One-pot synthesis of substituted 2,2'-bipyrroles. A straightforward route to aryl porphycenes

Article abstract of DOI:10.1021/ol802380g

A one-pot reaction for the synthesis of 4,4'-diaryl-and 4,4'-diheteroaryl-substituted 2,2'-bipyrroles is described. The new methodology is based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2'-

Full text of DOI:10.1021/ol802380g

ORGANIC
LETTERS
2009
Vol. 11, No. 1
77-79
One-Pot Synthesis of Substituted
2,2′-Bipyrroles. A Straightforward Route
to Aryl Porphycenes†
David Sánchez-García,* Jose´ I. Borrell, and Santi Nonell
Grup d’Enginyeria Molecular, Institut Qu´ımic de Sarria`, UniVersitat Ramon Llull,
Via Augusta, 390, E-08017 Barcelona, Spain
daVid.sanchez@iqs.edu
Received October 15, 2008
ABSTRACT
A one-pot reaction for the synthesis of 4,4′-diaryl- and 4,4′-diheteroaryl-substituted 2,2′-bipyrroles is described. The new methodology is
based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2′-bipyrroles can be used
as precursors in a expeditious synthesis of 2,7,12,17-tetraaryl-porphycenes.
The first investigations devoted to 2,2′-bipyrroles1 were
motivated by their presence as structural subunits in impor-
tant naturally occurring compounds such as prodigiosin2 and
vitamin B12.3 However, it is in the field of conducting
polymers,4 especially in the field of synthetic porphyrinoids,5
where 2,2′-bipyrroles have found their main applications. The
syntheses of isomeric and expanded forms of porphyins, such
as porphycenes,6 sapphyrins,7 and cyclopyrroles,8 are some
remarkable achievements in this area based on the use of
2,2′-bipyrroles as starting materials.
These porphyrinoids are endowed with properties of great
interest in a variety of fields ranging from sensors for
explosives9 to biomedicine.10 Nevertheless, the practical
application of these compounds is predicated on the easy
availability of substituted 2,2′-bipyrroles bearing groups able
to modify the behavior of the parent macrocycle, namely,
solubility or optical properties.
Unfortunately, present general methods to obtain 2,2′-
bipyrroles1,11,12 are usually limited since long syntheses are
involved. Besides, the introduction of diversity in positions
4 and 4′ is challenging.13
To reduce the number of synthetic steps, a strategy based
on an oxidative dimerization is most convenient since the
only requirement is one free R position in the starting pyrrole.
This kind of coupling has been applied successfully in the
construction of oligopyrroles14 and macrocycles.8
However, in the case of 4,4′-disubstituted-2,2′-bipyrroles
the application of this methodology is more complex because
the coupling must be carried out in a regioselective fash-
ion.15-17 In this regard, Waluk and co-workers have recently
prepared a tosyl-protected 4,4′-di-tert-butyl-2,2′-bipyrrole by
metalation of 3-tert-butyl-1-tosyl-1H-pyrrole with BuLi
followed by exposure to CuCl2.18
† Dedicated to Professor Emanuel Vogel on the occasion of his 80th
birthday.
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L. F. J.; Smith, E. L.; Todd, A. J. Chem. Soc. 1957, 1158.
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Schiavon, G.; Gatti, C.; Frigerio, G. Chem. Mater. 2000, 12, 1480–1489.
(5) Sessler, J. L.; Weghorn, S. J. Expanded, Contracted, and Isomeric
Porphyrins; Elsevier: Oxford, 1997.
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Soc. 1983, 105, 6429–6436.
Because the use of protecting groups implies the addition
of two extra steps, using a less reactive metal could make
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10.1021/ol802380g CCC: $40.75
Published on Web 12/03/2008
2009 American Chemical Society

Scheme 1. Synthetic Pathway of Porphycene 6
protecting groups unnecessary. Our first choice was tin,
tion, a variety of cinnamic esters were tested (Table 1).
Substituted bipyrroles were obtained with yields consistent
to those reported for the two processes (roughly 70-50%
for pyrrole formation and 50% for oxidative coupling of
related heterocycles).19,20
because stannanes have been used in C-C bound formation
and oxidative dimerizations. In fact, phenyl-2-trimethylstan-
nyl-pyrroles were obtained in 1998 by van Leusen and co-
workers in a single reaction.19
According to that report, when tosylmethyl isocyanide
(TosMIC) is reacted with 2 equiv of BuLi, a dilithiated
species is formed. It is now found that the sequential
exposure of this intermediate to an excess of Me3SnCl and
then to a variety of Michael acceptors provides selectively
2-(trimethylstannyl)pyrroles 2 with yields ranging from 40%
to 90% (Figure 1).
Table 1. Substrate Scope of the Synthesis of 2,2′-Bipyrroles
Figure 1. One-pot synthesis of 2,2′-bypirroles.
For preliminary studies, commercially available ethyl
cinnamate (1a, R ) Ph) was used, and the reaction was
conducted following the original procedure. Remarkably, the
crude material, after extraction and filtration through a short
pad of alumina, provided an almost pure pyrrole 2a (R )
Ph). This result prompted us to attempt the oxidative
dimerization without further purification of the starting
pyrrole. For this propose and following the methodology
reported by Quayle and co-workers,20 1 equiv of pyrrole 2a
was treated with an excess of Cu(NO3)2·3H2O in THF at
room temperature. To our delight, the starting material was
consumed in 30 min, and a bright fluorescent nonpolar spot
appeared on TLC, which was identified as the corresponding
2,2′-bipyrrole 3a.
At this juncture we decided to investigate the possibility
to combine these two separate processes into a one-pot
reaction. As expected, the reaction proceeded similarly and
gave bipyrrole 3a without significant losses of yield. To
assess the substrate scope of this one-pot-two-process reac-
It is noteworthy that although the crude reaction gave
a complex mixture, bipyrroles could be easily isolated
without chromatography by elimination of the copper salts
with diluted ammonia and subsequent precipitation with
ethyl acetate. In all of the studied examples the precipitate
78
Org. Lett., Vol. 11, No. 1, 2009

gave satisfactory analytical data. Additional structural
evidence for bypyrrole 3h was provided by X-ray dif-
fraction (Figure 2).
as a target porphycene. As anticipated the saponification and
decarboxylation of bipyrrole 3c proceeded smoothly and
provided the required free bipyrrole. Vilsmeier-Haack
formylation followed by McMurry coupling furnished por-
phycene 6 (R ) C6H4CH2OMe) in only four steps from
starting materials.21 This new synthesis of bipyrroles thus
gives access to 2,7,12,17-tetraaryl-porphycenes with a re-
markable reduction in the number of steps (8 steps are
necessary to prepare 2,7,12,17-tetraphenyl-porphycene by
earlier methods).23
To conclude, a concise one-pot method to obtain 4,4′-
substituted bipyrroles has been developed. This procedure
provides aryl- and heteroaryl-2,2′-bipyrroles with no need
of chromatographic purification on a multigram scale. These
compounds are the most suitable starting materials for the
synthesis of porphycenes.
Acknowledgment. We thank Dr. Brice Kauffmann (IECB,
France) for obtaining X-ray crystallographic data. Financial
support by the Spanish MCyT is gratefully acknowledged
(grant no. CTQ2007-67763-C03-01/BQU).
Supporting Information Available: Detailed synthetic
procedures and spectroscopic characterization of compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 2. X-ray structure of bipyrrole 3h.
With these bipyrroles in hand we devised a new shortened
synthesis of porphycenes.21,22 With this aim, 6 was selected
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