New chemistry of porphyrin β-ketoesters: Synthesis of a novel covalently-linked dimer

Article abstract of DOI:10.1039/a700384f

Porphyrinyl β-ketoesters dimerize to afford novel bistetrapyrrole systems by way of a radical process; the X-ray structure of one such bistetrapyrrole 14 is reported.

Full text of DOI:10.1039/a700384f

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New chemistry of porphyrin b-ketoesters: synthesis of a novel covalently-linked
dimer
Robert T. Holmes, Jack J. Lin, Richard G. Khoury, Colin P. Jones and Kevin M. Smith*†
Department of Chemistry, University of California, Davis, CA 95616, USA
Porphyrinyl b-ketoesters dimerize to afford novel
bistetrapyrrole systems by way of a radical process; the
X-ray structure of one such bistetrapyrrole 14 is reported.
accessible through porphyrins (e.g. 6) suitably substituted with
b-ketoester substituents (Scheme 2).
The precursor 7 of 6 was synthesized using established
pyrrole chemistry; it was initially anticipated that Dieckmann
cyclization of 7 would give 6. The Michael acceptor pyrrole 8
was obtained from the formylpyrrole 9 by way of a Horner–
Wadsworth–Emmons reaction (Scheme 3). Treatment of 8 with
the 2-unsubstituted pyrrole 10 in refluxing acetic acid contain-
ing TFA gave the unsymmetrical dihydrodipyrrin 11,9 which
upon catalytic bisdebenzylation gave 12. MacDonald (‘2 + 2’)
condensation between 1310 and the unsymmetrical dihy-
drodipyrrin dicarboxylic acid 12 in the presence of acid and zinc
acetate, followed by removal of zinc with acid and then a basic
work-up, did not yield the expected porphyrin 7. Instead, a
Oxophlorins 1 can be readily oxidized by dioxygen to form p-
stabilized radicals 2,1 oxo derivatives 3,2 or covalently linked
dimers 4,3 by mechanisms similar to those established in
phenolic chemistry (Scheme 1).4 An example of a very stable
(sterically encumbered) oxophlorin p-radical was recently
reported,5 and although porphyrins can readily undergo one-
electron oxidation (to give p-cation radicals) these transient
species usually decompose to the parent porphyrin.6 Based on
knowledge of phenolic chemistry and its analogies with
oxophlorin chemistry,7 one might anticipate that any porphyrin
system which could efficiently form a radical at a meso-
benzylic atom (e.g. the carbonyl oxygen in oxophlorins, or a
meso-benzylic methylene carbon) should undergo chemistry
similar to that of oxophlorins (e.g. carbon–carbon dimerization,
reaction with dioxygen). Literature precedent suggests8 that
benzylic porphyrin radicals (e.g. 5) should, in principle, be
1
green compound was isolated (lmax 424, 606 nm). H NMR
spectroscopy indicated a non-conjugated macrocycle had been
formed [d 12.67, 11.51 (each s, 1 H, NH)]. X-Ray crystallo-
graphic analysis‡ (Fig. 1) confirmed the structure of the
compound to be the novel 10, 10A-bismacrocycle 14. The
linking 10,10A carbon–carbon bond length is 1.58 Å. Along with
dimer 14, porphyrins 15 and 16 and the hydroxy-substituted
chlorin 17 [lmax 424, 606 nm; d 11.50, 8.93 (each br s, 1 H,
OH)] were isolated. The structural assignment of 17 is based on
spectroscopic similarities between 17 and the analogue in the
15-unsubstituted series, for which an X-ray crystal structure
(not shown) has been obtained.
R1
R1
R1
R1
O
O
Et
Et
Et
Et
Et
Et
Et
Et
NH
N
N
NH
N
HN
HN
It was possible to isolate the target dimethyl ester porphyrin
7 in good yield by purifying the crude reaction mixture on
neutral alumina instead of silica gel. Based on observations of
the reactivity of 7 it became clear that the b-ketoester function
HN
R1
R1
R2
2
R1
R1
R2
1
O
MeO2C
Me
CO2Me
Me
CO2Me
Me
R1
R1
Et
Et
O
Me Me
Me Me
Me
Me
NH
N
N
NH
N
N
R1
R1
Et
Et
Et
Et
N
HN
N
NH
N
N
HN
HN
R2
R1
O
Me
HN
NH
R1
Et
Ph
Et
Et
Ph
Et
7
6
R1
R1
O
Et
Et
Et
Et
H
O
3
CO2Me
R1 = Et, R2 = H
H
N
•
Me
R1
R2
R1
R1
O
Me
Me
Me
HN
N
NH
N
N
NH
R1
HN
Me
Et
Et
4
Et
Ph
Et
R1 = Me, R2 = alkyl, aryl
5
Scheme 1
Scheme 2
Chem. Commun., 1997
819

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was not being formed by way of a base-catalysed Dieckmann
process upon 7. Subsequently, non-basic methods were devel-
oped to permit the controlled synthesis of covalent dimer 14 (by
way of 6), and the side products, simply by adsorbing porphyrin
7 on silica gel under CH2Cl2 for 14 h. Presumably, water present
on the silica gel makes it possible for small amounts of the
bis(methoxycarbonylmethyl)porphyrin 7 to hydrolyse and form
monocarboxylic acid by-products such as 18 and 19. At this
point, decarboxylation would form porphyrin 15 (or 16,
depending upon which ester has been hydrolysed) or it could
follow a mechanism to form the corresponding ‘anhydro’
derivative. The so-called anhydro-reaction12,13 proceeds revers-
ibly by way of an acid catalysed equilibrium which, in this case,
would be driven by formation of the b-ketoester moiety on the
periphery of the porphyrin 6 via attack by the methylene
adjacent to the remaining ester in 18 upon a putative acylium
species formed from its acetic acid substituent.
MeO2C
Me
MeO2C
Me
CO2Me
O
P
EtO
EtO
CHO
CH2CO2Me
NH
NH
KOH, THF
CO2Bn
CO2Bn
9
8
Me
Me
CO2Bn
AcOH, TFA
HN
10
Me
Me
MeO2C
CO2Me
Me
Me
MeO2C
Et
Ph
N
HN
N
Me
Me
NH HN
CO2R
HO
NH
This work was supported by grants from the National Science
Foundation (CHE-96-23117) and the National Institutes of
Health (HL-22252).
CO2R
Et
11 R = Bn
12 R = H
H2 Pd/C
Me
Me
H
Me
Me
(see text)
Footnotes
CHO
CHO
H
† E-mail: smith@chem.ucdavis.edu
NH HN
‡ Crystal data for 14. Crystals were grown from CH2Cl2–cyclohexane. A
Me
Me
Et
Ph
Et
parallelepiped single crystal was selected with dimensions 0.18 3 0.13 3
N
HN
N
OH
–
0.05 mm. The unit cell was triclinic P1 with cell dimensions a = 11.208(2),
Et
Ph
13
Et
b
= 12.474(3), c = 14.368(3) Å, a = 78.35(3), b = 76.86(3),
CO2Me
g = 83.98(3)°, V = 1912.2(7) Å3, and Z = 2 (FW = 748.7). X-ray
diffraction data were collected on a Siemens P21 diffractometer with a fine-
focus sealed tube [l(Cu-Ka) = 1.54178 Å] at 130(2) K in q–2q scan mode
to 2qmax = 112°. Of 5278 reflections measured (±h,±k,±l) 3283 were
independent and 1932 had I > 2s (Rint = 0.039). The structure was solved
by direct methods and refined (based on F2 using all independent data) by
full-matrix least-squares methods (Siemens SHELXTL V. 5.02); number of
parameters = 441. Hydrogen atom positions were located by their idealized
geometry and refined using a riding model. An absorption correction was
applied using XABS2.11 Final R factors were R1 = 0.083 (based on
observed data) and wR2 = 0.1998 (based on all data). Atomic coordinates,
bond lengths and angles, and thermal parameters have been deposited at the
Cambridge Crystallographic Data Center (CCDC). See Information for
Authors, Issue No. 1. Any request to the CCDC for this material should
quote the full literature citation and the reference number 182/406.
NH
Me
Me
R2
Me
14
OH
R1
CO2Me
Me
Me
Me
HO
Me
Me
Me
Me
Me
NH
N
N
N
HN
N
HN
NH
Me
Me
Et
Et
Ph
Et
Et
Ph
17
References
15 R1 = H, R2 = CO2Me
16 R1 = CO2Me, R2 = H
18 R1 = CO2H, R2 = CO2Me
19 R1 = CO2Me, R2 = CO2H
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Scheme 3
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O(1)
O(3)
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N(1)
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N(4)
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N(4A)
N(3A)
N(2A)
N(1A)
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O(3A)
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O(1A)
O(2A)
Fig. 1 Molecular structure of dimer 14
Received, 14th January 1997; Com. 7/00384F
820
Chem. Commun., 1997