Corrole synthesis by dipyrromethane-dicarbinol and 2,2′-bipyrrole condensation

Article abstract of DOI:10.1016/S0040-4039(03)00617-8

A₃ and trans-A₂B tris-aryl corroles 1a-c have been synthesized in up to 12% yield by BF₃·Et₂O-catalyzed condensation of dipyrromethane-dicarbinol and 2,2′-bipyrrole (1:1 ratio) in acetonitrile at room temperatur

Full text of DOI:10.1016/S0040-4039(03)00617-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3323–3327
Corrole synthesis by dipyrromethane–dicarbinol and
2,2%-bipyrrole condensation
Richard A. Decre´au and James P. Collman*
Department of Chemistry, Stanford University, Stauffer II, CA 94305-5080, USA
Received 22 January 2003; revised 27 February 2003; accepted 28 February 2003
Abstract—A3 and trans-A2B tris-aryl corroles 1a–c have been synthesized in up to 12% yield by BF3·Et2O-catalyzed condensation
of dipyrromethane–dicarbinol and 2,2%-bipyrrole (1:1 ratio) in acetonitrile at room temperature for 24 h. © 2003 Elsevier Science
Ltd. All rights reserved.
Corroles are porphyrin analogues with a bipyrrole ring
junction. Recent improvements in their synthetic
methodologies have made them affordable, and they
have been studied as catalysts, photosensitizers for
PDT, etc.1a–g One can envision that recently reported
efficient synthetic methodologies of corroles (which
have a corrin-like molecular skeleton) might be a start-
ing point for the development of the synthesis of vit
B12 mimics. Indeed innovations in synthetic method-
ologies have been growing since 1997 allowing corroles
to be prepared in higher yields than the previous a,c-
biladiene cyclization method described by Johnson and
Kay.2 Gryko recently reviewed these new methods
which for the most part derive from optimization of
conditions used for porphyrin synthesis.3 Briefly, the
way to obtain corrole is by condensation of aldehyde
and pyrrole either following a modified Rothemund
reaction under acid-catalysis,4a,b or under solvent-free
conditions on a solid support.5a–c Corroles and struc-
turally modified corroles may be synthesized from
dipyrromethane condensation with aldehydes6a–c and
[2+2] condensation of dipyrromethane,6d [3+1] conden-
sation of tripyrrane and pyrrole carboxaldehyde,7 cou-
pling of tetrapyrromethane,8a–c or template reaction of
2,2%-bisdipyrrins with manganese.9 Corroles can result
from
a
porphyrin ring contraction, by detri-
fluoromethylation of porphyrin,10 which is reminiscent
of a previous method of sulfur extrusion with meso-
thiaporphyrin.11a Finally, methods of corroles and
modified corroles synthesis that involve the introduc-
tion of a bipyrrole or bifurryl unit at a last stage of the
synthetic scheme appear to be unfavorable. Indeed
MacDonald condensation of 5,5%-dicarboxylic acid–
dipyrromethane with 5,5%-diformyl-2,2%-bifuryl led to
21,24-dioxacorrole in low yield,11a while the same con-
densation performed with 5,5%-diformyl-2,2%-bipyrrole
was unsuccessful.11b,c The new method described in
here11d,e for the synthesis of the new 5,10,15-trimesityl
Scheme 1. Synthesis of corroles 1a–c by condensation of dipyrromethane dicarbinols 3a–c and 2,2%-bipyrrole 4. a: R1=R2=R3=
mesityl; b: R1=R2=R3=4-methylphenyl; c: R1=4-methylphenyl, R2=R3=phenyl.
Keywords: dipyrromethane-dicarbinol; 2,2%-bipyrrole; corrole synthesis.
* Corresponding author. Tel.: (650) 725-0283; fax: (650) 725-0259; e-mail: jpc@stanford.edu
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00617-8

3324
R. A. Decre´au, J. P. Collman / Tetrahedron Letters 44 (2003) 3323–3327
corrole 1a, the known 5,10,15-tris(4-methylphenyl) cor-
role 1b and 5,15-bis(phenyl),10-(4-methylphenyl) corrole
1c (Scheme 1) involving the [2+2] condensation of
dipyrromethane-dicarbinol and 2,2%-bipyrrole, is interest-
ing for two reasons: porphyrin analogues have been
successfully synthesized this way by dipyrromethane
dicarbinol condensation with dipyrromethane,12a–e and
recently Pawlicki et al. similarly showed that pyrrole-
carbinols undergo condensation with pyrroles leading to
corroles.13a,b
without salt (previous reports indicated that condensa-
tions catalyzed by TFA showed little or no salt effect12b),
30 min reaction time, followed by DDQ oxidation.12a–e
The reported condensation of dipyrromethane–
dicarbinol and dipyrromethane leading to porphyrin
used a 1:1 ratio, similarly the ratio dipyrromethane–
dicarbinol 3a–c to bipyrrole 4 was 1:1 since both species
contain two pyrrole units. A prior modification had to
be introduced to the published method due to the limited
solubility of 4. The maximum affordable concentration
of 4 was 1.1 mM which is in contrast to 2.5 and 10 mM
optimum concentration reported.12a,b
Both building blocks were prepared following literature
procedure12b,17a–d with some major modifications. Diacyl
dipyrromethane 2a–c12b were prepared by acylation of
5-mesityldipyrromethane14a,b in 55% yield15a (instead of
the 19% reported12b) and 5-(4-methylphenyl)dipyrro-
methane14a,b in 42% yield,15b respectively. The same
methodology was applied for the synthesis of 2b14a,b
following reported procedures.12,14 Subsequent reduction
of 2a with NaBH4 (300 mol equiv.) afforded the
dipyrromethane dicarbinol 3a; the low conversion is
probably due to steric hindrance of the methyl groups at
positions 2,6.16 However the conversion of 2b–c into 3b–c
using 50 mol equiv. NaBH4 was almost quantita-
tive.12,16b,c Bi-pyrrole 417a–d was prepared by benzoyl-
pyrrole coupling catalyzed by palladium acetate (5% mol
equiv.) in hot acetic acid, followed by amide hydrolysis.18
Yields of 1a on a micro-scale synthesis appears to be
strongly dependent upon the reaction time. A reaction
time of 30 min led to a maximum of 1.5% yield (entries
1–4) while prolonging the reaction time to 24 h gave
yields up to 12% (entries 5–9). The formation of 1a is also
dependent on the choice of acid-catalyst. After 30 min
reaction time, 1a was obtained in 1.5% yield with
BF3·Et2O catalyst (entries 1–2), but 1a was not formed
when TFA was used (entries 3–4). Similarly at 24 h
reaction time, a 9–12% yield of 1a was obtained with
BF3·Et2O (entries 5–6) and 4–5% with p-toluenesulfonic
acid (PTSA) (entry 7). These experiments clearly show
that BF3·Et2O is the best catalyst for the synthesis of 1a
in contrast to TFA. The possible advantage of TFA was
that previous reports showed that 5-mesityl
dipyrromethane species are less susceptible to acidolysis
in the presence of TFA than in the presence of
BF3·Et2O.20 But in fact no corrole is formed. However,
our results are in good agreement with previous reports
showing that BF3·Et2O was a good catalyst for the
synthesis of oxa-corroles species, in condensations of
hydroxymethylfuran and pyrroles,13 and also
dipyrromethane carbinols11e and dipyrromethane pre-
sumably due to its templating effect which should favor
the formation of corrole.11e,13 The temperature seems to
have a substantial effect in the formation of 1a since
Inspired by previously reported work on condensation
reactions
of
dipyrromethane
dicarbinol
with
dipyrromethane leading to porphyrins,12a–f condensation
of 3a–c and 4 was performed after careful examination
of each of the following parameters: the nature of solvent
and of the acid catalyst, concentration of reagents and
the acid, and the reaction time (Table 1).19a Published
conditions which work well for the synthesis of por-
phyrins were selected for the synthesis of 1a–c: the
reaction was performed in acetonitrile at 0°C or at room
temperature, using BF3·Et2O 2 mM as catalyst in the
presence of NH4Cl or NaCl 100 mM, or TFA 15–30 mM
Table 1. Yields of corroles 1a (entries 1–9), 1b (entries 10–11) and 1c (entries 12–13) by condensation of dipyrromethane–
dicarbinol 3a–c and bipyrrole 4 (each at 0.038 mmol/36 mL solvent) under various reaction conditions
Entry
Solvent
Acid-cat.
Salt
T (°C)
Time (h)
Yield (%)c
1
2
3
4
5
6
7
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN–CHCl3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
BF3·Et2O
BF3·Et2O
TFA
NH4Cl
NH4Cl
–
25
0
0
0.5
0.5
0.5
0.5
24
24
24
24
24
0.5
24
0.5
24
1.5
Traced
0
TFA
–
25
25
25
25
25
25
25
25
25
25
0
BF3·Et2O
BF3·Et2O
PTSA
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
NH4Cl
NH4Cl
NaCl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
12.0
9.0
5.0
3.2
1.0
0
6.2
Trace
8.1
8a
9b
10
11
12
13
Other amounts of 3a or 4:
a 0.258 mmol/245 mL.
b 0.088 mmol/36 mL (suspension).
c Isolated yields.
d This fraction (entry 2) was characterized by MS (ESI+) only, and checked by TLC against authentic standard.

R. A. Decre´au, J. P. Collman / Tetrahedron Letters 44 (2003) 3323–3327
3325
after 30 min only a trace amount of 1a was detected
when the reaction was performed at 0°C (entry 2), while
1.5% yield was obtained at room temperature (entry 1).
The reaction depends very little on the solvent since 9%
were obtained in a MeCN/CHCl3 mixture (entry 6),
while 12% was obtained in 100% MeCN (entry 5).
Scale-up appears to have a dramatic effect on the
corrole yield. Indeed the reaction performed under the
conditions described in entry 5 but after scale-up by 6.8
fold (0.254 mmol) led to 1 in only 3.2% yield (entry 8)
while 12% yield was obtained on a 0.038 mmol scale
(entry 5). Finally using an excess of reagents, getting
over the solubility limit by employing a suspension
(0.088 mmol/36 mL) and sonicating the mixture before
introducing acid, did not lead to any improvement
(entry 9). In all cases (entries 1–9) the formation of
significant side products was observed,19a whose origin
was not investigated (scrambling, acidolysis…). Condi-
tions described in entries 1 and 5 were applied for the
synthesis of less sterically encumbered corroles 1b and
1c. It was found that A3 corrole 1b was not formed
after 5 min (data not shown), neither after 30 min
(entry 10), and was obtained in 6.2% yield after 24 h
reaction time (entry 11).21a Similarly trans-A2B corrole
1c was obtained in trace amount after 30 min (entry
11), and in 8.1% yield after 24 h reaction time (entry
12).21b It appeared that long reaction times are crucial
for the formation of corroles 1a–c.
National Science Foundation under Grant No.
CHE0131206. R.A.D. thanks the French Foreign Min-
istry for Lavoisier fellowship. We also thank the Mass
Spectrometry Facility, University of California, San
Francisco, and the Stanford University Mass
Spectrometry.
References
1. (a) Gross, Z.; Golubkov, G.; Simkhovich, L. Angew.
Chem., Int. Ed. 2000, 39, 4045–4047; (b) Gross, Z.;
Simkhovich, L.; Galili, N. Chem. Commun. 1999, 39,
599–600; (c) Simkhovich, L.; Gross, Z. Tetrahedron Lett.
2001, 42, 8089–8092; (d) Simkhovich, L.; Mahammed, A.;
Goldberg, I.; Gross, Z. Chem. Eur. J. 2001, 7, 1041–1055;
(e) Aviezer, D.; Cotton, S.; David, M.; Segev, A.;
Khaselev, N.; Galili, N.; Gross, Z.; Yayon, A. Cancer
Res. 2000, 60, 2973–2980; (f) Kadish, K. M.; Ou, Z.;
Shao, J.; Gros, C. P.; Barbe, J.-M.; Jerome, F.; Bolze, F.;
Burdet, F.; Guilard, F. Inorg. Chem. 2002, 41, 3990–4005;
(g) Jerome, F.; Gros, C. P.; Tardieux, C.; Barbe, J.-M.;
Guilard, R. New J. Chem. 1998, 1327–1329.
2. Johnson, A. W.; Kay, I. T. J. Chem. Soc. 1965, 1620–
1629.
3. Gryko, D. T. Eur. J. Org. Chem. 2002, 11, 1735–1743.
4. (a) Paolesse, R.; Jaquinod, L.; Nurco, D. J.; Mini, S.;
Sagone, F.; Boschi, T.; Smith, K. M. Chem. Commun.
1999, 14, 1307–1308; (b) Paolesse, R.; Nardis, S.; Sagone,
F.; Khoury, R. G. J. Org. Chem. 2001, 66, 550–556.
5. (a) Gross, Z.; Galili, N.; Saltsman, I. Angew. Chem., Int.
Ed. 1999, 38, 1427–1429; (b) Gross, Z.; Galili, N.; Salts-
man, I.; Simkhovich, L.; Saltsman, I.; Botoshansky, M.;
Blaser, D.; Boese, R.; Goldberg, I. Org. Lett. 1999, 1,
599–602; (c) Collman, J. P.; Decreau, R. A. Tetrahedron
Lett. 2002, 44, 1207–1210.
6. (a) Gryko, D. T. Chem. Commun. 2000, 22, 2243–2244;
(b) Gryko, D. T.; Jadach, K. J. Org. Chem. 2001, 66,
4267–4275; (c) Gryko, D. T.; Piechota, K. E. J. Por-
phyrins Phthalocyanines 2002, 6, 81–97; (d) Cho, W. S.;
Lee, C. H. Tetrahedron Lett. 2000, 41, 697–701.
Other methods were checked for the preparation of 1a
to obtain a comparison of yields. Paolesse’s method4a,b
using condensation of mesitaldehyde and pyrrole in
refluxing acetic acid afforded 1a in only 0.32%,19b while
6% yield was reported with 1b.4b This condensation
performed under Gross’s conditions did not afford 1a5c
or 1b–c neither. Gryko’s approach6a–c applied to the
preparation of 1a, using the condensation of mesityl
dipyrromethane and mesitaldehyde, did not work well
in our hands since 1a was always obtained in only 0.5%
yield.19c However 1b–c were obtained in 5 and 6%,
respectively.
7. Sankar, J.; Anand, V. G.; Venkatraman, S.; Rath, H.;
Chandrashekar, T. K. Org. Lett. 2002, 4, 4233–4235.
8. (a) Ka, J.-W.; Cho, W.-S.; Lee, C.-H. Tetrahedron Lett.
2000, 41, 8121–8125; (b) Asokan, C. V.; Smeets, S.;
Dehaen, W. Tetrahedron Lett. 2001, 42, 4483–4485; (c)
Brinas, R. P.; Bruckner, C. Synlett 2001, 3, 442–444.
9. Broring, M.; Hell, C. Chem. Commun. 2001, 2336–2337.
10. Tse, M. K.; Zhang, Z.; Mak, T. C. W.; Chan, K. S.
Chem. Commun. 1998, 1199–2000.
11. (a) Broadhust, M. J.; Grigg, R.; Johnson, A. W. J. Chem.
Soc., Perkin Trans. 1 1974, 1124–1135; (b) Conlon, M.;
Johnson, A. W.; Overend, W. R.; Rajapaksa, D.; Elson,
C. M. J. Chem. Soc. Perkin Trans. 1 1973, 2281–2288; (c)
Vogel, E.; Broring, M.; Fink, J.; Rosen, D.; Schmiekler,
H.; Lex, J.; Chan, K. W. K.; Wu, Y.-D.; Plattner, D. A.;
Nendel, M.; Houk, K. N. Angew. Chem., Int. Ed. 1995,
34, 2514; (d) no experimental details have been reported
so far despite previous failure reported and mentionned
as unpublished results in Ref. 47 of Gryko’s review3 and
Geier’s reports at ACS meeting: Geier, G. R., III;
Grindrod, S. S.; Callinan, J. B.; Reid, C. G. Abstr. Papers
In conclusion, we have developed a new methodology
for corrole synthesis based on condensation of 2,2%-
bipyrrole and dipyrromethane dicarbinol giving up to
12% yield for the preparation of 1a–c. For comparison,
porphyrins
synthesized
by
condensation
of
dipyrromethane dicarbinol and dipyrromethane are
usually obtained in about 10–30% yield.12a–e The partic-
ular case described here may suffer from the low solu-
bility of 4 which might be overcome by introduction of
substituents increasing solubility (e.g. alkyl chains). A
particular application of this method would be (1) the
regioselective introduction of substituents at the
bipyrrole unit of corrole, by a prior preparation of
substituted bipyrrole synthon before condensation with
dipyrromethane–dicarbinol species, and (2) the synthe-
sis of ABC-corroles.
Acknowledgements
This material is based upon work supported by the

3326
R. A. Decre´au, J. P. Collman / Tetrahedron Letters 44 (2003) 3323–3327
Am. Chem. Soc. 2002, 224, 750; (e) oxacorrole formation
following Wallace et al.12f methodology but following the
procedure described for 2a–b using a same scale of start-
ing material (1 mmol) to afford 2c as brownish flakes
(0.115 g, 20%). TLC (silica, ethyl acetate–cyclohexane,
4.5:6.5 vol.) Rf 0.30. Mp 80–85°C (lit.12e mp 93–95°C.
16. (a) 1,9-Bis(mesitoyl)-5-mesityldipyrromethane-diol (3a)
was prepared as follows by adaptation of Cho’s proce-
was reported as a side product from the condensation
reaction of oxa-dipyrromethane dicarbinol with
dipyrromethane: Lee, C.-H.; Cho, W.-S.; Ka, H.-J.; Lee,
P. H. Bull. Korean Chem. Soc. 2000, 21, 429–433.
12. (a) Cho, W.-S.; Kim, H.-J.; Littler, B. J.; Miller, M. A.;
Lee, C.-H.; Lindsey, J. S. J. Org. Chem. 1999, 64, 7890–
7901; (b) Rao, P. D.; Dhanalekshmi, S.; Littler, B. J.;
Lindsey, J. S. J. Org. Chem. 2000, 65, 7323–7344; (c)
Geier, G. R.; Littler, B. J.; Lindsey, J. S. J. Chem. Soc.,
Perkin Trans. 2 2001, 712–718; (d) Geier, G. R.; Lindsey,
J. S. J. Chem. Soc., Perkin Trans. 2 2001, 687–700; (e)
Gryco, D.; Lindsey, J. S. J. Org. Chem. 2000, 65, 2249–
2252; (f) Geier, G. R.; Callinan, J. B.; Rao, P. D.;
Lindsey, J. S. J. Porphyrins Phthalocyanines 2001, 5,
810–823; (g) Wallace, D. M.; Leung, S. H.; Senge, M. O.;
Smith, K. M. J. Org. Chem. 1993, 58, 7245–7257.
13. (a) Pawlicki, M.; Latos-Grazynski, L.; Szterenberg, L. J.
Org. Chem. 2002, 67, 5644–5653; (b) Latos-Grazynski, L.;
Chmielewski, P.-J. New J. Chem. 1997, 21, 691–700.
14. (a) 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; (b) Although 2a–b were
prepared following Ref. 14 (a), the purification was not
achieved by bulb-to-bulb distillation but by chromatogra-
phy (SiO2, 27×6 cm, gradient elution hexane/
dichloromethane 3/1 vol. to 1/1 vol. (saturated with
ammonia, either by bubbling NH3 through for 2 min or
by extraction of ammonium hydroxide solution)) fol-
lowed by recrystallization in hexane/dichloromethane 2/1
vol.
dure reported for other dipyrromethane dicarbinol.12a
A
solution of diacyl–dipyrromethane 2a (0.230 g, 0.413
mmol) in dry THF/methanol (2:1 vol., 50 mL) under
magnetic agitation was reduced with portions of NaBH4
(3.12 g, 82.4 mmol) and stirred for 3 h at room tempera-
ture (internal temperature control sometimes indicated
temperature increase at ca. 38°C). As described for other
dipyrromethane–dicarbinol species,12a–e an initial yellow
spot showed up (supposed to be the mono-reduced spe-
cies Rf 0.3) followed by a second one (supposed to be the
bis-reduced compound (TLC, SiO2, ethyl acetate–
dichloromethane, 1:25 vol. Rf 0.15, ethyl acetate–hexanes
1:2 vol. Rf 0.5). Before complete reduction of 2 (ca. 30%
conversion) was achieved, new spots showed up on TLC.
The reaction was quenched with water (50 mL) at that
stage and the reaction mixture was extracted with CH2Cl2
(3×100 mL) and dried (K2CO3). The solvent was evapo-
rated, then the residue was resuspended in MeCN,
filtered and the yellow filtrate was evaporated to afford a
yellow oil containing 3a as the main product. Since 3a is
metastable (as previously reported with other
dipyrromethane dicarbinol species12a–e) no attempt of
purification or isomer separation was done, and the crude
mixture (IR: 3300 cm−1 (br s, OH)) was used for the next
step. (b) 1,9-Bis(benzoyl)-5-(phenyl)dipyrromethane-diol
(3b) was prepared following the procedure described for
2a on a 232 mmol scale of starting material 2b (110 mg) to
afford 3b as a pale yellow oil assuming quantitative yield.
TLC (silica, ethyl acetate–cyclohexane, 1:3 vol.). (c) 1,9-
Bis(benzoyl)-5-(4-methylphenyl)dipyrromethane-diol (3c)
was not prepared by LiAlH4 reduction as described by
Wallace et al.,12g but following an adaptation of the
procedure described for 3a–b on a 258 mmol scale of
starting material 2c (115 mg) to afford 3c as a yellow oil.
1H NMR TLC (silica, ethyl acetate–cyclohexane, 1:3 vol.)
Rf 0.40.
15. (a) 1,9-Bis(mesitoyl)-5-mesityldipyrromethane (2a): Fol-
lowing reported procedure12a but modified as follows: a
solution of EtMgBr (1.98 mL, 5 mmol) was carefully
added to a solution of mesityl–dipyrromethane14 (0.264 g,
1 mmol) in THF (25 mL) under N2. The pale-tan yellow-
ish solution was stirred for 30 min at room temperature
then a solution of mesitoyl chloride (prepared in situ)
(0.831 mL, 5 mmol) in THF (5 mL) was added dropwise.
The mixture was stirred for an additional 2 h at room
temperature, then quenched with a saturated solution of
NH4Cl (50 mL) and extracted with CH2Cl2. After wash-
ings with 1 M NaOH (250 mL) and water (2×150 mL),
the solvent was evaporated, the residue dried and sub-
jected to chromatography (SiO2, 17×3 cm, eluent
CH2Cl2–EtAc (25:1 vol.)). After elution of some red–pink
stuff, the desired yellow fraction was collected. Evapora-
tion of solvent afforded a red–brown residue which was
resuspended in hexanes (50 mL, sonication), and filtered
to afford a white solid (0.254 g, 55%). 1H NMR (400
MHz, DMSO-d6) l (ppm): 9.03 (brs, 2H), 6.91 (s, 2H),
6.84 (s, 4H), 7.94 (m, 4H), 6.40 (s, 2H), 6.11 (s, 2H), 5.84
(s, 1H), 2.29 (s, 3H), 2.28 (s, 6H), 2.13 (s, 12H), 2.07 (s,
6H). HR-MS (EI+, m/z)=556.3097 (calcd for
C38H40N2O2 556.3090), 410.2370 (M+−MesCO), 263.1518
17. (a) Itahara, T. J. Chem. Soc., Chem. Commun. 1980,
49–50; (b) Itahara, T. J. Chem. Soc., Chem. Commun.
1981, 254–255; (c) Itahara, T. J. Org. Chem. 1985, 50,
5272–5275; (d) Itahara, T. Heterocycles 1986, 24, 2557–
2562.
18. 2,2%-Bipyrrole (4) was prepared according to Itahara’s
procedure, but since the published conditions did not
work in our hands, the following modifications were
introduced. A solution of 1-benzoylpyrrole (1 g, 5.84
mmol) and palladium acetate (0.131 g, 0.584 mmol) in
acetic acid (800 mL) was heated at 65°C for several hours
and monitored by TLC. The mixture was evaporated to
give an orange oil which was filtered through an alumina
pad (8×2 cm, CH2Cl2–hexanes, 3/7 vol.). The residue was
treated in methanol–water (2:1 vol.) at 60°C for 6 h to
afford 4 (0.092 g, 12%). Spectroscopic data17c and the
melting point were compared against an authentic stan-
dard purchased from Alfa Aesar. Mp 185–188°C (lit.17a
mp 189–190°C).
(M+−MesCO).
dichloromethane, 1:25 vol.) Rf 0.40. (b) 1,9-Bis(4-methyl-
benzoyl)-5-(4-methylphenyl)dipyrromethane (2b) was
TLC
(silica,
ethyl
acetate–
prepared following the procedure described for 2a on a
same scale of starting material (1 mmol) to afford 2b12e
(0.188 g, 40%). TLC (silica, ethyl acetate–
dichloromethane, 1:25 vol.) Rf 0.35. (b) 1,9-Bis(benzoyl)-
5-(4-methylphenyl)dipyrromethane (2c) was not prepared

R. A. Decre´au, J. P. Collman / Tetrahedron Letters 44 (2003) 3323–3327
3327
19. 5,10,15-Tris(mesityl) corrole (1a). (a) Dipyrromethane–
dicarbinol method. Diol 3a (22 mg, 0.038 mmol (entries
1–7); or 150 mg, 0.258 mmol (entry 8) or 50 mg, 0.088
mmol (entry 9)) was immediately dissolved in 36 mL
(entries 1–7) or 245 ml (entry 8) of solvent (MeCN
(entries 1–4, 8–9) or MeCN–CHCl3 1:1 vol. (entry 6))
with 4 (4.8 mg, 0.038 mmol (entries 1–7); 32.6 mg, 0.258
mmol (entry 8), or 11 mg, 0.088 mmol (entry 9) from a
stock solution sonicated for 5 min). After stirring for a
few minutes (and cooling the solution at 0°C (ice
bath)(entries 2–3)), NH4Cl (46 mg, 0.887 mmol (entries
1–2, 5–6, 9); or 313 mg, 6 mmol (entry 8); or 46 mg, 0.887
mmol (entry 9)) or NaCl (51 mg, 0.887 mmol (entry 7))
was added followed by catalyst solution: BF3·Et2O (100
mL of a stock solution mM in MeCN, 0.008 mmol, 2
mM; entries 1–2, 5–6, 8; or 681 mL (entry 8)) or TFA (81
mL, 1.056 mmol, 30 mM, entries 3; or 40 uL, 0.525 mmol,
15 mM, entry 4) or PTSA (100 uL of a mM solution in
MeCN, entry 7) over a period of 1 min. While stirring,
the reaction was monitored by TLC and absorption
spectroscopy following Rao et al. procedure.12b After 30
min (entries 1–4) or 24 h (entries 5–8) stirring at room
temperature, DDQ (10 mM solution in toluene) was
carefully added to the system and stirring was carried on
for 1 h (portionwise addition (ca. 0.2–0.4 mL in total)
was carried out on 3 mL aliquots until the desired spot
becomes intense, making sure not to add too much DDQ,
that would lead to corrole over-oxidation and an incor-
rect diagnosis of no corrole formation). Then Et3N (0.139
mL, 1 mmol) was added and after 5 min stirring, the
entire reaction mixture was filtered through a silica pad
(13×3 cm) and eluted with CH2Cl2 until the eluent was no
longer dark (ca. 100 mL). After evaporation of the sol-
vent, the residue was subjected to chromatography (SiO2,
20×5 cm, gradient elution using hexanes–CH2Cl2 until the
ratio reaches 2:1 vol.) the violet fraction containing 1a
(TLC SiO2, CH2Cl2/toluene 95:1 vol. Rf 0.95) shows up
just before a pink and blue fractions at Rf 0.50–0.70. 1a
was obtained as a violet-green solid (0.3–3.2 mg, 1–12%
(entries 1–7); 5.3 mg, 3.2% (entry 8)) after recrystallisa-
tion in hexanes–CH2Cl2 (1:9 vol.). (b) Paolesse’s
method4a,b was applied to the synthesis of 1a by refluxing
a solution of mesitaldehyde (2.9 mL, 20 mmol) and
pyrrole (4.2 mL, 60 mmol) in acetic acid (250 mL) for 4
h. After cooling, addition of H2O (300 mL), NaCl (10 g)
and stirring for 30 min, the mixture was filtered. The
resulting cake was washed with CH2Cl2 (3×150 mL) and
the solution was filtered through a silica pad and chro-
matographed as described in Ref. 19a to afford 1a (0.010
g, 0.32%). (c) Gryko’s method6a–c applied to the synthesis
of 1a: to a degassed solution of mesityldipyrromethane
(0.264 g, 1 mmol) and mesitaldehyde (0.072 mL, 0.5
mmol) in CH2Cl2 (109 mL) was added BF3Et2O (0.052
mL, 0.038 mmol). After stirring for 4 h at room tempera-
ture under N2, DDQ powder was added (0.227 g, 1
mmol) and the reaction mixture was stirred for an addi-
tional 15 min. After filtration through a silica pad (13×2
cm, eluent CH2Cl2) and evaporation of the solvent, the
residue obtained was subjected to chromatography using
the same conditions as in Ref. 19a to afford 1a (0.017 g,
0.5%) and tetramesityl-porphyrin (0.035 g, 9%). (d) Spec-
troscopic data of 1a. 1H NMR (400 MHz, CDCl3) l
(ppm): 8.82 (d, J=3.38 Hz, 2H), 8.39 (d, J=4.72 Hz,
2H), 8.27 (d, J=3.90 Hz, 2H), 8.22 (d, J=4.67 Hz, 2H),
7.20 (m, 6H), 2.58 (s, 5,15-p-CH3, 6H), 2.56 (s, 10-p-CH3,
3H), 1.90 (s, 5,15-o-CH3, 12H), 1.85 (s, 10-o-CH3, 6H),
−3.0 (vbrs, 3H). UV–vis. (CH2Cl2) u (Abs.): 391 (sh,
0.87), 406 (1.05), 423 (sh, 1.19), 561 (0.11), 604 (0.07), 635
(0.04) nm. HR-MS (EI+, m/z)=652.3566 (calcd for
C46H44N4:
652.3566).
TLC
(silica,
hexane/
dichloromethane, 2:1) Rf 0.51.
20. Lee, C.-H.; Li, F.; Iwamoto, K.; Dadok, J.; Bothner-By,
A. A.; Lindsey, J. S. Tetrahedron 1995, 51, 11645–11672.
21. (a) 5,10,15-Tris(4-methylphenyl) corrole (1b)8c and 5,15-
bis(phenyl)-10-(4-methylphenyl) corrole (1c)4b were pre-
pared by adaptation of the dipyrromethane–dicarbinol
procedure described in Ref. 19 (a). They were character-
ized by 1H NMR, MS and UV–vis and were as previ-
ously described.4b,8c