Novel protecting strategy for the synthesis of porphyrins with different distal and proximal superstructures

Full text of DOI:10.1021/jo981834r

8
082
J . Org. Chem. 1998, 63, 8082-8083
Communications
Novel P r otectin g Str a tegy for th e Syn th esis
of P or p h yr in s w ith Differ en t Dista l a n d
P r oxim a l Su p er str u ctu r es
un-, mono-, and bistritylated TAPP’s. This mixture is then
absorbed on basic alumina and heated in toluene/heptane
for 15 h. In this process, 3.1-TrTAPP 2 and RRRR-TAPP 1a
are selectively enriched and can be conveniently isolated by
flash chromatography in 30% (2) and 26% (1a ) yield,
respectively (Scheme 1). The procedure resembles Lindsey’s
enrichment method for RRRR-TAPP in that the most polar
atropisomer builds up to the largest extent.6
J ames P. Collman,* Martin Br o¨ ring, Lei Fu,
Miroslav Rapta, Reinhold Schwenninger, and
Andrei Straumanis
,7
Department of Chemistry, Stanford University,
Stanford, California 94305-5080
To ensure the structural assignment beyond the NMR
analysis, 2 was transformed into the known RRR-tris(o-
3
pivaloylamido)phenyl-â-(o-aminophenyl)porphyrin by treat-
Received September 9, 1998
ment with pivaloyl chloride, followed by acidic removal of
the protection group. The NMR spectra and Rf value of the
material thus obtained were identical with those of an
authentic sample.
The four distinct atropisomers of tetrakis-5,10,15,20-(o-
aminophenyl)porphyrin (TAPP) 1a -d (Scheme 1), readily
available from the reduction of the corresponding nitro
compounds, provide four very different precursors for the
synthesis of superstructured porphyrins. A great number
of syntheses of porphyrin-based catalysts and functionalized
porphyrins modeling enzymatic activities have hinged on the
1
The availability of 3.1-TrTAPP 2 opens up unique pos-
sibilities for the rational design of heme models. This can
best be shown by the syntheses of the new cytochrome c
oxidase model ligands 3 and 4 (Scheme 2). Starting with 2,
8
acylation of the three R pickets with chloroacetyl chloride
9
or acryloyl chloride yields the porphyrins 5 and 6, respec-
derivatization of one of the four atropisomers of TAPP, the
tively, both carrying activated pickets exclusively on the
distal face. Simple acid treatment (HCl gas, dichloro-
methane, 10 min) quantitatively removes the trityl group
to give 7 and 8, respectively. No interference with the
reactive chloro- and acryloyl pickets was noticed. The
reactions of the aminoporphyrins 7 and 8 with pyridyl acid
chlorides (prepared in situ from the respective acids 11 and
12) produce 9 and 10 and thus finish the construction of the
proximal sites. 10 undergoes a 3-fold Michael addition
symmetric RRRR- and RâRâ-TAPP being the most popular.2
However, porphyrins with different distal and proximal
superstructures, which resemble the metalloporphyrin sites
in biological systems much better, are hard to obtain due to
the lack of discrimination of the amino groups.
Work in our group and elsewhere involving the prepara-
tions of “tailed” porphyrins employ the unique shape of the
RRRâ atropisomer 1b. However, the syntheses usually start
with RRRR-TAPP 1a , which circumvents the R versus â issue
reaction with triazacyclononane (TACN) to give 4 under
but adds a late, low-yield rotation step.3
-5
conditions similar to those described by us earlier.9
Our desire for a
generally applicable and more straightforward route led to
the development of an extremely useful RRRâ-TAPP ana-
logue with a protected â picket, allowing selective, high-yield
derivatizations of the three R amines. This communication
describes a method for the synthesis/enrichment of 2, which
we call â-trityl RRRâ-TAPP (3.1Tr-TAPP), and first examples
of its versatility as a preorganized synthon in the syntheses
of heme model ligands.
The introduction of the biologically more relevant imid-
azole ligands can best be achieved from 9 and the protected
1
0
imidazole 13 via a substitution/elimination sequence.
Nonprotected imidazoles predominantly quarternize during
this reaction, bridging two pickets and yielding only trace
amounts of the desired cytochrome c oxidase model ligand
3.
Applying the above reactions to 5 and 6, respectively, the
distal superstructures can also be completed first (Scheme
3). Under the chosen reaction conditions, this results in 14
and 15, with thermally induced detritylation occurring only
To obtain 2, TAPP (mixture of all four atropisomers) is
first reacted with 1 equiv of triphenylmethyl bromide,
yielding a statistical mixture of all possible atropisomeric
Sch em e 1
1
0.1021/jo981834r CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/27/1998

Communications
J . Org. Chem., Vol. 63, No. 23, 1998 8083
Sch em e 2
Sch em e 3
metrical porphyrins. Within this methodology, the build-
ing blocks “axial ligand” and “superstructure” become modu-
lar and thus easy to exchange. It can be foreseen that this
general approach will find broad application in the design
and synthesis of a large number of customized porphyrins.
Ack n ow led gm en t. We thank the NIH (Grant 1R01
GM-17880-28) and the NSF (Grant CHE 9612725) for
financial support. We also thank the Mass Spectrometry
Facility, University of California, San Francisco, supported
by the NIH (Grants RR 04112 and RR 01614).
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and characterization data for compounds 2-10, 14-17 (15
pages).
J O981834R
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(
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releases the aminoporphyrins 16 and 17, respectively, which
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(
2