Modular syntheses of star-shaped pyridine, bipyridine, and terpyridine derivatives by employing sonogashira reactions

Article abstract of DOI:10.1002/ejoc.201402778

A simple and flexible synthesis for a series of star-shaped pyridine, bipyridine, and terpyridine derivatives is reported by using a modular approach that combines the use of a ligand, spacer, and core unit. A fairly efficient method to prepare 4′-nonafloxy-functionalized terpyridine derivatives is described. The building blocks that contain the functionalized pyridine, bipyridine, or terpyridine derivatives were linked to different C₃-symmetrical core units. In most cases, Sonogashira reactions were employed in the crucial final steps of the synthesis. A star-shaped dodecafluorinated compound was also prepared in a straightforward fashion. A simple procedure for the preparation of partially silylated 1,3,5-triethynylbenzene derivatives is presented, which provides an approach to C₂-symmetrical star-shaped compounds that have only one terpyridine and two terphenyl units as "dummy" ligands. The absorption and emission spectra of the fully conjugated C₃-symmetrical pyridine derivatives were systematically investigated, and fairly large Stokes shifts were observed.

Full text of DOI:10.1002/ejoc.201402778

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FULL PAPER
DOI: 10.1002/ejoc.201402778
Modular Syntheses of Star-Shaped Pyridine, Bipyridine, and Terpyridine
Derivatives by Employing Sonogashira Reactions
Daniel Trawny,[a] Valentin Kunz,[a] and Hans-Ulrich Reissig*[a]
Dedicated to Professor Armin de Meijere on the occasion of his 75th birthday
Keywords: Nitrogen heterocycles / Alkynes / C–C coupling / UV/Vis spectroscopy / Fluorescence spectroscopy
A simple and flexible synthesis for a series of star-shaped
pyridine, bipyridine, and terpyridine derivatives is reported
by using a modular approach that combines the use of a li-
gand, spacer, and core unit. A fairly efficient method to pre-
pare 4Ј-nonafloxy-functionalized terpyridine derivatives is
described. The building blocks that contain the function-
alized pyridine, bipyridine, or terpyridine derivatives were
linked to different C3-symmetrical core units. In most cases,
Sonogashira reactions were employed in the crucial final
steps of the synthesis. A star-shaped dodecafluorinated com-
pound was also prepared in a straightforward fashion. A sim-
ple procedure for the preparation of partially silylated 1,3,5-
triethynylbenzene derivatives is presented, which provides
an approach to C2-symmetrical star-shaped compounds that
have only one terpyridine and two terphenyl units as
“dummy” ligands. The absorption and emission spectra of
the fully conjugated C3-symmetrical pyridine derivatives
were systematically investigated, and fairly large Stokes
shifts were observed.
Introduction
that were efficiently prepared by employing pathway C.[1a]
In the present report, we use pathway A and focus on the
syntheses of a series of star-shaped pyridine, bipyridine, and
terpyridine derivatives that have different substitution pat-
terns. To increase the compound library for our self-as-
sembly studies, we also present a simple and reliable syn-
thetic route to C2-symmetrical terpyridine derivatives by
employing partially protected core units.
Star-shaped multivalent pyridine derivatives are remark-
able compounds because of their self-assembly behavior at
the graphite surface.[1] The C3-symmetric core unit plays a
crucial role, as this molecular arrangement fits perfectly to
the graphite lattice. However, the pyridine end groups are
also important, if additional surface experiments are envi-
sioned, such as complexation with metal ions. This type of
compound can be prepared by employing three different
synthetic routes (see Scheme 1).[1a] The star-shaped target
compounds can be divided in the three moieties, that is,
ligand, spacer and core unit. Pathways A and B are exam-
ples of two common approaches that use coupling reac-
tions, such as the Sonogashira or Suzuki reactions.[2] Path-
way C illustrates a third strategy by using a trimerization
process to generate the central core unit from three func-
tionalized ligand-spacer portions.[3] The syntheses of C6-
symmetrical star-shaped derivatives that contain six pyr-
idine, bipyridine, and terpyridine moieties have also been
reported.[4] In previous studies, we described a C3-symmet-
rical tris(oxazole) derivative and its ability to form self-as-
sembled monolayers.[5] We also showed the remarkable self-
assembly behavior of star-shaped monopyridine derivatives
Scheme 1. Three routes to star-shaped C3-symmetrical compounds
with pyridine end groups.[1a]
[a] Institut für Chemie und Biochemie, Freie Universität Berlin,
Takustraße 3, 14195 Berlin, Germany
Results and Discussion
E-mail: hans.reissig@chemie.fu-berlin.de
Synthesis of Terpyridine Building Blocks
www.bcp.fu-berlin.de/en/chemie/chemie/forschung/OrgChem/
reissig
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402778.
We used mono-, bi-, and terpyridine ligands 1–4 as build-
ing blocks for the preparation of the desired star-shaped
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FULL PAPER
pyridine derivatives (see Scheme 2). 4-Bromopyridine (1) Claisen condensation, the liberated potassium ethoxide
could be purchased as its hydrochloride, whereas 4-bromo- caused the partial nucleophilic substitution at C-6 and C-
2,2Ј-bipyridine (2) was synthesized by using the protocols 6ЈЈ. Because separation of the obtained triketones was not
of Woodward and Wade starting from commercially avail- simple, the mixture was directly treated with ammonium
able 2,2Ј-bipyridine.[6,7]
acetate and subsequently with nonafluorobutanesulfonic
acid anhydride. Fortunately, the resulting mixture of terpyr-
idyl nonaflates 4, 7, and 8 could be separated by column
chromatography (three steps, 11% overall yield). Although
the combined overall yield was fairly low, these easily avail-
able precursors were now ready to be used as versatile
building blocks for the synthesis of various functionalized
terpyridine derivatives.[8]
Scheme 2. Mono-, bi-, and terpyridine building blocks 1–4 required
for the preparation of the star-shaped pyridine derivatives de-
scribed herein.
Terpyridine building blocks 3 and 4 were prepared by a
modified procedure that was reported by Constable et al.
(see Scheme 3).[8] By starting from ethyl 2-picolinate, tri-
ketone 5 was obtained in good yield through a twofold
Claisen condensation of acetone in the presence of sodium
hydride. In a glass pressure tube, the subsequent treatment
of 5 with ammonium acetate led to the formation of pyrid-
inone 6 in 68% yield. The nonaflyl group was introduced
by the addition of nonafluorobutanesulfonic acid anhydride
to a solution of pyridinone 6 in pyridine. The resulting ter-
pyridyl nonaflate 3, isolated in 64% yield, is an excellent
precursor for further functionalization by using a palla-
dium-catalyzed cross-coupling reaction.[9]
Scheme 4. Synthesis of 6,6ЈЈ-disubstituted terpyridyl nonaflates 4,
7, and 8.
Synthesis of C3-Symmetric Pyridine Derivatives
Almost all star-shaped multivalent pyridine derivatives
were prepared by using a Sonogashira reaction as the final
step (see Scheme 1, pathway A). For the syntheses of known
tris(pyridylethynyl)-substituted derivatives 9 and 10, the
Scheme 3. Synthesis of terpyridyl nonaflate 3 based on a protocol
by Constable et al.[8] (THF = tetrahydrofuran, ONf = nonaflate).
The preparation of the corresponding 6,6ЈЈ-disubstituted
terpyridyl nonaflates 4, 7, and 8 was achieved analogously
to the synthesis of compound 3. This modifications at the
6,6ЈЈ-positions should be very useful for the intended stud-
ies, as the solubility of the resulting star-shaped compounds
can be increased by further substitution at these (or other)
positions (see Scheme 4). We therefore attempted the prepa-
ration of 6,6ЈЈ-dichloro-substituted terpyridyl nonaflate 8
by starting from ethyl 6-chloropicolinate and then planned
to introduce different substituents by employing iron-cata-
Scheme 5. Structures of star-shaped pyridine derivatives 9 and
lyzed coupling reactions.[10] However, during the twofold 10[11] and synthesis of dodecafluorinated analogue 11.
2
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Star-Shaped Pyridines, Bipyridines and Terpyridines
protocols of Hupp and Clays were followed by using 4- maxima of nonprotonated and protonated 9 and 11 are al-
bromopyridine (1) and 1,3,5-triethynylbenzene or 1,3,5-tri- most identical (around 290 nm). The emission maxima of 9
ethynylmesitylene, respectively, to give the products in good (354 nm) was redshifted to 372 nm in its protonated form,
yields (see Scheme 5).[11] As an extension of our compound whereas the emission spectra of nonprotonated and proton-
library, dodecafluorinated compound 11 was also prepared ated 11 are identical, which indicates that the trifluoroacetic
by employing a simple nucleophilic aromatic substitution acid (TFA) is not able to protonate the electron-deficient
with pentafluoropyridine as the electrophile.[12] A threefold nitrogen atom (for details, see Supporting Information).
deprotonation of 1,3,5-triethynylbenzene by treatment with
The new star-shaped terpyridine derivatives 12 and 13
nBuLi followed by a reaction of the resulting species with were synthesized in an analogous manner to the synthesis
pentafluoropyridine furnished target compound 11 in 72% of 9 by using terpyridyl nonaflates 3 and 4 as precursors
yield.
(see Scheme 6). Because of the expected low solubility of
Surprisingly, the UV/Vis absorption of star-shaped com- the desired products, pyridine was used as the solvent along
pound 9 and its dodecafluorinated analogue 11 are only with the employment of higher temperatures. Although
slightly different in chloroform compared to a mixture of three subsequent coupling steps were required to produce
chloroform and trifluoroacetic acid (99:1). The absorption the target compounds, the C3-symmetrical products 12 and
Scheme 6. Synthesis of the star-shaped terpyridine derivatives 12 and 13.
Table 1. UV and fluorescence spectra of 12 (a) and 13 (b) in CHCl3 (solid lines) and CHCl3/TFA (99:1, dashed lines) as well as the
corresponding absorption and emission data.
CHCl3
Emission[b]
λmax [nm]
CHCl3/TFA (99:1)
Emission[b]
Absorption[a]
λmax [nm], (logε)
Stokes shift
[cm–1]
Absorption[a]
λmax [nm], (logε)
Stokes shift
[cm–1]
λmax [nm]
12
13
294, 309 sh[c]
311 (4.87)
356
377
5900
5600
290, 331[c]
368 (4.59)
417
444
10500, 6200[d]
4700
[a] Absorption: recorded at c = 10–5 molL–1 in 1 cm cuvettes. [b] Emission after excitation at the maximum absorption wavelength,
recorded at c = 10–6–10–5 molL–1 in 1 cm cuvettes. [c] Qualitative spectrum, logε could not be calculated because of solubility problems.
[d] Stokes shifts were calculated by using both absorption maxima.
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D. Trawny, V. Kunz, H.-U. Reissig
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13 were isolated in good yields. Nishihara and co-workers Table 2. Synthesis of the star-shaped bipyridine derivatives 15a–15e
with five different core units.
used a different strategy and prepared compound 12 by
using Stille reactions.[13] The laborious preparation of 4-
[(tributylstannyl)ethynyl]terpyridine and its toxicity as well
as the obtained lower yield of 65% make their synthesis less
attractive in comparison to our protocol.
The fully conjugated terpyridine derivatives 12 and 13
show remarkable photophysical properties. Their UV/Vis
absorption and fluorescence spectra were recorded in
chloroform or a mixture of chloroform and trifluoroacetic
acid (99:1) and are presented in Table 1. The introduction
of the electron-donating ethoxy group in compound 13 led
to a redshift for the absorption and the emission of approxi-
mately 20 nm in comparison to those of 12. The Stokes
shifts are 5900 cm–1 for 12 and 5600 cm–1 for 13, respec-
tively. Although the absorption maximum of protonated 12
is similar to that of the nonprotonated compound, a con-
siderable redshift of 61 nm was observed for the emission
of protonated 12. Furthermore, the absorption shoulder at
309 nm for 12 became a distinct second maximum at
331 nm after protonation. The absorption and emission
maxima of 13 are also strongly influenced by protonation
(see Table 1).
By using different core units and 4-bromobipyridine as
a ligand, five new star-shaped bipyridine derivatives were
prepared in a similar manner to the synthesis of 12 (see
Table 2). The building blocks 14a–14e were used as the cen-
tral core units, and they were either commercially available
(e.g., 14a; see Table 2, Entry 1) or prepared by following
modified literature procedures (e.g., 14b–14e, see Support-
ing Information for detailed experimental data; see Table 2,
Entries 2–5).[14] The reaction of 1,3,5-triethynylbenzene
with 4-bromobipyridine 2 afforded the corresponding star-
shaped compound 15a in 74% yield (see Table 2, Entry 1).
In comparison, the sterically more demanding 15b was ob-
tained in 61% yield. However, to obtain full conversion, the
reaction time had to be extended from 16 h to 2 d (see
Table 2, Entry 2). A longer reaction time was also needed
for the syntheses of the enlarged, fully conjugated star-
shaped derivatives 15c and 15d, which were obtained in
62% and 47% yield, respectively (see Table 2, Entries 3 and
4). For the preparation of 15d, the reaction temperature was
decreased to 40 °C to avoid the formation of unknown side
products that were produced when the reaction was con-
value did slightly increase. We assume that the methyl
ducted at 70 °C. We were also able to prepare unconjugated
groups slightly enhance the electron density of the central
derivative 15e, which contains an adamantane core unit.
benzene ring and lead to the observed redshift. Interest-
With respect to the bonding distances, this compound could
be compared to planar bipyridine derivative 15a. However,
in adamantane derivative 15e, the three side arms were ob-
viously forced out-of-plane.
Table 3. Absorption and emission data of star-shaped bipyridine
derivatives 15a–15d.
Entry
Absorption[a]
λmax [nm] (logε)
Emission[b]
λmax [nm]
Stokes shift
Again, we studied the photophysical properties of the
fully conjugated bipyridine derivatives 15a–15d and the un-
conjugated adamantane derivative 15e. Table 3 presents
their UV/Vis absorption and emission maxima as well as
the calculated Stokes shifts. As expected, the λmax values
increase as the π-systems are extended, with a maximum
redshift of 40 nm from 15a to 15d. Although the π-systems
[cm–1
]
1
2
3
4
15a
15b
15c
15d
290 (4.43)
304 (4.63), 324 sh 368
311 (4.66)
330 (5.65)
354, 368 sh
6200
7000
4400
3100
360
368, 377 sh
[a] Absorption: recorded at c = 10–5 molL–1 in 1 cm cuvettes.
[b] Emission after excitation at maximum absorption wavelength,
of 15b are not extended (in comparison to 15a), its λmax recorded at c = 10–6–10–5 molL–1 in 1 cm cuvettes.
4
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Star-Shaped Pyridines, Bipyridines and Terpyridines
ingly, the emission values do not vary significantly, which
A series of terphenyl ligands were prepared to test their
results in decreasing Stokes shifts of 6200 to 3100 cm–1 go- influence on the solubility of the desired C2-symmetrical
ing from 15a to 15d. As expected the unconjugated ada- star-shaped derivatives and determine their effect on the
mantane derivative 15e shows only a weak absorption self-assembly of these compounds (see Scheme 8). By start-
around 280 nm and no emission after excitation at this ab- ing from 1,3,5-tribromobenzene, the corresponding phenol
sorption wavelength.
17 was prepared under a standard protocol that involved a
bromine-lithium exchange, borate formation, and oxidation
by treatment with hydrogen peroxide.[17] Microwave-assisted
Suzuki reactions of 17 with three commercially available
phenylboronic acid derivatives afforded phenols 18–20 in
moderate to good yields. A final nonaflation with nona-
fluorobutanesulfonic acid anhydride furnished terphenyl
nonaflates 21–23 in excellent yields.
With terphenyl nonaflates 21–23 in hand, we started to
prepare the C2-symmetrical derivatives. The Sonogashira
reaction between terpyridyl nonaflate 3 and the monopro-
tected core unit 16a followed by deprotection with tetra-
n-butylammonium fluoride (TBAF) provided the desired
bis(terpyridine) derivative 24 in 30% yield (see Scheme 9).
The low yield is probably a result of purification difficulties
that arose from the scarcely soluble product. Subsequent
attempts to couple the terminal alkyne moiety of com-
pound 24 with terphenyl nonaflates 21–23 were unsuccess-
ful. Most likely, the low solubility of 24 and the generated
compounds caused these failures.
On the other hand, the Sonogashira reaction of terpyr-
idyl nonaflate 3 and diprotected core unit 16b led to the
formation of precursor 25 in 89% yield (see Scheme 10).
The subsequent deprotection of 25 by treatment with
TBAF furnished terminal dialkyne 26 in 93% yield. This
was coupled in the final step with terphenyl nonaflates 22
and 23 to furnish the desired star-shaped compounds 28
and 29 in moderate yields. Their UV/Vis absorption and
fluorescence spectra are very similar to that obtained for
12. Unfortunately, the coupling of 26 with terphenyl deriva-
tive 21 did not provide unsubstituted derivative 27, again
probably because of solubility problems. The prepared C2-
symmetrical terpyridines 28 and 29 are good candidates for
the generation and investigation of new supramolecular
architectures at the surface or in solution.
Synthesis of C2-Symmetric Terpyridine Derivatives
In addition to the described synthesis of C3-symmetrical
terpyridine derivatives, we also developed straightforward
methods for the preparation of new C2-symmetrical ana-
logues that have one of the pyridine ligands substituted by
a terphenyl unit as a “dummy” ligand. For this purpose,
1,3,5-triethynylbenzene was treated with nBuLi (1.5 equiv.)
following by quenching with triisopropylsilyl chloride
(TIPSCl) to give the partially protected core units 16a and
16b in 34 and 24% yield, respectively, after separation by
simple column chromatography (see Scheme 7). In addition,
the trisilylated compound was isolated in 8% yield. Al-
though, the syntheses of 16a and 16b were described in the
literature by using three steps for each of these com-
pounds,[15] our direct approach provides both compounds
in only one step. This simple method should also be appli-
cable to other trialkynes (core units). The partial protection
of 1,3,5-triethynylbenzene was also examined by using other
chorosilanes, however, TIPSCl gave the best total yield
when compared to other chlorosilanes.[16]
Scheme 7. Direct synthesis of partially protected 1,3,5-triethynyl-
benzene core units 16a and 16b by using TIPSCl.
Scheme 8. Synthesis of 4,4ЈЈ-disubstituted terphenyl nonaflates 21–23 [*Pd(PPh3)2Cl2 was used as catalyst].
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Scheme 9. Synthesis of bis(terpyridine) derivative 24.
Scheme 10. Synthesis of C2-symmetrical star-shaped terpyridine derivatives 28 and 29.
Conclusions
We were able to generate a library of star-shaped pyr- method should be applicable to other compounds of this
idine, bipyridine, and terpyridine derivatives by employing type. Other bipyridine or terpyridine derivatives that are of
a Sonogashira reaction in the crucial final step of their interest as ligands in catalytic processes[18] can certainly be
preparation. The employed methods are simple and flexible. prepared by employing the building blocks and reactions
Because our synthetic strategy is based on a modular con- presented herein. We also studied the photophysical proper-
struction principle that includes a ligand, spacer, and core ties of the fully conjugated pyridine derivatives and show
unit, quite a number of compounds were easily prepared. their remarkable absorption and fluorescence spectra. In
By using partially protected core units, we also presented the future, we will report our studies of the self-assembly
the syntheses of two C2-symmetrical star-shaped terpyrid- processes of the star-shaped compounds by using scanning
ine derivatives that contain two terphenyl groups as tunneling microscopy experiments and compare the results
“dummy” ligands, instead of the terpyridine units. This with the behavior of related compounds.[1,5]
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Star-Shaped Pyridines, Bipyridines and Terpyridines
ene (16b): 1,3,5-Triethynylbenzene (100 mg, 666 μmol) was dis-
solved in THF (8 mL), and n-butyllithium (2.5 m in hexanes,
0.4 mL, 1.00 mmol) was added at –78 °C. After 45 min, triisoprop-
ylsilyl chloride (330 μL, 1.99 mmol) was added, and the solution
was warmed to room temperature overnight. The mixture was
quenched with water, and the aqueous phase was extracted with
THF. The organic layer was washed with brine, dried with Na2SO4,
and concentrated to dryness. The residue was purified by
chromatography on a silica gel column (hexane) to give 16a (70 mg,
34%), 16b (75 mg, 24%), and the trisilylated derivative (32 mg, 8%)
as pale yellow gluey oils. Data of 16a: 1H NMR (400 MHz,
CDCl3): δ = 1.12 (br. s, 21 H, TIPS), 3.09 (s, 2 H, CϵCH), 7.52 (t,
J = 1.4 Hz, 1 H, 4-H), 7.55 (d, J = 1.4 Hz, 2 H, 2-H) ppm. This
compound was previously reported,[14a] but a different method was
employed for its synthesis. The observed analytical data agree with
those reported. Data of 16b: 1H NMR (400 MHz, CDCl3): δ =
1.09–1.14 (m, 42 H, TIPS), 3.08 (s, 1 H, CϵCH), 7.51 (t, J =
1.4 Hz, 1 H, 2-H), 7.52 (d, J = 1.4 Hz, 2 H, 4-H) ppm. This com-
pound was previously reported,[14b] but a different method was em-
ployed for its synthesis. The observed analytical data agree with
those reported. Data of trisilylated derivative: 1H NMR (400 MHz,
CDCl3): δ = 1.07–1.17 (m, 63 H, TIPS), 7.46 (s, 3 H, Ar) ppm. IR
Experimental Section
General Methods: See Supporting Information.
Typical Procedure 1: (2,2Ј:6Ј,2ЈЈ-Terpyridin)-4Ј-yl Nonafluorobut-
anesulfonate (3): Pyridinone 6[8] (1.26 g, 5.05 mmol) was dissolved
in dry pyridine (60 mL), and the solution was cooled to 0 °C.
Nonafluorobutanesulfonic acid anhydride (4.56 g, 7.58 mmol) was
added dropwise, and the mixture was warmed to room temperature
and stirred for 6 d. Ice was added, and after the mixture was stirred
for 30 min, a precipitate formed. This was collected by filtration.
Purification of this crude solid by recrystallization (hot hexane)
afforded nonaflate 3 (1.71 g, 64%) as colorless crystals; m.p. 94–
96 °C. 1H NMR (500 MHz, CDCl3): δ = 7.36 (ddd, J = 1.8, 4.8,
7.7 Hz, 2 H, 5-H), 7.86 (dt, J = 1.8, 7.7 Hz, 2 H, 4-H), 8.42 (s, 2
H, 3Ј-H), 8.59 (ddd, J = 0.8, 1.1, 7.7 Hz, 2 H, 3-H), 8.70 (ddd, J
= 0.8, 1.8, 4.8 Hz, 2 H, 6-H) ppm. 13C NMR (126 MHz, CDCl3):
δ = 113.1, 121.4, 124.8, 137.1, 149.5 (5 d, C-3Ј, C-3, C-5, C-4, C-6),
154.3, 158.8, 158.9 (3 s, 3 Ar) ppm. IR [attenuated total reflectance
(ATR)]: ν = 3100–3060 (=C–H), 1420 (S=O) cm–1. HRMS (ESI-
˜
TOF): calcd. for C19H10F9N3O3S [M + H]+ 532.0372; found
532.0394. C19H10F9N3O3S (531.4): calcd. C 42.95, H 1.90, N 7.91;
found C 43.00, H 1.71, N 7.88.
(ATR): ν = 2940, 2865 (C–H), 2160 (CϵC), 1460 (C–Si) cm–1.
˜
HRMS (EI, 270 °C, 80 eV): calcd. for C39H66Si3 [M]+· 618.4472;
found 618.4459.
1,3,5-Tris(perfluoropyridin-4-ylethynyl)benzene (11): A solution of
1,3,5-triethynylbenzene (60 mg, 400 μmol) in THF (10 mL) was
stirred at –78 °C under argon and then treated dropwise with n-
butyllithium (2.5 m in hexanes, 0.7 mL, 1.60 mmol). The resulting
mixture was stirred at –78 °C for 45 min, and pentafluoropyridine
(338 mg, 2.00 mmol) in THF (2 mL) was added dropwise. The mix-
ture was stirred at –78 °C for 30 min, and the solution was warmed
to room temperature overnight. The volatile components were re-
moved under reduced pressure. To the residue were added CH2Cl2
(10 mL) and hexane (3 mL), and the solution was cooled with an
ice bath. The resulting precipitate was removed by filtration,
washed with a small amount of cold CH2Cl2, and dried in vacuo
to provide 11 (239 mg, 72%) as a pale yellow solid; m.p. 148–
Typical Procedure 4: 1-[(2,2Ј:6Ј,2ЈЈ-Terpyridin)-4Ј-ylethynyl]-3,5-bis-
[(triisopropylsilyl)ethynyl]benzene (25): A mixture of alkyne 16b
(30 mg, 65 μmol), nonaflate 3 (41 mg, 77 μmol), Pd(PPh3)4 (7.5 mg,
6.5 μmol), triphenylphosphine (2 mg, 8 μmol), and CuI (1 mg,
5 μmol) in pyridine (2 mL) and triethylamine (420 μL) was heated
to 80 °C for 16 h under argon. The volatile components were re-
moved under reduced pressure, and the residue was purified by
chromatography on an aluminum oxide column (hexane/ethyl acet-
ate, 20:1) to give 25 (40 mg, 89%) as a pale yellow solid; m.p. 199–
201 °C. 1H NMR (500 MHz, CDCl3): δ = 1.15 (br. s, 42 H, TIPS),
7.34 (dd, J = 4.8, 7.7 Hz, 2 H, 5-H), 7.54 (t, J = 1.4 Hz, 1 H, 4ЈЈ-
H), 7.61 (d, J = 1.4 Hz, 2 H, 2ЈЈ-H), 7.85 (dt, J = 1.7, 7.7 Hz, 2 H,
4-H), 8.56 (s, 2 H, 3Ј-H), 8.60 (d, J = 7.7 Hz, 2 H, 3-H), 8.71 (br.
d, J = 4.8 Hz, 2 H, 6-H) ppm. 13C NMR (126 MHz, CDCl3): δ =
11.4 [d, SiCH(CH3)2], 18.8 (q, CH3), 88.5, 92.0, 92.6, 105.2 (4 s, 4
CϵC), 121.3, 122.9 (2 d, C-3, C-3Ј), 123.0 (s, Ar), 124.1 (d, C-5),
124.4, 132.9 (2 s, 2 Ar), 135.1, 135.2, 136.9, 149.3 (4 d, C-2ЈЈ, C-
1
151 °C. H NMR (400 MHz, CDCl3): δ = 7.94 (s, 3 H, Ar) ppm.
13C NMR (126 MHz, CDCl3): δ = 75.6 (t, JC,F = 4.2 Hz, CϵC),
102.6 (t, JC,F = 3.4 Hz, CϵC), 122.6 (s, C-1Ј), 136.9 (d, C-2Ј),
140.4–145.1 (3 m, 3 C-F) ppm. 19F NMR (376 MHz, CDCl3): δ =
–89.3 (s, 6 F, 2-F), –137.3 (s, 6 F, 3-F) ppm. IR (ATR): ν = 3080
˜
(=C–H), 2225 (CϵC) cm–1. UV/Vis (CHCl3): λ [log(ε/m–1 cm–1)] =
296 [3.32] nm. HRMS (EI): calcd. for C27H3F12N3 [M]+· 597.0136;
found 597.0103.
4ЈЈ, C-4, C-6), 155.6, 155.7 (2 s, 2 Ar) ppm. IR (ATR): ν = 3060–
˜
3010 (=C–H), 2945, 2865 (C–H), 2145 (CϵC), 1465 (C–Si) cm–1.
HRMS (ESI-TOF): calcd. for C45H55N3Si2 [M + Na]+ 716.3827;
found 716.3860.
Typical Procedure 2: 1,3,5-Tris[(2,2Ј:6Ј,2ЈЈ-terpyridin)-4Ј-ylethynyl]-
benzene (12):
A mixture of 1,3,5-triethynylbenzene (25 mg,
166 μmol), nonaflate 3 (310 mg, 583 μmol), Pd(PPh3)4 (19 mg,
17 μmol), triphenylphosphine (5 mg, 19 μmol), and CuI (3 mg,
16 μmol) in pyridine (5 mL) and triethylamine (0.2 mL) was heated
to 100 °C for 16 h under argon. The mixture was cooled to 0 °C,
and a precipitate formed. The solid was removed by filtration and
washed with CH2Cl2. Purification by recrystallization (hot pyr-
idine) afforded 12 (118 mg, 84%) as a pale brown solid; m.p.
Typical Procedure 5: 1-[(2,2Ј:6Ј,2ЈЈ-Terpyridin)-4Ј-ylethynyl]-3,5-bis-
(ethynyl)benzene (26): A solution of 25 (82 mg, 118 μmol) and
TBAF (1 m in THF, 320 μL, 320 μmol) in THF (4 mL) was stirred
at room temperature for 16 h. The volatile components were re-
moved under reduced pressure, and the residue was diluted with
CH2Cl2 (10 mL). Water (20 mL) was added, and the phases were
separated. The organic phase was washed with water (3ϫ 10 mL).
The organic layer was dried with Na2SO4 and then concentrated
to dryness. The residue was purified by chromatography on an alu-
minum oxide column (hexane/ethyl acetate, 10:1) to give 26 (42 mg,
93%) as a colorless solid; m.p. 189 °C. 1H NMR (500 MHz,
CDCl3): δ = 3.14 (s, 2 H, CϵCH), 7.35 (ddd, J = 1.0, 4.8, 7.7 Hz,
2 H, 5-H), 7.59 (t, J = 1.5 Hz, 1 H, 4ЈЈ-H), 7.64 (d, J = 1.5 Hz, 2
H, 2ЈЈ-H), 7.87 (dt, J = 1.7, 7.7 Hz, 1 H, 4-H), 8.56 (s, 2 H, 3Ј-H),
8.61 (br. d, J = 7.7 Hz, 2 H, 3-H), 8.71 (dd, J = 1.7, 4.8 Hz, 2 H,
6-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 78.9, 88.8, 91.5 (3 s,
3 CϵC), 81.7, 121.3, 123.0 (3 d, CϵCH, C-3, C-3Ј), 123.2, 123.4,
1
Ͼ235 °C. H NMR (400 MHz, CDCl3): δ = 7.34–7.42 (m, 6 H, 5-
H), 7.79 (s, 3 H, 2ЈЈ-H), 7.89 (t, J = 7.4 Hz, 6 H, 4-H), 8.56–8.70
(m, 12 H, 3-H, 3Ј-H), 8.72–8.79 (m, 6 H, 6-H) ppm. Because of
poor solubility, a satisfactory 13C NMR spectrum was not ob-
tained. IR (ATR): ν = 3060 (=C–H), 2220 (CϵC) cm–1. UV/Vis
˜
(CHCl3, qualitative because of the low solubility): λ = 294 nm.
HRMS (ESI-TOF): calcd. for C57H33N9 [M + H]+ 844.2932; found
844.2933.
Typical Procedure 3: 3,5-Diethynyl-1-[(triisopropylsilyl)ethynyl]-
benzene (16a) and 5-Ethynyl-1,3-bis[(triisopropylsilyl)ethynyl]benz-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O42778
/KAP1
Date: 20-08-14 17:01:05
Pages: 9
D. Trawny, V. Kunz, H.-U. Reissig
FULL PAPER
W. R z ysko, A. Cadeddu, T. R. Cook, P. J. Stang, P. Samorì, J.
Am. Chem. Soc. 2013, 135, 6942–6950.
˙
(2 s, 2 Ar), 124.3 (d, C-5), 132.8, (s, Ar), 135.5, 135.9, 137.0, 149.3
(4 d, C-2ЈЈ, C-4ЈЈ, C-4, C-6), 155.6, 155.7 (2 s, 2 Ar) ppm. IR
[2] a) H. L. Anderson, C. J. Walter, A. Vidal-Ferran, R. A. Hay,
P. A. Lowden, J. K. M. Sanders, J. Chem. Soc. Perkin Trans. 1
1995, 2275–2279; b) N. Kobayashi, M. Kijima, J. Mater. Chem.
2008, 18, 1037–1045; c) S. Winter, E. Weber, L. Eriksson, I.
Csoregh, New J. Chem. 2006, 30, 1808–1819.
[3] C. Engler, H. E. Berthold, Ber. Dtsch. Chem. Ges. 1874, 7,
1123–1125.
[4] V. Marvaud, D. Astruc, Chem. Commun. 1997, 773–774.
[5] T. Lechel, M. Gerhard, D. Trawny, B. Brusilowskij, L. Schefzig,
R. Zimmer, J. P. Rabe, D. Lentz, C. A. Schalley, H.-U. Reissig,
Chem. Eur. J. 2011, 17, 7480–7491.
[6] D. Wenkert, R. B. Woodward, J. Org. Chem. 1983, 48, 283–289.
[7] R. A. Jones, B. D. Roney, W. H. F. Sasse, K. O. Wade, J. Chem.
Soc. B 1967, 106–111.
(ATR): ν = 3290 (ϵC–H), 3070–2860 (=C–H), 2220 (CϵC) cm–1.
˜
HRMS (ESI-TOF): calcd. for C27H15N3 [M + H]+ 382.1339; found
382.1340.
Typical Procedure 6: 1-[(2,2Ј:6Ј,2ЈЈ-Terpyridin)-4Ј-ylethynyl]-3,5-
bis[5Ј-ethynyl-3,3ЈЈ-dimethoxy-(1,1Ј:3Ј,1ЈЈ-terphenyl)]benzene (29):
A mixture of 26 (25 mg, 66 μmol), nonaflate 3 (51 mg, 87 μmol),
Pd(PPh3)4 (4.5 mg, 4.0 μmol), triphenylphosphine (1 mg, 4 μmol),
and CuI (0.5 mg, 2.6 μmol) in pyridine (2 mL) and triethylamine
(230 μL) was heated to 60 °C for 16 h under argon. The volatile
components were removed under reduced pressure, and the residue
was purified by chromatography on an aluminum oxide column
(hexane/ethyl acetate, 10:1) to give 29 (12 mg, 32%) as a colorless
[8] E. C. Constable, M. D. Ward, J. Chem. Soc., Dalton Trans.
1990, 1405–1409.
1
solid; m.p. 68–71 °C. H NMR (700 MHz, CDCl3): δ = 3.92 (s, 12
H, CH3), 6.98 (ddd, J = 0.9, 2.1, 7.9 Hz, 4 H, 4ЈЈЈЈ-H), 7.23 (t, J =
2.1 Hz, 4 H, 2ЈЈЈЈ-H), 7.29 (ddd, J = 0.9, 2.1, 7.9 Hz, 4 H, 6ЈЈЈЈ-H),
7.39 (ddd, J = 1.1, 4.7, 7.7 Hz, 2 H, 5-H), 7.42 (t, J = 7.9 Hz, 4 H,
5ЈЈЈЈ-H), 7.78 (d, J = 1.6 Hz, 2 H, 2ЈЈ-H), 7.80 (d, J = 1.6 Hz, 4 H,
4ЈЈЈ-H), 7.81–7.82 (m, 3 H, 4ЈЈ-H, 2ЈЈЈ-H), 7.90 (dt, J = 1.8, 7.7 Hz,
2 H, 4-H), 8.63 (s, 2 H, 3Ј-H), 8.65 (br. d, J = 7.7 Hz, 2 H, 3-H),
8.76 (dd, J = 1.8, 4.7 Hz, 2 H, 6-H) ppm. 13C NMR (176 MHz,
CDCl3): δ = 55.4 (q, CH3), 87.9, 88.7, 90.8, 91.9 (4 s, 4 CϵC),
112.9, 113.4, 119.8, 121.2, 122.9 (5 d, C-2ЈЈЈЈ, C-4ЈЈЈЈ, C-6ЈЈЈЈ, C-3,
C-3Ј), 123.4, 123.6 (2 s, 2 Ar), 124.1 (d, C-5), 124.2 (s, Ar), 126.6,
129.5, 129.9 (3 d, C-2ЈЈЈ, C-4ЈЈЈ, C-5ЈЈЈЈ), 132.9 (s, Ar), 134.5, 134.9,
136.9 (3 d, C-2ЈЈ, C-4ЈЈ, C-4), 141.8, 142.0 (2 s, 2 Ar), 149.3
[9] a) M. Rottländer, P. Knochel, J. Org. Chem. 1998, 63, 203–208;
b) review: J. Högermeier, H.-U. Reissig, Adv. Synth. Catal.
2009, 351, 2747–2763; c) T. Ikawa, K. Saito, S. Akai, Synlett
2012, 23, 2241–2246.
[10] O. M. Kuzmina, A. K. Steib, D. Flubacher, P. Knochel, Org.
Lett. 2012, 14, 4818–4821.
[11] a) S. J. Lee, K. L. Mulfort, J. L. O’Donnell, X. Zuo, A. J. Go-
she, P. J. Wesson, S. T. Nguyen, J. T. Hupp, D. M. Tiede, Chem.
Commun. 2006, 4581–4583; b) I. Asselberghs, G. Hennrich, K.
Clays, J. Phys. Chem. A 2006, 110, 6271–6275.
[12] T. M. Fasina, J. C. Collings, D. P. Lydon, D. Albesa-Jove, A. S.
Batsanov, J. A. K. Howard, P. Nguyen, M. Bruce, A. J. Scott,
W. Clegg, S. W. Watt, C. Viney, T. B. Marder, J. Mater. Chem.
2004, 14, 2395–2404.
(d, C-6), 155.65, 155.70, 160.1 (3 s, 3 Ar) ppm. IR (ATR): ν =
˜
3060–2915 (=C–H), 2830 (C–H), 2215 (CϵC) cm–1. UV/Vis
(CHCl3): λ [log(ε/m–1 cm–1)] = 294 [4.04] nm. HRMS (ESI-TOF):
calcd. for C67H47N3O4 [M + H]+ 958.3639; found 958.3694.
[13] Y. Nishimori, K. Kanaizuka, M. Murata, H. Nishihara, Chem.
Asian J. 2007, 2, 367–376.
[14] a) N. Ohshiro, F. Takei, K. Onitsuka, S. Takahashi, J. Or-
ganomet. Chem. 1998, 569, 195–202; b) S. Sirilaksanapong, M.
Sukwattanasinitt, P. Rashatasakhon, Chem. Commun. 2012, 48,
293–295; c) N. Kobayashi, M. Kijima, J. Mater. Chem. 2008,
18, 1037–1045; d) W. Maison, J. V. Frangioni, N. Pannier, Org.
Lett. 2004, 6, 4567–4569.
Supporting Information (see footnote on the first page of this arti-
cle): General experimental methods, all experimental procedures
and characterization data.
[15] a) K. Onitsuka, M. Fujimoto, H. Kitajima, N. Ohshiro, F.
Takei, S. Takahashi, Chem. Eur. J. 2004, 10, 6433–6446; b)
E. C. Constable, O. Eich, C. E. Housecroft, J. Chem. Soc., Dal-
ton Trans. 1999, 1363–1364.
Acknowledgments
[16] The employed chlorosilanes are tert-butyldimethylsilyl chlor-
ide, tert-butyldiphenylsilyl chloride, trimethylsilyl chloride, and
tris(trimethylsilyl)silyl chloride. In the case of trimethylsilyl
chloride and tris(trimethylsilyl)silyl chloride, the resulting mix-
tures could not be separated by column chromatography.
[17] D. Laliberté, T. Maris, J. D. Wuest, J. Org. Chem. 2004, 69,
1776–1787.
[18] P. Hommes, C. Fischer, C. Lindner, H. Zipse, H.-U. Reissig,
Angew. Chem. Int. Ed. 2014, 53, 7647–7651; Angew. Chem.
2014, 126, 7778–7782, and references cited therein.
Received: June 19, 2014
The generous support of the Deutsche Forschungsgemeinschaft
(DFG) (SFB 765), the Evonik Foundation (Ph.D. fellowship to
D. T.), and Bayer HealthCare is gratefully acknowledged. The au-
thors thank Dr. Boris Brusilowskij (research group of Prof. Dr.
Christoph A. Schalley) for donating compounds 9, 10, and 14e and
Dr. Reinhold Zimmer for help during preparation of this manu-
script.
[1] a) D. Trawny, L. Vandromme, J. P. Rabe, H.-U. Reissig, Eur. J.
Org. Chem. 2014, 4985–4992; b) A. Ciesielski, P. J. Szabelski,
Published Online: ᭿
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42778
/KAP1
Date: 20-08-14 17:01:05
Pages: 9
Star-Shaped Pyridines, Bipyridines and Terpyridines
Star-Shaped Compounds
D. Trawny, V. Kunz,
H.-U. Reissig* ................................... 1–9
Modular Syntheses of Star-Shaped Pyrid-
ine, Bipyridine, and Terpyridine Deriva-
tives by Employing Sonogashira Reactions
Keywords: Nitrogen heterocycles / Alkynes /
C–C coupling / UV/Vis spectroscopy /
Fluorescence spectroscopy
Modular, simple, and efficient! A library of
C3-symmetrical compounds with benzene
cores and pyridine, bipyridine, and ter-
pyridine end groups were prepared from
simple precursors.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9