Palladium-Catalyzed Desulfitative Cross-Coupling of Arylsulfonyl Hydrazides with Terminal Alkynes: A General Approach toward Functionalized Internal Alkynes

Article abstract of DOI:10.1021/acs.joc.7b00899

A palladium-catalyzed Sonogashira-type coupling between arylsulfonyl hydrazides and terminal alkynes via Ar(C)-S bond cleavage is disclosed, which enables the general synthesis of functionalized internal alkynes, especially the Br-substituted ones, in good to excellent yields under acid- and base-free conditions.

Full text of DOI:10.1021/acs.joc.7b00899

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Article
Palladium-Catalyzed Desulfitative Cross-Coupling
of Arylsulfonyl Hydrazides with Terminal Alkynes: A
General Approach toward Functionalized Internal Alkynes
Liang-Wei Qian, Mengli Sun, Jianyu Dong, Qing Xu, Yongbo Zhou, and Shuang-Feng Yin
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 Jun 2017
Downloaded from http://pubs.acs.org on June 15, 2017
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The Journal of Organic Chemistry
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Palladium-Catalyzed Desulfitative Cross-Coupling of Arylsulfonyl
Hydrazides with Terminal Alkynes: A General Approach toward
Functionalized Internal Alkynes
LiangꢀWei Qian,a Mengli Sun,a Jianyu Dong,a,* Qing Xu,b Yongbo Zhou,a,* and ShuangꢀFeng Yina
aState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan
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University, Changsha 410082 Hunan, China
bCollege of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 Zhejiang, China
ABSTRACT
A palladiumꢀcatalyzed Sonogashiraꢀtype coupling between arylsulfonyl hydrazides and terminal alkynes via Ar(C)–S
bond cleavage is disclosed, which enables the general synthesis of functionalized internal alkynes, especially the
Brꢀsubstituted ones, in good to excellent yields under acidꢀ and baseꢀfree conditions.
INTRODUCTION
Internal alkynes, especially the functionalized ones, are an important class of unsaturated organic compounds that are
ubiquitously found in many natural products and molecular organic materials.1 They are extremely useful synthons in
organic chemistry toward heterocycles, biorelevant compounds, and materials.1,2 The transition metalꢀcatalyzed
Sonogashiraꢀtype crossꢀcoupling reactions that were independently developed by Sonogashira,3a Cassar,3b and Heck3c
have emerged as the most powerful tools for the construction of internal alkyne skeletons (Scheme 1).4 Over the past
two decades, great efforts have been made in the pursuit of new coupling partners, broader substrate scope, and/or
simpler reaction conditions.4–13 A number of electrophiles (ArZ) such as iodonium tetrafluoroborate,6
tetraarylphosphoniums,7 boronic acids,8 arenesulfonyl chlorides,9 tosylates,10 aryl amines,11 aryldiazonium salts,12 and
sodium sulfinates13 have been utilized as coupling partners for the synthesis of internal alkynes. Despite notable
achievements, there is a general need of additional bases or acids, which might lead to limited functional groups
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tolerance. Therefore, protocols for general and facile syntheses of these compounds are still desired.
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As a our continuous interest in selective transformation of terminal alkynes,14 we aim to develop a general method
for the synthesis of functionalized internal alkynes, and it is realized that the use of easily accessible electrophiles
under additional acidꢀ and baseꢀfree conditions would be a promising choice. Since the readily available and airꢀstable
arylsulfonyl hydrazides are good crossꢀcoupling partners for ready generation of reactive diazo compounds,15 we
envisioned that they might also be good electrophiles in Sonogashiraꢀtype cross coupling reactions to give the useful
internal alkynes. It is noted that the groups of Tian and Deng have independently employed arylsulfonyl hydrazides as
aryl sources in Heckꢀtype16 and direct C–H bond arylation reactions17 via desulfitation processes.
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Scheme 1. Synthesis of Internal Alkynes
Herein we describe a palladiumꢀcatalyzed Sonogashiraꢀtype reaction of arylsulfonyl hydrazides with terminal
alkynes for the synthesis of 1,2ꢀdisubstituted acetylenes under additional acidꢀ or baseꢀfree conditions. Both
Brꢀsubstituted arylsulfonyl hydrazides and terminal alkynes are well tolerated, providing a general synthesis of
Brꢀfunctionalized internal alkynes (Scheme 1).
Brꢀsubstituted compounds could be ideal precursors for many coupling reactions because of their easy availability
and suitable reactivity. However, Brꢀsubstituted internal alkynes could hardly be produced from easily available
Brꢀsubstituted substrates by the traditional Sonogashiraꢀtype crossꢀcoupling reactions under alkaline conditions due to
their instability under such conditions, consequently limiting the application of the synthesis of more complex targets
(Scheme 1). Only a few examples have been reported in alternative reactions.8b–e,12a–d,13 Very recently, several
Brꢀsubstituted diarylacetylenes (seven examples) have been successfully prepared from arylhydrazines and aromatic
alkynes by Song’s group, and moderate yields (50‒71%) were observed from 3.5 equiv of one starting material, and
aliphatic alkynes are far from being applicable.18
RESULTS AND DISCUSSION
In our initial research, we performed the reaction between 4ꢀmethylbenzenesulfonohydrazide (1a, 0.2 mmol) and
ethynylbenzene (2a, 1.0 equiv) in the presence of Pd(OAc)2 (5 mol %), 1,10ꢀphen (5 mol %), and Cu(OAc)2·H2O
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Table 1. Optimization of the Reaction Conditionsa,b
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aReaction conditions: 1a (0.2 mmol), 2a (0.2 mmol, 1.0 equiv), catalyst (5 mol %), ligand (5 mol %), oxidant (0.4
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b
mmol, 2.0 equiv), DMF (2.0 mL), N2, 100 °C, 0.5 h. Yields were based on the GC analysis with dodecane as the
internal standard. c10 mol % of ligand was used. d2a (1.2 equiv), Cu(OAc)2·H2O (2.4 equiv). ePd(OAc)2 1 mol %, dppp
1 mol %. fPd(OAc)2 3 mol %, dppp 3 mol %. g0.25 h. h120 °C. i80 °C.
(2.0 equiv) in DMF at 100 °C for 0.5 h. The desired desulfitative coupling product 1ꢀmethylꢀ4ꢀ(phenylethynyl)benzene
(3a) was obtained in a 20% yield (Table 1, entry 1). Subsequently, a range of ligands such as PPh3, PCy3,
bis(diphenylphosphino)methane
(dppm),
1,2ꢀbis(diphenylphosphino)ethane
(dppe),
and
1,3ꢀbis(diphenylphosphino)propane (dppp) were examined (Table 1, entries 2–6), and dppp gave the best yield
(78%,Table 1, entry 6). For palladium catalysts, PdCl2 and Pd(TFA)2 also showed good efficiency (Table 1, entries 7
and 8), whereas Pd(OH)2 and Pd2(dba)3 gave low yields of 3a (Table 1, entries 9 and 10). An assessment of oxidants
revealed that Cu(OAc)2·H2O was optimal for the reaction (Table 1, entry 6), molecular oxygen, benzoquinone (BQ),
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K2S2O8, and Ag2CO3 only gave a trace amount of the desired product (Table 1, entries 11–14). Other solvents such as
DMSO, dioxane, toluene, and CH3CN, were inferior to DMF (Table 1, entries 15–18). Greater loadings of 2a and
Cu(OAc)2·H2O further improved the yield of 3a (84%, Table 1, entry 19). Smaller loading of Pd(OAc)2 (1 and 3 mol %)
lowered the product yields (53 and 70%, respectively, entries 20 and 21). By reducing the reaction time to 0.25 h, the
yield of 3a decreased to 45% (Table 1, entry 22). The reaction was also sensitive to the reaction temperature, and a
lower yield of 3a was observed at temperature higher or lower than 100 °C (Table 1, entries 23 and 24).
Table 2. Substrate Scope of Terminal Alkynesa,b
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aReaction conditions: 1 (0.2 mmol), 2 (0.24 mmol, 1.2 equiv), Pd(OAc)2 (5 mol %), dppp (5 mol %), Cu(OAc)2·H2O
(0.48 mmol, 2.4 equiv), DMF (2.0 mL), N2, 100 °C, 0.5 h. bIsolated yields.
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Table 3. Synthesis of Br-substituted Internal Alkynesa,b
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R
Pd(OAc)2 (5 mol %)
SO2NHNH2
dppp
(5 mol %)
Ar
+
.
Ar
R
Cu(OAc)2 H2O (2.4 equiv)
DMF, N2, 100 oC, 0.5 h
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OH
Si
O
Ph
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Br
Br
Br
3w, 67%
3x, 51%
3y, 62%
n-Pr
O
N
O
Br
Br
Br
3z, 73%
3za, 74%
CN
Br
Fe
Br
Br
3zb, 75%
3zc, 62%
3zd, 80%
n-Pr
n-Pr
N
Br
Br
Br
R
3ze, 60%
3zf, 72%
3zh, R = 4-H,
3zi, R = 4-OMe, 57%
3zj, R = 4-tBu, 64%
3zg, 34%
3zl, R = 4-F,
3zm, R = 4-Cl, 81%
3zn, R = 3-Cl, 84%
Br
75%
85%
3zk, R = 4-Me,
71%
3zo, R = 4-NO2,
92%
Br
Br
Br
I
3zp, 56%
3zq, 86%
3zr, 48%
aReaction conditions: 1 (0.2 mmol), 2 (0.24 mmol, 1.2 equiv), Pd(OAc)2 (5 mol %), dppp (5 mol %), Cu(OAc)2·H2O
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(0.48 mmol, 2.4 equiv), DMF (2.0 mL), N2, 100 °C, 0.5 h. bIsolated yields.
With the optimized conditions in hand, we investigated the scope and generality of the reaction. As shown in Table 2,
this Sonogashiraꢀtype cross coupling reaction exhibited a wide scope of substrates and an outstanding tolerance toward
functional groups, producing various 1,2ꢀdisubstituted acetylenes in good to excellent isolated yields. Aromatic alkynes
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substituted with alkyl (3b‒h), F (3i), Cl (3j,k), OMe (3l), CH3CO (3m), NO2 (3n), CF3 (3o), and CN (3p) worked well
to give the corresponding internal alkynes in 69‒84% yields, regardless of steric hindrance. The attachment of strong
electronꢀwithdrawing groups such as F (3i), NO2 (3n), and CF3 (3o) resulted in slightly lower yields (69, 73, and 70%,
respectively). Aliphatic alkynes were also good substrates, producing the corresponding internal alkynes in 61‒85%
yields (3q‒u). Heteroaromatic alkyne that contains thiophene reacted efficiently, giving the corresponding product in a
72% yield (3v).
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Gratifyingly, the potentially labile Br that is reactive in many coupling reactions was inert in this reaction system,
regardless of where it is anchored in arylsulfonyl hydrazides and terminal alkynes (Table 3). A broad range of
Brꢀsubstituted internal alkynes were produced in good to excellent yields using this strategy (3w‒zr). Functional
groups, including primary alcohols (3w), ethers (3x,zi), silicane (3y), amides (3z), alkyl (3za,zj,zk), ferrocene (3zb),
CN (3zc), pyridine (3ze), F (3zl), Cl (3zm,zn), and NO2 (3zo), could survive together with Br. Internal alkyne 3zr
halogenated by both Br and I was also achieved, albeit in moderate yield. These clearly demonstrate the great potential
of this new methodology for accessing highly functionalized internal alkynes from these Brꢀsubstituted alkynes. In
contrast,
the
reaction
was
sensitive
to
a
the
steric
hindrance
in
arylsulfonyl
hydrazides.
2ꢀBromobenzenesulfonohydrazide only gave
34% yield of the desired product (3zg). Notably,
naphthaleneꢀ2ꢀsulfonohydrazide could be employed as the substrate to produce the corresponding product in high yield
(86%, 3zq), whereas a lower yield (56%, 3zp) was observed in the use of naphthaleneꢀ1ꢀsulfonohydrazide probably
due to its steric hindrance.
A gramꢀscale synthesis of 3zm was successfully achieved under the optimal conditions, giving a 70% isolated yield
(Scheme 2, a). In addition, the Brꢀsubstituted internal alkynes could be further functionalized by means of traditional
Sonogashira coupling, Suzuki coupling, and Heck coupling, respectively, and various complex internal alkyne
derivatives were successfully synthesized in high yields (Scheme 2, b‒d). For example, bis(arylethynyl)benzene
derivatives 4a could be achieved in a 79% yield (Scheme 2, b) via traditional Sonogashira crossꢀcoupling. This type of
conjugated oligoꢀphenyleneethynylenes is of potential interest as molecular wires19 or in the preparation of cruciꢀform
fluorophores.20
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Scheme 2. Scale up Experiment and Synthetic Utility
It is generally agreed on that copper(I) phenylacetylide and ArPdIIX species are reaction intermediates for
Sonogashiraꢀtype crossꢀcoupling.4a,4e,21 Indeed, copper(I) phenylacetylide reacted smoothly with 1a to give 3a in an 84%
yield under the optimized conditions (Scheme 3, eq 1). The oxidants other than Cu(OAc)2 were ineffective for the
reaction (Table 1), whereas, by replacement of Cu(OAc)2 with Ag2CO3, the reaction of copper(I) phenylacetylide with
1a produced 3a in a 21% yield. These results suggested that copper(I) acetylides were involved in the catalytic cycle.
We supposed that the formation of ArPdIIX occurred in the reaction, which was initiated by nitrogen extrusion from
arylsulfonyl hydrazides. Thus stoichiometric reactions of 1a with 1.0 and 2.0 equiv of Pd(OAc)2 were conducted,
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separately. In H NMR spectra, the signals of the two hydrogen atoms of ꢀNHNH2 disappeared in the presence of 1.0
equiv Pd(OAc)2, which was probably due to the formation of intermediate II (Scheme 4), and the signals of all three
hydrogen atoms disappeared when 2.0 equiv Pd(OAc)2 was added at room temperature, in which intermediate III was
probably produced. In the ESIꢀMS spectra, the peak at m/z 502.8 was assigned to [III+DMSOꢀH]¯ (calcd m/z 503.0),
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which also indicated the formation of intermediate III (for details, see Supporting Information). Extrusion of N2 and
SO2 from III might give the key intermediate V.
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Scheme 3. Control Experiments
Based on the study mentioned above and literature reports,16 a general mechanism is illustrated in Scheme 4. The
reaction of Pd(OAc)2 with arylsulfonyl hydrazide gives an ArPdIIOAc intermediate (V), which is formed via
successive deprotonation of the arylsulfonyl hydrazide, βꢀhydride elimination, and liberation of N2 and SO2.
Transmetallation of V with the copper acetylides species VI gives intermediate VII, which then undergoes reductive
elimination to give the desired crossꢀcoupling product 3. The PdII species are then regenerated through the oxidation of
the Pd0 species with Cu(OAc)2.
Scheme 4. Proposed Mechanism
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CONCLUSION
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In summary, we have developed a Sonogashiraꢀtype cross coupling reaction using readily available arylsulfony
hydrazides as arylation reagents under additional acidꢀ and baseꢀfree conditions, which shows a wide scope of
substrates and excellent functional groups tolerance and thus provides a general and facile means for accessing various
functionalized 1,2ꢀdisubstituted acetylenes. Brꢀsubstituted substrates exhibited excellent chemoselectivity, and only the
coupling reaction involving the sulfonylhydrazide groups occurred, making it an efficient synthesis of
Brꢀfunctionalized internal alkynes, and more complex target molecules could be prepared from them through the
traditional crossꢀcoupling reactions. Further investigations to gain a detailed mechanistic understanding of this reaction
are currently underway.
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EXPERIMENTAL SECTION
General Information. All reactions were carried out in ovenꢀdried Schlenk tubes under N2 atmosphere. Solvents were
distilled after treatment with calcium hydride. Reagents were used as received unless otherwise noted. Column
chromatography was performed using Silica Gel 60 (particle size 37–54 ꢁm). The pure products were obtained by
1
means of column chromatography (petroleum ether and ethyl acetate were used as the gradient eluting solvents). H
NMR, 13C NMR and 19F NMR data were acquired on a 400 spectrometer (400 MHz for 1H, 100 MHz for 13C, and 376
MHz for 19F NMR spectroscopy). Chemical shifts for 1H NMR are referred to internal CDCl3 (7.26 ppm for 1H NMR
and 77.00 ppm for 13C NMR) and reported as follows: chemical shift (δ ppm), multiplicity, coupling constant (Hz) and
integration. The ionization method of the highꢀresolution mass spectrum (HRMS) is Electron Impact (EI). The type of
the mass analyzer is quadrupole.
Synthesis of Starting Materials. Arylsulfonyl hydrazides were prepared according to the literature procedure.22
Hydrazinemonohydrate (25.0 mmol) was added dropwise to a solution of arylsulfonyl chloride (10.0 mmol) in dry
tetrahyrdofuran (15.0 mL) at 0 °C under N2. During the addition the mixture became brown and a white precipitate of
hydrazine hydrochloride was deposited. The mixture was stirred at 0 °C for 30 min, added ethyl acetate (60.0 mL), and
washed repeatedly with iceꢀcold 10% aqueous sodium chloride solution (3 x 20.0 mL). The organic layer was dried
over sodium sulfate, filtered, and added slowly to stirred hexane (500.0 mL) over 5 min. After being stirred for 10 min,
the mixture was filtered, and the collected solid was dried in vacuum.
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General Procedure for the Synthesis of Internal Alkynes. An oven dried Schlenk tube of 25 mL equipped with a
magnetic stir bar was charged with arylsulfonyl hydrazide 1 (0.2 mmol), Pd(OAc)2 (0.01 mmol, 5 mol %) , dppp (0.01
mmol, 5 mol %), and Cu(OAc)2·H2O (0.48 mmol, 2.4 equiv), after charging nitrogen for three times, terminal alkyne 2
(0.24 mmol) and DMF (2.0 mL) were added. The reaction mixture was heated at 100 °C for 0.5 h. After completion of
the reaction, the reaction mixture was cooled to room temperature and was quenched with H2O (2 mL). The crude
product was extracted with CH2Cl2 (5 mL), and the organic layer was dried over anhydrous Na2SO4 and was
concentrated under vacuum. The desired product was isolated by column chromatography over silica gen (300‒400
mesh) using petroleum ether/ethyl acetate as eluent.
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1H and 13C Spectral Data of the Products.
1ꢀmethylꢀ4ꢀ((4ꢀpropylphenyl)ethynyl)benzene (3f).
White solid; Yield: 37.5 mg, 80%; mp 56–57 °C. 1H NMR (CDCl3, 400 M): δ 7.43 (t, J = 7.6 Hz, 4H), 7.15 (d, J = 7.6
Hz, 4H), 2.60 (t, J = 8.0 Hz, 2H), 2.37 (s, 3H), 1.70–1.60 (m, 2H), 0.95 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100
MHz): δ 143.0, 138.1, 131.4, 129.1, 128.5, 120.6, 120.4, 88.9, 88.8, 37.9, 24.3, 21.5, 13.7. HRMS (EI) m/z: [M]+ calcd.
for C18H18 234.1409; found 234.1404.
1ꢀmethylꢀ4ꢀ((4ꢀpentylphenyl)ethynyl)benzene (3h).
White solid; Yield: 38.8 mg, 74%; mp 46–48 °C. 1H NMR (CDCl3, 400 M): δ 7.43 (t, J = 7.2 Hz, 4H), 7.15 (d, J = 8.0
Hz, 4H), 2.61 (t, J = 7.6 Hz, 2H), 2.37 (s, 3H), 1.65–1.58 (m, 2H), 1.37–1.27 (m, 4H), 0.90 (t, J = 6.8 Hz, 3H); 13C
NMR (CDCl3, 100 MHz): δ 143.2, 138.1, 131.4, 129.1, 128.4, 120.6, 120.4, 88.9, 88.8, 35.9, 31.4, 30.9, 22.5, 21.5,
14.0. HRMS (EI) m/z: [M]+ calcd. for C20H22 262.1722; found 262.1716.
2ꢀ(5ꢀ(4ꢀbromophenyl)pentꢀ4ꢀynꢀ1ꢀyl)isoindolineꢀ1,3ꢀdione (3z).
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Yellow solid; Yield: 53.7 mg, 73%; mp 109–110 °C. H NMR (CDCl3, 400 M): δ 7.81–7.79 (m, 2H), 7.67–7.65 (m,
2H), 7.33 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 3.85 (t, J = 6.8 Hz, 2H), 2.47 (t, J = 7.2 Hz, 2H), 2.04–1.97 (m,
2H); 13C NMR (CDCl3, 100 MHz): δ 168.4, 133.9, 132.9, 132.1, 131.3, 123.2, 122.5, 121.6, 90.0, 80.2, 37.3, 27.1, 17.3.
HRMS (EI) m/z: [M]+ calcd. for C19H14BrNO2 367.0208; found 367.0203.
4ꢀ((4ꢀbromophenyl)ethynyl)ꢀ4’ꢀpropylꢀ1,1’ꢀbiphenyl (3za).
White solid; Yield: 55.5 mg, 74%; mp 226–228 °C. 1H NMR (CDCl3, 400 M): δ 7.60–7.55 (m, 4H), 7.53–7.48 (m, 4H),
7.40 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 6.4 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H), 1.73–1.63 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H);
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13C NMR (CDCl3, 100 MHz): δ 142.4, 141.2, 137.6, 133.0, 132.0, 131.6, 129.0, 126.9, 126.8, 122.4, 122.3, 121.4, 90.6,
88.8, 37.7, 24.5, 13.8. HRMS (EI) m/z: [M]+ calcd. for C23H19Br 374.0670; found 374.0664.
1ꢀbromoꢀ3ꢀ((4ꢀpropylphenyl)ethynyl)benzene (3zf).
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White solid; Yield: 43.0 mg, 72%; mp 43–44 °C. H NMR (CDCl3, 400 M): δ 7.68 (s, 1H), 7.44 (d, J = 8.0 Hz, 4H),
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7.22–7.16 (m, 3H), 2.61 (t, J = 7.6 Hz, 2H), 1.70–1.61 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz):
δ 143.6, 134.2, 131.5, 131.1, 130.0, 129.7, 128.6, 125.5, 122.1, 119.9, 90.9, 87.2, 38.0, 24.3, 13.7. HRMS (EI) m/z:
[M]+ calcd. for C17H15Br 298.0357; found 298.0351.
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1ꢀbromoꢀ2ꢀ((4ꢀpropylphenyl)ethynyl)benzene (3zg).
Colorless liquid; Yield: 20.3 mg, 34%. 1H NMR (CDCl3, 400 M): δ 7.59 (d, J = 8.0 Hz, 1H), 7.54–7.47 (m, 3H), 7.28–
7.23 (m, 1H), 7.16–7.12 (m, 3H), 2.58 (t, J = 7.6 Hz, 2H), 1.68–1.58 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): δ 143.6, 133.1, 132.4, 131.6, 129.1, 128.5, 127.0, 125.6, 125.5, 120.0, 94.2, 87.4, 38.0, 24.3, 13.7.
HRMS (EI) m/z: [M]+ calcd. for C17H15Br 298.0357; found 298.0351.
1,4ꢀbis((4ꢀmethoxyphenyl)ethynyl)benzene (4a).
An oven dried Schlenk tube of 25 mL equipped with a magnetic stir bar was charged with 3zi (0.2 mmol),
Pd(PPh3)2Cl2 (4 mol %), and CuI (2 mol %). After charging nitrogen for three times, 1ꢀethynylꢀ4ꢀmethoxybenzene 2l
(0.24 mmol, 1.2 equiv), diisopropylmine (0.4 mmol, 2.0 equiv), and THF 1.0 mL was added order under nitrogen
atmosphere, and the mixture was refluxed at 90 °C for 15 h. After cooling down to room temperature, the reaction
mixture concentrated in vacuo. The residue was purified by column chromatography on silica gel and eluted with
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petroleum ether to afford the desired product as a light yellow solid. Yield: 53.5 mg, 79%; mp 214–216 °C. H NMR
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(400 M, CDCl3): δ 7.48–7.46 (m, 8H), 6.88 (d, J = 8.0 Hz, 4H), 3.83 (s, 6H); C NMR (100 MHz, CDCl3): δ 159.8,
133.1, 131.3, 123.1, 115.2, 114.0, 91.1, 87.9, 55.3. HRMS (EI) m/z: [M]+ calcd. for C24H18O2 338.1307; found
338.1301.
3ꢀ(4ꢀ((4ꢀ(tertꢀbutyl)phenyl)ethynyl)phenyl)thiophene (4b).
An oven dried Schlenk tube of 25 mL equipped with a magnetic stir bar was charged with 3zj (0.2 mmol),
thiophenꢀ3ꢀylboronic acid 5 (0.2 mmol), Pd(PPh)4 (5 mol %), and K2CO3 (2.0 equiv). After charging nitrogen for three
times, tolunene 1.0 mL was added order under nitrogen atmosphere, and the mixture was refluxed at 110 °C for 15 h.
After cooling down to room temperature, the reaction mixture concentrated in vacuo. The residue was purified by
column chromatography on silica gel and eluted with ethyl acetate/petroleum ether (1/20) to afford the desired product
as a white solid. Yield: 46.0 mg, 73%; mp 189–190 °C. 1H NMR (400 M, CDCl3): δ 7.46–7.43 (m, 5H), 7.38–7.36 (m,
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3H), 7.29–7.26 (m, 3H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 151.5, 141.6, 135.4, 132.0, 131.3, 126.4, 126.2,
126.1, 125.4, 122.1, 120.7, 120.2, 90.2, 88.7, 34.8, 31.2. HRMS (EI) m/z: [M]+ calcd. for C22H20S 316.1286; found
316.1280.
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(E)ꢀ2ꢀ(4ꢀ((4ꢀmethoxyphenyl)ethynyl)styryl)pyridine (4c).
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An oven dried Schlenk tube of 25 mL equipped with a magnetic stir bar was charged with 3zi (0.2 mmol), Pd(PPh3)4 (5
mol %), and NaOAc (2.0 equiv). After charging nitrogen for three times, 2ꢀvinylpyridine 6 (0.24 mmol, 1.2 equiv) and
tolunene 1.0 mL was added order under nitrogen atmosphere, and the mixture was refluxed at 110 °C for 15 h. After
cooling down to room temperature, the reaction mixture concentrated in vacuo. The residue was purified by column
chromatography on silica gel and eluted with ethyl acetate/petroleum ether (1/5) to afford the desired product as a
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yellow solid. Yield: 50.2 mg, 81%; mp 172–174 °C. H NMR (400 M, CDCl3): δ 8.61 (d, J = 4.0 Hz, 1H), 7.68–7.61
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(m, 2H), 7.56–7.47 (m, 6H), 7.37 (d, J = 7.6 Hz, 1H), 7.20–7.13 (m, 2H), 6.88 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H); C
NMR (100 MHz, CDCl3): δ 159.6, 155.4, 149.7, 136.6, 136.2, 133.1, 132.0, 131.7, 128.5, 127.0, 123.4, 122.3, 122.2,
115.3, 114.0, 90.7, 88.2, 55.3. HRMS (EI) m/z: [M]+ calcd. for C22H17NO 311.1310; found 311.1305.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: djyustc@hotmail.com
*Eꢀmail: zhouyb@hnu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support by the NSF of China (Grant Nos. 21573065, 21273066, and 21172062) and the NSF of Hunan
Province (Grant No. 2016JJ1007) is appreciated. We also thank Prof. C. T. Au (HNU adjunct professor) for manuscript
editing.
SUPPORTING INFORMATION
NMR tracing of the reaction, LCMS analysis of the control reaction, general experimental procedure, 1H NMR and 13C
1
NMR spectra data of the known products, references and copies of H, 13C and 19F NMR charts of products. This
material is available free of charge via the Internet at http://pubs.acs.org.
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