Synthesis of π-conjugated molecules based on 3,4-dioxypyrroles via Pd-mediated decarboxylative cross-coupling

Article abstract of DOI:10.1021/jo201770j

A general scheme for the synthesis of π-conjugated molecules based on 3,4-dioxypyrroles is presented. The π-conjugated molecules were synthesized via Pd-mediated decarboxylative cross-coupling using various 3,4-propylenedioxypyrrole carboxylic acids and a

Full text of DOI:10.1021/jo201770j

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pubs.acs.org/joc
Synthesis of π-Conjugated Molecules Based on 3,4-Dioxypyrroles via
Pd-Mediated Decarboxylative Cross-Coupling
Frank A. Arroyave and John R. Reynolds*
The George and Josephine Butler Polymer Research Laboratory, Department of Chemistry, Center for Macromolecular Science and
Engineering, University of Florida, Gainesville, Florida 32611, United States
S
* Supporting Information
ABSTRACT: A general scheme for the synthesis of π-
conjugated molecules based on 3,4-dioxypyrroles is presented.
The π-conjugated molecules were synthesized via Pd-mediated
decarboxylative cross-coupling using various 3,4-propylene-
dioxypyrrole carboxylic acids and aryl bromides, including the
base-sensitive electron acceptor 4,7-dibromobenzo[c][1,2,5]-
thiadiazole (BTD). N-Methylpyrrolidone was used as solvent,
Pd(acac)2 was employed as the palladium source and P(o-tol)3
as the ligand. The methodology was applied to 3,4-
dioxypyrrole monoacids and 3,4-dioxypyrrole diacids to
produce multi-ring π-conjugated systems containing phenyl,
thiophenyl, BTD, and pyridinyl units. In general, the method has yielded a practical approach for the synthesis of 3,4-
dioxypyrrole-based π-conjugated molecules in acceptable to high yields of 44−94%.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Electroactive polymers based on 3,4-dioxypyrrole molecules
[poly(3,4-alkylenedioxypyrroles), PXDOPs] display character-
istic optical and electrochemical properties, such as high
conductivity, multicolor cathodic and anodic coloring electro-
chromism, rapid redox switching,6 and stability to bioreduc-
tants.7 These properties make PXDOPs suitable candidates for
a wide range of applications, such as electrochromic and light-
emitting devices, conducting coatings, chemical sensors,
bioactive materials, and mechanical actuators.6 Due to their
electron-rich nature and tunability, XDOPs can produce
polymers able to combine high electronic band gaps with low
oxidation potentials;6 however, these desirable properties can
render XDOP monomer syntheses difficult and time-consum-
ing, and thus, non-2,5-substituted XDOPs must be handled
carefullythat is, under acid- and oxygen-free conditions.
Pd-mediated decarboxylative cross-coupling chemistry offers
a practical and useful approach for 3,4-dialkyloxypyrrole
molecules. Typically, organometallic cross-couplings involve
halo derivatives, yet monohalo-XDOPs tend to dimerize or to
decompose,8 and dihalo-XDOPs polymerize even at relatively
low temperatures.9 Direct arylation is possible for XDOPs, but
in this case, the reaction conversions and yields tend to be low.5
Another possibility in carrying out organometallic cross-
coupling on XDOPs is to synthesize the XDOP boron
derivative via direct borylation,10 with the boronic ester then
employed in the Suzuki coupling, but this approach adds two
steps to the synthetic route (decarboxylation5 and borylation10)
Carboxylic acids can be used as substrates in a wide variety of
chemical reactions,1 and although their use as sacrificial groups
in organometallic coupling was initially reported by Nilsson in
1966, the utilization of the tendency toward decarboxylation of
some organic molecules for cross-coupling became well-known
with the report made by Myers and co-workers in 2002.2
Nilsson’s reaction requires copper(I) oxide as the catalyst and
resembles the Ullmann cross-coupling;3 on the other hand,
Myers’ reaction utilizes a palladium catalyst and resembles the
Heck reaction. Another remarkable contribution to this type of
organometallic cross-coupling was presented in 20064 by
Goossen and co-workers, who reported a Pd-mediated reaction
using a copper(I) catalyst as the transmetallating agent and
demonstrated the practical use of the decarboxylative cross-
coupling by synthesizing a variety of biaryls and showing that it
can be applied in the large-scale production of an intermediate
of the agricultural fungicide Boscalid.
As shown in Scheme 1, we reported the synthesis of various
π-conjugated oligomers based on 3,4-dialkyloxypyrrole
(XDOP)5 employing a 3,4-propylenedioxy (ProDOP) mono-
carboxylic acid and demonstrated that the decarboxylative
cross-coupling is a suitable reaction to create π-conjugated
molecules based on XDOPs. Here, we complement the
previous report showing that the methodology can be expanded
to XDOP dicarboxylic acids and also applied to create XDOP
π-conjugated molecules containing the base-sensitive benzo[c]-
[1,2,5]thiadiazole (BTD) system.
Received: August 29, 2011
Published: October 13, 2011
© 2011 American Chemical Society
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Scheme 1. Synthesis of ProDOP-Based Molecules via Decarboxylative Cross-Coupling of ProDOP Carboxylic Acids
and requires the expensive iridium catalyst [Ir(OMe)(COD)]2.
To compare the Suzuki−Miyaura approach with the decarbox-
ylative cross-coupling,5 we synthesized the boronate compound
2 and used it in the Suzuki coupling to produce compound 3, as
shown in Scheme 2, with an overall yield of 80%. We also
work, we demonstrate that the Pd-mediated cross-coupling
reaction can be applied to dicarboxylic acids of the readily
decarboxylable 3,4-dioxypyrrole molecule.
In order to assess the appropriate decarboxylation temper-
ature and thermal stability of the XDOP carboxylates, we
performed thermogravimetric analysis (TGA) measurements
on the 3,4-propylenedioxypyrroles (ProDOPs) 4, 5, and 6 and
also on some corresponding potassium carboxylates (see
Supporting Information). As described in Scheme 3, the data
Scheme 2. Alternative Route for the Synthesis of XDOP-
Based π-Conjugated Oligomers via Suzuki Coupling
Scheme 3. Protodecarboxylation of Three Different ProDOP
Carboxylic Acids As Measured by TGA
synthesized the dipinacolyl diboronate analogue of 3,4-
propylenedioxypyrrole but were unable to purify it, as it
decomposed on both silica or alumina, and high vacuum
distillation also failed. These results showed that, in the case of
XDOPs, the decarboxylative cross-coupling can be a suitable
alternative to common cross-coupling methods such as the
Suzuki coupling.
Several reports of Pd-mediated decarboxylative cross-
coupling on aromatic rings have been made.1,5,11−22 It has
been previously demonstrated that the appropriate temperature
for the decarboxylative cross-coupling varies with the tendency
of the carboxylic acid to undergo decarboxylation, along with
other factors such as aryl halide, solvent, and ligand
employed.5,13 The reaction has been successfully applied to
monocarboxylic acids, but reports of decarboxylative cross-
coupling for a dicarboxylic acid have yet to be shown. In this
reveal that the decarboxylation temperature of the dicarboxylic
ProDOP diacid 4 is lower than the temperature needed to
decarboxylate the monoacid containing the ester group (6) and
higher than the temperature needed to decarboxylate the
corresponding monoacid 5. The temperatures presented in
Scheme 3 correspond to the minimum required temperature
for the protodecarboxylation to occur in the bulk molten
compound. Although we did not expect to have the same
reactivity on the respective potassium carboxylates, the TGA
data provide insight into the reactivity and relative stability of
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each carboxylateacids and potassium salts, with the latter
decomposing around 300 °C (see Supporting Information).
For our reactions, we used a 3,4-dioxypyrrole containing a
propylene bridge because the presence of the dioxepine ring
offers higher stability to the pyrrole ring than the ethylenedioxy
(EDOP) analogue and the open chain substituents such as
methoxy or hexyloxy. The relatively higher stability comes from
the torsion generated in the seven-membered ring, which
decreases the electron donation from the oxygen atoms into the
pyrrole ring, thus decreasing the electron density in the pyrrole
ring. In addition, ProDOPs also possess higher solubility than
their EDOP analogues, which we attribute to the lower
symmetry of the dioxepine ring, which decreases the possibility
of π-stacking.
Our initial experiments using the dicarboxylic acid 4 with
cesium or potassium carbonates failed under the previously
reported conditions,5 as even at high temperature (180 °C) the
reaction did not take place, and precipitation of the potassium
carboxylate was commonly observed. In an attempt to increase
the solubility of the dioxypyrrole dicarboxylate, the amount of
solvent (N-methylpyrrolidone) was increased, and the base was
switched to Li2CO3, but it did not produce any change in the
reaction outcome. Tetra(n-butyl)ammonium bromide was
added to the reaction mixture to increase the solubility of the
carboxylate, which had a favorable effect, and several products
were observed by TLC. A combination of 1−2 equiv of tetra(n-
butyl)ammonium bromide with 2−3 equiv of K2CO3 almost
exclusively produced the monosubstituted product 8 in 92%
yield (Scheme 4), which indicates that the potassium carbonate
is not sufficiently basic to form the potassium dicarboxylate of
4, which leads to a monodecarboxylative cross-coupling,
followed by a proto-decarboxylation to produce compound 8.
Scheme 5 demonstrates how the Pd-decarboxylative cross-
coupling reaction has been employed to build π-conjugated
molecules containing the ProDOP unit. The synthesis of the
ProDOP acids was carried out by controlled saponification of
the ProDOP diester 9 (shown in Scheme 5), and this way the
diacid 4 (shown in Scheme 3) and monoacid 6 can be obtained.
To synthesize the monoacid 5, compound 6 has to be
decarboxylated first and then subjected to a second hydrolysis
(as shown in Scheme 5). In all cases, the ProDOP acids were
isolated and then employed for the decarboxylative cross-
coupling according to the routes described in Scheme 5. As
aforementioned, potassium carbonate is not a suitable base to
carry out the cross-coupling in ProDOP diacids since it will lead
to monosubstitution; therefore, the best results for route A
were observed when the anhydrous potassium dicarboxylate 10
(shown Scheme 5) was presynthesized from the diacid 4 using
a strong base (e.g., KOH or t-BuOK) and employed in the Pd-
decarboxylative cross-coupling in combination with tetra(n-
butyl)ammonium bromide (compounds 11 and 12, presented
in entries 1 and 2, Table 1). In this case, the reaction
temperature was relatively low, and the reactions proceeded
slowly at 55 °C, thus, to speed up the chemical reactions, the
temperatures were typically increased to ∼70 °C. Route A
produced a π-conjugated system containing the ProDOP as
central core, and these types of molecules may be further
employed in the construction of more complex π-conjugated
systems such as oligomers and polymers.
Using route B presented in our previous report,5 we now
demonstrate that the coupling can be applied to synthesize π-
conjugated systems containing the base-sensitive benzo[c]-
[1,2,5]thiadiazole (BTD) unit (compounds 13 and 14, entries
3 and 4, Table 1). Inclusion of the BTD unit in a π-conjugated
molecule is a practical approach to decrease the band gap of the
systemoligomer or polymer through an electron donor−
acceptor interaction, and to increase its stability toward
oxidation.23 Unfortunately, the thiadiazole ring tends to
Scheme 4. Sequential Decarboxylative Cross-Coupling and
Proto-decarboxylation on a ProDOP Diacid
Scheme 5. General Scheme for the Synthesis of ProDOP-Based π-Conjugated Molecules via Palladium-Mediated
Decarboxylative Cross-Coupling (R = C12H25 in All Instances)
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Table 1. Several ProDOP-Based π-Conjugated Molecules Synthesized via Decarboxylative Cross-Coupling
a
b
c
NMP, Bu4NBr, 2 mol % of Pd(acac)2, 4 mol % of (o-tol)3P. NMP, KHCO3, 3 mol % of Pd(acac)2, 6 mol % of (o-tol)3P. NMP, K2CO3, Bu4NBr, 2
d
mol % of Pd(acac)2, 4 mol % of (o-tol)3P. NMP, KHCO3, 3 mol % of Pd(acac)2, 6 mol % of (o-tol)3P.
decompose under basic reaction conditions, such as those
employed for decarboxylative cross-coupling. Initial attempts to
include the BTD moiety in the ProDOP π-conjugated
molecules using the Pd-decarboxylative cross-coupling failed
because the bases K2CO3 and Cs2CO3 in N-methylpyrrolidone
(NMP) caused decomposition of 4,7-dibromo-BTD. Switching
to the milder base KHCO3, while keeping the temperature
under 90 °C and increasing dilution, allowed the reaction to
proceed in high yield (89% for 13 and 94% for 14).
Route B produces a π-conjugated system that still possesses
two ester groups and, as depicted in route C (Scheme 5), the
ester groups can be hydrolyzed and further employed to carry
out an additional decarboxylative cross-coupling to expand the
π-conjugated system (e.g., compounds 15 and 16, entries 5 and
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purification, unless otherwise noted. N-H-(2,5-COOEt)ProDOP,
[diethyl 3,4-(propylene-1,3-dioxy)pyrrole-2,5-dicarboxylate], was gen-
erously provided by BASF. All reactions were carried under argon
atmosphere unless otherwise mentioned.
6, Table 1). These potassium dicarboxylates obtained from the
hydrolysis of the ProDOP oligomers5 have low solubility in
water, which allowed a facile isolation after the basic hydrolysis,
and additionally, due to the low solubility of the potassium salts
also in organic solvents, route C requires tetra(n-butyl)-
ammonium bromide. Route C cannot be applied to BTD-
containing molecules since the BTD unit will decompose
during the basic hydrolysis, but this problem is circumvented by
employing route D, which generates a π-conjugated molecule
containing two unsubstituted positions on the 3,4-dioxypyrrole
molecule that may be employed for further reaction or
derivatization (e.g., compound 17, entry 7 in Table 1). We
assume that the moderate yield for formation of compound 17
was due to decomposition and possible ill-defined oligomeriza-
tion since, in addition to the desired compound, several side
products were also observed by TLC after 24 h of reaction,
which probably corresponds to oligomerization via direct
arylation, as has been observed previously under these reaction
conditions.5
Ethyl N-Dodecyl-3,4-(propylene-1,3-dioxy)-5-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)pyrrole-2-carboxylate (2). The
literature procedure10 was slightly modified as follows: To a dry 25 mL
round-bottom flask, containing a stir bar and under argon atmosphere,
and equipped with a condenser, were added [Ir(OMe)(COD)]2 (5.1
mg, 0.008 mmol, 1.5 mol %), 2,2′-bipyridine (2.4 mg, 0.015 mmol, 3
mol %), and bis(pinacolato)diboron (0.1295 g, 0.510 mmol, 1.1
equiv). Compound 15 was dissolved in 3 mL of degassed heptanes and
then transferred via syringe to the flask containing the other reagents,
the system was equipped with a bubbler. The mixture was stirred at 75
°C for 24 h. The reaction mixture was cooled to room temperature
and filtered through a short path of a mixture 4:1 of decolorizing
carbon/alumina activity 3. The decolorizing carbon/alumina mixture
was flushed with 80 mL of 30% diethyl ether in hexanes to recover the
entire product. After removal of the solvent, the crude was subjected to
high vacuum for 1 h at 60 °C to remove boron byproducts. The
1
product was isolated as a colorless oil, 0.198 g (84% yield): H NMR
In general, palladium acetylacetonate was used in combina-
tion with tri(o-tolyl)phosphine as the catalytic system, and the
amount employed was varied from 1 to 3% for the palladium
catalyst and 2 to 6% for the phosphine ligand; also it is possible
to use triphenylphosphine as the ligand, but lower yields may
be expected.5 N-Methylpyrrolidone proved to be a suitable
solvent since it can dissolve both the potassium and the tetra(n-
butyl)ammonium salts as well as the π-conjugated molecule
that is being formed.
In most cases, the cross-coupling reactions were monitored
by TLC to determine the optimal reaction time, which varied
depending of the ProDOP and the aryl bromide employed
(24−72 h; see Experimental Section). Time and temperature of
the reaction are two important factors that have to be
controlled; on one hand, temperatures higher than the ones
presented in Table 1 may lead to decomposition of the
carboxylates, and on the other hand, a long reaction time may
lead to decomposition of the π-electron-rich molecule, as was
observed in the case of route D (shown in Scheme 5), where
both decomposition and ill-defined oligomerization occurred.
(300 MHz, CDCl3) δ 4.41 (t, 2H, J = 7.4 Hz), 4.30 (q, 2H, J = 7.0
Hz), 4.15−4.08 (m, 4H), 2.22−2.12 (m, 2H), 1.59 (m, 2H), 1.40−
1.20 (br, 33H), 0.88 (t, 3H, J = 6.4 Hz); 13C NMR (75 MHz, CDCl3)
δ 161.1, 146.7, 142.6, 129.9, 113.3, 83.4, 71.7, 71.6, 60.1, 48.0, 33.8,
32.9, 32.1, 29.88, 29.85, 29.82, 29.64, 29.57, 27.0, 24.9, 22.9, 14.6, 14.3;
HRMS (ESI, M + H+) m/z calcd for C28H48BNO6H 506.3653, found
506.3696, (ESI, M + Na+) m/z calcd for C28H48BNO6Na 528.3472,
found 528.3480.
Diethyl 5,5′-(1,4-Phenylene)bis(N-dodecyl-3,4-(propylene-
1,3-dioxy)pyrrole-2-carboxylate) (3). To a 100 mL round-bottom
flask equipped with a condenser and containing a stir bar and under
argon atmosphere were added compound 2 (0.183 g, 0.3602 mmol,
2.1 equiv), K2CO3(0.320 g), n-Bu4NBr(28 mg, 0.0865 mmol, 0.5
equiv), and 1,4-dibromobenzene (40.7 mg, 0.1724 mmol, 1 equiv).
The system was purged with vacuum-argon four times and then
toluene (4.5 mL, previously degassed), and deionized water (4 mL,
previously degassed) was added. The mixture was stirred for 30 s, and
Pd(PPh)4 (approximately 3 mg) was added. The mixture was warmed
up to 85−90 °C and stirred vigorously for 18 h. The mixture was
cooled to room temperature and partitioned between water and
diethyl ether, washed with water (4×) and brine (1×), and dried over
Na2SO4; an oily material was obtained, which produced a white solid
after treatment with MeOH. For quantification purposes, the entire
crude was purified by a chromatographic column (silica, neutralized
with Et3N, and ethyl ether/hexanes 1:1), producing 137 mg of a white
solid in 95% yield. The compound showed the same spectroscopic
characteristics as previously reported.5
CONCLUSIONS
■
The decarboxylation of 3,4-dioxypyrrole carboxylic acids is a
feature that can be exploited in the Pd-mediated decarbox-
ylative cross-coupling to yield a practical and efficient
methodology for the synthesis of 3,4-dioxypyrrole-based π-
conjugated molecules, which may be of interest to the organic
electronics community. The methodology was successfully used
to create a family of π-conjugated systems, and some of these
molecules may be suitable for further derivatization to produce
more complex π-systems, or may be polymerized by chemical
or electrochemical methods. Importantly, we have shown that
the Pd-mediated decarboxylative cross-coupling can be applied
to build π-conjugated systems containing the base-sensitive
BTD unit which allows the inclusion of electron acceptor units
in electron-rich π-conjugated molecules. As has been illustrated
with numerous thiophene-based systems, creating new donor−
acceptor-based XDOP oligomers and polymers is expected to
increase their stability toward oxidation and also allow fine-
tuning of their redox and optoelectronic properties.
Diethyl N-Dodecyl-3,4-(propylene-1,3-dioxy)pyrrole-2,5-di-
carboxylate (9). N-H-(2,5-COOEt)ProDOP (5.952 g, 21.0112
mmol, 1 equiv), n-dodecylbromide (6.284 g, 25.2135 mmol, 1.2
equiv), ground anhydrous K2CO3 (8.7119 g, 63.0336 mmol, 3 equiv),
and DMF (80 mL) were stirred at 95 °C. The reaction was monitored
by TLC (silica, 1:2 ethyl ether/hexanes) until disappearance of the
starting material (approximately 48 h), then the solvent was removed
by rotary evaporation, and the resulting crude was partitioned between
water and ethyl acetate, the ethyl acetate was washed with water (3×)
and brine (1×), and dried over anhydrous sodium sulfate. The solvent
was removed by rotary evaporation, and the resulting crude was
purified by column (silica, 1:2 ethyl ether/hexanes). The product was
1
isolated as a colorless oil, 8.538 g (90% yield): H NMR (300 MHz,
CDCl3) δ 4.54 (t, 2H, J = 7.6 Hz), 4.32 (q, 4H, J = 7.1 Hz), 4.14 (t,
4H, J = 5.3 Hz), 2.21 (td, 2H, J = 5.3 Hz, J = 10.5 Hz), 1.70−1.55 (m,
2H), 1.35 (t, 6H, J = 7.1 Hz), 1.31−1.15 (m, br, 18H), 0.86 (t, 3H, J =
6.7 Hz); 13C NMR (75 MHz, CDCl3) δ 160.9, 142.0, 113.8, 71.8, 60.7,
46.5, 33.5, 32.2, 32.1, 29.9, 29.8, 29.8, 29.8, 29.5, 26.9, 22.9, 14.5, 14.3;
FTIR (NaCl, disc) νmax (cm−1) 2925.7 (s), 2854.9 (m), 1713.7 (vs),
EXPERIMENTAL SECTION
General Information. All reagents and starting materials were
purchased from commercial sources and used without further
■
̅
1531.0 (m), 1456.0 (m), 1435.5 (m), 1365.1 (m), 1351.3 (m), 1308.8
(m), 1249.5 (s), 1154.7 (s), 1082.3 (m), 1028.9 (m), 776.9 (w).
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N-Dodecyl-3,4-(propylene-1,3-dioxy)pyrrole-2,5-dicarbox-
ylic acid (4). To a 250 mL round-bottom flask containing a stir bar
were added compound 9 (1.534 g, 3.397 mmol), THF (15 mL), and
ethanol (30 mL), After the solid dissolved, 30 mL of KOH (3 M) was
added, and argon was bubbled through the reaction mixture for 5 min.
The flask was equipped with a condenser, and the reaction mixture was
heated to 75 °C with strong stirring under argon for 36 h. The organic
volatiles were carefully removed in a rotary evaporator, and the
aqueous solution was cooled in an ice bath, then the reaction mixture
was carefully acidified by slow addition of 3 M HCl. The resulting
white precipitate was filtered and washed with deionized water, air-
dried for about 40 min, then put under high vacuum overnight. The
resulting solid was stirred at ∼40 °C in 25 mL of a mixture 1:25 of
ethyl ether/pentanes for 5 min; the mixture was allowed to cool to
room temperature, filtered, and washed with cold pentanes. The
mixture was cooled to room temperature and partitioned between
diethyl ether and water in a separatory funnel, then washed with plenty
water (5×) and brine (1×) and dried over Na2SO4; the solvent was
removed in a rotary evaporator, and the resulting crude was purified by
chromatographic column on silica (previously neutralized with
triethylamine; using 1:2 diethyl ether/hexanes as eluent). The product
was isolated as a pale yellow oil, which was subjected to high vacuum
for 6 h, and then stored under argon atmosphere, 0.124 g (92% yield):
1H NMR (300 MHz, CD2Cl2) δ 7.34 (ddd, 1H, J = 1.3 Hz, J = 5.0 Hz,
J = 15.9 Hz), 7.09−7.04 (m, 1H), 7.01 (dd, 1H, J = 1.2 Hz, J = 3.5
Hz), 6.29 (s, 1H), 4.02−3.96 (m, 4H), 3.79 (t, 2H, J = 7.4 Hz), 2.02−
2.17 (m, 2H), 1.61 (td, 2H, J = 5.2 Hz, J = 10.4 Hz), 1.48−1.00 (m, br,
18H), 0.88 (t, 3H, J = 6.7 Hz); 13C NMR (75 MHz, D2CCl2) δ 138.9,
127.5, 127.4, 127.3, 126.5, 125.9, 125.3, 107.6, 73.1, 72.9, 48.2, 35.8,
32.5, 31.7, 30.2, 30.1, 30.0, 29.9, 29.7, 29.5, 27.1, 23.3, 14.5; HRMS
(ESI-DART, M + H+ ) m/z calcd for C23H35NO2SH 390.2461, found
390.2459.
1
product was isolated as a white solid, 1.303 g (97% yield): H NMR
(300 MHz, CDCl3) δ 10.13−8.80 (br, 2H), 4.82 (t, 2H, J = 7.6 Hz),
4.32 (t, 4H, J = 4.8 Hz), 2.38 (quint, 2H, J = 4.4 Hz), 1.64−1.72 (m,
2H), 1.29−1.24 (m, 18H), 0.87 (t, 3H, J = 6.3 Hz); 13C NMR (75
MHz, CDCl3) δ 159.2, 139.0, 112.8, 73.6, 46.5, 33.5, 32.1, 31.8, 29.9,
Potassium N-Dodecyl-3,4-(propylene-1,3-dioxy)pyrrole-2,5-
dicarboxylate (10). This compound can be prepared by two
different methods: To a dry 50 mL round-bottom flask containing a
stir bar and under argon atmosphere was added 0.2270 g of t-BuOK
(2.0228 mmol, 2 equiv); the flask was equipped with a septum, and
then 4 mL of anhydrous t-BuOH and 15 mL of anhydrous THF were
added via cannula. After the t-BuOK dissolved, a solution of
compound 4 (0.4000 g, 1.0114 mmol, 1 equiv) in 10 mL of
anhydrous THF was slowly added via cannula. The mixture was stirred
for 30 min, and then the solvent was carefully removed in a rotary
evaporator (anhydrous conditions were assured by flushing the rotary
evaporator with nitrogen). A pale tan solid was obtained, which was
subjected to high vacuum overnight, 0.4771 g (100% yield); FTIR
29.8, 29.8, 29.8, 29.7, 29.6, 29.5, 26.7, 22.9, 14.3; FTIR (KBr, pellet) ν
̅
(cm−1) 3223.6 (br, s), 2918.9 (br, s), 2850.5 (br, s), 2630.2 (br,
max
m), 1749.2, 1669.2, 1550.9, 1438.5, 1314.7 (s), 1270.8 (s) 1169.4 (s),
1082.0 (s), 733.2 (s).
N-Dodecyl-3,4-(propylene-1,3-dioxy)pyrrole-2-carboxylic
acid (5). To a 100 mL round-bottom flask was added compound 65
(1.2 g, 3.1618 mmol), then the flask was equipped with an vacuum
adapter and purged with argon-vacuum three times. The solid was
melted at 130 °C under vacuum until no bubbling was observed. The
resulting oil was dissolved in 1:1 DCM/hexanes and filtered through a
short path of basic alumina (or silica previously neutralized with
triethylamine). The solvent was removed by rotary evaporation, and
the resulting colorless oil was subjected to high vacuum for 1 h. The
product was redissolved using 10 mL of THF and 20 mL of EtOH,
and transferred to a 100 mL round-bottom flask equipped with a stir
bar and a condenser; then 15 mL of KOH (5 M) was added, and the
mixture was degassed by bubbling argon for 10 min. The mixture was
stirred under argon at 35−40 °C for 5 days. The volatiles were
removed by rotary evaporation at room temperature. Deionized water
(∼20 mL) was added to the resulting heterogeneous solution, and
then cooled to 5 °C and acidified by adding HCl (2 M) dropwise
(alternatively, the potassium salt can be isolated by filtration, and then
dried under vacuum). The resulting solid was washed with deionized
water and dried under high vacuum. The solid was stored under argon
at −20 °C, 0.780 g (70% yield). The NMR showed that the product is
(KBr, pellet) ν (cm−1) 3391.1 (br, w), 2925.8 (s), 2853.7 (s), 1618.5
̅
(s), 1589.9 (s), 1419.5 (s), 1340.5 (s), 1132.9 (m), 1081.3 (s), 806.1
(m). Alternatively, the procedure was also carried out using deionized
water (4 mL), potassium hydroxide (0.1135 g, 2.0228 mmol, 2 equiv),
and compound 4 (0.4000 g, 1.0114 mmol, 1 equiv). After removal of
the water by rotary evaporation, the resulting solid was dried under
vacuum at 60 °C for 3 h.
Route A: N-Dodecyl-2,5-di(thiophen-2-yl)-3,4-(propylene-
1,3-dioxy)pyrrole (11). To a dry 25 mL round-bottom flask
containing a stir bar and under argon atmosphere were added
compound 10 (0.112 g, 0.2375 mmol, 1 equiv), n-Bu4NBr (0.153 g,
0.4749 mmol, 2 equiv), tri(o-tolyl)phosphine (6.4 mg, 0.021 mmol, 4
mol %), and palladium(II) acetylacetonate (3.2 mg, 0.011 mmol, 2
mol %). The flask was equipped with an air-cooled condenser; then an
inlet vacuum adapter was connected to the top of the condenser, and
the system was purged with vacuum-argon four times; then 0.05 mL of
bromothiophene (0.0852 g, 0.5224 mmol, 2.2 equiv) and anhydrous
N-methylpyrrolidone (2 mL, previously degassed) was added via
syringe. The system was then equipped with silicone oil bubbler, and
the reaction mixture was warmed to 70−75 °C and stirred for 36 h.
On cooling to room temperature, the mixture was partitioned between
diethyl ether and water, washed with water (5×) and brine (1×), and
dried over Na2SO4. The organic solvent mixture (including the
residual NMP) was removed in a rotary evaporator. The resulting
crude was purified by chromatographic column on silica (previously
neutralized with Et3N) using 1:4 Et2O/hexanes as eluent. The product
1
a mixture 20:1 of compound 5 and ProDOP ester 1: H NMR (300
MHz, CDCl3) δ 9.93−9.02 (br, 1H), 6.49 (s, 1H), 4.23 (t, 2H, J = 4.9
Hz), 4.16 (t, 2H, J = 7.2 Hz), 4.01 (t, 2H, J = 4.9), 2.24 (td, 2H, J = 5.0
Hz, J = 10.0 Hz), 1.61−1.76 (m, 2H), 1.36−1.17 (m, 18H), 0.87 (t,
3H, J = 6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 159.6, 141.9, 135.6,
116.0, 106.6, 73.8, 72.2, 49.5, 34.4, 32.1, 31.5, 29.8, 29.8, 29.8, 29.7,
29.6, 29.5, 26.7, 22.9, 14.3; FTIR (NaCl Disc) νmax (cm−1) 3324.8 (br,
̅
w), 3105.4 (br, w), 2924.7, 2924.7 (vs), 2854.4 (s) 2645.5 (br, w),
1732.4 (s), 1652.3 (s), 1525.1 (m), 1456.2 (s), 1407.9 (s), 1365.2 (s),
1294.6 (m), 1062.9 (s), 795.7 (w).
N-Dodecyl-3,4-(propylene-1,3-dioxy)-2-(thiophen-2-yl)-
pyrrole (8). To a dry 25 mL round-bottom flask containing a stir bar
and under argon atmosphere were added diacid 4 (0.137 g, 0.3462
mmol, 1 equiv), finely ground anhydrous potassium carbonate (0.144
g, 1.0386 mmol, 3 equiv), and n-Bu4NBr (0.112 g, 0.3462 mmol, 1
equiv). The flask was equipped with an air-cooled condenser; a
vacuum adapter was connected to the top of the condenser, and the
system was purged with vacuum-argon four times; then N-
methylpyrrolidone (4 mL, previously degassed) was added via syringe.
The mixture was warmed to 70 °C and stirred for 1 h, and then 0.074
mL of 2-bromothiophene (0.124 g, 0.7615 mmol, 2.2 equiv), tri(o-
tolyl)phosphine (4.7 mg, 0.0152 mmol, 2 mol %), and palladium(II)
acetylacetonate (2.3 mg, 0.0076 mmol, 1 mol %) was added. The
system was then equipped with a septum and a bubbler (containing
silicon oil); the reaction mixture was stirred at 70−75 °C for 48 h. The
1
was isolated as a pale yellow paraffin-like solid, 0.078 g, 69% yield: H
NMR (300 MHz, CDCl3) δ 7.35 (dd, 2H, J = 2.4 Hz, J = 3.8 Hz),
7.11−7.07 (m, 4H), 4.05 (t, 4H, J = 5.0 Hz), 4.00 (t, 2H, J = 7.9 Hz),
2.07 (quint, 2H, J = 5.0 Hz), 1.49−1.41 (m, 2H), 1.34−1.09 (br, m,
18H), 0.90 (t, 3H, J = 6.8 Hz); 13C NMR (75 MHz, CDCl3) δ 137.3,
132.0, 127.2, 126.9, 125.5, 113.1, 72.5, 45.4, 35.0, 32.1, 31.1, 29.8, 29.7,
29.5, 29.1, 26.5, 22.9, 14.3; HRMS (ESI-TOF, M + H+) m/z calcd for
C27H37NO2S2H 472.2338, found 472.2357.
N-Dodecyl-2,5-diphenyl-3,4-(propylene-1,3-dioxy)pyrrole
(12). The reaction was performed using the same procedure as for
compound 11 using the potassium dicarboxylate 10 (0.100 g, 0.2120
mmol, 1 equiv), n-Bu4NBr (0.137 g, 0.4240 mmol, 2 equiv), tri(o-
tolyl)phosphine (5.7 mg, 0.019 mmol, 4 mol %), palladium(II)
acetylacetonate (2.8 mg, 0.009 mmol, 2 mol %), 0.05 mL of
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The Journal of Organic Chemistry
Featured Article
bromobenzene (0.0732 g, 0.4664 mmol, 2.2 equiv), and 2 mL of N-
methylpyrrolidone (previously degassed). The product was isolated as
a colorless paraffin-like solid, 70 mg (72% yield): 1H NMR (300 MHz,
CDCl3) δ 7.47−7.38 (m, 8H) 7.32−7.26 (m, 2H), 4.01 (t, 4H, J = 5.0
Hz), 3.88 (t, 2H, J = 7.1 Hz), 2.17 (quint, 2H, J = 5.0 Hz), 1.22−0.66
(br, m, 23H); 13C NMR (75 MHz, CDCl3) δ 137.3, 131.6, 129.8,
128.4, 126.6, 120.7, 72.4, 45.6, 35.2, 32.1, 30.1, 29.8, 29.8, 29.6, 29.5,
29.4, 28.9, 26.2, 22.9, 14.3; HRMS (ESI-TOF, M + H+) m/z calcd for
C31H41NO2H 460.3210, found 460.3196.
Potassium 5,5′-(1,4-Phenylene)bis(N-dodecyl-3,4-(propy-
lene-1,3-dioxy)pyrrole-2-carboxylate) (18). To a 50 mL round-
bottom flask containing a stir bar were added diester5 3 (0.262 g,
0.3145 mmol), THF (6 mL), and ethanol (6 mL). After the solid
dissolved, 3.8 mL of 5 M KOH (19 mmol, 60 equiv) was added, and
the mixture was degassed by bubbling argon for 10 min. The flask was
equipped with a condenser, and the reaction mixture was heated to
55−60 °C with strong stirring under argon for 72 h. The reaction
mixture was filtered using glass wool (to remove traces of palladium
black), and then the organic solvents (THF and ethanol) and part of
the water were carefully removed in a rotary evaporator at 25 °C,
which produced precipitation of the potassium decarboxylate salt. The
resulting solid was filtered, washed with slightly basic cold water, air-
dried for 5 min, and washed with hexanes. The pale yellow solid
(hydrated) was then put under vacuum (0.1 mmHg) at 115 °C for 72
h. The final product was received as a white solid, 0.247 g, 92% yield:
Route B: Diethyl 5,5′-(Benzo[c][1,2,5]thiadiazole-4,7-diyl)-
bis(thiophene-5,2-diyl)bis(N-dodecyl-3,4-(propylene-1,3-
dioxy)pyrrole-2-carboxylate) (13). To a dry 25 mL round-bottom
flask containing a stir bar and under argon atmosphere were added
compound 65 (0.060 g, 0.1417 mmol, 2.2 equiv) and finely ground
anhydrous potassium bicarbonate (0.0142 g, 0.1417 mmol, 2.2 equiv).
The flask was equipped with an air-cooled condenser; an inlet vacuum
adapter was connected to the top of the condenser, and the system
was purged with vacuum-argon four times, then NMP (5.5 mL,
previously degassed) was added via syringe. The mixture was warmed
to 50 °C and stirred for 1 h (vacuum was slightly applied several times
to remove CO2 and help the neutralization process), then 4,7-bis(5-
bromothiophen-2-yl)benzo[c][1,2,5]thiadiazole (29.5 mg, 0.0644
mmol, 1 equiv), tri(o-tolyl)phosphine (1.2 mg, 0.0039 mmol, 6 mol
%), and palladium(II) acetylacetonate (0.6 mg, 0.0019 mmol, 3 mol
%) were added. The system was then equipped with a septum and a
bubbler (containing silicon oil); the reaction mixture was warmed to
90 °C and stirred for 24 h. The solvent was removed in a rotary
evaporator at 80 °C, then the crude was dissolved in 3:1 hexanes/ethyl
acetate and filtered through a short path (∼1 cm) of neutral alumina
(activity 3); the alumina was flushed with the hexanes/AcOEt mixture
to recover the entire product. The solvent was removed in a rotary
evaporator, and the resulting crude oil was dissolved in hexanes,
washed with deionized water (3×) and brine (1×), and dried over
Na2SO4. The mixture was filtered, and the solvent was removed in a
rotary evaporator; the resulting sticky solid was put under vacuum
overnight, then 2 mL of ethanol was added and the mixture was
slightly warmed; then diethyl ether was added until the solid dissolved.
Slow evaporation of the diethyl ether produced a purple powdery
solid, which was filtered, washed with ethanol, and air-dried for 2 min,
then put under vacuum to remove the solvent traces, 60.8 mg (89%
1H NMR (300 MHz, DMSO-d ) δ 7.24 (s, 4H), 4.23 (t, 4H, J = 6.9
6
Hz), 3.82 (dd, 8H, J = 5.9 Hz, J = 9.5 Hz), 2.04−1.90 (m, 4H), 1.32−
0.90 (br, m, 40H), 0.84 (t, 6H, J = 6.5 Hz); FTIR (KBr, pellet) νmax
̅
(cm−1) 3395.5 (br, w), 2924.7 (s), 2853.5 (s), 1566.0 (s), 1447.9 (s),
1417.5 (s), 1356.9 (s), 1081 (s), 1138.1 (w), 806.3 (m).
Potassium 5,5′-(3,4-(Ethylene-1,2-dioxy)thiophene-2,5-diyl)-
bis(N-dodecyl-3,4-(propylene-1,3-dioxy)pyrrole-2-carboxy-
late) (19). The reaction was performed using a similar procedure as
for 18, using 2.521 g of the EDOT derivative5 (2.810 mmol), 54 mL of
THF, 54 mL of EtOH, and 34 mL of 5 M KOH. The workup was
slightly modified as follows: After removal of the volatiles, the resulting
gum-like solid was filtered, washed with slightly basic cold water, and
air-dried for 10 min. The pale yellow solid was subjected to vacuum
overnight at room temperature, yielding an amber solid which was
ground in a mortar, producing a fine yellow powder, 2.548 g, 99%
1
yield: H NMR (300 MHz, DMSO-d6) δ 4.25−4.10 (m, 8H), 3.90−
3.78 (m, 8H), 2.03−1.90 (m, 4H), 1.44−0.09 (m, 40H), 0.84 (t, 6H, J
= 6.5 Hz); 13C NMR (75 MHz, DMSO-d6) δ 163.7, 138.3, 137.2,
137.2, 136.7, 120.2, 105.9, 105.9, 71.3, 71.0, 64.0, 34.6, 31.4, 31.4, 31.2,
29.1, 29.0, 29.0, 28.9, 28.6, 26.4, 22.0, 13.8; FTIR (KBr, pellet) νmax
̅
(cm−1) 3392.1 (m), 2924.2 (s), 2853.7 (s), 1580.8 (s), 1510.7 (m),
1462.0 (s), 1420.6, 1420.6 (s), 1358.6 (s), 1080.6, 954.9 (w), 806.9
(w).
Route C: 5,5′-(1,4-Phenylene)bis(N-dodecyl-2-(pyridin-4-yl)-
3,4-(propylene-1,3-dioxy)pyrrole) (15). To a dry 50 mL round-
bottom flask containing a stir bar and under argon atmosphere were
added compound 18 (0.233 g, 0.2725 mmol, 1 equiv), 4-
bromopyridine hydrochloride (0.1113 g, 0.5723 mmol, 2.1 equiv),
anhydrous K2CO3 (0.083 g, 0.600 mmol, 2.2 equiv), n-Bu4NBr (0.220
g, 0.6814 mmol, 2.5 equiv), tri(o-tolyl)phosphine (7 mg, 0.0229 mmol,
4 mol %), and palladium(II) acetylacetonate (3.5 mg, 0.0114 mmol, 2
mol %). The flask was equipped with an air-cooled condenser; then an
inlet vacuum adapter was connected to the top of the condenser, and
the system was purged with vacuum-argon four times; then N-
methylpyrrolidone (6 mL, previously degassed) was added via syringe.
The system was then equipped with a silicone-oil bubbler, and the
reaction mixture was warmed to 70−75 °C and stirred for 60 h. The
reaction mixture was concentrated to ∼1 mL by rotary evaporation at
80 °C, and then it was cooled to room temperature, partitioned
between diethyl ether and water, and then washed with water (5×)
and brine (1×), and dried over Na2SO4. The resulting crude was
purified by chromatographic column on basic alumina, using a gradient
1:0 to 0:1 Et2O/EtOAc as eluent, yielding 0.147 g of a yellow solid,
1
yield): H NMR (300 MHz, CDCl3) δ 8.17 (d, 2H, J = 3.9 Hz), 7.89
(s, 2H), 7.24 (d, 2H, J = 3.9 Hz), 4.35 (q, 8H, J = 7.1 Hz), 4.20 (t, 4H,
J = 4.9 Hz), 4.09 (t, 4H, J = 5.1 Hz), 2.27−2.22 (m, 4H), 1.75−1.60
(m, 4H), 1.38 (t, 6H, J = 7.1 Hz), 1.15−1.10 (m, 34H), 0.84 (t, 6H, J
= 6.8 Hz); 13C NMR (75 MHz, CDCl3) δ 161.3, 152.8, 144.0, 140.5,
136.5, 131.8, 129.3, 127.9, 125.9, 125.7, 119.9, 109.3, 72.2, 72.1, 60.1,
46.5, 34.2, 32.1, 32.0, 29.9, 29.8, 29.8, 29.8, 29.6, 29.4, 26.8, 22.9, 14.8,
14.3; HRMS (DART-TOF, M + H+) m/z calcd for C58H78N4O8S3H
1055.5055, found 1055.5089.
Diethyl 5,5′-(Benzo[c][1,2,5]thiadiazole-4,7-diyl)bis(N-do-
decyl-3,4-(propylene-1,3-dioxy)pyrrole-2-carboxylate) (14).
Using compound 65 (0.1700 g, 0.4014 mmol, 2.1 equiv), finely
ground anhydrous potassium bicarbonate (0.0398 g, 0.3976 mmol,
2.08 equiv), NMP (9 mL, previously degassed), 4,7-dibromobenzo-
[c][1,2,5]thiadiazole (56.2 mg, 0.1911 mmol, 1 equiv), tri(o-
tolyl)phosphine (4.6 mg, 0.0153 mmol, 8 mol %), and palladium(II)
acetylacetonate (2.3 mg, 0.0077 mmol, 4 mol %), the reaction was run
for 72 h, using the same procedure as for 13, although the workup was
modified as follows: The solvent was concentrated by rotary
evaporation at 80 °C to ∼1 mL, then the mixture was dissolved in
diethyl ether, washed with water (5×) and brine (1×), and dried over
Na2SO4, then purified by chromatographic column on silica using 1:1
diethyl ether/hexanes as eluent. The product was isolated as an orange
solid (paraffin like), 0.160 g (94% yield): 1H NMR (300 MHz,
CDCl3) δ 7.63 (s, 2H), 4.50−3.80 (m, br, 16H), 2.30−2.10 (m, 4H),
1.50−1.28 (m, 10H), 1.28−0.88 (m, 36H), 0.84 (t, 6H, J = 7.1 Hz);
13C NMR (75 MHz, CDCl3) δ 161.3, 154.2, 144.3, 136.8, 131.5, 123.5,
1
64% yield: H NMR (300 MHz, CDCl3) δ 8.60 (d, 4H, J = 5.5 Hz),
7.49 (s, 4H) 7.37 (d, 4H J = 5.5 Hz), 4.03 (dd, 8H, J = 5.0 Hz, J = 9.7
Hz), 3.78 (t, 4H, J = 7.0 Hz), 2.28−2.13 (m, 4H), 1.24−0.72 (br, m,
46H); 13C NMR (75 MHz, CDCl3) δ 149.8, 139.6, 139.1, 137.7,
129.6, 129.4, 122.96−123.17 (br), 123.0, 118.5, 72.3, 46.4, 34.8, 30.1,
29,81−29.75 (br), 29.6, 29.50, 29.46, 29.0, 26.2, 22.9, 14.3; HRMS
(MALDI, M + H+) m/z calcd for C54H74N4O4H 843.5783, found
843.5765.
122.6, 109.5, 72.0, 72.0, 60.0, 46.9, 34.3, 32.0, 31.8, 29.8, 29.7, 29.6,
29.6, 29.5, 29.2, 26.6, 22.8, 14.7, 14.2; HRMS (DART, M + H+) m/z
calcd for C50H74N4O8SH 891.5300, found 891.5295.
5,5′-(3,4-(Ethylene-1,2-dioxy)thiophene-2,5-diyl)bis(N-do-
decyl-2-(pyridin-4-yl)-3,4-(propylene-1,3-dioxy)pyrrole) (16).
The reaction was performed using the same procedure as for 15,
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The Journal of Organic Chemistry
Featured Article
using 19 (0.250 g, 0.2725 mmol, 1 equiv), 4-bromopyridine
hydrochloride (0.1113 g, 0.5723 mmol, 2.1 equiv), anhydrous
K2CO3 (0.083 g, 0.600 mmol, 2.2 equiv), n-Bu4NBr (0.220 g,
0.6814 mmol, 2.5 equiv), tri(o-tolyl)phosphine (7 mg, 0.0229 mmol, 4
mol %), palladium(II) acetylacetonate (3.5 mg, 0.0114 mmol, 2 mol
%), and 6 mL of NMP. The product was isolated as a pale orange
(4) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662−
664.
(5) Arroyave, F. A.; Reynolds, J. R. Org. Lett. 2010, 12, 1328−1331.
(6) Walczak, R. M.; Reynolds, J. R. Adv. Mater. 2006, 18, 1121−
1131.
(7) Thomas, C. A.; Zong, K.; Schottland, P.; Reynolds, J. R. Adv.
Mater. 2000, 12, 222−225.
1
solid, 0.195 g (79% yield): H NMR (300 MHz, CDCl3) δ 8.56 (d,
4H, J = 6.1 Hz), 7.31 (d, 4H, J = 6.2 Hz), 4.28 (s, 4H) 4.07−3.98 (m,
8H), 3.92 (t, 4H, J = 7.1 Hz), 2.26−2.07 (m, 4H), 1.40−0.89 (br, m,
40), 0.84 (t, 6H, J = 6.8 Hz); 13C NMR (75 MHz, CDCl3) δ 149.8,
138.9, 138.6, 138.5, 138.2, 123.2, 118.4, 112.3, 106.8, 72.3, 64.8, 46.0,
34.8, 32.0, 30.6, 29.77, 29.75, 29.71, 29.6, 29.6, 29.5, 29.2, 26.6, 22.8,
14.2; HRMS (ESI-TOF, [M + H]2+) m/z calcd for C54H74N4O6SH2
454.2737, found 454.2743.
(8) Merz, A.; Kronberger, J.; Dunsch, L.; Neudeck, A.; Petr, A.;
Parkanyi, L. Angew. Chem., Int. Ed. 1999, 38, 1442−1446.
(9) Walczak, R. M.; Leonard, J. K.; Reynolds, J. R. Macromolecules
2008, 41, 691−700.
(10) Ishiyama, T.; Takagi, J.; Yonekawa, Y.; Hartwig, J., F.; Miyaura,
N. Adv. Synth. Catal. 2003, 345, 1103−1106.
́
(11) Goossen, L., J.; Lange, P., P.; Rodriguez, N.; Linder, C. Chem.
Route D: 4,7-Bis(N-dodecyl-3,4-(propylene-1,3-dioxy)pyrrol-
2-yl)benzo[c][1,2,5]thiadiazole (17). To a dry 25 mL round-
bottom flask containing a stir bar and under argon atmosphere were
added compound 5 (0.3 g, 0.8535 mmol, 2.5 equiv) and finely ground
anhydrous potassium bicarbonate (0.089 g, 0.8877 mmol, 2.6 equiv).
The flask was equipped with an air-cooled condenser; an inlet vacuum
adapter was connected to the top of the condenser, and the system
was purged with vacuum-argon four times; then NMP (15 mL,
previously degassed) was added via syringe. The mixture was warmed
to 35 °C and stirred for 1 h (vacuum was slightly applied several times
to remove CO2 and to help the neutralization process), then 4,7-
dibromobenzo[c][1,2,5]thiadiazole (0.100 g, 0.3414 mmol, 1 equiv),
tri(o-tolyl)phosphine (6.2 mg, 0.0205 mmol, 6 mol %), and
palladium(II) acetylacetonate (3.11 mg, 0.0102 mmol, 3 mol %)
were added. The system was then equipped with a septum and a
bubbler (containing silicon oil), and the reaction mixture was warmed
to 80−82 °C and stirred for 42 h. The solvent was removed in a rotary
evaporator at 80 °C. The crude was dissolved in dichloromethane and
washed with water. The dichloromethane was removed by rotary
evaporation, and the resulting crude was purified by chromatographic
column on silica (previously neutralized with triethylamine), using a
2:1 ether/hexanes mixture as eluent, yielding 0.112 g of a bright red oil
Eur. J. 2010, 16, 3906−3909.
(12) Bilodeau, F.; Brochu, M.-C.; Guimond, N.; Thesen, K. H.;
Forgione, P. J. Org. Chem. 2010, 75, 1550−1560.
(13) Shang, R.; Xu, Q.; Jiang, Y.-Y.; Wang, Y.; Liu, L. Org. Lett. 2010,
12, 1000−1003.
(14) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung, H. M.;
Lee, S. Org. Lett. 2008, 10, 945−948.
(15) Heim, A.; Terpin, A.; Steglich, W. Angew. Chem., Int. Ed. Engl.
1997, 36, 155−156.
(16) Goossen, L. J.; Zimmermann, B.; Knauber, T. Angew. Chem., Int.
Ed. 2008, 47, 7103−7106.
(17) Rodriguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030−
5048.
(18) Mitchell, D.; Coppert, D. M.; Moynihan, H. A.; Lorenz, K. T.;
Kissane, M.; McNamara, O. A.; Maguire, A. R. Org. Process Res. Dev.
2011, 15, 981−985.
(19) Wang, J.; Cui, Z.; Zhang, Y.; Li, H.; Wu, L.-M.; Liu, Z. Org.
Biomol. Chem. 2011, 9, 663−666.
(20) Zhao, H.; Wei, Y.; Xu, J.; Kan, J.; Su, W.; Hong, M. J. Org.
Chem. 2011, 76, 882−893.
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1
(44% yield): H NMR (300 MHz, DCM-d2) δ 7.55 (s, 2H), 6.45 (s,
2H), 4.03 (t, 4H, J = 4.3 Hz), 3.96 (t, 4H, J = 4.8 Hz), 3.71 (t, 4H, J =
7.2 Hz), 2.21−2.06 (m, 4H), 1.67−0.98 (m, br, 40 H), 0.87 (t, 6H, J =
6.7 Hz); 13C NMR (75 MHz, DCM-d2) δ 154.9, 139.4, 138.0, 131.1,
123.8, 115.7, 108.0, 73.1, 73.0, 48.9, 35.9, 32.5, 31.6, 30.2, 30.2, 30.1,
30.0, 29.9, 29.7, 27.1, 23.3, 14.5; HRMS (APCI, [M + H]+) m/z calcd
for C44H66N4O4SH 747.4878, found 747.4876.
(23) Beaujuge, P. M.; Reynolds, J. R. Chem. Rev. 2010, 110, 268−
320.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR for target products and TGA data for
compounds 4, 5, 6, and 9. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: reynolds@chem.ufl.edu.
ACKNOWLEDGMENTS
■
We gratefully acknowledge BASF and the AFOSR (FA95550-
09-1-0320) for the funding for this project. Dr. Michael R.
Craig is also acknowledged for his helpful discussions and effort
in developing this manuscript.
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