Expedient synthesis of corroles by oxidant-mediated, direct α-α' coupling of tetrapyrromethanes

Article abstract of DOI:10.1016/S0040-4039(00)01416-7

Oxidant mediated coupling of tetrapyrromethanes resulted in the exclusive formation of meso-substituted corroles in more than 60% yields. The similar coupling reaction of 1,14-unsubstituted 16-oxatripyrromethane with 5-tolyldipyrromethane carried out in acetonitrile also gave expanded corroles as a single product. In both cases acid catalysts are not necessary for the direct α-α' coupling reaction. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01416-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8121–8125
Expedient synthesis of corroles by oxidant-mediated, direct
a-a% coupling of tetrapyrromethanes
Jae-Won Ka, Won-Seob Cho and Chang-Hee Lee*
Department of Chemistry, Kangwon National University, Chun-chon 200-701, South Korea
Received 11 July 2000; revised 16 August 2000; accepted 18 August 2000
Abstract
Oxidant mediated coupling of tetrapyrromethanes resulted in the exclusive formation of meso-substi-
tuted corroles in more than 60% yields. The similar coupling reaction of 1,14-unsubstituted 16-oxa-
tripyrromethane with 5-tolyldipyrromethane carried out in acetonitrile also gave expanded corroles as a
single product. In both cases acid catalysts are not necessary for the direct a-a% coupling reaction. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: corroles; tetrapyrromethanes; oxidative-coupling; smaragdyrin.
The metal complexes of corroles and corrins are important biological cofactors and the study
of their physicochemical properties has contributed to the development of the chemistry of
corrinoid macrocycles.1 A recent report2 indicated the potential utilities of metallocorroles as
catalysts for oxygen activation and for cyclopropanation reaction. The more flexible nature of
the corrin ring system allows it to change the steric environment around the central metal ion
easily in comparison to the reduced porphyrins. This versatility is well adapted in vitamin B12.3,4
One of the well known synthetic methods of corroles is the cyclization of tetrapyrrolic
precursors. Paolesse et al. reported the acid-catalyzed cyclization of a,c-biladiene in various
solvents claiming that the conformational factors control the cyclization processes.5 More
recently, corrole has been isolated from the solventless condensation of aldehydes and pyrrole.6
It has been known that square-planar forming metal ions show a template effect and usually
enhance the yield of corroles.7 The mechanistic insight for the biladiene cyclization was also
investigated by Woodward and Hoffman.8 Previously, we reported a synthetic method for core-
modified corrole by a ‘2+2’ approach starting from two different dipyrromethanes.9 The reac-
tion involves acid-catalyzed condensation followed by direct intramolecular coupling. Current
results indicate that simple oxidative cyclization is operating in the intramolecular coupling of
tetrapyrrolic precursors and an acid catalyst is not necessary. Direct coupling of oligopyrro-
methanes in the presence of oxidizing agents resulted in the formation of corroles as a single
product with high yields. The oxidant-mediated intermolecular coupling of dipyrromethanes
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01416-7

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with tripyrromethanes also afforded smaragdyrin, an expanded corrole as a single product.
Herein, we report a convenient, rational synthesis of meso-substituted corroles as well as
expanded corroles by direct coupling of oligopyrromethanes.
The tetrapyrromethanes (3) are synthesized in reasonable yields (Scheme 1) by direct conden-
sation of aldehydes and pyrrole as reported previously.10 Improved yields of tetrapyrromethane
was achieved by reducing the pyrrole/aldehyde ratio to 3/1. The typical product ratios (1/2/3/4)
of 2/2/1/1 was obtained when benzaldehyde and pyrrole were condensed. Single column
chromatography is good enough to separate all the components. The oxidative coupling reaction
of (3) to obtain corroles was carried out as shown in Scheme 2.11
Scheme 1.
Scheme 2.

8123
The reaction gave desired corroles in a range of solvents and in the presence of inorganic
additives, including NH4Cl, KCl, NaCl, KBr and NH4NO3. No corroles were obtained when
pure dichloromethane was used as a solvent, while 16% of corrole was isolated by adding excess
NH4Cl. Low yield (ꢀ6%) of corrole was obtained in protic solvents such as methanol.
Acetonitrile usually gave ꢀ30% yield of corrole in the presence of inorganic additives, but
only ꢀ4% of corrole was isolated in the absence of the additives. Attempted coupling in
propionitrile dramatically improved the yield up to 65% and the addition of additives did not
alter the yield appreciably. Butyronitrile was also a good solvent for the coupling, but without
the improvement in yield (Table 1). The reaction proceeds smoothly in all cases and acid
catalysts are not necessary in the reaction. Corrole (5) was easily separated by column
chromatography on neutral alumina. Significant peak broadening of all the resonance lines was
observed when proton NMR spectra were taken in pure CDCl3. On the other hand, adding a
drop of methanol-d4 resulted in fully resolved spectra. This result indicates the flexible nature of
the molecule. Pyrrolic NꢀH signals were not detected in either solvents, but the spectra taken in
DMSO-d6 show broad signal at −2.67 ppm. The reaction carried out in the presence of
p-chloranil afforded only 10% of corroles and the reaction was much slower.
Table 1
Isolated yields of corrole in various solvents and inorganic additivesa
R
Solvent
Additives
Yield (%)
COOCH3
CH3CN
CH3OH
CH2Cl2
CH3CH2CH2CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
NH4Cl
NH4Cl
NH4Cl
NH4Cl
None
NH4Cl
KCl
NaCl
KBr
NH4NO3
None
NH4Cl
NaCl
NH4NO3
30
6
H
H
H
H
H
H
H
H
H
H
H
H
H
16b
61
4
30
28
26
26
22
53
60
61
65
CH3CN
CH3CH2CN
CH3CH2CN
CH3CH2CN
CH3CH2CN
a The reaction time was 60 min and the reactant concentration was 5×10−3 M. Ten equivalents of inorganic
additives were used in all cases.
b In this particular case, only trace amount of corrole was isolated in the absence of additives.
Similar oxidant-mediated coupling of dipyrromethane (1a) with 16-oxatripyrromethanes (6)12
resulted in the formation of smaragdyrin (7).13 The acid is not necessary in this reaction and
this ‘3+2’ type coupling gave expanded corrole (7) exclusively in 19.4% yield. Compound (7)
did not show any fluorescence on TLC under UV-light and appeared as a yellowish spot.
Attempted coupling of meso-tolyltripyrromethane or 16-thiatripyrromethane with meso-

8124
tolyldipyrromethane did not give corresponding expanded corroles. Obviously, the presence of
furanyl oxygen is essential in the case of ‘3+2’ type oxidative coupling. The template effect of a
Lewis acid must be involved in the coupling as previously indicated.14 The effect of inorganic
additives were not obvious, but somewhat related with applied solvent.
In conclusion, the direct oxidative coupling of tetrapyrromethanes is a convenient method of
obtaining high yields of corroles as the single product. In addition, the acid-free condition is
advantageous due to the lack of scrambling resulting from the reversible cleavage of starting
material. The preferable formation of corrole may be related with minimum macrocyclic angle
strain of the intermediate corrinogen. Due to the smaller cavity of corroles, their metal
complexes are even more efficient catalysts for various catalytic reactions than those mediated
by metalloporphyrins. The synthetic method described here could be an expedient way to the
various meso-substituted corroles and expanded corroles. The coupling of pentapyrromethanes
and other higher oligomers are under extensive investigation accompanying the studies of
physico-chemical properties of various metallocorroles.
Supplementary material
Proton NMR spectra, carbon spectra and MS data for compounds 3, 5 and 7 is available
electronically.
Acknowledgements
This work was supported by grants from the Korea Research Foundation (KRF-99-005-
D00042). NMR and Mass data were obtained from the central instrument facilities in Kangwon
National University.
References
1. (a) Smith, K. M. In Porphyrins and Metalloporphyrins; Smith, K. M. Ed.; Elsevier: Amsterdam, 1975; Vol. I, p.
3. (b) Genokhova, N. S.; Melent’eva, T. A.; Berezovskii, V. M. Russ. Chem. Rev. 1980, 49, 1056. (c) Melent’eva,
T. A. Russ. Chem. Rev. 1980, 52, 641.
2. Gross, Z.; Goldberg, I.; Simkhovich, L.; Galili, N.; Saltman, I.; Iyer, P.; Golubkov, G. Abstracts of ICPP-1
Dijon, France, 2000; p. 93.
3. Boschi, T.; Licoccia, S.; Paolesse, R.; Tagliatesta, P.; Azarnia, M. J. Chem. Soc., Dalton Trans. 1990, 463.
4. Kratky, C.; Farber, G.; Gruber, K.; Wilson, K.; Dauter, Z.; Nolting, H. F.; Konrat, R.; Krautler, B. J. Am.
Chem. Soc. 1995, 117, 4654.
5. Licoccia, S.; Luisa Di Vona, M.; Paolesse, R. J. Org. Chem. 1998, 63, 3190.
6. (a) Gross, Z.; Simkovich, L.; Galili, N. Chem. Commun. 1999, 599. (b) Gross, Z.; Galili, N.; Simkhovich, L.;
Saltman, I.; Botoshansky, M.; Blaser, D.; Boese, R.; Goldberg, I. Org. Lett. 1999, 1, 599.
7. Boschi, T.; Licoccia, S.; Paolesse, R.; Tagliatesta, P.; Tehran, M. A.; Pelizzi, G.; Vitali, F. J. Chem. Soc., Dalton
Trans. 1990, 463.
8. Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Eng. 1969, 8, 781.
9. Cho, W. S.; Lee, C. H. Tetrahedron Lett. 2000, 41, 697.
10. Ka, J. W.; Lee, C. H. Tetrahedron Lett. 2000, 41, 4609.
11. Typical procedure for the coupling: 5,10,15-triphenyltetrapyrromethane (50 mg, 0.094 mmol) and ammonium
chloride (49 mg, 0.94 mmol) was dissolved in propionitrile (47 mL), then DDQ (64 mg, 0.28 mmol) was added

8125
with stirring. The mixture was stirred for 1 h then the solvent was removed in vacuo. The pure corrole was
obtained by column chromatography of the remaining dark black solid on neutral alumina (CH2Cl2). Fast
moving light brown pigment, which is provisionally assigned as a bilatriene derivative, is eluted first, then the
1
desired corrole is eluted as a green pigment. Yield 30 mg (60%); H NMR (CDCl3+CD3OD) l 7.73–7.81 (m, 9H,
ArꢀH), 8.15 (d, 2H, Ar(o)ꢀH), 8.35 (d, 4H, Ar(o)ꢀH), 7.62 (bs, 4H, pyrrole-H), 8.85 (bs, 4H, pyrrole-H); UV–vis.
(CH2Cl2) umax (m×103) 645 (14), 613 (16.5), 575 (20.7), 414 (137.8); FAB-MS calcd for C37H26N4 526.22, found
527.32 (M++H).
12. 5,10-Di(p-tolyl)-16-oxatripyrromethane (6): 2,5-[a-hydroxy-a-(p-tolyl)]methylfuran (1.47 g, 4.78 mmol) was dis-
solved in pyrrole (26.5 mL, 0.32 mol) under N2 and BF3·OEt2 (0.61 mL, 4.78 mmol) was added. The mixture was
stirred for 30 min at room temperature. The reaction was then quenched by adding aq. NaOH (0.1N, 20 mL).
The mixture was extracted with CH2Cl2 (30 mL×3) and washed with water (30 mL). The organic layer was dried
(Ns2SO4) and the solvent and excess pyrrole was removed in vacuo and the remaining brown oil was purified by
column chromatography on silica (CH2Cl2/hexanes=2/1). Yield: 1.65 g (84.8%); Rf 0.45 (CH2Cl2/hexanes=2/1);
1H NMR (CDCl3) l 7.95 (bs, 2H, NꢀH), 7.11–7.06 (m, 8H, ArꢀH), 6.62–6.61 (m, 2H, pyrrole-H), 6.12–6.11 (m,
2H, pyrrole-H), 5.94 (d, J=2.4 Hz, 2H, furan-H), 5.90–5.87 (m, 2H, pyrrole-H), 5.35 (s, 2H, meso-H), 2.33 (s,
6H, ArꢀCH3).
13. ‘3+2’ coupling to give (7): 5,10-di(p-tolyl)-16-oxatripyrromethane (0.17 g, 0.42 mmol), p-tolyldipyrromethane
(0.10 g, 0.42 mmol) and ground NH4Cl (0.23 g, 4.22 mmol) were dissolved in acetonitrile (42.2 mL) in ice bath.
Then BF3·OEt2 (stock solution of 1 mM in acetonitrile, 5.4 mL, 0.43 mmol) was added and the mixture was
stirred for 60 min in ice-bath. DDQ (0.19 g, 0.84 mmol) was added and the mixture was stirred for 60 min at
room temperature. The mixture was combined with water and extracted with ethyl acetate (50 mL×3). The
organic layer was dried (Na2SO4) and the solvent was evaporated in vacuo. The resulting solid was purified by
column chromatography on silica (CH2Cl2/hexanes=2/1). Recrystallization from methanol afforded pure
1
product. Yield: 52 mg (19.4%); H NMR (CDCl3) l 9.44 (s, 2H), 9.34 (s, 2H), 8.94 (s, 2H), 8.73 (s, 2H), 8.42 (s,
2H), 8.27 and 7.65 (two doublets, J=6.8 Hz, 4H, ArꢀH), 8.07 and 7.60 (two doublets, J=6.8 Hz, 8H, ArꢀH),
2.72 (s, 9H, ArꢀCH3), −3.03 (bs, 3H, NꢀH); UV–vis (CH2Cl2/EtOH=3/1, base) umax (m×103): 444 (187), 457 (99),
556 (12), 597 (10), 636 (9.6), 697 (14); (CH2Cl2/EtOH=3/1, acid) umax (m×103): 422 (49), 447 (175), 480 (75), 604
(13), 659 (18), 721 (40); FAB calcd for C44H34N4O 634.27, found 635.23.
14. Lee, C. H.; Cho, W. S.; Ka, J. W.; Kim, H. J.; Lee, P. H. Bull. Kor. Chem. Soc. 2000, 21, 429.
.
.