Macrocycle contraction and expansion of a dihydrosapphyrin isomer

Article abstract of DOI:10.1021/ja4112644

Cyclization of a pentapyrrane with two terminal β-linked pyrroles afforded a dihydrosapphyrin isomer (1) with the pyrroles linked in a unique β,α-α,β mode, which was rather reactive, and thus it readily underwent a ring-contracted rearrangement to a pyrrolyl norrole (2), and succeeding ring expansion to a terpyrrole-containing isosmaragdyrin analogue (4). 1, 2, and 4 contain the internal ring pathways with a minimum of 17, 15, and 16 atoms, respectively. 1, 2, and 4 are almost nonfluorescent, whereas the complex of 2 with Zn²⁺ shows a distinct NIR emission peak at 741 nm. The unprecedented pyrrole transformation chemistry by confusion approach is illustrated.

Full text of DOI:10.1021/ja4112644

Communication
pubs.acs.org/JACS
Macrocycle Contraction and Expansion of a Dihydrosapphyrin
Isomer
Yongshu Xie,*,† Pingchun Wei,† Xin Li,§ Tao Hong,† Kai Zhang,† and Hiroyuki Furuta*,‡
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai
200237, P. R. China
‡Center for Molecular Systems, Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University,
Fukuoka 819-0395, Japan
§Department of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, SE-10691
Stockholm, Sweden
S
* Supporting Information
Chart 1. Representative Structures of Porphyrin, Corrole,
Sapphyrin, Smaragdyrin, Isosmaragdyrin, and Their Pyrrole-
Mislinked Isomers
ABSTRACT: Cyclization of a pentapyrrane with two
terminal β-linked pyrroles afforded a dihydrosapphyrin
isomer (1) with the pyrroles linked in a unique β,α−α,β
mode, which was rather reactive, and thus it readily
underwent a ring-contracted rearrangement to a pyrrolyl
norrole (2), and succeeding ring expansion to a terpyrrole-
containing isosmaragdyrin analogue (4). 1, 2, and 4
contain the internal ring pathways with a minimum of 17,
15, and 16 atoms, respectively. 1, 2, and 4 are almost
nonfluorescent, whereas the complex of 2 with Zn2+ shows
a distinct NIR emission peak at 741 nm. The
unprecedented pyrrole transformation chemistry by
confusion approach is illustrated.
acrocyclic frameworks widely occur in nature. The
M
development of novel macrocycles with specific
functionality has long been an interesting research topic for
chemists.1 In recent years, porphyrins and porphyrin analogues
have attracted considerable attention due to their versatile
structures and properties.2 Among them, the pyrrole-mislinked
isomers of porphyrin as well as their contracted and expanded
families are of particular interest because they could provide
diversity in structures and properties. Typical examples include
N-confused porphyrin,3 neo-confused porphyrin,4 neo-con-
fused corrole (norrole),5 corrorin,6 and hexaphyrins with
multiple N-confused pyrroles,7 in which one or more pyrrole
rings are connected through the α,β′ (confused), α,β, or N,β
(neo-confused) positions (Chart 1).4,5 The stability differs
largely among the different isomers, and transformation into
the other types of macrocycles, such as N-fused porphyrin, N-
fused sapphyrin, doubly N-confused hexaphyrin, etc., has
occasionally been observed.6a,8 As both the isomers and
transformed macrocycles exhibit unique properties and display
different functions compared with their parent compounds,
installing of confused (or mislinked) pyrroles into the
macrocyclic frameworks, which we call confusion approach, is
becoming one of the promising synthetic strategies to access to
the novel porphyrinoids with worthy features.9 Herein, we
describe the synthesis of a corrorin-type dihydrosapphyrin
isomer (1), to which we put a trivial name “dihydrosap-
phyrinarin”, its ring-contracted rearrangement to the pyrrolyl
norrole (2), its Zn2+ complex (3), and succeeding ring
expansion to the terpyrrole-containing isosmaragdyrin10
analogue (4). The unprecedented pyrrole transformation
chemistry is illustrated.
At first, we tried the cyclization of a pentapyrrane (P5) with
two terminal β-linked pyrroles, aiming to prepare the doubly N-
confused sapphyrin (N2CS)11 bearing two confused pyrroles in
a bipyrrole moiety (Scheme 1). However, contrary to our
expectations, the cyclization reaction proceeded in a β,α−α,β
mode instead of the β′,α−α,β′ one and afforded a
dihydrosapphyrinarin (1) with an sp3 meso-carbon, similar to
the cyclization of the doubly N-confused bilane to corrorin.6b
As inferred from the transformation of corrorin to oxy-
indolophyrin,6a the bipyrrole moiety with the β,α−α, β linkage
Received: November 8, 2013
Published: December 9, 2013
© 2013 American Chemical Society
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Communication
a
Scheme 1. Syntheses of 1−4
a
Conditions: (i) DDQ, CH2Cl2; (ii) Et3N, CH3CN, air; (iii)
Zn(OAc)2·2H2O, MeOH; (iv) DDQ, CH2Cl2.
in 1 was rather reactive, and the pentapyrrolic macrocycle 1
readily underwent a ring contraction reaction to afford a high
yield of tetrapyrrole macrocycle, pyrrolyl norrole (2, Scheme
1). Surprisingly, 2 further underwent a ring expansion reaction
to afford a novel pentapyrrolic macrocycle (4), in which two
confused pyrroles are linked in an unprecedented N,α−α,β
mode. It has only three meso carbons in the conjugated pathway
and a terpyrrole, and thus it can be described as an
isosmaragdyrin10 analogue.
To be more specific, the precursor, doubly terminal β-linked
pentapyrrane (P5), was synthesized from tripyrrane and β-
pyrrole carbinol, and then oxidized with 3.3 equiv of 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to afford 1 in
70% yield. 1 was stable in the air, but upon further addition of
DDQ, decomposed gradually. Interestingly, when 1 was treated
with Et3N in acetonitrile, it underwent ring contraction to
afford a norrole derivative 2 with an appended aroylpyrrole ring
in 90% yield. The reaction solvent is vital for this trans-
formation: the yield was decreased to 30% in CH2Cl2 and
almost no desired product was obtained in the alcoholic or
alkane solvents. In the next step, when 2 was treated with
Zn(OAc)2·2H2O in methanol, Zn2+ complexation was achieved
with the change of solution color from blue to green. The
resulting Zn2+ complex 3 was separated on a silica gel column
as a green solid in 87% yield. Furthermore, contrary to the ring
contraction from 1 to 2, the norrole 2 underwent a ring
expansion reaction to afford a novel pentapyrrolic isosmar-
agdyrin analogue 4 in 20% yield by treatment with 1 equiv of
DDQ in CH2Cl2.
Figure 1. Perspective and side views of molecular structures of 1 (a,c),
2 (b,d), 3 (e,g), and 4 (f,h), and the 1D chain (i) assembled by
intermolecular hydrogen bonds in crystal 3. C6F5 groups and the
hydrogens attached to carbons are omitted for clarity.
pyrroles are tilted from this plane with dihedral angles of 26.4°,
35.3°, and 89.5°, respectively. Within the macrocycle, N4 is
hydrogen bonded to H3 and H5 with N4···N3 and N4···N5
distances of 2.71 and 2.65 Å, respectively.
The crystal structure of 2 (Figure 1b,d) revealed that the
pentapyrrolic macrocycle 1 has been contracted to a
tetrapyrrolic macrocyclea norrole derivative with an
appended pyrrolic ring at the C19 positionand the internal
ring pathway contains a minimum of 15 atoms. The regular B
and C pyrrole rings are almost coplanar, and the pyrroles A and
D are tilted from this plane with dihedral angles of 19.3° and
55.3°, respectively. These values are significantly larger than
those (6.7° and 34.1°) observed for C19-unsubstituted
norrole,5a indicating the severe distortion of the molecule due
to the steric hindrance associated with the appended pyrrole E.
As expected, ring E is almost perpendicular to D with a dihedral
angle of 86.5°. Within the macrocycle, N2 is hydrogen bonded
to H1, H3A, and H5.
Complex 3 (Figure 1e,g) also has a nonplanar structure. 2
coordinates as a dianionic, tridentate ligand, with Zn1−N1,
Zn−N2, and Zn−N3 bond lengths of 1.954(5), 1.947(4), and
1.951(4) Å, respectively. The Zn center further coordinates
with a methanol molecule, with Zn1−O2 bond length of
2.044(4) Å. The pyrroles C and D are tilted from the plane
composed of rings A and B with the dihedral angles of 12.7°,
and 59.7°, respectively. The coordination moieties are
assembled by intermolecular hydrogen bonds between the
axially coordinated methanol and the carbonyl moieties to form
a 1D chain (Figure 1i).
The structures of compounds 1−4 were characterized by
single crystal X-ray diffraction analyses.12 The crystal of 1
(Figure 1a,c) demonstrated a nonplanar pentapyrrolic macro-
cycle with a directly linked bipyrrole in a unique β,α−α,β mode
and an sp3 meso-C atom, and the internal ring pathway contains
a minimum of 17 atoms. Within the molecule, the regular
pyrrole rings A and B are almost coplanar, and the C, D, and E
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In the crystal structure of 4 (Figure 1f,h), the appended
pyrrole in 2 has been merged into the macrocycle to afford a
pentapyrrolic macrocycle, and the internal ring pathway
contains a minimum of 16 atoms (Scheme 1). The pyrroles
D and E are linked directly in an unprecedented β,α−α,N
mode. The macrocycle framework is also severely distorted
from a planar structure. Namely, the regular pyrroles A and B
are almost coplanar, and C, D, and E pyrroles are tilted from
this plane with dihedral angles of 23.2°, 54.8°, and 57.6°,
respectively. Rings C and E are also tilted from D with large
dihedral angles of 71.9° and 53.1°, respectively. Similar to 1 and
2, multiple intramolecular hydrogen bonds are also observed.
The details of the formation mechanism for 2 and 4 are yet
unknown, but the above crystal structures strongly suggest
intramolecular rearrangements among the three pyrrole rings A,
D, and E, which are adjacent to each other (Figure 1). For 1,
ring D is located above ring A, and the distance between N1
(ring D) and C10 (ring A) is only 3.61 Å. Similarly, for 2, the
distance between N5 (ring E) and C1 (ring A) is only 3.37 Å.
Thus, we think the deprotonation of N1 in 1 by Et3N and N5
in 2 in the presence of DDQ, both of which afforded the
reactive nitrogen species, could trigger the peculiar rearrange-
ments, respectively (Scheme 2). It is noteworthy that the
rearrangement from 2 to 4 is an isomerization rather than an
oxidation reaction even though DDQ was used.
Figure 2. Relative energies (kJ/mol) and computed self-consistent
field energies (a.u.) for (a) the possible isomers of 1 and (b) 2 and 4.
Scheme 2. Plausible Mechanism for the Formation of 2 (a)
and 4 (b)
Figure 3. (a) UV−vis spectra and photographs showing the solution
colors of 1−4 in CH2Cl2. (b) Fluorescence spectra (λex = 422 nm) of 2
and 3 (10 μM) in CH2Cl2.
Consistent to these data, the addition of Zn2+ to the methanol
solution of 2 induced drastic absorption spectral changes, and
31-fold fluorescence enhancement at 736 nm (Figure S13,
Supporting Information), which may be ascribed to a chelation-
enhanced fluorescence (CHEF) mechanism.16 The diminished
fluorescence property of norrole skeleton5a in distorted 2 could
be recovered by fixing the molecular structure with metal
chelation. This observation indicated that 2 would be
developed as a prototype of Zn2+ probe with NIR emission,
which is now under research in our laboratory.
In summary, we have sequentially synthesized three types of
novel porphyrinoids 1, 2, and 4, which contain unique β,α−α,β,
α,α−N,β, and N,α−α,β, bipyrrole linkages in the 17-, 15-, and
16-membered macrocyclic frameworks, respectively. The
macrocycles 1, 2, and 4 exhibit extremely weak fluorescence.
In contrast, 3 exhibits a much stronger emission peak at 741
nm, and thus 2 may find applications in Zn2+ probing. The
present results do not merely add examples to the ring-size-
changing reaction in porphyrinoids17 but suggest the validity of
the confusion approach strategy. Because of the innumerable
combinations of confused and regular pyrroles, we believe
hitherto novel molecules with unprecedented frameworks and
interesting functions could be discovered by the confusion
approach strategy.
The facile formation of 1 instead of N2CS from the precursor
P5 was inferred from the comparison of relative energies of 1
and the dihydrogenated N2CS (Figures 2 and S12, Supporting
Information). The density functional theory (DFT) calcu-
lations13 on the reduced form of N2CS tautomers (1a, 79.4 kJ/
mol; 1b, 62.0 kJ/mol) have demonstrated much higher energies
than 1 (0.0 kJ/mol). These results indicate that the
incorporation of α,β′-linked pyrroles in this macrocyclic system
is unfavorable, and hence the partially oxidized compound 1
was obtained in the cyclization reaction. On the other hand, the
energy of 4 (−31.9 kJ/mol) is much lower than that of 2 (0.0
kJ/mol), which indicates that the ring expansion reaction is
energetically favorable, being consistent with the experimental
results.
The absorption spectra of 1−4 exhibit broad Soret-like and
Q-like bands with comparable intensities (Figure 3a), which
indicates the nonaromaticity of 1−4.14 It is noteworthy that 1,
2, and 4 exhibit extremely weak fluorescence in CH2Cl2, with
the quantum yields of 0.22%, 0.16%, and 0.31%, respectively.15
In contrast, 3 exhibits a much stronger emission peak at 741
nm (Figure 3b) with the quantum yield of 9.9% in CH2Cl2.15
ASSOCIATED CONTENT
* Supporting Information
Synthetic procedures and complete experimental details;
■
S
crystallographic details (CIF) for 1−4; spectroscopic and
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Journal of the American Chemical Society
Communication
(10) Yoon, Z. S.; Cho, D. G.; Kim, K. S.; Sessler, J. L.; Kim, D. J. Am.
Chem. Soc. 2008, 130, 6930−6931.
analytical data (UV−vis, FL, NMR); details on DFT
calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
́
(11) Sessler, J. L.; Cho, D. G.; Step̧ ien, M.; Lynch, V.; Waluk, J.;
Yoon, Z. S.; Kim, D. J. Am. Chem. Soc. 2006, 128, 12640−12641.
(12) CCDC 950263−950266 (1−4) contain the supplementary
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/date_request/cif.
(13) All the calculations were achieved with Gaussian09 program
package at the B3LYP/6-31G* level. See Supporting Information for
calculation details.
AUTHOR INFORMATION
■
Corresponding Authors
yshxie@ecust.edu.cn
hfuruta@cstf.kyushu-u.ac.jp
Notes
(14) More detailed descriptions on the aromaticity of 1−4 are
included in the Supporting Information.
The authors declare no competing financial interest.
(15) Relative to TPP (φfl = 0.11). Kim, J. B.; Leonard, J. J.; Longo, F.
R. J. Am. Chem. Soc. 1972, 94, 3986−3992.
ACKNOWLEDGMENTS
■
(16) (a) Huston, M. E.; Haider, K. W.; Czarnik, A. W. J. Am. Chem.
Soc. 1988, 110, 4460−4462. (b) Kim, H. N.; Ren, W. X.; Kim, J. S.;
Yoon, J. Chem. Soc. Rev. 2012, 41, 3210−3244.
This work was supported by NSFC/China (21072060,
91227201), National Basic Research 973 Program
(2013CB733700), the Oriental Scholarship, NCET-11-0638,
the Fundamental Research Funds for the Central Universities
(WK1013002), SRFDP (20100074110015) to Y.X., and the
Grant-in-Aid for Scientific Research (25248039) from the
MEXT, Japan to H.F.
(17) Typical examples of ring-size-changing reaction of porphyr-
inoidsPorphyrin to corrole: (a) Tse, M. K.; Zhang, Z.; Mak, T. C.
W.; Chan, K. S. Chem. Commun. 1998, 1199−1200. (b) Jeandon, C.;
Ruppert, R.; Callot, H. J. Chem. Commun. 2004, 1090−1091. Corrole
to porphyrin: (c) Gros, C. P.; Barbe, J.-M.; Espinosa, E.; Guilard, R.
Angew. Chem., Int. Ed. 2006, 45, 5642−5645. Porphyrin to isocorrole:
(d) Will, S.; Rahbar, A.; Schmickler, H.; Lex, J.; Vogel, E. Angew.
Chem., Int. Ed. 1990, 29, 1390−1393. Octaphyrin to porphyrin:
(e) Tanaka, Y.; Hoshino, W.; Shimizu, S.; Youfu, K.; Aratani, N.;
Maruyama, N.; Fujita, S.; Osuka, A. J. Am. Chem. Soc. 2004, 126,
3046−3047. Benziporphyrin to carbaporphyrin: (f) Szyszko, B.;
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