Synthesis of 5,10,15,20-tetrakis(4-tert-butyl-2,6-dicarboxyphenyl)porphyrin: A versatile bis-faced porphyrin synthon for D4-symmetric chiral porphyrins

Article abstract of DOI:10.1021/ol015780a

(formula presented) A versatile bis-faced porphyrin synthon, 5,10,15,20-tetrakis(4-tert-butyl-2,6-dicarboxyphenyl)porphyrin, was synthesized. The eight carboxyl groups were readily converted into various amide groups, and condensation with chiral amines l

Full text of DOI:10.1021/ol015780a

ORGANIC
LETTERS
2001
Vol. 3, No. 12
1805-1807
Synthesis of 5,10,15,20-Tetrakis(4-tert-
butyl-2,6-dicarboxyphenyl)porphyrin: A
Versatile Bis-Faced Porphyrin Synthon
for D -Symmetric Chiral Porphyrins
4
,‡
Hiroshi Nakagawa,† Tetsuo Nagano,† and Tsunehiko Higuchi*
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo,
Bunkyo-ku, Tokyo 113-0033, Japan, and Faculty of Pharmaceutical Sciences,
Nagoya City UniVersity, Tanabe-dori, mizuho-ku, Nagoya 467-8603, Japan
higuchi@phar.nagoya-cu.ac.jp
Received March 2, 2001 (Revised Manuscript Received May 13, 2001)
ABSTRACT
A versatile bis-faced porphyrin synthon, 5,10,15,20-tetrakis(4-tert-butyl-2,6-dicarboxyphenyl)porphyrin, was synthesized. The eight carboxyl
groups were readily converted into various amide groups, and condensation with chiral amines led to various D -symmetric chiral porphyrins
4
with rigid structures.
To synthesize porphyrins bearing a molecular recognition
site, porphyrin synthons that have functional groups at the
o-positions of the meso-phenyl groups are usually employed,
since the chemically modified functional groups can be
located near the central metal to enhance selectivity in the
porphyrin-catalyzed reactions. Among available synthons,
tetrakis(o-monosubstituted phenyl)porphyrins1 such as
5,10,15,20-tetrakis(o-aminophenyl)porphyrin have the dis-
advantage that it is difficult to isolate one atropisomer.
Tetrakis(o-disubstituted phenyl)porphyrin synthons have
several advantages: (1) as many as eight positions of meso-
phenyl groups can be used to form a molecular recognition
site; (2) separation of atropisomers is not required; and (3)
both sides of the porphyrin plane can be modified. However,
existing tetrakis(o-disubstituted phenyl)porphyrin synthons
have serious limitations. For example, 5,10,15,20-tetrakis-
(2,6-dihydroxyphenyl)porphyrin2 is widely used as a tetrakis-
(o-disubstituted phenyl)porphyrin synthon, but the flexible
ether linkage should be covalently bound with the neighbor-
ing ether functional group to form a bridged structure in order
to shape the rigid cavity above the porphyrin ring.3 As a
result, porphyrin synthesis requires multiple reaction steps
and is of limited practical use. The same problem arises with
o-(bromomethyl)-substituted tetraphenylporphyrin.4 Another
synthon, 5,10,15,20-tetrakis(4-tert-butyl-2,6-diaminophenyl)-
porphyrin,5 is difficult to synthesize6 and air-sensitive. In
(2) (a) Collman, J. P.; Lee, V. J., Zhang, X. Inorg. Synth. 1997, 31, 117.
(b) Tsuchida, E.; Komatsu, T.; Hasegawa, E.; Nishide, H. J. Chem. Soc.,
Dalton Trans. 1990, 2713.
(3) (a) Naruta, Y.; Ishihara, N.; Tani, F.; Maruyama, K. Bull. Chem.
Soc. Jpn. 1993, 66, 158. (b) Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077.
(4) Jux, N. Org. Lett. 2000, 2, 2129.
(5) Rose, E.; Kossanyi, A.; Quelquejeu, M.; Soleilhavoup, M.; Duwavran,
F.; Bernard, N.; Lecas, A. J. Am. Chem. Soc. 1996, 118, 1567.
(6) Condensation of 2,6-dinitrobenzaldehyde and pyrrole afforded a
poorer yield than expected, and reduction of nitro groups proved difficult
by the reported method.5
† University of Tokyo.
‡ Nagoya City University.
(1) (a) Collman, J. P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.; Lang,
G.; Robinson, W. T. J. Am. Chem. Soc. 1975, 97, 1427. (b) Leondiadis, L.;
Momenteau, M. J. Org. Chem. 1989, 54, 6135.
10.1021/ol015780a CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/23/2001

Scheme 1a
a Reagents and conditions: (a) CCl4, 40 °C, iron powder, Br2, 44%; (b) (1) CCl4, halogen lamp, N-bromosuccinimide (2) CH3CN, reflux,
AcOK (3) H2O, EtOH, reflux, KOH, 85% (based on 8); (c) CH2Cl2, 0 °C, 4-methoxy-2,2,6,6-tetramethylpiperidine N-oxyl (4-Me-TEMPO),
NaOCl, 10 was recovered in 85% yield (2) CH3CN, rt, tetra-n-propylammonium perruthenate (TPAP), N-methyl-morpholine N-oxide (NMO),
65%; (d) CHCl3, rt, pyrrole, BF3‚Et2O, DDQ, 22%; (e) DMF, reflux Zn(OAc)2‚2H2O, 80%; (f) N-methylpyrrolidone, reflux, CuCN, 61%;
(g) H2O, reflux, H2SO4; (h) (1) CH2Cl2, reflux, oxalyl chloride (2) CH2Cl2, rt, RNH2, 40-60% (based on 15).
addition, meso-o-acylaminophenyl porphyrins are known to
decompose to inactive isoporphyrins in the catalytic oxida-
tion.7
an equimolar amount of the undesirable product 9 was
obtained and could not be separated from 8 by distillation
or silica gel column chromatography. Therefore the mixture
was directly used in the following reactions. The 4-MeO-
TEMPO/NaOCl system could oxidize 11 selectively to the
corresponding aldehyde, and 10 was recovered with high
purity. The recovered 10 was oxidized to 12 with the TPAP/
NMO system. The target porphyrin synthon 1-dication was
obtained from 8 in eight steps. The 1-dication could be
condensed with amines without purification, and its reaction
with various amines afforded D4-symmetric porphyrins (3-
7, yields 40-60%).
Here we report a convenient synthesis of a versatile bis-
faced porphyrin synthon, 5,10,15,20-tetrakis(4-tert-butyl-2,6-
dicarboxyphenyl)porphyrin 1. From compound 1, various
derivatives of D4-symmetric chiral porphyrins with a chiral
cavity around a catalytic site containing a metal ion can be
easily prepared.
Synthesis of benzaldehydes such as 2,6-dicarboxybenz-
aldehyde is difficult, and in addition the condensation of these
benzaldehydes with pyrrole failed to afford the corresponding
porphyrins with eight carboxyl groups. On the other hand,
5,10,15,20-tetrakis(2,6-dibromophenyl)porphyrin8 may be
superior as the bromo functional groups can be converted
to carboxyl groups via cyano groups. These porphyrins9 are
insoluble in most solvents, and introduction of tert-butyl
groups is one approach to improve the solubility. We
therefore designed compound 1 as a candidate synthon for
the synthesis of bis-faced porphyrins (Scheme 1). At the first
step to synthesize 8, 4-tert-butyltoluene was brominated, but
Compound 3 was prepared to examine the orientation of
1
the amide groups by H NMR spectral analysis (Table 1).
The peak due to tert-butyl groups bonded to nitrogens
showed an upfield shift (0.05 ppm) due to the ring current
effect of the porphyrin ring. On the other hand, the shift of
the amide protons (5.15 ppm) was not large. This indicates
that the tert-butyl groups are positioned directly over the
porphyrin and inside the shielding cone of the porphyrin and
(9) 5,10,15,20-Tetrakis(2,6-dicyanophenyl)porphyrin was synthesized by
the same method as 14 to 15 but could not be purified sufficiently because
of low solubility. FAB mass measurement of the reaction mixture shows
[M - H]+ by FAB MS.
(7) El-Kasmi, A.; Lexa, D.; Maillard, P.; Momenteau, M.; Save´ant, J.-
M. J. Am. Chem. Soc. 1991, 113, 1586.
(8) Ostovic, D.; Bruice, T. C. J. Am. Chem. Soc. 1988, 110, 6906.
1806
Org. Lett., Vol. 3, No. 12, 2001

utilizing coplanarity of amide groups and ester groups
attributable to dipole repulsion of the carbonyl groups.10 The
signals of the methyl protons were shifted upfield by the
ring current effect (-1.09 ppm for 6, -0.62 and -0.32 ppm
for 7). This shows the amino acid residues to be positioned
inside the shielding cone of the porphyrin, which should form
a rigid chiral cavity above the reactive site of the metal-
loporphyrin.
In conclusion, a versatile new bis-faced porphyrin synthon,
5,10,15,20-tetrakis(4-tert-butyl-2,6-dicarboxy-phenyl)porphy-
rin 1, was synthesized. This porphyrin should allow the
construction of molecular recognition sites over both sides
of the porphyrin ring, since it is easy to condense amines to
its eight carboxyl groups and these amide groups have a
consistent orientation to form a recognition site directed
inside the porphyrin ring. Moreover, condensation with
amino esters affords rigid chiral cavities. Such compounds
could be effective asymmetric epoxidation catalysts11 since
the meso-carbons would be more electron-deficient than in
the porphyrins derived from previously known bis-faced
porphyrin synthons, and higher turnover numbers can be
expected. We are currently attempting to prepare such
asymmetric catalysts.
Table 1. 1H NMR Shifts (in ppm from TMS) of
5,10,15,20-Tetrakis(o-mono- or
bis(N-tert-butylcarbamoyl)phenyl)porphyrin and
N-tert-Butylcarbamoylbenzene
NHCO
N-tert-butyl
octa-substituted 3
tetra-substituted (R,R,R,R)1b
N-tert-butylcarbamoylbenzene
5.15
5.38
5.94
0.05
0.10
1.47
the amide protons are directed outside, as shown in Figure
1. Therefore, this porphyrin has a rigid structure.
Acknowledgment. This work was supported in part by
Grants-in-Aid for Scientific Reseach (12793009 and 11470494)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL015780A
Figure 1.
(10) Nagai, Y.; Kusumi, T. Tetrahedron Lett. 1995, 36, 1853.
(11) For recent review, see: Rose, E.; Quelquejeu, M.; Pandian, R. P.;
Lecas-Nawrocka, A.; Vilar, A.; Ricart, G.; Collman, J. P.; Wang, Z.;
Straumanis, A. Polyhedron 2000, 19, 581.
1
Figure 1 shows the H NMR spectra of 6 and 7. These
porphyrins were designed to form rigid chiral cavities by
Org. Lett., Vol. 3, No. 12, 2001
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