Synthesis of bis(phenanthropyrroles) via a tandem scholl oxidation

Article abstract of DOI:10.1021/jo302486x

An electron-rich 3,4-diarylpyrrole is shown to undergo a tandem inter- and intramolecular Scholl oxidation, providing access to bis(phenanthropyrroles), a new class of bipyrrole derivatives with extended π conjugation. Intermolecular coupling of two pyrrole molecues is found to be the initial step of this reaction. Bis(phenanthropyrroles) are characterized by restricted rotation around the α-α bond and exhibit strong blue fluorescence and large Stokes shifts.

Full text of DOI:10.1021/jo302486x

Note
pubs.acs.org/joc
Synthesis of Bis(phenanthropyrroles) via a Tandem Scholl Oxidation
Elzbieta Gonka, Damian Mysliwiec, Tadeusz Lis, Piotr J. Chmielewski, and Marcin Stępien*
́
́
́
̇
Wydział Chemii, Uniwersytet Wrocławski, ul. F. Joliot-Curie 14, 50-383 Wrocław, Poland
S
* Supporting Information
ABSTRACT: An electron-rich 3,4-diarylpyrrole is shown to
undergo a tandem inter- and intramolecular Scholl oxidation,
providing access to bis(phenanthropyrroles), a new class of
bipyrrole derivatives with extended π conjugation. Intermolec-
ular coupling of two pyrrole molecues is found to be the initial
step of this reaction. Bis(phenanthropyrroles) are characterized
by restricted rotation around the α−α bond and exhibit strong
blue fluorescence and large Stokes shifts.
Scheme 1. Synthesis of Bis(phenanthropyrroles) 2 and 3a−
2,2′-Bipyrrole is one of the most important structural motifs in
pyrrole chemistry. It occurs in certain natural products, such as
prodigiosins,1 and constitutes the trademark structural feature
of several macrocyclic systems, such as sapphyrins, corroles,
porphycenes, or cyclopyrroles.2 2,2′-Bipyrrole, the smallest
system containing a direct α−α linkage between pyrrole rings,
is also the defining motif of longer oligopyrrole molecules3 and
conducting pyrrole polymers4 and may be viewed as a potential
synthetic intermediate and a convenient structural model.
In the “classical” synthetic approach to 2,2′-bipyrroles, a
monopyrrole is substituted at position 2, and the substituent is
transformed into the second pyrrole nucleus using various
synthetic schemes.5 Symmetrical bipyrroles are now efficiently
obtained using Ullmann coupling of 2-iodopyrroles.6 This
approach is most successful for pyrroles that are thermally
stable and bear electron-withdrawing substituents. N-Protection
of the starting monopyrrole improves coupling yields,6l as it
prevents the competing N-arylation reaction. Alternatively, 2-
unsubstituted monopyrroles can be coupled oxidatively using a
variety of reagents, such as FeCl3, Cu(NO3)2, Pd(OAc)2, or
PIFA.7 We have recently reported that Scholl-type oxidations of
electron-rich β-aryl porphyrins provide a straightforward route
to peripherally fused tetraphenanthro- and tetrakis(benzo-
chryseno)porphyrins.8 This reaction offers a potentially general
method for preparing a variety of pyrrole-based condensed
heteroaromatics. Here we show that the Scholl oxidation
performed on the α-free monopyrrole 1 effects not only the
intramolecular ring closure described previously but also the
intermolecular α−α coupling of two pyrrole rings. Such a
tandem oxidation provides a facile and efficient route to
bis(phenanthropyrrole) 2,9 a structurally new fluorescent bis-
heterocycle (Scheme 1).
a
c
a
Reagents and conditions: (1) FeCl3 (4 equiv), CH2Cl2, 22 h, 71%;
(2) RBr (3b) or RI (3a, 3c), K2CO3, 18-crown-6, 22−63%.
an initial effort to obtain substituted bis(phenanthropyrrole)
derivatives, 2 was reacted with several alkyl halides to produce
the doubly N-alkylated compounds 3a−c. Inconsistent yields of
these reactions are a result of purification difficulties.
By gradually varying the amount of oxidant used (1−4 equiv;
see Supporting Information), it was found that, in the initial
step of the oxidation reaction, two molecules of 1 are combined
to yield tetraarylbipyrrole 4 (Scheme 2). Regardless of the exact
amount of oxidant used, 4 would never become the main
component of the crude reaction mixture, and consequently,
isolated yields were low (ca. 5%). When 1 or 2 equiv of FeCl3
was used, 4 was accompanied by a large amount of unreacted 1
and by traces of other products. Judging by the appearance of
Under optimized reaction conditions, a 10 mM solution of
pyrrole 1 in dry dichloromethane was treated with 4 equiv of
anhydrous iron(III) chloride (33% molar excess). After 22 h of
stirring and subsequent workup, bis(phenanthropyrrole) 2 was
isolated in 71% yield. Pure 2 exhibits fairly low solubility (less
than 140 mg/L in dichloromethane), but the crude material is
not observed to precipitate under typical workup conditions. In
1
low-field singlets (above 7.5 ppm) in the H NMR spectra of
crude reaction mixtures, these products contained phenan-
threne subunits. When the oxidation was performed at a lower
Received: November 19, 2012
© XXXX American Chemical Society
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accommodate the steric bulk of fused arene rings, the two
phenanthropyrrole fragments are noticeably tilted relative to
one another. The NCαCαN torsional angle is 62.8° in the
structure of 2, corresponding to a tilted syn conformation. In
the more sterically congested structure of 3a, the NCαCαN
angle is nearly 90°. In the solid-state geometry of 2, each of the
two phenanthropyrrole subunits is nearly planar, including the
attached carboxy group, whereas slight out-of-plane distortions
are observed in the subunits of 3a.
Scheme 2. Reaction Intermediates Discussed in the Text
The geometry of 2 observed in the solid state is accurately
reproduced by density functional theory (DFT) calculations
(ωB97XD10/6-31G(d,p), Table 1, Supporting Information),
Table 1. Computational Data for Bis(phenanthropyrroles)
(ωB97XD/6-31G(d,p), PCM Solvation in
Dichloromethane)
concentration (1 mM, 2 equiv of FeCl3), the conversion of the
starting material was similar and, interestingly, 4 was still the
dominant reaction product. Apparently, the intermolecular
coupling is a rapid process and can compete with the
intramolecular ring closure, suppressing the formation of
phenanthropyrrole 5. Further oxidation of 4 with additional
FeCl3 results in efficient formation of 2, with no significant
buildup of the expected intermediate 6. However, when a large
excess of the oxidant was used (e.g., 16 equiv), an intractable
mixture of products was obtained.
a
b
Erel
NCαCαN
(deg)
Cα−Cα
S0 → S1
(nm)
species state
(kcal/mol)
(Å)
2
S0
S1
S0
0.00
1.19
1.91
0.00
0.27
0.00
60.7
131.0
24.2
1.464
1.457
1.396
1.392
1.465
1.463
322
346
466
469
314
306
153.3
75.7
3a
102.5
a
Relative DFT energies (S0 states) and TD-DFT energies (S1 states).
Lowest-energy electronic transitions for the optimized geometries.
b
The molecular structures of 2 and 3a were confirmed by X-
ray structural analyses (Figure 1). In the crystal, the molecules
of both compounds are located on crystallographic C2 axes. To
including the relative orientation of phenanthropyrrole units.
However, the calculations predict the existence of an additional,
almost isoenergetic conformer, characterized by the NCαCαN
angle of 131°. For 3a, two energy minima were also found, with
NCαCαN torsions of 103 and 76°. These values cover a
narrower range of angles than observed for 2, indicating that
the torsional freedom in bis(phenanthropyrrole) is restricted
upon N-substitution.
The crystal structure of 2 is stabilized by a combination of
weak hydrogen bonding and π-stacking interactions (Figure 1,
bottom). Each NH hydrogen of 2 interacts with a pair of
adjacent OMe groups from a neighboring molecule (H···O
distances of 2.38 and 2.60 Å). The π surfaces of the
phenanthropyrrole units involved in H-bonding are partly
overlaid, with interplane separations of 3.42−3.56 Å. This
structural motif, combining π stacking with weak hydrogen
bonds, is repeated infinitely in one dimension, yielding
heterochiral strands of closely packed molecules.
As a consequence of their twisted conformation, compounds
2 and 3a−c can in principle be axially chiral, but their
configurational stability will depend on the rotation barrier
around the α−α bond. Because of the increased steric bulk, the
barrier is expected to be higher in the alkylated derivatives 3a−
c.7a,11 In the 1H NMR spectra of 2, 3a, and 3b, the CH2 signal
of the ester ethyl group shows diastereotopic splitting,
indicating that the rotation is slow on the NMR time scale.
Separation of enantiomers could be transiently observed for 2
on a chiral HPLC column, but their racemization was very
rapid. However, we were not able to observe any separation for
the alkylated derivatives, probably because of insufficient
column specificity.
Figure 1. Molecular structures of 2 (top) and 3a (middle) obtained
from X-ray structural analyses. Thermal ellipsoids are shown at the
50% probability level. Solvent molecules, hydrogen atoms, and
disordered alkoxy groups are omitted for clarity. Bottom: interaction
between adjacent molecules of 2 in the solid state.
To further explore the stereochemistry of bis(phenathro-
pyrroles), 2 was reacted with S-(+)-1-iodo-2-methylbutane.
The resulting dialkyl derivative 3c was isolated as a nearly
equimolar mixture of two diastereomers (SSRa and SSSa).
B
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These isomers differ in the configuration of the chirality axis
and yield distinct sets of signals in the H NMR spectrum. A
emission maxima of 2 and 3a are 473 and 465 nm, respectively,
corresponding to Stokes shifts in excess of 100 nm (Figure 2).
The observed fluorescence profiles are rather insensitive to
solvent polarity. The emission of bis(phenanthropyrrole)
derivatives is significantly red-shifted relative to symmetrically
substituted nonfused bipyrroles, which typically yield maxima in
the 380−420 nm range.6n,13 In fact, bipyrrole 4 shows the
emission maximum at 409 nm, corresponding to the Stokes
shift of 54 nm. Fluorescence quantum yields measured for 2
and 3a in dichloromethane are 0.33 and 0.19, respectively.
TD-DFT geometry optimizations12,14 show the existence of
two conformations for the S1 state of 2 (Table 1, Figure 3).
1
sample of 3c in p-xylene-d10 showed no signs of dynamic
broadening when heated to 410 K. Likewise, exchange between
the diastereomers of 3c was not observed in the ROESY
spectrum recoded under the same conditions. These results
indicate that the rotation barrier in N-substituted species might
be sufficiently high to ensure configurational stability at room
temperature.
The electronic effects of ring fusion in bis(phenanthro-
pyrrole) can be appreciated by comparing the absorption
spectra of 2 and its nonfused analogue 4 (Figure 2). The
Figure 3. Optimized geometry of the lowest-energy conformer of the
S1 state of 2 (ωB97XD/6-31G(d,p), dichloromethane PCM).
Hydrogen atoms (except for NH) are omitted for clarity.
The two conformers have very similar energies, and the
calculated S0 → S1 transitions are in very good agreement with
the experimental emission wavelength. In comparison with the
S0 geometries, the S1 state is characterized by more extensive π
coupling between the phenanthropyrrole subunits as evidenced
by the smaller deviations of the NCαCαN angles from planarity
and shorter Cα−Cα distances. Complete planarization of the S1
state is not possible because of steric repulsions between the
polycyclic subunits, and the resulting geometry shows a
characteristic puckering of the bipyrrole fragment.
The present work shows that Scholl-type oxidations provide
a simple yet effective synthetic route to arene-fused 2,2′-
bipyrroles. Tandem Scholl oxidations have previously been
observed in oligophenylene chemistry,15 but such reactions
yield mixtures of products and are prone to oligomerization.
This limitation stems from the difficulty to control the reactivity
of multifunctional substrates. The success of the present
approach apparently results from the intermolecular pyrrole
α−α coupling being faster than other possible oxidation routes.
The tandem oxidation strategy presented here can be extended
in two complementary ways: by elongation of the oligopyrrole
chain and by expansion of the attached polycyclic moieities.
Such systems are expected to combine strong emission with
high absorptivity, as already seen in 2, making them of potential
interest as electroactive materials.
Figure 2. Top: electronic absorption spectra of bis(phenanthro-
pyrroles) 2 and 3a and bipyrrole 4 (293 K, dichloromethane). Bottom:
normalized emission and excitation spectra of 2 and 3a (293 K,
dichloromethane).
absorption below 350 nm is significantly more intense in the
spectrum of 2, with the largest extinction coefficients reaching
70 000 M−1 cm−1. In contrast, the longest wavelength band of 2
(364 nm) is only slightly red-shifted relative to the
corresponding band in 4 (355 nm). The absorption profile of
3a is very similar to that of 2 except for the lowest-energy band
which is hypsochromically shifted and has a significantly
reduced intensity. This effect can be tentatively attributed to
the larger tilt of phenanthropyrrole subunits in 3a, which
reduces electronic coupling between the two π systems. Vertical
excitation energies for 2 and 3a have been calculated using
time-dependent density functional theory (TD-DFT). Calcu-
lations performed at the B3LYP/6-31G(d,p) level of theory
provided a significantly underestimated value of the first
excitation energy (λmax > 420 nm), which may result from the
known deficiency of hybrid DFT functionals.12 More realistic
values could be obtained using the range-separated hybrid
functional ωB97XD (Table 1).
EXPERIMENTAL SECTION
■
General. Tetrahydrofuran was dried using a commercial solvent
purification system. Dichloromethane was distilled from calcium
hydride when used as a reaction solvent. All other solvents and
reagents were used as received. Compound 1 was synthesized as
described previously.8 1H NMR spectra were recorded on high-field
spectrometers (1H frequency at 500.13 or 600.13 MHz), equipped
Bis(phenanthropyrroles) display intense blue fluorescence in
the solid state and in solution. In dichloromethane, the
C
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with broad-band inverse gradient probeheads. Spectra were referenced
to the residual solvent signals (chloroform-d, 7.24 ppm, xylene-d10
assumed to be 2.30 ppm). Two-dimensional NMR spectra were
recorded with 2048 data points in the t2 domain and up to 2048 points
in the t1 domain, with a 1−1.5 s recovery delay. All 2D spectra were
recorded with gradient selection, with the exception of ROESY. The
ROESY spinlock time was 300 ms. 13C NMR spectra were recorded
with 1H broad-band decoupling and referenced to solvent signals
(13CDCl3, 77.0 ppm). High-resolution mass spectra were recorded
using ESI or MALDI ionization in the positive mode. Fluorescence
quantum yields were calculated following a literature procedure,16 with
quinine sulfate as a standard.17
Computational Methods. Density functional theory (DFT and
TD-DFT) calculations were performed using Gaussian 09.18 Ground-
state DFT geometry optimizations were carried out in unconstrained
C1 symmetry, using X-ray geometries as starting models. Vertical
excitation energies and excited-state geometries were calculated by
means of time-dependent density functional theory (TD-DFT). DFT
geometries were refined to meet standard convergence criteria, and the
existence of a local minimum was verified by a normal-mode frequency
calculation (the frequency calculation was not performed for the TD-
DFT optimized S1 states, for which analytic second derivatives were
not available). DFT calculations were performed using the hybrid
functional B3LYP19 and the range-separated ωB97XD20 functional
combined with the 6-31G(d,p) basis set.
X-ray Crystallography. X-ray quality crystals were grown by slow
diffusion of methanol into a dichloromethane solution (2·2MeOH)
and via slow evaporation o a dichloromethane solution (3a·3CH2Cl2).
Diffraction measurements were performed on a κ-geometry diffrac-
tometer (ω and ϕ scans) with graphite-monochromatized Mo Kα
(2·2MeOH) and Cu Kα radiation (3a·3CH2Cl2). Data were corrected
for Lorentz and polarization effects. An analytical absorption
correction was applied to the data of 3a·3CH2Cl2 with the use of
diffractometer software. The structures were solved by direct methods
with the SHELXS-97 program and refined using SHELXL-9721 with
anisotropic thermal parameters for non-H atoms. All H atoms were
found in difference Fourier maps. In the final refinement cycles, all H
atoms were treated as riding atoms in geometrically optimized
positions. In the structure of 2·2MeOH, one of the methoxy groups
and the ethyl group of the ester were positionally disordered.
General Procedure for the Oxidation of Ethyl 3,4-Bis(3,4-
dimethoxyphenyl)-1H-pyrrole-2-carboxylate (1). Ethyl 3,4-bis-
(3,4-bismethoxyphenyl)-1H-pyrrole-2-carboxylate (1) was dissolved in
deoxygenated dichloromethane. Anhydrous iron(III) chloride was
added, and the reaction mixture was stirred under argon for 20−36 h.
The progress of the reaction was monitored with thin-layer
chromatography. The reaction mixture was diluted with aqueous
potassium thiocyanate and extracted with dichloromethane. The
extracts were dried over anhydrous magnesium sulfate, and the solvent
was removed on a rotary evaporator. The dark residue was crystallized
from methanol/dichloromethane. The product was isolated as grayish
crystals.
Compound 4 was separated from the reaction mixture by fractional
crystallization from dichloromethane/methanol as brownish crystals
(9.6 mg, 4.8%). 1H NMR (500 MHz, chloroform-d, 300 K): δ 8.98 (s,
2H), 6.87 (d, 2H, 3J = 8.22 Hz), 6.84 (dd, 2H, 3J = 8.12 Hz, 4J = 1.91
Hz), 6.79 (dd, 2H, 3J = 8.22 Hz, 4J = 2.00 Hz), 6.73 (d, 2H, 4J = 1.91
3
4
Hz), 6.71 (d, 2H, J = 8.31 Hz), 6.67 (d, 2H, J = 1.91 Hz), 4.06 (q,
3
4H, J = 7.13 Hz), 3.87 (s, 6H), 3.81 (s, 6H), 3.70 (s, 6H), 3.62 (s,
3
6H), 1.09 (t, 6H, J = 7.12 Hz). 13C NMR (125 MHz, chloroform-d,
300 K): δ 159.8, 149.4, 148.7, 147.9, 147.7, 131.3, 126.6, 125.5, 123.8,
123.5, 123.3, 123.1, 117.9, 114.2, 113.9, 111.6, 110.2, 60.1, 56.0, 55.8,
55.7, 55.7, 14.0. UV−vis (dichloromethane, 293 K) λ [nm] (log ε in
M−1 cm−1): 279 (4.52), 342 (4.37), 355 (4.35). HR-MS (MALDI-
FTMS+): m/z 820.3195 [M+], calcd for C46H48N2O12 820.3202; mp
234−235 °C.
General Procedure for the Alkylation of Diethyl
5,5′,6,6′,9,9′,10,10′-Octamethoxy-2H,2′H-[1,1′-bidibenzo[e,g]-
isoindole]-3,3′-dicarboxylate. In a dry pressure tube equipped with
magnetic stirring, diethyl 5,5′,6,6′,9,9′,10,10′-octamethoxy-2H,2′H-
[1,1′-bidibenzo[e,g]isoindole]-3,3′-dicarboxylate (2, 50 mg, 0.061
mmol) was dissolved in dry tetrahydrofuran. Freshly ground
anhydrous potassium carbonate (33.74 mg, 0.244 mmol) and 18-
crown-6 (34.40 mg, 0.122 mmol) were added. The mixture was stirred
under nitrogen for 30 min, and alkyl halide was added. The pressure
tube was closed, placed in an oil bath, and heated at 90 °C for 24 h.
Subsequently, the second portion of potassium carbonate (33.74 mg,
0.244 mmol) was added, and the heating was continued for the next 24
h. Hydrochloric acid (3 M solution) was used to neutralize the
reaction mixture. The reaction mixture was diluted with water and
extracted with dichloromethane. The extracts were dried over
anhydrous magnesium sulfate, and the solvent was removed on a
rotary evaporator. The product was purified by column chromatog-
raphy and crystallization.
Diethyl 5,5′,6,6′,9,9′,10,10′-Octamethoxy-2,2′-dimethyl-
2H,2′H-[1,1′-bidibenzo[e,g]isoindole]-3,3′-dicarboxylate (3a).
3a was prepared according to the general procedure by using
tetrahydrofuran (2 mL) and methyl iodide (0.122 mmol, 17.31 mg,
7.59 μL) as the alkylating agent. Reaction time was 48 h. The yellow
residue was crystallized from methanol/dichloromethane. The product
1
was isolated as pale yellow crystals (17.87 mg, 35%). H NMR (500
MHz, chloroform-d, 300 K): δ 8.68 (s, 2H), 7.74 (s, 2H), 7.67 (s, 2H),
6.48 (s, 2H), 4.56 (m, 4H), 4.09 (s, 6H), 4.08 (s, 6H), 3.97 (s, 6H),
3
3.79 (s, 6H), 3.18 (s, 6H), 1.46 (t, 6H, J = 7.1 Hz). 13C NMR (125
MHz, chloroform-d, 300 K): δ 163.5, 148.8, 148.6, 148.2, 148.0, 124.6,
123.2, 120.9, 120.5, 120.4, 120.4, 118.6, 108.6, 105.0, 104.9, 103.7,
61.4, 56.1, 56.1, 56.0, 55.1, 35.0, 14.5. UV−vis (dichloromethane, 293
K) λ [nm] (log ε in M−1 cm−1): 254 (4.84), 280 (4.80), 287 (4.80),
313 (4.61). HR-MS (MALDI-FTMS+): m/z 844.3196 [M+], calcd for
C48H48N2O12 844.3202; mp 287−290 °C.
Diethyl 2,2′-Didodecyl-5,5′,6,6′,9,9′,10,10′-octamethoxy-
2H,2′H-[1,1′-bidibenzo[e,g]isoindole]-3,3′-dicarboxylate (3b).
3b was prepared according to the general procedure by using
tetrahydrofuran (2 mL) and 1-bromododecane (0.122 mmol, 30.40
mg, 29.22 μL) as the alkylating agent. Reaction time was 48 h. The
crude product was purified by column chromatography (silica gel, 1%
methanol in dichloromethane). The product eluted as the third
fraction. The solvent was removed on a rotary evaporator. The
product was finally purified by crystallization from methanol/
dichloromethane and was isolated as white crystals (15.6 mg, 22%).
1H NMR (500 MHz, chloroform-d, 300 K): δ 8.54 (s, 2H), 7.73 (s,
Diethyl 5,5′,6,6′,9,9′,10,10′-Octamethoxy-2H,2′H-[1,1′-bidi-
benzo[e,g]isoindole]-3,3′-dicarboxylate (2). Obtained from 1
(200 mg, 0.481 mmol) and anhydrous iron(III) chloride (312 mg,
1.924 mmol) in dichloromethane (48.6 mL) Reaction time was 22 h.
1
Grayish crystals (142 mg, 71%). H NMR (600 MHz, chloroform-d,
300 K): δ 10.37 (s, 2H), 9.57 (s, 2H), 7.54 (s, 4H), 7.05 (s, 2H), 4.52
(m, 4H), 4.14 (s, 6H), 4.02 (s, 6H), 3.95 (s, 6H), 2.82 (s, 6H), 1.48 (t,
6H, 3J = 7.0 Hz). 13C NMR (150 MHz, chloroform-d, 300 K): δ 160.6,
148.7, 148.5, 148.3, 148.1, 125.1, 124.8, 123.4, 121.7, 120.8, 120.7,
118.6, 115.4, 110.6, 105.1, 104.8, 104.3, 61.1, 56.3, 56.2, 55.9, 55.0,
14.9. UV−vis (dichloromethane, 293 K) λ [nm] (log ε in M−1 cm−1):
253 (4.84), 287 (4.82), 313 (4.60), 364 (4.20). HR-MS (MALDI-
FTMS+): m/z 816.2875 [M+], calcd for C46H44N2O12 816.2889; mp
330 °C (decomposition).
Diethyl 3,3′,4,4′-Tetrakis(3,4-dimethoxyphenyl)-1H,1′H-
[2,2′-bipyrrole]-5,5′-dicarboxylate (4). Prepared from 1 (200
mg, 0.481 mmol) and anhydrous iron(III) chloride (234 mg, 1.443
mmol) in dichloromethane (48.6 mL). Reaction time was 20 h.
2H), 7.63 (s, 2H), 6.60 (s, 2H), 4.55 (m, 4H), 4.08 (s, 6H), 4.06 (s,
3
6H), 3.95 (s, 6H), 3.01 (s, 6H), 1.58 (m, 4H), 1.46 (t, 6H, J = 7.1
3
Hz), 1.07 (m, 40H), 0.83 (t, 6H, J = 7.3 Hz). 13C NMR (125 MHz,
chloroform-d, 300 K): δ 164.0, 148.44, 148.41, 148.1, 147.9, 124.6,
123.04, 122.98, 120.6, 120.5, 120.2, 120.1, 117.6, 108.4, 105.0, 104.8,
104.6, 61.4, 56.04, 55.95, 55.94, 54.9, 48.0, 31.9, 31.7, 29.6, 29.5, 29.4,
29.3, 29.1, 28.9, 26.8, 22.7, 14.4, 14.1. HR-MS (MALDI-FTMS+): m/z
1152.6587 [M+], calcd for C70H92N2O12 1152.6645.
Diethyl 5,5′,6,6′,9,9′,10,10′-octamethoxy-2,2′-bis((S)-2-
methylbutyl)-2H,2′H-[1,1′-bidibenzo[e,g]isoindole]-3,3′-dicar-
boxylate (3c). In a dry pressure tube equipped with magnetic stirring,
D
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Note
compound 2 (0.037 mmol, 30 mg) was dissolved in dry
tetrahydrofuran (2 mL). Freshly ground anhydrous potassium
carbonate (0.148 mmol, 20.46 mg) and 18-crown-6 (0.074 mmol,
19.66 mg) were added. The mixture was stirred under nitrogen for 30
min, and S-(+)-1-iodo-2-methylbutane (0.148 mmol, 29.31 mg, 19.21
μL) was added. The pressure tube was closed, placed in an oil bath,
and heated at 90 °C for 24 h. Subsequently, the second portion of
potassium carbonate (20.46 mg, 0.148 mmol) and S-(+)-1-iodo-2-
methylbutane (0.148 mmol, 29.31 mg, 19.21 μL) were added, and the
heating was continued for the next 24 h. Hydrochloric acid (3 M
solution) was used to neutralize the reaction mixture. The reaction
mixture was diluted with water and extracted with dichloromethane.
The extracts were dried over anhydrous magnesium sulfate, and the
solvent was removed on a rotary evaporator. The crude product was
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1
analyzed by H NMR and subjected to another round of the above
alkylation procedure, in which the last heating step was extended to 48
h. The product was purified by crystallization from n-hexane/
dichloromethane. The product was isolated as grayish crystals (22.6
1
mg, 64%). H NMR (600 MHz, chloroform-d, 300 K, combined data
for both isomers): δ 8.51 (s, 2H), 8.47 (s, 2H), 7.740 (s, 2H), 7.735 (s,
2H), 7.29 (s, 2H), 7.23 (s, 2H), 4.63 (m, 4H), 4.55 (m, 2H), 4.47 (m,
4H), 4.44 (m, 2H), 4.094 (s, 6H), 4.092 (s, 6H), 4.07 (s, 6H), 4.06 (s,
6H), 3.97 (s, 6H), 3.96 (s, 6H), 3.72 (m, 2H), 3.48 (m, 2H) 2.76 (s,
6H), 2.74 (s, 6H), 1.50 (m, 2H), 1.483 (t, 6H), 1.476 (t, 6H), 1.44 (m,
2H), 1.15 (m, 2H), 0.86 (m, 2H), 0.85 (m, 2H), 0.66 (d, 3H), 0.61
(m, 2H), 0.57 (t, 3H), 0.34 (d, 3H), 0.24 (t, 3H). 13C NMR (151
MHz, chloroform-d, 300 K, combined data for both isomers): δ 164.42
(×2), 148.4, 148.36, 148.12, 148.10, 148.06, 148.03, 147.88, 147.86,
124.4, 124.3, 122.99, 122.97, 122.2, 122.1, 120.8, 120.61, 120.56,
120.53, 120.50, 120.48, 120.47, 120.45, 118.8, 118.5, 108.24, 108.22,
105.7, 105.4, 105.0 (×2), 104.4, 61.5, 61.4, 56.08, 56.06, 55.92, 55.90,
55.82, 55.80, 54.80, 54.77, 53.6, 52.8, 36.7, 36.5, 26.9, 26.8, 17.4, 16.9,
14.43, 14.41, 11.1, 10.7. HR-MS (MALDI-FTMS+): m/z 956.4460
[M+], calcd for C56H64N2O12 956.4454; mp (mixture of isomers) 92−
97 °C.
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Nonell, S. Org. Lett. 2009, 11, 77.
(8) Mysl
́
iwiec, D.; Donnio, B.; Chmielewski, P. J.; Heinrich, B.;
Stępien
́
, M. J. Am. Chem. Soc. 2012, 134, 4822−4833.
ASSOCIATED CONTENT
* Supporting Information
■
(9) The IUPAC name of this ring system is 1,1′-bidibenzo[e,g]
S
isoindole.
(10) Chai, J. D.; Head-Gordon, M. Phys. Chem. Chem. Phys. 2008, 10,
6615.
NMR and MS spectra, spectral assignments, X-ray tables,
HPLC chromatograms, computational data, and Cartesian
coordinates. This material is available free of charge via the
Internet at http://pubs.acs.org.
(11) 2,2′-Bipyrroles typically require the presence of substituents in
positions 1,1′,3,3′ to achieve configurational stability. See: (a) Thir-
umalairajan, S.; Pearce, B. M.; Thompson, A. Chem. Commun. 2010,
46, 1797−1812. (b) Gribble, G. W.; Blank, D. H.; Jasinski, J. P. Chem.
Commun. 1999, 2195. (c) Blank, D. H.; Gribble, G. W.; Schneekloth, J.
S.; Jasinski, J. P. J. Chem. Cryst. 2002, 32, 541−546. (d) Skowronek, P.;
Lightner, D. A. Monatsh. Chem. 2003, 134, 889−899 In ref 11d, the
enantiomers were not separated.
AUTHOR INFORMATION
Corresponding Author
*E-mail: marcin.stepien@chem.uni.wroc.pl.
■
Notes
(12) Dreuw, A.; Head-Gordon, M. Chem. Rev. 2005, 105, 4009−
4037.
The authors declare no competing financial interest.
(13) Che, C.-M.; Wan, C.-W.; Lin, W.-Z.; Yu, W.-Y.; Zhou, Z.-Y.; Lai,
W.-Y.; Lee, S.-T. Chem. Commun. 2001, 721−722.
(14) For the performance of ωB97XD in TD-DFT calculations, see:
(a) Rohrdanz, M. A.; Martins, K. M.; Herbert, J. M. J. Chem. Phys.
ACKNOWLEDGMENTS
■
Financial support from the National Science Center (Grant No.
N204 199340) is kindly acknowledged. Quantum chemical
calculations were performed in the Wrocław Center for
Networking and Supercomputing. We thank Piotr Stefanowicz
and Mirosław Karbowiak for technical assistance with mass
spectrometry and fluorescence measurements.
̀
2009, 130, 054112. (b) Jacquemin, D.; Perpete, E. A.; Ciofini, I.;
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