N-confused and N-fused meso-aryl sapphyrins

Article abstract of DOI:10.1002/anie.200705984

(Chemical Presented) A state of (con)fusion: The introduction of a confused pyrrole ring into a meso-aryl sapphyrin framework destabilizes the macrocycle and forces a fusion reaction to occur. Subsequent metalation with rhenium results in further mutation to form a domino-fused sapphyrin with a fused penta-ring system (see scheme).

Full text of DOI:10.1002/anie.200705984

Angewandte
Chemie
DOI: 10.1002/anie.200705984
Porphyrinoids
N-Confused and N-Fused meso-Aryl Sapphyrins**
Iti Gupta, Alagar Srinivasan, Tatsuki Morimoto, Motoki Toganoh, and Hiroyuki Furuta*
Mutation and selection are fundamental processes in the
evolution of biosystems.[1] The generation of artificial mutants
is a major strategy in biological science to enable properties of
biomolecules to be exploited that have remained hidden
under the natural conditions.[2] By using this as a guiding
principle, we have been studying porphyrin analogues,
especially the porphyrin mutants, namely N-confused por-
phyrin (NCP)[3] and other confused porphyrinoids,[4] includ-
ing expanded porphyrins.[5] In particular, we have been trying
to use a strategy to direct mutation (or evolution) to introduce
one or more confused (that is, a,b’-linked) pyrrole ring(s) into
the macrocycles. We have called this the confusion
approach,[4a] and have aimed to create novel porphyrinoids
that exhibit unique properties unseen in the standard
porphyrins.
The mutant NCP, with a tetrapyrrolic framework, is less
stable, both thermally and photochemically, than ordinary
porphyrin. However, this instability turns to an advantage
when NCP transforms into another species, such as N-fused
porphyrin (NFP).[6] In the pentapyrrolic system, N-confused
meso-aryl pentaphyrin (NCP5) is unstable and exists as N-
fused pentaphyrin (NFP5) or doubly N-fused pentaphyrin.[7]
In contrast, in the hexaphyrin system, the doubly N-confused
dioxohexaphyrins are rather stable and can even be derived
from standard hexaphyrins,[8] while the corresponding fused
species have not yet been found. Here the question arises as
to the relationship between the fate of the confused pyrrole
ring and the size of the macrocycles, especially in the
sapphyrin system, an intermediate compound between por-
phyrins and pentaphyrins, and perhaps the oldest member of
the expanded porphyrin family.[9] Previously, we and the
Chandrashekar research group reported diselena and dithia
derivatives of N-confused meso-aryl sapphyrin;[10] however,
the genuine meso-aryl N-confused sapphyrin remains an
important synthetic target to clarify the intrinsic role of the
confused pyrrole unit in the pentapyrrolic macrocycle. Herein
we report the first synthesis of N-confused all-aza-meso-aryl
sapphyrin (NC-Sap) and N-fused sapphyrin (NF-Sap), and
demonstrate the utility of the confusion approach in synthe-
sizing porphyrin analogues.
The synthesis of N-confused 5,10,15,20-tetrakis(penta-
fluorophenyl)sapphyrin (1) was successfully achieved by both
[5+0] and [3+2] routes from appropriate precursors
(Scheme 1).[11] Briefly, N-confused pentapyrromethane 3
bearing four pentafluorophenyl groups was treated with
NH4Cl in acetonitrile at room temperature for 3 h, followed
by oxidation with 2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ), which resulted in the formation of 1 and N-fused
5,10,15,20-tetrakis(pentafluorophenyl)sapphyrin (2) as a side
product. Purification of the crude reaction mixture by column
chromatography on silica gel afforded 1 as a green solid in 6%
yield and 2 as a red solid in less than 2% yield. Alternatively, 1
could also be prepared in 6% yield by the condensation
between the biscarbinol derivative of N-confused tripyrro-
methane[12] 4 and 2,2-bipyrrole (5) in dichloromethane using
trifluoroacetic acid (TFA) as a catalyst, followed by oxidation
[*] Dr. I. Gupta,[+] Dr. A. Srinivasan, Dr. T. Morimoto, Dr. M. Toganoh,
Prof. Dr. H. Furuta
Department of Chemistry and Biochemistry
Graduate School of Engineering
Kyushu University, Fukuoka 819-0395 (Japan)
Fax: (+81)92-802-2865
E-mail: hfuruta@cstf.kyushu-u.ac.jp
[+] Current address:
BITS-Pilani, Goa Campus, Near NH-17B
Bye Pass Road Zuarinagar, Goa 403 726 (India)
[**] I.G. thanks the JST and JSPS for fellowships, and H.F. thanks
PRESTO, JST, and a Grant-in-Aid for the Global COE Program,
“Science for Future Molecular Systems” from the MEXT (Japan) for
financial support.
Supporting information for thisarticle isavailable on the WWW
under http://www.angewandte.org or from the author.
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Scheme 1. The [5+0] and [3+2] routes for the synthesis of N-confused meso-aryl and N-fused sapphyrins (1, 2, respectively).
with DDQ. The standard type of sapphyrin with four
pentafluorophenyl groups was also prepared by the [3+2]
route for comparison.[11] The MALDI-TOF mass spectrum of
1 shows the signal for the M+ ion at m/z 1039, thus indicating
the presence of a pentapyrrolic macrocycle. The signal for the
M+ ion for 2 appears at m/z 1037, which is two mass units less,
thus reflecting the ring fusion. The structures of 1 and 2 were
shown in Scheme 1.[11] This tautomeric form is different from
that of the previously reported dithiasapphyrin, which takes a
less aromatic form.[5,10] For 1, in accordance with the
tautomeric structure above, a 22p aromatic system is indi-
cated by the difference in the chemical shifts between the
outer and inner protons (Dd = 12.6 ppm) in 1, which is slightly
less than that of the all-aza-meso-tetrakis(pentafluorophe-
nyl)sapphyrin (Dd = 14.8 ppm),[11] but much higher than that
of N-confused dithiasapphyrin (Dd = 7.06 ppm)[10] and the
recently reported inverted b-alkylated sapphyrin (Dd =
4.79 ppm).[13] Reflecting the aromatic nature of 1, two intense
bands are observed in the Soret region at 395 and 497 nm in
the absorption spectrum, and four small Q-type bands are
observed at 625, 679, 750, and 871 nm (Figure 1).
1
fully characterized by H NMR spectroscopy (see below).
The formation of 2 during the synthesis of 1 clearly shows
that the ring fusion is a usual phenomenon among N-confused
pentapyrrolic macrocycles.[7,8] Our synthetic studies showthat
2 can be formed only as a side product when 1 is synthesized
by a [5+0] route (path a). We found that 2 can also be made
directly from 1 by following a similar strategy as used for the
synthesis of NFP[6] (path c). Although the exact mechanism of
ring fusion is still not known, a plausible explanation could be
that the ring-fusion step occurs during the oxidation process
of a sapphyrinogen intermediate through the nucleophilic
attack of the adjacent pyrrolic N atom on the a-position of the
inverted N-confused pyrrole unit. The occurrence of the ring-
fusion step after oxidation of a confused sapphyrinogen is
ruled out, since our efforts to make 2 by direct oxidation of 1
with DDQ were not successful (path d). Furthermore, the
reaction conditions may not be favorable for ring fusion, since
2 was not obtained from a [3+2] route (path b).
On the other hand, NF-Sap (2), which is a higher
homologue of NFP, lacks the 1H NMR signal for the Ha
proton of the confused pyrrole ring because of the ring
fusion. The chemical shifts of the peripheral protons of the
The inverted structure of 1 in solution was inferred by the
1H NMR chemical shifts of the signal for the inner CH (Ha)
proton of the confused pyrrole ring at d = 1.64 ppm, signals
for the three NH protons at d = 0.78, À0.92, and À2.48 ppm,
and a signal for the outer CH (Hb) proton at d = 10.24 ppm
(CD2Cl2, 183 K). The location of the three NH protons is not
straightforward, but they are on the ordinary pyrrole moieties
and not on the confused pyrrole ring. This is evident because
the signal corresponding to the Ha proton was not affected by
the addition of D2O, a process that usually results in a smaller
scalar coupling with the neighboring NH proton. The most
probable tautomeric form derived from DFT calculations is
Figure 1. Absorption spectra of 1, 2, and meso-tetrakis-(pentafluoro-
phenyl)sapphyrin in toluene.
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core rings are in the range of d = 7.5 to 8.7 ppm, and the
signals for the two inner NH protons appear as broad singlets
at d = 5.56 and 8.30 ppm, which suggests a 22p aromaticity
within the macrocycle. The large downfield shifts of the NH
signals can be attributed to the presence of strong intra-
molecular hydrogen-bonding interactions in the cavity, where
the distances between the neighboring nitrogen atoms are
estimated from DFT calculations to be 2.62 and 2.92 Š (see
Figure S17 in the Supporting Information). The absorption
spectrum of 2 shows split Soret bands at 366 and 500 nm, and
four small Q-type bands between 655 and 963 nm (Figure 1).
Such long-wavelength absorption in the near-infrared region
is a typical feature of N-fused porphyrinoids.[6,7]
and N2···N3 are 2.693, 2.683, and 2.856 Š, respectively, which
are within hydrogen-bonding distances.
´
Previously, Latos-Graz˙ynski and co-workers reported that
meso-tetraphenylsapphyrin takes an inverted conformation in
the neutral form, but changes to a planar form (that is, with all
the N atoms pointing inward) upon protonation.[9c] To see
whether the ring flipping is a general property in the meso-
aryl sapphyrin system, the protonation behavior of 1 was
1
examined. The H NMR spectrum of monoprotonated NC-
Sap (1+), which was obtained by the addition of one
equivalent of TFA in CD2Cl2 at 183 K, shows signals for the
four inner NH and inner a-CH (Ha) protons at d = À1.05,
À1.61, À2.32, À3.03, and À0.75 ppm, respectively, and the
signal for the outer b-CH (Hb) proton at d = 11.01 ppm.
Further addition of acid (5 equiv) afforded the diprotonated
form of NC-sap (12+) which shows signals for five NH protons
at d = 5.30 (overlapped with CH2Cl2; d = 5.88 ppm in CDCl3
at 223 K), À2.13, À2.56 (2H), and À3.11 ppm, and the signals
for the inner CH and outer CH protons at 2.14 and 11.05 ppm,
respectively. The observed NH signal at d = 5.30 ppm is
assigned to that of the inverted confused pyrrole ring on the
basis of the difference in the chemical shift from that of the
inner CH (Ha) proton (Dd = ca. 3 ppm). These data indicate
that, in contrast to the standard meso-aryl sapphyrin, ring
flipping of the confused pyrrole of 1 does not take place in the
protonated states.
Direct proof for the structure of 1 came from X-ray
crystallographc analysis (Figure 2). Attempts to crystallize 1
To gain insight into the conformation and the location of
the NH atoms in 1, DFT calculations were performed on all
the tautomers in various ionic states (monoanionic, neutral,
monocationic, and dicationic), but with the pentafluoro-
phenyl groups replaced by hydrogen atoms or phenyl groups
for simplicity. The most stable inverted tautomers in each
ionic state and their relative energies compared to those of
standard sapphyrin are shown in Figure S18 in the Supporting
Information. The calculations showthat 1 prefers the inverted
structures except in diprotonated 12+.[17] Since the planar
conformation of the skeleton in all the ionic states was found
by calculations to be more stable, it appears that steric
hindrance from the meso-aryl groups is more significant in the
planar conformation than in the inverted one.[11] Furthermore,
it is noteworthy that the total energy of 1À is lower than that of
the corresponding standard sapphyrin (DE in kcalmolÀ1):
À1.2 (anion), + 2.6 (neutral), + 5.0 (monocation), + 8.3
(dication)), which suggests that 1 is more acidic than the
standard sapphyrin. As illustrated in the X-ray structure, the
intramolecular hydrogen bonds of the inverted confused
pyrrole ring in the core may contribute significantly to the
stabilization of 1À.
Interestingly, NF-Sap (2) undergoes further fusion during
metalation. When 2 was treated with [Re2(CO)10] in o-
dichlorobenzene at reflux for 12 h, the ReI complexes 6 and 7
were obtained in yields of 7 and 55%, respectively, after
column chromatography (Scheme 2). The X-ray structure of
the major product 7 shows a peculiar [5.5.5.5.6] domino-fused
penta-ring system, which is formed by connection between
the b-carbon atom of the tricyclic ring and the ortho position
of the meso-pentafluorophenyl group of 6 (Figure 3).[14] The
Re center is connected to the central nitrogen atom (N1) of
the fused ring and two bipyrrole nitrogen atoms (N2, N3),
Figure 2. X-ray structures of 1À: top: top view (the Bu4N+ ion and
solvent molecules are not shown); bottom: side view showing the
deviationsof the N-confused pyrrole ring A from the plane of the
macrocycle. The pentafluorophenyl groupsare omitted for clarity.
Thermal ellipsoids are shown at the 30% probability level.
in the presence of tetrabutylammonium fluoride resulted in
an ion pair [1À·Bu4N+] in the crystal, with 1 present in a
deprotonated anionic form and a tetrabutylammonium ion
associated as a counter cation.[14,15] In the crystal, 1À and
Bu4N+ stack in an alternate fashion to form a single strand.
The sapphyrin core in 1À is slightly distorted from a least-
squares plane consisting of 29 (N1–C24) atoms (plane I), with
a mean deviation of 0.271 Š. The confused pyrrole ring
(ring A) is inverted and significantly tilted with respect to the
core plane. The tilting angles (8) of the pyrrole rings (A–E) to
the plane I are: A, 27.5; B, 4.3; C, 5.9; D, 9.6; E, 13.3. The two
pyrrole rings C and E possess protonated nitrogen atoms
(NH) while the other three rings (A, B, and D) contain imino-
type nitrogen atoms (N).[16] The distances N1···N5, N4···N5,
Angew. Chem. Int. Ed. 2008, 47, 4563 –4567
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NF-Sap. When an additional
perturbation (that is, metala-
tion) is supplied, the mutated
NF-Sap can further transform
into a domino-fused sapphyrin
bearing a fused penta-ring that
has novel absorption proper-
ties. In the case of N-confused
porphyrinoids, the confused
pyrrole ring is usually more
reactive than other a,a’-linked
pyrrole rings in the macrocycle
because of the exposed elec-
Scheme 2. Formation of Re complexes 6 and 7 of NF-Sap derivatives.
tron-rich a (and b) positions,
which are susceptible to ring
fusion. On the other hand, in some cases the inverted
confused pyrrole ring could stabilize the system by intra-
molecular hydrogen bonding, as seen in 1À and doubly N-
confused dioxohexaphyrins.[8] Thus, the repeated introduction
of confused rings in the macrocycles would eventually lead to
the stable confused porphyrinoids, whose properties are
useful. Thus, we believe our confusion approach method
will become a powerful strategy to access these novel
functional molecules in the near future.
Received: December 30, 2007
Published online: May 5, 2008
Keywords: fused-ring systems · porphyrinoids · rhenium ·
.
sapphyrins
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Figure 3. X-ray structure of 7: top: top view; bottom: side view.
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with bond lengths of 2.285, 2.150, and 2.334 Š, respectively,
which are slightly longer than those in the ReI complex of
NFP (avge: 2.13 Š).[6b,c] The effect of the extension of the
p system in 7 is seen in the absorption spectrum, where broad
bands appear in the Soret region at 403, 484, and 564 nm,
while the edge of the Q-type bands exceeds 1300 nm in
toluene.[11]
In general, when the system becomes destabilized, the
perturbed system starts to gradually move to a stable state.
The introduction of a confused pyrrole ring into the sapphyrin
framework destabilizes the macrocycle and forces the mole-
cule (NC-Sap) to undergo reaction (namely, fusion) to give
[9] a) M. J. Broadhurst, R. Grigg, A. W. Johnson, Chem. Commun.
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Chemie
wicz, Chem. Eur. J. 1995, 1, 68; c) K. Rachlewicz, N. Sprutta, L.
19.945(4) Š, b = 113.111(2)8, V= 8967(3) Š3, Z = 8, 1calcd
1.906 gcmÀ3
T= 123 K, 22508 measured reflections, 8072
unique reflections (Rint = 0.1011), 4576 with I ꢀ 2s(I) used in
=
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refinement,
R = 0.0648,
wR = 0.1342,
GOF = 0.909.
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T. K. Chandrashekar, B. S. Joshi, R. Roy, H. Furuta, J. Am.
Chem. Soc. 2001, 123, 5138.
CCDC 671795 ([1À·Bu4N+]) and 671935 (7) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[11] See the Supporting Information.
[12] P.-Y. Heo, K. Shin, C.-H. Lee, Tetrahedron Lett. 1996, 37, 197.
[13] J. L. Sessler, D.-G. Cho, M. Stepien, V. Lynch, J. Waluk, Z. S.
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[15] Recently a similar ion-pair crystal of a deprotonated trans
doubly N-confused porphyrin anion and the Bu4N+ cation was
reported: H. Maeda, T. Morimoto, A. Osuka, H. Furuta, Chem.
Asian J. 2006, 1, 832.
[16] The location of the NH protons was unambiguously determined
from the peak heights obtained from the Fourier synthesis.
[17] Calculations on 10,15-dimethylsapphyrin also showed a discrep-
ancy with the experimental results, which infers the importance
of the counter anion for the calculations on the diprotonated
[14] Crystallographic data for 1À·Bu4N+: C48H12F20N5·C16H36N·
C2H4Cl2, Mr = 1380.04, monoclinic, space group P21/n, a =
8.3138(17), b = 30.100(6), c = 25.870(5) Š, b = 95.327(5)8, V=
6446(2) Š3, Z = 4, 1calcd = 1.422 gcmÀ3, T= 173 K, 36741 mea-
sured reflections, 11649 unique reflections (Rint = 0.044), 7423
with I ꢀ 2s(I) used in refinement, R = 0.0894, wR = 0.2580,
GOF = 1.041. For 7: C51H9F19N5O3Re, Mr = 1286.83, monoclinic,
space group C2/c, a = 45.318(8), b = 10.7861(19), c =
´
species: L. Szterenberg, L. Latos-Graz˙ynski, J. Mol. Struct. 1999,
490, 33.
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