Rational Synthesis of Trans-Substituted Porphyrin Building Blocks Containing One Sulfur or Oxygen Atom in Place of Nitrogen at a Designated Site

Article abstract of DOI:10.1021/jo9909305

The use of heteroatom-substituted porphyrins in bioorganic and materials chemistry requires the ability to position a variety of substituents in a controlled manner about the porphyrin periphery. We describe a rational route to trans-AB₂C-type

Full text of DOI:10.1021/jo9909305

7890
J . Org. Chem. 1999, 64, 7890-7901
Ra tion a l Syn th esis of Tr a n s-Su bstitu ted P or p h yr in Bu ild in g
Block s Con ta in in g On e Su lfu r or Oxygen Atom in P la ce of
Nitr ogen a t a Design a ted Site
Won-Seob Cho,† Han-J e Kim,† Benjamin J . Littler,‡ Mark A. Miller,‡ Chang-Hee Lee,*,† and
J onathan S. Lindsey*,‡
Department of Chemistry, Kangwon National University, Chun-Cheon 200-701, Korea, and Department of
Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204
Received J une 8, 1999
The use of heteroatom-substituted porphyrins in bioorganic and materials chemistry requires the
ability to position a variety of substituents in a controlled manner about the porphyrin periphery.
We describe a rational route to trans-AB2C-type porphyrins bearing one oxygen atom (N3O) or one
sulfur atom (N3S) in a designated location in the porphyrin core. The synthesis involved four
stages: (1) Acid-catalyzed condensation of a furyl- or thienylcarbinol in excess pyrrole afforded the
aryl-substituted furyl- or thienylpyrromethane in high yield. (2) Treatment of the furyl- or
thienylpyrromethane with an acid chloride catalyzed by SnCl4 or AlCl3 afforded the corresponding
diketo product. (3) Reduction with NaBH4 in alcoholic solvents gave the furyl- or thienylpyr-
romethanediols. (4) Reaction of a furylpyrromethanediol, thienylpyrromethanediol, or dipyr-
romethanediol with a dipyrromethane in a one-flask process of condensation followed by oxidation
gave the corresponding porphyrin. Reaction conditions previously identified to minimize scrambling
in a dipyrromethane-aldehyde condensation were found to be effective in this application. Thus,
reaction with 10 mM reactants in acetonitrile at 0 °C containing BF3‚Et2O and NH4Cl followed by
oxidation with DDQ resulted in the desired porphyrin (10-20% yields) without acidolysis. In this
manner, N3O-, N3S-, or N4-porphyrins bearing 5-(p-iodophenyl), 15-[4-(2-(trimethylsilyl)ethynyl)-
phenyl], and 10,20-di-p-tolyl groups have been made. This set of trans-substituted porphyrin building
blocks is expected to be useful in the synthesis of biomimetic energy transduction systems.
In tr od u ction
for the vectorial flow of excited-state energy in light-har-
vesting arrays. To systematically exploit the distinctive
properties afforded by heteroatom substitution requires
the ability to locate the heteroatom in a specified position
in the core of the porphyrin with respect to different
substituents arranged about the porphyrin perimeter.
Heteroatom-substituted porphyrins were first prepared
by Broadhurst and Grigg, who performed a 3 + 1
condensation of a â-substituted tripyrrane and 2,5-
diformyl furan (or thiophene) to give the N3O (or N3S)
porphyrin.8 The synthesis of meso-substituted, hetero-
atom-substituted porphyrins was pioneered by Ulman
and Manassen, who reacted 2,5-bis(R-phenyl-R-hydroxy-
methyl)thiophene with pyrrole in toluene containing
chloroacetic acid to afford the NSNS tetra-p-tolylporphy-
rin.9 Alternatively, the thiophenediol was converted by
reaction with pyrrole to a dihydrotripyrrin analogue,
which upon reaction with a 2,5-bis(R-aryl-R-hydroxy-
methyl)thiophene afforded the NSNS-porphyrin bearing
two types of meso substituents in a cis configuration.10
More recently, Latos-Grazynski and Chmielewski re-
acted a 2,5-bis(R-aryl-R-hydroxymethyl)thiophene with
an aldehyde and pyrrole, affording the N3S-porphyrin
bearing two types of meso substituents in a cis configu-
ration (eq 1).11 This strategy afforded the core-modified
The ability to systematically tune the properties of the
porphyrin macrocycle is of central importance to a broad
range of studies in biomimetic and materials chemistry.
One approach for altering the porphyrin involves replace-
ment of one or more of the four pyrrolic nitrogen atoms
with heteroatoms such as oxygen, sulfur, selenium, or
tellurium. Such heteroatom porphyrins have altered
metal coordination properties,1 acid-base strength,2 re-
dox potentials,3 electronic energy levels4 (as evidenced
by the shifted absorption and fluorescence spectra),5 and
excited-state lifetimes.6 We recently proposed that a set
of heteroatom porphyrins arranged in a linear series with
a progressive decrease in energy levels could provide the
basis for an energy cascade.7 Such an array could be used
† Kangwon National University.
‡ North Carolina State University.
(1) (a) Latos-Grazynski, L.; Chmielewski, P. New J . Chem. 1997,
21, 691-700. (b) Latos-Grazynski, L.; Lisowski, J .; Olmsted, M. M.;
Balch, A. L. Inorg. Chem. 1989, 28, 1183-1188.
(2) Broadhurst, M. J .; Grigg, R.; J ohnson, A. W. J . Chem. Soc. C
1971, 3681-3690.
(3) (a) Ulman, A.; Manassen, J .; Frolow, F.; Rabinovich, D. Inorg.
Chem. 1981, 20, 1987-1990. (b) Pandian, R. P.; Chandrashekar, T.
K. Inorg. Chem. 1994, 33, 3317-3324.
(4) Gopinath, C. S.; Pandian, R. P.; Manoharan, P. T. J . Chem. Soc.,
Dalton Trans. 1996, 1255-1259.
(5) (a) Ulman, A.; Manassen, J .; Frolow, F.; Rabinovich, D. Tetra-
hedron Lett. 1978, 167-170. (b) Ulman, A.; Manassen, J .; Frolow, F.;
Rabinovich, D. Tetrahedron Lett. 1978, 1885-1886.
(6) (a) Hill, R. L.; Gouterman, M.; Ulman, A. Inorg. Chem. 1982,
21, 1450-1455. (b) Pandian, R. P.; Chandrashekar, T. K.; Saini, G. S.
S.; Verma, A. L. J . Chem. Soc., Faraday Trans. 1993, 89, 677-682. (c)
Ravikumar, M.; Pandian, R. P.; Chandrashekar, T. K. J . Porphyrins
Phthalocyanines 1999, 3, 70-77.
(7) Van Patten, P. G.; Shreve, A. P.; Lindsey, J . S.; Donohoe, R. J .
J . Phys. Chem. B 1998, 102, 4209-4216.
(8) Broadhurst, M. J .; Grigg, R. J . Chem. Soc., Chem. Commun.
1969, 1480-1482.
(9) Ulman, A.; Manassen, J . J . Am. Chem. Soc. 1975, 97, 6540-
6544.
(10) Ulman, A.; Manassen, J . J . Chem. Soc., Perkin Trans. 1, 1979,
1066-1069.
10.1021/jo9909305 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/29/1999

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7891
Ch a r t 1
porphyrins with replacement of one nitrogen atom with
an oxygen,12 sulfur,13 selenium,14 or tellurium atom.15 The
reaction of 2-(R-phenyl-R-hydroxy)methyl-5-hydroxy-
methylfuran with p-tolualdehyde and pyrrole gave the
5-phenyl-10,15-di-p-tolyl-21-thiaporphyrin, the only ex-
ample of a core-modified porphyrin with three different
meso substituents.12 These mixed condensations afford
heteroatom porphyrins possessing a cis configuration of
meso substituents among a mixture of porphyrins and
require chromatographic separation. The reliance on
statistical condensations in these methods limits access
to heteroatom porphyrin building blocks.
Our groups have been working toward the development
of porphyrin building blocks for the modular construction
of biomimetic assemblies and molecular devices. In
Korea, we have explored routes to a variety of core-
modified porphyrins, including porphyrins containing one
or two heteroatoms, N-confused porphyrins, and N-
confused heteroatom porphyrins.16-19 In the U.S., we have
developed and refined an efficient one-flask synthesis of
5-substituted dipyrromethanes,20,21 investigated a step-
wise approach toward porphyrins bearing four different
meso substituents,22 and identified nonscrambling condi-
tions for the dipyrromethane-aldehyde condensation
leading to trans-substituted porphyrins.23 A major em-
phasis in this latter work has been to develop rational
(nonstatistical) syntheses of multiply substituted por-
phyrins and to minimize the use of chromatography at
all stages. Here we present rational routes to porphyrin
building blocks containing one oxygen atom (N3O) or one
sulfur atom (N3S) with regiospecific control over the
location of the heteroatom as well as the meso-substituted
functional groups. Porphyrins with no core modification
(N4) also are available by this general route.
Resu lts a n d Discu ssion
The building block porphyrins required for a linear
array are shown in Chart 1. The bifunctional building
blocks (AB2C-type) possess a trans configuration of iodo
and ethyne groups that provide versatile handles for
incorporation into a variety of architectures.24 Two aryl
groups are included at the remaining meso positions for
solubility purposes. We initially hoped to use mesityl
groups because these have been used previously to
solubilize multiporphyrin arrays.25 However, because we
were unable to find suitable reduction conditions for
sterically hindered mesitoyl groups (vide infra), we chose
to employ p-tolyl groups instead. We also prepared
monofunctional building blocks (A3B-type) containing one
ethyne group and tetraarylporphyrins (A4-type) to serve
as benchmarks for the building block porphyrins.
Our synthetic strategy toward these building blocks
and the benchmarks involves the synthesis of furyl- or
thienylpyrromethanes, bis-acylation, and then reduction
to afford the corresponding diol and condensation of the
diol with a dipyrromethane to form the porphyrin (Scheme
1). This strategy parallels that employed in our prior
synthesis of porphyrins with four different meso substit-
uents and is critically dependent on the use of non-
scrambling conditions in the final condensation.22
In principle, either the dipyrromethane or the furyl/
thienylpyrromethane could be converted to the corre-
sponding diol. In a brief study (described in the Support-
ing Information), we showed that condensation of a
furylpyrromethane or a thienylpyrromethane with a
(11) Chmielewski, P.; Grzeszczuk, M.; Latos-Grazynski, L.; Lisowski,
J . Inorg. Chem. 1989, 28, 3546-3552.
(12) Chmielewski, P.; Latos-Grazynski, L.; Olmsted, M. M.; Balch,
A. L. Chem. Eur. J . 1997, 3, 268-278.
(13) Latos-Grazynski, L.; Lisowski, J .; Olmsted, M. M.; Balch, A.
L. J . Am. Chem. Soc. 1987, 109, 4428-4429.
(14) Latos-Grazynski, L.; Pacholska, E.; Chmielewski, P.; Olmsted,
M. M.; Balch, A. L. Inorg. Chem. 1996, 35, 566-573.
(15) Latos-Grazynski, L.; Pacholska, E.; Chmielewski, P.; Olmsted,
M. M.; Balch, A. L. Angew. Chem., Int. Ed. Engl. 1995, 34, 2252-
2254.
(16) Heo, P. Y.; Shin, G.; Lee, C. H. Tetrahedron Lett. 1996, 37, 197-
200.
(17) Heo, P. Y.; Lee, C. H. Bull. Korean Chem. Soc. 1996, 17, 515-
520.
(18) Lee, C. H.; Kim, H. J . Tetrahedron Lett. 1997, 38, 3935-3938.
(19) Cho, W. S.; Lee, C. H. Bull. Korean Chem. Soc. 1998, 19, 314-
319.
(20) Lee, C. H.; Lindsey, J . S. Tetrahedron 1994, 50, 11427-11440.
(21) 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.
(22) Lee, C.-H.; Li, F.; Iwamoto, K.; Dadok, J .; Bothner-By, A. A.;
Lindsey, J . S. Tetrahedron 1995, 51, 11645-11672.
(23) Littler, B. J .; Ciringh, Y.; Lindsey, J . S. J . Org. Chem. 1999,
64, 4, 2864-2872.
(24) Lindsey, J . S. In Modular Chemistry; Michl, J ., Ed.; NATO ASI
Series C: Mathematical and Physical Sciences, Vol. 499; Kluwer
Academic Publishers: Dordrecht, 1997; pp 517-528.
(25) Wagner, R. W.; J ohnson, T. E.; Lindsey, J . S. J . Am. Chem.
Soc. 1996, 118, 11166-11180.

7892 J . Org. Chem., Vol. 64, No. 21, 1999
Cho et al.
Sch em e 1
Sch em e 2
dipyrromethanediol also affords heteroatom porphyrins.
However, we did not pursue this synthetic approach
further because in any condensation between a dipyr-
romethanediol and a furyl/thienylpyrromethane there is
the complicating factor of differential reactivity between
the pyrrole ring and the furyl/thienyl ring.26 In contrast,
incorporating the heteroatom into the diol moiety mini-
mizes the reactivity differences and allows condensation
with a symmetrical dipyrromethane.
(1) Syn th esis of F u r yl-, Th ien yl-, or Dip yr r o-
m eth a n es. Dipyrromethanes 1-4 were prepared by
condensation of the aldehyde in neat excess pyrrole (eq
2).21 Bulb-to-bulb distillation removed the higher oligo-
matic aldehyde afforded the corresponding 2-R-hydroxy-
methylated compounds 5-8 in high yield (84-95%). A
small amount of deiodination occurred during the reac-
tion of p-iodobenzaldehyde with lithiated furan or
thiophene. Therefore, we developed a complementary
two-step route to p-iodophenyl carbinols that utilized
Freidel-Crafts acylation of furan28 or thiophene29 with
p-iodobenzoyl chloride to give the ketone (9 or 10) (54-
67%), followed by reduction with NaBH4 to afford the 2-R-
hydroxymethylated compounds 11 or 12 (99%) with no
deiodination.
On the basis of the conditions previously employed for
the formation of dipyrromethanes from 2-(R-hydroxy)-
methylpyrroles,20 carbinols 5-8, 11, or 12 were treated
mers and recrystallization removed the N-confused dipyr-
romethane, readily affording multigram batches of pure
dipyrromethane.
The furylpyrromethanes and thienylpyrromethanes
were prepared as shown in Scheme 2. Treatment of furan
or thiophene with n-butyllithium27 followed by an aro-
(27) Chadwick, D. J .; Willbe, C. J . Chem. Soc., Perkin Trans. 1 1977,
887-893.
(28) Caunt, D.; Crow, W. D.; Haworth, R. D. J . Chem. Soc. 1951,
1313-1318.
(29) Weitkamp, A. W.; Hamilton, C. S. J . Am. Chem. Soc. 1937, 59,
2699-2702.
(26) Marino, G. Adv. Heterocycl. Chem. 1971, 13, 235-314.

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7893
with BF3‚Et2O (1 mol equiv)30 in neat excess pyrrole (23-
66 mol equiv)31 to afford furyl- and thienylpyrromethanes
13-18 in excellent yield (88-93%). Examination of the
crude reaction mixtures produced from each furyl- or
thienylcarbinol by GC-MS showed the presence of a
byproduct of mass identical to that of the desired product.
We assigned this impurity as the “N-confused” pyrrol-3-
yl species by analogy to the byproduct formed in the
condensation of an aldehyde in neat excess pyrrole.21
Purification of the crude reaction mixture by column
chromatography, bulb-to-bulb distillation, or direct re-
crystallization, followed by recrystallization from ethanol
or washing with hexanes, afforded pure furylpyrro-
methanes 13-15. GC analysis of thienylpyrromethanes
16-18 showed that approximately 1% of the pyrrol-3-yl
species remained after the standard purification proce-
dures. These materials are readily available on a multi-
gram scale and were used directly in the acylation step.
(2) Acyla tion of th e F u r ylp yr r om eth a n es, Th i-
en ylp yr r om eth a n es, a n d Dip yr r om eth a n es. In our
previous study on the acylation of dipyrromethanes, we
were most interested in developing conditions that led
to the monoacyldipyrromethane.22 Optimal ratios for
monoacylation (63%) with little diacylation (19%) were
found to be 5-phenyldipyrromethane (1) (1.0 mol equiv),
EtMgBr (2.2 mol equiv), and p-toluoyl chloride (1.4 mol
equiv). Use of a larger excess of the acylation reagents
[1: EtMgBr/p-toluoyl chloride (1.0: 3.0: 2.2 mol equiv)]
increased the quantity of the diacyldipyrromethane (33%)
relative to the monoacyldipyrromethane (41%). In this
study, to further increase the amount of diacyldipyr-
romethane produced, we utilized an even greater excess
of the Grignard reagent and the acid chloride. Thus,
treatment of 1 with EtMgBr (5 mol equiv) in THF
followed by p-toluoyl chloride (5 mol equiv) gave 64% of
the diacylated product (19) and 31% of the monoacylated
product (eq 3).32 Identical treatment of 5-(p-iodophenyl)-
Sch em e 3
sired iodoethynylporphyrin was prepared using a comple-
mentary route via diacylation of 5-[4-(2-trimethylsilyl)-
ethynyl)phenyl]dipyrromethane (3) affording 20. In each
case, column chromatography enabled isolation of gram
batches of the diacyldipyrromethane free from the mono-
acyldipyrromethane.
Because furan and thiophene rings are unable to form
a species analogous to an N-metalated pyrrole, diacyla-
tion of the furyl- or thienylpyrromethanes cannot be
achieved using Grignard reagents. Previously, the 1,9-
diacylation of dithienylmethane or difurylmethane was
achieved under Freidel-Crafts reaction conditions,19 so
we studied analogous conditions for the diacylation of
furyl- or thienylpyrromethanes (Scheme 3). Our objective
was to achieve clean acylation of both heterocyclic nuclei
without forming excessive amounts of mono- or multi-
acylated products, since such a mixture would be difficult
to separate. Initial studies focused on the acylation of the
furylpyrromethane 15 with mesitoyl chloride (2.5 mol
equiv) utilizing SnCl4 (3.8 mol equiv). Purification of
(30) Use of TFA as an alternate catalyst was briefly examined.
Reaction of 11 in pyrrole (64 mol equiv) catalyzed by TFA (1 mol equiv)
also gave furylpyrromethane 15 in excellent yield (88%). However,
reaction of 12 using TFA (1 mol equiv) gave 18 in 28% yield. More
TFA (4 mol equiv) increased the yield to 76%.
(31) The furyl-/thienylpyrromethane yields were insensitive to the
excess of pyrrole over the range studied (23-66 mol equiv).
(32) Greater than 5-fold excesses of ethylmagnesium bromide and
p-toluoyl chloride did not significantly increase the ratio of diacyl-
dipyrromethane to monoacyldipyrromethane.
dipyrromethane (2) afforded a similar mixture of diacy-
lated and monoacylated products, but also there was
deiodination of the dipyrromethane. Therefore, the de-

7894 J . Org. Chem., Vol. 64, No. 21, 1999
Cho et al.
the crude product mixture by flash column chromatog-
raphy readily removed the small amounts of the mono-
and triacyl byproducts and afforded the diacylated prod-
uct 21 in 81% yield. Identical treatment of thienylpyr-
romethane 18 gave 22 in 82% yield.
We were ultimately unable to reduce the sterically
hindered mesitoyl groups (vide infra), so we used p-
toluoyl substituents instead. However, changing mesitoyl
chloride for p-toluoyl chloride resulted in a more complex
mixture of products that was difficult to separate. For
example, when 15 was treated with p-toluoyl chloride (2.5
mol equiv) and SnCl4 (3.8 mol equiv), the diacyl com-
pound 24 was isolated in 39% yield, but only after lengthy
chromatography.33 The use of more SnCl4 (5.5 mol equiv)
gave indiscriminate acylation. Use of AlCl3 (3.8 mol
equiv) as an alternate Lewis acid for reaction of 15 with
p-toluoyl chloride (2.5 mol equiv) gave a crude reaction
mixture that proved much easier to purify, affording pure
24 in 47% yield after a single flash column. Comparable
results were obtained upon reaction of furyl- and thie-
nylpyrromethanes 14, 17, and 18. Thus, diacyl com-
pounds 23-26 were readily prepared in 0.4-1.2 g batches
(26-53% yield) by AlCl3-catalyzed acylation with p-
toluoyl chloride followed by column chromatography.
(3) Red u ction To F or m th e Diol. In our prior
synthesis of porphyrins bearing four different meso
substituents, the diacyldipyrromethane intermediates
were reduced to the corresponding dipyrromethanediols
using a large excess of NaBH4 in THF/ethanol (1:1), but
the reduction product was used directly in the next step
and not characterized.22 Other reports have utilized
LiAlH4 in THF to reduce aroylpyrroles.16,34 We examined
these reaction conditions for the reduction of diacyldipyr-
romethane 19 and attempted to isolate and characterize
the dipyrromethanediol product.
A detailed description of these diketone reduction
studies is included in the Supporting Information. The
key findings were as follows: (1) treatment of 19 with
LiAlH4 in THF led to over-reduction of the acyl-moiety;
1H NMR spectroscopy showed the presence of one ben-
zylic group, not the expected two hydroxymethyl groups.
(2) No reduction was observed when 19 was treated with
NaBH4 in neat THF. (3) No reaction was observed over
1 h when 19 was treated with NaBH4 (5 mol equiv) in
THF/ethanol (1:1). (4) Treatment of 19 with NaBH4 (10
mol equiv) in THF/methanol (7:3) gave reduction to the
diol. The facile reduction in methanol likely involves a
reducing agent derived by reaction of NaBH4 with
methanol, since NaBH4 is known to decompose rapidly
in methanol.35
isolated if the reaction was quenched and worked up
under nonacidic conditions. Examination of the crude
reaction product by 1H NMR and IR spectroscopy showed
complete reduction of the carbonyl groups to hydroxy
groups with no over-reduction as well as no dehalogena-
tion of any p-iodophenyl groups.36 1H NMR spectroscopy
showed that a mixture of diastereomers was produced
(each diol contains three stereocenters), but all attempts
to separate the diastereomers by column chromatography
resulted in decomposition. Although the furyl-, thienyl-,
or dipyrromethanediols can be handled for a few hours,
significant decomposition yielding dark materials oc-
curred over 2 days upon storage in the freezer. Therefore,
the crude diols were not purified or stored but were
directly condensed with the dipyrromethane.
The sterically hindered mesitoyl-substituted dipyr-
romethanes 21 and 22 were not reduced under the
conditions applied for the reduction of 19, 20, and 23-
26. Use of stronger reducing agents (LiAlH4, NaAlH4,
LiBH4) in a variety of solvents afforded complex mixtures.
Accordingly, the mesityl-substituted heteroatom porphy-
rins could not be prepared despite the attractive solubility
features imparted by mesityl groups that have been
observed in other porphyrin building blocks.25
In general, the p-toluoyl-substituted compounds (19,
20, and 23-26) were effectively reduced to the diol using
a large excess of NaBH4 (50-100 mol equiv) in THF/
methanol (1:1-3:1) (eq 4). In each case, the reaction was
followed by TLC; initially, a monoreduced species was
observed, but further reduction afforded the diol as a
single component with a lower Rf value that was readily
(4) Exa m in a tion of Rea ction Con d ition s for P or -
p h yr in F or m a tion . We recently employed a rapid
small-scale assay based on LD-MS to identify reaction
conditions that minimize acid-catalyzed scrambling dur-
ing the condensation of sterically unhindered dipyr-
romethanes with aldehydes to form trans-substituted
porphyrins.23 We applied the same assay in this study
to survey conditions for the related condensation of a
dipyrromethanediol and a dipyrromethane. We chose the
(33) The complex mixture arises from the production of monoacy-
lation and triacylation. The identity of the major byproducts produced
in the acylation of compounds 24, 25, and 26 have been provisionally
assigned by 1H NMR spectroscopy of isolated samples. (Original NMR
spectra of these byproducts are provided in the Supporting Informa-
tion.)
(34) Wallace, D. M.; Leung, S. H.; Senge, M. O.; Smith, K. M. J .
Org. Chem. 1993, 58, 7245-7257.
(35) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley
& Sons: New York, 1967; p 1049.
(36) 1H NMR spectroscopy requires neutralization of the com-
mercially supplied CDCl3 over K2CO3 in order to prevent rapid acid-
catalyzed decomposition of the diols.

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7895
condensation of 19-d iol with 5-phenyldipyrromethane (1)
as our model system (eq 5) for two reasons: (1) The
combination of phenyl and p-tolyl substituents allows
resolution of scrambled porphyrins in the LD-MS spec-
trum while minimizing steric and electronic differences
and is analogous to the model system used in the
dipyrromethane-aldehyde study. (2) Both materials are
readily available.
F igu r e 1. Yield (determined spectroscopically) vs time for
reaction of 19-d iol (10 mM) and 1 (10 mM) (see eq 5). ]: with
TFA (17.8 mM) in CH2Cl2 at room temperature. b: with BF3‚
Et2O (1.0 mM) and NH4Cl (100 mmol/L) in acetonitrile at 0
°C. Scrambling levels23 are shown in parentheses: 0 ) no
scrambling; 1 ) trace scrambling; 2 ) significant scrambling.
(5) P r ep a r a tion of th e Heter oa tom P or p h yr in s.
We applied reaction conditions of diol (10 mM) and
dipyrromethane (10 mM) in acetonitrile at 0 °C catalyzed
by BF3‚Et2O (1 mM) in the presence of NH4Cl (100 mmol/
L) to the preparation of porphyrins 27-33 (eq 6).
Spectroscopic monitoring of the reactions forming N4-
porphyrin 27 and N3O-porphyrins 28-30 showed that the
yield rapidly maximized (within 5 min) in each case. In
contrast, condensations forming N3S-porphyrins 31-33
gave inconsistent yields and rates of reaction when
catalyzed by 1 mM BF3‚Et2O. This problem increased
with the scale of the condensation, and in certain cases
no porphyrin was formed even after 2 h. Increasing the
amount of BF3‚Et2O to 2 mM gave reliably fast reactions
(complete within 20 min) with no detectable scrambling.
In exploring higher acid concentrations for forming
thiaporphyrin 30, we found that 5 mM BF3‚Et2O resulted
in a crude reaction mixture comprising species consistent
with scrambled byproducts (LD-MS analysis). These
results show that an intermediate acid concentration is
most effective in achieving porphyrin formation in good
yield without detectable scrambling.
(6) P h ysica l P r op er ties of th e Heter oa tom P or -
p h yr in s. Oxaporphyrins are significantly more basic
than thiaporphyrins or N4-porphyrins,2 a feature that had
three significant ramifications in the isolation and char-
acterization procedures of the N3O-porphyrins. (1) The
basicity of the N3O-porphyrins (28-30) required separa-
tion of the porphyrin from the black nonporphyrin
pigments produced in the DDQ oxidation step to be
performed using basic alumina. The N3S-porphyrins (31-
33) were substantially less basic than the N3O-porphyrins
and could be separated from the DDQ oxidation byprod-
ucts using nonbasic alumina. Final purification of por-
phyrins 27-33 was achieved by recrystallization from
ethanol or methanol. The nonporphyrin pigments were
typically not isolated or characterized; however, during
the preparation of 5,10,15,20-tetra-p-tolyl-21-oxaporphy-
rin (28) we also isolated an N3O-tri(p-tolyl)corrole pro-
duced in less than 1% yield.38
During our study to prepare porphyrins bearing four
different meso substituents (ABCD-type porphyrins), we
identified that in CHCl3 use of TFA gave less scrambling
than BF3‚Et2O.22 We therefore screened the condensation
of 19-d iol and 1 under two sets of reaction conditions.
(1) Conditions similar to those used in the ABCD study:
dipyrromethanediol (10 mM) and dipyrromethane (10
mM) in CH2Cl2 catalyzed by TFA (17.8 mM). (2) Low-
scrambling conditions identified in the dipyrromethane/
aldehyde condensation: dipyrromethanediol (10 mM) and
dipyrromethane (10 mM) in acetonitrile at 0 °C in the
presence of NH4Cl (100 mmol/L) catalyzed by BF3‚Et2O
(1 mM). The time dependency of the spectroscopic yield
and the extent of scrambling are shown in Figure 1. Both
reactions have an initial phase (<1 min) during which
the porphyrin is rapidly formed with no detectable
scrambling. However, for the reaction in CH2Cl2 the
spectroscopic yield continues to increase from 1 to 30 min
in tandem with an undesirable increase in the amount
of scrambling. In contrast, the reaction in acetonitrile
shows no increase in either the spectroscopic yield or
scrambling from 1 to 30 min. Thus, the previously
identified low-scrambling conditions were even more
effective in the dipyrromethanediol/dipyrromethane con-
densation versus dipyrromethane/aldehyde condensation
because (1) the reaction was much more rapid (<1 min
vs ca. 4 h), (2) yields were higher (14% vs 9%), and (3)
scrambling was eliminated (undetectable vs trace).37
(37) The signal-to-noise ratio of LD-MS typically exceeded 100:1.
The MS method cannot exclude the selective scrambling yielding only
the cis-porphyrin or the movement of the heteroatom within the core.
However, rearrangement processes leading to such isomers would be
expected to form a distribution of porphyrin products, including those
of other masses. See ref 23.

7896 J . Org. Chem., Vol. 64, No. 21, 1999
Cho et al.
porphyrins are less sensitive and can be examined in
CDCl3 without base treatment.
1
The H NMR spectrum of porphyrin 30 or 33 revealed
the asymmetric structure around the macrocycle. Due to
the regiospecific placement of a furan or thiophene ring
and three types of meso substituents, each pyrrole unit
is unique. Using a 300 MHz spectrometer, all of the
resonances arising from the â-protons were clearly
separated, confirming the integrity of the AB2C-type
heteroatom porphyrin.
The UV-vis absorption spectra in toluene of the N3O-
and N3S-porphyrins displayed the Qx(0,0) band at ∼675
or ∼680 nm, respectively, to be compared with that of
the N4-porphyrin (27) at 649 nm. The Soret band of the
N3O- or N3S-porphyrins appeared at ∼423 or ∼432 nm,
respectively, to be compared with that of the N4-porphy-
rin at 422 nm. The Soret band of the N3O- or N3S-
porphyrins exhibited ꢀλmax ∼(2-3) × 105 M-1 cm-1 with
slight broadening (fwhm 15-19 nm). Previous compari-
sons of the effects of oxygen substitution on spectral
properties relied on an N3O-porphyrin bearing only three
meso substituents, which displayed the Qx(0,0) band at
664 nm.7,12 Thus, the N3O- and N3S-porphyrins bearing
identical substituents exhibit very similar red-shifts
compared with the parent N4-porphyrin. Knowledge of
the effects of heteroatom substitution on electronic energy
levels is essential for the rational design of energy
transduction systems based on heteroatom porphyrins.
The emission spectra in toluene of the N3O- and N3S-
porphyrins are characteristically red-shifted. The Q(0,0)
and Q(0,1) bands of the N3O-porphyrins appeared at
∼679 and ∼750 nm, respectively, while those of the N3S-
porphyrins appeared at ∼686 and ∼757 nm, to be
compared with the N4-porphyrin standard tetraphe-
nylporphyrin (TPP), which emits at 652 and 718 nm. The
fluorescence quantum yield of N3O-porphyrins 28 and 29
were 0.093 and 0.097 respectively, which are similar to
that of TPP (Φf ) 0.11). The N3S-porphyrins 31 and 32
exhibited fluorescence quantum yields of 0.023 and 0.016,
respectively. The diminished fluorescence intensity of
N3S-porphyrins compared to TPP has been noted pre-
viously.6b,c
(2) The absorption spectrum of an N3O-porphyrin in
neat CH2Cl2 typically shows a long-wavelength shoulder
on the Soret band due to formation of the protonated
porphyrin. Addition of triethylamine, or use of a more
basic solvent such as CH2Cl2/ethanol (3:1), causes disap-
pearance of the shoulder. The N3S-porphyrin is less easily
protonated and can be examined in CH2Cl2 alone.
(3) The 1H NMR spectrum of the N3O-porphyrins
collected in commercially supplied CDCl3 results in
disappearance of the N-H resonance. Treatment of the
CDCl3 with K2CO3 results in sharp peaks. The N3S-
Con clu sion
We have developed a rational route to trans-AB2C-type
porphyrins bearing one oxygen atom (N3O) or one sulfur
atom (N3S) in a designated location in the porphyrin core.
The key step in this route involves porphyrin formation
via condensation of a furylpyrromethanediol or thie-
nylpyrromethanediol with a dipyrromethane without any
acid-catalyzed scrambling. Typically, the single porphyrin
product is readily isolated in excellent purity in 10-20%
yield utilizing only trivial chromatography followed by
recrystallization. Simple and general synthetic methods
that readily allow the preparation of the diols in gram
batches have been developed. Therefore, the synthetic
route described in this paper enables the rapid prepara-
tion of trans-AB2C-type porphyrins with control over the
placement of a heteroatom within the porphyrin core and
the meso substituents around the porphyrin perimeter.
(38) The corrole structure must arise via the acid-catalyzed cleavage
of a polypyrrane, but the site of the R,R-linkage cannot be conclusively
determined from the spectral data collected: 1H NMR (CDCl3) δ 9.52
(d, J ) 4.2 Hz, 1 H), 9.22 (m, 1 H), 9.04 (d, J ) 3.6 Hz, 1 H), 8.87 (m,
3 H), 8.74 (m, 1 H), 8.63 (d, J ) 4.2 Hz, 1 H), 8.18 (m, 4 H), 8.06 (d, J
) 7.2 Hz, 2 H), 7.62 (d, J ) 8.1 Hz, 2 H), 7.61 (d, J ) 8.1 Hz, 2 H), 7.53
(d, J ) 8.1 Hz, 2 H), 2.70 (s, 9 H), -2.93 (br s, 1 H); λabs (toluene) nm
405, 486, 554, 607, 423; C40H31N3O calcd exact mass 569.2467, obsd
568.8 (LD-MS); obsd 569.2493 (FAB-MS). Therefore, at present the
exact mechanism leading to production of the corrole is uncertain.
Further studies are required to determine whether corrole production
is ubiquitous from the condensation of a furylpyrromethanediol,
thienylpyrromethanediol, or dipyrromethanediol with a dipyrromethane
catalyzed by BF3‚Et2O in acetonitrile in the presence of NH4Cl.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra and absorption
spectra were collected routinely. Elemental analyses were

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7897
performed by Atlantic MicroLab, Inc. Melting points are
uncorrected. A standard-size Kugelrohr short-path distillation
apparatus was purchased from Aldrich Chemical Co. Column
chromatography was performed on silica (Baker, 40 µm
average particle size), alumina (Fisher, 80-200 mesh), and
basic alumina (Fisher, Brockman activity I, 60-325 mesh).
The furyl-, thienyl-, and dipyrromethanes were examined by
GC analysis. Samples were analyzed with a GC system
equipped with a FID detector [temperature gradient: tem-
perature 1, 100 °C (3 min); temperature 2, 270 °C (10 min);
rate 10 °C/min, total run time 30 min]. GC-MS analysis was
performed identically to confirm the identity of N-confused
product. In each case, the estimated percentage of N-confused
product is based on relative peak areas without calibration
based on working curves concerning the response of the FID
detector.
The quantitative absorption spectral measurements were
performed using a HP8453 spectrometer with 1-nm resolution
(for comparison, meso-tetraphenylporphyrin has fwhm ) 13
nm in toluene). Fluorescence spectra and emission yield
determinations were made as previously described.40
For acylation reactions, CH2Cl2 was distilled from K2CO3.
THF was distilled from Na/benzophenone. All other chemicals
are reagent grade and were used as obtained. Unless otherwise
indicated, all reagents were obtained from Aldrich Chemical
Co., and all solvents were obtained from Fisher Scientific.
4-Iodobenzaldehyde was obtained from Karl Industries, Inc.
The furyl-, thienyl-, and dipyrromethanes and their corre-
sponding diols were easily visualized upon exposure of TLC
plates to Br2 vapor.
Porphyrins (from crude reaction mixtures, or following
purification) were analyzed by laser desorption ionization mass
spectrometry (LD-MS) without a matrix39 using a Bruker
Proflex II spectrometer without calibration. The progress of
the N4- and N3S-porphyrin-forming reactions was monitored
spectroscopically, and the extent of scrambling in the crude
reaction mixture was determined as described previously.22
Due to the basicity of the N3O-porphyrins, two modifications
were made to the standard monitoring procedure: (1) 25 µL
of triethylamine was added to the solution in the cuvette
(containing crude oxidized spectroscopic aliquots diluted in
CH2Cl2/ethanol (3:1)) prior to UV-vis analysis. (2) The crude
oxidized spectroscopic aliquots were spotted directly onto an
LD-MS target without prior filtration through a pad of silica
in a Pasteur pipet.
in THF (30 mL) using a double-tipped needle. The solution
was stirred for an additional 30 min at room temperature,
quenched with saturated aqueous NH4Cl, and extracted with
diethyl ether. The organic layer was dried (Na2SO4) and the
solvent removed. Column chromatography (silica; CH2Cl2)
afforded an oil (0.86 g, 84%). Spectroscopic data were identical
to those previously reported.42
2-[r-Hyd r oxy-r-(p-tolyl)]m eth ylfu r a n (6). Furan (2.00
mL, 27.5 mmol), TMEDA (6.50 mL, 43.1 mmol), n-butyllithium
(1.6 M in hexanes, 18.0 mL, 28.8 mmol), and hexanes (70 mL)
were treated as described for 5 to afford a yellow solid (2.90 g,
1
84%): mp 36-37 °C; H NMR (CDCl3) δ 7.39 (d, J ) 2.2 Hz,
1 H), 7.32 (d, J ) 8.0 Hz, 2 H), 7.18 (d, J ) 8.0 Hz, 2 H), 6.31
(m, 1 H), 6.12 (m, 1 H), 5.80 (d, J ) 3.7 Hz, 1 H), 2.36 (s, 3 H),
2.31 (br d, J ) 4.7 Hz, 1 H); 13C NMR (CDCl3) δ 156.07, 142.47,
137.88, 137.81, 129.15, 126.53, 110.15, 107.24, 70.02, 21.13;
m/z 188.0833 (HRMS), C12H12O2 requires 188.0837.
2-(r-Hyd r oxy-r-p h en yl)m eth ylth iop h en e (7). Thiophene
(0.51 mL, 6.37 mmol), TMEDA (1.50 mL, 9.94 mmol), n-
butyllithium (2.5 M in hexanes, 2.8 mL, 7.00 mmol), and
benzaldehyde (0.64 mL, 6.3 mmol) in hexanes (15 mL) were
treated as described for 5 to afford a solid (1.06 g, 89%): mp
55 °C (lit.43 mp 55.5 °C). Spectroscopic data were identical to
those previously reported.43
2-[r-Hydr oxy-r-(p-tolyl)]m eth ylth ioph en e (8). Thiophene
(4.40 mL, 55.0 mmol), TMEDA (9.40 mL, 62.3 mmol), n-
butyllithium (37.0 mL, 59.2 mmol, 1.6 M in hexanes), and
p-tolualdehyde (5.59 mL, 47.5 mmol) in hexanes (80 mL) were
treated as described for 5 to afford an oil that solidified upon
standing in a freezer for 1 week. Washing the solid with
hexanes afforded a tan solid (9.18 g, 95%): mp 48 °C; 1H NMR
(CDCl3) δ 7.33 (d, J ) 7.5 Hz, 2 H), 7.25 (m, 1 H), 7.17 (d, J )
7.5 Hz, 2 H), 6.93 (m, 1 H), 6.88 (m, 1 H), 6.02 (d, J ) 3.6 Hz,
1 H), 2.37 (d, J ) 3.6 Hz, 1 H), 2.35 (s, 3 H). Anal. Calcd for
C
12H12OS: C, 70.55; H, 5.92. Found: C, 70.42; H, 5.82.
2-(4-Iod oben zoyl)fu r a n (9). A sample of AlCl3 (0.34 g, 2.6
mmol) was added to an ice-cold solution of furan (0.25 mL,
3.4 mmol) and 4-iodobenzoyl chloride (0.45 g, 1.7 mmol) in CH2-
Cl2 (30 mL). The mixture was then heated at reflux for 2 h,
an additional sample of AlCl3 (0.57 g, 4.3 mmol) was added,
and the heating was continued for 1 h. The mixture was
combined with saturated aqueous NaHCO3 and then extracted
with CHCl3. The organic layer was washed with water and
then dried (MgSO4), and the solvent was removed to afford a
black solid. Column chromatography [silica; CH2Cl2/hexanes
(1:1)] and then recrystallization (ethanol/water) afforded a pale
5-[4-(2-(T r i m e t h y ls i ly l)e t h y n y l)p h e n y l]d i p y r r o -
m eth a n e (3). A solution of 4-(2-(trimethylsilyl)ethynyl)benz-
aldehyde41 (3.53 g, 17.3 mmol) in pyrrole (30 mL, 0.43 mol)
was degassed with a stream of Ar for 10 min. Then TFA (133
µL, 1.73 mmol) was added, the reaction mixture was stirred
for 5 min, and ethyl acetate and 0.1 M NaOH were added.
The organic phase was washed with 0.1 M NaOH and water
and then dried (Na2SO4) and the solvent removed. Bulb-to-
bulb distillation [170-180 °C (0.03 mmHg)] and then recrys-
tallization (ethanol) afforded colorless crystals (3.48 g, 63%):
1
yellow powder (0.27 g, 54%): mp 64 °C; H NMR (CDCl3): δ
7.88-7.85 (m, 2 H), 7.73-7.69 (m, 3 H), 7.25 (d, J ) 3.7 Hz, 1
H), 6.62-6.60 (m, 2 H). Anal. Calcd for C11H7IO2: C, 44.32;
H, 2.37; I, 42.57. Found: C, 44.50; H, 2.35; I, 42.67.
2-(4-Iod oben zoyl)th iop h en e (10). A sample of SnCl4 (0.90
mL, 7.7 mmol) was added to an ice-cold solution of thiophene
(0.43 mL, 5.4 mmol) and 4-iodobenzoyl chloride (1.4 g, 5.2
mmol) in benzene (20 mL). The mixture was heated at reflux
for 4 h, an additional sample of SnCl4 (1.5 mL, 13 mmol) was
added, and the heating was continued for 12 h. The mixture
was combined with 10 vol % HCl and then extracted with CH2-
Cl2. The organic layer was washed with water and then dried
(MgSO4) and the solvent removed to afford a black solid.
Column chromatography [silica; CH2Cl2/hexanes (2:1)] and
then recrystallization (ethanol) afforded colorless crystals (1.09
1
mp 120 °C; H NMR (CDCl3) δ 8.01 (br s, 1 H), 7.41 (d, J )
7.9 Hz, 2 H), 7.14 (d, J ) 7.9 Hz, 2 H), 6.69 (m, 2 H), 6.15 (m,
2 H), 5.87 (m, 2 H), 5.44 (s, 1 H), 0.25 (s, 9 H); 13C NMR (CDCl3)
δ 142.47, 132.13, 131.87, 128.21, 121.69, 117.36, 108.41,
107.31, 104.76, 94.23, 43.69, -0.10; m/z 318.1549 (HRMS),
C
20H22N2Si requires 318.1552.
1
g, 67%): mp 105.5 °C (lit.28 mp 106.5 °C); H NMR (CDCl3) δ
2-(r-Hyd r oxy-r-p h en yl)m eth ylfu r a n (5). Furan (0.77
7.88-7.84 (m, 2 H), 7.74 (m, 1 H), 7.63-7.55 (m, 3 H), 7.17
(dd, 1 H, J ) 5.1, 3.7 Hz). Anal. Calcd for C11H7IOS: C, 42.06;
H, 2.25; I, 40.40. Found: C, 42.22; H, 2.23; I, 40.49.
mL, 11 mmol) was added to a solution of TMEDA (2.5 mL, 17
mmol) and n-butyllithium (4.5 mL, 11 mmol, 2.5 M in hexanes)
in hexanes (25 mL). The mixture was heated at reflux for 30
min and then allowed to cool slightly and directly introduced
into an ice-cold solution of benzaldehyde (0.60 mL, 5.9 mmol)
2-[r-H yd r oxy-r-(4-iod op h en yl)]m et h ylfu r a n (11). A
sample of NaBH4 (0.17 g, 4.4 mmol) was added to a solution
of 9 (0.39 g, 1.3 mmol) in THF/methanol (5:1, 30 mL). The
mixture was stirred at room temperature for 10 min, quenched
(39) Srinivasan, N.; Haney, C. A.; Lindsey, J . S.; Zhang, W.; Chait,
B. T. J . Porphyrins Phthalocyanines 1999, 3, 283-291.
(40) Hsiao, J .-S.; Krueger, B. P.; Wagner, R. W.; J ohnson, T. E.;
Delaney, J . K.; Mauzerall, D. C.; Fleming, G. R.; Lindsey, J . S.; Bocian,
D. F.; Donohoe, R. J . J . Am. Chem. Soc. 1996, 118, 11181-11193.
(41) Ravikanth, M.; Strachan, J .-P.; Li, F.; Lindsey, J . S. Tetrahe-
dron 1998, 54, 7721-7734.
(42) Einhorn, J .; Luche, J . L. J . Org. Chem. 1987, 52, 4124-4126.
Lee, G. C. M.; Syage, E. T.; Harcourt, D. A.; Holmes, J . M.; Garst, M.
E. J . Org. Chem. 1991, 56, 7007-7014.
(43) Struha´rik, M.; Toma, S. J . Organomet. Chem. 1994, 464, 59-
63.

7898 J . Org. Chem., Vol. 64, No. 21, 1999
Cho et al.
108.18, 107.34, 45.27, 21.00; m/z 253.0938 (HRMS), C16H15
with water, and extracted with CH2Cl2 and the organic layer
dried (Na2SO4). Removal of the solvent afforded a brown solid
-
NS requires 253.0925. GC detected 17 (16.44 min, 98.4%) and
(p-tolyl)(thien-2-yl)(pyrrol-3-yl)methane (17.73 min, 1.6%).
(4-Iod op h en yl)(t h ien -2-yl)(p yr r ol-2-yl)m et h a n e (18).
Compound 12 (0.74 g, 2.3 mmol) was treated with pyrrole (8.0
mL, 120 mmol) and BF3‚Et2O (0.31 mL, 2.4 mmol) as described
for 13, except that the solid crude product was directly
recrystallized (hexanes or ethanol) to afford a brown solid (0.80
g, 93%): mp 91 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (br s, 1
H), 7.60 (d, J ) 8.2 Hz, 2 H), 7.17 (d, J ) 5.0 Hz, 1 H), 6.97 (d,
J ) 8.2 Hz, 2 H), 6.91 (dd, J ) 4.9 and 3.6 Hz, 1 H), 6.75 (d,
J ) 3.0 Hz, 1 H), 6.65 (m, 1 H), 6.12 (m, 1 H), 5.88 (s, 1 H),
5.56 (s, 1 H). Anal. Calcd for C15H12INS: C, 49.33; H, 3.31; N,
3.84. Found: C, 49.34; H, 3.37; N, 3.76. GC detected 18 (20.69
min, 98.7%) and (4-iodophenyl)(thien-2-yl)(pyrrol-3-yl)methane
(22.22 min, 1.3%).
1
(0.39 g, 99%): mp 48 °C; H NMR (CDCl3) δ 7.67 (d, J ) 8.1
Hz, 2 H), 7.36 (m, 1 H), 7.15 (d, J ) 8.1 Hz, 2 H), 6.29 (m, 1
H), 6.09 (d, J ) 3.0 Hz, 1 H), 5.72 (s, 1 H), 2.73 (br s, 1 H).
Anal. Calcd for C11H9IO2: C, 44.03; H, 3.02. Found: C, 44.40;
H, 3.07.
2-[r-Hyd r oxy-r-(4-iod op h en yl)]m eth ylth iop h en e (12).
A solution of 10 (0.74 g, 2.4 mmol) in THF/methanol (5:1, 30
mL) was treated with NaBH4 (0.55 g, 15 mmol) as described
for 11 to afford a gray solid (0.74 g, 99%): mp 85 °C; 1H NMR
(CDCl3) δ 7.69 (d, J ) 8.1 Hz, 2 H), 7.25 (m, 1 H), 7.20 (d, J )
8.1 Hz, 2 H), 6.95 (m, 1 H), 6.89 (m, 1 H), 6.01 (d, J ) 3.7 Hz,
1 H), 2.38 (d, J ) 3.7 Hz, 1 H). Anal. Calcd for C11H9IOS: C,
41.79; H, 2.87. Found: C, 42.04; H, 2.89.
P h en yl(fu r a n -2-yl)(p yr r ol-2-yl)m eth a n e (13). A solution
of 5 (1.05 g, 6.04 mmol) and pyrrole (10.0 mL, 144 mmol) cooled
by a water bath was degassed with N2 for 5 min, and then
BF3‚Et2O (0.80 mL, 6.3 mmol) was added. The mixture was
stirred for 30 min, quenched with 0.1 M NaOH, and extracted
with ethyl acetate. The combined organic layers were washed
with water and then dried (MgSO4), and the solvent was
removed to afford a black solid. Column chromatography
(silica; CH2Cl2) afforded a colorless oil (1.19 g, 88%): 1H NMR
(CDCl3) δ 8.04 (br s, 1 H), 7.38-7.19 (m, 6 H), 6.71 (m, 1 H),
6.32 (m, 1 H), 6.15 (q, J ) 2.9 Hz, 1 H), 6.06 (d, J ) 2.9 Hz, 1
H), 5.93 (m, 1 H), 5.46 (s, 1 H); 13C NMR (CDCl3) δ 155.58,
141.95, 131.03, 128.51, 128.41, 128.28, 127.02, 117.29, 110.15,
1,9-Bis(p-tolu oyl)-5-p h en yld ip yr r om eth a n e (19). A so-
lution of ethylmagnesium bromide (10.0 mL, 10 mmol, 1.0 M
in THF) was carefully added to a stirred solution of 5-phenyl-
dipyrromethane21 (1) (444 mg, 2.0 mmol) in THF (5 mL) under
Ar. An exothermic reaction with gas evolution ensued. After
30 min, a solution of p-toluoyl chloride (1.32 mL, 10.0 mmol)
in THF (5.0 mL) was slowly added. The reaction mixture was
stirred for an additional 2 h and then quenched with saturated
aqueous NH4Cl and extracted with CH2Cl2. The organic phase
was washed with water and then dried (MgSO4) and the
solvent removed to afford a dark oil. Column chromatography
[silica; CH2Cl2/ethyl acetate (20:1 to 5:1 gradient elution)]
initially afforded the monoacylated byproduct 1-(p-toluoyl)-5-
phenyldipyrromethane22 (209 mg, 31%) as a foam. Further
elution afforded 19 (585 mg, 64%) as an amorphous solid.22
1,9-Bis(p-tolu oyl)-5-[4-(2-(tr im eth ylsilyl)eth yn yl)p h en -
yl]d ip yr r om eth a n e (20). Compound 3 (3.00 g, 9.42 mmol)
was treated with ethylmagnesium bromide (47.1 mL, 47 mmol,
1.0 M in THF) and p-toluoyl chloride (6.23 mL, 47.1 mmol) as
described for 19, affording a pale brown solid. Recrystallization
(ethanol) afforded a colorless solid (1.22 g, 23%): mp 242-
108.21, 107.41, 107.21, 44.20; m/z 223.0991 (HRMS), C15H13
NO requires 223.0997. GC detected no phenyl(furan-2-yl)-
(pyrrol-3-yl)methane.
-
(p-Tolyl)(fu r a n -2-yl)(p yr r ol-2-yl)m et h a n e (14). Com-
pound 6 (1.24 g, 6.58 mmol) was treated with pyrrole (30 mL,
430 mmol) and BF3‚Et2O (0.84 mL, 6.6 mmol) as described for
13. Column chromatography (silica; CH2Cl2) afforded a color-
less oil (1.39 g, 89%): 1H NMR (CDCl3) δ 8.04 (bs, 1 H), 7.36
(m, 1 H), 7.14-7.08 (m, 4 H), 6.71 (m, 1 H), 6.31 (m, 1 H),
6.15 (m, 1 H), 6.05 (m, 1 H), 5.93 (m, 1 H), 5.42 (s, 1 H), 2.33
(s, 3 H); 13C NMR (CDCl3) δ 155.81, 141.88, 137.65, 136.65,
131.25, 129.25, 128.18, 117.16, 110.12, 108.25, 107.24, 107.08,
43.85, 21.00; m/z 237.1153 (HRMS), C16H15NO requires
237.1154. GC detected no (p-tolyl)(furan-2-yl)(pyrrol-3-yl)-
methane.
1
243 °C; H NMR (CDCl3) δ 11.05 (br s, 2 H), 7.69 (d, J ) 9.0
Hz, 4 H), 7.49 (d, J ) 9.0 Hz, 2 H), 7.42 (d, J ) 8.1 Hz, 2 H),
7.21 (d, J ) 7.8 Hz, 4 H), 6.58 (m, 2 H), 5.95 (m, 2 H), 5.63 (s,
1 H), 2.40 (s, 6 H), 0.26 (s, 9 H); IR (cm-1) 1614 (s, CdO). Anal.
Calcd for C36H34N2O2Si: C, 77.94; H, 6.18; N, 5.05. Found: C,
77.86; H, 6.22; N, 4.97.
(4-Iod op h en yl)(fu r a n -2-yl)(p yr r ol-2-yl)m et h a n e (15).
Compound 11 (0.39 g, 1.3 mmol) was treated with pyrrole (5.0
mL, 72 mmol) and BF3‚Et2O (0.17 mL, 1.3 mmol) as described
for 13. Column chromatography [silica; CH2Cl2/hexanes (1:2)]
then recrystallization (ethanol) afforded a pink solid (0.41 g,
89%): mp 78 °C; 1H NMR (CDCl3) δ 8.04 (br s, 1 H), 7.61 (m,
2 H), 7.36 (m, 1 H), 6.93 (m, 2 H), 6.71 (m, 1 H), 6.32 (dd, J )
2.7 and 1.5 Hz, 1 H), 6.14 (q, J ) 2.9 Hz, 1 H), 6.06 (m, 1 H),
5.90 (m, 1 H), 5.39 (s, 1 H). Anal. Calcd for C15H12INO: C,
51.60; H, 3.46; N, 4.01. Found: C, 51.73; H, 3.50; N, 3.94. GC
detected no (4-iodophenyl)(furan-2-yl)(pyrrol-3-yl)methane.
P h en yl(th ien -2-yl)(p yr r ol-2-yl)m eth a n e (16). Compound
7 (0.598 g, 3.14 mmol) was treated with pyrrole (5.0 mL, 72
mmol) and BF3‚Et2O (0.4 mL, 3.16 mmol) as described for 13,
except that the reaction flask was not placed in a water bath.
Recrystallization of the crude product (hexanes) afforded a
pink solid (0.68 g, 91%): mp 54-55 °C; 1H NMR (CDCl3) δ
7.90 (br s, 1 H), 7.35-7.20 (m, 6 H), 6.94 (dd, J ) 5.1 and 3.7
Hz, 1 H), 6.81 (m, 1 H), 6.71 (m, 1 H), 6.16 (q, J ) 2.9 Hz, 1
H), 5.93 (m, 1 H), 5.67 (s, 1 H); 13C NMR (CDCl3) δ 146.76,
142.76, 133.06, 128.51, 128.28, 126.99, 126.57, 125.73, 124.50,
(4-Iod op h en yl)[5-(m esit oyl)fu r a n -2-yl][5-(m esit oyl)-
p yr r ol-2-yl]m eth a n e (21). A sample of SnCl4 (0.40 mL, 3.4
mmol) was added to an ice-cold solution of 15 (0.32 g, 0.9 mmol)
and mesitoyl chloride (0.38 mL, 2.3 mmol) in toluene (20 mL).
The mixture was stirred for 40 min at room temperature, and
then 2.0 M HCl was added. The solution was extracted with
ethyl acetate, and the combined organic phases were washed
with 0.1 M NaOH and water and then dried (Na2SO4). Two
bands were observed by TLC [silica; hexanes/ethyl acetate (3:
1)] at Rf 0.67 (monoacyl product) and 0.55 (21). The solvent
was removed and the resulting solid purified by column
chromatography [silica; hexanes/ethyl acetate (3:1)]. Com-
pound 21 eluted as the second band. Recrystallization (ethanol)
1
afforded a tan solid (0.47 g, 81%): mp 109-110 °C; H NMR
(CDCl3) δ 9.42 (br s, 1 H), 7.68 (d, J ) 8.1 Hz, 2 H), 6.99 (d, J
) 8.1 Hz, 2 H), 6.86 (s, 4 H), 6.83 (d, J ) 2.9 Hz, 1 H), 6.38 (m,
1 H), 6.18 (d, J ) 2.9 Hz, 1 H), 5.94 (m, 1 H), 5.53 (s, 1 H),
2.31 (s, 6 H), 2.15 (s, 6 H), 2.14 (s, 6 H); 13C NMR (CDCl3) δ
189.09, 187.35, 159.78, 152.84, 138.88, 138.30, 137.97, 136.36,
135.61, 134.55, 134.45, 134.39, 132.71, 130.38, 128.28, 128.12,
121.46, 120.33, 111.03, 110.73, 93.45, 44.43, 21.10, 19.39,
19.19; m/z 641.1415 (HRMS), C35H32INO3 requires 641.1427.
(4-Iod op h en yl)[5-(m esitoyl)th ien -2-yl][5-(m esitoyl)p yr -
r ol-2-yl]m eth a n e (22). A mixture of 18 (0.418 g, 1.14 mmol)
and mesitoyl chloride (0.48 mL, 2.9 mmol) was treated with
SnCl4 (0.51 mL, 4.4 mmol) as described for 21, except that the
reaction time was 45 min. Two bands were observed by TLC
[silica; hexanes/ethyl acetate (5:1)] at Rf 0.57 (monoacyl
product) and 0.43 (22). The solvent was removed and the
resulting solid purified by column chromatography [silica;
hexanes/ethyl acetate (5:1)]. Compound 22 eluted as the second
band. Recrystallization (ethanol) afforded a yellow solid (0.63
117.16, 108.21, 107.47, 45.59; m/z 239.0769 (HRMS), C15H13
-
NS requires 239.0760. GC detected 16 (16.34 min, 98.7%) and
phenyl(thien-2-yl)(pyrrol-3-yl)methane (17.65 min, 1.3%).
(p -Tolyl)(t h ien -2-yl)(p yr r ol-2-yl)m et h a n e (17). Com-
pound 8 (5.20 g, 25.5 mmol) was treated with pyrrole (44.2
mL, 0.64 mol) and BF3‚Et2O (3.07 mL, 25.0 mmol) as described
for 13 to afford an oil (5.96 g, 92%): 1H NMR (CDCl3) δ 7.74
(br s, 1 H), 7.30-7.23 (m, 5 H), 7.04 (dd, J ) 5.1 and 3.6 Hz,
1 H), 6.92 (m, 1 H), 6.75 (m, 1 H), 6.26 (m, 1 H), 6.06 (m, 1 H),
5.72 (s, 1 H), 2.30 (s, 3 H); 13C NMR (CDCl3) δ 147.09, 139.85,
136.58, 133.29, 129.22, 128.18, 126.54, 125.63, 124.40, 127.10,

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7899
g, 82%): mp 124-125 °C; 1H NMR (CDCl3) δ 9.64 (br s, 1 H),
7.68 (d, J ) 8.8 Hz, 2 H,), 7.16 (d, J ) 3 Hz, 1 H), 7.01 (d, J )
8.8 Hz, 2 H), 6.87 (s, 4 H), 6.78 (d, J ) 3.0 Hz, 1 H), 6.40 (br
s, 1 H), 5.99 (m, 1 H), 5.67 (s, 1 H), 2.31 (s, 6 H), 2.16 (m, 12
H); 13C NMR (CDCl3) δ 189.45, 155.36, 144.47, 140.63, 140.37,
138.91, 138.59, 138.24, 136.62, 134.88, 134.65, 134.39, 132.84,
130.51, 128.48, 128.38, 127.80, 120.59, 111.13, 93.61, 46.28,
21.33, 19.62, 19.55; m/z 657.1223 (HRMS), C35H32INSO2
requires 657.1199.
(p-Tolyl)[5-(p-tolu oyl)fu r a n -2-yl][5-(p-tolu oyl)p yr r ol-2-
yl]m eth a n e (23). A solution of 14 (935 mg, 3.94 mmol) in CH2-
Cl2 (10 mL) was added to an ice-cold solution of p-toluoyl
chloride (1.19 mL, 8.97 mmol) and AlCl3 (1.35 g, 10.13 mmol)
in CH2Cl2 (40 mL) under Ar. The mixture was stirred for 2 h
at room temperature, saturated aqueous NaHCO3 was care-
fully added followed by CHCl3, and the mixture was filtered
through Celite to remove insoluble salts. The organic phase
was isolated and then washed successively with saturated
aqueous NaHCO3, 2 M NaOH, and water, and then dried
(MgSO4) and the solvent removed. TLC [silica; hexanes/ethyl
acetate (3:1)] showed many bands, including Rf 0.23 (23).
Column chromatography [silica; hexanes/ethyl acetate (3:1)]
afforded 23 (540 mg) contaminated with a small amount of
an impurity. Further column chromatography [silica; hexanes/
ethyl acetate (3:1)] followed by recrystallization (ethanol)
afforded pure 23 as a solid (443 mg, 26%): mp 66 °C; 1H NMR
(CDCl3) δ 9.33 (br s, 1 H), 7.82 (d, J ) 8.1 Hz, 2 H), 7.77 (d, J
) 8.1 Hz, 2 H), 7.28-7.24 (m, 4 H), 7.18-7.16 (m, 5 H), 6.81
(m, 1 H), 6.29 (d, J ) 2.9 Hz, 1 H), 6.11 (m, 1 H), 5.60 (s, 1 H),
2.42 (s, 6 H), 2.35 (s, 3 H); IR (cm-1) 1640 (m, CdO), 1605 (s,
CdO). Anal. Calcd for C32H27NO3: C, 81.16; H, 5.75; N, 2.96.
Found: C, 80.98; H, 5.91; N, 2.90.
product, 35%) and 0.35 (26). Purification by column chroma-
tography [silica; CHCl3/ethyl acetate, (24:1)] afforded 26 a pale
green solid (600 mg, 36%): mp 104-106 °C; 1H NMR (CDCl3)
δ 9.86 (br s, 1 H), 7.77 (d, J ) 8.1 Hz, 2 H), 7.74 (d, J ) 8.1
Hz, 2 H), 7.66 (d, J ) 8.3 Hz, 2 H), 7.47 (d, J ) 3.9 Hz, 1 H),
7.29-7.26 (m, 4 H), 7.03 (d, J ) 8.3 Hz, 2 H), 6.87 (d, J ) 3.8
Hz, 1 H), 6.82 (m, 1 H), 6.10 (m, 1 H), 5.73 (s, 1 H), 2.43 (s, 6
H); 13C NMR (CDCl3) δ 187.80, 184.73, 154.1, 143.31, 143.21,
142.80, 140.27, 139.82, 138.16, 135.52, 135.23, 134.67, 131.27,
130.43, 129.45, 129.27, 129.25, 129.18, 127.39, 120.15, 110.95,
93.53, 46.01, 21.72; m/z 601.0585 (HRMS), C31H24INO2S
requires 601.0573.
1,9-Bis[r-h yd r oxy-r-(p -t olyl)m et h yl]-5-p h en yld ip yr -
r om eth a n e (19-d iol). A sample of NaBH4 (1.33 g total, 35.2
mmol, 50 mol equiv) was carefully added in small portions
(∼400 mg each) over 20 min to a stirred solution of 19 (323
mg, 0.704 mmol) in THF/methanol (2:1, 20 mL). The progress
of the reduction was followed by TLC [alumina; ethyl acetate/
hexanes (1:1)]. Within 5 min, a new spot at Rf 0.5 was observed
(monoreduced product), but this new component was fully
converted to a second spot at Rf 0.2 (diol) after 40 min. The
reaction mixture was quenched with water and then extracted
with CH2Cl2. The organic phase was dried (K2CO3) and the
solvent removed to afford a pale yellow oil: 1H NMR (CDCl3)
δ 10.24 (m, 2 H), 7.39-7.19 (m, 5 H), 7.17-7.04 (m, 8 H), 5.75-
5.64 (m, 4 H), 5.45-5.30 (m, 3 H), 2.33 (br s, 6 H), 1.96-1.91
(br m, 2 H); IR (cm-1) 3290 (br s, OH).
5-(4-Iod op h e n yl)-15-[4-(2-(t r im e t h ylsilyl)e t h yn yl)-
p h en yl]-10,20-d i(p-tolyl)p or p h yr in (27). A solution of com-
pound 20 (224 mg, 0.40 mmol) in THF/methanol (3:1, 20 mL)
was reduced with NaBH4 (800 mg, 21.1 mmol) as described
for 19-d iol to afford an oil (20-d iol): 1H NMR (CDCl3) δ 10.11
(br m, 2 H), 7.43-7.35 (m, 2 H), 7.31-7.23 (m, 2 H), 7.13-
7.10 (m, 8 H), 5.74-5.61 (m, 4 H), 5.39-5.30 (m, 3 H), 2.33
(br s, 6 H), 0.25 (s, 9 H); IR (cm-1) 3290 (br m, OH).
(4-Iod op h en yl)[5-(p -t olu oyl)fu r a n -2-yl][5-(p -t olu oyl)-
p yr r ol-2-yl]m eth a n e (24). A solution of 15 (1.38 g, 3.96
mmol) in CH2Cl2 (10 mL) was treated with p-toluoyl chloride
(1.30 mL, 9.83 mmol) and AlCl3 (1.91 g, 14.3 mmol) in CH2Cl2
(100 mL) as described for 23, except that the reaction time
was 4 h. TLC [silica; hexanes/ethyl acetate (3:1)] showed bands
at Rf 0.69 (monoacyl product, trace), 0.53 (monoacyl product,
0.64 g, 34%), 0.46 (24), and 0.15 (triacyl product, trace).
Column chromatography [silica; CH2Cl2/ethyl acetate (25:1)]
afforded 24 contaminated with a small amount of an unidenti-
fied impurity. Further column chromatography [silica; CH2-
Cl2/ethyl acetate (10/1)] afforded pure 24 as a tan solid (1.10
Due to limited stability 20-d iol (ca. 0.40 mmol) was im-
mediately dissolved in acetonitrile (40 mL) and 5-(4-iodophen-
yl)dipyrromethane21 (2) (149 mg, 0.40 mmol) was added. The
solution was cooled in an ice bath under Ar for 10 min, and
then NH4Cl (214 mg, 4.0 mmol) was added followed by BF3‚
Et2O (5.0 µL, 0.04 mmol, 1 mM). The solution instantly
darkened, and the progress of the reaction was followed by
UV spectroscopy. After 5 min, the spectroscopic porphyrin yield
had stopped increasing, and then DDQ (136 mg, 0.60 mmol)
and triethylamine (ca 0.5 mL) were added and the mixture
was stirred at room temperature for 1 h. The entire reaction
mixture was then filtered through a pad of alumina (eluted
with CH2Cl2) until the eluant was no longer dark. Removal of
the solvent gave a dark solid that was fully redissolved in CH2-
Cl2/hexanes (1:1, 50 mL) and filtered through a pad of silica
[CH2Cl2/hexanes (1:1)]. The porphyrin eluted as a purple band.
Removal of the solvent followed by recrystallization (ethanol)
afforded a purple solid (36 mg, 10% from 20): 1H NMR (CDCl3)
δ 8.90-8.86 (m, 4 H), 8.81-8.78 (m, 4 H), 8.15 (d, J ) 8.1 Hz,
2 H), 8.09-8.07 (m, 6 H), 7.94 (d, J ) 8.1 Hz, 2 H), 7.86 (d, J
) 8.1 Hz, 2 H), 7.55 (d, J ) 8.1 Hz, 4 H), 2.70 (s, 6 H), 0.37 (s,
9 H), -2.81 (br s, 2 H); λabs (toluene) nm (ꢀ, mM-1 cm-1), 422
(330, fwhm ) 15 nm), 516 (14), 552 (8.0), 593 (4.4), 649 (3.7);
1
g, 47%): mp 74-75 °C; H NMR (CDCl3) δ 9.41 (br s, 1 H),
7.83-7.77 (m, 4 H), 7.70 (d, J ) 8.1 Hz, 2 H), 7.29-7.26 (m, 4
H), 7.17 (d, J ) 3.7 Hz, 1 H), 7.03 (d, J ) 8.8 Hz, 2 H), 6.82
(m, 1 H), 6.30 (d, J ) 3.7 Hz, 1 H), 6.09 (m, 1 H), 5.59 (s, 1 H),
2.43 (s, 6 H); 13C NMR (CDCl3) δ 184.77, 182.05, 159.17,
152.32, 143.50, 142.79, 138.49, 138.14, 138.04, 135.59, 134.62,
131.42, 130.55, 129.61, 129.32, 129.22, 121.30, 120.37, 110.90,
93.55, 44.60, 21.81, 21.75; IR (cm-1) 1640 (m, CdO), 1605 (s,
CdO); m/z 585.0810 (HRMS), C31H24IN3O requires 585.0801.
(p-Tolyl)[5-(p-tolu oyl)th ien -2-yl][5-(p-tolu oyl)p yr r ol-2-
yl]m eth a n e (25). A solution of 17 (0.401 g, 1.58 mmol) in CH2-
Cl2 (5 mL) was treated with p-toluoyl chloride (0.48 mL, 3.6
mmol) and AlCl3 (0.55 g, 4.1 mmol) in CH2Cl2 (30 mL) as
described for 23, except that the reaction time was 14 h. TLC
[silica; hexanes/ethyl acetate (3:1)] showed bands at Rf 0.56
(monoacyl product, trace), 0.46 (monoacyl product, 0.25 g,
26%), 0.38 (25), and 0.13 (triacyl product, trace). Column
chromatography [silica; CHCl3/ethyl acetate (24:1)] afforded
25 as a solid (0.41 g, 53%): mp 76-77 °C; 1H NMR (CDCl3) δ
9.54 (br s, 1 H), 7.80-7.74 (m, 4 H), 7.49 (d, J ) 3.9 Hz, 1 H),
7.30-7.27 (m, 4 H), 7.22-7.16 (m, 4 H), 6.91 (d, J ) 3.9 Hz, 1
H), 6.83 (m, 1 H), 6.14 (m, 1 H), 5.73 (s, 1 H), 2.44 (s, 6 H),
C
51H41IN4Si calcd mass 864.2, obsd 863.8 (LD-MS); calcd exact
mass 864.2145, obsd 864.2148 (FAB-MS).
5,10,15,20-Tetr a (p-tolyl)-23H-21-oxa p or p h yr in (28). A
solution of 23 (102 mg, 0.21 mmol) in THF/methanol (7:3, 20
mL) was reduced as described for 19-d iol to afford an oil (23-
d iol): 1H NMR (CDCl3): δ 8.72-8.55 (br m, 1 H), 7.19-7.04
(m, 12 H), 5.86-5.80 (m, 2 H), 5.69-5.49 (m, 4 H), 5.26 (m, 1
H), 3.56-3.11 (br m, 2 H), 2.32-2.29 (m, 9 H); IR (cm-1) 3345
(br s, OH).
2.36 (s, 3 H); IR (cm-1) 1605 (s, CdO); Anal. Calcd for C32H27
-
NO2S: C, 78.49; H, 5.56; N, 2.86. Found: C, 78.24; H, 5.53;
N, 2.77.
Condensation of freshly prepared 23-d iol (98 mg, 0.21
mmol) and 5-(p-tolyl)dipyrromethane21 (4) (48 mg, 0.20 mmol)
in acetonitrile (20 mL) in the presence of NH4Cl (110 mg, 21
mmol) catalyzed by BF3‚Et2O (20.4 µL, 0.021 mmol, 1.01 M in
acetonitrile, 1.0 mM) was performed as described for 27. DDQ
(139 mg, 0.610 mmol) and triethylamine (10 µL) were added
after 20 min. After 1 h of stirring at room temperature, the
mixture was combined with water and extracted with ethyl
(4-Iod op h en yl)[5-(p -t olu oyl)t h ien -2-yl][5-(p -t olu oyl)-
p yr r ol-2-yl]m eth a n e (26). A solution of 18 (1.01 g, 2.77
mmol) in CH2Cl2 (10 mL) was treated with p-toluoyl chloride
(1.27 g, 8.22 mmol) and AlCl3 (1.46 g, 1.09 mmol) in CH2Cl2
(100 mL) as described for 23, except that the reaction time
was 10 h. TLC analysis showed two bands at Rf 0.59 (monoacyl

7900 J . Org. Chem., Vol. 64, No. 21, 1999
Cho et al.
acetate. The organic phases were combined and dried (Na2-
SO4), and the solvent was removed. Flash column chromatog-
raphy [silica; 30 mm diameter × 100 mm; THF/CH2Cl2 (1:9)]
separated a fast moving black band that contained a corrole38
(less than 1% yield) from desired porphyrin that eluted slowly.
The column was then eluted using THF/CH2Cl2 (1:1) until no
red fluorescence was observed in the eluant using a UV lamp
(365 nm). Further purification by flash column chromatogra-
phy [basic alumina (Brockman activity I); CH2Cl2] eluted an
unidentified fast-moving blue band. The porphyrin was then
eluted as a bright green band using ethyl acetate/hexanes (1:
5). Removal of the solvent followed by recrystallization (etha-
nol) afforded a purple solid (17 mg, 12% from 23-d iol): 1H
NMR (400 MHz, CDCl3) δ 9.17 (s, 2 H), 8.87 (s, 2 H), 8.61 (d,
J ) 4.6 Hz, 2 H), 8.54 (d, J ) 4.6 Hz, 2 H), 8.06-8.04 (m, 8
H), 7.54-7.52 (m, 8 H), 2.70 (s, 6 H), 2.69 (s, 6 H), -1.53 (br
s, 1 H); λabs (toluene) nm (ꢀ, mM-1 cm-1), 422 (160, fwhm ) 19
nm), 509 (16), 541 (6.1), 613 (5.3), 675 (4.0); λem (toluene) 679,
750 nm; C48H37N3O calcd mass 671.3, obsd 673.1 (LD-MS);
calcd exact mass 672.3015 (MH+), obsd 672.3027 (FAB-MS).
5,10,20-tr i(p-tolyl)-15-[4-(2-(tr im eth ylsilyl)eth yn yl)ph en -
yl]-23H-21-oxa p or p h yr in (29). A solution of compound 23
(159 mg, 0.336 mmol) in THF/methanol (3:1, 40 mL) was
reduced as described for 19-d iol to afford 23-d iol as an oil.
Condensation of 23-d iol (ca. 0.336 mmol) and 3 (106 mg,
0.336 mmol) in acetonitrile (33 mL) in the presence of NH4Cl
(178 mg, 3.36 mmol) catalyzed by BF3‚Et2O (33 µL, 33 mmol,
1 M in acetonitrile, 1 mM) was performed as described for 27.
DDQ (151 mg, 0.665 mmol) was added after 10 min. The crude
product was dissolved in CH2Cl2 and purified by flash column
chromatography [basic alumina (Brockman activity I); hex-
anes/ethyl acetate (6:1)]. A blue band containing no porphyrin
eluted first, followed by a green band that contained the
porphyrin and some unidentified nonporphyrin pigments. The
pigments were removed by reoxidation with DDQ (151 mg) in
toluene (25 mL) at reflux for 1 h. Once the mixture had cooled
to room temperature, triethylamine (ca 100 µL) was added and
the mixture filtered through a chromatography pad [basic
alumina (Brockman activity I); hexanes/ethyl acetate (6:1)] to
afford a purple solid (25 mg, 10% from 23): 1H NMR (CDCl3)
δ 9.19 (m, 2 H), 8.89 (m, 1H), 8.81 (m, 1 H), 8.62 (m, 1 H),
8.59-8.54 (m, 3 H), 8.12 (d, J ) 8.1 Hz, 2 H), 8.05 (d, J ) 7.3
Hz, 6 H), 7.84 (d, J ) 8.1 Hz, 2 H), 7.53 (d, J ) 7.3 Hz, 6 H),
2.69 (s, 9 H), 0.37 (s, 9 H), -1.60 (br s, 1 H); λabs (toluene) nm
(ꢀ, mM-1 cm-1), 423 (290, fwhm ) 15 nm), 509 (26), 541 (7.1),
615 (4.1), 676 (5.8); λem (toluene) 680, 751 nm; C52H43N3OSi
calcd mass 753.4, obsd 754.5 (LD-MS); calcd exact mass
754.3254 (MH+), obsd 754.3262 (FAB-MS).
5-(4-Iod op h e n yl)-15-[4-(2-(t r im e t h ylsilyl)e t h yn yl)-
p h en yl]-10,20-d i(p-tolyl)-23H-21-oxa p or p h yr in (30). A so-
lution of 24 (530 mg, 0.905 mmol) in methanol/ethanol (2:1,
150 mL) was reduced as described for 19-d iol to afford an oil
(24-d iol): 1H NMR (CDCl3) δ 8.21 (m, 1 H), 7.60 (d, J ) 8.1
Hz, 2 H), 7.28-7.23 (m, 4 H), 7.15 (d, J ) 7.3 Hz, 4 H), 6.93
(d, J ) 8.1 Hz, 2 H) 5.96 (m, 1 H), 5.91 (m, 1 H), 5.81-5.76
(m, 1 H), 5.73-5.66 (m, 3 H), 5.66 (m, 1 H), 5.30-5.29 (m, 1
H), 2.35 (s, 6 H), 2.21 (br s, 2 H); IR (cm-1) 3355 (br s, OH);
m/z 589.1123 (HRMS) C31H28INO3 requires 589.1114.
Condensation of 24-d iol (424 mg, 0.719 mmol) and 3 (228
mg, 0.718 mmol) in acetonitrile (72 mL) in the presence of NH4-
Cl (383 mg, 7.17 mmol) catalyzed by BF3‚Et2O (9.1 µL, 0.072
mmol) was performed as described for 27. Samples of DDQ
(1.13 g, 4.97 mmol) and triethylamine (0.50 mL) were added
after 20 min, and the mixture was stirred for an additional 1
h at room temperature before being combined with water and
extracted with ethyl acetate. The organic layer was dried (Na2-
SO4) and the solvent removed. Column chromatography [silica;
50 mm diameter × 100 mm; THF/CH2Cl2 (1:9)] separated
unidentified fast moving black materials from the desired
porphyrin that eluted slowly. The column was eluted until no
red fluorescence was observed in the eluant using a UV lamp
(365 nm). Further purification [basic alumina (Brockman
activity I): 35 mm diameter × 200 mm; ethyl acetate/hexanes
(1:6)] eluted the desired porphyrin as a green band. Recrys-
tallization (ethanol) afforded a purple solid (55 mg, 9% from
24-diol): 1H NMR (CDCl3) δ 9.22 (d, J ) 5.1 Hz, 1 H), 9.14 (d,
J ) 5.1 Hz, 1 H), 8.90 (d, J ) 5.1 Hz, 1 H), 8.82 (d, J ) 5.1 Hz,
1 H), 8.64 (d, J ) 4.5 Hz, 1 H), 8.56 (m, 2 H), 8.50 (d, J ) 5.1
Hz, 1 H), 8.13-8.03 (m, 8 H), 7.92-7.84 (m, 4 H), 7.56-7.53
(m, 4 H), 2.70 (s, 3 H), 2.69 (s, 3 H), 0.37 (s, 9 H); λabs (toluene)
nm (ꢀ, mM-1 cm-1) 424 (270, fwhm ) 19 nm), 510 (26), 542
(7.8), 615 (5.0), 675 (6.4); C51H40IN3OSi calcd mass 865.2, obsd
867.0 (LD-MS); calcd exact mass 866.2064 (MH+), obsd 866.2077
(MH+) (FAB-MS).
5,10,15,20-Tetr a (p-tolyl)-23H-21-th ia p or p h yr in (31). A
solution of compound 25 (238 mg, 0.486 mmol) in THF/
methanol (1:1, 50 mL) was reduced by NaBH4 (1.84 g, 48.6
mmol) as described for 19-d iol to afford an oil (25-d iol): 1H
NMR (CDCl3) δ 8.08 (br s, 1 H), 7.29-7.20 (m, 4 H), 7.15-
7.05 (m, 8 H), 6.62 (m, 1 H), 6.56 (m, 1 H), 5.86 (m, 1 H), 5.76
(m, 2 H), 5.68 (m, 1 H), 5.43 (s, 1 H), 2.43 (br s, 2 H), 2.33-
2.30 (m, 9 H); IR (cm-1) 3375 (br s, OH); m/z 493.2062 (HRMS),
C
32H31NO2S requires 493.2076.
Condensation of 25-d iol (ca. 0.49 mmol) and 5-(p-tolyl)-
dipyrromethane21 (4) (115 mg, 0.486 mmol) in acetonitrile (49
mL) in the presence of NH4Cl (260 mg, 4.86 mmol) catalyzed
BF3‚Et2O (49 µL, 49 mmol, 1 M stock in acetonitrile, 1 mM)
was performed as described for 27. DDQ (221 mg, 0.972 mmol)
was added after 18 min and the mixture stirred for 1 h.
Triethylamine (ca. 1 mL) was added and the entire reaction
mixture filtered through an alumina pad (CH2Cl2). TLC (silica;
CH2Cl2) showed the crude product contained the desired
porphyrin contaminated with some pigments, so the crude
product was reoxidized with DDQ (227 mg, 1.0 mmol) in
toluene (50 mL) at reflux for 1 h. Addition of triethylamine
(ca. 1 mL) and CH2Cl2 (25 mL) to the cooled mixture followed
by filtration through an alumina pad (CH2Cl2) afforded the
porphyrin and trace amounts of undesired non-porphyrin
pigments. Final purification by flash column chromatography
[silica; CH2Cl2/hexanes (1:1)] followed by recrystallization
(ethanol) afforded a purple solid (50 mg, 15% from 25): 1H
NMR (CDCl3) δ 9.75 (s, 2 H), 8.93 (d, J ) 1.5 Hz, 2 H), 8.68
(d, J ) 5.1 Hz, 2 H), 8.61 (d, J ) 4.4 Hz, 2 H), 8.13 (d, J ) 8.1
Hz, 2 H), 8.07 (d, J ) 7.6 Hz, 2 H), 7.62 (d, J ) 8.1 Hz, 2 H),
7.54 (d, J ) 7.3 Hz, 2 H), 2.70 (s, 12 H), -2.68 (br s, 1 H); λabs
(toluene) nm (ꢀ, mM-1 cm-1), 431 (190, fwhm ) 17 nm), 515
(27), 550 (11), 621 (5.9), 680 (8.2); λem (toluene) 686, 756 nm;
C
48H37N3S calcd mass 687.3, obsd 688.6 (LD-MS); calcd exact
mass 688.2786 (MH+), obsd 688.2787 (FAB-MS).
5,10,20-Tr i(p -t olyl)-15-[4-(2-(t r im et h ylsilyl)et h yn yl)-
p h en yl]-23H-21-th ia p or p h yr in (32). A solution of compound
25 (98 mg, 0.20 mmol) in THF/methanol (3:1, 16 mL) was
reduced by NaBH4 (378 mg, 10.0 mmol) as described for 19-
d iol to afford 25-d iol as an oil.
Condensation of 25-d iol (ca. 0.20 mmol) and 3 (64 mg, 0.20
mmol) in acetonitrile (20 mL) in the presence of NH4Cl (108
mg, 2.0 mmol) catalyzed BF3‚Et2O (5.0 µL, 0.40 mmol, 2.0 mM)
was performed as described for 27. DDQ (68 mg, 0.30 mmol)
was added after 4 min, and the mixture stirred for 1 h.
Triethylamine (ca. 0.5 mL) was added and the entire reaction
mixture filtered through an alumina pad (CH2Cl2). Removal
of the solvent afforded a black solid that was purified by
filtration through a silica pad [CH2Cl2/hexanes (1:1)] followed
by recrystallization (methanol) to afford a purple solid (29 mg,
18% from 25): 1H NMR (CDCl3) δ 9.76 (s, 2 H), 8.96 (d, J )
2.1 Hz, 1 Η), 8.95 (d, J ) 1.5 Hz, 1 H), 8.88 (d, J ) 2.1 Hz, 1
H), 8.86 (d, J ) 1.5 Hz, 1 H), 8.70 (d, J ) 4.5 Hz, 1 H), 8.69 (d,
J ) 4.5 Hz, 1 H), 8.62 (d, J ) 4.5 Hz, 1 H), 8.55 (d, J ) 4.5 Hz,
2 H), 8.14 (d, 8 H), 8.07 (d, J ) 7.2 Hz, 4 H), 7.86 (d, J ) 8.1
Hz, 4 H), 7.63 (d, 8 H), 7.556 (d, J ) 7.2 Hz, 4 H) 2.70 (s, 9 H),
0.38 (s, 9 H), -2.72 (s, 1 H); λabs (toluene) nm (ꢀ, mM-1 cm-1),
432 (250, fwhm ) 17 nm), 515 (18), 551 (6.5), 621 (2.5), 681
(4.6); λem (toluene) 687, 758 nm; C52H43N3SSi calcd mass 769.3,
obsd 770.7 (LD-MS); calcd exact mass 769.2947, obsd 769.2930
(FAB-MS).
5-(4-Iod op h e n yl)-15-[4-(2-(t r im e t h ylsilyl)e t h yn yl)-
p h en yl]-10,20-d i(p-tolyl)-23H-21-th ia p or p h yr in (33). A
solution of compound 26 (120 mg, 0.20 mmol) in THF/methanol
(3:1, 16 mL) was reduced by NaBH4 (378 mg, 10.0 mmol) as
described for 19-d iol to afford an oil (26-d iol): 1H NMR

Synthesis of Trans-Substituted Porphyrin Building Blocks
J . Org. Chem., Vol. 64, No. 21, 1999 7901
(CDCl3) δ 8.07 (br s, 1 H), 7.59 (d, J ) 7.3 Hz, 2 H), 7.28 (d, J
) 7.3 Hz, 2 H), 7.22 (d, J ) 8.1 Hz, 2 H), 7.16-7.12 (m, 4 H),
6.95 (d, J ) 7.3 Hz, 2 H), 6.64 (m, 1 H), 6.55 (m, 1 H), 5.88 (s,
1 H), 5.77 (m, 1H), 5.73-5.70 (m, 2H), 5.42 (s, 1 H), 2.34 (s, 6
H), 2.25 (br s, 2 H); IR (cm-1) 3400 (br s, OH).
Ack n ow led gm en t. This work was supported by the
NIH (GM36238) and by the Korea Science and Engi-
neering Foundation (KOSEF 985-0300-001-2). Mass
spectra were obtained at the NC State University Mass
Spectrometry Laboratory for Biotechnology. Partial
funding for the Facility was obtained from the North
Carolina Biotechnology Center and the National Science
Foundation.
Condensation of 26-d iol (ca. 0.20 mmol) and 3 (64 mg, 0.20
mmol) in acetonitrile (20 mL) in the presence of NH4Cl (108
mg, 2.0 mmol) catalyzed BF3‚Et2O (5.0 µL, 0.40 mmol, 2.0 mM)
was performed as described for 27. DDQ (68 mg, 0.30 mmol)
was added after 18 min and the mixture stirred for 1 h.
Triethylamine (ca. 0.5 mL) and CH2Cl2 (50 mL) were added,
and the entire reaction mixture was filtered through an
alumina pad (CH2Cl2). Removal of the solvent afforded a black
solid that was purified by filtration through a silica pad [CH2-
Cl2/hexanes (1:1)] followed by recrystallization (ethanol) to
afford a purple solid (19 mg, 11% from 26): 1H NMR (CDCl3)
δ 9.77 (d, J ) 5.2 Hz, 1 H), 9.68 (d, J ) 5.2 Hz, 1 H), 8.96 (dd,
J ) 5.2, 1.5 Hz, 1H), 8.88 (dd, J ) 5.2, 1.5 Hz), 8.70 (d, J )
4.4 Hz, 1 H), 8.63 (m, 2 H), 8.55 (d, J ) 4.4 Hz, 1 H), 8.15-
8.11 (m, 4 H), 8.16 (d, J ) 8.1 Hz, 2 H), 7.96 (d, J ) 8.8 Hz, 2
H), 7.85 (d, J ) 8.1 Hz, 2 H), 7.62 (d, J ) 7.3 Hz, 2 H), 7.53 (d,
J ) 8.1 Hz, 2 H), 2.70 (s, 6 H), 0.37 (s, 9 H); λabs (toluene) nm
(ꢀ, mM-1 cm-1), 432 (280, fwhm ) 15 nm), 515 (50), 550 (37),
621 (30), 679 (30); C51H40IN3SSi calcd mass 881.2, obsd 883.4
(LD-MS); calcd exact mass 881.1757, obsd 881.1793 (FAB-MS).
Su p p or tin g In for m a tion Ava ila ble: Full descriptions of
the study into the condensation of a furylpyrromethane or a
thienylpyrromethane with a dipyrromethanediol, and the
study into the reduction of diacyldipyrromethanes to dipyr-
1
romethanediols; H NMR spectra of compounds 3, 6, 13, 14,
16, 17, 21, 22, 24, byproducts of 24, byproducts of 25, 26, a
byproduct of 26, 19-d iol, 20-d iol, the diols of 23-26, 27, the
corrole byproduct of 28, 29-34, and 34-d iol; LD-MS spectra
of porphyrins 27, 29-33, and the corrole byproduct of 28; UV-
vis absorption spectra of porphyrins 27 and 29-33; emission
spectra of porphyrins 28, 29, 31, and 32. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O9909305