Direct synthesis of palladium porphyrins from acyldipyrromethanes

Article abstract of DOI:10.1021/jo050120v

(Chemical Equation Presented) Palladium porphyrins are valuable photosensitizers and luminescent agents in biology and materials chemistry. New methodology is described wherein a 1-acyldipyrromethane is converted into the palladium chelate of a trans-A₂B₂ porphyrin via a one-flask reaction. The reaction entails self-condensation of the 1-acyldipyrromethane in refluxing ethanol containing KOH (5-10 mol equiv) and Pd(CH₃CN)₂Cl₂ (0.6 mol equiv) exposed to air. This direct route to palladium porphyrins is more expedient than the four steps of the traditional synthesis: (1) reduction of the 1-acyldipyrromethane; (2) acid-catalyzed condensation; (3) oxidation of the porphyrinogen intermediate; and (4) metal insertion. The new synthesis requires neither acid nor DDQ and formally entails only a 2e^- + 2H⁺ oxidation overall versus the traditional multistep synthesis which requires a 2e^- + 2H ⁺ reduction per each 1-acyldipyrromethane (4e^- + 4H ⁺ overall) followed by a 6e^- + 6H⁺ oxidation. The analogous reaction of a 1,9-diacyldipyrromethane and a dipyrromethane also gives the palladium porphyrin. Seven palladium porphyrins have been prepared in yields of 25-57%. The direct route also can be used with Cu(OAc) ₂·H₂O to give the copper porphyrin albeit in low yield. In summary, this methodology readily affords palladium porphyrins directly from acyldipyrromethanes.

Full text of DOI:10.1021/jo050120v

Direct Synthesis of Palladium Porphyrins from
Acyldipyrromethanes
Duddu S. Sharada, Ana Z. Muresan, Kannan Muthukumaran, and Jonathan S. Lindsey*
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204
jlindsey@ncsu.edu
Received January 20, 2005
Palladium porphyrins are valuable photosensitizers and luminescent agents in biology and materials
chemistry. New methodology is described wherein a 1-acyldipyrromethane is converted into the
palladium chelate of a trans-A2B2 porphyrin via a one-flask reaction. The reaction entails self-
condensation of the 1-acyldipyrromethane in refluxing ethanol containing KOH (5-10 mol equiv)
and Pd(CH3CN)2Cl2 (0.6 mol equiv) exposed to air. This direct route to palladium porphyrins is
more expedient than the four steps of the traditional synthesis: (1) reduction of the 1-acyldipyr-
romethane; (2) acid-catalyzed condensation; (3) oxidation of the porphyrinogen intermediate; and
(4) metal insertion. The new synthesis requires neither acid nor DDQ and formally entails only a
2e- + 2H+ oxidation overall versus the traditional multistep synthesis which requires a 2e- + 2H+
reduction per each 1-acyldipyrromethane (4e- + 4H+ overall) followed by a 6e- + 6H+ oxidation.
The analogous reaction of a 1,9-diacyldipyrromethane and a dipyrromethane also gives the
palladium porphyrin. Seven palladium porphyrins have been prepared in yields of 25-57%. The
direct route also can be used with Cu(OAc)2‚H2O to give the copper porphyrin albeit in low yield.
In summary, this methodology readily affords palladium porphyrins directly from acyldi-
pyrromethanes.
Introduction
the course of this work, we made the surprising finding
that some metal reagents, particularly those containing
palladium and to a lesser extent copper, result in direct
conversion of the acyldipyrromethane to the metallo-
porphyrin.
Palladium porphyrins are of interest owing to their
high yield of intersystem crossing and long lifetime of
the resulting triplet state in diverse media.3 Palladium
porphyrins have found applications as luminescent mark-
ers,4 oxygen sensors,5 sensitizers for singlet oxygen
formation,6 and photoinduced protein cross-linking agents.7
Pyrroles that bear R-acyl groups (such as pyrrole-2-
carboxaldehyde) are known to form coordination com-
plexes with a variety of metals [e.g., Cu(II), Ni(II), Pd(II),
Pt(II)] and other ligands.1 As part of a study aimed at
developing a nonchromatographic method for purifying
1-acyldipyrromethanes (which contain the R-acylpyrrole
motif), we screened a variety of metal reagents for
formation of stable complexes of 1-acyldipyrromethanes.
Dialkylboron reagents ultimately were found to serve as
excellent complexation aids for the isolation of 1-acyl-
dipyrromethanes from the crude acylation mixture.2 In
(2) Muthukumaran, K.; Ptaszek, M.; Noll, B.; Scheidt, W. R.;
Lindsey, J. S. J. Org. Chem. 2004, 69, 5354-5364.
(3) (a) Eastwood, D.; Gouterman, M. J. Mol. Spectrosc. 1970, 35,
359-375. (b) Callis, J. B.; Gouterman, M.; Jones, Y. M.; Henderson,
B. H. J. Mol. Spectrosc. 1971, 39, 410-420.
(1) (a) Perry, C. L.; Weber, J. H. J. Inorg. Nucl. Chem. 1971, 33,
1031-1039. (b) Mehta, P.; Mehta, R. K. J. Indian Chem. Soc. 1984,
LXI, 571-572. (c) Adams, H.; Bailey, N. A.; Fenton, D. E.; Moss, S.;
Rodriguez de Barbarin, C. O.; Jones, G. J. Chem. Soc., Dalton Trans.
1986, 693-699. (d) Tayim, H. A.; Salameh, A. S. Polyhedron 1986, 5,
687-689. (e) Kanungo, P. K.; Sankhla, N. K.; Mehta, R. K. J. Indian
Chem. Soc. 1986, LXIII, 335-336. (f) Birdsall, W. J.; Weber, B. A.;
Parvez, M. Inorg. Chim. Acta 1992, 196, 213-220. (g) Hu¨bler, K.;
Hu¨bler, U. Z. Anorg. Allg. Chem. 2000, 626, 1224-1236.
(4) Papkovsky, D. B.; O’Riordan, T.; Soini, A. Biochem. Soc. Trans.
2000, 28, 74-77.
(5) Borisov, S. M.; Vasil’ev, V. V. J. Anal. Chem. 2004, 59, 155-
159.
(6) Wiehe, A.; Stollberg, H.; Runge, S.; Paul, A.; Senge, M. O.; Ro¨der,
B. J. Porphyrins Phthalocyanines 2001, 5, 853-860.
10.1021/jo050120v CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/31/2005
3500
J. Org. Chem. 2005, 70, 3500-3510

Synthesis of Palladium Porphyrins from Acyldipyrromethanes
CHART 1
In(OAc)3, SnF4, SbCl5, TeCl4, CeI3, EuCl3, Dy(OTf)3, Yb-
(OTf)3, Pt(C6H5CN)2Cl2, TlOAc, and BiCl3. The expected
complex (for divalent metals) is shown in eq 1. The survey
was carried out under two conditions: (1) mild conditions
at room temperature in methanol in the absence of base2
or (2) more forcing conditions in refluxing ethanol
containing excess base. The survey under the former
conditions was generally unsuccessful but led eventually
to the discovery of dialkylboron triflates as complexation
aids.2 The results of the survey under the latter condi-
tions are presented herein.
The first synthesis of palladium tetraphenylporphyrin
(PdTPP) was reported in 1959.8 Palladium porphyrins
typically are prepared by metalation of the free base
porphyrin using PdCl2 in refluxing acetic acid,8 Pd(OAc)2
in refluxing benzonitrile,9 or Pd(OAc)2 in CH2Cl2/MeOH
at room temperature.6
In this paper, we describe the results of the screen of
a wide variety of metal reagents with 1-acyldipyr-
romethanes. We then focus on palladium and copper
reagents and explore the scope of 1-acyldipyrromethanes
that yield the trans-A2B2-porphyrin. The optimized condi-
tions are applied to the reaction of a 1,9-diacyldi-
pyrromethane + a dipyrromethane to give the corre-
sponding porphyrin. The reactants thus include dipyr-
romethane (1),10 1-acyldipyrromethane (2),2,11 and 1,9-
diacyldipyrromethane (3)12 species (Chart 1). These
studies are complemented by an examination of optimal
conditions for forming palladium porphyrins from the
corresponding free base porphyrins. Taken together, this
work provides new routes to palladium porphyrins. More
broadly, this work identifies a new pathway to porphyrins
that employs less reduced species (acyldipyrromethanes
rather than dipyrromethanecarbinols), employs basic
conditions, and does not require the use of a quinone
oxidant.
A mixture of 2a (42 mM) and KOH (420 mM) in
ethanol was treated with a metal reagent at reflux for 1
Results and Discussion
1. Survey of Metal Reagents. A broad survey of
metal reagents was performed using 1-(p-toluoyl)-5-
phenyldipyrromethane (2a)11 to identify suitable com-
plexation aids for isolation of 1-acyldipyrromethanes. The
metals examined include Mg(OAc)2‚4H2O, Sc(OTf)3, TiF4,
MnCl2, Mn(OAc)2, FeBr3, Fe(OAc)2, Fe(acac)3, Co(OAc)2‚
4H2O, Ni(OAc)2‚4H2O, Cu(OAc)2‚H2O, Zn(OAc)2‚2H2O,
GeI4, MoCl3, RuCl3‚H2O, Pd(OAc)2, AgOTf, CdCl2, InCl3,
(7) Kim, K.; Fancy, D. A.; Carney, D.; Kodadek, T. J. Am. Chem.
Soc. 1999, 121, 11896-11897.
(8) Thomas, D. W.; Martell, A. E. J. Am. Chem. Soc. 1959, 81, 5111-
5119.
(9) Buchler, J. W. In Porphyrins and Metalloporphyrins; Smith, K.
M., Ed.; Elsevier Scientific Publishing Co.: Amsterdam, 1975; pp 157-
231.
(10) Laha, J. K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J. S. Org. Process Res. Dev. 2003, 7, 799-812.
(11) Rao, P. D.; Littler, B. J.; Geier, G. R., III; Lindsey, J. S. J. Org.
Chem. 2000, 65, 1084-1092.
(12) Zaidi, S. H. H.; Muthukumaran, K.; Tamaru, S.-I.; Lindsey, J.
S. J. Org. Chem. 2004, 69, 8356-8365.
J. Org. Chem, Vol. 70, No. 9, 2005 3501

Sharada et al.
TABLE 1. Survey of Conditions for the
Self-Condensation of 2aa
h. Most of the metal reagents examined either gave no
reaction or formed multiple components. However, both
Cu(OAc)2‚H2O and Pd(OAc)2 gave the corresponding
metalloporphyrin. The reaction with Cu(OAc)2‚H2O only
afforded a trace of the copper porphyrin, but under more
forcing conditions [2a (83 mM) and KOH (830 mM) in
ethylene glycol (bp ∼196-198 °C) containing Cu(OAc)2‚
H2O at reflux for 18 h in air] the copper porphyrin
Cu-4a was obtained in 13% yield. The reaction of 2a with
Pd(OAc)2 in refluxing ethanol (bp 78 °C) containing KOH
exposed to air afforded the corresponding palladium
porphyrin Pd-4a in 42% yield (eq 2). The formation of
variation from the standard
yield of
entry
conditions
Pd-4ab (%)
1
2
3
4
5
6
7
8
9
none
55
55
68
5
Pd(acac)2 in place of Pd(OAc)2
Pd(CH3CN)2Cl2 in place of Pd(OAc)2
PdBr2 in place of Pd(OAc)2
PdCl2 in place of Pd(OAc)2
Pd(OH)2 in place Pd(OAc)2
omission of Pd(OAc)2
5
0
0c
0
omission of KOH
omission of Pd(OAc)2, refluxing 1-pentanol
in place of EtOH, at reflux for 18 h
TEA/THF, NaH/THF, pyridine/toluened
or NaOAc/DMSOd in place of KOH/EtOH
TEA/DME or NaOAc/DMSO in place of
KOH/EtOHe
0c
1
the Pd-porphyrin was confirmed by H NMR spectros-
10
11
12
0
copy, laser-desorption mass spectrometric (LD-MS) analy-
sis,13 and the characteristic visible absorption bands at
418 and 524 nm. No other porphyrin species were
observed by LD-MS and TLC analysis.
2-3
0
NaOMe/THF in place of KOH/EtOH,
under Ar
DBU in place of KOH
Ba(OH)2‚8H2O in place of KOH
Reaction at room temperature
2. Optimization of Reaction Conditions for Pal-
ladium Porphyrin Formation. A. Reagents. The self-
condensation of 2a in the presence of Pd(OAc)2 and KOH
in ethanol to give palladium porphyrin Pd-4a prompted
a broader survey of conditions that encompassed the
nature of the palladium reagent, the nature of the base,
and the absolute requirement for various components.
The general protocol entailed addition of ethanol to the
three solids (1-acyldipyrromethane, palladium reagent,
KOH) followed by heating exposed to air. The resulting
mixture was heterogeneous, and palladium porphyrin
often appeared as a purple film on the walls of the flask.
Accordingly, yields were determined by removal of the
volatile solvent, addition of a known quantity of THF to
dissolve the porphyrin, followed by quantitative analysis
by absorption spectroscopy.
The results of the survey are listed in Table 1. Among
several palladium reagents, Pd(CH3CN)2Cl2 afforded the
highest yield (entries 1-6). The omission of palladium
reagent or KOH resulted in no porphyrin (entries 7, 8).
Indeed, omission of the palladium reagent while carrying
out the reaction in refluxing 1-pentanol (bp 136-138 °C)
gave no free base porphyrin even after 18 h, thus
emphasizing the lack of reactivity of the 1-acyldi-
pyrromethane in the absence of the palladium reagent
(entry 9). The reaction was quite sensitive to the nature
of the base, with poor results provided by TEA, NaH, and
DBU (entries 10-13), though Ba(OH)2‚8H2O gave por-
phyrin in yield comparable with that of the KOH reaction
(entry 14). It is noteworthy that a number of the failed
solvent/base combinations in entries 10 and 11 resemble
those used with excellent success in Pd-mediated aerobic
oxidation processes.14-16 The reaction at room-tempera-
ture succeeded but was quite slow (entry 15). The effect
of the number of equivalents of KOH (relative to 2a) also
was studied with the following results: 1 equiv, 5%; 2
equiv, 23%; 5 equiv, 53%; 10 equiv, 56% yield.
13
14
15
12
55
48 (18 h)
a The standard conditions entail use of 2a (0.125 mmol, 40 mM),
KOH (1.25 mmol), and Pd(OAc)2 (0.063 mmol) in refluxing ethanol
exposed to air for 1 h. b The yield of porphyrin Pd-4a was
determined spectroscopically (see the Experimental Section). c No
free base porphyrin was observed, but a trace of 1-acyldipyrrin
was observed (see the Supporting Information). d The reaction was
performed using 2a (0.10 mmol, 100 mM), base (0.50 mmol),
Pd(OAc)2 (0.06 mmol), and bubbling oxygen at 75 °C for 1 h. e The
reaction was performed using 2a (0.10 mmol, 100 mM), base (0.50
mmol), and Pd(OAc)2 (0.06 mmol) at 65 °C exposed to air for 1 h.
to air. On the other hand, when the palladium reagent
was combined with a solution of ethanol and KOH (in
the absence of the 1-acyldipyrromethane), a black pre-
cipitate formed. Addition of the 1-acyldipyrromethane 2a
to the mixture gave significant quantities of the free base
1-acyldipyrrin and only a small amount of porphyrin (2%
yield at room temperature; 17% at 75 °C). The key finding
from several experiments is that the precipitate formed
upon interaction of the palladium reagent with ethanolic
KOH alone is relatively inactive in the porphyrin-forming
reaction (see the Supporting Information for a complete
description of these experiments).
C. Effect of Concentration. The effect of concentra-
tion was examined by performing the reaction of 2a at
concentrations ranging from 10 mM to 1 M in ethanol at
75 °C exposed to air for 1 h. The concentrations of KOH
and Pd(CH3CN)2Cl2 were altered as required to maintain
fixed ratios with respect to the concentration of 2a. Note
that the term concentration is used to facilitate compari-
son even though the reaction mixtures generally are
heterogeneous. The highest yields (48-65%) were ob-
tained with 2a in the range of 10-178 mM (Figure 1A).
D. Time Course. The formation of palladium porphy-
rin using 2a (100 mM), KOH (500 mM) and Pd(CH3-
CN)2Cl2 (60 mM) in ethanol at 75 °C exposed to air was
examined over the course of 3 h. The maximum yield of
porphyrin (53%) was obtained within 60 min and showed
no significant change thereafter (Figure 1B).
B. Order of Addition Effects. The typical order of
addition was to combine the three solids (1-acyldi-
pyrromethane, palladium reagent, KOH), add ethanol,
then heat the resulting heterogeneous mixture exposed
E. Effect of Pd Oxidation State. The effect of
different oxidation states of palladium [Pd(0), Pd(II),
Pd(IV)] was examined under anaerobic conditions at 70
°C for 1 h. The Pd(0) and Pd(IV) oxidation states were
probed using Pd(PPh3)4 and Na2PdCl6, respectively.
Reactions were monitored over time, and the yields
(13) Srinivasan, N.; Haney, C. A.; Lindsey, J. S.; Zhang, W.; Chait,
B. T. J. Porphyrins Phthalocyanines 1999, 3, 283-291.
(14) Nishimura, T.; Uemura, S. Synlett 2004, 201-216.
(15) Stoltz, B. M. Chem. Lett. 2004, 33, 362-367.
(16) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400-3420.
3502 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Palladium Porphyrins from Acyldipyrromethanes
tions with Pd(II) and Pd(IV) are quite similar under
aerobic conditions.
In summary, the highest yields of palladium porphyrin
were observed with a modest concentration of 2a (31.6
mM) in hot ethanolic KOH (158 mM) containing Pd(CH3-
CN)2Cl2 (18.9 mM) exposed to air for 1 h. These condi-
tions were identified by studies that employed yield
determination via spectroscopic monitoring of the reac-
tions. For scale-up purposes, the reaction at slightly
higher concentration [2a (100 mM), KOH (500 mM) and
Pd(CH3CN)2Cl2 (60 mM)] gave Pd-4a as a purple crystal-
line solid in 53% isolated yield. No other porphyrin
species were observed upon LD-MS analysis of the crude
reaction mixture.
3. Scope. A. Acyldipyrromethane Substituents.
Exploration of the generality of the palladium porphyrin
forming conditions required access to a set of 1-acyldi-
pyrromethanes bearing a variety of substituents at the
1- and 5-positions. The 1-acyldipyrromethanes were
prepared by reaction11 of a dipyrromethane (1a-c)10 with
EtMgBr at -78 °C in THF followed by addition of a S-2-
pyridyl thioate17 (Mukaiyama reagent, 5a-e) (Scheme
1). Each Mukaiyama reagent is known,2,12,17,18 although
the synthesis of 5e was carried out under a refined
procedure12 by the reaction of mesitoyl chloride and
2-pyridylthiol. To facilitate purification of the 1-acyl-
dipyrromethane, a boron-complexation strategy2 was
employed wherein the crude acylation mixture is treated
with a dialkylboron triflate and TEA. The resulting
hydrophobic dialkylboron complex of the 1-acyldipyr-
romethane can be isolated by precipitation/crystallization
with limited or no chromatography. Dialkylboron com-
plexes were obtained of 2a-d and 2f. A dialkylboron
complex was not attempted for either 2e or 2g, which
were prepared following a known procedure.11,19 The
1-acyldipyrromethane-dialkylboron complexes 2-BR2 were
decomplexed by treatment with 1-pentanol in refluxing
THF, affording the 1-acyldipyrromethanes. 1-Formyl-
dipyrromethane 2h was prepared following a known
procedure.20
The generality of the palladium porphyrin forming
conditions was examined with 1-acyldipyrromethanes
2b-h (Scheme 2). The reaction conditions entailed the
1-acyldipyrromethane (100 mM), KOH (500 mM), and Pd-
(CH3CN)2Cl2 (60 mM) in ethanol at 75 °C exposed to air.
The presence of electron-releasing rather than electron-
withdrawing substituents at the 1- and 5-positions
resulted in porphyrins with higher yields. The di-
pyrromethane with a 1-pentafluorobenzoyl group (2c) led
to a porphyrin containing two ethoxy substituents in
place of fluoro atoms. On the basis of the well-docu-
mented susceptibility of the para position of penta-
fluorophenyl groups to nucleophilic substitution,21 the
FIGURE 1. (A) Effect of concentration on the self-condensa-
tion of 1-acyldipyrromethane 2a affording the palladium
porphyrin. The yields were determined spectroscopically. The
reaction was carried out in ethanol containing KOH and Pd-
(CH3CN)2Cl2 at 75 °C exposed to air for 1 h. The concentrations
of KOH and Pd(CH3CN)2Cl2 were altered as required to
maintain fixed ratios with respect to the concentration of 2a.
(B) Time course for the self-condensation affording the pal-
ladium porphyrin. The yields were determined spectroscopi-
cally. The reaction of 1-acyldipyrromethane 2a (100 mM) was
carried out in ethanol containing KOH (500 mM) and Pd(CH3-
CN)2Cl2 (60 mM) at 75 °C exposed to air.
TABLE 2. Effect of Pd Oxidation State on Porphyrin
Formationa
porphyrin yieldsb (%)
reaction
conditions
Pd(0)(PPh3)4 Pd(II)(CH3CN)2Cl2 Na2Pd(IV)Cl6
anaerobic
anaerobic +
DDQd
0
0
32, 32c
27
7c
12
aerobic
0
48, 53c
38, 35c
a Reaction of 2a (100 mM) in ethanol containing the palladium
reagent (60 mM) and KOH (500 mM) was performed for 1 h at 70
°C under the specified conditions, affording porphyrin Pd-4a.
b Yields were determined spectroscopically (see the Experimental
Section). c Isolated yield. d Reaction was performed under anaero-
bic conditions; samples were removed and treated with DDQ prior
to yield determination via spectroscopy.
(17) Araki, M.; Sakata, S.; Takei, H.; Mukaiyama, T. Bull. Chem.
Soc. Jpn. 1974, 47, 1777-1780.
(18) Imamoto, T.; Kodera, M.; Yokoyama, M. Synthesis 1982, 134-
136.
(19) Rao, P. D.; Dhanalekshmi, S.; Littler, B. J.; Lindsey, J. S. J.
Org. Chem. 2000, 65, 7323-7344.
observed at 1 h are shown in Table 2. In the case of
Pd(0), there was no porphyrin formed under anaerobic
conditions even with subsequent DDQ oxidation, or under
aerobic conditions. With Pd(IV), the porphyrin was
isolated in 7% yield under anaerobic conditions but 35%
yield under aerobic conditions. The results of the reac-
(20) Bru¨ckner, C.; Posakony, J. J.; Johnson, C. K.; Boyle, R. W.;
James, B. R.; Dolphin, D. J. Porphyrins Phthalocyanines 1998, 2, 455-
465.
(21) (a) Kadish, K. M.; Araullo-McAdams, C.; Han, B. C.; Franzen,
M. M. J. Am. Chem. Soc. 1990, 112, 8364-8368. (b) Battioni, P.;
Brigaud, O.; Desvaux, H.; Mansuy, D.; Traylor, T. G. Tetrahedron Lett.
1991, 32, 2893-2896.
J. Org. Chem, Vol. 70, No. 9, 2005 3503

Sharada et al.
SCHEME 1
product is proposed as porphyrin Pd-4c. With the mesi-
toyl group in the 1-position of the dipyrromethane (2e),
no palladium porphyrin was observed. The addition of
DDQ also gave no porphyrin, thereby suggesting that the
3504 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Palladium Porphyrins from Acyldipyrromethanes
SCHEME 2
(CH3CN)2Cl2 (60 mM), and KOH (500 mM) in ethanol at
75 °C exposed to air. All substrates examined were
known compounds with the exception of 1-acyldipyrrin
6a. The latter was obtained in 68% yield by the oxidation
of 1-acyldipyrromethane 2a with DDQ, in the same
manner as for oxidation of dipyrromethanes23 (eq 3). The
results of the survey are shown in Table 3.
The self-condensation of a more reduced (dipyrro-
methane-1-carbinol 2a-OH11) or more oxidized (1-acyl-
dipyrrin 6a) species gave the palladium porphyrin but
in lower yield (22% or 23%) than for reaction with the
1-acyldipyrromethane 2a (48%) (entries 1 and 2). The
self-condensation of 2-benzoylpyrrole (7)24 for 24 h did
not give any of the corresponding porphyrin PdTPP
(entry 3). The condensation of benzaldehyde with 5-
phenyldipyrromethane (1a) or pyrrole proceeded poorly,
affording the palladium porphyrin in 8% yield or not at
all (entries 4 and 5). The condensation of 1,9-diacyldi-
pyrromethane 3a12 with 1a under the standard condi-
tions gave palladium porphyrin Pd-4a in 27% yield (entry
6). The same 30 metal reagents as used in the initial
survey (vide supra) were applied to the reaction of 3a +
1a, but no porphyrin was observed except in the case of
Pd(OAc)2, which afforded Pd-4a in 22% yield. The
condensation of a 1,9-diacyldipyrrin (8)25 with 1a gave
the Pd-porphyrin in 8% yield (entry 7). An attempt to
decomplex the 1-acyldipyrromethane-BR2 complex (2a-
BBN)2 in situ was examined by treating a suspension of
2a-BBN in refluxing ethanolic KOH for 1 h, followed by
addition of Pd(CH3CN)2Cl2 with continued reflux for 1
h. The palladium porphyrin was observed in 22% yield
(entry 8).
failure of the reaction lies in condensation rather than
oxidation processes. The reaction at elevated temperature
(in 1-pentanol instead of ethanol) again showed no
palladium porphyrin even after 18 h. In the case of 2g,
which contains pentafluorophenyl substituents in both
the 1-acyl and 5-positions, a trace amount (∼2%) of
palladium porphyrin was observed spectroscopically but
none was isolated. Neither addition of DDQ nor reaction
at elevated temperature gave any porphyrin. Other than
two failures, the isolated yields ranged from 29 to 57%.
Among Pd-4a-h, only Pd-4f22 has been prepared previ-
ously. Each palladium porphyrin was examined by
fluorescence spectroscopy, which showed the absence of
any contaminating free base porphyrin species.
The success with palladium reagents prompted reex-
amination of congeners of palladium, although both Ni-
(OAc)2‚4H2O and Pt(C6H5CN)2Cl2 were included in the
initial survey. The use of Ni(OAc)2‚4H2O or Pt(C6H5-
CN)2Cl2 in the self-condensation of 2a under the opti-
mized palladium porphyrin forming conditions using
B. Reactivity of Distinct Substrates. A variety of
substrates related to 1-acyldipyrromethanes were exam-
ined under the standard reaction conditions, which
generally entail the acylpyrrolic species (100 mM), Pd-
(23) Yu, L.; Muthukumaran, K.; Sazanovich, I. V.; Kirmaier, C.;
Hindin, E.; Diers, J. R.; Boyle, P. D.; Bocian, D. F.; Holten, D.; Lindsey,
J. S. Inorg. Chem. 2003, 42, 6629-6647.
(24) (a) Jones, R. A.; Laslett, R. L. Aust. J. Chem. 1964, 17, 1056-
1058. (b) Nicolaou, K. C.; Claremon, D. A.; Papahatjis, D. P. Tetra-
hedron Lett. 1981, 22, 4647-4650.
(22) Honeybourne, C. L.; Hill, C. A. S. J. Phys. Chem. Solids 1998,
49, 315-321.
(25) Tamaru, S.-I.; Yu, L.; Youngblood, W. J.; Muthukumaran, K.;
Taniguchi, M.; Lindsey, J. S. J. Org. Chem. 2004, 69, 765-777.
J. Org. Chem, Vol. 70, No. 9, 2005 3505

Sharada et al.
TABLE 3. Reactivity of Distinct Substrates Yielding Pd-Porphyrins
a The reactions were performed in ethanol containing the reactant (100 mM), KOH (500 mM), and Pd(CH3CN)2Cl2 (60 mM) at 75 °C
exposed to air for the specified time unless noted otherwise. The reactant 2a gave Pd-4a in 48% yield under these conditions. b The yield
of porphyrin was determined spectroscopically (see the Experimental Section). c The reaction employed Pd(CH3CN)2Cl2 at 30 mM. d The
reaction employed both 1a and benzaldehyde at 100 mM. e The reaction employed pyrrole (400 mM), benzaldehyde (400 mM), KOH (1
M), and Pd(CH3CN)2Cl2 (100 mM). f Isolated yield. g A suspension of 2a-BBN (100 mM) and KOH (500 mM) in ethanol was refluxed for
1 h, followed by addition of Pd(CH3CN)2Cl2 (60 mM) with continued reflux for 1 h.
refluxing 1-pentanol in the place of ethanol indicated
∼1% metalloporphyrin formation by UV-vis analysis.
Application of the standard method to the synthesis
of a chlorin afforded a mixture of porphyrin and chlorin,
both in <3% yield (see the Supporting Information).
4. Reaction Course. Formation of the palladium
porphyrin from the 1-acyldipyrromethane (2) in a one-
flask process raises a number of questions concerning
both porphyrin chemistry and palladium chemistry. The
striking features from the porphyrin perspective are that
the 1-acyldipyrromethane is reactive, the condensation
occurs under basic conditions, and a quinone oxidant is
not required. By contrast, the traditional synthesis of a
metalloporphyrin from a 1-acyldipyrromethane entails
four steps: (1) reduction of the 1-acyldipyrromethane to
give the dipyrromethane-1-carbinol; (2) acid-catalyzed
condensation of the dipyrromethane-1-carbinol; (3) oxida-
tion of the porphyrinogen intermediate; and (4) metal
insertion into the intact free base porphyrin. The two
syntheses are outlined in Scheme 3.
The stepwise synthesis employs a 2 × (2e- + 2H+)
reduction of the 1-acyldipyrromethane and a 6e- + 6H+
oxidation of the resulting porphyrinogen, whereas the
direct synthesis involves only a 2e- + 2H+ oxidation
overall (formally equivalent to oxidation of only one of
the two 1-acyldipyrromethanes that participate in por-
phyrin formation). The presumed oxidant is molecular
oxygen, although anaerobic reactions only diminished the
yield by ∼2-fold. Assuming that molecular oxygen acts
as a 4e- + 4H+ acceptor, self-condensation of 1 mmol of
a 1-acyldipyrromethane stoichiometrically requires 0.25
mmol of O2 (which corresponds to 6.1 mL of O2 or 29 mL
of air). The amount of oxygen dissolved in 10 mL of
ethanol under an air atmosphere is 0.021 mmol (0.5
mL),26 which is 12 times less than necessary, indicating
that aeration of the reaction mixture is necessary. While
no proof is in hand that molecular oxygen is the oxidant,
(26) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photo-
chemistry, 2nd ed.; Marcel Dekker: New York, 1993; p 290.
3506 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Palladium Porphyrins from Acyldipyrromethanes
SCHEME 3
of this type would be plausible, we synthesized the
corresponding calixpyrrole species having a geminal
dimethyl group at the meso-position. Thus, 5,5-dimeth-
yldipyrromethane (1d)29,30 was subjected to 1-acylation
with S-2-pyridyl benzothioate (5f,11 prepared via a refined
procedure12), affording the 1-acyldipyrromethane 2i in
76% yield. Treatment of 2i to the standard conditions for
forming the palladium porphyrin did not give any isolated
Pd-9, and subsequent quantitative analysis of the reac-
tion mixture indicated that Pd-9 was present in ∼0.6%
yield (see Supporting Information). On the other hand,
reduction of 2i gave 2i-OH, which upon self-condensation
under mild Lewis acid catalysis31 gave the dihydropor-
phyrin 9 accompanied by calix[6]phyrin (10). An alterna-
tive route to 932 and a route to analogues33 of 9 and 10
have been reported. Treatment of 9 to new conditions for
palladium insertion into free base porphyrins [Pd(O2-
CCF3)2 in 1,2-dichloroethane/methanol (4:1) at 45 °C; vide
infra] gave the corresponding palladium chelate Pd-9 in
22% yield (Scheme 4).
The fact that Pd-9 is only formed in trace quantity in
the direct synthesis suggests the importance of removing
the meso-proton in the 1-acyldipyrromethane, thereby
generating a dipyrrin species, for the success of the direct
synthesis. Whether dipyrrin formation entails a tau-
tomerization involving the 1-acyl group (generating an
enol) or an oxidation process is not known. It is worth
noting, however, that exposure of a 1-acyldipyrromethane
(2a) in ethanol/KOH at 70 °C to air (without any
palladium reagent) gave no porphyrin and only a trace
amount (∼0.3%) of the corresponding 1-acyldipyrrin (6a).
Thus, removal of the meso-proton does not occur to a
significant degree in the hot, basic, aerobic conditions,
but must be driven by interaction with a palladium
species.
oxygen is a well-known oxidant in porphyrin-forming
reactions at elevated temperatures,27 and a number of
Pd-catalyzed aerobic oxidations have been developed.14-16
The reaction yielding palladium porphyrins differs in
several ways from other palladium-mediated reactions.
(1) The structural changes accompanying conversion of
the 1-acyldipyrromethane to the palladium porphyrin
have no apparent analogue in the palladium literature.
Some Pd-mediated aerobic oxidations entail C-C bond-
forming reactions,14-16 but the substrates are consider-
ably different from 1-acyldipyrromethanes (although one
reaction involves R-alkylation of indole28). (2) Pd-medi-
ated reactions in general are designed to be catalytic in
palladium with high turnover numbers, whereas the
direct synthesis described herein results in inclusion of
a stoichiometric quantity of Pd2+ in the reaction product
as a stable coordination complex (the palladium porphy-
rin). (3) Attempts to use solvents and bases similar to
those in Pd-mediated aerobic oxidations were generally
unsuccessful (Table 1, entries 10 and 11). While an in-
depth study of mechanism is beyond the scope of this
paper, we pursued two lines of inquiry to address possible
reaction intermediates.
B. Isotopic Studies. The results in Table 3 show that
species more reduced (dipyrromethanecarbinol 2a-OH)
or more oxidized (1-acyldipyrrin 6a) than the benchmark
1-acyldipyrromethane 2a undergo reaction to give the
palladium porphyrin. We wondered whether PdX2
/KOH
might cause reduction at the R-acyl position of the
dipyrromethane, thus forming the dipyrromethane-
carbinol (or a related palladium complex thereof), which
could then react via the traditional path for porphyrin
formation. Although reduction at the carbonyl group
might seem at odds with the requirement for oxidation
to give the porphyrin, the addition of the palladium
reagent to ethanolic KOH in the absence of a 1-acyldipyr-
romethane results in a black precipitate (resembling
those with reactions of Pd(0) species). The results from
such omission experiments are described in the Support-
ing Information.
To probe reaction at the R-carbon position, we prepared
a set of 1-acyldipyrromethanes and derivatives labeled
A. Examination of a Calixpyrrole. One possible
intermediate in the direct synthesis is a palladium-
chelated 5,15-dihydroporphyrin, where the 1-acyldipyr-
romethane meso-position has remained untouched while
C-C bond-formation occurred at the respective pyrrole
and R-acyl positions. To determine whether a structure
(29) Brown, W. H.; French, W. N. Can. J. Chem. 1958, 36, 371-
377.
(30) Littler, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O’Shea,
D. F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391-1396.
(31) Geier, G. R., III; Callinan, J. B.; Rao, P. D.; Lindsey, J. S. J.
Porphyrins Phthalocyanines 2001, 5, 810-823.
(32) Hong, S.-J.; Ka, J.-W.; Won, D.-H.; Lee, C.-H. Bull. Korean
Chem. Soc. 2003, 24, 661-663.
(33) Kra´l, V.; Sessler, J. L.; Zimmerman, R. S.; Seidel, D.; Lynch,
V.; Andrioletti, B. Angew. Chem., Int. Ed. 2000, 39, 1055-1058.
(27) Adler, A. D.; Longo, F. R.; Shergalis, W. J. Am. Chem. Soc. 1964,
86, 3145-3149.
(28) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2003, 125,
9578-9579.
J. Org. Chem, Vol. 70, No. 9, 2005 3507

Sharada et al.
SCHEME 4
CHART 2
The reaction of 2j under standard conditions afforded
the corresponding 13C-labeled palladium porphyrin Pd-
4j in 42% yield. Studies of the reaction of 2j at various
temperatures (rt, 50 °C and 70 °C) with monitoring by
13C NMR spectroscopy were inconclusive concerning
specific intermediates; examination of the mixture at
room temperature at 10 min after addition of Pd(CH3-
CN)2Cl2 showed the peak characteristic of starting mate-
rial 2j (184.74 ppm) and of porphyrin Pd-4j (121.64 ppm),
as well as three additional, unassigned peaks at 185.65,
185.80, and 185.95 ppm. Compound 11, which cannot
form the porphyrin, was examined similarly. TLC analy-
sis of the reaction mixture showed several new less-polar
components, the starting material, and extensive streak-
ing from the origin. 13C NMR spectroscopic examination
of the crude reaction mixture upon dissolution in THF
showed the expected peak of the 13C-labeled carbonyl at
184.12 ppm, three low intensity peaks (184.37, 184.57,
184.69 ppm), and several other low intensity peaks of
unknown origin throughout the 13C NMR spectrum.
Although specific intermediates were not identified, the
reaction of 11 did not show any signal characteristic of a
dipyrromethane-carbinol, though signals close to that of
the dipyrrin 6j were observed. Reactive intermediates
such as a carbinol or other species may have low steady-
state concentrations prohibiting detection by NMR spec-
troscopy. Thus, the overall pathway for the new synthesis
remains to be determined.
with 13C at the R-position (acyl group or equivalent). The
13C-labeled compounds include 1-acyldipyrromethane 2j,
the monocarbinol 2j-OH, the 1-acyldipyrrin 6j, an ana-
logue of 2j (11) wherein the 9-methyl group is present to
block reaction and trap possible reaction intermediates,
and the palladium porphyrin Pd-4j derived from 2j
(Chart 2). The syntheses follow the methods described
herein and are presented in the Supporting Information.
The chemical shift of the labeled carbon in each com-
pound is as follows: 6j (δ ) 185.75 ppm); 2j (δ ) 184.75
ppm); 11 (δ ) 184.0 ppm); Pd-4j (δ ) 121.64 ppm); and
2j-OH (δ ) 70.36 and 70.45 ppm).
5. Palladium Metalation. A traditional method for
palladium insertion into free base porphyrins entails
3508 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Palladium Porphyrins from Acyldipyrromethanes
TABLE 4. Effect of Solvents and Reagents on Palladium Insertion (H2TPP f PdTPP)a
solvent
PdBr2
Pd(OAc)2
Pd(acac)2
Pd(O2CCF3)2
ClCH2CH2Cl
0%
20%
0%
2%
6%
7%
11%
0%
40%
80%
13%
70%
ClCH2CH2Cl +MeOH (4:1)
ClCH2CH2Cl +Pyridine (5%)
THF
0%
0%
20%
3%
a The standard conditions entail use of H2TPP (0.1 mmol, 50 mM) and palladium reagent (100 mM) at 60 °C for 1 h. Yields were
determined spectroscopically via multicomponent analysis.
reaction of Pd(OAc)2 in refluxing benzonitrile.9 More
B. Analysis of Scrambling. The extent of scrambling in
crude reaction mixtures or purified samples was determined
recently, palladium metalation was achieved using
by laser desorption ionization mass spectrometry (LD-MS)
Pd(OAc)2 in CH2Cl2/MeOH at room temperature.6 The
without a matrix.13
latter results were followed up in an effort to determine
the best choice of palladium reagent and solvent for the
palladium insertion, using metalation of meso-tetra-
C. Reaction Media. Absolute ethanol was used in all
studies of porphyrin formation. The reactions were carried out
exposed to air unless noted otherwise. The reactions were
phenylporphyrin (H2TPP) as the benchmark example.
Analytical-scale reactions were performed using H2TPP
(0.1 mmol, 50 mM) and 2 equiv of a palladium reagent
(100 mM) at 60 °C for 1 h. Among the different solvents
and reagents examined, the best results were obtained
with Pd(O2CCF3)2 in 1,2-dichloroethane/methanol (4:1)
or THF (Table 4), which afforded rapid metalation. The
synthesis at larger scale afforded PdTPP in 64% isolated
yield.
carried out in ethanol at reflux or at 70 or 75 °C using
temperature controllers. Such temperature control was gener-
ally employed to minimize solvent loss during experimentation
in open vessels.
II. General Reaction Protocols. A. Screening of Metal
Reagents for Metalloporphyrin Formation. (i) From a
1-Acyldipyrromethane. A solution of 2a (43.0 mg, 0.125
mmol) in ethanol (3 mL) was treated with KOH (70.0 mg, 1.25
mmol) followed by the metal reagent (0.063 mmol). The
mixture was stirred at reflux with exposure to air for 1 h. The
reaction was examined by UV-vis spectroscopy and TLC
(silica, CH2Cl2) for porphyrin formation. Yield determination
was performed spectroscopically at the end of the reaction (see
Section I.A).
(ii) From a 1,9-Diacyldipyrromethane + a Dipyrro-
methane. A solution of 3a (57.0 mg, 0.125 mmol) and 1a (28.0
mg, 0.125 mmol) in ethanol (3 mL) was treated with KOH (140
mg, 2.50 mmol) followed by the metal reagent (0.125 mmol).
The mixture was stirred at reflux with exposure to air for 1 h.
The reaction was examined by UV-vis spectroscopy and TLC
(silica, CH2Cl2) for porphyrin formation. Yield determination
was performed spectroscopically at the end of the reaction (see
Section I.A).
B. Survey of Conditions (Solvents and Bases). A sample
of 2a (34.4 mg, 100 µmol) in a given solvent (1.0 mL) was
treated with a base (0.5 mmol) followed by Pd(OAc)2 (13.5 mg,
60.0 µmol). The mixture was stirred and heated with exposure
to air for 1 h. Yield determination was performed spectroscopi-
cally at the end of the reaction (see Section I.A). The results
are shown in Table 1.
C. Self-Condensation of a 1-Acyldipyrromethane:
[5,15-Bis(4-methylphenyl)-10,20-diphenylporphinato]-
palladium(II) (Pd-4a). Samples of 2a (0.340 g, 1.00 mmol),
KOH (0.280 g, 5.00 mmol), and Pd(CH3CN)2Cl2 (0.155 g, 0.600
mmol) were placed in a 25 mL round-bottom flask fitted with
a condenser exposed to air. Ethanol (10.0 mL) was added, and
the heterogeneous reaction mixture was stirred and heated
to 75 °C for 1 h. The solvent was evaporated. The residue was
dissolved in CH2Cl2 and passed through a pad of alumina (CH2-
Cl2). The resulting porphyrin-containing fraction was concen-
trated to give an orange-purple solid. The solid was triturated
with methanol and dried in vacuo, affording a crystalline
orange-purple solid (0.199 g, 53%): 1H NMR δ 2.69 (s, 6H),
7.53 (d, J ) 8.0 Hz, 4H), 7.70-7.81 (m, 6H), 8.04 (d, J ) 8.0
Hz, 4H), 8.14-8.19 (m, 4H), 8.79 (d, J ) 5.1 Hz, 4H), 8.83 (d,
J ) 5.1 Hz, 4H), (m, 8H); 13C NMR δ 21.7, 121.8, 122.0, 126.9,
127.7, 127.9, 131.1, 131.2, 134.3, 134.3, 137.6, 139.0, 141.7,
141.9, 142.1; LD-MS obsd 746.3; FABMS obsd 746.1685, calcd
746.1661 (C46H32N4Pd); λabs in nm (log ꢀ) 418 (5.46), 464 (3.38),
485 (3.50), 524 (4.44), 554 (3.36).
Outlook
The synthesis of a palladium porphyrin directly from
self-condensation of a 1-acyldipyrromethane or condensa-
tion of a 1,9-diacyldipyrromethane + a dipyrromethane
is in contrast with the four reaction steps (reduction, acid-
catalyzed condensation, oxidation, and palladium inser-
tion) of the traditional synthesis. The multistep synthesis
involves a 2e- + 2H+ reduction of each 1-acyldipyr-
romethane (4e- + 4H+ overall) followed by a 6e- + 6H+
oxidation whereas the direct synthesis involves only a
2e- + 2H+ oxidation overall. The direct synthesis avoids
the use of acid (for condensation) and DDQ (for oxidation
of the intermediate porphyrinogen). The use of basic
reaction conditions avoids the tendency of dipyrromethanes
to undergo cleavage, which is a source of scrambled
porphyrinic products. The new reaction conditions also
work to a modest extent for the synthesis of copper
porphyrins. Although the mechanism of this heteroge-
neous reaction process remains to be elucidated, the
simplicity of approach makes this strategy useful for
preparing selected metalloporphyrins.
Experimental Section
I. Porphyrin-Forming Reactions. A. Spectroscopic
Yield Determination. The palladium porphyrin forming
reactions generally were heterogeneous. To assess the yield
of the porphyrin-forming reactions, the entire reaction mixture
was concentrated to dryness and then dried in vacuo. The
residue was dissolved in a known amount of THF, and an
aliquot from this solution was diluted in CH2Cl2/ethanol (3:1)
solution, which was then examined by absorption spectroscopy.
The yield of porphyrin was determined by the intensity of the
Soret band (assuming ꢀSoret ) 300 000 M-1 cm-1) measured
from the apex to the inflection point at the base of the red
edge of the band. Use of ꢀSoret ) 300 000 M-1 cm-1 was chosen
on the basis of the reported range of ꢀSoret values (80 000-
337 000 M-1 cm-1) for six palladium porphyrins6 and the ꢀSoret
values (170 000-355 000 M-1 cm-1) for eight palladium por-
phyrins prepared herein.
D. Condensation of a 1,9-Diacyldipyrromethane with
a Dipyrromethane, Affording Pd-4a. Samples of 1a (0.111
g, 0.500 mmol), 3a (0.229 g, 0.500 mmol), KOH (0.280 g, 5.00
mmol), and Pd(CH3CN)2Cl2 (0.155 g, 0.600 mmol) were placed
J. Org. Chem, Vol. 70, No. 9, 2005 3509

Sharada et al.
in a 25 mL round-bottom flask fitted with a condenser exposed
to air. Ethanol (10.0 mL) was added, and the mixture was
stirred and heated at 75 °C for 1 h. The solvent was evapo-
rated. The residue was dissolved in CH2Cl2 and passed through
a pad of alumina (CH2Cl2). The porphyrin-containing eluant
was concentrated to give an orange-purple solid. The solid was
triturated with methanol and dried in vacuo, affording a
crystalline orange-purple solid (0.093 g, 25%) with satisfactory
characterization data (1H NMR, 13C NMR, LD-MS and FABMS
spectra) as described above.
solvent was evaporated. The reaction mixture was dissolved
in CH2Cl2 and purified by column chromatography [silica, CH2-
Cl2/ethyl acetate (25:1)] affording a pale brown amorphous
powder (1.15 g, 68%): mp 120-122 °C; 1H NMR δ 2.45 (s, 3H),
6.38 (d, J ) 4.0 Hz, 1H), 6.57 (d, J ) 4.4 Hz, 1H), 6.81 (d, J )
4.4 Hz, 1H), 6.82-6.84 (m, 1H), 7.30 (d, J ) 8.0 Hz, 2H), 7.43-
7.54 (m, 5H), 7.87 (d, J ) 8.0 Hz, 2H), 8.09 (s, 1H), 12.90-
13.40 (br, 1H); 13C NMR δ 21.8, 119.1, 122.2, 125.4, 128.0,
129.2, 129.3, 129.5, 130.9, 135.0, 135.6, 136.7, 138.2, 139.3,
140.4, 143.1, 150.6, 159.6, 185.4; λabs (CH2Cl2) 302 nm (ꢀ )
15,300 M-1cm-1), 432 nm (ꢀ ) 22,800 M-1cm-1). Anal. Calcd
for C23H18N2O: C, 81.63; H, 5.36; N, 8.28. Found: C, 81.70;
H, 5.33; N, 8.24.
G. Palladium Insertion. (i) Survey of Conditions. A
sample of meso-tetraphenylporphyrin (0.1 mmol, 50 mM) in a
4-mL conical reaction vial was dissolved in 2 mL of solvent.
The palladium reagent (0.2 mmol, 100 mM) was added, and
the mixture was stirred magnetically. Samples (1 µL) were
removed periodically and diluted into toluene for absorption
spectroscopy. TLC analysis was performed on silica (hexanes/
CH2Cl2, 3:1). Multicomponent analysis over the range 450-
750 nm was performed using known extinction coefficients for
H2TPP34 and PdTPP.6
(ii) Preparative Synthesis of (meso-Tetraphenylpor-
phinato)palladium(II) (PdTPP). A sample of H2TPP (0.922
g, 1.50 mmol, 50 mM) in 1,2-dichloroethane/methanol (4:1, 30
mL) was treated with Pd(O2CCF3)2 (0.997 g, 3.00 mmol), and
the heterogeneous mixture was stirred and heated to 45 °C
for 1 h. The mixture was chromatographed [alumina, hexanes/
CH2Cl2, (2:1)]. The porphyrin fraction was concentrated to give
an orange-purple solid. The solid was triturated with methanol
and dried in vacuo, affording a crystalline orange-purple solid
(0.690 g, 64%): 1H NMR δ 7.69-7.80 (m, 12H), 8.14-8.22 (m,
8H), 8.81 (s, 8H); 13C NMR δ 121.9, 126.9, 128.0, 131.2, 134.3,
141.7, 142.0; MALDI-MS (POPOP) obsd 719.0; FABMS obsd
718.1384, calcd 718.1349 (C44H28N4Pd); λabs in nm (log ꢀ) 417
(5.41), 485 (3.31), 523 (4.41), 554 (3.17).
E. Study of Pd Reagents in Distinct Oxidation States.
(i) Method. Each reaction was carried out under an atmo-
sphere of argon using a Schlenk line. The ethanol was
degassed prior to use by several cycles of freeze-pump-thaw
using a liquid nitrogen trap and an argon atmosphere.
Standard reactions were performed in a 15-mL Schlenk tube
in which the solid reagents were also degassed. The ethanol
was cannulated into the reaction vessel and the resulting
mixture was stirred at 70 °C for 1 h. The progress of the
porphyrin-forming reactions was monitored by removing ali-
quots (25 µL) periodically from the reaction vessel via syringe.
In some cases, the aliquots were injected into 300 µL of a 10
mM solution of DDQ in toluene. A 25-µL sample from this
mixture was diluted in 3.00 mL of CH2Cl2/EtOH (3:l) and the
visible absorption spectrum was recorded. The yield of por-
phyrin was determined by the intensity of the Soret band
(assuming ꢀSoret ) 300 000 M-1 cm-1) measured from the apex
to the inflection point at the base of the red edge of the band.
A set of determinations also was done with omission of DDQ,
in which case the 25-µL reaction samples were diluted in 300
µL of CH2Cl2 and the resulting solution was further diluted
in 3.00 mL of CH2Cl2/EtOH (3:l) to record the absorption
spectrum. Note that reaction sampling in this manner entailed
removal of samples from heterogeneous mixtures; isolated
yields obtained in several instances gave general agreement
with the observed trends.
(ii) Exemplary Reaction with Dichlorobis(aceto-
nitrile)palladium(II). Samples of 2a (0.17 g, 0.50 mmol), Pd-
(CH3CN)2Cl2 (77 mg, 0.30 mmol), and KOH (0.14 g, 2.5 mmol)
were added to a Schlenk flask. The mixture was subjected to
several cycles of degassing. Degassed ethanol was then added
via cannula and the reaction mixture was heated to 70 °C.
After 1 h, the spectroscopic yield was 32% without adding DDQ
and 27% for the aliquots exposed to oxidation with DDQ. Then
the mixture was concentrated and the resulting residue was
dissolved in CH2Cl2 and passed through a pad of alumina (CH2-
Cl2). The resulting porphyrin-containing solution was concen-
trated to give an orange-purple solid. The solid was triturated
with methanol and dried in vacuo, affording a crystalline
orange-purple solid (60 mg, 32%): LD-MS obsd 746.0; FABMS
obsd 746.1713, calcd 746.1662 (C46H32N4Pd); λabs 416, 523 nm.
F. Oxidative Conversion of a 1-Acyldipyrromethane
to a 1-Acyldipyrrin. 1-(4-Methylbenzoyl)-5-phenyldipyr-
rin (6a). Following a standard procedure,23 a solution of 2a
(1.7 g, 5.0 mmol) in THF (16 mL) was treated dropwise with
a solution of DDQ (1.13 g, 5.00 mmol) in THF (16 mL). After
the mixture was stirred for 1 h at room temperature, the
Acknowledgment. This work was supported by the
NIH (GM36238). Mass spectra were obtained at the
Mass Spectrometry Laboratory for Biotechnology at
North Carolina State University. Partial funding for the
facility was obtained from the North Carolina Biotech-
nology Center and the NSF.
Supporting Information Available: Studies and results
concerning reaction course (e.g., order-of-addition effects);
synthesis of 13C-labeled 1-acyldipyrromethanes; synthesis of
a palladium chlorin; complete Experimental Section; spectral
data for selected compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO050120V
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