hz, 2H). 13C
NMR (125 MHz, DMSO-d6) δ: 20.9, 55.2, 114.2, 118.3, 121.7, 122.2, 126.7, 127.2,
128.7, 128.9, 129.3, 129.5, 129.6, 129.7, 137.0, 147.9, 150.9, 159.2, 165.5. HRESIMS
calcd. for C25H21O4 (M+H+): 385.1440; found 385.1446.
3-(4-Chlorophenyl)-2-(4-methoxyphenyl)-5-(p-tolyl)-4-(4-(trifluoromethyl)phenyl)fu
o
ran (5a). White solid (63%, 82mg), Mp: 186 – 187 C, IR (neat) ν 2931, 1612, 1508,
1
1320, 1254, 831 cm-1. H NMR (500 MHz, CDCl3) δ: 2.34 (s, 3H), 3.80 (s, 3H), 6.81 –
6.85 (m, 2H), 7.02 – 7.07 (m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.21 – 7.26 (m, 4H), 7.33 (d,
J = 8.2 Hz, 2H), 7.38 – 7.43 (m, 2H), 7.50 (d, J = 8.1 Hz, 2H). 13C NMR (125 MHz,
CDCl3) δ: 21.4, 55.4, 114.1, 121.8, 122.6, 123.3, 124.3 (q, J = 272.0 Hz), 125.6 (q, J =
4.0 Hz), 126.2, 127.6, 127.6, 129.0, 129.4, 130.8, 131.6, 131.8, 133.4, 137.2 (q, J = 1.7
Hz), 137.9, 148.4, 159.3. HRESIMS calcd. for C31H22ClF3NaO2 (M+Na+): 541.1158;
found 541.1160.
3-(4-Chlorophenyl)-2-(4-fluorophenyl)-5-(4-methoxyphenyl)-4-(p-tolyl)furan (5b).
o
White solid (78%, 91mg), Mp: 178 – 179 C, IR (neat) ν 2954, 1594, 1493, 1223, 828
cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.34 (s, 3H), 3.80 (s, 3H), 6.79 – 6.84 (m, 2H), 6.94 –
7.02 (m, 4H), 7.04 – 7.09 (m, 4H), 7.20 – 7.25 (m, 2H), 7.41 – 7.47 (m, 4H). 13C NMR
(125 MHz, CDCl3) δ: 21.4, 55.4, 114.0, 115.7 (d, J = 21.7 Hz), 123.4, 123.6, 123.7, 127.2,
(d, J = 3.1 Hz), 128.7, 128.9, 129.5, 130.0, 130.4, 130.6, 131.8, 132.0, 133.3, 137.1,
146.7, 148.2, 159.2, 162.2 (d, J = 247.5 Hz). HRESIMS calcd. for C30H23ClFO2 (M+H+):
469.1371; found 469.1374.
2-(4-Chlorophenyl)-4-(4-fluorophenyl)-3-phenyl-5-(p-tolyl)furan (5c). White solid
(65%, 71mg), Mp: 190 – 192 oC, IR (neat) ν 2914, 1597, 1492, 1217, 819 cm-1. 1H NMR
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(500 MHz, CDCl3) δ: 2.34 (s, 3H), 6.91 – 6.70 (m, 2H), 7.06 – 7.17 (m, 6H), 7.20 – 7.29
(m, 5H), 7.35 – 7.44 (m, 4H). 13C NMR (125 MHz, CDCl3) δ: 21.5, 115.7, 115.8, 123.7,
126.2, 127.2, 127.7, 128.0, 128.9, 129.3 (d, J = 3.3 Hz), 129.5, 129.6, 130.5, 130.7,
132.3 (d, J = 8.1 Hz), 133.2 (d, J = 21.1 Hz), 137.9, 146.7, 148.7, 162.4 (d, J = 246.2
Hz). HRESIMS calcd. for C29H21ClFO (M+H+): 439.1265; found 439.1262.
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2-(4-Methoxyphenyl)-5-phenyl-3-(p-tolyl)-4-(4-(trifluoromethyl)phenyl)furan (5d)
White solid (80%, 97mg), Mp: 218 – 219 oC, IR (neat) ν 2925, 1605, 1496, 1327 cm-1.
1H NMR (500 MHz, CDCl3) δ: 2.33 (s, 3H), 3.79 (s, 3H), 6.78 – 6.85 (m, 2H), 6.98 – 7.02
(m, 2H), 7.04 – 7.08 (m, 2H), 7.21 – 7.31 (m, 5H). 7.42 – 7.51 (m, 10 H). 13C NMR (125
MHz, CDCl3) δ: 21.2, 55.2, 113.9, 123.1, 124.3 (q, J = 273 Hz), 123.6, 125.3 (q, J = 4
Hz), 126.1, 127.4, 127.6, 128.5, 129.1, (q, J = 33 Hz), 129.4, 129.7, 130.2, 130.6, 130.7,
137.0, 137.4, 147.7, 148.3, 159.1. HRESIMS calcd. for C31H24F3O2 (M+H+): 485.1728;
found 485.1724.
Methyl 2-(4-methoxyphenyl)-5-(p-tolyl)furan-3-carboxylate (6a). White solid (67%,
108mg), Mp: 120 – 121 oC, IR (neat) ν 2950, 1720, 1605, 1494, 1090, 1028, 834, 768
cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.38 (s, 3H), 3.86 (s, 3H), 3.88 (s, 3H), 6.97 – 7.02
(m, 2H), 7.00 (s, 1H), 7.23 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 7.8 Hz, 2H), 8.04 – 8.09 (m,
2H). 13C NMR (125 MHz, CDCl3) δ: 21.5, 51.7, 55.5, 107.1, 113.7, 114.1, 122.6, 124.0,
127.3, 129.6, 130.0, 138.0, 152.1, 156.7, 160.5, 164.3. HRESIMS calcd. for C20H18NaO4
(M+Na+): 345.1103; found 345.1101.
Methyl 5-(4-fluorophenyl)-2-(4-methoxyphenyl)furan-3-carboxylate (6b). White
solid (58%, 95mg), Mp: 165 – 166 oC, IR (neat) ν 2959, 1722, 1588, 1495, 1215, 1088,
1026, 834, 769 cm-1. 1H NMR (500 MHz, CDCl3) δ: 3.86 (s, 3H), 3.88(s, 3H), 6.97 – 7.01
(m, 2H), 7.00 (s, 1H), 7.09 – 7.14 (m, 2H), 7.67 – 7.72 (m, 2H), 8.03 – 8.07 (m, 2H). 13C
NMR (125 MHz, CDCl3) δ: 51.7, 55.3, 107.4 (d, J = 1.3 Hz), 113.7, 114.1, 115.9 (d, J =
22.0 Hz), 122.3, 125.7 (d, J = 8.0 Hz), 126.2 (d, J = 3.4 Hz), 129.9, 150.8, 156.9, 160.6,
162.4 (d, J = 248.0 Hz), 164.0. HRESIMS calcd. for C19H16FO4 (M+H+): 327.1033; found
327.1036.
Methyl 5-(4-chlorophenyl)-2-(p-tolyl)furan-3-carboxylate (6c). White solid (48%,
78mg), Mp: 103 – 104 oC, IR (neat) ν 2980, 2936, 1714, 1463 cm-1. 1H NMR (500 MHz,
CDCl3) δ: 2.42 (s, 3H), 3.86 (s, 3H), 7.07 (s, 1H), 7.28 (d, J = 8.2 Hz, 2H), 7.37 – 7.41 (m,
2H), 7.63 – 7.68 (m, 2H), 7.96 (d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 21.6,
51.8, 108.4, 115.1, 125.3, 126.9, 128.4, 128.5, 129.1, 129.2, 133.9, 140.0, 151.1, 157.4,
164.1. HRESIMS calcd. for C19H16ClO3 (M+H+): 327.0788; found 327.0787.
Methyl 2-phenyl-5-(p-tolyl)furan-3-carboxylate (6d). White solid (62%, 91mg), Mp:
88 – 89 oC, IR (neat) ν 2949, 1719, 1596, 1486, 754 cm-1. 1H NMR (500 MHz, CDCl3) δ:
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3.85 (s, 3H), 3.86 (s, 3H), 6.95 (s, 1H), 6.92 – 6.99 (m, 2H), 7.38 – 7.43 (m, 1H), 7.64 –
7.70 (m, 2H), 8.03 – 8.09 (m, 2H). 13C NMR (125 MHz, CDCl3) δ: 51.6, 55.3, 106.2,
114.3, 115.4, 122.8, 125.5, 128.2, 128.2, 129.2, 129.9, 152.6, 156.1, 159.7, 164.2.
HRESIMS calcd. for C19H17O4 (M+H+): 309.1127; found 309.1131.
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Methyl 5-(2-methoxyphenyl)-2-(thiophen-2-yl)furan-3-carboxylate (6e). Yellow solid
(80%, 126mg), Mp: 102 - 103 oC, IR (neat) ν 2942, 1704, 1579, 1489, 1248, 1094 cm-1.
1H NMR (500 MHz, CDCl3) δ: 3.92 (s, 3H), 3.99 (s, 3H), 6.99 (d, J = 8.4 Hz, 1H), 7.03 –
7.10 (m, 1H), 7.14 (dd, J = 3.9 and 5.1 Hz, 1H), 7.27 – 7.32 (m, 2H), 7.45 (dd, J = 1.1
and 4.9 Hz, 1H), 7.9 (dd, J = 1.5 and 7.7 Hz, 1H), 8.14 (dd, J = 1.1 and 3.7 Hz, 1H). 13C
NMR (125 MHz, CDCl3) δ: 51.7, 55.6, 111.1, 112.3, 114.0, 118.6, 120.9, 126.1, 127.7,
128.0, 128.9, 132.0, 148.4, 151.4, 156.0, 164.3. HRESIMS calcd. for C17H14NaO4S
(M+Na+): 337.0511; found 337.0514.
Methyl 5-(4-(benzyloxy)-3-methoxyphenyl)-2-(4-fluorophenyl)furan-3-carboxylate
(6f). White solid (70%, 151mg), Mp: 140 - 141 oC, IR (neat) ν 2952, 1721, 1600, 1497,
1214, 1097 cm-1. 1H NMR (500 MHz, CDCl3) δ: 3.86 (s, 3H), 3.97 (s, 3H), 5.21 (s, 2H),
6.93 (d, J = 8.3 Hz, 1H), 6.95 (s, 1H), 7.12 – 7.18 (m, 2H), 7.21 – 7.26 (m, 2H), 7.30 –
7.35 (m, 1H), 7.38 (t, J = 7.5 Hz, 2H), 7.45 (d, J = 7.4 Hz, 2H), 8.04 – 8.11 (m, 2H). 13
C
NMR (125 MHz, CDCl3) δ: 51.8, 56.3, 71.2, 106.7, 107.9, 114.3, 115.3, 115.5 (d, J =
21.8 Hz), 117.1, 123.4, 126.2 (d, J = 3.3 Hz), 127.5, 128.2, 128.8, 130.5 (d, J = 8.5 Hz),
137.0, 148.6, 150.1, 152.6, 155.5, 163.4 (d, J = 250.2 Hz), 164.2. HRESIMS calcd. for
C26H21FNaO5 (M+Na+): 455.1271; found 455.1266.
Methyl 5-(9-ethyl-9H-carbazol-3-yl)-2-(p-tolyl)furan-3-carboxylate (6g). Yellow solid
(40%, 82mg), IR (neat) ν 2947, 1713, 1594, 1488, 1223, 1090 cm-1. 1H NMR (500 MHz,
CDCl3) δ: 1.46 (t, J = 7.2 Hz, 3H), 2.43 (s, 3H), 3.88 (s, 3H), 4.40 (t, J = 7.2 Hz, 2H), 7.07
(s, 1H), 7.26 – 7.33 (m, 3H), 7.43 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.5 Hz, 1H), 7.50 (td, J
= 1.1 and 7.7 Hz, 1H), 7.84 (dd, J = 1.8 and 8.5 Hz, 1H), 8.00 – 8.05 (m, 2H), 8.17 (d, J
= 7.8 Hz, 1H), 8.46 (d, J = 1.5 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ: 13.8, 21.5, 37.6,
51.6, 105.9, 108.8, 115.0, 116.2, 119.3, 120.7, 121.2, 122.3, 123.0, 123.3, 126.1, 127.3,
128.3, 129.0, 139.4, 139.8, 140.5, 153.6, 156.3, 164.4. HRESIMS calcd. for
C27H23NNaO3 (M+Na+): 432.1576; found 432.1579.
Methyl 4-bromo-2-(4-methoxyphenyl)-5-(p-tolyl)furan-3-carboxylate (6Br-a). White
solid (92%, 92mg), Mp: 131 – 132 oC, IR (neat) ν 2953, 1710, 1609, 1495, 1230, 1119,
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1034, 836 cm-1. H NMR (500 MHz, CDCl3) δ: 2.40 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H),
6.95 – 7.01 (m, 2H), 7.23 – 7.30 (m, 2H), 7.73 – 7.78 (m, 2H), 7.88 - 7.94 (m, 2H). 13C
NMR (125 MHz, CDCl3) δ: 21.5, 51.9, 55.5, 96.6, 113.8, 114.8, 122.0, 126.2, 126.4,
129.3, 129.7, 138.7, 148.8, 155.6, 160.7, 163.6. HRESIMS calcd. for C20H17BrNaO4
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(M+Na+): 425.0187; found 425.0183.
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Methyl
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(6Br-b). White solid (87%, 88mg), Mp: 161 – 162 C, IR (neat) ν 2958, 1713, 1606,
1494, 1220, 1117, 1032, 836 cm-1. H NMR (500 MHz, CDCl3) δ: 3.87 (s, 3H), 6.95 –
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7.01 (m, 2H), 7.12 – 7.19 (m, 2H), 7.72 – 7.77 (m, 2H), 7.98 – 8.03 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ: 52.0, 55.5, 97.1, 114.0, 115.0, 115.8 (d, J = 21.8 Hz), 121.9, 125.5
(d, J = 3.3 Hz), 128.4 (d, J = 8.2 Hz), 129.9, 147.9, 156.1, 161.1, 162.9 (d, J = 248.8 Hz),
163.6. HRESIMS calcd. for C19H14BrFNaO4 (M+Na+): 426.9957; found 426.9954.
Methyl 4-bromo-5-(4-chlorophenyl)-2-(p-tolyl)furan-3-carboxylate (6Br-c). White
solid (73%, 74mg), Mp: 138 – 139 oC, IR (neat) ν 2956, 1714, 1585, 1502, 1235, 1118,
1035, 816 cm-1. 1H NMR (500 MHz, CDCl3) δ: 2.42 (s, 3H), 3.88 (s, 3H), 7.27 (d, J = 7.7
Hz, 2H), 7.41 – 7.45 (m, 2H), 7.67 (d, J = 8.3 Hz, 2H), 7.96 – 8.00 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ: 21.6, 52.1, 97.8, 115.9, 126.5, 127.5, 127.7, 128.1, 129.0, 129.3,
134.7, 140.4, 147.9, 156.2, 163.5. HRESIMS calcd. for C19H14BrClNaO3 (M+Na+):
426.9713; found 426.9708.
Methyl 4-bromo-5-(4-methoxyphenyl)-2-phenylfuran-3-carboxylate (6Br-d). White
solid (92%, 89mg), Mp: 99 – 100 oC, IR (neat) ν 2949, 1706, 1567, 1486, 1026 cm-1. 1H
NMR (500 MHz, CDCl3) δ: 3.87 (s, 3H), 3.88 (s, 3H), 6.93 – 7.05 (m, 2H), 7.36 – 7.52 (m,
3H), 7.71 – 7.86 (m, 2H), 7.88 – 8.06 (m, 2H). 13C NMR (125 MHz, CDCl3) δ: 51.9, 55.3,
95.7, 114.0, 116.0, 121.7, 127.9, 127.9, 128.4, 129.4, 129.5, 149.3, 154.8, 160.0, 163.5.
HRESIMS calcd. for C19H16BrO4 (M+H+): 387.0232; found 387.0234.
Methyl 5-(4-methoxyphenyl)-2-phenyl-4,5-dihydrothiophene-3-carboxylate 3d-S.
Dihydrofuran (3d, 0.25 mmol, 1 equiv.) and Lawesson reagent (0.55 equiv.) and
dry-toluene were added to a dram vial equipped with a stir bar and a screw cap and the
resulting mixture was stirred at 110 oC for 20 h. After this time, the contents of the flask
were concentrated by rotary evaporation. The residue was purified by flash
chromatography, eluting with hexane/EtOAc to afford the dihydrothiophene 3d-S
(yellow oil (75%, 61mg)). IR (neat) ν 2947, 1707, 1511, 1249 cm-1. 1H NMR (500 MHz,
CDCl3) δ: 3.49 (dd, J = 8.1 and 16.3 Hz, 1H), 3.57 (s, 3H), 3.70 (dd, J = 9.4 and 16.3 Hz,
1H), 3.81 (s, 3H), 4.93 (dd, J = 8.2 and 9.3 Hz, 1H), 6.86 – 6.93 (m, 2H), 7.34 – 7.47 (m,
7H). 13C NMR (126 MHz, CDCl3) δ: 46.7, 51.0, 51.3, 55.5, 114.3, 118.7, 128.1, 128.4,
128.8, 129.3, 133.9, 134.0, 156.9, 159.4, 164.1. HRESIMS calcd. for C19H19O3S
(M+H+): 327.1055; found 327.1062.
Methyl
5-(4-methoxyphenyl)-2-phenylthiophene-3-carboxylate
(7).
The
dihydrothiophene 3d-S (0.25 mmol, 1 equiv) dissolved in toluene was taken into a dram
vial equipped with a stir bar and a screw cap. DDQ (0.60 mmol) was added and the
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reaction mixture was stirred at 110 oC for 12 h. After this time, the contents of the flask
were concentrated by rotary evaporation. The residue was purified by flash
chromatography, eluting with hexane/EtOAc to afford the product 7 (white solid (51%,
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41mg)). Mp: 118 – 119 C, IR (neat) ν 2949, 1718, 1608, 1494, 1463, 1252 cm-1. H
NMR (500 MHz, CDCl3) δ: 3.76 (s, 3H), 3.85 (s, 3H), 6.92 – 6.96 (m, 2H), 7.39 – 7.44 (m,
3H), 7.52 – 7.57 (m, 4H), 7.60 (s, 1H). 13C NMR (125 MHz, CDCl3) δ: 51.6, 55.4, 114.5,
124.4, 126.2, 127.1, 128.1, 128.3, 128.7, 129.8, 133.4, 142.7, 149.2, 159.7, 163.9.
HRESIMS calcd. for C19H16NaO3S (M+Na+): 347.0718; found 347.0711.
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Methyl 4-bromo-5-(4-methoxyphenyl)-2-phenylthiophene-3-carboxylate (7Br). 7
(0.25 mmol, 1 equiv.) and NBS (1.05 equiv.) and CH3CN were added to a dram vial
equipped with a stir bar and a screw cap and the resulting mixture was stirred at 50 oC
for 12 h. After this time, the contents of the flask were concentrated by rotary
evaporation. The residue was purified by flash chromatography, eluting with
hexane/EtOAc to afford the bromide 7Br (white solid (95%, 95mg)). IR (neat) ν 2948,
1
1718, 1604, 1456, 1437, 1249, 1031 cm-1. H NMR (500 MHz, CDCl3) δ: 3.80 (s, 3H),
3.87 (s, 3H), 6.97 – 7.02 (m, 2H), 7.38 – 7.49 (m, 5H), 7.55 – 7.61 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ: 52.5, 55.4, 106.5, 114.1, 124.5, 128.2, 128.8, 128.9, 130.7, 130.9,
132.6, 138.7, 144.1, 160.0, 165.0. HRESIMS calcd. for C19H15BrNaO3S (M+Na+):
424.9823; found 424.9829.
Methyl
5-(4-methoxyphenyl)-2-phenyl-4-(p-tolyl)thiophene-3-carboxylate
(8).
PdCl2(dppf) (5 mol%), bromide 7Br (0.25 mmol, 1 equiv.), and p-methylphenylboronic
acid (2 equiv.) were added under air to a dram vial equipped with a stir bar and a screw
cap. DMF and 2M Na2CO3 aq. (2 mL/mmol, 4 equiv.) were added to the mixture under
nitrogen atmosphere (charged by general N2 (99.95%) gas flow) and the reaction
o
mixture was stirred at 80 C for 12 h. After this time, the contents of the flask were
filtered through the plug of silica gel, and then concentrated by rotary evaporation. The
residue was purified by flash chromatography, eluting with hexane/EtOAc and GPC
(Gel Permeation Chromatography) to afford the product 8 (white solid (81%, 84mg)).
Mp: 174 – 175 oC, IR (neat) ν 2953, 1720, 1603, 1457, 1422 cm-1. 1H NMR (500 MHz,
CDCl3) δ: 2.35 (s, 3H), 3.53 (s, 3H), 3.78 (s, 3H), 6.74 – 6.79 (m, 2H), 7.08 – 7.16 (m,
6H), 7.34 – 7.44 (m, 3H), 7.50 – 7.55 (m, 2H). 13C NMR (125 MHz, CDCl3) δ: 21.4, 52.1,
55.3, 114.0, 126.0, 128.5, 128.7, 128.8, 129.1, 129.8, 130.5, 131.8, 132.7, 133.5, 137.1,
137.6, 139.4, 143.1, 159.3, 166.7. HRESIMS calcd. for C26H23O3S (M+H+): 415.1368;
found 415.1366.
5-(4-Methoxyphenyl)-2-phenyl-4-(p-tolyl)thiophene-3-carboxylic acid 8OH. Ester 8
(0.25 mmol, 1 equiv.) in 0.5 M NaOH aq. (2 eqiv. 4 mL/mmol) and 1,4-dioxane was
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stirred at 100 oC for 12 hr. At this time, the mixture was acidified by conc. HCl aq. and
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extracted with EtOAc to afford the carboxylic acid 8OH (white solid (95%, 95mg)), Mp:
o
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243 – 244 C, IR (neat) ν 2924, 1684, 1603, 1460, 1435 cm-1. H NMR (500 MHz,
CDCl3) δ: 2.35 (s, 3H), 3.77 (s, 3H), 6.74 – 6.78 (m, 2H), 7.08 – 7.16 (m, 6H), 7.37 –
7.43 (m, 3H), 7.53 – 7.57 (m, sH). 13C NMR (126 MHz, CDCl3) δ: 21.4, 55.3, 114.0,
125.9, 128.7, 128.8, 129.0, 129.2, 129.9, 130.2, 130.6, 132.5, 133.3, 137.2, 137.8,
139.7, 145.1, 159.3, 169.3. HRESIMS calcd. for C25H20NaO3S (M+Na+): 423.1031;
found 423.1041.
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2-(4-Methoxyphenyl)-5-phenyl-3-(p-tolyl)-4-(4-(trifluoromethyl)phenyl)thiophene
(9). PdCl2(dppf) (10 mol%), carboxylic acid 8OH (0.25 mmol,
1
equiv.),
1-iodo-4-(trifluoromethyl)benzene (2 equiv.), Cs2CO3 (3 equiv.) MS4A (300 mg/mmol)
were added under air to a dram vial equipped with a stir bar and a screw cap. Mesitylene
was added to the mixture under nitrogen atmosphere (charged by general N2 (99.95%)
o
gas flow) and the reaction mixture was stirred at 170 C for 12 h. After this time, the
contents of the flask were filtered through the plug of silica gel, and then concentrated
by rotary evaporation. The residue was purified by flash chromatography, eluting with
hexane/EtOAc and GPC (Gel Permeation Chromatography) to afford the product 9
(white solid (70%, 84mg)), IR (neat) ν 2956, 1605, 1485, 1454, 1327, 1120 cm-1. H
1
NMR (500 MHz, CDCl3) δ: 2.28 (s, 3H), 3.79 (s, 3H), 6.75 – 6.79 (m, 2H), 6.81 (d, J =
8.1 Hz, 2H), 6.94 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 7.14 – 7.20 (m, 4H), 7.21
– 7.25 (m, 3H), 7.36 (d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 21.3, 55.3, 114.0,
124.5 (q, J = 271.1 Hz), 124.9 (q, J = 3.8 Hz), 126.7, 127.6, 128.7, 128.7 (d, J = 32.6
Hz), 129.0, 129.5, 130.5, 130.8, 131.4, 133.2, 134.1, 136.6, 138.0, 138.6, 138.8, 139.0,
140.7, 159.1. HRESIMS calcd. for C31H23F3NaOS (M+Na+): 523.1319; found 523.1311.
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ASSOCIATED CONTENT
Supporting Information
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Optimization studies for the couplings and spectroscopic data for all new compounds are available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
nisikata@yamaguchiꢀu.ac.jp
ACKNOWLEDGMENT
Financial support provided by program to disseminate tenure tracking system, MEXT, Japan is gratefully
acknowledgement. We also thank Prof. Dr. Akio Kamimura (YU) for measuring HRMS.
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