Synthesis of chiral porphyrins through Pd-catalyzed [3+2] annulation and heterochiral self-assembly

Article abstract of DOI:10.1002/anie.200801269

Positive discrimination: Palladium-catalyzed [3+2] annulation of meso-bromoporphyrin with norbornene derivatives efficiently provides novel chiral meso, b-fused porphyrins with a rigid structure (as shown). A chiral benzoazanorbornene-fused zinc porphyrin assembles selectively to form the slipped cofacial dimer in a heterochiral association, which allows construction of a heterodimer from two porphyrin components through chiral discrimination. (Chemical Equation Presented)

Full text of DOI:10.1002/anie.200801269

Communications
DOI: 10.1002/anie.200801269
Self-Assembly
Synthesis of Chiral Porphyrins through Pd-Catalyzed
[3+2] Annulation and Heterochiral Self-Assembly**
Masatoshi Mizumura, Hiroshi Shinokubo,* and Atsuhiro Osuka*
Well-ordered constructions of self-assembled porphyrins have
been intriguing targets in terms of potential applications in
materials science, reaction catalysis, and duplication of
photosynthetic functions. The coordination interaction
between the central metal atom and the peripheral ligand of
a porphyrin has often been employed to construct self-sorting
porphyrin architectures.[1,2] We have also reported the self-
sorting assembly of pyridine-appended meso-meso-linked
zinc(II) diporphyrins.[3] However, formation of a porphyrin
assembly on the basis of selective heterochiral recognition is
quite rare,[4] despite its wider potential in the programmed
construction of molecular systems, in which several different
functions are integrated by noncovalent interactions.
cyclization sequence. Although there are several examples of
Pd-catalyzed annulation of norbornenes,[7] its application to
porphyrins has not been investigated. The reaction of
5-bromo-10,15,20-tris(3,5-di-tert-butylphenyl)porphyrinato
nickel(II) (1Ni) with norbornene proceeded smoothly to
afford 2Ni in 79% yield in the presence of Pd(OAc)2/ P(o-
tol)3 as the catalyst (Scheme 1). Locos and Arnold reported
the Heck reaction of meso-bromoporphyrins with styrene and
Chiral porphyrins have also been receiving much atten-
tion as scaffolds for precise molecular recognition, construc-
tion of supramolecular structures, and asymmetric catalysis.[5]
The synthetic strategy towards chiral porphyrins often
involves the introduction of chiral motifs to the porphyrin
periphery. Alternatively, a restricted bond rotation at steri-
cally encumbered positions can generate axial chirality.
However, in many cases, a chiral element is connected to a
porphyrin through a single bond, thus giving some flexibility
to the system. In contrast, chirality that is supported rigidly by
some fused structures would be advantageous to provide a
defined chiral environment. Here we wish to describe the
efficient palladium-catalyzed synthesis of novel fused chiral
porphyrins. Owing to the unsymmetrical meso,b-fused struc-
tures, these porphyrins are chiral in a rigid situation. The
formation of heterodimers of benzoazanorbornene-fused
porphyrins through chiral discrimination is also reported.
To incorporate a chiral fused structure into the porphyrin
periphery, we undertook a Pd-catalyzed [3+2] annulation
strategy, since of meso-bromoporphyrins with alkynes pro-
vided 7,8-dehydropurpurins.[6] We anticipated that the use of
reactive strained alkenes such as norbornene derivatives
instead of alkynes would furnish novel fused norbornene-
substituted porphyrins through the similar carbopalladation/
Scheme 1. Pd-catalyzed [3+2] annulation of meso-bromoporphyrin
with norbornene derivatives.
methyl acrylate, but such an olefinic Heck product was not
detected in this reaction.[8] The parent mass ion signal of 2Ni
[*] M. Mizumura, Prof. Dr. H. Shinokubo, Prof. Dr. A. Osuka
Department of Chemistry
was
observed
at
m/z 1045.5635
(calcd
for
(C69H80N4NiNa)+:1045.5629 [M+Na]+) in the high resolution
Graduate School of Science
Kyoto University
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3970
E-mail: hshino@kuchem.kyoto-u.ac.jp
osuka@kuchem.kyoto-u.ac.jp
1
ESI-TOF mass spectrum. The H NMR spectrum of 2Ni in
CDCl3 showed six doublets and a singlet which were assigned
to b protons, thus confirming the unsymmetrical meso,b-fused
structure. The use of benzooxanorbornene and benzoazanor-
bornene as the reactive alkene partners also yielded the
corresponding products 3Ni and 4H in good yields from 1Ni
and 1H, respectively. Free base porphyrin 1H underwent this
annulation without metalation by palladium. The addition of
the porphyrin moiety to the norbornene skeleton was
[**] This work was supported by a Grant-in-Aid for Scientific Research
(No. 18685013) from MEXT. We thank Prof. H. Tamiaki (Ritsumei-
kan University) for CD measurements.
Supporting information for thisarticle isavailable on the WWW
under http://dx.doi.org/10.1002/anie.200801269.
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Angew. Chem. Int. Ed. 2008, 47, 5378 –5381

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perfectly stereoselective in each case, and X-ray diffraction
analysis of 3Ni revealed an exo-fused stereochemistry (see
the Supporting Information).[9]
both in an enantiomerically pure form. Their 1H NMR
spectra in CDCl3 were identical. All signals for the b protons
were again shifted upfield, but importantly the spectrum was
totally different from that of the heterochiral dimer (5Znrac)2.
This indicates that 5Znchi (5Znchi represents either 5ZnR,S or
5ZnS,R) also assembles into discrete, but different porphyrin
oligomers. The homochiral dimeric structure of (5ZnR,S)2 was
elucidated by X-ray diffraction analysis (Figure 1c,d).[9] It
was also found that the minor peaks in the 1H NMR spectrum
of 5Znrac correspond to those of heterochiral dimer (5Znchi)2,
with (5Znrac)2 predominant in CDCl3 (ratio of 10:1). These
results reveal that heterochiral dimer (5Znrac)2 and homo-
chiral dimer (5Znchi)2 coexist in a solution of 5Znrac in CDCl3
with strong preference for the heterochiral dimer. The UV/
Vis absorption spectra of 5Znchi in CHCl3 showed no changes
in the range from 10À7 to 10À5 m, but the fluorescence spectra
With an efficient protocol to synthesize these chiral
porphyrins in hand, we then examined the self-assembly of
the zinc porphyrins. Benzoazanorbornene-fused porphyrin
5Znrac, namely a racemic mixture of 5ZnR,S and 5ZnS,R, was
prepared by removal of the tert-butoxycarbonyl (Boc) group
of 4H followed by insertion of a ZnII center.[10] The 1H NMR
spectrum of 5Znrac in CDCl3 showed substantial upfield shifts
for the b protons. This is typical of face-to-face porphyrin
dimers because of the shielding effect of the porphyrin ring.
All the b protons appeared in the similar region as those of
1Ni in the 1H NMR spectrum of 5Znrac in [D5]pyridine. These
facts strongly suggested that 5Znrac forms a discrete assembly
in CDCl3. In addition, several minor signals were also
observed (see below). Finally, X-ray diffraction analysis
revealed that 5Znrac formed a dimeric assembly mediated
by the complementary coordination between the nitrogen and
zinc atoms (Figure 1a,b).[9] Importantly, 5Znrac assembles
into a heterochiral dimer (5Znrac)2, where one enantiomer of
5Znrac favors dimerization with its antipode.
were concentration-dependent in the range of 10À9 to 10À7
m
(see the Supporting Information). These observations indi-
cate that some (5Znchi)2 dissociates into monomer 5Znchi
under dilute conditions. A good fit for the observed sigmoidal
curve was obtained by assuming formation of a porphyrin
dimer, which affords an association constant of Khomo = 1.2 ”
107 mÀ1 for the homochiral dimer. On the other hand, an
association constant of Khetero = 1.8 ” 108 mÀ1 was determined
for the heterochiral dimer, thereby confirming the preference
for this species.
Efficient chiral separation of 4H by HPLC was accom-
plished with ethyl acetate/hexane (1:2) as eluent. Each
fraction was separately converted into 5ZnR,S and 5ZnS,R
The X-ray crystal structure of (5Znrac)2 shows the two
porphyrin macrocycles are parallel with an interplanar
distance of 4.56 Š. The plane consisting of C5, Zn1, and
C15 is also parallel to the plane consisting of C5’, Zn2, and
C15’. On the other hand, two macrocycles in (5Znchi)2, are
tilted at 14.088. The plane consisting of C5, Zn1, and C15 is
tilted at 11.368 to the plane consisting of C5’, Zn2, and C15’.
This kinked structure of (5Znchi)2 means that the dipole
moment is not cancelled out, which leads to the preferential
formation of the heterochiral dimer.
The selective assembly of the heterochiral dimer is due to
chiral discrimination of one enantiomer with its antipode.
This assembly allows the formation of a porphyrin heterodi-
mer, which would be an ideal platform to incorporate two
different functions into self-assembled molecules. To confirm
this, porphyrin 6Zn, having 4-tert-butylphenyl groups at the
meso positions, was synthesized in a similar manner. 1H NMR
measurements of 6Zn confirmed the same assembling
behavior as 5Zn (see the Supporting Information). The NH
signals of (5ZnR,S)2 and (6ZnS,R)2 were observed at different
chemical shifts in the NMR spectrum recorded in CDCl3
(Figure 2a,b). After mixing (5ZnR,S
) and (6ZnS,R) and
2
2
heating at 408C, the signals due to (5ZnR,S)2 and (6ZnS,R
)
2
almost completely disappeared and the signals assigned to the
heterodimer 5ZnR,S·6ZnS,R became predominant (Figure 2c).
These results clearly indicated the formation of the hetero-
dimer through a pseudo-heterochiral association and that
5ZnR,S·6ZnR,S is more stable than each homochiral associa-
Figure 1. X-ray structures of porphyrin dimers. a) Top and b) side
viewsof (5Znrac)2, c) top and d) side views of (5ZnR,S)2, and e) view of
heterodimer 5ZnS,R·6ZnR,S. Ar1 =3,5-di-tert-butylphenyl, Ar2 =4-tert-
butylphenyl. The thermal ellipsoids are at the 50% probability level.
The meso-aryl substituents and hydrogen atoms are omitted for clarity
except (e).
tion. In sharp contrast, the similar experiment using (5ZnR,S
)
2
and (6ZnR,S)2 led to the appearance of two small new NH
signals corresponding to 5ZnR,S·6ZnR,S. The changes in the
spectra were only minor even after heating at reflux for three
days in chloroform (Figure 2 f). Finally, the heterodimeric
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Communications
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1
Figure 2. Change in the NH signals in the H NMR spectra:
a) (5ZnR,S)2, b) (6ZnS,R)2, and c) after heating the mixture of (5ZnR,S
and (6ZnS,R)2 (1.3”10À3 m); d) (5ZnR,S)2, e) (6ZnR,S)2, and f) after
heating the mixture of (5ZnR,S)2 and (6ZnR,S)2 (1.5”10À3 m).
)
2
[4] Very recently, the effect of a sulfur-centered chirality on the self-
assembly of meso-sulfinylporphyrins was reported, although the
level of discrimination was not high enough, see: Y. Matano, T.
Shinokura, K. Matsumoto, H. Imahori, H. Nakano, Chem. Asian
J. 2007, 2, 1417.
structure of 5ZnS,R·6ZnR,S was unambiguously elucidated by
X-ray diffraction analysis of a crystal grown by vapor
[5] a) H. Ogoshi, T. Mizutani, Acc. Chem. Res. 1998, 31, 81; b) J.-C.
Marchon, R. Ramasseul in The Porphyrin Handbook, Vol. 11
(Eds.: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press,
San Diego, 2003, p. 75; c) G. Simonneaux, P. Le Maux, Coord.
Chem. Rev. 2002, 228, 43.
diffusion of methanol into a solution of (5ZnS,R
)
and
2
(6ZnR,S)2 in chloroform (Figure 1e).[9]
In summary, we have achieved the expeditious synthesis
of novel chiral porphyrins with fused norbornene moieties by
the use of a Pd-catalyzed [3+2] annulation strategy. The
versatility of this strategy has been demonstrated in the
synthesis of benzoazanorbornene-fused zinc porphyrins,
which assemble to form a stable heterochiral dimer by
complementary coordination in both the solid and solution
states. The heterochiral assembly enables the formation of a
heterodimer constructed from two components through chiral
recognition. All these self-assembled porphyrin dimers were
unambiguously characterized by X-ray diffraction analysis.
These novel chiral porphyrins could also serve as chiral
catalysts in combination with central metal ions. This issue
would be a further challenging subject. Investigations on
functionalized heterolytic porphyrin dimers are currently
underway.
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J. Org. Chem. 2002, 67, 9276; c) M. Catellani, A. Del Rio, Russ.
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[9] Crystal data for 3Ni: C79H86N4NiO, Mr = 1166.23, triclinic, space
¯
group P1 (No. 2), a = 14.234(6), b = 14.559(5), c = 16.564(5) Š,
a = 108.939(9), b = 90.923(12), g = 95.734(12)8, V=
3226.3(19) Š3, Z = 2, 1calcd = 1.200 gcmÀ3, T= 123(2) K, 25317
measured reflections, 11184 unique reflections, R = 0.0920-
(I>2.0s(I)), Rw = 0.2493 (all data), GOF = 1.017 (I > 2.0s(I)).
Crystal data for (5Znrac)2: C148H162Cl12N10Zn2, Mr = 2637.06,
monoclinic, space group P21/c (No. 14), a = 13.029(2), b =
25.898(5) c = 21.281(5) Š„ b = 108.272(7)8, V= 6819(2) Š3,
Z = 4, 1calcd = 1.284 gcmÀ3, T= 123(2) K, 62760 measured reflec-
tions, 15366 unique reflections, R = 0.0708 (I > 2.0s(I)), Rw =
0.1977 (all data), GOF = 1.049 (I > 2.0s(I)). Crystal data for
(5ZnS,R)2: C146.37H160.75Cl4.88N10.37O0.25Zn2, Mr = 2373.12, mono-
clinic, space group P21 (No. 4), a = 16.673(3), b = 18.289(3), c =
Received: March 17, 2008
Published online: June 11, 2008
Keywords: chirality · coordination modes· palladium ·
.
porphyrinoids · self-assembly
23.215(4) Š, b = 110.970(3)8, V= 6610.2(2) Š3, Z = 2, 1calcd
=
[1] a) T. Imamura, K. Fukushima, Coord. Chem. Rev. 2000, 198, 133;
1.192 gcmÀ3, T= 90(2) K, 37895 measured reflections, 25705
unique reflections, R = 0.0997 (I > 2.0s(I)), Rw = 0.2866 (all
´
b) J. Wojaczynski, L. Latos-Graz˙ynski, Coord. Chem. Rev. 2000,
5380
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Angew. Chem. Int. Ed. 2008, 47, 5378 –5381

Angewandte
Chemie
data), GOF = 0.994 (I > 2.0s(I)). Crystal data for 5ZnS,R·6ZnR,S
266H270Cl7N20Zn4, Mr = 4256.65, monoclinic, space group P21
(No 4), a = 16.665(5), b = 30.973(5), c = 22.024(5) Š, b =
96.602(5)8, V= 11293(5) Š3, Z = 2, 1calcd = 1.142 gcmÀ3
T=
:
((5ZnS,R)2), and 679587 (5ZnS,R·6ZnR,S) contain the supplemen-
C
tary 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.
,
90(2) K, 68724 measured reflections, 37921 unique reflections,
R = 0.0569 (I > 2.0s(I)), Rw = 0.1492 (all data), GOF = 1.023 (I >
2.0s(I)). CCDC 680365 (3Ni), 679585 ((5Znrac)2), 679586
[10] For a b,b-azanorbornene-fused zinc porphyrin, see Ref. [2b].
This porphyrin is not chiral because of its symmetric structure.
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5381