Improved synthesis of functionalized 2,2′-bipyrroles

Article abstract of DOI:10.1021/jo701310k

(Chemical Equation Presented) A series of 2,2′-bipyrroles has been efficiently synthesized using an improved synthetic approach based on Pd(0-catalyzed homocoupling of various 2-iodopyrroles. This new synthetic approach takes place at room temperature and

Full text of DOI:10.1021/jo701310k

couplings,3-4,7 usually the Ullmann reaction, are the most widely
used for access to 2,2′-bipyrroles. Due to the drastic conditions
of the Ullmann coupling reaction, sensitive substituents (such
as formyl groups), cannot be carried through intact; thus, direct
access to compound 1 is not possible. Since the original
preparation of compounds of type 1 by Vogel and co-workers2
during their synthesis of porphycene 2, only a few variants of
the seminal synthetic methodology have been described.3,7 All
except one8 are based on the Ullmann-type dimerization of a
preformed halopyrrole (Scheme 1).
Improved Synthesis of Functionalized
2,2′-Bipyrroles
Lijuan Jiao, Erhong Hao, M. Grac¸a H. Vicente, and
Kevin M. Smith*
Department of Chemistry, Louisiana State UniVersity,
Baton Rouge, Louisiana 70803
kmsmith@lsu.edu
Synthesis of 1, as reviewed in detail in the literature,8
normally requires four key steps: (1) Ullmann coupling of a
2-iodopyrrole-5-carboxylic ester, (2) hydrolysis of the diester,
(3) decarboxylation of the resulting 5,5′-dicarboxylic acid, and
(4) Vilsmeier-type diformylation. The Ullmann synthesis of
biaryls by the copper-induced reductive coupling of aromatic
halides is of broad synthetic use.9a Although some substrates
will undergo Ullmann reductive coupling under mild conditions,
the typical Ullmann coupling is conducted at high temperature.9b
Ullmann-type reductive couplings of pyrroles are best when
there is one or more electron-withdrawing group present; high
temperature is usually required.9b
Recently, Liebeskind and co-workers reported an ambient-
temperature Ullmann-type coupling reaction,9c but the require-
ment of specific type of substrates or specific positions of the
substituent limits its synthetic application. They stated that the
“most noticeable limitation of this process is the lack of reaction
of aromatic halide substrates not possessing a coordinating ortho-
substituent”.9c Sessler et al.7a developed an efficient procedure
for the preparation of alkyl-substituted 2,2′-bipyrroles by
protection of the pyrrole nitrogen atom before an Ullmann-type
coupling reaction; this was followed by deprotection of the
resulting N-substituted 2,2′-bipyrroles. Vogel7b et al. later
improved the Sessler method by changing the solvent from DMF
to toluene. Since the nature of substituents on the pyrrole ring
greatly influences the performance of the literature reactions,
thus precluding the synthesis of some attractive target com-
pounds, the current number of compounds 1 is still very small.
The above synthetic limitations encouraged us to develop a
new expedited methodology for the synthesis of bipyrroles 1.
Inspired by the rapidly developing field of metal-catalyzed
coupling reactions, and especially some recently developed
palladium-catalyzed couplings of aryl halides under mild
ReceiVed June 19, 2007
A series of 2,2′-bipyrroles has been efficiently synthesized
using an improved synthetic approach based on Pd(0)-
catalyzed homocoupling of various 2-iodopyrroles. This new
synthetic approach takes place at room temperature and in
the presence of water. Functional groups such as formyl,
ester, and nitrile are able to survive these reaction conditions.
Solvents are found to play an important role in this reaction.
The 2,2′-bipyrrole motif occurs in a number of polypyrrole
pigments, many of which have attracted increasing attention in
coordination chemistry, medicinal chemistry, and material
science.1 5,5′-Diformyl-2,2′-bipyrroles 1 are key synthetic
precursors for porphycene 2,2,3 sapphyrin 3,4 and other expanded
porphyrin analogues.5 Available synthetic routes to 2,2′-bipyr-
roles are limited3-4,6-7 to oxidative coupling and reductive
coupling methodologies. Oxidative coupling6 works only in a
limited number of cases and often in low yield, so reductive
(1) (a) The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: San Diego, 2000; Vol 6. (b) Gale, P. A.;
Anzenbacher, P., Jr.; Sessler, J. L. Coord. Chem. ReV. 2001, 222, 57. (c)
Kleemann, A.; Engl, J.; Kutscher, B.; Reichert, D. Pharmaceutical
Substances: Synthesis, Patents, Applications, 4th ed.; Georg Thieme:
Stuttgart, 2001.
(2) (a) Vogel, E.; Kocher, M.; Schmickler, H.; Lex, J. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 257. (b) Sessler, J. L.; Weghorn, S. J. Expanded,
Contracted and Isomeric Porphyrins; Pergamon: New York, 1997.
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O. Angew. Chem., Int. Ed. Engl. 1987, 26, 928. (b) Nonell, S.; Bou, N.;
Borrell, J. I.; Teixido, J.; Villanueva, A.; Juarranz, A,; Canete, M.
Tetrahedron Lett. 1995, 36, 3405. (c) Gavalda, A.; Borrell, J. I.; Teixido,
J.; Nonell, S.; Arad, O.; Grau, R.; Canete, M.; Juarranz, A,; Villanueva,
A.; Stockert, J. C. J. Porphyrins Phthalocyanines 2001, 5, 846. (d) Richert,
C.; Wessels, J. W.; Muller, M.; Kisters, M.; Benninghaus, T.; Goetz, A. Z.
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Sato, H.; Murata, D.; Hisaeda, Y. J. Am. Chem. Soc. 2002, 124, 11226. (f)
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Chem. Soc. 1983, 105, 6429. (b) Broadhurst, M. J.; Grigg, R.; Johnson, A.
W. J. Chem. Soc., Perkin Trans. 1 1972, 2111. (c) Sessler, J. L.; Cyr, M.
J.; Lynch, V.; McGhee, E.; Ibers, J. A. J. Am. Chem. Soc. 1990, 112, 2810.
(d) Schevchuk, S. V.; Davis, J. M.; Sessler, J. L. Tetrahedron Lett. 2001,
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(5) (a) Sessler, J. L.; An, D.; Cho, W.-S.; Lynch, V. Angew. Chem., Int.
Ed. 2003, 42, 2278. (b) Setsune, J.-I.; Tsukajima, A.; Watanabe, J.
Tetrahedron Lett. 2006, 47, 1817. (c) Geier, G. R., III.; Grindrod, S. C. J.
Org. Chem. 2004, 69, 6404. (d) Decre´au, R. A.; Collman, J. P. Tetrahedron
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(6) (a) Ceacareanu, D. M.; Gerstenberger, M. R. C.; Haas, A. J.
Heterocycl. Chem. 1985, 22, 281. (b) Wasserman, H. H.; Petersen, A. K.;
Xia, M.; Wang, J. Tetrahedron Lett. 1999, 40, 7567. (c) Oda, K.; Sakai,
M.; Ohno, K.; Machida, M. Heterocycles 1999, 40, 277. (d) Dohi, T.;
Morimoto, K.; Maruyama, A.; Kita, Y. Org. Lett. 2006, 8, 2007.
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E.; Deponte, R. U.S. Patent, 5,756,724. (c) Skowronek, P.; Lightner, D. A.
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10.1021/jo701310k CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/21/2007
J. Org. Chem. 2007, 72, 8119-8122
8119

SCHEME 1. Previous Methodologies for the Synthesis of
SCHEME 2. New Synthetic Route to
5,5′-Diformyl-2,2′-bipyrroles 1
5,5′-Diformyl-2,2′-bipyrroles 1
TABLE 1. Reductive Coupling of 2-Iodopyrroles 4 Using 10%
Pd-C and Zn at Room Temperature in Toluene/Water (1:1)
Steps: a) oxidation; b) iodinative decarboxylation; c) Ullmann coupling;
d) de-esterification; e) decarboxylation; f) Vilsmeier diformylation.
conditions,10-11 we decided to try different metals (other than
copper) for homocoupling of iodopyrroles.
The use of palladium-catalyzed reductive couplings in
carbon-carbon bond-forming reactions has attracted consider-
able attention in modern synthetic organic chemistry.12a-e These
include the Stille,12b Suzuki,12c Heck,12d and Sonogashira12e
coupling reactions to name only a few. Early usage of Pd-C
as the catalyst for the Ullmann coupling, under phase-transfer
conditions, required refluxing at 100 °C, but the high temper-
ature for this reaction limits its application in the synthesis of
biaryls possessing functional groups.12
Recently, Pd-C co-catalyzed biaryl synthesis was reported
to take place at room temperature by simply adding water to
the reaction conditions.11 Meanwhile, 2-formyl-5-iodopyrroles
have been used in Sonogashira coupling reactions with TMS-
acetylene to build acetylenic and diacetylenic diformyl-dipyr-
roles.13 Encouraged by these results, we selected Pd-C as our
catalyst and a mixture of organic solvents, along with water as
a co-solvent. Though our procedure can be applied to the
synthesis of all commonly available 5,5′-disubstituted 2,2′-
bipyrroles from the corresponding 5-substituted 2-iodopyrroles,14
we chose to demonstrate the approach using 5-formyl-2-
iodopyrroles 4 because they are easily available, and if our
scheme was successful, could form bipyrroles 1, critically
important for porphycene synthesis, in one step.
After attempting several coupling systems, we settled on
Pd-C with zinc as a suitable catalyst for the homocoupling of
compound 4 at room temperature; the aldehyde group on the
pyrrole ring was able to survive these conditions. We also
discovered that toluene/water is a better solvent system than
acetone/water.
Our overall synthesis of 2,2′-bipyrroles from readily available
2-iodopyrroles 4a-e is shown in Scheme 2. In our synthetic
approach, the homocoupling reactions of 2-iodopyrroles to
generate 2,2′-bipyrroles were performed in the solvent mixture
of toluene/water (1:1) at room temperature under argon, with a
combination of Pd-C and activated zinc metal as the catalyst.
The reaction was easily followed using TLC since the target
bipyrroles display characteristic blue fluorescence under ultra-
violet (366 nm) light. The yields of this coupling reaction were
moderate, as shown in Table 1, and the aldehyde group was
able to survive these mild reaction conditions. As usual in these
coupling reactions, the major byproduct was the protiodehalo-
genated compound.
(10) (a) Hassan, J.; Sevigon, M.; Gozzi, C.; Schultz, E.; Lemaire, M.
Chem. ReV. 2002, 102, 1359. (b) Shezad, N.; Clifford, A. A.; Rayner, C.
M. Green Chem. 2002, 4, 64.
(11) (a) Venkatraman, S.; Li, C.-J. Org. Lett. 1999, 1, 1133. (b)
Venkatraman, S.; Li, C.-J. Tetrahedron Lett. 2000, 41, 4831.
(12) (a) Trost, B. M. Acc. Chem. Res. 1990, 23, 34. (b) Stille, J. F. Angew.
Chem., Int. Ed. Engl. 1986, 75, 508. (c) Miyaura, N.; Suzuki, A. Chem.
ReV. 1995, 95, 2457. (d) Heck, R. H. Acc. Chem. Res. 1979, 12, 146. (e)
Sonogashira, K. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.;
Pergamon; Oxford, 1991. (f) Bamfield, P.; Quan. P. M. Synthesis 1978,
537.
(13) Cho, D. H.; Lee, J. H.; Kim, B. H. J. Org. Chem. 1999, 64, 8048.
(14) (a) For example, using benzyl 2-iodo-3,4-dimethylpyrrole-5-car-
boxylate and Pd-C/Zn in acetone/water, dibenzyl 3,3′,4,4′-tetramethyl-2,2′-
bipyrrole-5,5′-dicarboxylate was obtained in 75% yield (Supporting Infor-
mation). This bipyrrole was previously obtained by oxidative coupling in
25% yield,14b and by Ullmann coupling in 57% yield.14c (b) Falk, H.; Flo¨dl,
H. Monatsh. Chem. 1988, 119, 247. (c) Grigg, R.; Johnson, A. W. J. Chem.
Soc. 1964, 3315.
It was noticed that substituting toluene with acetone caused
the yield of the protiodehalogenated product to increase. The
reason that the toluene/water system gave the best results may
be because toluene is able to stabilize the Pd-coupling inter-
mediate, for which there is precedent in the literature.15 Another
(15) Itahara, T. J. Org. Chem. 1985, 50, 5272.
8120 J. Org. Chem., Vol. 72, No. 21, 2007

SCHEME 3. Synthesis of 2-Formyl-5-iodopyrroles 4a,b,d
from Benzyl 2-Methylpyrrole-5-carboxylates 5a,b,d
SCHEME 4. Synthesis of 2-Formyl-5-iodopyrrole 4c from
Benzyl Pyrrole-5-carboxylate 5c
Reagents: a) CAN, HOAc, THF-H2O; b) Pd-C, H2, THF; c) I2, KI,
NaHCO3, C2H4Cl2-H2O.
Reagents: a) POCl3, DMF, CH2Cl2, AcONa; b) Pd-C, H2, THF; c) I2,
KI, NaHCO3, C2H4Cl2-H2O.
issue worth mentioning is that water plays an important role in
this reaction:16 first, it increased the reaction rate compared with
the anhydrous system, and second, we believe it allows the
reaction to be performed at room temperature. Under anhydrous
conditions, when acetone or toluene was used as the solvent,
no reaction occurred and all the starting materials were recovered
after periods up to 4 days.
SCHEME 5. Synthesis of 2-Formyl-5-iodopyrrole 4e from
Ethyl 2-Methylpyrrole-5-carboxylate 5e
The key starting materials, 2-formyl-5-iodopyrroles 4a-e are
very easy to generate in three steps from the corresponding
2-methylpyrrole in high yields (as shown in Scheme 3),
involving (1) regioselective oxidation of the R-methyl group
of pyrrole 517 using ceric ammonium nitrate18 to give pyrrole
6;18 (2) catalytic debenzylation of the esters using Pd-C in THF
under H2 to give pyrrole 7, and (3) direct iodination to generate
pyrrole 4. An alternative method was used to prepare pyrrole
6c from 5c17g through a Vilsmeier reaction (92% yield) as shown
in Scheme 4. As for ethyl ester 4e in Scheme 5, effective
hydrolysis with LiOH in THF without aldehyde protection was
achieved in >90% yield according to a literature procedure.13
The yield in each step is very high, and there is normally no
need for chromatography. The overall yield for the three steps
is generally higher than 65%.
The photophysical properties of 5,5′-dialdehyde-2,2′-bipyr-
roles 1 are summarized in Table 2. As previously observed with
certain 2,2′-bipyrroles20 (and even with arylpyrroles),21 all the
functionalized bipyrroles shown in Table 2 are highly lumines-
cent materials at room temperature. Their absorptions occur
between 231 and 401 nm, and they are strongly luminous at
∼410 nm. We observed large Stokes shifts for most of the
Reagents: a) CAN, HOAc, THF-H2O; b) LiOH, THF; c) I2, KI,
NaHCO3, C2H4Cl2-H2O.
TABLE 2. Photophysical Data for 5,5′-Diformyl-2,2′-bipyrroles 1
in CH2Cl2 at Room Temperature
absorption λmax
nm (log ꢀ)
emissiona
fluorescenceb
quantum yield
Stokes
shift (nm)
cmpd
λ
max (nm)
1a
233 (4.08),
280 (3.90),
363 (4.32)
232 (4.21),
268 (4.00),
361 (4.41)
235 (4.27),
382 (4.59),
401 (4.58)
232 (4.04),
262 (3.82),
356 (4.24)
231 (3.79),
275 (3.64),
361 (4.05)
410
0.356
0.321
0.411
0.326
0.320
37
49
14
52
49
1b
1c
1d
1e
410
415
408
410
(16) (a) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H.
C.; Sharpless, K. B. Angew. Chem., Int. Ed. 2005, 44, 3275. (b) Hayashi,
Y. Angew. Chem., Int. Ed. 2006, 45, 8103. (c) Li, C.-J. Chem. ReV. 2005,
105, 3095.
(17) (a) Kleinspehn, G. G. J. Am. Chem. Soc., 1955, 77, 1546. (b) John,
K. D.; Pearce, W. A.; Pyke, S. M. J. Porphyrins Phthalocyanines 2002, 6,
661. (c) Takaya, H.; Kojima, S.; Murahashi, S. -I. Org. Lett. 2001, 3, 421.
(d) Smith, K. M.; Martynenko, Z.; Pandey. R. K.; Tabba, H. D. J. Org.
Chem. 1983, 48, 4296. (e) Smith, K. M.; Milgrom, L. R.; Kenner, G. W.
J. Chem. Soc., Perkin Trans. 1 1981, 2065. (f) Smith, K. M.; Pandey, R.
K. J. Chem. Soc., Perkin Trans. 1 1987, 1229. (g) Smith, K. M.; Minnetian,
O. M. J. Org. Chem. 1985, 50, 2073.
(18) Thyrann, T.; Lightner, D. A. Tetrahedron Lett. 1995, 36, 4345.
(19) (a) Tu, B.; Lightner, D. A. J. Heterocycl. Chem. 2003, 40, 707. (b)
Jacobi, P. A.; Pippin, D. Org. Lett. 2001, 3, 827.
(20) 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.
a Excitation at 350 nm. b Calculated using quinine sulfate 5% H2SO4
solution as the standard.
bipyrroles, between 37 and 52 nm, except for bipyrrole 1c,
which has a Stokes shift of 14 nm and a strong red-shifted long
wavelength absorption band compared with the other bipyrroles.
Bipyrrole 1c was also found to have the largest quantum yield
of all the bipyrroles studied. Since these bipyrroles are blue
luminous materials, they may find application in the material
science area as blue-light-emitting devices.
(21) Kuo, W.-J.; Chen, Y.-H.; Jeng, R.-J.; Chan, L.-H.; Lin, W.-P.; Yang,
Z.-M. Tetrahedron 2007, 63, 7086.
J. Org. Chem, Vol. 72, No. 21, 2007 8121

6H), 1.56-1.10 (m, 6H). 13C NMR (250 MHz, CDCl3) ppm 177.8,
135.9, 128.9, 128.2, 119.2, 16.9, 16.1, 9.3. HRMS (ESI) Calcd for
C16H21N2O2 [M + H]+: 273.1597. Found: 273.1601.
In summary, we have developed an improved general
methodology for the synthesis of 2,2′-bipyrroles, and more
specifically, of 5,5′-diformyl-2,2′-bipyrroles 1; the formyl group
was our benign functionality because of the importance of
diformylbipyrroles in the synthesis of porphycene and related
macrocycles.2 This improved synthetic method uses Pd-C and
activated metallic zinc as the catalysts, and the presence of water
in the reaction system is critically important. These mild reaction
conditions allow functional groups such as formyl, ester, and
nitrile to be carried through the sequence intact. By using this
improved route, six 5,5′-diformyl-2,2′-bipyrroles 1 were syn-
thesized in four steps each from commonly available monopy-
rroles. The bipyrroles are strongly luminescent, and the new
approach should provide a ready access to new materials for
light-emitting devices.
5,5′-Diformyl-4,4′-bis(2-methoxycarbonylethyl)-3,3′-dimethyl-
2,2′-bipyrrole 1b. After separation by use of the silica gel column,
the title compound was obtained as a white solid in 54% yield (52.4
1
mg). mp >330 °C (dec). H NMR (250 MHz, DMSO-d6) δ 11.7
(s, 2H), 9.60(s, 2H), 3.57 (s, 6H), 3.00-2.95 (m, 4H), 2.58-2.48
(m, 4H), 1.93 (s, 6H). 13C NMR (250 MHz, CDCl3) δ 178.3, 172.6,
131.7, 129.3, 127.8, 119.7, 51.3, 34.5, 19.2, 9.3. Anal. Calcd for
C20H24N2O6‚0.5H2O: C, 60.47; H, 6.34; N, 7.05. Found: C, 60.6;
H, 6.1; N, 6.9. HRMS (ESI) Calcd for C20H25N2O6[M + H]+:
389.1707. Found: 389.1707.
3:4,3′:4′-Bisbutano-5,5′-diformyl-2,2′-bipyrrole 1c. After sepa-
ration by use of the silica gel column, the title compound was
obtained as a white solid in 41% yield (30.3 mg). mp >310 °C
1
(dec). H NMR (300 MHz, DMSO-d6) δ 11.50 (s, 2H), 9.54 (s,
2H), 2.80 (m, 4H), 2.50 (m, 4H), 1.67 (br, 8H). 13C NMR (250
MHz, DMSO-d6) δ 177.3, 128.4 (2C), 126.9, 121.6, 22.9, 22.4,
21.8, 21.2. Anal. Calcd for C18H20N2O2‚H2O: C, 68.77; H, 7.05;
N, 8.91. Found: C, 69.1; H, 6.7; N, 8.6. HRMS (ESI) Calcd for
C18H21N2O2 [M + H]+: 297.1597. Found: 297.1605.
Experimental Section
General Procedure for the Reductive Coupling of 4. Activated
zinc was obtained by washing zinc dust with 3 M HCl, then filtering
through filter paper, washing successively with water, ethanol, and
diethyl ether, and then drying under vacuum. The following
describes the reductive coupling of 4a as a representative example
of the procedure for synthesis of 5,5′-diformyl-2,2′-bipyrroles 1.
A mixture of Pd-C (10.0 mg, 10%) and activated zinc dust (100
mg, 1.5 mmol) was placed in a dry 50 mL round-bottom flask.
After being evacuated, the flask was filled with argon. Then, 4 mL
of toluene/water (1:1) was added and the mixture was stirred at
room temperature under argon for 15 min. 2-Iodopyrrole (132 mg,
0.5 mmol) in 8 mL of toluene was added through a syringe. Finally,
8 mL of distilled water was added and the mixture was stirred
vigorously at room temperature under argon. The reaction was
usually complete within 24 h. [Using TLC to follow reaction
progress, all of the five 5,5′-diformyl-2,2′-bipyrroles 1 display a
characteristic blue fluorescence under UV irradiation (around 366
nm) on silica gel TLC plates. Their CH2Cl2, acetone, DMSO, and
THF solutions also show strong blue luminescence under the same
wavelength illumination at ambient conditions, unlike the starting
material monopyrroles 4]. The reaction was stopped when all
starting material was used up (TLC); CH2Cl2 (40 mL) was added
to the mixture and it was sonicated to form two layers. After the
water layer was removed, the remaining solution was filtered
through Celite which was washed three times with CH2Cl2 (100
mL). The organic solvents were collected and dried over anhydrous
Na2SO4 before evaporation under vacuum. The pure target com-
pounds were separated using a silica gel column eluted with EtOAc/
hexane (1:2). Further purification can be performed by recrystal-
lization from CH2Cl2/hexane or from ethanol.
4,4′-Bis(2-cyanoethyl)-5,5′-diformyl-3,3′-dimethyl-2,2′-bipyr-
role 1d. After separation by use of the silica gel column, the title
compound was obtained as a white solid in 26% yield (20.9 mg).
1
mp >330 °C (dec). H NMR (250 MHz, acetone-d6) δ 9.71 (s,
2H), 9.65 (s, 2H), 3.18-3.12 (m, 4H), 2.71-2.65 (m, 4H), 2.18
(s, 6H). 13C NMR (250 MHz, acetone-d6) δ 178.9, 131.0, 130.7,
128.3, 121.4, 120.2, 20.8, 19.0, 9.7. Anal. Calcd for C18H18N4O2‚
0.25H2O: C, 66.18; H, 5.70; N, 17.15. Found: C, 66.4; H, 5.3; N,
17.4. HRMS (ESI) Calcd for C18H19N4O2 [M + H]+: 323.1502.
Found: 323.1504.
5,5′-Diformyl-3,3′,4,4′-tetramethyl-2,2′-bipyrrole 1e.4a After
separation by use of the silica gel column, the title compound was
obtained as a white solid in 40% yield (24.4 mg). mp >307 °C
1
(dec) [lit4a mp 305-307 °C (dec)]. H NMR (250 MHz, DMSO-
d6) δ 11.66 (s, 2H), 9.61 (s, 2H), 2.25 (s, 6H), 1.91 (s, 6H). 13C
NMR (250 MHz, DMSO-d6) δ 177.9, 129.5 (2C), 128.1, 119.9,
9.4, 9.0. HRMS (ESI) Calcd for C14H17N2O2 [M + H]+: 245.1284.
Found: 245.1289.
Acknowledgment. This work was supported by the National
Science Foundation, Grants No. CHE-304833 and CHE-
0296012.
Supporting Information Available: Synthetic procedures for
compounds 6a-d, 4a-d, and dibenzyl 3,3′,4,4′-tetramethyl-2,2′-
bipyrrole-5,5′-dicarboxylate, spectroscopic characterization and 1H
NMR/13C NMR spectra of compounds 1a-e, 6a-d, 4a-d, and
dibenzyl 3,3′,4,4′-tetramethyl-2,2′-bipyrrole-5,5′-dicarboxylate; ESI
HRMS spectra for compounds 1a-e, 4c, 4d, and dibenzyl 3,3′,4,4′-
tetramethyl-2,2′-bipyrrole-5,5′-dicarboxylate. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
3,3′-Diethyl-5,5-diformyl-4,4′-dimethyl-2,2′-bipyrrole 1a.4c Af-
ter the silica gel column was used for the separation, the title
compound was obtained as a white solid in 35% yield (23.7 mg,
35%). mp 240-242 °C (lit4c mp 241-242 °C). 1H NMR (250 MHz,
CDCl3) δ11.71(s, 2H), 9.61 (s, 2H), 2.74-2.71 (m, 4H), 1.95 (s,
JO701310K
8122 J. Org. Chem., Vol. 72, No. 21, 2007