to the porphyrin ꢀ,ꢀ′-positions via the Heck reaction in
order to subsequently attempt 6-π electrocyclization6 and
then aromatization as an entry to functionalized fused
benzene rings.
Scheme 1
Symmetrical tetrabenzoporphyrins were first synthesized
by condensing highly reactive isoindoles7 or by condens-
ing phthalimides with CH-acid compounds at high tem-
perature (300-400 °C). Fairly complex mixtures of
benzoporphyrins were obtained and required laborious
purifications.8 More versatile approaches relied on tradi-
tional acid-catalyzed condensation of dihydroisoindoles
and aldehydes followed by an aromatization step. Bicyclo-
octadiene-fused pyrrole or tetrahydroisoindole gave por-
phyrins that were aromatized to tetrabenzoporphyrins by
a thermal retro-Diels-Alder reaction9 or an oxidative
dehydrogenation with DDQ, respectively.10 Benzopor-
phyrins can also be obtained from ꢀ-functionalized
porphyrins: via olefin ring-closure metathesis11 or via
Diels-Alder reactions on vinylporphyrins,12 pyrrolo[3,4-
b]-porphyrins,13 or sulfolenoporphyrins.14
One drawback of most methods is the lack of functional
groups introduced at the fused aromatic rings. Availability
of regioselectively ꢀ-brominated porphyrins15 and of a
large variety of substituted alkenes led us to investigate
the Heck reaction, which has been previously described
with monobromoporphyrins.16 As shown in Scheme 1, we
(7) Remy, D. E. Tetrahedron Lett. 1983, 24, 1451–1454.
(8) Filatov, M. A.; Cheprakov, A. V.; Beletskaya, I. P. Eur. J. Org.
Chem. 2007, 3468–3475. (b) Bender, C. O.; Bonnett, R.; Smith, R. G.
J. Chem. Soc., Chem. Commun. 1969, 345. (c) Bender, C. O.; Bonnett, R.;
Smith, R. G. J. Chem. Soc. C 1970, 1251.
(9) (a) Ito, S.; Murashima, T.; Uno, H.; Ono, N. Chem. Commun. 1998,
1661–1662. (b) Ono, N.; Hironaga, H.; Ono, K.; Kaneko, S.; Murashima,
T.; Ueda, T.; Tsukamura, C.; Ogawa, T. J. Chem. Soc., Perkin Trans. 1
1996, 417–423.
(10) (a) Filatov, M. A.; Lebedev, A. Y.; Vinogradov, S. A.; Cheprakov,
A. V. J. Org. Chem. 2008, 73, 4175–4185. (b) Finikova, O. S.; Cheprakov,
A. V.; Beletskaya, I. P.; Carroll, P. J.; Vinogradov, S. A. J. Org. Chem.
2004, 69, 522–535. (c) Finikova, O. S.; Cheprakov, A. V.; Carroll, P. J.;
Vinogradov, S. A. J. Org. Chem. 2003, 68, 7517–7520. (d) Vicente,
M. G. H.; Tome, A. C.; Walter, A.; Cavaleiro, J. A. S. Tetrahedron Lett.
1997, 38, 3639–3642. (e) Vicente, M. G. H.; Jaquinod, L.; Khoury, R. G.;
Madrona, A. Y.; Smith, K. M. Tetrahedron Lett. 1999, 40, 8763–8766. (f)
Gottumukkala, V.; Ongayi, O.; Baker, D. G.; Lomax, L. G.; Vicente,
M. G. H. Bioorg. Med. Chem. Lett. 2006, 14, 1871–1879. (g) Ongayi, O.;
Gottumukkala, V.; Fronczek, F. R.; Vicente, M. G. H. Bioorg. Med. Chem.
Lett. 2005, 15, 1665–1668.
attempted a tetra-fold Heck coupling of 2,3,12,13-tetra-
bromoporphyrin 3 and 415a with excess of methyl acrylate
in the presence of in situ generated Pd0 catalyst at 128 °C
for 3 days under strict air-free conditions. opp-Diben-
zoporphyrin 7 and 8 were obtained in 55% and 60% yield,
respectively. The direct Heck products (A) were not
isolated. When the Heck reaction was carried out at lower
temperature, e.g., 110 °C, or for shorter reaction times (1
day), a complex mixture resulted with complete consump-
(11) Jiao, L. J.; Hao, E. H.; Fronczek, F. R.; Vicente, M. G. H.; Smith,
K. M. Chem. Commun. 2006, 3900–3902.
1
tion of the starting porphyrins. H NMR of the mixture
(12) (a) Morgan, A. R.; Pangka, V. S.; Dolphin, D. J. Chem. Soc., Chem.
Commun. 1984, 1047–1048. (b) Silva, A. M. G.; de Oliveira, K. T.; Faustino,
M. A. F.; Neves, M.; Tome, A. C.; Silva, A. M. S.; Cavaleiro, J. A. S.;
Brandao, P.; Felix, V. Eur. J. Org. Chem. 2008, 704–712.
showed olefinic doublets in the range of 4-6 ppm
indicating that the Heck reaction occurred, but the ring
closure was not complete.
(13) Vicente, M. G. H.; Jaquinod, L.; Khoury, R. G.; Madrona, A. Y.;
Smith, K. M. Tetrahedron Lett. 1999, 40, 8763–8766.
1H NMR of 7 (see Supporting Information) displays a
singlet at 7.40 ppm assigned to the fused benzene protons.
The one-pot formation of 7 was further confirmed by
MALDI-TOF (m/z, 1114.45) and the resolution of an X-ray
crystal structure (Figure 1). Due to the fusion of the two
benzene rings to the porphyrin macrocycle through ꢀ,ꢀ′-
positions and crowding on the porphyrin periphery, the
porphyrin core is deviated from planarity and assumes a
saddle-type conformation, similar to that found in other fused
benzoporphyrins.2
(14) (a) Lee, S. H.; Smith, K. M. Tetrahedron Lett. 2005, 46, 2009–
2013. (b) Vincente, M. G. H.; Tome, A. C.; Walter, A.; Cavaleiro, J. A. S.
Tetrahedron Lett. 1997, 38, 3639–3642.
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Jayaraj, K.; Austin, R. N.; Gold, A.; White, P. S.; Brigaud, O.; Battioni,
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Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,R., Eds.;
Academic Press: San Diego, 2000; Vol. 1, pp 201-237.
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opp-Dibenzoporphyrins were obtained in two steps starting
from unfunctionalized free base tetraarylporphyrins. The
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