Unusual regioselective mercuration of metalloporphyrins and its potential applications

Article abstract of DOI:10.1039/b618464b

The reaction of Hg(CF₃CO₂)₂ with metalloporphyrins produces mercurated porphyrins regioselectively, the reaction, surprisingly occurring at the most hindered β^B-position; this behavior is in marked contrast to the usual electrophilic substitution reactions of porphyrins, whose reactions produce meso-substituted porphyrins; the obtained mercurated porphyrins are active to transition metal-catalyzed coupling reactions, such as the Mizoroki-Heck reaction. The Royal Society of Chemistry.

Full text of DOI:10.1039/b618464b

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Unusual regioselective mercuration of metalloporphyrins and its
potential applications{
Ken-ichi Sugiura,*ab Aiko Kato,ac Kentaro Iwasaki,d Hitoshi Miyasaka,ae Masahiro Yamashita,abe
Shojun Hinodf and Dennis P. Arnold*c
Received (in Cambridge, UK) 19th December 2006, Accepted 9th March 2007
First published as an Advance Article on the web 27th March 2007
DOI: 10.1039/b618464b
5,15-disubstituted porphyrins (substituents = aryl or alkyl)
encouraged us to study the reaction of those compounds with
Hg(II) salts and the potential applications of the corresponding
mercury-substituted porphyrins.
The reaction of Hg(CF3CO2)2 with metalloporphyrins pro-
duces mercurated porphyrins regioselectively, the reaction,
surprisingly occurring at the most hindered bB-position; this
behavior is in marked contrast to the usual electrophilic
substitution reactions of porphyrins, whose reactions produce
meso-substituted porphyrins; the obtained mercurated porphyr-
ins are active to transition metal-catalyzed coupling reactions,
such as the Mizoroki–Heck reaction.
As porphyrins have a high reactivity towards electrophiles, an
electrophilic substitution reaction seemed to be the best candidate
for obtaining mercury-substituted porphyrins. Treatment of
5,15-bis(3,5-di-tert-butylphenyl)porphyrinato nickel (1a) with
Hg(CF3CO2)2 for 30 min smoothly produced the mercury-
substituted porphyrin. Due to the instability of the initial product,
the –HgOCOCF3-substituted porphyrin, the replacement of
Organomercury compounds have long attracted much attention1
from the viewpoint of their specific reactivity, attributable to the
electropositive character of mercury (electronegativity x = 2.00),2
despite their toxicity. The traditional and widely employed reaction
is the transmetallation reaction, i.e., the replacement of mercury
with a more electropositive metal such as Mg (x = 1.31), Zn (1.65)
and Ga (1.81); e.g., the formation of MgMe2, ZnMe2 and GaMe3
by the reactions of HgMe2 with metallic Mg, Zn and Ga,
respectively, for which the corresponding organometal compounds
are hard to obtain by direct metallation reactions.1
Organomercurials are also useful for the transmetallation of less
electropositive metals (e.g., Pd) by the substitution of halides.1
Recent interest focuses on the aryl coupling reactions with olefins
in the presence of transition metal catalysis, i.e., Mizoroki–Heck
reactions.3 Contemporary interdisciplinary research on porphyrins
requires advanced multi-functions, attributable to both the
porphyrin and the introduced functional group(s) (FG).4 To
create novel porphyrin FG-linked systems, peripherally-metallated
porphyrins (PMPs),5 including mercury-substituted porphyrins6
and the corresponding aryl coupling reactions, have been
extensively studied. The recent wide applications of functionalized
2
CF3CO2 with Cl2 was required, giving the –HgCl-substituted
analogue.7,8 Mono-mercurated product 2a was isolated as the
main product, after silica gel chromatography, in an acceptable
yield (33%) as a purple solid that was stable towards moisture, air
and light. In marked contrast to the usual meso-regioselectivity for
the electrophilic reactions of 5,15-disubstituted porphyrins, e.g.,
formylation and halogenation, the main product was characterized
as 2a; i.e., this mercuration reaction occurred at the more hindered
bB-position.9 Some metal dependence was observed for this
mercuration reaction, 1b and 1c affording 2b and 2c in 17 and
21% yields, respectively. The similar reaction behavior of 5,15-
dialkylporphyrin 1d to give 2d (23%) discounts a mercury–aryl
p-interaction reaction mechanism. No formation of the regio-
isomers, i.e., bA-substituted porphyrins, was observed by our very
careful chromatographic analyses of these four reactions.
To demonstrate the versatility of the mercury porphyrins
obtained in our study, we report three types of reactions of 2a.
Firstly, protolysis with trifluoroacetic acid (TFA) quantitatively
regenerates the starting material 1a, although 2a is stable under
treatment with acetic acid or water. An experiment using TFA-d
induced the regioselective ipso-substitution to give the correspond-
ing deuterated porphyrin 3.
aDepartment of Chemistry, Graduate School of Science and Engineering,
Tokyo Metropolitan University, 1-1 Minami-Ohsawa, Hachi-Oji,
Tokyo 192-0397, Japan. E-mail: sugiura@porphyrin.jp;
Fax: +81 42-677-2525; Tel: +81 42-677-2550
Secondly, the coupling reaction with methyl acrylate in the
presence of Pd catalysis, a Mizoroki–Heck reaction, was examined.
Initially, we attempted to use the widely-used reaction conditions,
e.g., a catalytic amount of Pd(OAc)2 and PPh3 as a ligand (condi-
tions (iv) in Scheme 1). Unexpectedly, rearrangement product 4
was obtained as a major product, along with the desired 5. The
replacement of PPh3 with a more bulky ligand, such as PtBu2-
biphenyl, produced only 4, suggesting that steric repulsion in the
Pd-inserted intermediate triggered the subsequent rearrangement
reaction. Omission of the phosphine ligand resolved the problem,
affording 5 as the sole product (conditions (v) in Scheme 1).
Thirdly, treatment with iodine achieved a perfect ipso-substitu-
tion, producing 6 quantitatively. The resultant bB-iodide should
bCREST, Japan Science and Technology Corporation, Kawaguchi
Center Building, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
cSchool of Physical and Chemical Sciences, Queensland University of
Technology, GPO Box 2434, Brisbane 4001, Australia.
E-mail: d.arnold@qut.edu.au; Fax: +61 7-3864-1804;
Tel: +61 7-3864-2482
dDepartment of Information and Image Science, Faculty of Engineering,
Chiba University, Inageku, Chiba 263-8522, Japan
eDepartment of Chemistry, Graduate School of Science, Tohoku
University, Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan
fDepartment of Material Science and Biotechnology, Graduate School of
Engineering, Ehime University, Bunkyo-Cho 3, Matsuyama, Ehime
790-8577, Japan
{ Electronic supplementary information (ESI) available: Experimental and
characterisation data. See DOI: 10.1039/b618464b
2046 | Chem. Commun., 2007, 2046–2047
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Fellowship from the Australian Academy of Science and the Japan
Society for the Promotion of Science. We gratefully acknowledge
the technical assistance of Mrs Yumiko Iwaki and M.S. Satoshi
Matsunaga, and the helpful discussion of Dr Kazunori
Hirabayashi and Dr Motoko S. Asano of Tokyo Metropolitan
University.
Notes and references
1 (a) F. Jensen and B. Rickborn, Electrophilic Substitution of
Organomercurials, McGraw-Hill, New York, 1968; (b) R. C. Larock,
Organomercury Compounds in Organic Synthesis, Springer-Verlag,
Berlin, 1985.
2 J. E. Huheey, E. A. Keiter and R. L. Keiter, in Inorganic Chemistry,
Harper Collins, New York, 1993, ‘‘Pauling’s electronegativity’’ from
Table 5.6, pp. 187–190.
3 Review: A. de Meijere and F. E. Meyer, Angew. Chem., Int. Ed. Engl.,
1994, 33, 2379.
4 The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and
R. Guilard, Academic Press, San Diego, 2000, vol. 6, ch. 40–46.
5 The following PMPs are reported: (a) Boron: A. G. Hyslop,
M. A. Kellett, P. M. Iovine and M. J. Therien, J. Am. Chem. Soc.,
1998, 120, 12676; (b) Magnesium and zinc: M. J. Therien, US Pat.
2002104072, 2002; Chem. Abstr., 2002, 138, p. 63589; (c) Palladium and
platinum: R. D. Hartnell and D. P. Arnold, Eur. J. Inorg. Chem., 2004,
1262 and references therein.
6 Few organomercury porphyrins have been reported: I. K. Morris,
K. M. Snow, N. W. Smith and K. M. Smith, J. Org. Chem., 1990, 55,
1231 and references therein.
7 Experimental details including spectroscopic data are described in
Electronic supplementary information (ESI{). General procedure of
mercuration reactions: A mixture of porphyrin (e.g. 1a: 0.9 mmol) and
Hg(CF3CO2)2 (0.9 mmol, 1.0 eq., Aldrich) dissolved in dry dichloro-
methane (170 mL) was stirred under ambient conditions for 30 min.
Saturated aq. NaCl (7 mL) was added and the mixture was stirred for a
further 30 min. The solution was washed with two portions of water and
the organic phase was removed under reduced pressure. The residue was
chromatographed on silica gel, eluting with a mixed solvent of CH2Cl2
and hexane (1 : 3), to give 2a.
8 All new materials were characterized by spectroscopic methods. X-Ray
photoelectron spectroscopy (XPS) also supports the formation of the
mercurated porphyrins. The XPS core ionization potentials of Hg 4f7/2
for 2a, 2b, 2c and 2d are 101.6, 101.3, 101.5 and 101.8 eV, respectively
(the spectrometers were calibrated such that the Au 4f7/2 peak of the
clean sputtered metals appeared at 84.0 eV).
Scheme 1 Reagents and conditions: (i) 1.0y1.5 equiv. Hg(CF3CO2)2,
CH2Cl2, r.t. for 30 min, then NaCl aq.; (ii) CF3CO2H, then NaHCO3 aq.;
(iii) CF3CO2D, then NaHCO3 aq.; (iv) Pd(CH3CO2)2, PPh3 or PtBu2-
biphenyl, K2CO3, methyl acrylate, THF—these conditions afforded
a mixture of 4 and 5; (v) Pd(CH3CO2)2, K2CO3, methyl acrylate,
THF—these conditions afforded the sole product 5; (vi) I2, THF; (vii)
PhB(–OCMe2CMe2O–), Pd0(PPh3)4, Ba(OH)2 aq., diglyme.
also be useful for the functionalization of porphyrins, e.g., as an
important substrate for aryl coupling reactions, such as the
Suzuki–Miyaura reaction. The reaction of 6 with phenylboronic
acid ester in the presence of Pd0(PPh3)4 produces the correspond-
ing bB-phenyl porphyrin 7. No rearrangement was observed in this
Pd-catalyzed reaction.
9 A preliminary single crystal diffraction study of 2a also supports the
substitution position:
Although the detailed reaction mechanism of the regioselective
mercuration is still unclear, the mercuration reaction of 5,15-
disubstituted porphyrins selectively occurred at the bB-position of
the porphyrin. With the inclusion of our new discoveries, chemists
can now regioselectively functionalize 5,15-disubstituted porphyr-
ins at the bB (via our mercuration), bA (via Osuka et al.’s
Ir-catalyzed boronation10) or meso (via usual electrophilic
substitution) positions.
¯
Crystal data: Triclinic, P1 (#2), a = 13.224(3), b = 17.378(3), c = 21.090(3) s,
a = 69.703(9), b = 71.092(9), c = 85.79(1)u, V = 4296.2(1) s3. CCDC
638202. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b618464b.
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan, and a Short-Term Visiting
10 H. Hata, H. Shinokubo and A. Osuka, J. Am. Chem. Soc., 2005, 127,
8264.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 2046–2047 | 2047