Synthesis of Corroies Bearing up to Three Different Meso Substituents

Article abstract of DOI:10.1021/ol027003w

(Matrix Presented) We have developed a new method that affords regioisomerically pure corroles possessing up to three different substituents at the meso positions. The corrole formation reaction involves the acid-catalyzed condensation of a dipyrromethane

Full text of DOI:10.1021/ol027003w

ORGANIC
LETTERS
2002
Vol. 4, No. 25
4491-4494
Synthesis of Corroles Bearing up to
Three Different Meso Substituents
,†
,‡
Roger Guilard,* Daniel T. Gryko,* Gabriel Canard,† Jean-Michel Barbe,†
Beata Koszarna,‡ Ste´phane Brande`s,† and Mariusz Tasior‡
Institute of Organic Chemistry of the Polish Academy of Sciences, 01-224 Warsaw,
Poland, and Laboratoire d’Inge´nierie Mole´culaire pour la Se´paration et les
Applications des Gaz (LIMSAG), UMR 5633, 6, Bd Gabriel, 21100, Dijon, France
daniel@icho.edu.pl
Received October 1, 2002
ABSTRACT
We have developed a new method that affords regioisomerically pure corroles possessing up to three different substituents at the meso
positions. The corrole formation reaction involves the acid-catalyzed condensation of a dipyrromethane-dicarbinol with pyrrole followed by
oxidation with DDQ. ABC-Type corroles were synthesized for the first time according to this procedure.
Corroles,1 considered as intermediates between corrins and
porphyrins, are currently one of the most intriguing research
targets among porphyrinoids. Interest in corroles was induced
by the discovery of their remarkable ability to stabilize high
oxidation states of metals2 and by the considerable synthetic
developments made during past few years. Progress in
coordination chemistry of corroles3 led also to the use of
their complexes as catalysts in different oxidation reactions.4
The discovery of simple procedures for the synthesis of
meso-substituted corroles5 has prompted several groups to
develop a research program in this area.6-8 Although these
methods provide efficient routes to A3-corroles and trans-
A2B-corroles, the inevitable formation of porphyrins as side-
products is a troublesome limitation. Indeed, it is well-known
that the separation of porphyrins and corroles is very difficult
due to their similar physical properties. Moreover, for
particular purposes corroles with up to three different meso
substituents are needed. The recent synthesis of ABCD-
porphyrins appeared to us as a model pathway for the
preparation of meso-substituted ABC-corroles.
Indeed, the reaction of dipyrromethane-dicarbinols with
dipyrromethanes under carefully optimized nonscrambling
conditions afforded porphyrins in 14-40% yield.9-11
* Corresponding authors. E-mail address for R.G.: roger.guilard@
u-bourgogne.fr.
† Laboratoire d’Inge´nierie Mole´culaire pour la Se´paration et les
Applications des Gaz.
‡ Institute of Organic Chemistry of the Polish Academy of Sciences.
(1) (a) Paolesse, R. In The Porphyrin Handbook; Kadish, K. M.; Smith,
K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 2, pp
201-232. (b) Montforts, F.-P.; Glasenapp-Breiling, M.; Kusch, D. In
Houben-Weyl Methods of Organic Chemistry; Schaumann, E., Ed.; Thi-
eme: Stuttgart, 1998; Vol. E9d, pp 665-672. (c) Gryko, D. T. Eur. J. Org.
Chem. 2002, 1735-1742. (d) Guilard, R.; Barbe, J.-M.; Stern, C.; Kadish,
K. M. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Elsevier Science: New York, in press.
(2) Vogel, E.; Will, S.; Schulze-Tilling, A.; Neumann, L.; Lex, J.; Bill,
E.; Trautwein, A. X.; Wieghardt, K. Angew. Chem., Int. Ed. Engl. 1994,
33, 731-735.
(3) Erben, C.; Will, S.; Kadish, K. M. In The Porphyrin Handbook
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000; Vol. 2, pp 233-300.
(4) (a) Simkhovich, L.; Mahammed, A.; Goldberg, I.; Gross, Z. Chem.
Eur. J. 2001, 7, 1041-1055. (b) Golubkov, G.; Bendix, J.; Gray, H. G.;
Mahammed, A.; Goldberg, I.; DiBilio, A. J.; Gross, Z. Angew. Chem., Int.
Ed. 2001, 40, 2132-2134.
(5) (a) Paolesse, R.; Nardis, S.; Sagone, F.; Khoury, R. G. J. Org. Chem.
2001, 66, 550-556. (b) Gross, Z.; Galili, N.; Saltsman, I. Angew. Chem.,
Int. Ed. 1999, 38, 1427-1429.
(6) Gryko, D. T.; Koszarna, B. Org. Biomol. Chem., in press.
(7) (a) Gryko, D. T. Chem. Commun. 2000, 2243-2244. (b) Brin˜as, R.
P.; Bru¨ckner, C. Synlett 2001, 442-444. (c) Gryko, D. T.; Jadach, K. J.
Org. Chem. 2001, 66, 4267-4275. (d) Asokan, C. V.; Smeets, S.; Dehaen,
W. Tetrahedron Lett. 2001, 42, 4483-4485.
(8) Gryko, D. T.; Piechota, K. E. J. Porphyrins Phthalocyanines 2002,
6, 81-97.
10.1021/ol027003w CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/21/2002

Scheme 1a
Keeping this in mind, we assumed that the reaction of the
tive formation of porphyrinogens and thereby open an avenue
to the synthesis of a broad range of corroles bearing various
substituents in different positions.
corresponding dicarbinols with pyrrole would lead to bilanes
(tetrapyrranes) then into corroles by oxidative radical cou-
pling.12 This multiple-step method would eliminate competi-
The dipyrromethane-dicarbinol precursor is the key de-
4492
Org. Lett., Vol. 4, No. 25, 2002

rivative of such a method. Either it can be directly trans-
formed to the desired corrole in a one-pot reaction (method
A) or the cyclization can be performed in two steps with
intermediate purification of the bilane (method B).
Symmetrical diacyl dipyrromethanes 1a-g were obtained
according to Lindsey procedures (see Supporting Informa-
tion).9 Diacyldipyrromethane 1b has been chosen to optimize
the reaction conditions in method A (Table 1, Scheme 1).
The difficulties encountered to improve the yield of
reaction led us to use solventless conditions (entries 6-12).
In this case, due to the very high reactivity of dicarbinols
and being aware of possible scrambling, much lower amounts
of TFA were used. After formation of the bilane, the reaction
mixture was diluted with solvent and DDQ was added
(entries 6-12).
This initial optimization study clearly shows that: (a) a
small rather than large amount of TFA should be used
(entries 7 and 8); (b) CH2Cl2 is a convenient solvent for the
final radical oxidative cyclization (entries 6 and 7); (c)
dilution of the bilane solution improves the yield of corrole
5a, which finally reaches 30% (entries 10 and 12). The
optimized procedure (bilane formation: 50 equiv of pyrrole
as a solvent, TFA (mM)/1b (mM) ) 0.026, 10 min; oxidative
cyclization: CH2Cl2, 3 equiv of DDQ) was successfully used
in the preparation of various corroles (Scheme 1). Altogether
nine diacyldipyrromethanes have been employed in the three-
reaction sequence. Among them were one precursor of A3-
type corrole, six precursors of trans-A2B-type corrole and
two precursors of ABC-type corrole.
Table 1. Optimization of Conditions for Transformation of
Dicarbinol Derived from Diacyldipyrromethane 1b into Corrole
5aa
time of
solvent first step
solvent
TFA/1b yield of 5a
entry (first step) (min) (second step) (mM/mM)
(%)b
1c,d
2
3
4e
5f
6
7
8
9
10
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
pyrrole
pyrrole
pyrrole
pyrrole
pyrrole
pyrrole
pyrrole
5
1
40
1
1
4
4
4
4
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2g
12
1.2
Yb(OTf)3
1.2
1.2
0.026
0.026
1.3
0.13
0.026
0.026
0.026
0
15
2
14
0
15
25
7
12
30
21
18
Scheme 2
10
15
10
11
12
a All reactions were performed under the following conditions. First step:
reduction of diacyldipyrromethane to dicarbinol, 1:3 MeOH/THF, 50 equiv
of NaBH4. Second step: scale of 0.1 mmol of diacyldipyrromethane-
dicarbinol, 50 equiv of pyrrole. Third step: 40 mL of solvent, 3 equiv of
DDQ. b Isolated yields. c Used 2 equiv of DDQ. d Used 6 equiv of pyrrole.
e In this experiment, pyrrole has been evaporated. f Used 6 equiv of DDQ.
g Used 10 mL of CH2Cl2.
The absence of scrambling was carefully checked in each
experiment, and the starting conditions were analogous to
those described for the synthesis of porphyrins (entry 1).
When only a slight excess of pyrrole was present in the
reaction mixture, corrole did not form. In contrast, when the
amount of TFA was decreased by a factor of 10 and at the
same time the amount of pyrrole was increased to 50 equiv,
corrole 5a was obtained in 15% yield (entry 2). Taking into
account that DDQ may form with pyrrole the so-called
“pyrrole red”,13 the amount of DDQ was doubled in the next
experiment (entry 5). No corrole was formed, indicating that
further reaction of corroles with DDQ is faster than pyrrole
red formation. The removal of pyrrole before DDQ addition
(entry 4) has no effect on the reaction yield. The reaction in
the presence of ytterbium triflate11 afforded corrole in only
2% yield (entry 3).
(9) Rao, P. D.; Dhanalekshmi, S.; Littler, B. J.; Lindsey, J. S. J. Org.
Chem. 2000, 65, 7323-7344.
(10) Geier, G. R., III; Littler, B. J.; Lindsey, J. S. J. Chem. Soc., Perkin
Trans. 2 2001, 712-718.
(11) Geier, G. R., III; Callinan, J. B.; Rao, P. D.; Lindsey, J. S. J.
Porphyrins Phthalocyanines 2001, 5, 810-823.
(12) (a) Lee, C. H.; Li, F. R.; Iwamoto, K.; Dadok, J.; Bothnerby, A.
A.; Lindsey, J. S. Tetrahedron 1995, 51, 11645-11672. (b) Ka, J. W.; Cho,
W. S.; Lee, C. H. Tetrahedron Lett. 2000, 41, 8121-8125.
(13) Smith, G. F. AdV. Heterocyl. Chem. 1963, 2, 287.
Org. Lett., Vol. 4, No. 25, 2002
4493

Monoacylation of dipyrromethane 7, using thioester 814
followed by a second acylation,9 afforded two unsymmetrical
diacyl dipyrromethanes 2a and 2b in reasonable yields
(Scheme 2). The presence of pentafluorophenyl substituents
improves the stability of corroles in solution. All but one
two-step process gave rise to the expected corroles 4, 5a-
e, and 6b in 16-54% yield (Scheme 1). The only exception
was the reaction starting from diacyldipyrromethane 1e,
which failed to give corrole 5d probably due to an unfavor-
able conformation of the corresponding bilane. No scram-
bling was observed in any of these reactions on the basis of
ESI-MS and TLC.
To optimize the conditions further and improve the yield
of corroles, the purification of bilanes (method B) was
performed according to the findings of Lee and co-workers.12
In this case, slightly different conditions were chosen for
bilane formation with the use of BF3‚Et2O as an acid catalyst
(Scheme 1). The best synthesis of the bilane was found to
proceed from 1.0 mol of dipyrromethane, 145 equiv of
pyrrole as a solvent, and 0.15 equiv of BF3‚Et2O. After
dilution in CH2Cl2 and neutralization by NaOH (0.1 M), the
bilane was isolated by column chromatography. Two bilanes
3a and 3b were isolated in 62 and 65% yields, respectively.
They were oxidized to corroles 5f and 6a, respectively, with
DDQ using EtCN as a solvent in the presence of NH4Cl in
66 and 55% yields.
the meso positions, the Soret band is split and they exhibit
a pink-violet color in solutions (only 5c). The other com-
pounds have no split Soret band and exhibit a green-blue
color in solutions.
The present method is complementary to the previously
developed approach from dipyrromethanes and aldehydes for
the synthesis of trans-A2B-type corroles.7 While the latter
method is very efficient for polar aldehydes, the separation
of corrole from porphyrins is tedious for unpolar ones.
However, the phenyl substituents that can be introduced into
corroles using the methodology presented here are limited
by their compatibility with Grignard reagents.15 Yet, it is
applicable when nonpolar substituents are present at the 10
meso-position of the corrole ring.
This paper establishes the foundation for the first synthesis
of meso-substituted ABC-corroles. This approach, based on
Lindsey’s method, is also particularly efficient for preparing
A3-type and trans-A2B-type corroles. We are now expanding
the scope of this preliminary work with a special focus on
further simplification of the purification process.
Acknowledgment. This work was partially funded by the
State Committee for Scientific Research (Project 7 T09A
005 21). D.T.G. thanks the Foundation for Polish Science
for the scholarship. The “Centre National de la Recherche
Scientifique”, “Air Liquide”, and the “Conseil Re´gional de
Bourgogne” are gratefully acknowledged for financial sup-
port (R.G.) and for a Ph.D. grant (G.C.).
The ultimate choice between the above-described methods
depends on the nature of the dipyrromethane precursor.
Method A is potentially faster, while the main advantage of
Method B is a simpler final chromatographic purification of
the desired corrole. Needless to say, the absence of porphyrin
greatly simplifies the chromatography in both cases.
The simple analysis of electronic spectra of prepared
corroles confirmed the previous observation.8 For corroles
possessing at least two 2,6-disubstituted aryl substituents at
Supporting Information Available: Experimental pro-
cedures and analytical data for compounds 2a,b, 3a-b, 4,
5a-f, and 6a,b. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL027003W
(14) Rao, P. D.; Littler, B. J.; Geier, G. R., III; Lindsey, J. S. J. Org.
Chem. 2000, 65, 1084-1092.
(15) Non-Grignard-based methodologies for the synthesis of acyldipyr-
romethanes are also known (see ref 12a).
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Org. Lett., Vol. 4, No. 25, 2002