A facile and versatile preparation of bilindiones and biladienones from tetraarylporphyrins

Article abstract of DOI:10.1039/b414299c

Bilindiones and biladienones carrying aryl groups at the meso positions were prepared using coupled oxidation reactions of iron tetraarylporphyrins in 20-63% yield. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b414299c

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A facile and versatile preparation of bilindiones and biladienones from
tetraarylporphyrins{
Takae Yamauchi,a Tadashi Mizutani,*b Kenji Wada,a Shoji Horii,b Hirotaka Furukawa,a
Shigeyuki Masaoka,a Ho-Chol Changa and Susumu Kitagawaa
Received (in Cambridge, UK) 16th September 2004, Accepted 6th December 2004
First published as an Advance Article on the web 21st January 2005
DOI: 10.1039/b414299c
that of 1 and the 13C NMR spectrum showed one sp3 carbon
Bilindiones and biladienones carrying aryl groups at the meso
resonance (C-20) at 76.4 ppm, while the 13C NMR spectrum of 1
showed one at 75.0 ppm. The 1H NMR spectrum is similar to that
positions were prepared using coupled oxidation reactions of
iron tetraarylporphyrins in 20–63% yield.
of 1, except for one upfield shifted NH resonance and one
Linear tetrapyrroles such as bilindiones are a family of compounds
that have various biological and chemical functions due to their
redox activity,1 photochemical isomerisation and energy transfer,2
coordinating ability,3 and conformational flexibility, and a
chiral framework applicable to various enantioselective processes.4
In nature, these compounds are biosynthesized from porphyrin
via enzymatic oxidation catalysed by heme oxygenase.5
Phytochromobilin is one of such compounds that undergo
photochemical cis–trans isomerisation and act as a sensory
chromophore in a photoreceptor protein.6 Although bilindiones
have potential multi-functional properties, the synthesis of
bilindiones requires a multi-step route owing to the low symmetry
of the molecule.7 This is one of the reasons that the compounds
are less frequently employed as a scaffold for functional
materials compared to well-studied porphyrins. Because a variety
of tetraarylporphyrins have been prepared as models for photo-
synthesis and redox enzymes, a synthetic procedure converting
tetraarylporphyrins to bilindiones should be a versatile and
efficient route to these compounds. In this paper we report the
oxidation of iron tetraarylporphyrin by dioxygen in the presence of
a reductant as the new synthetic route to a series of bilindiones
and biladienones. Oxidation of metalloporphyrins by dioxygen is
also important as a degradation pathway of porphyrin catalysts
during cytochrome P-450 type oxidations. Therefore, investigation
of reactivity of iron porphyrin with dioxygen is important for its
application as a catalyst and an oxygen carrier.
downfield shifted b-pyrrole resonance, that are ascribed to the
N21H proton and H-3 of the lactam A-ring, respectively. These
NMR data suggest that the red isomer is (EZ)-biladienone 2. The
structural assignment was corroborated by comparisons of the 1H
NMR with that of EZ-15-butylbiladienone reported by Callot
et al..9 Biladienone 2 can be photochemically isomerised to 1, while
the reverse isomerisation from 1 to 2 did not proceed.{
When the coupled oxidation was carried out in refluxing
chloroform for 1.5 h, more polar fractions 3 and 4 appeared as
blue spots on silica gel TLC, in addition to 1 and 2. The FAB mass
spectrum of 3 showed an M+ peak at m/z 558, suggesting that it is
bilindione. Compound 3 showed a simple 1H NMR spectrum
exhibiting only four b-pyrrole proton resonances, implying that the
product has a symmetrical framework. On the basis of COSY,
NOESY, and HMBC spectra, we identified this product as
(ZZZ)-bilindione 3, the yield of which was 20%. The simple NMR
spectrum can be attributable to the fast proton tautomeric
isomerisation of the NH proton on the B-ring pyrrole.
As a typical reaction, a solution of [5,10,15,20-tetraphenyl-
porphyrinato]iron(II) in chloroform was treated with pyridine,
ascorbic acid and dioxygen at room temperature for 30 min. The
oxidation proceeded smoothly, and usual work-up, i.e. precipita-
tion with NaBF4 and treatment with HCl, afforded a violet spot
and a more polar red spot on silica gel TLC.
After silica gel column purification, the violet fraction was
isolated as the major product in 63% yield. Its spectroscopic data
coincided with that for biladienone 1, which had been obtained in
the photochemical oxidation of the tetraphenylporphyrin dianion
by Cavaleiro and co-workers.8 The second red fraction was
obtained in 15% yield. Its mass spectrum was almost identical with
Scheme 1 Reagents: (a) O2, ascorbic acid, pyridine in CHCl3, 30 min, rt,
(b) NaBF4, (c) 1 M HCl.
A slightly more polar, blue fraction 4, was obtained in an equal
amount to 3. Compound 4 showed a UV-visible spectrum and a
mass spectrum almost identical to those of 3, while the 1H NMR
spectrum of 4 was complex, exhibiting eight b-pyrrole resonances.
The diagnostic resonances are one NH proton at 9.11 ppm, shifted
downfield relative to that of 3, which showed an NOE with the
{ Electronic supplementary information (ESI) available: experimental
details and NMR data and spectra for 1–4. See http://www.rsc.org/
suppdata/cc/b4/b414299c/
*tmizutan@mail.doshisha.ac.jp
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Table 1 Substituent effects on the reaction yield of ZZ-biladienonea
para-Substituent R
Yield (%)
Reaction time (min)
H
63
73
72
31
30
15
30
90
OMe
n-C12H25
CN
a
form a column of helix in the crystal. Compared to the bilindiones
with alkyl substituents at the b-positions of pyrrole, 3 has a
narrower helix with a larger helix pitch. The distance between C5
˚
˚
and C15 is 6.17 A, shorter than that of biliverdin (6.70 A).
Introduction of phenyl groups at the meso position makes the
bond angles of C4–C5–C6, C9–C10–C11, and C14–C15–C16,
smaller than those of biliverdin,12 leading to better spatial overlap
of the terminal A, D pyrroles. The average of the three bond
angles of 3 was 123.1u, while that of biliverdin was 126u12a and
127.8u12b on the basis of X-ray crystallographic structures. This
difference should be important in bilindione chemistry such as
the dynamic process of helix inversion13 and the coordination to
metal ions.
Fig. 1 ORTEP view of 3 with thermal ellipsoids at 30% probability.
most downfield resonance of the b-pyrrole protons appearing at
7.58 ppm. These features can be best explained by assuming that
the A-ring pyrrole is connected via a double bond with the E
configuration, and the NH proton at 7.1 ppm and the b-proton at
7.58 ppm are assigned to those of the A-ring pyrrole. Then the
b-pyrrole proton on the A-ring should be close to the NH proton
of the D ring, resulting in the observed NOE. The COSY and
HMBC spectra also support the assignment and the structure of 4
shown in Scheme 1.
The reaction is applicable to tetraarylporphyrins with various
substituents on the aryl groups. The effects of para-substituents on
the aryl groups on the reactivity are summarized in Table 1.
Electron-withdrawing groups such as a cyano group lowered the
yield while an electron-donating group improved the yield. The
coupled oxidation of [5,10,15,20-tetramesitylporphyrinato]iron
did not proceed even in refluxing chloroform, with the starting
porphyrin recovered. Thus, introduction of ortho-substituents
strongly inhibited the oxidation. These observations imply that
the oxidation occurs via intramolecular electrophilic attack of the
coordinated oxygen on the meso carbon. We previously demon-
strated that the coupled oxidation of b-substituted porphyrin
occurs selectively at the electron-rich meso carbon, by using a
trifluoromethyl group as a directing substituent.14
Illumination with visible light converts 3 to 4 and vice versa. The
1H NMR spectrum of the illuminated sample indicated that the
steady-state mixture contains 3 and 4 in a 0.9 to 1 ratio. Molecular
orbital calculations at the B3LYP/6-31G* level indicated that the
ZZZ isomer of etiobiliverdin was more stable than the EZZ
isomer by 5.0 kcal mol21, while 3 was more stable than 4 only by
0.3 kcal mol21. The energy difference between the ZZZ and EZZ
isomer of etiobiliverdin is ascribed to the steric repulsion between
the b-alkyl groups and the pyrrole ring. Lack of such steric
repulsion in 4 lead to almost equal distribution of the isomers in
triphenylbilindiones.
Compared to the photo-oxidation and the oxidation with metal
salts (Ce and Tl), the coupled oxidation described here gave the
products in a higher yield with less by-products.10 Preparation of
2–4 has not been reported before.
In summary, the coupled oxidation of iron tetraarylporphyrins
afforded products with different oxidation levels. The reaction
mechanism leading to 1–4 is not known, and further investigation
is necessary to elucidate it, which should shed light on the reaction
of heme oxygenase.
A crystal of 3 suitable for the single-crystal X-ray crystal-
lographic analysis was obtained by diffusion of hexane to a
chloroform solution of 3. The crystal structure of 3 demonstrated
that it is a ZZZ,syn,syn,syn diketo11 isomer with a helicoidal
conformation (Fig. 1).§ The dihedral angles of exocyclic single and
double bonds are 9.9 (N21–C4–C5–C6), 15.9 (C4–C5–C6–N22), 9.6
(N22–C9–C10–C11), 9.9 (C9–C10–C11–N23), 7.4 (N23–C14–C15–C16),
1.1u (C14–C15–C16–N24), showing that the A-ring pyrrole is
distorted from coplanarity with the D-ring pyrrole. This can be
attributed to the repulsion of the N–H dipoles of the A- and B-ring
pyrroles. In the crystal, the NH group of the A-ring is hydrogen
bonded to the D-ring carbonyl group of the neighboring molecule,
to form a homochiral column. The three NH protons were located
in the difference Fourier maps. In a unit cell, there are four
bilindione molecules and two are P- and the other two are M-helix.
The bilindione molecules with the same chirality are stacked to
Takae Yamauchi,a Tadashi Mizutani,*b Kenji Wada,a Shoji Horii,b
Hirotaka Furukawa,a Shigeyuki Masaoka,a Ho-Chol Changa and
Susumu Kitagawaa
aDepartment of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto University,
Kyotodaigaku-katsura, Nishikyo-ku, Kyoto, 615-8510, Japan
bDepartment of Molecular Science and Technology, Faculty of
Engineering, Doshisha University, Kyotanabe, Kyoto, 610-0321, Japan.
E-mail: tmizutan@mail.doshisha.ac.jp; Fax: +81-774-65-6794
Notes and references
{ Geometry optimisation of 1 by molecular orbital calculations at the
B3LYP/6-31G* level indicated that the 15-hydroxy group is hydrogen
bonded to the 1O-carbonyl group, while this is not the case for 2. This
1310 | Chem. Commun., 2005, 1309–1311
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hydrogen bond and the hydrogen bond between N21–H–N22 can stabilise 1
compared to 2, to result in one-way isomerisation.
§ Crystal data. C37H26N4O2, M 5 558.64, monoclinic, a 5 5.905 (1),
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3
˚
˚
b 5 22.765 (4), c 5 21.913 (4) A, b 5 100.031 (4), U 5 2900 (1) A ,
,
T 5 243.2 K, space group P21/c (no. 14), Z 5 4, m(Mo–Ka) 5 0.081 mm21
6541 reflections measured, 4036 unique which were used in all calculations.
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