Efficient synthesis and reactions of 1,2-dipyrrolylethynes

Article abstract of DOI:10.1142/S1088424611003331

Various dipyrroles possess important motifs for construction of pyrrole-containing pigments. A series of 1,2-dipyrrolylethynes (4ad) has been efficiently synthesized using an improved one-pot double Sonagashira coupling from trimethylsilylethyne and vario

Full text of DOI:10.1142/S1088424611003331

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2011; 15: 412–420
DOI: 10.1142/S1088424611003331
Published at http://www.worldscinet.com/jpp/
Efficient synthesis and reactions of 1,2-dipyrrolylethynes
Hillary K. Tanuia, Erhong Haob, Moses I. Ihachia, Frank R. Fronczeka,
Kevin M. Smitha and M. Graça H. Vicente*a
a Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
b Anhui Key Laboratory of Functional Molecular Solids and Anhui Key Laboratory of Molecular Based Materials,
College of Chemistry and Material Science, Anhui Normal University, Wuhu, Anhui 241000, China
Dedicated to Professor John A. Shelnutt on the occasion of his 65th birthday
Received 15 April 2011
Accepted 7 May 2011
ABSTRACT: Various dipyrroles possess important motifs for construction of pyrrole-containing
pigments. A series of 1,2-dipyrrolylethynes (4a–d) has been efficiently synthesized using an improved
one-pot double Sonagashira coupling from trimethylsilylethyne and various 2-iodopyrroles. The resulting
1,2-dipyrrolylethynes were further transformed into novel indolyl-, ethenyl- and carboranyl-dipyrroles
(5–7) using the Larock indole synthesis, stereoselective catalytic hydrogenation, or B10H14. Indolyl-
dipyrroles were found to selectively bind fluoride ions using one pyrrolic and the indolyl NHs, whereas
the carboranyl- and ethenyl-dipyrroles are potentially valuable precursors for the synthesis of porphyrin
isomers and expanded pigments.
KEYWORDS: carborane, dipyrrole, indole, Larock, Sonagashira.
least two column separations are required for purification
before the target compound is isolated.
INTRODUCTION
In recent years, the chemistry of pyrrole-containing
pigments has received increasing attention in coordina-
We are interested in new approaches to compound
A due to its synthetic utility as a conjugated pyrrole-
tion chemistry, medicinal chemistry, and material science
containing precursor for cycloadditive macrocyclization.
[1].Various kinds of dipyrroles have been synthesized and
Furthermore, the rich chemistry of the alkyne function-
some have been used as building blocks in the construc-
ality provides the opportunity to synthesize other novel
tion of various functional molecules [2]. Among these,
dipyrrolylethynes such as A in Fig. 1, can be found only
sparsely in the literature (five examples according to a
SciFinder search). Compound A was first synthesized by
Vogel and coworkers as a key intermediate during their
synthesis of 22 π-electron expanded (or “stretched”) por-
phycene-(2.2.2.2) via B (Fig. 1) [3, 4]. Later, Lightner and
dipyrrole motifs. Inspired by Grieco’s recently developed
one-pot synthesis of biarylalkynes [6], we have developed
and now report a one-pot synthesis of dipyrrolylethynes.
Our ethynyl products were then further transformed
into various related dipyrroles (5–7) using the Larock
indole synthesis, stereoselective catalytic hydrogena-
tion, or reaction with decaborane. In particular, the new
coworkers adapted this methodology for the sysnthesis of
indolyl-dipyrroles were found to have high fluorescence
alkynyl-homobilirubins [5]. The method for synthesis of
quantum yields and to selectively bind fluoride ions in
dipyrrolylethynes involves a three-step 60% overall yield
sequence (coupling-desilylation-coupling), using trim-
ethylsilylethyne as the source of the alkyne bridge. At
a 2:1 (host:F-) complex. Pyrrole and indole-based fluo-
ride probes have been incorporated within conjugated
systems for colorimetric and/or fluorescence detection
of fluoride ions, because of their strong hydrogen bond-
SPP full member in good standing
ing [F-••••H-N] interactions, as well as their high stabil-
ity over a wide range of pH values [7–9]. On the other
hand, the carboranyl- and ethenyl-dipyrroles are valuable
*Correspondence to: M. Graça H. Vicente, email: vicente@lsu.
edu, tel: +1 225-578-7442
Copyright © 2011 World Scientific Publishing Company

EffICIEnt SynthESIS anD rEaCtIOnS Of 1,2-DIPyrrOlylEthynES
413
the coupling reaction was performed using trimethylsi-
lylethyne instead of ethyne, with DBU as the base. The
reaction was followed using TLC since the target dipyr-
rolylethyne displays characteristic bright blue fluores-
cence under ultraviolet (366 nm) light. The workup of
NH
N
N
HN
NH
HN
CHO
OHC
the reaction was very simple and required no chromato-
graphic purification; after extraction with ethyl acetate
it only required methanol washing to obtain analyti-
cally pure product. The 1-step methodology proved to
(a)
(b)
Fig. 1. Structures of dipyrrolylethyne (a) and expanded porphy-
cene precursor (b) synthesized by Vogel and coworkers [3]
be reproducible and routinely gave 55–65% yields of the
target dipyrrolylethyne products, on a 10 mmol scale.
Use of another solvent, such as acetonitrile in place of
benzene, also gave similar results. The one-pot reaction
was extended to the synthesis of dipyrrolylethynes (4b)
and (4c) in 52 and 54% yields, respectively (Table 1).
However, when N-tosyl-2-bromopyrrole (1d) was used,
a poor yield of dipyrrolylethyne 4d was obtained (8%)
using these conditions.
We were able to grow suitable crystals for X-ray
analysis of all dipyrrolylethynes 4a–d, by slow evapora-
tion of dichloromethane solutions. The X-ray structures
of 4a and 4c are shown in Figs 2 and 3, respectively. In
compound 4a, the two pyrrole rings are twisted about
the triple-bond line with a dihedral angle of 33.26(3)º,
and the C–C triple bond distance is 1.205(2) Å. The
molecule lies on a twofold axis in the crystal. In com-
pound 4c, the molecule does not lie on a symmetry
element in the crystal, and the pyrroles are twisted con-
siderably more than in 4a, forming a dihedral angle of
69.25(6)º. The triple-bond distance is 1.203(3) Å. The
difference in conformation between 4a and 4c appears
to be related to hydrogen bonding. In both, each pyrrole
and adjacent ester C=O form an intermolecular cyclic
hydrogen bond dimer. However, in 4a, these 10-mem-
bered rings lie on inversion centers, thus the pyrroles
are strictly parallel. In 4c, they deviate sharply from
parallelism, forming a dihedral angle of 64.59(6)º. We
precursors for the synthesis of porphyrin isomers and
other polypyrrolic materials [10, 11].
RESULTS AND DISCUSSION
Our overall synthesis of dipyrrole (4a) from readily
available 2-iodopyrrole (1a) [12] is shown in Scheme 1.
First, a three-step sequence (coupling-desilylation-cou-
pling) using trimethylsilylethyne as the source of the
2-atom alkynyl bridge was used, as previously described
[13]. Classical Sonagashira coupling between 1a and
trimethylsilylethyne gave pyrrole 2 in 89% yield. Desi-
lylation using tetrabutylammonium fluoride (TBAF) pro-
vided the terminal ethynylpyrrole (3) in 95% yield. The
final coupling between compounds 1a and 3 afforded
dipyrrolylethyne (4a) in 73% yield. Alternatively, a
1-step procedure for the formation of 4a using a double
Sonagashira coupling reaction between 2-iodopyrrole
1a and trimethylsilyllethyne was investigated. Although
Vogel [3] and later Kim [4] both reported very low
yields for the direct formation of the dipyrrolylethyne
using iodopyrrole and ethyne, using Grieco’s method
[6] we were able to develop a one-pot reaction between
2-iodopyrrole 1a and trimethylsilylethyne (Scheme 1)
which gave 4a in 62% yield. In this synthetic approach,
Pd(PPh3)2Cl2, CuI
Et2NH,
I
BnO2C
BnO2C
N
N
H
1a
SiMe3
SiMe3
H
2
89%
Pd(PPh3)2Cl2, CuI
n-Bu4NF, THF
95%
62%
SiMe3
DBU, benzene, H2O
Pd(PPh3)2Cl2, CuI
Et2NH, 1a
CO2Bn
BnO2C
N
N
BnO2C
73%
N
H
H
H
4a
3
Scheme 1. Synthesis of dipyrrolylethyne 4a using two different routes
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414
h.K. tanuI et al.
Table 1. Dipyrrolylethyne (4a–d) yields from one-pot coupling of 2-iodopyrroles (1),
or 2-bromopyrrole
R1
R2
R3
R2
R3
R1
R2
R3
R1
Pd(PPh3)2Cl2, CuI
SiMe3
X
DBU, benzene, H2O
N
R4
N
R4
N
R4
1
4
Compound
R1
R2
R3
R4
X
Yield of 4, %
a
b
c
Me
Me
Me
H
Et
Me
Me
H
CO2Bn
CO2Bn
CO2Et
H
H
H
I
I
62
52
54
8
H
I
d
Ts
Br
The X-ray structure of 5c is shown in Fig. 4. One pyr-
role at the α-position of the indole moiety is rotated to
present its NH group approximately coplanar with that
of the indole, forming an N–C–C–N torsion angle of
30.7(3)º. Thus, both of these two NH groups are able to
donate their hydrogen bonds to the same acceptor, form-
ing two convergent intermolecular hydrogen bonds to an
ester carbonyl O atom.
Fig. 2. Molecular structure of dipyrrolylethyne 4a, with 50%
ellipsoids
The photophysical properties of indolyl-dipyrroles
5a and 5c were investigated, compared with those of
the dipyrrolylethyne precursors, and the results obtained
are summarized in Table 2. Interestingly, dipyrroles 5a
and 5c show strong absorption bands centered around
300 nm (blue shifted from those of the corresponding
dipyrrolylethynes 4), and strong fluorescence emission
bands at ~440 nm with surprisingly high quantum yields
(0.91 for 5a and 0.88 for 5c) [18]. Fluorescence titration
experiments using dipyrroles 5 and TBAF, revealed dra-
matic fluorescence quenching upon addition of TBAF, as
seen in Fig. 5. Addition of other anions, such as bromide,
Fig. 3. Molecular structure of dipyrrolylethyne 4c, with 50%
ellipsoids
have previously reported the molecular struc-
tures of 4b and 4d [14].
R
R
Novel indolyldipyrroles 5a and 5c were pre-
pared in 55–60% yields via the Larock indole
synthesis [15] from the corresponding dipyrrolyl-
ethynes 4a,c, as shown in Scheme 2. On the other
hand, with several dipyrrolylethynes available we
explored the Lindlar reduction of the alkyne bond
to generate novel 1,2-dipyrrolylethene deriva-
tives. Using Lindlar’s catalyst [16] in the absence
of quinoline, dipyrrolylethene (6) was synthe-
sized from 4c in 31% yield. Stereoselective semi-
hydrogenation employing HSiEt3 as the reductant
[17] also yielded the cis-dipyrrolylalkene 6. This
CO2R1
R1O2C
N
N
H
H
NH2
4
Pd(OAc)2, LiCl
K2CO3, DMF
55-60%
Lindlar's
catalyst, H2
EtOAc
I
31%
R
HN
R
NH
HN
NH
HN
EtO2C
CO2Et R1O2C
CO2R1
transformation opens up the possibility for syn-
thesis of porphycenes by way of Ullmann type
self-coupling of derivatives of 6, and also of
expanded 22 π-electron stretched porphycenes.
6
5a: R = Et; R1 = Bn
5c: R = Me; R1 = Et
Scheme 2. Synthesis of dipyrroles 5 and 6
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EffICIEnt SynthESIS anD rEaCtIOnS Of 1,2-DIPyrrOlylEthynES
415
B10H14-SEt2
toluene
BnO2C
CO2Bn
NH
HN
N
N
29%
BnO2C
CO2Bn
H
H
7
4a
BH
C
Scheme 3. Synthesis of carboranyldipyrrole 7
Fig. 4. Molecular structure of bipyrrole 5c, with 50% ellipsoids
Fig. 6. Job’s plot (a) and Hill plot (b) of 5c:F- complex with a
2:1 stoichiometry, (F0 – F) = change in fluorescence, [5c] and
r[5c] = moles and mole fraction for 5c, excitation at 290 nm
chloride, and hydrogenosulfate did not cause such pro-
nounced fluorescence quenching, probably due to their
lower affinity for binding to the pyrrole and indole NH
and their larger size. The Job’s plot shown in Fig. 6a
indicates that compound 2a chelates with TABF in a 2:1
stoichiometry, with an association constant (K) of 8.32 ×
104 M-1 based on the Hill plot shown in Fig. 6b. Although
compound 5c also chelated with bromide and hydrogeno-
sulfate in a 2:1 molar ratio with binding constants 5.89 ×
104 M-1 and 7.94 × 103 M-1, respectively, the Hill coef-
ficients are greater than one, suggesting that these two
systems are positively cooperative. The crystal structure
Fig. 5. Fluorescence titration of 5c (a, 5 × 10-6 M in CH2Cl2,
λ
ex = 290 nm) and 5a (b, 5 × 10-6 M in CH2Cl2, λex = 290 nm)
with TBAF (0-100 eq)
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416
h.K. tanuI et al.
complex with TBAF in which the fluoride
ion is chelated by four hydrogen-bonded
pyrrole N–H groups. Two of the N–F
distances are quite short, 2.566(4) and
2.574(4) Å, and those hydrogen bonds are
fairly linear, with N–H–F angles 168 and
169º. The other two are longer, 2.855(4),
2.938(4) Å and less linear, in bifurcated
hydrogen bonds with ester carbonyl accep-
tors. The TBA cation perches on top of this
hydrogen-bonded aggregate, with N–F
distance 3.894(5) Å.
Fig. 7. Molecular structure of the 2:1 molar-ratio 5c-fluoride complex
Inspired by electropolymerization
results previously reported [10] for carboranyl-contain-
ing pyrroles and thiophenes, in particular for the ortho-
carboranyl systems which produced the most conjugated
and conductive polymers, we turned our attention to the
synthesis of ortho-carboranyldipyrrole 7, as shown in
Scheme 3. The ortho-carborane cluster was obtained in
29% yield by reaction of dipyrrolylethyne 4a with decab-
orane and diethylsulfide in toluene [18]. Interestingly
carboranyl-dipyrrole 7 showed the highest fluorescence
quantum yield (0.98) of all dipyrroles synthesized.
The X-ray structure of 7 is shown in Fig. 8. In the solid
state, the two pyrroles are cofacial, presenting their NH
groups on the same side of the carborane cage. The pyr-
role rings are not parallel, forming a dihedral angle of
63.05(5)º. As in 4a and 4c, the pyrroles and their adja-
cent ester carbonyls form intermolecular hydrogen bonds
within 10-membered rings. In this case, two molecules
of 7 form a hydrogen-bonded dimer via four hydrogen
bonds in two 10-membered rings, as shown in Fig. 8
Table 2. Photophysical properties of dipyrroles 4 and 5 in
CH2Cl2 at room temperature
Compound
λmax, nm
λ
ema, nm
Φb
Stokes’ shift, nm
4c
4a
5c
5a
339
343
292
295
414
400
439
440
0.01
0.01
0.88
0.91
75
57
147
145
a Excitation at 290 nm. b Fluorescence quantum yield calculated
using quinine sulfate as the standard (0.56 in 0.1 M H2SO4
aqueous solution).
obtained of dipyrrole 5c in the presence of 10 equiva-
lents excess of fluoride shows the formation of a dimer
complex consisting of two molecules of 5c coordinating
one fluoride ion that occupies the center of the molecule,
as shown in Fig. 7. Dipyrrole 5c forms a 2:1 crystalline
Fig. 8. Molecular structure of bipyrrole 7 (50% ellipsoids, left) and its hydrogen bonded dimer (right)
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EffICIEnt SynthESIS anD rEaCtIOnS Of 1,2-DIPyrrOlylEthynES
417
(right panel). Carboranyl-dipyrrole 7 is a very valuable
starting material to built carborane-containing macro-
cycles and polymers.
15 mmol), dichlorobis(triphenylphosphine)palladium(II)
(125 mg, 0.175 mmol), and copper(I) iodide (65 mg,
0.35 mmol). The homogeneous mixture was stirred at
50 °C for 2 h until TLC showed that no starting mate-
rial remained. After evaporation of the solvent under
vacuum, the residue was subjected to chromatography on
a short silica gel column with hexane/dichloromethane/
ethyl acetate (5:1:1) as eluent, to give 2 (3.02 g, 89%).
To a solution of 2 (2.71 g, 8.0 mmol) in THF (50 mL)
was added Bu4NF (1.0 M THF solution, 8 mL). After
being stirred for 1 h, the resulting mixture was concen-
trated under reduced pressure. The crude residue was
subjected to chromatography on a short silica gel column
with dichloromethane as eluent to give 3 as a white solid
(2.03 g, 95% yield). 1H NMR (CDCl3, 250 MHz): δ, ppm
9.19 (1H, s), 7.31–7.36 (5H, m), 5.28 (2H, s), 3.29 (1H,
s), 2.47–2.50 (2H, m), 2.25 (3H, s), 1.00–1.11 (3H, m).
13C NMR (CDCl3, 75 MHz): δ, ppm 161.2, 136.6, 133.7,
129.0, 128.9, 128.6, 126.5, 119.8, 114.1, 82.6, 75.5, 66.4,
18.4, 15.3, 10.8. MS (EI): m/z 267.15 [M]+.
EXPERIMENTAL
General
Reagents were purchased as reagent-grade and used
without further purification unless otherwise stated.
Solvents were used as received from commercial sup-
pliers unless noted otherwise. THF was freshly distilled
from sodium benzophenone ketyl. All reactions were
performed using oven-dried or flame-dried glassware
unless otherwise stated, and were monitored by TLC
using 0.25 mm silica gel plates with UV indicator (60F-
254). Carborane was detected by immersion into PdCl2
in aqueous HCl solution (1 g PdCl2 in 80 mL water and
20 mL conc. HCl) and heated to develop a black spot on
1
TLC. H and 13C NMR were obtained on a 250 MHz or
1,2-bis[2-(5-benzyloxycarbonyl-4-ethyl-3-methyl-
pyrrolyl)]ethyne (4a). Method A: To a solution of benzyl
4-ethyl-5-iodo-3-methylpyrrole-2-carboxylate (1a) (1.85 g,
5 mmol) and benzyl 5-ethynyl-4-ethyl-3-methylpyrrole-2
-carboxylate (3) (1.34 g, 5 mmol) in diethylamine (50 mL)
were added dichlorobis(triphenylphosphine)palladium(II)
(59 mg, 0.08 mmol) and copper(I) iodide (30 mg,
0.16 mmol). The homogeneous mixture was stirred at
50 °C for 3 h. After evaporation of the solvent in vacuo,
the residue was subjected to chromatography on a short
silica gel column with hexane/dichloromethane/ethyl
acetate (5:1:1) as eluent to give 4a (1.75 g, 73%). Method
B: A 250 mL Schlenk tube with a teflon-coated magnetic
stir bar was charged with PdCl2(PPh3)2 (210 mg, 6 mol%),
CuI (188 mg, 10 mol%) and benzyl 4-ethyl-5-iodo-3-
methylpyrrole-2-carboxylate (1a) (3.69 g, 10 mmol).
The system was pumped with a vacuum pump and
refilled with nitrogen gas three times. Then dry benzene
40 mL, sparged with dry argon was added by syringe.
Argon-sparged DBU (9.0 mL, 6 equiv.) in 5 mL dry ben-
zene was then added via syringe and ice-chilled trimeth-
ylsilylethyne (0.71 mL, 0.50 equiv.) in 5 mL dry benzene
was added by syringe, followed immediately by distilled
water (73 μL, 40 mol%). The reaction flask was covered
with aluminum foil and left stirring at a high rate of speed
for 2 d until no starting material was left according to
TLC; the reaction mixture was partitioned between ethyl
acetate and brine (200 mL each). The organic layer was
washed with 10% HCl (3 × 200 mL), saturated aqueous
NaCl (200 mL), dried over anhydrous NaSO4, gravity-
filtered and the solvent then removed in vacuo. The crude
product was washed with methanol and dried under vac-
uum, giving 1.57 g (62% yield) of the title compound.
1H NMR (CDCl3, 250 MHz): δ, ppm 8.86 (2H, s), 7.38–
7.41 (10H, m), 5.31 (4H, s), 2.53–2.56 (4H, m), 2.30
(6H, s), 1.11–1.14 (6H, m). 13C NMR (CDCl3, 75 MHz):
δ, ppm 162.2, 137.7, 134.6, 133.6, 130.2, 129.8, 127.9,
300 MHz spectrometer at room temperature. Chemical
shifts (δ) are given in ppm relative to CDCl3 7.26 (1H)
and 77 ppm (13C) or to internal TMS. High-resolution
mass spectra were obtained by using quadrupole time-
of-flight mass spectrometry with a nano LC system.
MALDI-TOF mass spectra were obtained on an Applied
Biosystems QSTAR XL instrument, using positive mode
with dithranol as matrix unless otherwise indicated.
Compounds 1a–c were prepared according to the litera-
ture [12]. UV-visible absorption spectra and fluorescence
emission spectra were recorded on commercial spectro-
photometers. The slit width was 2.5 nm for excitation
and 5.0 nm for emission. Relative quantum efficiencies
of fluorescence of dipyrroles were obtained by compar-
ing the areas under the corrected emission spectrum of
the test sample with that of quinine sulfate as the standard
(0.56 in 0.1 M H2SO4 aqueous solutions). Non-degassed,
spectroscopic grade solvents and a 10 mm quartz cuvette
were used. Dilute solutions (0.01 < A < 0.05) were used
to minimize reabsorption effects. Quantum yields were
determined using the following equation [19]:
ΦX = ΦS (IX/IS) (AS/AX) (ηX/ηS)2
(1)
where ΦS is the reported quantum yield of the standard,
I is the integrated emission spectra, A is the absorbance
at the excitation wavelength and η is the refractive index
of the solvent being used (η = 1 when the same solvent
was used for both the test sample and the standard). An
X subscript refers to the test sample, and an S subscript
is for the standard.
Synthesis
Benzyl 5-ethynyl-4-ethyl-3-methylpyrrole-2-carboxy-
late (3). To a solution of benzyl 4-ethyl-5-iodo-3-methylpyrrole-
2-carboxylate(1a)(3.69g,10mmol)indiethylamine(100mL)
were added under argon (trimethylsilyl)acetylene (1.5 g,
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418
h.K. tanuI et al.
121.2, 115.8, 86.6, 67.6, 19.8, 16.5, 11.9. HRMS (ESI-
TOF): m/z 509.2444 [M + H]+, calcd. for C32H33N2O4
509.2435.
The organic phase was dried over anhydrous NaHCO3 and
concentrated under reduced pressure. The crude mixture
was purified by flash column chromatography on silica
gel using hexane/ethyl acetate (7:1) as eluant. The prod-
uct (5c) was obtained (0.25 g) in 55% yield and recrys-
tallized from dichloromethane to give colorless crystals.
mp 45–47 °C. 1H NMR (250 MHz, CDCl3): δ, ppm 8.86
(1H, s), 8.83 (1H, s), 8.47 (1H, s), 7.53 (1H, d, J = 7.45
Hz), 7.45 (1H, d, J = 7.91 Hz), 7.24 (2H, m), 4.33 (2H,
q, J = 7.12 Hz), 4.23 (2H, q, J = 6.98 Hz), 2.37 (3H, s),
2.30 (3H, s), 2.11 (3H, s), 1.79 (3H, s), 1.39 (3H, t, J =
7.19 Hz), 1.32 (3H, t, J = 6.96 Hz). 13C NMR (63 MHz,
CDCl3): δ, ppm 9.9, 10.4, 10.7, 11.2, 14.7, 14.9, 60.3,
60.4, 105.9, 111.4, 119.5, 119.6, 120.0, 120.2, 121.3,
123.6, 124.6, 126.6, 128.1, 128.2, 128.8, 136.1, 161.6,
161.2. HRMS (ESI-TOF): m/z 448.2221 [M + H]+, calcd.
for C26H30N3O4 448.2231.
2,3-bis[2-(5-benzyloxycarbonyl-3,4-dimethyl-
pyrrolyl)]-indole (5a). Prepared using above method
from 4a in 54% yield and recrystallized from dichlo-
romethane to give colorless crystals. mp 53–54 °C.
1H NMR (250 MHz, CDCl3): δ, ppm 8.82 (1H, s), 8.80
(1H, s), 8.30 (1H, s), 7.34 (14H, m), 5.28 (2H, s), 5.18
(2H, s), 2.60 (2H, q, J = 7.56 Hz), 2.31 (3H, s), 2.34 (3H,
s), 2.23 (2H, q, J = 7.58 Hz), 1.11 (3H, t, J = 7.53 Hz),
0.82 (3H, t, J = 7.58 Hz). 13C NMR (63 MHz, CDCl3):
δ, ppm 10.6, 11.2, 15.2, 15.7, 18.1, 66.0, 106.1, 111.4,
119.5, 119.8, 123.6, 126.3, 127.3, 128.4, 128.5, 128.8,
128.9, 129.2, 136.0, 136.6, 161.7. HRMS (ESI-TOF): m/z
600.2889 [M + H]+, calcd. for C38H38N3O4 600.2863.
Cis-1,2-[2-(5-ethoxycarbonyl-4-ethyl-3-methylpyr-
rolyl)]ethene (6). Commercially available Lindlar’s cat-
alyst (5 wt.% Pd on CaCO3, poisoned with lead; 150 mg,
100 wt.%) was added to a solution of alkyne 4c (150 mg,
0.42 mmol) in dry ethyl acetate (15 mL). The flask was
evacuated and flushed with hydrogen gas (two freeze/
thaw cycles) and the mixture was stirred under hydrogen
gas for 12 h. The resulting mixture was then filtered over
a Celite cake and washed with ethyl acetate (2 × 30 mL).
The solvent was removed under reduced pressure and
the crude residue was purified by silica gel column chro-
matography eluting with ethyl acetate/dichloromethane/
hexanes (1:1:5) to yield the title product as a yellow oil
that solidified to a yellow powder (47 mg, 0.13 mmol,
31% yield). 1H NMR (450 MHz, CDCl3, 293 K): δ, ppm
8.73 (2H, s, NH), 6.33 (2H, s, CHCH), 4.26 (4H, q, CH2),
2.29 (6H, s, CH3), 1.99 (6H, s, CH3), 1.30 (6H, t, CH3).
HRMS (ESI-TOF): m/z 359.1965 [M + H]+, calcd. for
C20H27N2O4 359.1971.
1,2-bis[2-(5-benzyloxycarbonyl-3,4-dimethylpyr-
rolyl)]ethyne (4b). This compound was obtained in 54%
yield using the above method B and recrystallized from
1
dichloromethane to afford colorless crystals. H NMR
(250 MHz, CDCl3): δ, ppm 11.99 (2H, s), 7.47–7.32
(10H, m), 5.29 (4H, s), 2.2 (6H, s), 2.0 (6H, s). MS (EI):
m/z 480.129 [M]+.
1,2-bis[2-(5-ethoxycarbonyl-3,4-dimethylpyrro-
lyl)]ethyne (4c). This compound was obtained in 52%
yield using the above method B and recrystallized from
1
dichloromethane to afford colorless crystals. H NMR
(250 MHz, CDCl3): δ, ppm 8.80 (2H, s), 4.34 (4H. q, J =
7.01 Hz), 2.35 (6H, s), 2.10 (6H, s), 1.37 (6H, t, J = 7.05
Hz). 13C NMR (63 MHz, CDCl3): δ, ppm 10.3, 10.9, 14.9,
60.6, 86.0, 114.8, 120.3, 126.9, 160.6. HRMS (MALDI-
TOF): m/z 357.1807 [M + H]+, calcd. for C20H25N2O4
357.1808.
1,2-bis(N-tosylpyrrolyl)ethyne (4d). To a 50 mL round
bottom flask was added 2-bromo-1-tosyl-pyrrole (0.3 g,
1 mmol) followed by Pd(PPh)2Cl2 (0.042 g, 0.06 mmol)
and CuI (0.038 g, 0.2 mmol). The flask was sealed and
placed in a dry ice bath under N2. Trimethylsilylethyne
(0.072 mL, 0.5 mmol), DBU (0.9 mL, 6 mmol) and water
(0.0072 mL, 40 molar equiv.) were dissolved in benzene
(5 mL) and added to the reaction flask. After freezing the
mixture in a dry ice bath, the flask was evacuated and
nitrogen gas was added. The resulting reaction mixture
was allowed to warm slowly to room temperature and was
stirred until complete disappearance of the starting mate-
rial, as monitored by TLC. The mixture was worked up by
adding ethyl acetate (100 mL), and washing the organic
layer three times with brine. The organic phase was dried
over anhydrous Na2CO3 and concentrated under reduced
pressure. The crude mixture was purified by flash column
chromatography using hexane/ethyl acetate (5:1) for elu-
tion. The bispyrrolylethyne (4d) was obtained in 8.4%
yield (0.02 g) and recrystallized from dichloromethane
1
to afford colorless crystals. mp 185–186 °C. H NMR
(250 MHz, CDCl3,): δ, ppm 7.9 (4H, br), 7.4 (4H, br), 7.3
(2H, br, 2H), 6.71 (2H, br), 6.34 (2H, br), 2.42 (6H, s).
HRMS (MALDI-TOF): m/z 465.0939 [M + H]+, calcd.
for C24H21O4N2S2 465.0943.
2,3-bis[2-(5-ethoxycarbonyl-3-ethyl-4-methylpyr-
rolyl)]-indole (5c). 1,2-bis[2-(5-ethoxycarbonyl-3,4-
dimethylpyrrolyl)]ethyne (4c) (0.36 g, 1 mmol) was added
to a 100 mL reaction tube together with 2-iodoaniline
(0.44 g, 2 mmol), Pd(OAc)2 (0.02 g, 0.1 mmol), LiCl
(0.04 g, 1 mmol), and K2CO3 (1.38 g, 10 mmol) and dis-
solved in 25 mL of DMF. The mixture was placed in a
dry ice bath, evacuated, purged with nitrogen gas and
then allowed to warm to room temperature and heated at
80 °C for 2 d. The reaction was monitored by TLC. Ethyl
acetate (150 mL) was added to the reaction mixture and
the organic layer was washed with brine (3 × 100 mL).
1,2-bis[2-(5-benzyloxycarbonyl-3-ethyl-4-
methylpyrrolyl)]-dodecaborane (7). A mixture of
dodecaborane (2.44 g, 3.0 mmol) and Et2S (9.0 mL,
37 mmol) in 20 mL of dry toluene was heated at 40 °C for
2 h under Ar, then raised to 60 °C for 3 h. Then 4a (1.06 g,
2 mmol) in 20 mL toluene was added into the mixture
via a syringe, and the mixture was heated to 80 °C for
2 d under argon. After TLC indicated no 4a remained,
Copyright © 2011 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2011; 15: 418–420

EffICIEnt SynthESIS anD rEaCtIOnS Of 1,2-DIPyrrOlylEthynES
419
the mixture was cooled to room temperature and excess
β = 91.123(9), γ = 92.222(7)˚, V = 1670.0(5)Å3, T =
115.0(5) K, Z = 2, ρcalcd = 1.246 g cm-3, µ(MoKα) =
0.075 mm-1. 35,739 total data, θmax = 26.0˚. R = 0.044
for 4850 data with Fo2 > 2σ(Fo2) of 6566 unique data and
444 refined parameters, CCDC 821406.
Crystallographic data have been deposited at the
Cambridge Crystallographic Data Center (CCDC) under
above-cited deposition numbers. Copies can be obtained
on request, free of charge, via www.ccdc.cam.ac.uk/
conts/retrieving.html or from the Cambridge Crystallo-
graphic Data Center, 12 Union Road, Cambridge CB2
1EZ, UK (fax: +44 1223-336-033 or email: deposit@
ccdc.cam.ac.uk).
decarborane was destroyed by adding methanol. The sol-
vent was removed under reduced pressure and ethanol
was added to allow codistillation of Et2S. The residue was
purified on a silica gel column using 25% ethyl acetate in
hexane as eluant, giving the title compound (0.363 g) in
29% yield as a light yellow power. 1H NMR (300 MHz,
CDCl3): δ, ppm 8.60 (2H, s), 7.37–7.43 (10H, m), 5.27
(4H, s), 2.61–2.69 (4H, q), 2.18 (6H, s), 1.50–3.50 (br,
10H), 1.03–1.08 (6H, t). 13C NMR (CDCl3, 75 MHz):
δ, ppm 161.8, 137.2, 133.1, 130.2, 129.9, 129.8, 129.5,
122.1, 121.6, 84.6, 67.9, 18.9, 16.5, 11.8. MALDI-TOF:
[M]+ 624.76.
X-ray crystallographic data
CONCLUSION
Crystals of 4a, 4c, 5c, 5c-F- complex and 7 for X-ray
crystallographic analysis were grown by slow evapora-
tion of their dichloromethane solutions. Diffraction data
were collected at low temperature on a Nonius Kap-
paCCD diffractometer equipped with MoKα radiation
(λ = 0.71073 Å) and an Oxford Cryosystems Cryostream
chiller. Refinement was by full-matrix least squares
using SHELXL, with H atoms in idealized positions,
except for NH hydrogen atoms, which were located by
difference maps and their positions refined. One of the
ethyl groups in 4c was disordered into two orientations,
as is one of the DCM molecules in the 5c fluoride com-
plex. Crystallographic data: For 4a: C32H32N2O4, mono-
clinic space group P2/c, a = 9.870(2), b = 10.635(2),
c = 13.545(2) Å, β = 105.469(10)˚, V = 1370.3(4) Å3,
T = 90.0(5) K , Z = 2, ρcalcd = 1.233 g cm-3, µ(MoKα) =
0.081 mm-1. A total of 20,271 data was collected at to
θ = 28.8˚. R = 0.041 for 2783 data with Fo2 > 2σ(Fo2)
of 3549 unique data and 178 refined parameters, CCDC
821407. For 4c: C20H24N2O4, orthorhombic space group
Pbca, a = 13.889(2), b = 14.845(4), c = 18.920(5) Å, V =
3901.0(16)Å3, T = 120.0(5) K , Z = 8, ρcalcd = 1.214 g cm-3,
µ(MoKα) = 0.085 mm-1. 19,130 total data, θmax = 22.5˚.
R = 0.042 for 1838 data with Fo2 > 2σ(Fo2) of 3549 unique
data and 264 refined parameters, CCDC 779360. For 5c:
C26H29N3O4, triclinic space group P-1, a = 10.244(2),
b = 10.789(2), c = 12.516(3) Å, α = 107.091(12), β =
111.886(10), γ = 97.204(13)˚, V = 1183.1(5)Å3, T = 90.0(5)
K, Z = 2, ρcalcd = 1.256 g cm-3, µ(MoKα) = 0.086 mm-1.
18,860 total data, θmax = 26.4˚. R = 0.048 for 3352 data
with Fo2 > 2σ(Fo2) of 4813 unique data and 312 refined
parameters, CCDC 779361. For 5c-F- complex: (C16H36N)
(C26H29N3O4)2F . 1.5(CH2Cl2) triclinic space group P-1,
a = 8.7265(10), b = 15.106(2), c = 27.490(3) Å, α =
74.955(6), β = 84.843(7), γ = 78.574(7)˚, V = 3427.4(7)
Å3, T = 90.0(5) K, Z = 2, ρcalcd = 1.244 g cm-3, µ(MoKα)
= 0.195 mm-1. 51,056 total data, θmax = 27.1˚. R = 0.108
for 8547 data with Fo2 > 2σ(Fo2) of 14,946 unique data
and 819 refined parameters, CCDC 779362. For 7:
C32H42B10N2O4, triclinic space group P-1, a = 11.651(2),
b = 11.903(2), c = 12.1444(17) Å, α = 96.959(10),
We have developed an efficient one-pot double Sona-
gashira coupling reaction from which a series of dipyr-
rolylethynes (4a–d) has been synthesized using an
improved route from trimethylsilylethyne and various
2-halopyrroles. The resulting dipyrrolylethynes were
further transformed into various novel dipyrroles (5–7)
using the Larock indole synthesis, stereoselective cata-
lytic hydrogenation, or reaction with B10H14. These novel
dipyrroles should be valuable building blocks for the
construction of elaborate pyrrole-containing functional
molecules and materials. In addition, indolyl-dipyrroles
5 were found to selectively bind fluoride ions with high
affinity, forming a 2:1 complex involving one pyrrolic
NH and the indole NH.
Acknowledgements
The work described was supported by grants from the
US National Institutes of Health, (CA 132861; KMS)
and the US National Science Foundation (CHE 0911629;
MGHV). The purchase of the X-ray diffractometer was
made possible by Grant No. LEQSF(1999-2000)-ENH-
TR-13, administered by the Louisiana Board of Regents.
REFERENCES
1. a) The Porphyrin Handbook, Vol. 6, Kadish KM,
Smith KM and Guilard R. (Eds.) Academic Press:
San Diego, 2000. b) Dismukes GC. Science 2001;
292: 447. c) Chang CJ, Chng LL and Nocera DG.
J. Am. Chem. Soc. 2003; 125: 1866.
2. a) Sessler JL, An D, Cho W-S and Lynch V. Angew.
Chem. Int. Ed. 2003; 42: 2278. b) Sessler JL, An D,
Cho WS and Lynch V. J. Am. Chem. Soc. 2003; 125:
13646. c) Geier GR III and Grindrod SC. J. Org.
Chem. 2004; 69: 6404. d) Jolicoeur B and Lubell WD.
Org. Lett. 2006; 8: 6107. e) Roznyatovskiy VV,
Roznyatovskaya NV, Weyrauch H, Pinkwart K,
Tubke J and Sessler JL. J. Org. Chem. 2010; 75:
8355. f) Jiao L, Yu C, Liu M, Cong K, Meng T,
Wang Y and Hao E. J. Org. Chem. 2010; 75: 6035.
Copyright © 2011 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2011; 15: 419–420

420
h.K. tanuI et al.
g) Sessler JL and Weghorn SJ. Expanded, Con-
tracted and Isomeric Porphyrins, Pergamon Press:
New York, 1997.
Macromolecules 2006; 39: 112. c) Hao E, Fabre B,
Fronczek FR and Vicente MGH. Chem. Commun.
2007; 4387. d) Hao E, Fabre B, Fronczek FR and
Vicente MGH. Chem. Mater. 2007; 19: 6195.
11. a) Lee DA, Xie H, Senge MO and Smith KM.
J. Chem. Soc., Chem. Commun. 1994; 791. b) Xie H,
Lee DA, Wallace DM, Senge MO and Smith KM.
J. Org. Chem. 1996; 61: 8508.
12. a) Jiao LJ, Hao EH, Fronczek FR, Vicente MGH
and Smith KM. J. Porphyrins Phthalocyanines
2011; 15: 433. b) Jiao L, Hao E, Vicente MGH and
Smith KM. J. Org. Chem. 2007; 72: 8119.
13. Chinchilla R and Najera C. Chem. Rev. 2007; 107:
874.
14. a) Tanui H, Fronczek FR and Vicente MGH. Acta
Crystallogr. 2007; E64: o75. b) Tanui H, Fronczek
FR and Vicente MGH. Acta Crystallogr. 2007; E64:
o130.
15. Larock RC and Yum EK. J. Am. Chem. Soc. 1991;
113: 6689.
16. a) Lindlar H and Dubuis R. Org. Synth. 1973; 5:
880. b) Takeda H, Watanabe H and Nakada M.
Tetrahedron 2006; 62: 8054.
17. Luo F, Pan C, Wang W, Ye Z and Cheng J. Tetrahe-
dron 2010; 66: 1399.
18. Jiang W, Knobler CB and Hawthorne MF. Inorg.
Chem. 1996; 35: 3056.
19. Fery-Forgues S and Lavabre D. J. Chem. Educ.
1999; 76: 1260.
3. Jux N, Koch P, Schmickler H, Lex J and Vogel E.
Angew. Chem. Int. Ed. 1990; 29: 1385.
4. Cho DH, Lee JH and Kim BH. J. Org. Chem. 1999;
64: 8048.
5. Tu B, Ghosh B and Lightner DA. J. Org. Chem.
2003; 68: 8950.
6. Mio MJ, Kopel LC, Braun JB, Gadzikwa TL, Hull
KL, Brisbois RG, Markworth CJ and Grieco PA.
Org. Lett. 2002; 4: 3199.
7. a) Black CB, Andrioletti B, Try AC, Ruiperez C and
Sessler JL. J. Am. Chem. Soc. 1999; 121: 10438.
b) Anzenbacher Jr. P, Try AC, Miyaji H, Jursíková
K, Lynch VM, Marquez M and Sessler JL. J. Am.
Chem. Soc. 2000; 122: 10268. c) Mizuno T, Wei
W-H, Eller LR and Sessler JL. J. Am. Chem. Soc.
2002; 124: 1134. d) Sessler JL, Maeda H, Mizuno
T, LynchVM and Furuta H. J. Am. Chem. Soc. 2002;
124: 13474. e) Yoo J, Kim M-S, Hong S-J, Sessler
JL and Lee C-H. J. Org. Chem. 2009; 74: 1065.
8. Ghosh T, Maiya BG and Wong MW. J. Phys. Chem.
A 2004; 108: 11249.
9. Amendola V, Esteban-Gómez D, Fabbrizzi L and
Licchelli M. Acc. Chem. Res. 2006; 39: 343.
10. a) Clark JC, Fabre B, Fronczek FR and Vicente
MGH. J. Porphyrins Phthalocyanines 2005; 9:
803. b) Fabre B, Clark JC and Vicente MGH.
Copyright © 2011 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2011; 15: 420–420