Catalytic Activation of Trimethylsilylacetylenes: A One-Pot Route to Unsymmetrical Acetylenes and Heterocycles

Article abstract of DOI:10.1021/acs.joc.8b00998

For the synthesis of unsymmetrical acetylenes, a Sonogashira coupling-deprotection-Sonogashira coupling reaction sequence is often used. Removal of protecting groups requires harsh conditions or an excess of difficult to handle and expensive reagents. Herein, we disclose a novel catalytic method for the selective deprotection of trimethylsilylacetylenes in Sonogashira reaction. The reagent hexafluorosilicic acid, an inexpensive nontoxic compound, was used to promote the selective desilylation. This method enables the efficient synthesis of unsymmetric acetylenes with other silylated functional groups present. Further possibilities of the method were explored by synthesis of heterocycles.

Full text of DOI:10.1021/acs.joc.8b00998

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Article
Catalytic Activation of Trimethylsilylacetylenes: A “One –
Pot” Route to Unsymmetrical Acetylenes and Heterocycles
Dániel Lasányi, Ádám Mészáros, Zoltán Novák, and Gergely László Tolnai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00998 • Publication Date (Web): 29 May 2018
Downloaded from http://pubs.acs.org on May 30, 2018
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The Journal of Organic Chemistry
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Catalytic Activation of Trimethylsilylacetylenes: A “One –Pot” Route to Unsymmetrical Acety-
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lenes and Heterocycles
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Dániel Lasányi,a Ádám Mészáros,a Zoltán Novák,a,* Gergely L. Tolnaia,*
a Institute of Chemistry, Eötvös University, Pázmány P. stny 1/a, H1117, Budapest, Hungary
novakz@elte.hu; web: http://zng.elte.hu, tolnai@chem.elte.hu, web: http://tolnai.chem.elte.hu
ABSTRACT: For the synthesis of unsymmetrical acetylenes, a Sonogashira coupling-deprotection-So-
nogashira coupling reaction sequence is often used. Removal of protecting groups requires harsh condi-
tions or an excess of difficult to handle and expensive reagents. Herein we disclose a novel catalytic
method for the selective deprotection of trimethylsilylacetylenes in Sonogashira reaction. The reagent
hexafluorosilicic acid, an inexpensive non-toxic compound was used to promote the selective desilylation.
This method enables the efficient synthesis of unsymmetric acetylenes with other silylated functional
groups present. Further possibilities of the method was explored by synthesis of heterocycles.
INTRODUCTION
Diaryl acetylenes are widely used compounds not only because of their synthetic utility, but their unique
optical and electronic properties.1 In the art of molecular engineering diaryl acetylenes are often used as
linear building blocks.2 Their synthesis therefore is a useful conquest of organic chemistry and has differ-
ent solutions. The first synthesis of diaryl acetylenes consists of elimination and/or rearrangement strate-
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gies, usually requires strong bases and harsh reaction conditions.3 The synthesis strategies for aryl acety-
lenes has changed with the Sonogashira reaction4 that is one of the most efficient sp-sp2 carbon-carbon
bond forming reactions. The modern synthesis of unsymmetrical acetylenes preliminary use tandem So-
nogashira reactions.5
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Despite their obvious drawbacks, the use of protecting groups has an inevitable positive impact on or-
ganic synthesis. For the efficient synthesis of the unsymmetrical acetylenes, the choice of the right C2
source is crucial. Carbinols are one of the cheapest acetylene sources,5-6 however the deprotection requires
harsh alkaline conditions in the Sonogashira coupling. (Scheme 1) Propiolic acid can also be used as the
alkyne source.7 The alkynylcarboxilyc acid can be activated by excess tetrabutylammoniumfluoride
(TBAF) or DBU. The most extensively used acetylene source in tandem Sonogashira reaction is trime-
thylsilylacetylene8,9 due to the ease of deprotection with excess of KOH, or fluoride source, preliminary
TBAF. This hygroscopic and expensive fluoride source disables the feasibility of the synthesis of complex
substrates, as other silyl groups, or base-sensitive functionalities cannot be present elsewhere on the mol-
ecule. Established methods for Sonogashira couplings directly from alkynylsilanes require the addition of
sub-stoichiometric amount of silver or copper metal, or the addition of equivalent fluoride source.10 These
conditions often result in side-products,11 as well as desilylation of other protected functionalities. Another
general drawback of these methods are the high temperature and high Pd-loading.
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Scheme 1. Tandem Sonogashira Protocols
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There is an interesting, yet very specialized method of using catalytic TBAF for the desilylation of TMS-
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acetylenes in the synthesis of steroidal oral contraceptives. The deprotection only happens in the very
basic conditions of carbonyl addition, and took advantage of the nearby alkoxide, that –according to the
authors– was able to regenerate the fluoride ion from TMSF.12
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A general mild catalytic desilylation method was published by Philipps, using buffer solutions (Scheme
2, left).13 The method utilizes TBAF or CsF as a fluoride source. An elegant fluoride ion free alternative
has been shown by Han and coworkers (Scheme 2, right).14 With catalytic amount of KOTMS, wide
variety of alkynylsilanes could be deprotected. Both methods are effectively removing TES, TBDMS,
TIPS protecting groups from oxygen and alkynes.
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Scheme 2. Catalytic Protodesilylation Strategies
However, these methods serve a useful way to gain terminal acetylenes, those type of compounds are
rarely the goal of synthesis. Terminal acetylenes are usually serve as building block for internal acetylenes
or heterocycles.15
DeShong’s studies on deprotection of O benzyl-silyl ethers showed, that hexafluorosilicic acid is a very
potent compound in cleavage of Si-O bonds.16 Later studies (Scheme 3) proved, that using H2SiF6 in a
sub-stoichiometric manner provide selective removal of TBDMS over TIPS from benzyl-ethers.17
Scheme 3. Selective Deprotection of O-Si Bond with H2SiF6
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RESULTS AND DISCUSSION
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These results and our experience on desilylation of alkynylacetamides18 inspired us to find a general
selective catalytic desilylation method in tandem Sonogashira reactions. H2SiF6 is a very cheap19 indus-
trial starting material available as an aqueous solution, used in water fluorination of drinking water.20 The
fact, that the compound is able to remove the silyl group in a sub-equivalent fashion, encouraged us to
further improve its efficiency to establish a general tandem Sonogashira reaction that is able to generate
unsymmetrical acetylenes with a wide scope.
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To elucidate the frontiers of the desilylating agent in the Sonogashira conditions, iodobenzene (1a) and
TMS-phenylacetylene (2) were applied as model substrates, and the coupling reactions were performed
in the presence of common 3 mol% Pd(PPh3)2Cl2, and CuI catalyst system. To our delight 1.0 and 0.5
equivalent of the addition of hexafuorosilicic acid resulted in complete conversion by GC under the So-
nogashira conditions (Table 1, entries 1-2). The addition of 1 % of this compound resulted in 28 % con-
version (entry 3). As the H2SiF6 is in a 34 % aqueous solution, we assumed, that the lack of nucleophile
could have led to the loss of activity in our case. Thus, adding 10 equivalents of water increased the yield
to 60 % in 24 h and to 100% in 48 h (entries 4 and 6), but only in the presence of hexafluorosilicic acid
(entry 5). Other hexafluorosilicates (entries 7-9) had were less asctive, as 10, 18 and 37 % conversions
with potassium-, sodium- and ammonium-hexafluorosilicates were observed in the same conditions at
20% catalyst loadings. This might be the result of the low solubility of these compounds in the media.
However, the reaction resulted in full conversion in 48 h, it was found, that increasing the temperature
sped up the reaction without noticeable side effects. The reaction led to 91 % conversion in 24 h on 60 °C
(entry 11) with only 1% of desilylating agent. As the presence of water turned out to be an important
factor, different amounts of water was added over the aqueous solution (entries 12-14). No loss of activity
was observed down to 5 equivalents of H2O, but either increasing to 20 equivalents, or decreasing to 1
equivalent was inferior to 5 or 10 equivalents in these conditions. With 1% HCl, from a 36 % aqueous
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solution and 10 equivalents of water, the conversion was 5 % (entry 15). A control experiment omitting
hexafluorosilicic acid resulted in only 7% yield in our condition (entry 16). The low efficiency of “sila”
Sonogashira coupling under these mild conditions predicts the good efficiency of tandem reaction, as the
homocoupling could be suppressed, without a further manipulation with catalysts or temperature. The
conditions of entry 11 gave no coupled product with chlorobenzene, and led to a 55% conversion with
bromobenzene.
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Table 1. Optimization of Reaction Conditions
Desilylating
agent
H2O added Time
Yielda
(%)
Entry
mol%
T (°C)
(equiv)
(h)
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H2SiF6
H2SiF6
H2SiF6
H2SiF6
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traces
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H2SiF6
K2SiF6
Na2SiF6
(NH4)2SiF6
H2SiF6
H2SiF6
H2SiF6
H2SiF6
H2SiF6
HCl
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0.5
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[a] As determined by GC-FID, on 0.5 mmol scale
With the optimized reaction condition in hand, we turned our attention to establish conditions for a
tandem coupling reaction. As predicted by the preliminary results, the deprotection of the acetylene was
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not likely to occur without the H2SiF6. Indeed, the first Sonogashira coupling proceeded to complete con-
version, enabling a one-pot procedure for the coupling. To establish the synthetic utility of the method,
we examined the scope of this reaction with 1 mmol of the starting aryl halides, in the presence of only 1
mol% of the desilylating agent.
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First, we ran a series of experiments with different monofunctionalized aryl iodides, TMS-acetylene and
iodobenzene. As expected, diaryl acetylenes (Scheme 4, 3a-f) were obtained with different functionalities,
including electron donating and electron withdrawing in medium to excellent yields. For medicinal chem-
istry applications, the use of heterocyclic compounds is very important. Our one pot method proved to be
excellent in this field, as iodo- pyridine, indole, thiophene and quinoline (3g-j) provided the corresponding
internal acetylenes in very good to excellent yields.
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Scheme 4. Synthesis of Unsymmetric Acetylenes (I)
Acetylenic thiophenes are present in material science as conducting polymers and nonlinear optical ma-
terials.21 Using the developed conditions, series of unsymmetrical thienyl acetylenes (Scheme 5, 3k-m)
were synthesized in good yields. Continuing the exploration of the substrate scope of acetylene products,
series of acetylenes with different aryl groups (3n-t) were synthesized.
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Multicyclic hydrocarbons 3u-v, with extended conjugation were also synthesized with good efficiency.
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Synthesis of the molecular rod 3u provided 82 % yield, with 2.2 equivalent TMSA and 0.5 % H2SiF6
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Scheme 5. Synthesis of Unsymmetric Acetylenes (II)
To further challenge our synthetic methodology, we aimed to explore the stability of different silyl
groups. Primary silyl ethers are the most labile silyl ethers due to the lack of steric hindrance. 3-Iodobenzyl
alcohol was protected with different silyl protecting groups. As a first example, coupling and selective
TMS-acetylene activation was demonstrated with the TES, TBDPS, TBDMS and TIPS groups (Scheme
6, 3w-z). All of these aryl-iodides provided the unsymmetrical diaryl acetylene. Competing deprotection
in a ratio of 1:9 was only observed in the case of O-TES, indicating that the low yield might only be a
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problem with the workup. Iodoindole, with a TIPS-protected acetylene at position 3 was coupled with
TMS-acetylene, and one pot coupled with iodopyridine, by the aid of 1% H2SiF6. To our delight the ex-
pected product 3aa was isolated in 71% yield, and no sign of TIPS-deprotection was observed. In a further
control experiment (Scheme 6, down), the mixture the 1 equivalent of iodobenzene was reacted in our
optimized conditions with equimolar TES- and TMS-phenylacetylenes. As a result, full conversion of PhI
and only ~1% of TMS-phenylacetylene was detected after 24 h. The TES-protected acetylene remained
intact.
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Scheme 6. Synthesis of Internal Acetylenes with Various Silyl Protecting Groups Present
One of the preliminary uses of aromatic acetylenes in organic synthesis is applying them as building
blocks for the construction of heterocycles. Utilizing the exact same conditions, a 4 step one-pot synthesis
of benzofurans was performed, where the Sonogashira coupling, the deprotection and the second coupling
followed by ring closing takes place. A series of complex heterocycles were produced (Scheme 7, 4a-f).
This procedure affects the formation of 3 new C-C or C-O bonds. However the conditions are unoptimized
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and this lead to some degree of (presumably) polymerized side-products in the case of 4a and f, the yields
are ranging up to 93% (4b-e)
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Scheme 7. Synthesis of Benzofurans
An other general use of acetylenes are synthesizing triazoles, therefor the general conditions were chal-
lenged to examine to scope of a tandem reaction of this kind. Same condition has been applied to generate
a small set of triazoles (Scheme 8, 5a-c) via CuAAC type of ring construction. To our delight the catalytic
coupling-desilylation protocol was useful in synthesizing this class of compounds in one-pot. Importantly,
5a-c, along with other compounds like 3r-t and 4f, could be further modified by other cross-coupling
methods.
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Scheme 8. Synthesis of Triazoles
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The mechanistic aspects of this reaction are not clear at the moment. Generally observed side products
of this reaction were silyl ethers. The need of water for the efficient synthesis could suggest the prelimi-
nary formation of a terminal acetylene. Control experiment on coupling with bis(trimethylsilyl)acetylene
(Scheme 9, 6) with 2 equivalents of 1a led to high yield of 3a (95%), instead of generating ethyn. This
could be due to the direct transmetalation from Si to Cu or Pd or the immediate Sonogashira reaction in
this condition therefore avoiding the formation of HCCH.
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Scheme 9. Investigation on Mechanism
These results were examined more in depth: in a control experiment iodobenzene was omitted from the
coupling of TMS-phenylacetylene (Scheme 9). Surprisingly, instead of protodesilylation, no change was
observed on the starting materials after 24 h. One pathway would be the formation of –OTMS, from water
and the protecting group in situ. This version does not seem likely, as Han’s method14 is a general desi-
lylation process, and there is a high TMS selectivity in our case. As a plausible reaction scheme, hex-
afluorosilicic acid is first hydrolyzed. The transmetalation to the transition metal can be accelerated by
the coordination of the SiFx as a Lewis acid. Transmetalation from Si to Cu is suggested in the literature.22
CONCLUSIONS
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In conclusion, a new catalyst, the cheap and easy to handle H2SiF6 was introduced for the selective
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desilylation of TMS alkynes in tandem Sonogashira cross-coupling reaction. With the optimized protocol
a tandem Sonogashira condition was developed, where great variety of unsymmetrical acetylenes were
synthetized, with very low catalyst loading. The new selective trimethylsilane activating agent enabled
the coupling of substrates with the generally used Si-O and Si-acetylene protecting groups present. More-
over, the synthetic utility was demonstrated in the synthesis of benzofuran and triazole heterocycles.
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EXPERIMENTAL SECTION
Unless otherwise indicated, all starting materials were obtained from commercial suppliers, and were
used without further purifcation. Analytical thin-layer chromatography (TLC) was performed on Merck
DC precoated TLC plates with 0.25 mm Kieselgel 60 F254. Visualization was performed with a 254 nm
UV lamp. The 1H (250 MHz), 13C (63 MHz) and 19F (235 MHz) NMR spectra were recorded on a Bruker
Avance-250 spectrometer and in CDCl3, and DMSO-d6, at room temperature. Chemical shifts are ex-
pressed in parts per million (δ) using residual solvent protons as internal standards (δ 7.26 for 1H, δ 77.0
for 13C) for CDCl3 and (δ 2.50 for 1H, δ 39.5 for 13C) for DMSO-d6. Coupling constants (J) are reported
in Hertz (Hz). Splitting patterns are designated as s (singlet), d (doublet), t (triplet), q (quartet), m (multi-
plet). Combination gas chromatography and low resolution mass spectrometry was obtained on an Agilent
6890N Gas Chromatograph (30 m x 0.25 mm column with 0.25 µm HP-5MS coating, He carrier gas) and
Agilent 5973 Mass Spectrometer (Ion source: EI+, 70eV, 230 °C; interface: 300 °C). IR spectra were
obtained on a Bruker IFS55 spectrometer on a single-reaction diamond ATR unit. All melting points were
measured on Büchi 501 apparatus and are uncorrected. High-resolution mass spectra were acquired on an
Agilent 6230 time-of-flight mass spectrometer equipped with a Jet Stream electrospray ion source in pos-
itive ion mode. Injections of 0.1-0.3 µl were directed to the mass spectrometer at a flow rate of 0.5 ml/min
(70% acetonitrile-water mixture, 0.1 % formic acid), using an Agilent 1260 Infinity HPLC system. Jet:
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drying gas (N2) flow and temperature: 10.0 l/min and 325 °C, respectively; nebulizer gas (Stream param-
eters N2) pressure: 10 psi; capillary voltage: 4000 V; sheath gas flow and temperature: 325 °C and 7.5
l/min; TOFMS parameters: fragmentor voltage: 120 V; skimmer potential: 120 V; OCT 1 RF Vpp:750 V.
Full-scan mass spectra were acquired over the m/z range 100-2500 at an acquisition rate of 250 ms/spec-
trum and processed by Agilent MassHunter B.03.01 software.
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Synthesis of Starting Materials
Triethyl((3-iodobenzyl)oxy)silane 1w
Chlorotriethylsilane (301.4 mg, 2.0 mmol, 1.0 equiv) was added to a stirring solution of imidazole (163.4
mg, 2.4 mmol, 1.2 equiv) and 3-iodo-benzylalcohol (468.1 mg, 2.0 mmol, 1.0 equiv) in CH2Cl2 (8 mL).
The reaction was sealed and stirred at room temperature for overnight. CH2Cl2 (15 mL) was added, the
organic layer was washed twice with H2O (30 mL). The aqueous layers were combined and extracted with
CH2Cl2 (30 mL). The organic layers were combined, washed with brine (50 mL), dried over MgSO4 and
concentrated under reduced pressure.
Colorless oil (578 mg, yield 83%), Rf.: 0.23 (in hexanes: EtOAc 100:1). 1H NMR (250 MHz, CDCl3) δ
= 7.61 (s, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.21 (d, J = 7.7 Hz, 1H), 6.98 (t, J = 7.7 Hz, 1H), 4.60 (s, 2H),
0.90 (t, J = 7.9 Hz, 9H), 0.57 (q, J = 8.1 Hz, 6H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 144.1, 136.3,
135.5, 130.4, 125.7, 94.7, 64.2, 7.2, 4.8 ppm. IR (thin film, ATR) νmax 2952, 2876, 1693, 1567 cm-1. MS
(EI, 70 eV) m/z (%): 348(1), 319(100, [M+]), 289(21), 217(34), 163(19), 90(23). HRMS calcd for
C13H21IOSi [M]+ 348.0406 found 348.03969
tert-Butyl((3-iodobenzyl)oxy)diphenylsilane 1x
tert-Butyldiphenylchlorosilane (549.7 mg, 2.0 mmol, 1.0 equiv) was added to a stirring solution of im-
idazole (163.4 mg, 2.4 mmol, 1.2 equiv) and 3-iodo-benzylalcohol (468.1 mg, 2.0 mmol, 1.0 equiv) in
CH2Cl2 (8 mL). The reaction was sealed and stirred at room temperature for overnight. CH2Cl2 (15 mL)
was added, the organic layer was washed twice with H2O (30 mL). The aqueous layers were combined
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and extracted with CH2Cl2 (30 mL). The organic layers were combined, washed with brine (50 mL), dried
over MgSO4 and concentrated under reduced pressure.
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Colorless oil (583.4 mg, yield 62%), Rf.: 0.25 (in hexanes: EtOAc 100:1). 1H NMR (250 MHz, CDCl3)
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δ = 7.70 (dt, J = 6.4, 1.8 Hz, 5H), 7.60 (d, J = 7.7 Hz, 1H), 7.50 – 7.29 (m, 7H), 7.08 (t, J = 7.7 Hz, 1H),
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4.72 (s, 2H), 1.12 (s, 9H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 143.8, 136.3, 135.9, 135.5, 133.6,
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130.4, 130.2, 128.2, 125.6, 94.6, 65.1, 27.2, 19.7 ppm. IR (thin film, ATR) νmax 2961, 2931, 2892, 2856,
1592, 1567 cm-1. MS (EI, 70 eV) m/z (%): 415(100, [M+]), 385(15), 337(15), 217(35), 211(25), 183(36),
90(27). HRMS calcd for C19H16IOSi [M-C4H9]+ 415.0015 found 415.0000
tert-Butyl((3-iodobenzyl)oxy)dimethylsilane23 1y
tert-Butyldimethylchlorosilane (302 mg, 2.0 mmol, 1.0 equiv) was added to a stirring solution of imid-
azole (163.4 mg, 2.4 mmol, 1.2 equiv) and 3-iodo-benzylalcohol (468 mg, 2.0 mmol, 1.0 equiv) in CH2Cl2
(8 mL). The reaction was sealed and stirred at room temperature for overnight. CH2Cl2 (15 mL) was
added, the organic layer was washed twice with H2O (30 mL). The aqueous layers were combined and
extracted with CH2Cl2 (30 mL). The organic layers were combined, washed with brine (50 mL), dried
over MgSO4 and concentrated under reduced pressure.
Colorless oil (486.2 mg, yield 70%), Rf.: 0.24 (in hexanes: EtOAc 100:1). 1H NMR (250 MHz, CDCl3)
δ = 7.57 (s, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 6.96 (t, J = 7.7 Hz, 1H), 4.58 (s, 2H),
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0.84 (s, 9H), 0.00 (s, 6H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 144.2, 136.3, 135.4, 130.4, 125.5,
94.7, 64.5, 26.3, 18.8, -4.9 ppm. IR (thin film, ATR) νmax 2958, 2933, 2885, 2858, 1567 cm-1. MS (EI, 70
eV) m/z (%): 291(100, [M+]), 261(40), 217(41), 149(19), 90(21).
((3-Iodobenzyl)oxy)triisopropylsilane 1z
Triisopropylchlorosilane (386 mg, 2.0 mmol, 1.0 equiv) was added to a stirring solution of imidazole
(163.4 mg, 2.4 mmol, 1.2 equiv) and 3-iodo-benzylalcohol (468 mg, 2.0 mmol, 1.0 equiv) in CH2Cl2 (8
mL). The reaction was sealed and stirred at room temperature for overnight. CH2Cl2 (15 mL) was added,
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the organic layer was washed twice with H2O (30 mL). The aqueous layers were combined and extracted
with CH2Cl2 (30 mL). The organic layers were combined, washed with brine (50 mL), dried over MgSO4
and concentrated under reduced pressure.
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Colorless oil (706 mg, yield 90%), Rf.: 0.38 (in hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.72 (s, 1H),
7.58 (d, J = 7.7 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.08 (t, J = 7.7 Hz, 1H), 4.79 (s, 2H), 1.11 (app. s, 21H)
ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 144.5, 136.1, 135.1, 130.4, 125.2, 94.6, 64.5, 18.4, 12.4 ppm.
IR (thin film, ATR) νmax 2943, 2867, 1592, 1567 cm-1. MS (EI, 70 eV) m/z (%): 364(2), 347(100, [M+]),
319(20), 217(32), 91(17). HRMS calcd for C24H33OSi [M+H]+ 365.2301 found 365.2299
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5-Iodo-3-((triisopropylsilyl)ethynyl)-1H-indole24 1aa
1-[(Triiso-propylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one (1027 mg, 2.40 mmol, 1.2 equiv) was added
to a stirring solution of AuCl (4.6 mg, 0.020 mmol, 0.01 equiv) and 5-iodoindole (2.0 mmol, 1.0 equiv)
in Et2O (40 mL). The reaction was sealed and stirred at room temperature overnight. Et2O (50 mL) was
added, the organic layer was washed twice with NaOH 0.1 M (75 mL). The aqueous layers were combined
and extracted with Et2O (100 mL). The organic layers were combined, washed with saturated NaHCO3
(100 mL), brine (100 mL), dried over MgSO4 and concentrated under reduced pressure.
Brown solid (767.3 mg, yield 91%) Mp.= 75- 77 °C (Ref.: 75-77 °C), Rf.: 0.20 (in hexanes: Et2O 7:3).
1H NMR (250 MHz, CDCl3) δ = 8.14 (s, 1H), 7.96 (dd, J = 1.6, 0.8 Hz, 1H), 7.41 (dd, J = 8.5, 1.7 Hz,
1H), 7.29 (d, J = 2.7 Hz, 1H), 7.06 (dd, J = 8.5, 0.6 Hz, 1H), 1.09 (app. s, 21H) ppm. 13C{1H}NMR (63
MHz, CDCl3) δ = 134.5, 131.6, 129.5, 129.2, 113.6, 99.6, 99.3, 92.9, 84.8, 19.2, 11.8 ppm. IR (thin film,
ATR) νmax 2943, 2865, 2144, 1451, 1410 cm-1. MS (EI, 70 eV) m/z (%): 423(43), 381(23), 380(100, [M+]),
310(50), 210(65), 168(75), 142(23), 59(11).
General procedure for the one-pot synthesis
Into a 7 mL screw cap vial CuI (5.7 mg, 0.03 mmol, 0.03 equiv.) and Pd(PPh3)2Cl2 (21.1 mg, 0.03 mmol,
0.03 equiv.) was and the starting aryl halide (1 mmol, 1 equiv.) if a solid, was filled. The vial was closed,
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and the atmosphere was changed 3 times to Ar. DIPA (4 mL) was added, and the starting aryl halide (1
mmol, 1 equiv.) if a liquid. Trimethylsilylacetylene (154 µL, 1.1 mmol, 1.1 equiv.) was added via a syringe
and the mixture was stirred at 60 °C for 1 h. The completion of the first coupling was verified by TLC,
then the second aryl halide (1 mmol, 1 equiv.) was added. Hexafluorosilicic acid (34 % in aqueous solu-
tion, 3 µL, 0.01 mmol, 0.01 equiv.) and water (180 µL) was added via Hamilton syringes. The mixture
was stirred for 24 h at 60 °C. The mixture was diluted with EtOAc (15 mL) and water (15 mL), the pH of
the aqueous phase was adjusted to neutral. The layers were separated, then the aqueous phase was ex-
tracted with EtOAc (2 x15 mL). The combined organic layers were dried over MgSO4. The solvent was
removed under reduced pressure, and the crude product was purified by column chromatography.
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1,2-Diphenylethyne25 3a
The general procedure was followed. White solid (175.5 mg, yield 98%), Mp.: 54-55 °C (Ref.: 54-55
°C), Rf.: 0.53 (in hexanes:EtOAc 25:1). 1H NMR (250 MHz, CDCl3) δ = 7.70 – 7.51 (m, 4H), 7.48 – 7.30
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(m, 6H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 132.1, 128.8, 128.7, 123.7, 89.8 ppm. IR (thin film,
ATR) νmax 1599, 1571, 1492, 1441 cm-1. MS (EI, 70 eV) m/z (%): 178 (100, [M+]), 152 (20), 126 (10),
76 (15).
5 mmol Scale Experiment
Into a 50 mL round bottomed flask CuI (28.6 mg, 0.15 mmol, 0.03 equiv.) and Pd(PPh3)2Cl2 (105.3 mg,
0.15 mmol, 0.03 equiv.) was and the starting aryl halide (5 mmol, 1 equiv.) if a solid, was filled. The flask
was closed, and the atmosphere was changed 3 times to Ar. DIPA (20 mL) was added, and the starting
aryl halide (5 mmol, 1 equiv.) if a liquid. Trimethylsilylacetylene (780 µL, 5.5 mmol, 1.1 equiv.) was
added via a syringe and the mixture was stirred at 60 °C for 1 h. The completion of the first coupling was
verified by TLC, then the second aryl halide or azide (1 mmol, 1 equiv.) was added. Hexafluorosilicic
acid (34 % in aqueous solution, 15.2 µL, 0.01 mmol, 0.01 equiv.) and water (900 µL) was added via
Hamilton syringes. The mixture was stirred for 24 h at 60 °C. The mixture was diluted with EtOAc (75
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mL) and water (75 mL), the pH of the aqueous phase was adjusted to neutral. The layers were separated,
then the aqueous phase was extracted with EtOAc (2 x50 mL). The combined organic layers were dried
over MgSO4. The solvent was removed under vacuum, and the crude was purified by column chromatog-
raphy. White crystals. (868.6 mg, 98 %) Analytical data is the same as at 1 mmol scale.
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1-(4-(Phenylethynyl)phenyl)ethan-1-one25 3b
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The general procedure was followed. White solid (154.2 mg, yield 70%) Mp.= 96-97 °C (Ref.: 95-96
°C), Rf.: 0.23 (in hexanes: EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 7.86 (d, J = 8.5 Hz, 2H), 7.57 –
7.41 (m, 4H), 7.34 – 7.23 (m, 3H), 2.53 (s, 3H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 197.7, 136.6,
132.1, 132.1, 129.2, 128.8, 128.7, 128.6, 123.0, 93.1, 89.0, 27.0 ppm. IR (thin film, ATR) νmax 2222, 1680,
1603, 1486 cm-1. MS (EI, 70 eV) m/z (%): 220(75), 205(100, [M+]), 176(70), 151(32).
1-Methoxy-4-(phenylethynyl)benzene25 3c
The general procedure was followed. White solid (119.2 mg, yield 57%) Mp.= 58-59 °C (Ref.: 59-60
°C), Rf.: 0.29 (in hexanes: EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 7.60 – 7.41 (m, 4H), 7.39 – 7.29
(m, 3H), 6.97 – 6.83 (m, 2H), 3.84 (s, 3H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 160.0, 133.4, 131.8,
128.7, 128.3, 124.0, 115.8, 114.4, 89.8, 88.5, 55.7 ppm. IR (thin film, ATR) νmax 2212, 2162, 1604, 1592,
1266, 1506, 1457 cm-1. MS (EI, 70 eV) m/z (%): 208 (100, [M+]), 193 (46), 165 (40), 139 (12), 104 (5).
The sample contains 5 % of ((4-methoxyphenyl)ethynyl)trimethylsilane. Yield is corrected with purity.
1-Methyl-4-(phenylethynyl)benzene25 3d
The general procedure was followed. White solid (107.0 mg, yield 56%) Mp.= 70-72 °C (Ref.: 70-72
°C), Rf.: 0.60 (in hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.47 – 7.36 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H),
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7.27 – 7.17 (m, 3H), 7.04 (d, J = 7.9 Hz, 2H), 2.25 (s, 3H) ppm. C{1H}NMR (63 MHz, CDCl3) δ =
138.6, 131.9, 131.9, 129.5, 128.7, 128.5, 123.6, 120.4, 90.1, 89.0, 21.7 ppm. IR (thin film, ATR) νmax
2923, 2138, 1593, 1508, 1483 cm-1. MS (EI, 70 eV) m/z (%): 192 (100, [M+]), 191 (50), 165 (20), 152
(5), 115 (5).
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3-(Phenylethynyl)aniline26 3e
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The general procedure was followed. Brown solid (170.1 mg, yield 88%) Mp.= 46-48 °C, Rf.: 0.25 (in
hexanes: EtOAc 5:1). 1H NMR (250 MHz, CDCl3) δ = 7.51 – 7.35 (m, 2H), 7.32-7.19 (m, 3H), 7.05 (t, J
= 7.8 Hz, 1H), 6.95 – 6.82 (m, 1H), 6.78 (t, J = 1.9 Hz, 1H), 6.64 – 6.50 (m, 1H), 3.60 (s, 2H) ppm.
13C{1H}NMR (63 MHz, CDCl3) δ = 146.52, 132.0, 129.7, 128.7, 128.6, 124.3, 123.7, 122.6, 118.3, 115.8,
90.0, 89.2 ppm. IR (thin film, ATR) νmax 2216, 1678, 1599, 1494, 1445 cm-1. MS (EI, 70 eV) m/z (%):
263(100, [M+]), 227(35), 200(40), 131(10).
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3-(Phenylethynyl)benzonitrile27 3f
The general procedure was followed. Yellow oil (140.8 mg, yield 90%) Rf.: 0.48 (in hexanes:EtOAc
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5:1). H NMR (250 MHz, CDCl3) δ = 7.87 – 7.78 (m, 1H), 7.73 (dt, J = 7.8, 1.4 Hz, 1H), 7.60 (dt, J =
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7.8, 1.4 Hz, 1H), 7.57 – 7.31 (m, 6H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 136.0, 135.3, 132.1,
131.7, 129.7, 129.4, 128.9, 125.4, 122.7, 118.5, 113.3, 92.2, 87.3 ppm. IR (thin film, ATR) νmax 2233,
2213, 1601, 1574, 1493 cm-1. MS (EI, 70 eV) m/z (%): 203 (100, [M+]), 176 (15), 151 (10), 101 (10).
3-(Phenylethynyl)pyridine28 3g
The general procedure was followed. White solid (168.2 mg, yield 93%) Mp.= 50-51°C (Ref.: 49-51
°C), Rf.: 0.29 (in hexanes: EtOAc 20:1). 1H NMR (250 MHz, CDCl3) δ = 8.72 (s, 1H), 8.50 (dd, J = 4.9,
1.7 Hz, 1H), 7.76 (dt, J = 7.9, 2.0 Hz, 1H), 7.41-7.58 (m, 2H), 7.39 – 7.13 (m, 4H) ppm. 13C{1H}NMR
(63 MHz, CDCl3) δ = 152.5, 148.8, 138.9, 132.1, 129.2, 128.8, 123.5, 122.9, 120.9, 93.1, 86.3 ppm. IR
(thin film, ATR) νmax 2224, 1559, 1488, 1472, 1413 cm-1. MS (EI, 70 eV) m/z (%): 179(100, [M+]),
151(20), 126(30), 100(15).
2-(Phenylethynyl)thiophene29 3h
The general procedure was followed. Pale rose crystals (134.8 mg, yield 73%) Mp.= 52-54 °C, Rf.: 0.58
(in hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.60 – 7.46 (m, 2H), 7.44 – 7.25 (m, 5H), 7.03 (dd, J = 5.0,
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3.8 Hz, 1H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 132.3, 131.8, 128.8, 128.8, 127.6, 127.51, 123.7,
123.3, 93.4, 83.0 ppm. IR (thin film, ATR) νmax 2209, 1594, 1516, 1484 cm-1. MS (EI, 70 eV) m/z (%):
184(100, [M+]), 152(21), 139(33).
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5-(Phenylethynyl)-1H-indole30 3i
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The general procedure was followed. Yellow solid (179.1 mg, yield 83%) Mp.= 126-128 °C (Ref.: 124-
128 °C), Rf.: 0.27 (in hexanes:EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 8.20 (s, 1H), 7.91 (s, 1H),
7.58 (m, J = 4.7, 2.7 Hz, 2H), 7.47 – 7.28 (m, 5H), 7.23 (t, J = 2.8 Hz, 1H), 6.58 (t, J = 2.6 Hz, 1H) ppm.
13C{1H}NMR (63 MHz, CDCl3) δ = 135.8, 131.9, 128.7, 128.2, 128.2, 126.1, 125.51, 125.1, 124.34,
114.8, 111.56, 103.3, 91.5, 87.5 ppm. IR (thin film, ATR) νmax 2208, 1595, 1490, 1467 cm-1. MS (EI, 70
eV) m/z (%): 217(100, [M+]), 189(30), 108(15).
6-(Phenylethynyl)quinoline31 3j
The general procedure was followed. Yellow solid (201.1 mg, yield 88%) Mp.= 94-96 °C, Rf.: 0.35 (in
hexanes: EtOAc 1:1). 1H NMR (250 MHz, CDCl3) δ = 8.89 (d, J = 4.3 Hz, 1H), 8.21 – 7.91 (m, 3H), 7.81
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(d, J = 8.7 Hz, 1H), 7.58 (dd, J = 6.8, 3.0 Hz, 2H), 7.44 – 7.28 (m, 4H) ppm. C{1H}NMR (63 MHz,
CDCl3) δ = 151.25, 147.96, 136.16, 132.58, 132.10, 131.47, 129.94, 128.98, 128.83, 128.40, 123.30,
122.12, 122.00, 91.10, 89.38 ppm. IR (thin film, ATR) νmax 1590, 1567, 1496, 1441, 1372, 1333, 1129,
1071, 1027, 920, 889, 839, 800, 759, 692 cm-1. MS (EI, 70 eV) m/z (%): 229(100, [M+]), 228(20),
200(10), 114(6).
Methyl 4-(thiophen-2-ylethynyl)benzoate32 3k
The general procedure was followed. Yellow crystals (185 mg, yield 76%) Mp.= 107-109 °C (Ref.: 104-
105 °C), Rf.: 0.23 (in hexanes: EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 7.92 (d, J = 8.3 Hz, 2H),
7.47 (d, J = 8.2 Hz, 2H), 7.27 – 7.15 (m, 2H), 6.93 (dd, J = 4.9, 3.9 Hz, 1H), 3.82 (s, 3H) ppm.
13C{1H}NMR (63 MHz, DMSO) δ 136.1, 132.0, 128.2, 128.0, 127.1, 124.5, 124.1, 123.3, 112.3, 112.2,
101.8, 95.5, 80.2 ppm. IR (thin film, ATR) νmax 2209, 1711, 1603, 1439, 1408 cm-1. MS (EI, 70 eV) m/z
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(%): 243(16), 242(100, [M+]), 211(95), 183(20), 139(67), 91(10). HRMS calcd for C14H11O2S [M+H]+
243.0480 found 243.0471.
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5-(Thiophen-2-ylethynyl)-1H-indole 3l:
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The general procedure was followed. Brown solid (135 mg, yield 60%) Mp.= 154-156 °C, Rf.: 0.20 (in
hexanes: EtOAc 5:1). 1H NMR (250 MHz, DMSO-d6) δ 11.35 (s, 1H), 7.77 (s, 1H), 7.58 (m, 1H), 7.47 –
7.30 (m, 3H), 7.23 (dd, J = 8.4, 1.6 Hz, 1H), 7.09 (dd, J = 5.2, 3.6 Hz, 1H), 6.46 (t, J = 2.5 Hz, 1H). 1H
NMR (250 MHz, CDCl3) δ = 8.16 (s, 1H), 7.80 (s, 1H), 7.30 (m, 2H), 7.23 – 7.08 (m, 3H), 6.95 (dd, J =
5.2, 3.6 Hz, 1H), 6.50 (t, J = 2.6 Hz, 1H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 133.4, 129.1, 125.6,
124.9, 124.4, 123.3, 123.0, 122.4, 122.0, 111.8, 109.1, 100.8, 92.6, 78.1 ppm. IR (thin film, ATR) νmax
2931, 2207, 1612, 1590, 1469 cm-1. MS (EI, 70 eV) m/z (%): 224(16), 223(100, [M+]), 195(12), 152(10),
111(5). HRMS calcd for C14H10NS [M+H]+ 224.0534 found 224.0535.
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2-((3,5-bis(Trifluoromethyl)phenyl)ethynyl)thiophene 3m:
The general procedure was followed. White crystals (260 mg, yield 81%), Mp.: 43-45 °C Rf.: 0.31 (in
hexanes). 1H NMR (250 MHz, CDCl3) ) δ = 7.94 (s, 2H), 7.82 (s, 1H), 7.43 – 7.32 (m, 2H), 7.06 (dd, J =
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5.0, 3.8 Hz, 1H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 133.6, 132.4 (q, J = 34.2 Hz), 131.5 (m),
129.0, 127.7, 125.6, 123.3 (d, J = 273.3 Hz), 122.1, 121.9 (p, J = 3.8 Hz), 90.4, 86.6 ppm. 19F NMR (235
MHz, CDCl3) δ = -63.21 ppm. IR (thin film, ATR) νmax 2214, 1383, 1349, 1277 cm-1. MS (EI, 70 eV) m/z
(%): 320(100, [M+]), 301(20), 251(10), 206(10), 160(5), 69(10). HRMS calcd for C14H6F6S [M+H]+
320.0094 found 320.00843.
1-((3-Fluorophenyl)ethynyl)-3,5-dimethylbenzene 3n
The general procedure was followed. White crystals (198 mg, yield 88%), Mp.: 38-40 °C Rf.: 0.37 (in
hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.33 – 7.14 (m, 5H), 7.10 – 6.90 (m, 2H), 2.33 (s, 6H) ppm.
13C{1H}NMR (63 MHz, CDCl3) δ = 162.8 (d, J = 245.6 Hz), 138.4, 130.9, 130.3 (d, J = 8.4 Hz), 129.7,
127.8 (d, J = 3.0 Hz), 125.7 (d, J = 8.6 Hz), 122.8, 118.7 (d, J = 23.8 Hz), 115.8 (d, J = 23.8 Hz), 91.1,
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87.8, 21.5 ppm. 19F NMR (235 MHz, CDCl3) δ = -113.07 ppm. IR (thin film, ATR) νmax 2920, 2863, 2219,
1610, 1580, 1489, 1436, 1379, 1335, 1304 cm-1. MS (EI, 70 eV) m/z (%): 295(100, [M+]), 276(10),
233(30), 190(20), 163(15), 138(10), 108(5), 75(10). HRMS calcd for C16H13F [M+H]+ 224.1001 found
224.09905.
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1-Chloro-4-((4-fluorophenyl)ethynyl)benzene33 3o
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The general procedure was followed. White solid (121 mg, yield 53%), Mp.: 112-113 °C, (Ref.: 113 °C)
Rf.: 0.26 (in hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.57 – 7.40 (m, 4H), 7.38 – 7.26 (m, 2H), 7.15 –
6.96 (m, 2H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 163.0 (d, J = 250.0 Hz), 134.7, 133.9 (d, J = 8.5
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Hz), 133.2, 129.1, 122.0, 119.4 (d, J = 3.5 Hz), 116.1 (d, J = 22.9 Hz), 89.6, 88.3 ppm. F NMR (235
MHz, CDCl3) δ = -110.48 ppm. IR (thin film, ATR) νmax 2021, 1601, 1506, 1400, 1226 cm-1. MS (EI, 70
eV) m/z (%): 230(100, [M+]), 194(32), 175(15), 144(5), 115(5), 97(5).
1-Methoxy-4-((4-nitrophenyl)ethynyl)benzene34 3p
The general procedure was followed. Yellow solid (114 mg, yield 45%), Mp.: 122- 124 °C (Ref.: 122-
124 °C), Rf.: 0.25 (in hexanes: EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 8.09 (d, J = 8.9 Hz, 2H),
7.52 (d, J = 8.9 Hz, 2H), 7.40 (d, J = 8.9 Hz, 2H), 6.81 (d, J = 8.9 Hz, 2H), 3.75 (s, 3H) ppm. 13C{1H}NMR
(63 MHz, CDCl3) δ = 160.8, 147.0, 133.8, 132.4, 131.1, 124.0, 114.6, 95.6, 87.0, 78.0, 55.7 ppm. IR (thin
film, ATR) νmax 2211, 1589, 1511, 1464 cm-1. MS (EI, 70 eV) m/z (%): 253(100, [M+]), 223(20), 207(20),
163(80), 152(15), 87(10).
5-Chloro-2-(p-tolylethynyl)aniline35 3q
The general procedure was followed. Off-white solid. (177 mg, yield 79%) Mp.= 135 - 137 °C (Ref.:
not given), Rf (Hex.-EtOAc = 5:1) = 0.50; 1H NMR (250 MHz, CDCl3) δ = 7.28 (d, J = 8.0 Hz, 2H), 7.13
(d, J = 8.3 Hz, 1H), 7.00 (d, J = 8.1 Hz, 2H), 6.68 – 6.45 (m, 2H), 4.46 (s, 2H), 2.22 (s, 3H) ppm.
13C{1H}NMR (63 MHz, CDCl3) δ = 148.0, 138.8, 135.2, 133.1, 131.5, 129.3, 119.9, 118.7, 114.6, 107.3,
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The Journal of Organic Chemistry
95.9, 84.2, 21.7 ppm. IR (thin film, ATR): 1614, 1558, 1486 cm-1. MS (EI, 70 eV) m/z (% relative inten-
sity, ion): 243(32, [M+]), 241(100, [M+]), 204(23), 178(14), 164(6), 120(7), 105(15), 89(16), 76(6).
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2-((4-Chlorophenyl)ethynyl)-4-(trifluoromethyl)aniline 3r
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The general procedure was followed. Brown crystals (260 mg, yield 81%), Mp.: 61-63 °C Rf.: 0.21 (in
hexanes:EtOAc 5:1). 1H NMR (250 MHz, CDCl3) δ = 7.62 (s, 1H), 7.51 – 7.41 (m, 2H), 7.40 – 7.31 (m,
3H), 6.74 (d, J = 8.5 Hz, 1H), 4.57 (s, 2H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 150.6, 135.1, 133.1,
130.0 (q, J = 3.6 Hz), 129.2, 127.2 (q, J = 3.6 Hz), 124.7 (q, J = 270.9 Hz), 121.5, 120.3 (q, J = 33.1 Hz),
114.2, 107.5, 94.8, 85.8 ppm. 19F NMR (235 MHz, CDCl3) δ = -61.46 ppm. IR (thin film, ATR) νmax 2021,
1623, 1490 cm-1. MS (EI, 70 eV) m/z (%): 295(100, [M+]), 276(10), 233(30), 190(20), 163(15), 138(10),
108(5), 75(10). HRMS calcd for C15H10ClF3N [M+H]+ 296.0454 found 296.0458.
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3-((3-Bromophenyl)ethynyl)-2-methylquinolin-4-amine 3s
The general procedure was followed. Light brown solid (211 mg, yield 63%). Mp.= 177 - 179 °C. Rf
(EtOAc) = 0.53; 1H NMR (250 MHz, DMSO-d6) δ = 8.27 (d, J = 8.2 Hz, 1H), 7.98 (t, J = 1.6 Hz, 1H),
7.74 – 7.53 (m, 5H), 7.43 – 7.32 (m, 2H), 7.13 (s, 2H), 2.64 (s, 3H) ppm. 13C{1H}NMR (63 MHz, DMSO-
d6) δ = 158.9, 152.5, 146.7, 133.3, 130.9, 130.5, 130.0, 129.9, 128.4, 125.5, 123.9, 122.5, 121.6, 116.0,
97.7, 95.0, 86.7, 24.5 ppm. MS (EI, 70 eV) m/z (% relative intensity, ion): 338(92, [M+]), 336(100, [M+]),
281(15), 256 (55), 207 (61), 193(20), 147(24), 128(41), 114(14), 94(13), 73(59). IR (thin film, ATR):
2200, 1642, 1614, 1570 cm-1. HRMS m/z [M+H]+ calculated for C18H14N2Br+: 337.0340; found:
337.0339.
7-Chloro-4-(phenylethynyl)quinolone 3t
The general procedure was followed. Brown solid (154 mg, yield 70%) Mp.= 95-96 °C, Rf.: 0.28 (in
hexanes: EtOAc 10:1). 1H NMR (250 MHz, CDCl3) δ = 8.89 (d, J = 4.5 Hz, 1H), 8.29 (d, J = 8.9 Hz, 1H),
8.13 (d, J = 2.2 Hz, 1H), 7.74 – 7.50 (m, 4H), 7.49 – 7.32 (m, 3H) ppm. 13C{1H}NMR (63 MHz, CDCl3)
δ = 151.0, 148.6, 136.4, 132.4, 130.5, 130.0, 129.0, 129.0, 128.6, 127.8, 126.6, 124.0, 122.3, 99.8, 84.9
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ppm. IR (thin film, ATR) νmax 2217, 1608, 1574, 1496 cm-1. MS (EI, 70 eV) m/z (%): 263(100, [M+]),
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227(35), 200(40), 131(10). HRMS calcd for C17H11ClN [M+H]+ 264.0580 found 264.0582.
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1,4-bis(Phenylethynyl)benzene36 3u
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The general procedure was modified. (1,4-iiodobenzene (1 mmol, 330 mg), trimethylsilylacetylene (2.2
equiv., 2.2 mmol) and iodobenzene (2.0 equiv., 2 mmol) were used) Yellow crystals (228 mg, yield 82%)
mp.= 175-176 °C (Ref.: 178-179 °C), Rf.: 0.25 (in hexanes). 1H NMR (250 MHz, CDCl3) δ = 7.55 (dd, J
= 6.7, 3.1 Hz, 4H), 7.53 (s, 4H), 7.37 (dd, J = 5.0, 1.7 Hz, 6H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ =
132.0, 131.9, 128.9, 128.8, 123.5, 123.5, 91.6, 89.5 ppm. IR (thin film, ATR) νmax 1594, 1514, 1441, 1070,
839, 752, 690 cm-1. MS (EI, 70 eV) m/z (%): 278(100, [M+]), 276(15), 139(18).
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2-(Naphthalen-2-ylethynyl)-9H-fluorene 3v
The general procedure was followed. Orange solid (283 mg, yield 45%), Rf.: 0.20 (in hexanes: EtOAc
100:1). Mp.: 137-139 °C 1H NMR (250 MHz, CDCl3) δ = 8.40 (d, J = 8.2 Hz, 1H), 7.93 – 6.94 (m, 13H),
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3.82 (d, J = 7.6 Hz, 2H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 144.0, 143.7, 142.4, 141.5, 133.7,
133.6, 131.0, 130.7, 129.0, 128.7, 128.6, 127.6, 127.4, 127.2, 126.8, 126.7, 125.7, 125.5, 121.8, 121.5,
120.6, 120.3, 95.6, 88.0, 37.2 ppm. IR (thin film, ATR) νmax 2964, 2897, 2829, 2205, 1585 cm-1. MS (EI,
70 eV) m/z (%): 316 (100, [M+]), 156(35), 143(10), 73(5).
Triethyl((3-(phenylethynyl)benzyl)oxy)silane 3w
The general procedure was followed. Yellow oil (131 mg, yield 41%), Rf.: 0.25 (in hexanes: EtOAc
100:1). 1H NMR (250 MHz, CDCl3) δ = 7.57 – 7.38 (m, 3H), 7.37 – 7.18 (m, 6H), 4.64 (s, 2H), 0.90 (t, J
= 7.8 Hz, 9H), 0.58 (q, J = 7.9 Hz, 6H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 142.0, 132.0, 130.6,
129.7, 128.7, 128.7, 128.6, 126.6, 123.7, 123.5, 90.0, 89.6, 64.7, 7.2, 4.9 ppm. IR (thin film, ATR) νmax
2958, 2912, 2878, 1604, 1493, 1459, 1413, 1368, 1239, 1201, 1101, 1078, 1005, 974, 915, 889, 817, 784,
754, 728, 689 cm-1. MS (EI, 70 eV) m/z (%): 322(15), 293(95), 263(33), 235(20), 206(20), 191(100, [M+]),
165(30), 95(15), 59(10). HRMS calcd for C21H26OSiNa [M+Na]+ 345.1651 found 345.1650.
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The Journal of Organic Chemistry
tert-Butyldiphenyl((3-(phenylethynyl)benzyl)oxy)silane 3x
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The general procedure was followed. Yellow oil (382 mg, yield 86%), Rf.: 0.27 (in hexanes: EtOAc
100:1). 1H NMR (250 MHz, CDCl3) δ = 7.68 – 7.57 (m, 4H), 7.54 – 7.15 (m, 15H), 4.67 (s, 2H), 1.02 (s,
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9H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 141.7, 136.0, 133.7, 132.1, 130.6, 130.2, 129.6, 128.8,
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128.7, 128.7, 128.2, 126.5, 123.7, 123.5, 90.0, 89.6, 65.6, 27.3, 19.8 ppm. IR (thin film, ATR) νmax 2960,
2933, 2856, 1603, 1493 cm-1. MS (EI, 70 eV) m/z (%): 389(90), 311(83), 189(100, [M+]), 165(45),
105(15), 77(10). HRMS calcd for C31H31OSi [M+H]+ 447.2144 found 447.2143.
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tert-Butyldimethyl((3-(phenylethynyl)benzyl)oxy)silane 3y
The general procedure was followed. Yellow oil (261 mg, yield 82%), Rf.: 0.25 (in hexanes: EtOAc
100:1). 1H NMR (250 MHz, CDCl3) δ = 7.50 – 7.34 (m, 3H), 7.33 – 7.14 (m, 6H), 4.62 (s, 2H), 0.84 (s,
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9H), 0.00 (s, 6H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 142.1, 132.0, 130.6, 129.5, 128.7, 128.7,
128.6, 126.5, 123.7, 123.5, 89.9, 89.5, 65.0, 26.4, 18.9, -4.8 ppm. IR (thin film, ATR) νmax 2958, 2934,
2883, 2857, 1604, 1493 cm-1. MS (EI, 70 eV) m/z (%): 322(2), 265(100, [M+]), 235(55), 191(90), 165(20),
75(5). HRMS calcd for C21H26OSiNa [M+Na]+ 345.1651 found 345.1656.
Triisopropyl((3-(phenylethynyl)benzyl)oxy)silane 3z
The general procedure was followed. Colorless oil (281 mg, yield 77%), Rf.: 0.23 (in hexanes: EtOAc
100:1). 1H NMR (250 MHz, CDCl3) δ = 7.73 – 7.50 (m, 3H), 7.48 – 7.31 (m, 6H), 4.86 (s, 2H), 1.13 (app.
s, 21H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 142.3, 132.0, 130.5, 129.3, 128.7, 128.7, 128.6, 126.2,
123.8, 123.4, 90.0, 89.5, 65.0, 18.5, 12.4 ppm. IR (thin film, ATR) νmax 2942, 2894, 2886, 1604, 1493,
1462 cm-1. MS (EI, 70 eV) m/z (%): 364(2), 321(100, [M+]), 293(10), 249(15), 206(25), 191(90), 165(24),
133(10), 95(10), 59(10). HRMS calcd for C24H33OSi [M+H]+ 365.2301 found 365.2299.
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5-(Pyridin-2-ylethynyl)-3-((triisopropylsilyl)ethynyl)-1H-indole 3aa
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The general procedure was followed. Green solid (284 mg, yield 71%). Mp.= 168-170 °C, Rf.: 0.21 (in
hexanes: EtOAc 2:1). 1H NMR (250 MHz, CDCl3) δ = 9.34 (s, 1H), 8.72 (s, 1H), 8.43 (dd, J = 4.8, 1.4
Hz, 1H), 7.85 (s, 1H), 7.78 (dt, J = 7.9, 1.8 Hz, 1H), 7.37 (d, J = 2.6 Hz, 1H), 7.34 – 7.18 (m, 3H), 1.09
(app. s, 21H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 152.2, 148.0, 139.1, 135.6, 130.1, 129.2, 126.9,
124.4, 123.7, 121.8, 114.7, 112.2, 100.0, 99.8, 95.0, 92.8, 84.4, 19.2, 11.8 ppm. IR (thin film, ATR) νmax
2944, 2865, 2725, 2211, 2150, 1589 cm-1. MS (EI, 70 eV) m/z (%): 398(32), 355(100, [M+]), 313(43),
285(50), 149(37), 135(27), 59(10). HRMS calcd for C26H31N2Si [M+H]+ 399.2257 found 399.2249.
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Ethyl 4-(benzofuran-2-yl)benzoate18 4a
The general procedure was followed. Light yellow solid (0.067 g, 26%). Mp.= 109 - 111 °C (Ref.: 109
- 111 °C), Rf (Hex.-EtOAc = 5:1) = 0.55; 1H NMR (250 MHz, CDCl3) δ = 7.98 (dt, J = 8.5, 1.6 Hz, 2H),
7.77 (dt, J = 8.5, 1.6 Hz, 2H), 7.46 (dd, J = 7.3, 1.5 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.23 – 7.05 (m,
2H), 6.99 (s, 1H), 4.26 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H) ppm. 13C{1H}NMR (63 MHz, CDCl3)
δ = 166.3, 155.3, 154.8, 134.5, 130.2, 130.2, 129.0, 125.1, 124.7, 123.3, 121.4, 111.5, 103.5, 61.2, 14.5.
MS (EI, 70 eV) m/z (% relative intensity, ion): 266(100, [M+]), 238 (55), 221(63), 193(13), 165(62),
163(22), 139(11), 110(10), 82(13). IR (thin film, ATR): 1708, 1614, 1454, 1411 cm-1.
2-(4-Methoxyphenyl)benzofuran5 4b
The general procedure was followed. White crystals (0.177 g, 79%). Mp.= 140 – 141 °C (Ref.: 143 –
144 °C), Rf (Hex.-EtOAc = 5:1) = 0.60; 1H NMR (250 MHz, CDCl3) δ = 7.70 (td, J = 10, 2.5 Hz, 2H),
7.49 – 7.37 (m, 3H), 7.21 – 7.06 (m, 2H), 6.88 (td, J = 32, 2.0 Hz, 2H), 6.78 (d, J = 0.8 Hz, 1H), 3.75 (s,
3H) ppm. 13C{1H}NMR (63 MHz, CDCl3) δ = 160.1, 156.2, 154.8, 129.6, 126.5, 123.9, 123.5, 123.0,
120.7, 114.4, 111.1, 99.8, 55.5 ppm. MS (EI, 70 eV) m/z (% relative intensity, ion): 224(100, [M+]),
209(78), 181(53), 152(37), 126(8), 112(10), 63(7). IR (thin film, ATR): 1611, 1506, 1456 cm-1.
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The Journal of Organic Chemistry
2-(4-Nitrophenyl)benzofuran37 4c
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The general procedure was followed a second column chromatographic purification was needed. Orange
solid (0.103 g, 43%). Mp.= 169 – 171 °C (Ref.: 181 - 183 °C), Rf (Hex.-EtOAc = 5:1) = 0.55; 1H NMR
(250 MHz, CDCl3) δ = 8.16 (d, J = 8.6 Hz, 2H), 7.84 (d, J = 8.6 Hz, 2H), 7.50 (d, J = 7.5 Hz, 1H), 7.41
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(d, J = 8.0 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.09 (s, 1H) ppm. C{1H}NMR
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(62.5 MHz, CDCl3) δ = 155.5, 153.4, 147.3, 136.4, 128.8, 126.0, 125.3, 124.4, 123.7, 121.8, 111.6, 105.2
ppm. MS (EI, 70 eV) m/z (% relative intensity, ion): 239(100, [M+]), 209(25), 181(25), 165(98), 163(35),
152(11), 115(10), 63(10). IR (thin film, ATR): 1601, 1573, 1519, 1452, 1346 cm-1.
Methyl 2-(1H-indol-5-yl)benzofuran-6-carboxylate 4d
The general procedure was followed. Light brown solid (0.271 g, 93%). Mp.= 134 - 136 °C, Rf (Hex.-
EtOAc = 5:1) = 0.23; δ = 1H NMR (250 MHz, DMSO-d6) δ = 11.30 (s, 1H), 8.12 (s, 1H), 8.05 (s, 1H),
7.78 (dd, J = 8.2, 1.3 Hz, 1H), 7.63 (m, 2H), 7.45 (d, J = 8.5 Hz, 1H), 7.37 (m, 1H), 7.29 (s, 1H), 6.49 (s,
1H), 3.80 (s, 3H) ppm. 13C{1H}NMR (63 MHz, DMSO-d6) δ = 166.4, 160.7, 153.4, 136.6, 134.1, 127.9,
126.8, 124.6, 124.1, 120.3, 120.2, 118.8, 117.5, 112.2, 111.6, 102.0, 99.6, 52.1 ppm. MS (EI, 70 eV) m/z
(% relative intensity, ion): 291(37, [M+]), IR (thin film, ATR): 1700, 1614, 1577 cm-1. HRMS m/z [M+H]+
+
calculated for C18H14NO3 : 292.0974; found: 292.0975.
6-Chloro-2-(thiophen-2-yl)benzofuran 4e
The general procedure was followed. White powder (0.159 g, 68%). Mp.= 142 - 143 °C, Rf (Hex.-EtOAc
= 5:1) = 0.68; 1H NMR (250 MHz, CDCl3) δ = 7.49 (m, 2H), 7.43 – 7.33 (m, 2H), 7.22 (dd, J = 8.7, 2.0
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Hz, 1H), 7.11 (t, J = 1 Hz, 1H), 6.79 (s, 1H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 153.3, 153.1,
133.1, 130.9, 129.1, 128.4, 126.8, 125.5, 124.8, 120.6, 112.4, 100.9 ppm. MS (EI, 70 eV) m/z (% relative
intensity, ion): 236(37, [M+]), 234(100, [M+]), 205(6), 171(44), 145(6), 126(7), 117(8), 85(8). IR (thin
film, ATR): 1586, 1448 cm-1. HRMS m/z [M]+ calculated for C12H7ClOS+: 233.9901; found: 233.9903.
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7-Chloro-4-(5-fluorobenzofuran-2-yl)quinoline 4f
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The general procedure was followed. Yellow solid (0.105 g, 36%). Mp.= 208 - 210 °C, Rf (Hex.-EtOAc
= 1:1) = 0.55; 1H NMR (250 MHz, CDCl3) δ = 8.97 (d, J = 4.6 Hz, 1H), 8.47 (d, J = 9.1 Hz, 1H), 8.20 (d,
J = 2.1 Hz, 1H), 7.74 (d, J = 4.6 Hz, 1H), 7.63 – 7.49 (m, 2H), 7.34 (dd, J = 8.3, 2.6 Hz, 1H), 7.26 (s, 1H),
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7.13 (td, J = 9.0, 2.6 Hz, 1H) ppm. C{1H}NMR (63 MHz, CDCl3) δ = 161.8(d, J = 242 Hz), 158.0,
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154.4, 152.0, 150.9, 149.4, 136.3, 136.1, 129.4 (d, J = 10.9 Hz), 129.2, 128.0 (d, J = 110.4 Hz), 123.4,
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120.2, 114.2 (d, J = 26.6 Hz), 112.7 (d, J = 9.6 Hz), 109.3 (d, J = 3.8 Hz), 107.6, 107.2 ppm. F NMR
(235 MHz, CDCl3) δ -119.5. MS (EI, 70 eV) m/z (% relative intensity, ion): 299(37, [M+]), 297(100,
[M+]), 270(6), 262(20), 234(13), 207(17), 148(4), 135(6), 117(6), 103(8). IR (thin film, ATR): 1596,
1577, 1497 cm-1. HRMS m/z [M+H]+ calculated for C17H10NOClF+: 298.0435; found: 298.0428.
5-(1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)-1H-indole 5a
The general procedure was followed. Pale yellow solid (0.165 g, 47%). Mp.= 173 - 176 °C, Rf (Hex.-
EtOAc = 1:1) = 0.30; 1H NMR (250 MHz, DMSO-d6) δ = 11.18 (s, 1H), 8.51 (s, 1H), 8.03 (s, 1H), 7.60
(d, J = 8.4 Hz, 3H), 7.44 (d, J = 8.4 Hz, 1H), 7.38 – 7.28 (m, 3H), 6.47 (s, 1H), 5.62 (s, 2H) ppm.
13C{1H}NMR (63 MHz, DMSO-d6) δ = 148.3, 135.7, 135.6, 131.7, 130.2, 127.9, 126.1, 121.6, 121.4,
120.3, 119.0, 116.9, 111.7, 101.4, 52.2 ppm. MS (EI, 70 eV) m/z (% relative intensity, ion): 354(9, [M+]),
352(10, [M+]), 325(33), 281(7), 245(15), 218(16), 207(25), 171(18), 169(39), 155(100), 141 (10),
128(44), 122(11), 101(18), 90(24), 77(11), 73(24), 63(10). IR (thin film, ATR): 1491, 1439, 1417, 1350,
+
cm-1. HRMS m/z [M+H]+ calculated for C17H14BrN4 : 353.0402; found: 353.0399.
4-(3-Bromophenyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole18 5b
The general procedure was followed. Yellow powder (0.138 g, 39%). Mp.= 88 - 90 °C (Ref.: 90 – 93
°C), Rf (Hex.-EtOAc = 1:1) = 0.43; 1H NMR (250 MHz, DMSO-d6) δ = 8.79 (s, 1H), 8.25 (d, J = 8.6 Hz,
2H), 8.05 (s, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H), 7.53 (d, J = 8.9 Hz, 3H), 7.41 (t, J =
7.8 Hz, 1H), 5.85 (s, 2H) ppm. 13C{1H}NMR (63 MHz, DMSO-d6) δ = 147.3, 145.3, 143.2, 132.8, 131.1,
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130.7, 129.1, 127.7, 124.1, 124.0, 122.7, 122.3, 52.2 ppm. MS (EI, 70 eV) m/z (% relative intensity, ion):
360(5, [M+]), 358(6, [M+]),281(7), 207(24), 196(98), 194(100), 169(13), 167(14), 147(10), 136(15),
121(36), 120(28), 115(26), 106(18), 102(12), 90(30), 89(44), 88(24), 78(40), 73(30), 63(17), 51(10). IR
(thin film, ATR): 1607, 1568, 1519, 1346 cm-1.
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4-(1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)-7-chloroquinoline 5c
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The general procedure was followed. Brown solid (0.264 g, 66%). Mp.= 128 - 130 °C, Rf (EtOAc) =
0.55; 1H NMR (250 MHz, DMSO-d6) δ = 9.00 (s, 1H), 8.97 (d, J = 4.6 Hz, 1H), 8.86 (d, J = 9.1 Hz, 1H),
8.13 (d, J = 2.2 Hz, 1H), 7.83 (d, J = 4.6 Hz, 1H), 7.71 (dd, J = 9.1, 2.3 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H),
7.39 (d, J = 8.4 Hz, 2H), 5.75 (s, 2H) ppm. 13C{1H}NMR (63 MHz, DMSO-d6) δ = 151.6, 149.0, 143.8,
135.6, 135.1, 134.2, 131.8, 130.4, 128.2, 128.1, 127.7, 125.9, 123.2, 121.6, 120.4, 52.5 ppm. MS (EI, 70
eV) m/z (% relative intensity, ion): 400(10, [M+]), 398(7, [M+]), 371(9), 369(7), 291(10), 281(8), 203(29),
201(100), 182(11), 171(69), 169(80), 166(17), 147(17), 90(54), 89(39), 75(10), 73(24). IR (thin film,
ATR): 1590, 1491 cm-1. HRMS m/z [M+H]+ calculated for C17H14N4Br+: 353.0402; found: 353.0397.
ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Author
* novakz@elte.hu, *tolnai@chem.elte.hu
ACKNOWLEDGMENT
PPD003/2016 and Janos Bolyai Research Scholarship of Hungarian Academy of Science is gratefully
acknowledged for financial support. Ms. M. Woodward is acknowledged for proofreading the manuscript.
Supporting Information
NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org.
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