Palladium-catalyzed dimerization of meso-bromoporphyrins: highly regioselective meso-bβ coupling through unprecedented remote C-H bond cleavage

Article abstract of DOI:10.1002/chem.200902143

Linked porphyrins: A porphyrin undergoes unique homocoupling in the reaction of meso-bromoporphyrins under palladium catalysis (see scheme). Formal remote C - H bond cleavage leads directly to the construction of meso-Bβ-linked diporphyrins in good yields

Full text of DOI:10.1002/chem.200902143

DOI: 10.1002/chem.200902143
Palladium-Catalyzed Dimerization of meso-Bromoporphyrins: Highly
À
Regioselective meso–b Coupling through Unprecedented Remote C H Bond
Cleavage
Sumito Tokuji,[a] Taiga Yurino,[a] Naoki Aratani,[a] Hiroshi Shinokubo,*[b] and
Atsuhiro Osuka*[a]
In the past three decades, considerable synthetic efforts
have been devoted towards directing porphyrin oligomers as
biomimic models of photosynthetic systems and oxygen re-
ducing enzymes, photonic materials, and functional molecu-
lar devices.[1] Among these, directly-linked porphyrin oligo-
mers have been a unique and promising focus because of
their large electronic coupling, orthogonal molecular geome-
tries, potential large nonlinear optical properties, and so
forth.[2] We found that one-electron oxidation of 5,15-diaryl-
substituted porphyrins led to the formation of meso–meso-
and meso–b-linked porphyrins for which the coupling regio-
selectivity is determined by the HOMO characteristics,
either a1u or a2u.[3] The chemistry of meso–meso coupling of
porphyrins has been later extended to an extremely long
linear 1024-mer,[4] extensively p-conjugated porphyrin
tapes,[5] and three-dimensional supramolecular arrays.[6]
A recent popular trend is to apply transition-metal-cata-
lyzed reactions to porphyrin substrates for which the reac-
tion routes follow the same expected outcomes as those of
nonporphyrinic substrates.[7,8] Recently, however, meso- and
b-unsubstituted porphyrins have been demonstrated to be
an interesting platform to achieve unique reactions under
transition-metal catalysis.[9] We have developed iridium-cata-
lyzed regioselective borylation of porphyrins at the b-posi-
tions which are distant from meso-aryl substituents (denoted
as ba-positions; see Scheme 1). This direct borylation fur-
Scheme 1. Regioselective synthesis of directly meso–bb-linked diporphy-
rin 2.
nishes useful precursors for the synthesis of novel porphyr-
ins.[10,11] Intrinsic unique potential of porphyrin peripheries
has also been indicated by [3+2] annulation reactions of
meso-bromoporphyrins with internal acetylenes or norbor-
nene substrates under palladium-catalysis, both of which in-
[a] S. Tokuji, T. Yurino, Dr. N. Aratani, Prof. Dr. A. Osuka
Department of Chemistry
Graduate School of Science, Kyoto University
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax : (+81)75-753-3970
a
[12]
À
volve C H bond cleavage at the b -position. In contrast,
selective reaction at the b-positions that are close to meso-
aryl substituents (denoted as bb-positions) is quite rare.[13]
Herein we disclose the novel dimerization of meso-bromo-
porphyrins to provide meso–bb directly linked diporphyrins.
Usually, Pd-catalyzed homocoupling affords symmetrical
coupling products, however, in contrast, this reaction yields
unsymmetrical diporphyrins with perfect regioselectivity.
E-mail: osuka@kuchem.kyoto-u.ac.jp
[b] H. Shinokubo
Department of Applied Chemistry
Graduate School of Engineering, Nagoya University
Chikusa-ku, Nagoya 464-8603 (Japan)
Fax : (+81)52-789-5113
E-mail: hshino@apchem.nagoya-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902143.
À
Quite unexpectedly, this coupling formally involves the C
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COMMUNICATION
H bond cleavage at the bb-position that is remote from the
brominated meso-position, where the coupling reaction is
probably initiated.
meso–b-linked diporphyrins that have an unsubstituted
meso-position.
After extensive optimization of the reaction conditions,
the yield of 2a was improved to 42% by the use of indi-
During our attempts to explore novel coupling reaction of
1
porphyrin substrates, after analysis of the H NMR spectrum
umACTHNGUTERNNUG
(III) chloride tetrahydrate as a Lewis acid.[16] Further-
of the crude reaction mixture, we noticed the formation of
porphyrin dimer 2a in ꢀ3% yield in addition to debromi-
nated porphyrin 3a. This was achieved by heating 5-bromo-
10,15,20-triphenyl zinc(II) porphyrin (1a) at 1308C in
DMF–toluene for 48 h in the presence of Herrmannꢁs cata-
lyst[14] (5 mol%) and zirconium tetrachloride (Scheme 1.
R1 =R2 =Ph, M=Zn, Lewis acid=ZrCl4). The parent mass
ion peak of 2a was observed at m/z 1233.2112 (calcd for
[C76H46N8Zn2Cl]À =1233.2122 [M+Cl]À) in its high-resolu-
tion electrospray-ionization time-of-flight (HR-ESI-TOF)
mass spectrum, indicating the formation of a dimeric prod-
more, employment of microwave heating drastically short-
ened the reaction time: 2a was obtained in 49% yield at
1608C for 1 h under microwave irradiation. Under the same
conditions, the use of 5 mol% of the bispalladium complex
provided 2a in 31% yield, indicating that this reaction pro-
ceeds in a catalytic manner. Further optimization of the re-
action conditions confirmed that the combination of Herr-
mannꢁs catalyst and Bu4NBr is very effective for this reac-
tion (Table 1, entries 3 and 6). In the absence of Herrmannꢁs
catalyst, 2a was not obtained at all, and the use of [Pd-
AHCTUNGRTEGNUN(N OAc)2] provided only 3a along with 1a (entries 1 and 4).
1
uct. The analysis of the H NMR spectrum of 2a revealed
When PPh3 exists in the reaction mixture, 1a was all con-
verted into 3a (entries 2 and 5). The presence of a small
amount of water has been confirmed to be important for the
reliable and reproducible yield of 2a (entry 7).
the presence of six b-pyrrolic doublet peaks and two singlet
signals derived from one porphyrin subunit and only four b-
pyrrolic doublet peaks from another porphyrin. This indicat-
ed that the two porphyrin subunits are not equivalent and
that diporphyrin 2a should have a plane symmetric struc-
ture. Notably, the signals at d=6.66, 4.62, and 3.63 ppm,
which are assigned to be ortho-, meta-, and para-protons of
one of the phenyl groups, are strongly upfield-shifted, prob-
ably because of a diatropic current of the aromatic porphy-
rin macrocycle. These results suggest a rather unexpected
structure, meso–bb-linked diporphyrin, for 2a.
Table 1. Screening of palladium catalysts for synthesis of meso–b-linked
diporphyrin 2a.[a]
Finally, the X-ray crystallographic analysis of 2c (R1 =
R2 =Ph, M=Cu) unambiguously elucidated its meso–bb-
linked dimeric structure (Figure 1).[15] The phenyl ring at the
5-position in the porphyrin subunit A is located above the
porphyrin subunit B with an interplanar distance of only
2.959 ꢂ and a tilt angle of 13.48. The mean planes of por-
phyrin macrocycles as defined by four pyrrolic nitrogen
atoms are almost orthogonal to each other with a dihedral
angle of 71.38. These structural features are similar to the
meso–b-linked diporphyrin reported by Senge et al.[2j] The
UV/Vis absorption spectrum shows a split Soret band, as a
consequence of the exciton coupling in line with the directly
linked dimeric structure (see the Supporting Information).
This is, to the best of our knowledge, the first example of
Entry
Catalyst system
Yield[e] [%]
1
2
3
4
5
6
7
[Pd
[Pd
U
0
0
7
0
0
Herrmannꢁs cat.
[Pd
[Pd
G
[b,c]
49[f]
16
Herrmannꢁs cat./Bu4NBr[b,d]
[a] Reaction conditions: 1a (25 mmol), Pd cat. (30 mol%Pd), InCl3·4H2O
(1 equiv), Na2CO3 (3 equiv), DMF (0.5 mL), toluene (0.5 mL), H2O
(20 mL), 1608C, 1 h, under microwave irradiation. [b] Bu4NBr (60 mol%).
[c] PPh3 (70 mol%). [d] No addition of H2O. [e] Calculated yield based
1
on H NMR spectra. [f] 43% isolated yield.
The reaction proceeded cleanly without any by-products
except for the debrominated porphyrin 3. Importantly, the
dimerization was perfectly regioselective, and none of other
isomeric diporphyrins were detected in the crude reaction
mixture. The dimerization reaction of various bromopor-
phyrins is summarized in Table 2. Nickel porphyrin under-
went the dimerization to afford the corresponding dipor-
phyrin 2b in good yields. Copper porphyrin or a porphyrin
with 3,5-di-tert-butylphenyl groups furnished diporphyrin 2c
or 2d in a lower yield, presumably as a result of the reduced
solubility or the steric hindrance of the bulky substituents,
respectively. Interestingly, the reaction proceeded in almost
Figure 1. X-ray crystal structure of 2c. The thermal ellipsoids are at the
50% probability level. Hydrogen atoms are omitted for clarity.
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H. Shinokubo, A. Osuka et al.
Table 2. The effect of substituents (R1 and R2) and central metals (M)
(see Scheme 1, Lewis acid=InCl3·4H2O).[a]
Entry R Group
Metal Product Yield [%]
1
2
3
4
5
6
R1 =R2 =Ph
Zn
Ni
Cu
Zn
Zn
Zn
2a
2b
2c
2d
2e
2 f
43
47
26
26
39
46
R1 =R2 =Ph
R1 =R2 =Ph
R1 =R2 =3,5-di-tert-butylphenyl
R1 =R2 =n-C6H13
R1 =n-C6H13, R2 =Ph
[a] Reaction conditions: bromoporphyrin (25 mmol), Herrmannꢁs cat.
(15 mol%), InCl3·4H2O (1 equiv), Bu4NBr (60 mol%), Na2CO3
(3 equiv), DMF (0.5 mL), toluene (0.5 mL), H2O (20 mL), 1608C, 1 h,
under microwave irradiation.
the same yields with the same regioselectivity in the case of
meso-alkylporphyrin (R1 =n-hexyl or n-pentyl). Conse-
quently, the unexpected regioselectivity of dimerization
cannot be explained by the directing effect of the aromatic
substituent. The UV/Vis absorption spectrum of 2e shows a
clearly split Soret band that is distinctly different from that
of 2a, reflecting the electron-donating property of meso-sub-
stituents (SI).
Scheme 2. A proposed reaction mechanism.
The reaction mechanism is not clear at this stage. Howev-
er, we confirmed that reduced porphyrin 3 does not partici-
pate in the dimerization reaction. A crossover experiment
with 1a and 3g (R1 =Ph, R2 =p-tolyl, M=Zn) yielded only
homocoupled diporphyrin 2a without any trace amount of
the cross-coupled diporphyrin (Figure S7 and S8). Porphyrin
3g was recovered quantitatively. It is quite reasonable to
consider that the oxidative addition of the palladium(0) spe-
cies to the Cmeso-Br bond of 1 would initiate this coupling to
provide meso-palladioporphyrin A. We propose that intra-
molecular Heck-addition-elimination might be involved in
this unusual coupling: meso-palladioporphyrin
A could
Scheme 3. Synthesis of a porphyrin tetramer.
attack another molecule of A at the pyrrolic C=C bond
through bridged bispalladium species B (Scheme 2). Then
the meso-position would be reduced to provide the product
2 through hydridopalladium species D, which would be re-
sulted from b-elimination from C.
The newly synthesized meso–bb-linked diporphyrin has
still a reactive meso-position, which indicates a possibility to
functionalize furthermore. We examined AgI-promoted cou-
pling of diporphyrin 2a. Diporphyrin 2a was heated at 458C
with 1.5 equiv of AgPF6 and 1% DMA[17] in CHCl3 for 24 h
to construct 4 in 20% yield along with the recovery of 2a
(60%) (Scheme 3). The porphyrin tetramer 4 was fully char-
acterized by HR-MS, 1H NMR, UV/Vis absorption, and
fluorescence measurements. Figure 2 shows the UV/Vis ab-
sorption spectra of 2a and 4.
In conclusion, we found the Pd-catalyzed unprecedented
homocoupling reaction of meso-bromoporphyrins to furnish
directly meso–b-linked diporphyrins in good yields with per-
fect regioselectivity. Curiously, the reaction proceeds
Figure 2. UV/Vis absorption spectra of 2a (dashed line) and 4 (solid line)
in CH2Cl2.
À
through formal direct C H functionalization of porphyrin at
metal-catalyzed reactions. Along this line, we are currently
À
the most hindered b-position. The reaction mechanism clear-
ly needs further investigation, but these results indicate the
high potentiality of porphyrin peripheries toward transition-
exploring further direct C H functionalizations of porphyr-
ins by taking advantage of transition metal-catalyzed trans-
formation.
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Coupling of Bromoporphyrins
COMMUNICATION
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Acknowledgements
This work was supported by Grants-in-Aids for Scientific Research (No.
19205006, 20108001 “pi-Space”, and No. 21685011) from MEXT, Japan.
H.S. gratefully acknowledges financial support from the Asahi Glass
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kan University) for MALDI-TOF MS measurements.
À
Keywords: arylation
·
C C coupling
·
palladium
·
porphyrinoids
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Received: August 1, 2009
Published online: October 15, 2009
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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