Customized, core-modified corroles from [2+2] condensation of dipyrromethanes

Article abstract of DOI:10.1016/S0040-4039(99)02142-5

Corroles and core-modified corroles were synthesized by acid-catalyzed condensation under low-scrambling conditions. The synthesis utilized [2+2] condensation of two different dipyrromethanes. The condensation afforded different corroles bearing heteroatoms in a predesignated location depending on the starting dipyrromethanes. Selective α-α' linkage was achieved by positioning a linking carbon unit at a different site of dipyrromethanes. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02142-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 697–701
Customized, core-modified corroles from [2+2] condensation of
dipyrromethanes
Won-Seob Cho and Chang-Hee Lee ∗
Department of Chemistry, Kangwon National University, Chun-Cheon 200-701, South Korea
Received 12 October 1999; revised 4 November 1999; accepted 8 November 1999
Abstract
Corroles and core-modified corroles were synthesized by acid-catalyzed condensation under low-scrambling
conditions. The synthesis utilized [2+2] condensation of two different dipyrromethanes. The condensation afforded
different corroles bearing heteroatoms in a predesignated location depending on the starting dipyrromethanes.
Selective α–α0 linkage was achieved by positioning a linking carbon unit at a different site of dipyrromethanes.
© 2000 Elsevier Science Ltd. All rights reserved.
Keywords: corrole; dipyrromethanes; [2+2] condensation.
The corrin ring is more flexible than chlorins and allows easy change of the steric environment around
the central metal ion. This steric versatility facilitates the catalysis of carbon–carbon bond formation
in vitamin B12.1 Most of the corrole synthesis known so far includes biladiene cyclization,2 meso-
carbon or sulfur extrusion of meso-thiaporphyrin,3 or direct synthesis from substituted pyrroles.4 The
primary target for the corrole research has been focused on the synthetic access to the ring structure of
corrin and corroles. Although corroles have the bipyrrole ring junction, they usually exhibit the same
dynamic range as found in porphyrins and chlorins. The first synthesis of corroles was reported in
1965 by photochemical cyclization of a,c-biladiene.8 A synthesis of core modified corroles containing
oxygen or sulfur has been reported by Broadhurst et al. However, McDonald type condensation of
dipyrromethanes and 2,20-bifuran or 2,20-bithiophene at elevated temperature resulted in a complex
mixture of products due to scrambling of starting material.5 The synthesis of meso-aryl corroles from
monopyrrole precursors has been reported.6,10 The reaction proceeds only in the presence of cobalt(II) ion
and these classical approaches have been extensively applied for various model systems and yields have
been improved.9a Direct synthesis of corrole from pyrrole and aldehydes has been reported recently.9b,c
The peripheral substitution usually induce electronic properties and is known to have reversed energy
levels compared with porphyrin.6 But little has been known for the synthetic method of corrole by direct
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02142-5
tetl 16070

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[2+2] condensation of dipyrromethanes. We here report the synthesis and characterization of new free
base oxacorroles bearing an oxygen atom in a designated position in the core.
The synthesis of p-tolyl-(furan-2-yl)-(pyrrol-2-yl)methane (1) was achieved by acid catalyzed con-
densation of 2-[α-hydroxy-α-(p-tolyl)]methylfuran with pyrrole. As shown in Scheme 1, Lewis acid
catalyzed acylation of 1 resulted in two products (2 and 3). The monoacylated 3 was obtained as the
major product in 36.6% yield. 1,9-Bisacylated product 2 was also isolated in 16.0% yield. The dominant
formation of 3 reflects higher reactivity of furan toward electrophilic species. Treatment of 1 with EtMgBr
(5.0 equiv.) in THF followed by p-toluoyl chloride (2 equiv.) gave 63% yield of 4 as a single product.
In our prior synthesis of core-modified porphyrin, the 1,9-bisacyldipyrromethanes were reduced to the
corresponding diol using a large excess of reducing agents.11 Treatment of 3 or 4 with NaBH4 (100 molar
equiv.) in MeOH:EtOH (2:1) gave clean reduction to the corresponding alcohols 5 and 6, respectively.
The use of a large excess amount of reducing agent is crucial in order to complete the reduction. The
TLC analysis showed single spot and the disappearance of carbonyl stretching associated with the
appearance of –O–H stretching was clearly observed in IR. The reduced compounds were unstable in
air and extensive decomposition was observed in 24 h even if it was stored in a freezer. Thus, the crude
alcohols were not purified further and directly used in the next step.
Scheme 1.
We applied the previously identified low-scrambling and acid-catalyzed conditions in synthesizing
core-modified porphyrins by [2+2] condensation.12 As shown in Scheme 2, during the preparation
of 5,10,15,20-tetra-(p-tolyl)-21-oxaporphyrin (8)7b by [2+2] condensation of diol (7) with meso-(p-
tolyl)dipyrromethane (10), we were able to isolate a trace amount of corrole (9).
Scheme 2.
The formation of corrole (9) from the condensation of 1013 with 7 must arise via cleavage of the furan-
C2 and 2α–C bond of 7. The site of cleavage was verified by independent synthesis of authentic corrole

699
(9) (Scheme 3). Acid-catalyzed condensation of 5 with dipyrromethane (10) exclusively afforded corrole
(9) in 9% yield. The spectroscopic data of corrole (9) obtained from the reaction shown in Scheme
2 were identical with the corrole isolated from the condensation of 10 with 5. Scheme 3 shows two
different types of [2+2] condensation. Different α–α linkage could be achieved depending on the position
of 2α-hydroxy group. Although the exact mechanism leading to the corrole is not certain yet, all the
experimental evidence indicates that the presence of BF3 is important in the formation of α–α linkage.
Only a small amount of corrole was isolated when the same condensation was carried out in the presence
of TFA. The major product was self-condensed, ONON type porphyrin.
Scheme 3.
The Soret band was observed in 402 nm in 9 and 412 nm in 11.14 These values are somewhat red-
shifted compared with those which do not have meso-substituents. The blue-shifted Soret band of 9
indicates that 9 must be less flexible and more stable than 11. These facts indicate that the α–α connection
of pyrrole–furan is more stable than the pyrrole–pyrrole connection. The other possible tautomeric form
of 11 must be a less stable isomer. The spectroscopic evidence also support those observations; the
β-pyrrolic resonances of 9 are shifted further down than those of 11. The inner N–H resonances in 9
was shown at –3.00 ppm while 11 was shown at –1.85 ppm as broad singlet. Only one N–H resonance
was observed in both cases. This is the first example of core-modified corroles obtained from the direct
condensation of two different dipyrromethanes.
Attempted condensation of 5-(p-tolyl)-1-[α-hydroxy-α-(p-tolyl)]methyldipyrromethane (12) with
dipyrromethane (10) in the presence of BF3·OEt2 did not give any corrole component, but self-condensed
13 was isolated in 11% yield (Scheme 4). However, condensation performed in the presence of p-
toluenesulfonic acid afforded a mixture of 5,10,15-tri(p-tolyl)corrole in trace amounts (ꢀ∼1%) and
porphyrin 13 in 10% yield. The condensation of 14 with 10 under the same conditions (BF3·OEt2, 1
mM) also afforded porphyrin 1515 in 12% as a single product. On the other hand, the condensation of 16
with 10 did not result in any porphyrinoid components. Exceptional interaction of furan with BF3 seems
important in the intramolecular cyclization. BF3 seems to make a strong complex with tetrapyrrolic inter-
mediate and consequently the intermediate becomes more electrophilic so that intramolecular coupling
is possible.
In conclusion, customized corrole could be synthesized by acid-catalyzed (BF3·OEt2) condensation
of two different dipyrromethanes. The extension of this reaction will give a variety of corroles bearing
different meso-substituents. The scope and limitation of the reaction will be reported in due course.

700
Scheme 4.
Acknowledgements
Support from the Korea Science and Engineering Foundation (grant no. 985-0300-001-2) is gratefully
acknowledged. The author thanks Professor J. S. Lindsey at North Carolina State University for helpful
discussions.
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13. meso-(p-Tolyl)dipyrromethane (10) was synthesized from the condensation of p-tolualdehyde and pyrrole as reported.7
1
14. Corrole (9): H NMR (CDCl3): δ 9.52 (d, 1H, J=4.2 Hz), 9.22 (d, 1H, J=4.4 Hz), 9.04 (d, 1H, J=4.2 Hz), 8.89–8.84 (m,
3H), 8.74–8.73 (m, 1H), 8.63 (d, 1H, J=4.5 Hz), 8.21–8.17 (m, 4H), 8.06 (d, 2H, J=7.8 Hz), 7.63–7.60 (m, 4H), 7.54 (d,
2H, J=7.8 Hz), 2.69 (s, 3H, Ar–CH3), 2.68 (s, 6H, Ar–CH3), −3.00 (bs, 1H, N–H). 13C NMR (CDCl3): δ 152.32, 150.15,
147.27, 139.44, 139.34, 137.65, 137.52, 137.01, 136.70, 135.99, 134.78, 134.49, 134.24, 134.08, 133.63, 131.66, 130.32,

701
128.91, 128.45, 127.63, 126.20, 125.27, 123.28, 123.26, 120.19, 117.11, 115.02, 113.35, 112.32, 106.97, 21.48, 21.43.
UV–vis (CH2Cl2:EtOH, 3:1) λmax (ε×10−3) 402 (93), 418 (49), 488 (3.2), 524 (7.2), 551 (19), 604 (7.4). FAB-MS calcd
1
for C40H31N3O 569.25, found 570.07 (M++H). (11): Yield 35.09 mg (15.1%); H NMR (CDCl3): δ 9.07 (d, 1H, J=5.1
Hz), 9.02–9.01 (m, 1H), 9.00 (d, 1H, J=4.0 Hz), 8.81 (d, 1H, J=4.3 Hz), 8.78 (d, 1H, J=4.8 Hz), 8.76 (d, 1H, J=5.1 Hz),
8.55–8.54 (m, 1H), 8.34 (d, 1H, J=4.5 Hz), 8.19–8.15 (m, 4H), 7.99 (d, 2H, J=7.8 Hz), 7.61–7.59 (m, 4H), 7.54 (d, 2H,
J=7.7 Hz), 2.68 (s, 3H, Ar–CH3), 2.67 (s, 6H, Ar–CH3), −1.85 (br s, 1H, N–H). 13C NMR (CDCl3): δ 150.44, 149.84,
145.44, 142.75, 138.50, 137.78, 137.63, 137.29, 137.05, 135.78, 134.70, 134.00, 133.88, 133.74, 132.23, 129.20, 129.00,
128.56, 128.27, 124.75, 123.71, 123.19, 123.17, 122.76, 121.21, 120.09, 120.02, 114.75, 108.79, 108.73, 105.29, 21.54,
21.48, 21.44. UV–vis (CH2Cl2:EtOH, 3:1) λmax (ε×10−3) 412 (211), 498 (13), 529 (13), 583 (6.2), 634 (20). FAB-MS calcd
for C40H31N3O 569.25, found 570.48 (M++H).
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