A novel and facile Zn-mediated intramolecular five-membered cyclization of β-tetraarylporphyrin radicals from β-bromotetraarylporphyrins

Article abstract of DOI:10.1039/b509972b

A novel and facile method for the Zn-mediated intramolecular cyclization of β-porphyrin radicals has been developed for the convenient and effective construction of newly fused five-membered porphyrin systems from readily available β-bromotetraarylporphyr

Full text of DOI:10.1039/b509972b

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
A novel and facile Zn-mediated intramolecular five-membered
cyclization of b-tetraarylporphyrin radicals from
b-bromotetraarylporphyrins{
Dong-Mei Shen, Chao Liu and Qing-Yun Chen*
Received (in Cambridge, UK) 14th July 2005, Accepted 22nd August 2005
First published as an Advance Article on the web 9th September 2005
DOI: 10.1039/b509972b
zinc (activated by washing with aqueous HCl)9 in DMSO at 60 uC
A novel and facile method for the Zn-mediated intramolecular
cyclization of b-porphyrin radicals has been developed for the
convenient and effective construction of newly fused five-
membered porphyrin systems from readily available b-bromo-
tetraarylporphyrins.
for 30 min. It was found that the starting material was consumed
completely and two new products were yielded. To our surprise,
no porphyrin–Zn reagent was obtained. According to spectral
analysis, one was a hydrogenated product ZnTPP (Zn3a), the
other an intramolecular cyclization product Zn2a, whose mass
spectrometry indicated the expected mass ion with loss of the
bromine atom and whose NMR spectrum revealed significant loss
of symmetry as shown by an increase in the number of signals for
the b-hydrogens, as opposed to the normal one singlet pattern
found for tetraarylporphyrins. As expected, due to the variation of
the conformation and conjugate pathway by the formation of the
newly fused five-membered ring, the Uv-visible spectrum exhibited
a much larger bathochromic shift and broadening of the Soret
band (Fig. 1).10
Porphyrins, by the nature of their electronic and redox properties,
play a key role in many fields, such as oxygen activation and
transfer, electron transfer, binding or transport of small molecules,
light harvesting, and photosynthesis.1 Secondary ring systems
fused onto the macrocyclic core are of interest owing to their
special optical, coordination and redox properties. So far, synthetic
routes for these compounds mainly include the intermolecular
reactions of an exocyclic double bond of the porphyrin in Diels–
Alder reactions,2 1,3-dipolar cycloadditions3 and carbene addi-
tions,4 and the intramolecular reactions of functional groups on a
porphyrin b-position attacking the ortho-carbon of a phenyl ring
on the adjacent meso-position and the inverse reaction between an
ortho-functionalized meso-phenyl and unsubstituted b-position.5
Because of the existence of functional groups such as formyl, aryl
chloride groups, alkyl or nitro groups, a newly fused six-membered
ring was usually formed. However, a palladium(0)-catalyzed intra-
molecular coupling on ortho-iodinated meso-phenyl porphyrins to
form five-membered fused porphyrins has been recently reported.6
But this method suffered from a lack of easy availability of
the starting materials. Very recently, we also discovered a facile
synthesis of various meso-, b-perfluoroalkylated porphyrins as
well as five-, six-, seven-, and eight-membered fluorinated fused
porphyrins through b-perfluoroalkyl porphyrin radicals.7 Here, as
a part of our study toward porphyrin intramolecular cyclization
via a radical pathway, we wish to present a novel and facile
Zn-mediated intramolecular cyclization reaction of b-porphyrin
radicals for formation of newly fused five-membered porphyrin
systems.
With these encouraging results, various brominated porphyrins
H2TAP(Br) (1)11and H2TAP(Br)4 (4)12 for this reaction were then
prepared by the controlled bromination of 5,10,15,20-tetraaryl-
porphyrin (H2TAP) (3) with NBS via the free-base porphyrin
according to the literature procedure11,12(Scheme 1), after which
we turned our attention to modifying the reaction conditions for
the cyclization reaction. Systematic variation of amounts of Zn,
solvents and reaction temperatures revealed that the optimal
condition was 50 equiv. of Zn in DMSO (the most effective solvent
among the screened solvents DMSO, DMF, HMPA, CH3CN,
THF, benzene, ClCH2CH2Cl, dioxane) at 85 uC. The addition of
It is well known that organozinc reagents can be efficiently and
rapidly prepared from organic bromine compounds by using
activated metallic Zn.8 For generating porphyrin–Zn reagent, a
first attempt to activate ZnTPP(Br) (Zn1), a most readily available
brominated porphyrin, was carried out by treating it with metallic
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
200032, China. E-mail: Chenqy@mail.sioc.ac.cn;
Fax: (internat.) +86-21-64166128
{ Electronic supplementary information (ESI) available: experimental
details and NMR data and spectra for new compounds. See http://
dx.doi.org/10.1039/b509972b
Fig. 1 The Uv-visible spectrum of ZnTPP (Zn3a), mono-cyclization
porphyrin Zn2a and double-cyclization porphyrin Zn(6a+7a).
4982 | Chem. Commun., 2005, 4982–4984
This journal is ß The Royal Society of Chemistry 2005

View Article Online
Scheme 1 Synthesis of various brominated porphyrins.
Fig. 2 Two views of the X-ray crystal structure of double-cyclization
porphyrin Zn6a (phenyl groups, hydrogen atoms and the THF molecule
coordinated to the Zn center are omitted for clarity). Representative bond
more reactive metal zinc–copper couples8 instead of zinc
powder resulted in a poor yield of the cyclization product. The
fact that the reaction could be completely inhibited in the presence
of an electron-transfer scavenger, i.e., p-dinitrobenzene (p-DNB)
(20 mol%) or radical inhibitor, i.e., hydroquinone (HQ) (20 mol%)
indicated the radical nature of the reaction.
˚
lengths (A) and angles (u) are as follows: Zn–N1 1.954(3), Zn–N2 2.157(2),
Zn–N3 1.945(3), Zn–N4 2.086(3), C3–C22 1.466(4), C12–C32 1.472(4);
C3–C4–C5 112.4(3), C2–C1–C20 128.4(3), C10–C11–C12 113.1(3), C13–
C14–C15 128.4(3).
In order to explore the effect of the substituents on the
porphyrin meso-aryl groups, a series of substrates with diverse
steric and electronic properties were investigated. As illustrated in
Table 1, under the optimal conditions, various substrates could be
subjected to smooth cyclization reaction. The result that the
reactivity of a substrate with an electron-withdrawing group was
somewhat higher than that with an electron-donating group
can probably be ascribed to the nucleophilic properties of the
b-porphyrin radicals.13
When 2,3,12,13-tetrabromoporphyrin ZnTPP(Br)4 (Zn4a)12 was
used as a substrate under similar conditions, a red band and a
green band were obtained. Spectral analysis of the red band by
mass spectrometry, NMR spectroscopy and elemental analysis
indicated that it was a mixture of isomers Zn6a and Zn7a instead
of the expected product Zn5a, which could not be separated by the
usual flash column chromatography because of the virtually
identical Rf values. The isomers display complicated 1H NMR
signals, which cannot be clearly identified. The mass spectrum
gives the expected mass ion at m/z 672 (M+) with loss of the
bromine atoms. The Uv-visible spectrum for the isomers
demonstrated a large bathochromic shift and broadening of the
Soret band (Fig. 1). On the other hand, fortunately, one of the
single crystals of the double-cyclization isomers, Zn6a, was
obtained from THF solution of the isomers into which petroleum
ether was allowed to slowly diffuse. As illustrated in Fig. 2, the
X-ray structure{ of Zn6a reveals a Zn(II) porphyrin skeleton that
displays a mixture of the traditional ruffle/saddle distortions. The
bond lengths of Zn–N(1) and Zn–N(3) are notably shorter than
those of Zn–N(2) and Zn–N(4). Significant contractions of the
fused C(3)–C(4)–C(5) and C(10)–C(11)–C(12) bond angles are
also observed in comparisons of C(2)–C(1)–C(21) and C(13)–
C(14)–C(15). All these features might be the consequence of
carbon–carbon bond formation that locks the meso-phenyl groups
into the plane of the newly formed five-membered ring. When
using ZnT(p-Me)PP(Br)4 (Zn4b) and ZnT(p-MeO)PP(Br)4 (Zn4c)
as substrates under similar conditions, similar results were
obtained (Scheme 2).
Table 1 Zn-mediated intramolecular cyclization reaction of
b-ZnTAP radicalsa
The diversity and complexity of the reaction were further
indicated by demetalation of the mixture of the green band, which
Entry
Reactant
Zn1a
Time (min)
Product
Yield (%)b
1
2
3
4
a
10
20
30
5
Zn2a
Zn3a
Zn2b
Zn3b
Zn2c
Zn3c
Zn2d
Zn3d
30
62
23
71
20
72
35
58
Zn1b
Zn1c
Zn1d
Reactions were carried out in 10 mL DMSO under N2 with
ZnTAP(Br) (Zn1) (100 mg, 1.0 equiv.) and Zn (50 equiv.) at 85 uC.
Isolated yields.
b
Scheme 2
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 4982–4984 | 4983

View Article Online
data). CCDC 267633. See http://dx.doi.org/10.1039/b509972b for crystal-
lographic data in CIF or other electronic format.
1 The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and
R. Guilard, Academic Press, San Diego, 2000–2003, Vol. 1–20.
2 (a) A. C. Tome´, P. S. S. Lacerda, M. G. P. M. S. Neves and
J. A. S. Cavaleiro, Chem. Commun., 1997, 1199; (b) A. M. G. Silva,
A. C. Tome´, M. G. P. M. S. Neves and J. A. S. Cavaleiro, Tetrahedron
Lett., 2000, 41, 3065.
3 (a) X. G. Liu, Y. Q. Feng, X. Chen, F. Li and X. G. Li, Synlett, 2005, 6,
1030; (b) A. M. G. Silva, A. C. Tome´, M. G. P. M. S. Neves,
A. M. S. Silva and J. A. S. Cavaleiro, J. Org. Chem., 2005, 70, 2306; (c)
J. A. S. Cavaleiro, M. G. P. M. S. Neves and A. C. Tome´, Arkivoc,
2003, xiv, 107; (d) A. M. G. Silva, A. C. Tome´, M. G. P. M. S. Neves,
A. M. S. Silva, J. A. S. Cavaleiro, D. Perrone and A. Dondoni,
Tetrahedron Lett., 2002, 43, 603; (e) A. M. G. Silva, A. C. Tome´,
M. G. P. M. S. Neves and J. A. S. Cavaleiro, Synlett, 2002, 1155; (f)
A. M. G. Silva, A. C. Tome´, M. G. P. M. S. Neves, A. M. S. Silva and
J. A. S. Cavaleiro, J. Org. Chem., 2002, 67, 726; (g) A. Desjardins,
J. Flemming, E. D. Sternberg and D. Dolphin, Chem. Commun., 2002,
2622; (h) J. Flemming and D. Dolphin, Tetrahedron Lett., 2002, 43,
7281; (i) A. M. G. Silva, A. C. Tome´, M. G. P. M. S. Neves,
A. M. S. Silva and J. A. S. Cavaleiro, Chem. Commun., 1999, 1767.
4 H. J. Callot, Tetrahedron Lett., 1972, 11, 1011.
Scheme 3
Scheme 4
5 (a) S. Richeter, C. Jeandon, J. P. Gisselbrecht, R. Graff, R. Ruppert and
H. J. Callot, Inorg. Chem., 2004, 43, 351; (b) S. Richeter, C. Jeandon,
N. Kyritsakas, R. Ruppert and H. J. Callot, J. Org. Chem., 2003, 68,
9200; (c) S. Richeter, C. Jeandon, J. P. Gisselbrecht, R. Ruppert and
H. J. Callot, J. Am. Chem. Soc., 2002, 124, 6168; (d) S. Richeter,
C. Jeandon, R. Ruppert and H. J. Callot, Chem. Commun., 2001, 91; (e)
K. Henrick, P. G. Owston, R. Peters, P. A. Tasker and A. Dell, Inorg.
Chim. Acta, 1980, 45, L161–163; (f) H. J. Callot, E. Schaeffer, R. Cromer
and F. Metz, Tetrahedron, 1990, 46, 5253; (g) Y. V. Ishkov and
Z. I. Zhilina, Zh. Org. Khim., 1995, 31, 136; (h) S. Richeter, C. Jeandon,
R. Ruppert and H. J. Callot, Tetrahedron Lett., 2001, 42, 2103; (i)
L. Barloy, D. Dolphin, D. Dupre´ and T. P. Wijesekera, J. Org. Chem.,
1994, 59, 7976; (j) G. L. Li, A. Graham, W. Potler, Z. D. Grossman,
A. Oseroff, T. J. Dongherty and R. K. Padey, J. Org. Chem., 2001, 66,
1316; (k) M. Nath, M. Pink and J. M. Zaleski, J. Am. Chem. Soc., 2005,
127, 478; (l) H. Aihara, L. Jaquinod, D. J. Nurco and K. M. Smith,
Angew. Chem., Int. Ed., 2001, 40, 3439; (m) M. Nath, J. C. Huffman and
J. M. Zaleski, Chem. Commun., 2003, 858; (n) M. Nath, J. C. Huffman
and J. M. Zaleski, J. Am. Chem. Soc., 2003, 125, 11484.
afforded three different products 8, 9, 10. Their structures have
been assigned by 1H NMR, MS spectrometry, Uv-visible spectro-
scopy and HRMS or elemental analysis (Scheme 3).
In order to further explore the generality of the reaction,
dibromoporphyrin Zn117b was then synthesized for the reaction.
As expected, intramolecular cyclization product Zn12 was obtained
as the main product and debrominated porphyrins Zn13 and Zn14
as the minor products (Scheme 4).
Finally, an attempt to trap the b-porphyrin radicals generated
from ZnTPP(Br) (Zn1a) with an electron-deficient alkene or
alkyne (i.e. acrylonitrile or ethyl propiolate) under similar
conditions met with failure, the intramolecular cyclization product
Zn2a and hydrogenated product Zn3a still being the main
products.
In conclusion, we have developed a novel and facile method for
the Zn-mediated intramolecular cyclization of b-porphyrin radicals
for the convenient and effective construction of newly fused five-
membered porphyrin systems from readily available brominated
porphyrins. Because of the ready availability of the starting
material, this method might be useful for some applications in
areas such as materials, biomimetics and medicine.
6 S. Fox and R. W. Boyle, Chem. Commun., 2004, 1322.
7 (a) C. Liu and Q. Y. Chen, Synlett, 2005, 8, 1306; (b) Z. Zeng, C. Liu,
L. M. Jin, C. C. Guo and Q. Y. Chen, Eur. J. Org. Chem., 2005, 306; (c)
L. Chen, L. M. Jin, C. C. Guo and Q. Y. Chen, Synlett, 2005, 6, 963; (d)
C. Liu and Q. Y. Chen, Eur. J. Org. Chem., 2005, 3680; (e) L. M. Jin,
L. Chen, C. C. Guo and Q. Y. Chen, J. Porphyrins Phthalocyanines,
2005, 9, 109; (f) L. M. Jin, Z. Zeng, C. C. Guo and Q. Y. Chen, J. Org.
Chem., 2003, 68, 3912.
8 E. Erdik, Tetrahedron, 1987, 43, 2203.
We thank the Natural Science Foundation of China for support
of this work (No. 20272026 and D20032010).
9 M. S. Newman and F. J. Arens, J. Am. Chem. Soc., 1955, 77, 946.
10 K. M. Kadish, E. Van Caemelbecke and G. Royal, in The Porphyrin
Handbook, ed. K. M. Kadish, K. M. Smith, R. Guilard, Academic
Press, Boston, MA, 2000, Vol. 8, p. 3.
11 H. J. Callot, Bull. Soc. Chim. Fr., 1974, 1492.
12 D. K. Kumar, P. Bhyrappa and B. Varghese, Tetrahedron Lett., 2003,
40, 4849.
13 (a) D. P. Curran, in Comprehensive Organic Synthesis, ed. B. M. Trost,
I. Fleming, Pergamon Press plc, Oxford, 1991, Vol. 4, p. 715–831; (b)
B. Giese, Angew. Chem., Int. Ed., 1983, 22, 753.
Notes and references
{ Crystal data. C51H39N4OZn, M 5 789.23, triclinic, a 5 12.6037 (13),
˚
b 5 13.0941 (13), c 5 13.6336 (13) A , a 5 75.970 (2), b 5 71.209 (2),
3
˚
c 5 63.453 (2)u, V 5 1892.6 (3) A , T 5 293 (2) K, space group P-1, Z 5 2,
Dc 5 1.385 g cm23, 10463 reflections measured, 7314 unique which were
used in all calculations. R(int) 5 0.0853. The final wR(F2) was 0.0572 (all
4984 | Chem. Commun., 2005, 4982–4984
This journal is ß The Royal Society of Chemistry 2005