Access to Substituted Thiophenes through Xanthate-Mediated Vinyl C(sp2)-Br Bond Cleavage and Heterocyclization of Bromoenynes

Article abstract of DOI:10.1021/acs.joc.0c01733

An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and safe EtOCS2K as a thiol surrogate and tetrabutylphosphonium bromide and H2O as a mixed solvent, the reaction provided a range of substituted thiophenes in moderate to good yields. In addition, 2,3,4,5-tetrasubstituted thiophenes were able to be prepared under mild reaction conditions by electrophilic heterocyclization with NH4I and EtOCS2K in good yields.

Full text of DOI:10.1021/acs.joc.0c01733

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Article
Access to Substituted Thiophenes through Xanthate Mediated Vinyl
C(sp2)-Br Bond Cleavage and Heterocyclization of Bromoenynes
Guoling Huang, Jian Li, Jianrong Li, Jiaming Li, Minghua Sun,
Peng Zhou, Lu Chen, Yubing Huang, Shaohua Jiang, and Yibiao Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01733 • Publication Date (Web): 10 Sep 2020
Downloaded from pubs.acs.org on September 12, 2020
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Access to Substituted Thiophenes through Xanthate Mediated Vinyl C(sp2)-Br
Bond Cleavage and Heterocyclization of Bromoenynes
Guoling Huanga, Jian Lia, Jianrong Lia, Jiaming Lia, Minghua Suna, Peng Zhoub, Lu Chena,
Yubing Huanga, Shaohua Jiang a*, and Yibiao Lia*
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R2
R3
R2
R2
I
TBPB
H2O
R1
Br
NH4I or I2
DMSO
+
R3
R3
R1
R1
32 examples
S
S
S
5 examples
EtO
SK
 Transition-metal-free
 EtOCS2K as thiol surrogate
 One-pot synthesis
 High efficiency and high selectivity
ABSTRACT: An environmentally sustainable strategy for the chemoselective heterocyclization of
bromoenynes through transition-metal-free sulfuration/cyclization processes is reported. Using
inexpensive and safe EtOCS2K as a thiol surrogate and tetrabutylphosphonium bromide and H2O as a
mixed solvent, the reaction provided a range of substituted thiophenes in moderate to good yields. In
addition, 2,3,4,5-tetrasubstituted thiophenes were able to be prepared under mild reaction conditions
by electrophilic heterocyclization with NH4I and EtOCS2K in good yields.
INTRODUCTION
Substituted thiophenes are an important class of sulfur-containing heterocycles,1 which are
regarded as key structural scaffolds in many natural products and pharmaceuticals.2 Furthermore,
substituted thiophenes have applications in material science,3 coordination chemistry, and organic
synthesis.4 Despite the many synthetic strategies that have been established, continued exploration
of efficient and sustainable strategies for synthesizing substituted thiophenes using simple
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conditions and readily available raw materials is still required.5-6 The general synthetic approaches
synthesis of functionalization thiophene ring are mainly based on condensation-like reactions.7 In
comparison, the annulation of suitably substituted enynes is an attractive alternative method,8-10
which allows the regioselective synthesis of thiophenes and the direct introduction of required
functional groups. The cyclization of functionalized alkynes bearing a suitable thiol group is a
powerful methodology for the regioselective synthesis of substituted thiophenes.9 Another method
for regioselective synthesis is the sulfuration/annulation of bromoenynes.10 Sanz has described a
Pd-catalyzed tandem C-S coupling/heterocyclization reaction that provided access to tri-substituted
thiophenes from bromoalkynes, where triisopropylsilanethiol was used as a hydrogen sulfide
surrogate (Scheme 1a). Interestingly, in this reaction, common effective sulfidation agents, such as
Na2S·9H2O, were less effective, mainly because of their incompatibility with sensitive functional
groups and the palladium catalytic system. Despite the diversity of methods available for
synthesizing thiophenes, the continued development of efficient and environmentally friendly
sulfidation agents and sulfidation systems is still desirable. Xanthates have been applied widely in
organic synthesis because of their availability and high reactivity.11 Xanthates can be readily
prepared on a large scale from alcohols and carbon disulphide,12 which are regarded as inexpensive
and safe starting materials. Using EtOCS2K as a thiol surrogate, our group has recently realized a
series of organic transformations,13 including the synthesis of functionalized heterocycles, such as
isothiazoles,13a (Z)-tetrahydrothiophenes,13b and thienopyridines.13c-d To further explore the potential
reactivity of xanthates, herein, we describe a transition-metal-free sulfuration/cyclization strategy for
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the synthesis of substituted thiophene derivatives, in which a thiyl radical is produced in situ from a
xanthate and acts as an active intermediate (Scheme 1b).
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Scheme 1. Methods for the Synthesis of Substituted Thiophenes from Bromoenynes
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a) Previous work:
Two steps
Si
SH
R2
R2
[Pd], Xantphos, LiHMDS
R3
R3
R1
R1
Br
S
S
？
EtO
SK
One-pot
b) This work:
Transition-metal-free
Additive-free
RESULTS AND DISCUSSION
To test our hypothesis,
we
investigated
the
reaction
using
methyl
(Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene (1a) and EtOCS2K as a model system.
Bromoenyne derivatives, which were prepared by the Pd-catalyzed bromoalkynylation of alkynes,14
were selected as model substrates for the optimization of reaction conditions. The optimal conditions
were determined to be as follows: bromoenyne 1a (1.0 mmol) and EtOCS2K (2.0 mmol) in DMF (2
mL) at 130 °C for 24 h. Under these conditions, the reaction gave 5-phenyl-2,3-dipropylthiophene 2a
in 84% yield (See ESI). Unfortunately, for bromoenynes with alkyl substitutions on the alkynyl side
chain (such as (7-bromo-6-propyldec-6-en-4-yn-1-yl)benzene and 4-bromo-5-propyltridec-4-en-6-
yne), this reaction did not occur. To expand the utility of this reaction, we further explored the
reaction conditions. Because the synthesis of substituted thiophenes by the sulfuration/cyclization
processes is based on a nucleophilic substitution reaction, we postulated that a highly polarized ionic
liquid may promote the reaction. Ionic liquids, which are composed of organic cations and organic or
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inorganic anions, have attracted attention as alternative green solvents to classical solvents mainly
because of their high thermal and chemical stability, negligible vapor pressure, easy separation, and
tunable properties. Because ionic liquids are often solids at room temperature, we designed a reaction
system with an ionic liquid and water as a mixed solvent. After screening various ionic liquids, the
pyrrole-based ionic liquid L1 was found to give the product in 32% yield (Scheme 2). Ionic liquids
containing an imidazole were generally not effective. Surprisingly, phosphine-based ionic liquids
achieved good results, and the desired products were obtained in 82% yield. Other ionic liquids, such
as trimethylsulfonium iodide and piperidine- and morpholine-based ions, were not effective. Finally,
the long-chain phosphine ionic liquid L9 was found to have an effect similar to L5. Continued
screening of phosphine-based ionic liquids found that tetrabutylphosphonium bromide (TBPB, L10)
was superior to the other reagents and gave the desired product in 89% yield. Tetrabutylammonium
bromide, a phase transfer catalyst commonly used in the chemical industry, was ineffective in this
reaction.
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Scheme 2. Optimization of Reaction Conditions with Ionic Liquids as Accelerators a
C3H7
C3H7
C3H7
S
C3H7
H2O (0.5 mL)
130 oC, 20 h
+
EtO
SK
S
Ph
Br
Ph
1a
2a
N
N
N
N
N
N
I
N
Br
BF6
BF4
L1, 32%
L4, <5%
O
L2, <5%
L3, 37%
P
I
I
S
N
N
I
Br
L6, <5%
L5, 82%
L7, <5%
L8, <5%
C11H23
P
P
N
Br
Br
L10, 89%
Br
L9, 85%
L11, 31%
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Reaction conditions: 1a (0.6 mmol), EtOCS2K (1.2 mmol) in ionic liquids (L1–L11) (1.2 mmol)
5
6
7
and H2O (0.5 mL) at 130 °C for 20 h.
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With the optimized conditions in hand, a series of bromoenynes with aromatic or heterocyclic
side chains on the alkynyl group were subsequently examined, and the results are shown in Scheme
3. Firstly, we explored the reactivity of different bromoenynes containing a para substituent on the
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t
n
benzene ring of the R1 group. Gratifyingly, both electron-donating substituents (Et, Bu, Bu, and
MeO) and electron-withdrawing substituents (Cl, Br, CF3, and Ac) were tolerated and the desired
thiophene products (2a–2i) could be achieved in good to excellent yields. In particular, substrates
with a halogen substituent could be converted into the desired products (2f and 2g) in 92% and 85%
yields, respectively. When Br or F was present at the para position of the phenyl ring, the reaction
proceeded smoothly to give the corresponding products (2j and 2k) in 87% and 81% yields,
respectively. Probably because of the effect of steric hindrance, substrates containing an ortho
substituent on the benzene ring had lower reactivity and were transformed into the desired products
(2l–2n) in lower yields. When the R1 group was naphthalene or thiophene, the bromoenyne
substrates were transformed smoothly into the corresponding products (2o and 2p) with yields of
86% and 77%, respectively. Notably, a peralkyl-substituted bromoenyne also successfully underwent
the cyclization reaction, affording 5-(3-phenylpropyl)-2,3-dipropylthiophene 2q in 75% yield.
Unfortunately,
trialkylsilyl
substituted
bromoenynes,
such
as
(Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)trimethylsilane (2r), only afforded a mixture of products
because the trimethylsilyl group is unstable under basic conditions and desilylation was observed.
Scheme 3. Substrate Scope of Bromoenynes with Different R1 Groups on the Alkynyl Group a
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nC3H7
nC3H7
n
C3H7
nC3H7
Br
S
H2O (0.5 mL)
+
TBPB, 130 oC
EtO
SK
R1
S
2
1
R1
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
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S
S
S
tBu
Et
2c, 83%
2a, 89%
nC3H7
2b, 80%
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
S
S
S
Cl
nBu
MeO
2f, 92%
2d, 82%
2e, 77%
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
S
S
S
O
F3C
Br
Br
2i, 88%
2g, 85%
Me
2h, 76%
nC3H7
nC3H7
nC3H7
OMe
nC3H7
nC3H7
nC3H7
F
S
S
S
2l, 48%
S
2j, 87%
2k, 81%
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
nC3H7
S
S
Me
Me
2m, 58%
nC3H7
Cl
Cl
2o, 86%
nC3H7
nC3H7
2r, <5%
2n, 52%
nC3H7
nC3H7
2p, 77%
Ph
nC3H7
2q, 75%
S
S
TMS
S
S
a Reaction conditions: bromoenyne 1 (0.6 mmol), EtOCS2K (1.2 mmol), TBPB (1.2 mmol), and H2O
(0.5 mL) at 130 °C for 20 h. TBPB = tetrabutylphosphonium bromide.
To investigate the scope of this approach for the synthesis of substituted thiophenes, we
subsequently examined various substituted bromoenynes (Scheme 4). When both the R2 and R3
groups were ethyl, a methyl substituent on the phenyl ring in R1 appeared to affect the reactivity of
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the substrate, resulting in a lower reaction yield (2s). The reaction proceeded smoothly when both R2
and R3 groups were alkyl (butyl or pentyl), the desired products (2uand 2w) were obtained in yields
of 79% and 83%, respectively. The addition of a fluorine atom did not appreciably affect the
reaction, as 2w was delivered in 81% yield. Changing R2 and R3 to hydrogen appeared to reduce the
reactivity of the substrates, substrates containing 4-bromophenyl and 4-fluorophenyl were converted
to the desired products (2x and 2y) in 69% and 73% yields, respectively. Attaching a benzene ring at
R3 or R2, had little effect on the reactivity of the substrates, both 2z and 2aa were obtained with good
yields. When the R3 group was a hydrogen, bromoenynes with different R2 groups (thienyl or
3-fluorophenyl) were suitable substrates to be transformed into the corresponding products in
moderate yields (2ab and 2ac). When R2 and R3 were 4-chlorophenyl and isopentyl, respectively, the
reaction proceeded smoothly and delivered 2ad in 71% yield. Substrates containing phenyl groups at
both the R2 and R3 positions could react well, and were converted to 2ae and 2af in 83% and 85%
yields, respectively.
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Scheme 4. Diversity of Substituted Bromoenynes a
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R2
R3
Br
R2
S
H
H2O (0.5 mL)
TBPB, 130 oC
+
R3
EtO
SK
R1
S
2
R1
1
nC4H9
nC4H9
9
C2H5
C2H5
C2H5
H
H
H
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C2H5
S
S
S
Me
2s, 91%
nC5H11
2t, 88%
2u, 79%
nC5H11
H
H
H
nC5H11
nC5H11
Br
S
S
S
F
2x, 69%
2v, 83%
2w, 81%
H
H
H
S
F
S
2y, 73%
H
S
2z, 85%
Cl
2aa, 86%
F
H
S
H
iPr
S
S
S
2ac, 70%
2ab, 87%
2ad, 71%
H
H
S
S
Br
2ae, 83%
2af, 85%
a Reaction conditions: bromoenyne 1 (0.6 mmol), EtOCS2K (1.2 mmol), TBPB (1.2 mmol), and H2O
(0.5 mL) at 130 °C for 20 h. TBPB = tetrabutylphosphonium bromide.
To continue investigating this electrophilic cyclization for the synthesis of multi-substituted
thiophenes, we added NH4I as an iodine source to construct iodothiophenes, in which the iodine
substituent allowed subsequent functionalization. Several bromoenynes were then examined
(Scheme 5). When the R2 and R3 groups were both either propyl or butyl, bromoenynes containing a
bromine or ethyl substituent on the benzene ring in R1 were suitable substrates, and were converted
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into iodothiophene derivatives with good to excellent yields (3a–3d). Bromoenynes with
phenylpropyl as the R1 group could also be applied in this electrophilic cyclization, and the desired
product (3e) was obtained in 72% yield. It was noteworthy that when I2 is used as the iodine source,
the reaction can also proceed smoothly and afforfed the iodocyclization product 3a in 89% yield.
Scheme 5. Synthesis of Thiophenes by Electrophilic Cyclization a
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R2
R2
R3
Br
I
S
DMSO (2 mL)
130 oC
+
+
NH4I
R3
EtO
SK
R1
S
1
R1
I
3
nC4H9
nC4H9
nC3H7
nC3H7
nC3H7
nC3H7
I
I
S
S
S
Br
Br
3a, 87%, 89%b
nC4H9
3c, 85%
3b, 82%
I
I
nC3H7
nC3H7
nC4H9
S
Ph
S
Et
3e, 72%
3d, 86%
a
Reaction conditions: bromoenyne 1 (0.6 mmol), EtOCS2K (1.2 mmol), and NH4I (1.2 mmol) in
DMSO (2.0 mL) at 130 °C for 24 h. b I2 (1.2 mmol) instead of NH4I.
To simplify the reaction steps, we attempted to synthesize substituted thiophenes from
bromoalkynes and alkynes in a one-pot synthesis (Scheme 6). (Bromoethynyl)benzene and oct-4-yne
could successively undergo the palladium-catalyzed bromoalkynylation of the alkyne and the
sulfuration/cyclization processes, and were converted into the desired product 2a in 78% yield.14c
The above experiment indicated that it is possible to synthesize thiophenes through a one-pot
method, and this reaction was highly efficient when a symmetrical alkyne was used as the substrate.
Scheme 6. One-Pot Synthesis of Thiophenes from Bromoalkynes and Alkynes
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(1) Pd(OAc)2 (5 mol%),
H
nC3H7
nC3H7
nC3H7
nC3H7
CH3CN, rt, 10 h,
Ph
1 mmol
Br
+
(2) EtOCS2K (2.2 mmol)
Ph
1.2 mmol
S
TBPB (1.5 mmol)
130 oC, 20 h
2a
, 78%
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The utility of iodothiophene as a building block to synthesize complex molecules was
subsequently examined through transition-metal-catalyzed coupling reactions (Scheme 7).
Iodothiophene could be smoothly converted into the desired product 4a in 91% yield through the
Suzuki−Miyaura coupling reaction.
Scheme 7. Synthetic Use.
Pd(Ph3)4 (10 mol%)
Cs2CO3 (2 equiv)
I
B(OH)2
+
4a, 91%
THF (2 mL), H2O (0.2 mL)
60 oC, 8 h
S
S
Under N2 conditions, the heterocyclization product 2a was obtained in 76% yield (Scheme 8a).
The result indicated that the ionic reaction mechanism could be the dominant pathway. In addition,
the reaction of (Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene in D2O (0.5 mL) produced the
deuterium-containing product 2a-D in 81% yield, suggesting that water acted as a proton donor in
the sulfuration/cyclization processes.
Scheme 8. Mechanistic Studies
C3H7
C3H7
Br
C3H7
C3H7
S
H
H2O (0.5 mL)
+
(a)
(b)
EtO
SK
TBPB(1.2 mmol)
S
Ph
o
N (1 atm)
, 130 C
2
Ph
1, 0.6 mmol
2a
, 76%
C3H7
1.2 mmol
S
C3H7
C3H7
Br
D
D2O (0.5 mL)
+
C3H7
2a-D
, 81%
EtO
SK
TBPB(1.2 mmol)
130 oC
S
Ph
Ph
1, 0.6 mmol
1.2 mmol
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A postulated mechanism, based on the literature and our previous report, is depicted in Scheme
9.15 Initially, alkenyl-substituted xanthate intermediate A is formed through a nucleophilic
substitution between bromoenyne and EtOCS2K at high temperature (130 °C). Subsequently, by
releasing COS and EtOH molecules,16 intermediate A is converted to thiolate B (which may be
formed by partial deprotonation of the thiol by the xanthate salt), followed by a 5-endo-dig
cyclization of thiolate B via the Csp-Csp triple bond to give the thiophene anion intermediate C,
which is then protonated by water to give the thiophene product 2. In this transformation process, the
phosphonium salt may be attacked by the triple bond of the bromoenyne to form the
π-complex B, which can directly activate the triple bond of the alkyne. In addition, I2 is generated
through a series of reactions, as shown in equations. 1 and 2.17 The coordination of the triple bond of
xanthate A to I2 generates the iodonium D18, then an anti-attack of the triple bond forms the
intermediate E, and subsequently the thioate group is removed from intermediate E with the aid of
an iodide anion or other base to afford the iodothiophene 3.
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Scheme 9. Possible Reaction Mechanism.
NH3
S
(1)
(2)
NH4I
+
HI
I2
O
+
+
H2O
EtOCS2K
+ 2 HI
S
S
R2
R3
R2
R3
R2
R3
S
EtOCS2H
R
P
R
R
EtO
SK
130 oC
OEt
R
SK
+
SH
H2O
COS + EtOH
R2
R3
Br
S
R1
R1
R2
B'
R1
B
A
5-exo-dig
cyclization
I2
I
R2
R3
1
R2
R3
S
H
R2
R3
R1
R2
I
OEt
S
H2O
R1
S
R3
R1
I
R1
R1
R3
I
S
3
S
2
S
C
S
OEt
R1
D
E
CONCLUSION
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In summary, we have reported a transition-metal-free strategy for the synthesis of functionalized
substituted thiophenes from bromoenynes and EtOCS2K. This method provides straightforward
access to a wide range of substituted thiophenes in moderate to good yields through the formation of
C-S bonds and subsequent heterocyclization processes. It is worth noting that a one-pot synthesis of
substituted thiophenes from bromoalkynes and alkynes is also feasible. Current efforts in our
laboratory are aimed at further applying this protocol to synthesize more complex sulfur-containing
heterocyclic molecules.
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EXPERIMENTAL SECTION
General Information: Unless otherwise noted, all commercial materials and solvents were used
without further purification and all the reactions were carried out in a Schlenk tube equipped with
1
magnetic stir bar. H NMR spectra were recorded in CDCl3 at 500 MHz or 600 MHz and 13C {1H}
1
NMR NMR spectra were recorded in CDCl3 at 125 MHz or 150 MHz respectively, H and 13C {1H}
NMR NMR were referenced to CDCl3 at δ 7.26 and 77.0 respectively. GC–MS was obtained using
electron ionization (Agilent Technologies 7890A/5975C). HRMS spectra were acquired using an
Agilent 6210 ESI/TOF mass spectrometer and MAT 95XP (Double-focusing Magnetic Sector
Analyzer), Thermo (EI, 70eV). TLC was performed using commercially prepared 100-400 mesh
silica gel plates (GF254), and visualization was effected at 254 nm. All the other chemicals were
purchased from Aldrich Chemicals, Energy Chemical and Leyan Chemical. Commercial reagents
were used without further purification.
General procedures for synthesis of bromoalkenynes 1: [14c] A 25 mL Schlenk tube was charged
with Pd(OAc)2, (12 mg, 0.05 mmol), CH3CN (2 mL), phenylethynyl bromide (216 mg, 1.2 mmol)
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and 4-octyne (110 mg, 1 mmol) and a magnetic stirring bar. The Schlenk tube was stirring for 12 h at
30 oC. After the reaction finished, the solution was filtered though a small amount of silica gel. The
residue was purified by silica gel preparative TLC (n-hexane), which furnished
(Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene 1a (244 mg, 84%) as a pale-yellow liquid.
General procedures for synthesis of bromoalkenynes 1z, 1ae and 1af: [14a] A 25 mL Schlenk tube
was charged with [JohnPhosAu(NCMe)]SbF6, (40 mg, 0.05 mmol, 5 mol%), dry 1,2-dichloroethane
(DCE) (3 mL), phenylethynyl bromide (1.0 mmol, 180 mg) and ethynylbenzene (2 mmol, 204 mg,
2.0 equiv.) and a magnetic stirring bar. The mixture was stirred at room temperature until full
conversion of the phenylethynyl bromide and the reaction time is approximately 48 hours. After the
reaction finished, the solution was filtered though a small amount of silica gel. The residue was
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purified
by
silica
gel
preparative
TLC
(n-hexane),
which
furnished
(Z)-(1-bromobut-1-en-3-yne-1,4-diyl)dibenzene 1z (203 mg, 72%) as a pale-yellow liquid.
General procedures for synthesis of (Z)-1-bromo-4-(4-bromobut-3-en-1-yn-1-yl)benzene 1x: To
a solution of the 1-bromo-4-(4,4-dibromobut-3-en-1-yn-1-yl)benzene 1x-a (180 mg, 0.5 mmol) in
toluene (5 mL) cooled to 0 °C was added Pd(PPh3)4 (60 mg, 0.05 mmol) followed by Bu3SnH (175
mg, 0.6 mmol), and the mixture was stirred at 0 °C for 5 h. Then, petroleum ether (50 mL) was
added and the organic phase washed with H2O (2×25 mL) and dried (Na2SO4). After evaporation of
the solvent the residue was adsorbed on silica gel and the crude product was purified by column
chromatography using hexane as the eluent, affording the bromoalkenyne 1x as a yellow sticky
liquid in 47% yield.
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General procedures for synthesis of thiophenes 2: A 25 mL Schlenk tube was charged with
bromoalkenynes (0.6 mmol), potassium xanthate (1.2 mmol, 192 mg, 2.0 equiv),
tetrabutylphosphonium bromide (1.2 mmol, 410 mg, 2.0 equiv), H2O (0.5 mL) and a magnetic
stirring bar. The Schlenk tube was then immersed in an oil bath at 130 oC stirring for 20 h. After the
reaction finished, the reaction mixture was diluted with ethyl acetate and passed through Celite. After
evaporation of the solvent the residue was adsorbed on silica gel and the crude product was purified
by column chromatography using hexane as the eluent, affording the thiophenes as a yellow liquid.
General procedures for synthesis of iodothiophenes 3: A 25 mL Schlenk tube was charged with
bromoalkenynes (0.6 mmol), potassium xanthate (1.2 mmol, 192 mg, 2.0 equiv), NH4I (1.2 mmol,
174 mg, 2.0 equiv.), DMSO (2.0 mL), and a magnetic stirring bar. The Schlenk tube was then
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immersed in an oil bath at 130 C stirring for 24 h. After the reaction finished, the reaction mixture
was diluted with ethyl acetate and passed through Celite. After evaporation of the solvent the residue
was adsorbed on silica gel and the crude product was purified by column chromatography using
hexane as the eluent, affording the iodothiophenes as a yellow liquid.
General procedures for one-pot synthesis of thiophenes: A mixture of Pd(OAc)2, (12 mg, 0.05
mmol), CH3CN (2 mL), 4-octyne (132 mg, 1.2 mmol), phenylethynyl bromide (1.0 mmol, 180 mg,)
and a magnetic stirring bar was added successively in Schlenk tube. After stirring for 10 h at 30 oC,
the bromoalkynylation reaction was complete. Then the potassium xanthate (2.2 mmol, 320 mg),
tetrabutylphosphonium bromide (1.5 mmol, 507 mg), and H2O (0.5 mL) was added successively in
o
Schlenk tube. The Schlenk tube was then immersed in an oil bath at 130 C stirring for 20 h. After
the reaction finished, the reaction mixture was diluted with ethyl acetate and passed through Celite.
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After evaporation of the solvent the residue was adsorbed on silica gel and the crude product was
purified by column chromatography using hexane as the eluent, affording the thiophenes as a yellow
liquid.
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General procedures for synthesis of tetraphenylthiophene 4a: A 25 mL Schlenk tube was
charged with 3-iodo-2,4,5-triphenylthiophene (0.5 mmol, 219 mg), PhB(OH)2 (0.75 mmol, 92 mg),
Pd(PPh3)4 (10 mol%, 60 mg), Cs2CO3 (1.0 mmol, 326 mg, 2.0 equiv.), THF (2.0 mL), H2O (0.2 mL),
and a magnetic stirring bar. The Schlenk tube was then immersed in an oil bath at 60 oC stirring for 8
h under N2 condition. After the reaction finished, the reaction mixture was diluted with ethyl acetate
and passed through Celite. After evaporation of the solvent the residue was adsorbed on silica gel
and the crude product was purified by column chromatography using hexane as the eluent, affording
the tetraphenylthiophene as a yellow solid (The 3-iodo-2,4,5-triphenylthiophene was prepared
directly from the previous step, after simple column chromatography, without complete purification).
Synthesis of 5-phenyl-2,3-dipropylthiophene (2a) in mmol-scale: A 25 mL Schlenk tube was
charged with (Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene 1a (1.0 mmol, 290 mg), potassium
xanthate (2.0 mmol, 290 mg, 2.0 equiv), tetrabutylphosphonium bromide (2.0 mmol, 680 mg), H2O
o
(0.6 mL) and a magnetic stirring bar. The Schlenk tube was then immersed in an oil bath at 130 C
stirring for 30 h. After the reaction finished, the reaction mixture was diluted with ethyl acetate and
passed through Celite. After evaporation of the solvent the residue was adsorbed on silica gel and the
crude product was purified by column chromatography using hexane as the eluent, affording the
thiophenes as a yellow liquid in 82 % yield (200 mg).
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14c
(Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene (1a).
Yellow liquid (244 mg, 84% yield);
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Rf = 0.65 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.60 – 7.51 (m, 2H), 7.37 (dd, J = 5.1, 2.1
Hz, 3H), 2.65 (t, J = 7.6 Hz, 2H), 2.35 (t, J = 7.6 Hz, 2H), 1.72 (ddd, J = 14.8, 9.7, 7.5 Hz, 4H), 1.03
(dt, J = 11.4, 7.4 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 132.8, 131.4 (2C), 128.2 (2C), 128.1,
124.2, 123.4, 93.1, 90.3, 38.9, 35.1, 21.9, 21.9, 13.6, 13.2. GC-MS (EI, 70 eV) m/z 290, 165 (100%),
152, 139, 115. HRMS (ESI-TOF) m/z [M+H]+: calcd for C16H20Br 291.0743; found 291.0745.
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-ethylbenzene (1b). Yellow liquid (280 mg, 88%
yield); Rf = 0.45 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.42 (d, J = 8.1 Hz, 2H), 7.15 (d, J
= 8.1 Hz, 2H), 2.68 – 2.55 (m, 4H), 2.29 (t, J = 7.6 Hz, 2H), 1.66 (dt, J = 14.9, 7.5 Hz, 4H), 1.23 (t, J
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= 7.6 Hz, 4H), 0.97 (q, J = 7.5 Hz, 6H); C {1H} NMR (125 MHz, CDCl3) δ 144.6, 132.4, 131.5
(2C), 127.8 (2C), 124.4, 120.6, 93.3, 89.7, 39.0, 35.2, 28.8, 22.0, 21.9, 15.4, 13.7, 13.2. GC-MS (EI,
70 eV) m/z 318, 181, 165 (100%), 152, 115. HRMS (ESI-TOF) m/z [M+H]+: calcd for C18H24Br
319.1056; found 319.1056.
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-butylbenzene (1c). Yellow liquid (308 mg, 89%
yield); Rf = 0.65 (petroleum ether); Rf = 0 (petroleum); 1H NMR (500 MHz, CDCl3) δ 7.39 (d, J = 8.1
Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 2.59 (dd, J = 14.7, 6.9 Hz, 4H), 2.32 – 2.23 (m, 2H), 1.65 (dt, J =
14.7, 7.4 Hz, 4H), 1.58 (dd, J = 9.0, 6.6 Hz, 2H), 1.34 (dd, J = 15.0, 7.4 Hz, 2H), 1.02 – 0.88 (m, 9H);
13C {1H} NMR (125 MHz, CDCl3) δ 143.3, 132.4, 131.4 (2C), 128.4 (2C), 124.4, 120.5, 93.4, 89.7,
39.0, 35.6, 35.2, 33.4, 22.3, 22.0, 21.9, 13.9, 13.7, 13.2. GC-MS (EI, 70 eV) m/z 346, 195, 181, 165
(100%), 157. HRMS (ESI-TOF) m/z [M+H]+: calcd for C20H28Br 347.1369; found 347.1369.
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14c
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-(tert-butyl)benzene (1d).
Yellow liquid (318
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1
mg, 92% yield); Rf = 0.65 (petroleum ether); H NMR (500 MHz, CDCl3) δ 7.44 – 7.40 (m, 2H), 7.36 –
7.31 (m, 2H), 2.63 – 2.54 (m, 2H), 2.32 – 2.23 (m, 2H), 1.70 – 1.60 (m, 4H), 1.32 (d, J = 8.6 Hz, 9H), 0.96
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(td, J = 7.4, 5.9 Hz, 6H); C {1H} NMR (125 MHz, CDCl3) δ 151.4, 132.5, 131.2 (2C), 125.2 (2C), 124.4,
120.4, 93.3, 89.7, 39.0, 35.2, 34.78, 31.1 (3C), 22.0, 21.9, 13.7, 13.3. GC-MS (EI, 70 eV) m/z 346, 333,
165 (100%), 152. HRMS (ESI-TOF) m/z [M+H]+: calcd for C20H28Br 347.1369; found 347.1373.
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-methoxybenzene (1e). 14c Yellow liquid (269 mg,
84% yield); Rf = 0.65 (petroleum ether/ethyl acetate = 50:1); 1H NMR (500 MHz, CDCl3) δ 7.47 – 7.37
(m, 2H), 6.90 – 6.77 (m, 2H), 3.81 (s, 3H), 2.58 (t, J = 7.6 Hz, 2H), 2.28 (t, J = 7.6 Hz, 2H), 1.64 (dt, J = 14.8,
7.5 Hz, 4H), 0.96 (dt, J = 8.7, 7.4 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 159.6, 133.0, 132.1
(2C), 124.4, 115.6, 114.0 (2C), 93.1, 89.1, 55.3, 39.0, 35.2, 22.0, 21.9, 13.7, 13.2. GC-MS (EI, 70 eV)
m/z 320 (100%), 197, 184, 165, 152. HRMS (ESI-TOF) m/z [M+H]+: calcd for C17H22BrO 321.0849;
foundn321.0848.
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(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-chlorobenzene (1f).
Yellow liquid (279 mg,
86% yield); Rf = 0.71 (petroleum ether/ethyl acetate = 80:1); 1H NMR (500 MHz, CDCl3) δ 7.43 (d,
J = 8.5 Hz, 2H), 7.35 – 7.28 (m, 2H), 2.62 (t, J = 7.6 Hz, 2H), 2.31 (t, J = 7.6 Hz, 2H), 1.67 (dd, J =
14.9, 7.5 Hz, 4H), 0.99 (dd, J = 15.7, 7.5 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 134.1, 133.4,
132.7 (2C), 128.6 (2C), 124.1, 121.9, 91.9, 91.3, 39.0, 35.1, 22.0, 21.9, 13.6, 13.2. GC-MS (EI, 70
eV) m/z 324, 179, 165 (100%), 152, 138. HRMS (ESI-TOF) m/z [M+Na]+: calcd for C16H18BrClNa+
347.0173; found 347.0170.
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14c
(Z)-1-bromo-4-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene (1g).
Yellow liquid (305 mg,
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83% yield); Rf = 0.72 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 2H), 7.34
(d, J = 8.4 Hz, 2H), 2.59 (t, J = 7.6 Hz, 2H), 2.28 (t, J = 7.6 Hz, 2H), 1.64 (dd, J = 14.9, 7.4 Hz, 4H),
0.96 (dd, J = 15.6, 7.6 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 133.5, 132.9 (2C), 131.5 (3C),
124.1, 122.3, 91.9, 91.4, 39.0, 35.0, 22.0, 21.9, 13.6, 13.2. GC-MS (EI, 70 eV) m/z 368, 280. 181,
169 (100%), 152, 138. HRMS (ESI-TOF) m/z [M+H]+: calcd for C16H19Br2 368.9848; found
368.9846.
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(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-4-(trifluoromethyl)benzene (1h). Yellow liquid
(279 mg, 78% yield); Rf = 0.42 (petroleum ether/ethyl acetate = 80:1); 1H NMR (500 MHz, CDCl3) δ
7.61 – 7.53 (m, 4H), 2.60 (t, J = 7.6 Hz, H), 2.29 (t, J = 7.6 Hz, 2H), 1.66 (dd, J = 14.9, 7.5 Hz, 4H),
0.96 (dt, J = 8.7, 7.4 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 134.3, 131.7 (4C), 129.9, 126.1
(q, J =333 Hz, 1C), 125.2 (q, J = 4.35 Hz, 1C), 123.9, 92.7, 91.6, 39.1, 35.0, 22.0, 21.9, 13.6, 13.2.
GC-MS (EI, 70 eV) m/z 358, 235, 183, 165 (100%), 152, 69. HRMS (ESI-TOF) m/z [M+H]+: calcd
for C17H19BrF3 359.0617; found 359.0616.
(Z)-1-(4-(4-bromo-3-propylhept-3-en-1-yn-1-yl)phenyl)ethan-1-one (1i). Yellow liquid (252 mg,
76% yield); Rf = 0.60 (petroleum ether/ethyl acetate = 50:1); 1H NMR (500 MHz, CDCl3) δ 7.90 (d,
J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 2.67 – 2.53 (m, 5H), 2.35 – 2.22 (m, 2H), 1.70 – 1.59 (m,
4H), 0.96 (dt, J = 10.0, 7.4 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 197.4, 136.0, 134.3, 131.6
(2C), 128.3, 128.2 (2C), 124.0, 93.6, 92.2, 39.1, 35.0, 26.6, 22.0, 21.9, 13.6, 13.2. GC-MS (EI, 70 eV)
m/z 332, 181, 165 (100%), 152, 115. HRMS (ESI-TOF) m/z [M+H]+: calcd for C18H22BrO 333.0849;
found 333.0846.
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(Z)-1-bromo-3-(4-bromo-3-propylhept-3-en-1-yn-1-yl)benzene (1j). Yellow liquid (309 mg, 84%
yield); Rf = 0.71 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.62 (s, 1H), 7.43 (ddd, J = 13.9,
7.4, 4.3 Hz, 2H), 7.18 (t, J = 7.9 Hz, 1H), 2.68 – 2.52 (m, 2H), 2.31 – 2.25 (m, 2H), 1.64 (dd, J =
14.9, 7.4 Hz, 4H), 0.96 (dd, J = 15.5, 7.6 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 134.1, 133.8,
131.2, 130.0, 129.7, 125.4, 124.0, 122.1, 91.6, 91.4, 39.0, 35.0, 22.0, 21.9, 13.6, 13.2. GC-MS (EI,
70 eV) m/z 368, 181, 165 (100%), 152, 139, 126. HRMS (ESI-TOF) m/z [M+H]+: calcd for
C16H19Br2 368.9848; found 368.9850.
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(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-3-fluorobenzene (1k). Yellow liquid (256 mg, 83%
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yield); Rf = 0.70 (petroleum ether/ethyl acetate = 80:1); H NMR (500 MHz, CDCl3) δ 7.32 – 7.27
(m, 2H), 7.23 – 7.18 (m, 1H), 7.07 – 7.00 (m, 1H), 2.62 (t, J = 7.6 Hz, 2H), 2.32 (t, J = 7.6 Hz, 2H),
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1.68 (ddd, J = 14.9, 7.5, 1.7 Hz, 4H), 1.00 (dt, J = 9.6, 7.4 Hz, 6H); C {1H} NMR (125 MHz,
CDCl3) δ 162.3 (d, J = 244.9 Hz, 1C), 133.7, 129.8 (d, J = 8.38 Hz, 1C), 127.3, 125.2 (d, J = 9.38 Hz,
1C), 124.0, 118.2 (d, J = 22.8 Hz, 1C), 91.7 (d, J = 3.38 Hz, 1C), 91.2, 39.0, 35.0, 21.9, 21.9, 13.6,
13.2. GC-MS (EI, 70 eV) m/z 308 (100%), 183, 170, 157, 133, 109. HRMS (ESI-TOF) m/z [M+H]+:
calcd for C16H19BrF 309.0649; found 309.0648.
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-2-methoxybenzene (1l). Yellow liquid (234 mg,
73% yield); Rf = 0.60 (petroleum ether/ethyl acetate = 50:1); 1H NMR (500 MHz, CDCl3) δ 7.48 (dd,
J = 7.6, 1.7 Hz, 1H), 7.30 (ddd, J = 8.3, 7.5, 1.8 Hz, 1H), 6.92 (ddd, J = 17.9, 12.2, 4.7 Hz, 2H), 3.90
(s, 3H), 2.62 (J = 7.6 Hz, 2H), 2.33 (J = 7.6 Hz, 2H), 1.75 – 1.62 (m, 4H), 0.99 (dt, J = 12.8, 7.4 Hz,
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6H); C {1H} NMR (125 MHz, CDCl3) δ 160.0, 133.3, 132.2, 129.6, 124.6, 120.3, 112.7, 110.7,
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94.2, 89.6, 55.8, 39.0, 35.2, 21.9, 21.9, 13.7, 13.2. GC-MS (EI, 70 eV) m/z 320 (100%), 181, 169,
152, 139, 115. HRMS (ESI-TOF) m/z [M+H]+: calcd for C17H22BrO 321.0849; found 321.0847.
(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-2,4-dimethylbenzene (1m). Yellow liquid (258 mg,
81% yield); Rf = 0.70 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 7.8 Hz, 1H), 7.03
(s, 1H), 6.99 – 6.91 (m, 1H), 2.66 – 2.56 (m, 2H), 2.47 (s, 3H), 2.35 – 2.29 (m, 5H), 1.74 – 1.61 (m,
4H), 1.06 – 0.91 (m, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 140.1, 138.3, 132.0, 131.9 (2C),
130.3 (2C), 126.2, 124.6, 120.1, 93.4, 92.5. 39.0, 35.3, 22.0, 21.9, 21.4, 20.9, 13.7, 13.2. GC-MS (EI,
70 eV) m/z 318 (100%), 209, 195, 179, 165, 152. HRMS (ESI-TOF) m/z [M+H]+: calcd for C18H24Br
319.1056; found 319.1052.
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(Z)-1-(4-bromo-3-propylhept-3-en-1-yn-1-yl)-2,4-dichlorobenzene (1n). Yellow liquid (304 mg,
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85% yield); Rf = 0.0.52 (petroleum ether); H NMR (500 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 1H),
7.41 (d, J = 2.1 Hz, 1H), 7.19 (dd, J = 8.4, 2.1 Hz, 1H), 2.64 – 2.57 (m, 2H), 2.34 – 2.26 (m, 2H),
1.66 (ddd, J = 18.0, 14.9, 7.4 Hz, 4H), 0.96 (q, J = 7.4 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ
136.6, 134.4, 134.2, 133.9, 129.3, 126.9, 124.1, 122.1, 96.2, 88.9, 39.2, 35.1, 21.9, 21.9, 13.7, 13.3.
GC-MS (EI, 70 eV) m/z 358, 215, 199, 179, 165 (100%), 152. HRMS (ESI-TOF) m/z [M+Na]+:
calcd for C16H17BrCl2Na 380.9783; found 380.9770.
(Z)-2-(4-bromo-3-propylhept-3-en-1-yn-1-yl)naphthalene (1o). Yellow liquid (296 mg, 87%
1
yield); Rf = 0.61 (petroleum ether); H NMR (500 MHz, CDCl3) δ 8.07 – 8.02 (m, 1H), 7.88 – 7.77
(m, 3H), 7.61 – 7.56 (m, 1H), 7.52 – 7.47 (m, 2H), 2.65 (t, J = 7.6 Hz, 2H), 2.36 (t, J = 7.6 Hz, 2H),
1.79 – 1.66 (m, 4H), 1.06 – 0.98 (m, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 133.1, 133.0, 132.7,
131.2, 128.4, 127.9, 127.7 (2C), 126.5, 126.4, 124.3, 120.7, 93.5, 90.7, 39.0, 35.2, 22.0, 21.9, 13.7,
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13.2. GC-MS (EI, 70 eV) m/z 340, 215, 202 (100%), 189, 176, 152. HRMS (ESI-TOF) m/z [M+H]+:
calcd for C20H22Br 341.0899; found 341.0894.
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(Z)-3-(4-bromo-3-propylhept-3-en-1-yn-1-yl)thiophene (1p). Yellow liquid (201 mg, 68% yield);
Rf = 0.65 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.47 (dd, J = 3.0, 1.1 Hz, 1H), 7.28 – 7.26
(m, 1H), 7.15 (dd, J = 5.0, 1.1 Hz, 1H), 2.58 (t, J = 7.5 Hz, 2H), 2.27 (t, J = 7.5 Hz, 2H), 1.64 (ddd, J
= 14.9, 7.5, 1.8 Hz, 4H), 0.95 (q, J = 7.3 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 143.3, 132.4,
131.4, 128.4, 124.4, 120.5, 93.4, 89.7, 39.0, 35.6, 35.2, 33.4, 22.3, 22.0, 21.9, 13.9, 13.7, 13.2.
GC-MS (EI, 70 eV) m/z 296 (100%), 187, 173, 147, 115, 97. HRMS (ESI-TOF) m/z [M+H]+: calcd
fo C14H18BrS 297.0307r; found 397.0308.
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(Z)-(7-bromo-6-propyldec-6-en-4-yn-1-yl)benzene (1q). Yellow liquid (262 mg, 79% yield); Rf =
0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.32 – 7.27 (m, 2H), 7.24 – 7.18 (m, 3H), 2.80
(t, J = 7.6 Hz, 2H), 2.54 (t, J = 7.6 Hz, 2H), 2.39 (t, J = 6.9 Hz, 2H), 2.25 – 2.14 (m, 2H), 1.93 – 1.83
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(m, 2H), 1.61 (dd, J = 14.2, 7.0 Hz, 4H), 0.94 (td, J = 7.4, 2.9 Hz, 6H); C {1H} NMR (125 MHz,
CDCl3) δ 141.8, 131.1, 128.6 (2C), 128.3 (2C), 125.8, 124.5, 93.9, 82.0, 38.8, 35.5, 34.7, 30.4, 21.9,
21.9, 19.0, 13.7, 13.2. GC-MS (EI, 70 eV) m/z 332, 253, 169, 117, 105, 91 (100%), 77. HRMS
(ESI-TOF) m/z [M+Na]+: calcd for C19H25BrNa 355.1032; found 355.1030.
(Z)-(4-bromo-3-propylhept-3-en-1-yn-1-yl)trimethylsilane (1r).14c Yellow liquid (232 mg, 81%
yield); Rf = 0.75 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 2.52 (t, J = 7.6 Hz, 2H), 2.28 (t, J
= 7.5 Hz, 2H), 1.62-1.55 (m, 4H), 0.92 (td, J = 7.4, 4.0 Hz, 6H), 0.21 (s, 9H); 13C {1H} NMR (125
MHz, CDCl3) δ 133.4, 124.4, 105.3, 98.6, 39.0, 35.0, 29.7, 21.8, 13.7, 13.3, -0.08
(3C). GC-MS (EI, 70 eV) m/z 286, 271, 137 (100%), 105, 91.
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(Z)-(4-bromo-3-ethylhex-3-en-1-yn-1-yl)benzene (1s).19 Yellow liquid (231 mg, 88% yield); Rf =
0.65 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.53 – 7.46 (m, 2H), 7.36 – 7.29 (m, 3H), 2.64
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MHz, CDCl3) δ 134.0, 131.5 (2C), 128.2 (2C), 128.2, 124.9, 123.35, 93.1, 90.0, 30.8, 26.5, 13.5
(2C). GC-MS (EI, 70 eV) m/z 262, 183, 167, 152 (100%), 115, 77. HRMS (ESI-TOF) m/z [M+H]+:
calcd for C14H16Br 263.0430; found 263.0435.
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(Z)-1-(4-bromo-3-ethylhex-3-en-1-yn-1-yl)-4-methylbenzene (1t). Yellow liquid (235 mg, 85%
yield); Rf = 0.75 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.39 (d, J = 8.1 Hz, 2H), 7.13 (d, J
= 7.9 Hz, 2H), 2.63 (q, J = 7.4 Hz, 2H), 2.35 (s, 3H), 2.32 (q, J = 7.4 Hz, 2H), 1.22 – 1.12 (m, 6H);
13C {1H} NMR (125 MHz, CDCl3) δ 138.3, 133.5, 131.4 (2C), 129.0 (2C), 125.0, 120.3, 93.4, 89.4,
30.8, 26.6, 21.5, 13.5 (2C). GC-MS (EI, 70 eV) m/z 276, 167, 152, 139, 115 (100%), 91.
(Z)-(4-bromo-3-butyloct-3-en-1-yn-1-yl)benzene (1u). Yellow liquid (313 mg, 86% yield); Rf =
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0.60 (petroleum ether); H NMR (500 MHz, CDCl3) δ 7.50 (ddd, J = 7.4, 4.2, 2.1 Hz, 2H), 7.36 –
7.25 (m, 3H), 2.64 – 2.57 (m, 2H), 2.35 – 2.27 (m, 2H), 1.64 – 1.58 (m, 4H), 1.38 (ddd, J = 15.0,
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10.8, 7.5 Hz, 4H), 0.95 (td, J = 7.3, 1.1 Hz, 6H); C {1H} NMR (125 MHz, CDCl3) δ 132.9, 131.5
(2C), 128.2 (2C), 128.1, 124.2, 123.4, 93.0, 90.4, 37.0, 32.9, 30.9, 30.8, 22.2, 21.9, 13.9, 13.9.
GC-MS (EI, 70 eV) m/z 318, 165, 152 (100%), 141, 115. HRMS (ESI-TOF) m/z [M+H]+: calcd for
C18H24Br 319.1056; found 319.1055.
(Z)-(4-bromo-3-pentylnon-3-en-1-yn-1-yl)benzene (1v). Yellow liquid (308 mg, 89% yield); Rf =
0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.54 – 7.45 (m, 2H), 7.39 – 7.29 (m, 3H), 2.60
(t, J = 7.6 Hz, 2H), 2.30 (t, J = 7.6 Hz, 2H), 1.62 (dd, J = 14.4, 6.7 Hz, 4H), 1.39 – 1.29 (m, 8H),
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0.92 (t, J = 6.9 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 133.0, 131.5 (2C), 128.2 (2C), 128.1,
124.2, 123.4, 93.0, 90.4, 37.2, 33.2, 31.3, 30.9, 28.4, 28.3, 22.5 (2C), 14.0, 14.08. GC-MS (EI, 70 eV)
m/z 346, 165, 152, 141, 115, 91 (100%). HRMS (ESI-TOF) m/z [M+H]+: calcd for C20H28Br
347.1369; found 347.1367.
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(Z)-1-(4-bromo-3-pentylnon-3-en-1-yn-1-yl)-4-fluorobenzene (1w). Yellow liquid (289 mg, 79%
yield); Rf = 0.765 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.60 – 7.40 (m, 2H), 7.14 – 6.87
(m, 2H), 2.67 – 2.53 (m, 2H), 2.37 – 2.23 (m, 2H), 1.60 (s, 4H), 1.33 (dt, J = 15.3, 7.5 Hz, 8H), 0.91
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(t, J = 7.0 Hz, 6H); C {1H} NMR (125 MHz, CDCl3) δ 163.4 (d, J = 247.8 Hz, 1C), 133.4 (d, J =
8.38 Hz, 2C), 133.1, 124.1, 119.5, 115.6 (d, J = 21.9Hz, 2C), 91.9, 90.1, 37.2, 33.1, 31.3, 30.9, 28.4,
22.5 (2C), 14.0. GC-MS (EI, 70 eV) m/z 366, 183, 170, 133, 109, 55 (100%). HRMS (ESI-TOF) m/z
[M+H]+: calcd for C20H27BrF 365.1275; found 365.1282.
1-bromo-4-(4,4-dibromobut-3-en-1-yn-1-yl)benzene (1x-a). Yellow liquid (308 mg, 85% yield);
1H NMR (500 MHz, CDCl3) δ 7.48 – 7.45 (m, 2H), 7.36 – 7.32 (m, 2H), 6.75 (s, 1H); 13C NMR (125
MHz, CDCl3) δ 132.9, 131.8, 123.4, 121.3, 119.3, 102.4, 95.9, 87.2. HRMS (ESI-TOF) m/z [M+K]+:
calcd for C10H5Br3K 400.7573; found 400.7575.
(Z)-1-bromo-4-(4-bromobut-3-en-1-yn-1-yl)benzene (1x). Yellow sticky liquid (133 mg, 47%
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yield); Rf = 0.75 (petroleum ether); H NMR (500 MHz, CDCl3) δ 7.51 – 7.43 (m, 2H), 7.39 – 7.34
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(m, 2H), 6.67 (d, J = 7.6 Hz, 1H), 6.50 (d, J = 7.6 Hz, 1H); C NMR (125 MHz, CDCl3) δ 133.1
(2C), 131.7 (2C), 123.1, 121.7, 118.4, 115.4, 95.9, 86.2. GC-MS (EI, 70 eV) m/z 284 (100%), 205,
126 77. HRMS (ESI-TOF) m/z [M+H]+: calcd for C10H7Br2 284.8909; found 284.8904.
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(Z)-1-(4-bromobut-3-en-1-yn-1-yl)-4-fluorobenzene (1y). Yellow liquid (47 mg, 21 % yield); Rf =
0.75 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.49 (dd, J = 8.4, 5.5 Hz, 2H), 7.03 (t, J = 8.6
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Hz, 2H), 6.64 (d, J = 7.6 Hz, 1H), 6.51 (d, J = 7.6 Hz, 1H); C {1H} NMR (125 MHz, CDCl3) δ
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133.6 (d, J = 8.3 Hz, 2C), 125.6 (d, J = 32.3 Hz, 1C), 118..8 (d, J = 3.4 Hz, 1C), 118.0, 115.8, 115.6
(d, J = 12.9 Hz, 2C), 96.0, 84.9. GC-MS (EI, 70 eV) m/z 224, 145, 125, 98, 74 (100%), 57, HRMS
(ESI-TOF) m/z [M+H]+: calcd for C10H7BrF 224.9710; found 224.9708.
(Z)-(1-bromobut-1-en-3-yne-1,4-diyl)dibenzene (1z). 21 Yellow liquid (147 mg, 52% yield); Rf =
0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.67 – 7.61 (m, 2H), 7.59 – 7.53 (m, 2H), 7.42
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– 7.34 (m, 6H), 6.67 (s, 1H); C {1H} NMR (125 MHz, CDCl3) δ 138.2, 135.0, 131.6 (2C), 129.5,
128.7, 128.5 (2C), 128.4 (2C), 127.4 (2C), 123.0, 111.2, 97.2, 87.9. GC-MS (EI, 70 eV) m/z 282, 202
(100%), 150, 126, 77. HRMS (ESI-TOF) m/z [M+H]+: calcd for C16H12Br 283.0117; found
283.0113.
(Z)-(4-bromobut-3-en-1-yne-1,3-diyl)dibenzene (1aa). 22 Yellow liquid (220 mg, 78% yield); Rf =
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0.60 (petroleum); 1H NMR (500 MHz, CDCl3) δ 7.63-7.58 (m, 4H), 7.42-7.38 (m, 6H); C NMR
(125 MHz, CDCl3) δ 136.8, 131.8 (2C), 130.2, 128.9, 128.7 (2C), 128.6, 128.4 (2C), 126.3 (2C),
122.7, 113.1, 97.8, 86.5. GC-MS (EI, 70 eV) m/z 282, 202, 176, 150, 126, 77. HRMS (ESI-TOF) m/z
[M+H]+: calcd for C16H12Br 283.0117; found 283.0113.
(Z)-1-(4-bromo-7-methyl-1-phenyloct-3-en-1-yn-3-yl)-4-chlorobenzene
(1ab-1)
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(Z)-1-(1-bromo-5-methyl-2-(phenylethynyl)hex-1-en-1-yl)-4-chlorobenzene (1ab-2). Yellow
liquid (247 mg, 64% yield,); Rf = 0.65 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.56 – 7.45
(m, 4H), 7.39 – 7.33 (m, 8H), 7.33 – 7.27 (m, 6H), 2.58 – 2.16 (m, 4H), 1.57 – 1.48 (m, 6H), 0.82 (d,
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J = 6.2 Hz, 12H); 13C {1H} NMR (125 MHz, CDCl3) δ 137.8, 137.6, 136.3, 134.5, 133.8, 131.6 (2C),
131.5 (2C), 130.3 (2C), 129.9 (2C), 128.7 (2C), 128.6 (2C), 128.5 (2C), 128.4 (2C), 128.3 (2C),
127.4, 124.7, 124.0, 123.0, 122.9, 95.9, 94.5, 90.1, 89.7, 38.1, 37.8, 35.9, 32.3, 27.5, 27.4, 22.4 (2C),
22.3 (2C). GC-MS (EI, 70 eV) m/z 386, 281, 251, 236, 215 (100%), 202. HRMS (ESI-TOF) m/z
[M+H]+: calcd for C21H21BrCl 387.0510; found 387.0507.
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(Z)-(1-bromobut-1-en-3-yne-1,2,4-triyl)tribenzene (1ac).19 Yellow solid (183 mg, 51% yield); Rf =
0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.59 (dd, J = 6.6, 3.0 Hz, 2H), 7.40 – 7.36 (m,
3H), 7.28 (dd, J = 6.2, 2.7 Hz, 4H), 7.21 (tt, J = 5.0, 2.5 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3)
δ 139.4, 137.6, 131.7 (2C), 130.1 (2C), 129.8, 129.5 (2C), 128.7, 128.6, 128.3 (2C), 128.1 (2C),
128.0 (2C), 127.6, 126.3, 123.0, 96.05, 91.3. GC-MS (EI, 70 eV) m/z 358, 279 (100%), 202, 138, 77.
HRMS (ESI-TOF) m/z [M+H]+: calcd for C22H16Br 359.0430; found 359.0426.
(Z)-(1-bromo-4-(4-bromophenyl)but-1-en-3-yne-1,2-diyl)dibenzene (1ad). Yellow sticky liquid
(232 mg, 53% yield); Rf = 0.50 (petroleum ether/ethyl acetate = 80:1); 1H NMR (500 MHz, CDCl3) δ
7.51 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.30 – 7.18 (m, 10H); 13C {1H} NMR (125 MHz,
CDCl3) δ 139.2, 137.4, 133.1 (2C), 131.6 (2C), 130.3, 130.0 (2C), 129.4 (2C), 128.7, 128.1 (2C),
128.0 (2C), 127.7, 126.0, 123.0, 121.9, 94.7, 92.4. GC-MS (EI, 70 eV) m/z 440, 438, 436, 357, 278
(100%), 200, 77. HRMS (ESI-TOF) m/z [M+H]+: calcd for C22H15Br2 436.9535; found 436.9529.
(Z)-1-bromo-4-(4-bromo-3-butyloct-3-en-1-yn-1-yl)benzene ((1ae). Yellow liquid (341 mg, 86%
yield); Rf = 0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 2H), 7.34 (d, J
= 8.3 Hz, 2H), 2.65 – 2.54 (m, 2H), 2.35 – 2.25 (m, 2H), 1.58 (t, J = 7.5 Hz, 4H), 1.37 (dt, J = 15.7,
7.9 Hz, 4H), 0.94 (t, J = 7.3 Hz, 6H); 13C {1H} NMR (125 MHz, CDCl3) δ 133.6, 132.9 (2C), 131.5
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(2C), 124.0, 122.4, 122.4, 91.9, 91.5, 37.0, 32.8, 30.9, 30.7, 22.2, 21.9, 13.9 (2C). GC-MS (EI, 70 eV)
m/z 396, 195, 179, 165 (100%), 152, 139. HRMS (ESI-TOF) m/z [M+H]+: calcd for C18H23Br2
397.0161; found 397.0165.
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(Z)-1-(4-bromo-3-butyloct-3-en-1-yn-1-yl)-4-ethylbenzene (1af). Yellow liquid (318 mg, 92%
yield); Rf = 0.60 (petroleum ether); 1H NMR (500 MHz, CDCl3) δ 7.41 (d, J = 8.1 Hz, 2H), 7.15 (d, J
= 8.0 Hz, 2H), 2.63 (dt, J = 24.2, 7.6 Hz, 4H), 2.35 – 2.27 (m, 2H), 1.66 – 1.56 (m, 4H), 1.37 (dt, J =
9.1, 7.5 Hz, 4H), 1.23 (t, J = 7.6 Hz, 3H), 0.95 (t, J = 7.4 Hz, 6H); 13C {1H} NMR (125 MHz,
CDCl3) δ 144.6, 132.5, 131.5(2C), 127.8 (2C), 124.3, 120.6, 93.3, 89.7, 36.9, 33.0, 30.9, 30.8, 28.8,
22.2, 21.9, 15.4, 13.9, 13.9. GC-MS (EI, 70 eV) m/z 346, 195, 165 (100%), 152, 139, 119. HRMS
(ESI-TOF) m/z [M+H]+: calcd for C20H28Br 347.1369; found 347.1368.
5-phenyl-2,3-dipropylthiophene (2a).10 Yellow liquid (130.3 mg, 89% yield); 1H NMR (500 MHz,
CDCl3) δ 7.56-7.54 (m, 2H), 7.35 – 7.31 (m, 2H), 7.24 – 7.20 (m, 1H), 7.05 (s, 1H), 2.71 (t, J=7.6
Hz, 2H), 2.50 (t, J=7.6 Hz, 2H), 1.73 – 1.65 (m, 2H), 1.65 – 1.58 (m, 2H), 1.01 (t, J = 7.3 Hz, 3H),
0.97 (t, J = 7.3 Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 139.3, 138.7, 134.7, 131.4, 128.6 (2C),
126.6, 125.2 (2C), 124.7, 30.3, 29.8, 25.0, 23.9, 13.9, 13.8.
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5-(4-ethylphenyl)-2,3-dipropylthiophene (2b). Yellow liquid (130.6 mg, 80% yield); H NMR
(500 MHz, CDCl3) δ 7.48 – 7.44 (m, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.01 (s, 1H), 2.71 (t, J = 7.7 Hz,
2H), 2.65 (q, J = 7.6 Hz, 2H), 2.49 (t, J = 7.7 Hz, 2H), 1.73 – 1.58 (m, 4H), 1.25 (t, J = 7.6 Hz, 3H),
1.01 (t, J = 7.4 Hz, 3H), 0.97 (t, J = 7.3 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ 142.9, 139.6,
138.7, 138.2, 132.3, 128.2 (2C), 125.3 (2C), 124.3, 30.4, 29.9, 28.5, 25.1, 24.0, 15.5, 14.1, 13.9.
HRMS (ESI): C18H25S [(M+H)+]: calcd for 273.1671; found 273.1667.
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5-(4-(tert-butyl)phenyl)-2,3-dipropylthiophene (2c). Yellow liquid (149.4 mg, 83% yield); H
NMR (500 MHz, CDCl3) δ 7.52 – 7.48 (m, 2H), 7.40 – 7.36 (m, 2H), 7.03 (s, 1H), 2.73 (t, J =7.6 Hz,
2H), 2.51 (t, J = 7.7 Hz, 2H), 1.75 – 1.59 (m, 4H), 1.35 (s, 9H), 1.02 (t, J = 7.5 Hz, 3H), 0.98 (t, J =
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7.5 Hz, 3H). C {1H} NMR (125 MHz, CDCl3) δ 149.8, 139.5, 138.6, 138.2, 132.0, 125.6 (2C),
125.0 (2C), 124.4, 34.5, 31.3, 30.4, 29.9, 25.1, 24.0, 14.0, 13.9. HRMS (ESI-TOF) m/z [M+H]+:
calcd for C20H29S 301.1984; found 301.1982.
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5-(4-butylphenyl)-2,3-dipropylthiophene (2d). Yellow liquid (147.6 mg, 82% yield); H NMR
(400 MHz, CDCl3) δ 7.44 (d, J = 7.8 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 6.99 (s, 1H), 2.69 (t, J = 7.7
Hz, 2H), 2.58 (t, J = 7.8 Hz, 2H), 2.48 (t, J = 7.7 Hz, 2H), 1.70 – 1.57(m, 6H), 1.35 (q, J = 7.4 Hz,
2H), 1.00 – 0.92 (m, 9H); C {1H} NMR (100 MHz, CDCl3) δ 141.7, 139.8, 138.8, 138.3, 132.4,
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128.9 (2C), 125.4 (2C), 124.4, 35.4, 33.7, 30.6, 30.1, 25.2, 24.1, 22.5, 14.2, 14.1, 14.0. HRMS
(ESI-TOF) m/z [M+H]+: calcd for C20H29S 301.1984; found 301.1981.
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5-(4-methoxyphenyl)-2,3-dipropylthiophene (2e). Yellow liquid (126.6 mg, 77% yield); H NMR
(500 MHz, CDCl3) δ 7.49 – 7.45 (m, 2H), 6.94 (s, 1H), 6.89 – 6.86 (m, 2H), 3.83 (s, 3H), 2.71 (t, J =
7.6 Hz, 2H), 2.49 (t, J = 7.7 Hz, 2H), 1.73 – 1.58 (m, 4H), 1.01 (t, J =7.3 Hz, 3H), 0.97 (t, J = 7.3 Hz,
3H). 13C {1H} NMR (125 MHz, CDCl3) δ 158.8, 139.5, 138.8, 137.8, 127.9, 126.7 (2C), 123.9,
114.2 (2C), 55.4, 30.5, 30.1, 25.3, 24.1, 14.2, 14.1. HRMS (ESI-TOF) m/z [M+H]+: calcd for
C17H23OS 275.1464; found 275.1458.
5-(4-chlorophenyl)-2,3-dipropylthiophene (2f).10 Yellow liquid (153.5 mg, 92% yield); H NMR
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(600 MHz, CDCl3) δ 7.48 – 7.45 (m, 2H), 7.31 – 7.28 (m, 2H), 7.02 (s, 1H), 2.71 (t, J = 7.8 Hz, 2H),
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2.49 (t, J = 7.2 Hz, 2H), 1.71-1.58 (m, 4H), 1.01 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.2 Hz, 3H). C
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{1H} NMR (125 MHz, CDCl3) δ 139.3, 139.0, 138.1, 133.3, 132.6, 128.8 (2C), 126.4 (2C), 125.2,
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5-(4-bromophenyl)-2,3-dipropylthiophene (2g). Yellow oil (164.2 mg, 85% yield); H NMR (400
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MHz, CDCl3) δ 7.43 – 7.36 (m, 4H), 7.00 (d, J = 2.1 Hz, 1H), 2.72 – 2.65 (m, 2H), 2.50 – 2.44 (m,
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2H), 1.71 – 1.55 (m, 4H), 1.02 – 0.92 (m, 6H). C {1H} NMR (100 MHz, CDCl3) δ 139.3, 139.0,
138.1, 133.8, 131.7 (2C), 126.7 (2C), 125.1, 120.4, 30.3, 30.0, 25.0, 23.9, 14.0, 13.9; HRMS
(ESI-TOF) m/z [M+H]+: calcd for C16H20BrS 323.0464; found 323.0461.
2,3-dipropyl-5-(4-(trifluoromethyl)phenyl)thiophene (2h).10 Yellow oil, (142.3 mg, 76% yield).
1H NMR (600 MHz, CDCl3) δ 7.64 – 7.61 (m, 2H), 7.59 – 7.56 (m, 2H), 7.13 (s, 1H), 2.75 – 2.71
(m, 2H), 2.52 – 2.48 (m, 2H), 1.73 – 1.66 (m, 2H), 1.66 – 1.59 (m, 2H), 1.01 (t, J = 7.3 Hz, 3H), 0.97
(t, J = 7.3 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ 140.6, 139.3, 138.1, 137.6 , 128.2, 126.4 (q,
J = 270.0 Hz.) , 126.2 (2C), 125.7 (q, J = 3.7 Hz.), 125.2 (2C), 30.5, 30.2, 25.2, 24.1, 14.2, 14.0.
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1-(4-(4,5-dipropylthiophen-2-yl)phenyl)ethan-1-one (2i). Yellow oil (151.0 mg, 88% yield), H
NMR (500 MHz, CDCl3) δ 7.94 – 7.89 (m, 2H), 7.63 – 7.58 (m, 2H), 7.18 (s, 1H), 2.73 (t, J = 7.8
Hz, 2H), 2.60 (s, 3H), 2.50 (t, J = 7.8 Hz, 2H), 1.72 – 1.59 (m, 4H), 1.01 (t, J = 7.2 Hz, 3H), 0.97 (t,
J = 7.2 Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 197.4, 141.0, 139.4, 139.2, 138.0, 135.0, 129.0
(2C), 126.5, 124.8 (2C), 30.30, 30.0, 26.5, 25.0, 23.9, 14.0; HRMS (ESI-TOF) m/z [M+H]+: calcd for
C18H23OS 287.1464; found 287.1460.
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5-(3-bromophenyl)-2,3-dipropylthiophene (2j). Yellow oil (168.1mg, 87% yield); H NMR (500
MHz, CDCl3) 1H NMR (500 MHz, CDCl3) δ 7.70 (t, J = 1.8 Hz, 1H), 7.46 (ddd, J = 7.8, 1.8, 1.0 Hz,
1H), 7.34 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H), 7.20 (t, J = 7.9 Hz, 1H), 7.06 (s, 1H), 2.72 (J = 7.5 Hz, 2H),
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2.52 – 2.47 (J = 7.5 Hz, 2H), 1.73 – 1.65 (m, 2H), 1.65 – 1.58 (m, 2H), 1.01 (t, J = 7.4 Hz, 3H), 0.97
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(t, J = 7.4 Hz, 3H); C {1H} NMR (125 MHz, CDCl3) δ 139.8, 139.0, 137.6, 136.8, 130.2, 129.5,
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for C16H20BrS 323.0464; found 323.0459.
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5-(3-fluorophenyl)-2,3-dipropylthiophene (2k). Yellow oil (127.3 mg, 81% yield); H NMR (500
MHz, CDCl3) δ 7.34 – 7.31 (m, 1H), 7.30 – 7.23 (m, 2H), 7.07 (s, 1H), 6.94-6.89 (m, 1H), 2.72 (t, J
= 7.5 Hz, 2H), 2.50(t, J = 7.5 Hz, 2H), 1.74 – 1.58 (m, 4H), 1.02 (t, J = 7.5 Hz, 3H), 0.98 (t, J = 7.5
Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 163.2 (d, J = 245.0 Hz), 139.8 , 139.1 , 138.2 (d, J =
2.7 Hz), 137.1 (d, J = 8.3 Hz), 130.3 (d, J = 9.1 Hz), 125. 7 , 121.0 (d, J = 2.7 Hz), 113.6 (d, J = 21.1
Hz), 112.1 (d, J = 22.5 Hz), 30.3, 29.9, 25.0, 23.9, 14.0, 13.9. HRMS (ESI-TOF) m/z [M+H]+: calcd
for C16H20FS 263.1264; found 263.1262.
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5-(2-methoxyphenyl)-2,3-dipropylthiophene (2l). Yellow oil (78.9 mg, 48% yield). H NMR (400
MHz, CDCl3) δ 7.59 – 7.56z (m, 1H), 7.23 (s, 1H), 7.22 – 7.18 (m, 1H), 6.98 – 6.93 (m, 2H), 3.92
(s, 3H), 2.72 (t, J = 7.6 Hz, 2H), 2.51 (t, J = 7.6 Hz, 2H), 1.73 – 1.58 (m, 4H), 1.03 – 0.94 (m, 6H);
13C {1H} NMR (100 MHz, CDCl3) δ 155.5, 139.1, 137.6, 134.7, 128.1, 127.6, 127.5, 123.8, 121.8,
111.5, 55.5, 30.4, 29.9, 25.1, 24.12, 14.1, 14.0. HRMS (ESI-TOF) m/z [M+H]+: calcd for C17H23OS
275.1464; found 275.1458.
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5-(2,4-dimethylphenyl)-2,3-dipropylthiophene (2m). Yellow liquid (94.7 mg, 58% yield); H
NMR (500 MHz, CDCl3) δ 7.32 (d, J = 7.8 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.79 (s,
1H), 2.79 – 2.71 (m, 2H), 2.57 – 2.50 (m, 2H), 2.45 (s, 3H), 2.36 (s, 3H), 1.73 (dt, J = 15.1, 7.4 Hz,
2H), 1.64 (dd, J = 15.1, 7.5 Hz, 2H), 1.04 (t, J = 7.3 Hz, 3H), 1.00 (t, J = 7.3 Hz, 3H); C {1H}
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