Selective substitution of corroles: Nitration, hydroformylation, and chlorosulfonation

Article abstract of DOI:10.1021/ja025851g

This work demonstrates the feasibility and powerfulness of electrophilic substitution on the peripheral carbon atoms of triarylcorroles as a synthetic tool to new derivatives. The large difference in the reactivity of the various carbon atoms on the macrocycle was shown to be of electronic rather than steric origin. A careful choice of reagents and a delicate control of reaction conditions allowed the selective syntheses of novel derivatives, in all of which substitution took place selectively in only the directly joined pyrrole rings of the macrocycle. This was proven by a combination of X-ray crystallography of the various products and detailed analysis of their NMR spectra.

Full text of DOI:10.1021/ja025851g

Published on Web 05/24/2002
Selective Substitution of Corroles: Nitration,
Hydroformylation, and Chlorosulfonation
Irena Saltsman,† Atif Mahammed,† Israel Goldberg,*,‡ Elena Tkachenko,†
Mark Botoshansky,† and Zeev Gross*,†
Contribution from the Department of Chemistry and Institute of Catalysis Science and
Technology, Technion - Israel Institute of Technology, Haifa 32000, Israel, and
School of Chemistry, Tel AViV UniVersity, Tel AViV 69978, Israel
Received February 7, 2002
Abstract: This work demonstrates the feasibility and powerfulness of electrophilic substitution on the
peripheral carbon atoms of triarylcorroles as a synthetic tool to new derivatives. The large difference in the
reactivity of the various carbon atoms on the macrocycle was shown to be of electronic rather than steric
origin. A careful choice of reagents and a delicate control of reaction conditions allowed the selective
syntheses of novel derivatives, in all of which substitution took place selectively in only the directly joined
pyrrole rings of the macrocycle. This was proven by a combination of X-ray crystallography of the various
products and detailed analysis of their NMR spectra.
Introduction
efficient catalysts for atom (oxygen) and group (carbene, nitrene)
transfer to organic substrates.6 In fact, for the latter reactions,
For decades, the chemistry of corroles was almost entirely
limited to derivatives with fully alkylated â-pyrrole positions,1
with only three examples of meso-only substituted corroles.2
This situation changed dramatically in 1999 with the disclosure
of the first facile methodologies for the synthesis of 5,10,15-
triarylcorroles from simple aldehydes and pyrrole;3 about 80
new corroles that are substituted only at the three meso-carbon
atoms were reported by now.4 This development finally opened
the gate for extensive investigations of corroles in the many
applications that tetraarylporphyrins are constantly utilized.5
Particularly, the metal complexes of 5,10,15-tris(pentafluo-
rophenyl)corrole (1 in Scheme 1) were shown to be very
the corrole metal complexes are significantly more efficient than
analogous porphyrins.6c,e In addition, a water-soluble derivative
of 1 (obtained by replacing its para-F atoms by pyridylium
cations) was shown to be more efficient in inhibiting growth
factors in tumor cells than analogous porphyrins, and novel
photophysical properties of nontransition metal corroles were
recently disclosed.7,8
The two major structural peculiarities of corroles relative to
porphyrins are the presence of three rather than two NH protons
in the coordination core and the lower symmetry. Large
emphasis was given to the first feature, particularly for stabiliza-
tion of metal ions in high oxidation states,9 while the other one
was ignored. For example, although N-substituted corroles were
reported as early as 1965,10 the fact that these molecules are
chiral was not appreciated until most recently.11 A different
aspect is the possibility of selective substitution of the macro-
cycle’s protons, which could not be explored for the traditional
corroles because they were fully alkylated at the â-pyrrole
carbon atoms.12 On the other hand, electrophilic substitution of
* To whom correspondence should be addressed. E-mail: (Z.G.)
chr10zg@tx.technion.ac.il, (I.G.) goldberg@chemsg7.tau.ac.il.
† Israel Institute of Technology.
‡ Tel Aviv University.
(1) (a) Expanded, Contracted, & Isomeric Porphyrins; Sessler, J. L., Weghorn,
S. J., Eds.; Pergamon: Oxford, 1997; Chapter 1. (b) Paolesse, R. In The
Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic Press: New York, 2000; Vol. 2, Chapter 11, pp 201-232.
(2) (a) Loim, N. M.; Grishko, E. V.; Pyshnograeva, N. I.; Vorontsov, E. V.;
Sokolov, V. I. IzV. Akad. Nauk, Ser. Khim. 1994, 5, 925. (b) Rose, E.;
Kossanyi, A.; Quelquejeu, M.; Soleihavoup, M.; Duwavran, F.; Bernard,
N.; Lecas, A. J. Am. Chem. Soc. 1996, 118, 1567. (c) Tse, M. K.; Zhang,
Z.; Mak, T. C. W.; Chan, K. S. Chem. Commun. 1998, 1199.
(6) (a) Gross, Z.; Simkhovich, L.; Galili, N. Chem. Commun. 1999, 599. (b)
Gross, Z.; Golubkov, G.; Simkhovich, L. Angew. Chem., Int. Ed. 2000,
39, 4045. (c) Simkhovich, L.; Mahammed, A.; Goldberg, I.; Gross, Z.
Chem.-Eur. J. 2001, 7, 1041. (d) Golubkov, G.; Bendix, J.; Gray, H. B.;
Mahammed, A.; Goldberg, I.; DiBilio, A. J.; Gross, Z. Angew. Chem., Int.
Ed. 2001, 40, 2132. (e) Simkhovich, L.; Gross, Z. Tetrahedron Lett. 2001,
42, 8089.
(7) Aviezer, D.; Cotton, S.; David, M.; Segev, A.; Khaselev, N.; Galili, N.;
Gross, Z.; Yayon, A. Cancer Res. 2000, 60, 2973.
(8) (a) Bendix, J.; Dmochowski, I. J.; Gray, H. B.; Mahammed, A.; Simkhovich,
L.; Gross, Z. Angew. Chem., Int. Ed. 2000, 39, 4048. (b) Mahammed, A.;
Gross, Z. J. Inorg. Biochem. 2002, 88, 305.
(9) (a) Gross, Z. J. Biol. Inorg. Chem. 2001, 6, 733. (b) 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, Chapter 12,
pp 233-300.
(10) Johnson, A. W.; Kay, I. T. J. Chem. Soc. 1965, 1620.
(11) Gross, Z.; Galili, N. Angew. Chem., Int. Ed. 1999, 38, 2366. (b) Simkhovich,
L.; Iyer, P.; Goldberg, I.; Gross, Z. Chem.-Eur. J. 2002, 8, 2595.
(3) (a) Gross, Z.; Galili, N.; Saltsman, I. Angew. Chem., Int. Ed. 1999, 38,
1427. (b) Gross, Z.; Galili, N.; Simkhovich, L.; Saltsman, I.; Botoshansky,
M.; Blaser, D.; Boese, R.; Goldberg, I. Org. Lett. 1999, 1, 599.
(4) (a) Paolesse, R.; Jaquinod, L.; Nurco, D. J.; Mini, S.; Sagone, F.; Boschi,
T.; Smith, K. M. Chem. Commun. 1999, 1307. (b) Simkhovich, L.;
Goldberg, I.; Gross, Z. J. Inorg. Biochem. 2000, 80, 235. (c) Cho, W.-S.;
Lee, C.-H. Tetrahedron Lett. 2000, 41, 697. (d) Gryko, D. T. Chem.
Commun. 2000, 2243. (e) Brin˜as, R. P.; Bru¨ckner, C. Synlett. 2001, 442.
(f) Gryko, D. T.; Jadach, K. J. Org. Chem. 2001, 66, 4267. (g) Ka, J.-W.;
Cho, W.-S.; Lee, C.-H. Tetrahedron Lett. 2000, 41, 8121. (h) Paolesse,
R.; Nardis, S.; Sagone, F.; Khoury, R. G. J. Org. Chem. 2001, 66, 550. (i)
Asokan, C. V.; Smeets, S.; Dehaen, W. Tetrahedron Lett. 2001, 42, 4483.
(5) Expanded, Contracted, & Isomeric Porphyrins; Sessler, J. L., Weghorn,
S. J., Eds.; Pergamon: Oxford, 1997; Chapter 10. (b) Metalloporphyrins
Catalyzed Oxidations; Montanari, F., Casella, L., Eds.; Kluwer Academic
Publishers: Dordrecht, 1994. (c) Sternberg, E. D.; Dolphin, D.; Bruckner,
C. Tetrahedron 1998, 54, 4151.
9
10.1021/ja025851g CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 7411-7420
7411

A R T I C L E S
Saltsman et al.
Scheme 1. Structures of 1 and 4 and the 139 Possible Products in Their Nonselective Electrophilic Substitution
Scheme 2. Selective Chlorosulfonation of Corrole 1
porphyrins and phthalocyanines either proceeds to completion
or provides an almost intractable mixture of products and
isomers.13 For example, even a bis-sulfonated phthalocyanine
that was separated from mono- and multisulfonated products
was shown to be a mixture of at least eight isomers.14 In
principle, the situation for meso-only substituted corroles could
be better if the four different â-pyrrole carbon atoms display
highly significant different reactivities. Otherwise, the number
of possible products will be exceedingly large, up to 140
(Scheme 1).
3, in which the clear separation of the hydrophilic residues from
the lipophilic parts provides amphiphilicity, a highly desirable
feature in many applications. We now demonstrate that the
selective functionalization of corroles is not limited to chloro-
sulfonic acid and also present several metal complexes of 3.
Experimental Section
Physical Methods. The NMR spectra were recorded on a Bruker
1
AM200 spectrometer, operating at 200 MHz for H and 188 MHz for
19F. Chemical shifts in the 1H NMR spectra are reported in ppm relative
to residual hydrogens in the deuterated solvents: δ ) 7.20 and 7.24
for benzene and chloroform, respectively, and to CFCl3 (δ ) 0.00) in
the 19F NMR spectra. Coupling constants J are reported in Hz. A HP
8452A diode array spectrophotometer was used to record the electronic
spectra. Mass spectroscopy was performed on a Finnigan TSQ 70
instrument with isobutane as carrier gas. The diffraction measurements
were carried out on a Nonius Kappa CCD diffractometer, using graphite
monochromated Mo KR radiation (λ ) 0.7107 Å).
In a recent preliminary publication, we have shown that
chlorosulfonation of 1 proceeds with excellent selectivity as to
produce the bis-functionalized corrole 2 in high yield (Scheme
2).15 Hydrolysis of 2 provided the bis-sulfonic acid derivative
(12) For hydroformylation of the meso-positions of corroles, see: Paolesse, R.;
Jaquinod, L.; Senge, M. O.; Smith, K. M. J. Org. Chem. 1997, 62, 6193.
(13) Bartoli, J. F.; Battioni, P.; De Foor, W. R.; Mansuy, D. J. Chem. Soc.,
Chem. Commun. 1994, 23. Ozette, K.; Leduc, P.; Palacio, M.; Bartoli, J.-
F.; Barkigia, K. M.; Fajer, J.; Battioni, P.; Mansuy, D. J. Chem. Soc. 1997,
119, 6442. Garcia-Ortega, H.; Ribo, J. M. J. Porphyrins Phthalocyanines
2000, 4, 564.
Materials. All reagents were purchased from commercial sources
and used as received unless otherwise noted. Acetonitrile was dried
over P2O5 and distilled.
(14) Bishop, S. M.; Khoo, B. J.; MacRobert, A. J.; Simpson, M. S. C.; Phllips,
D.; Beeby, A. J. Chromatogr. 1993, 646, 345.
(15) Mahammed, A.; Goldberg, I.; Gross, Z. Org. Lett. 2001, 3, 3443.
9
7412 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Selective Substitution of Corroles
A R T I C L E S
Synthetic Methods. The synthetic details for the preparation of
5,10,15-tris(pentafluorophenyl)corrole (H3(tpfc), 1) and 5,10,15-tris-
(pentafluorophenyl)corrolato gallium(III)(pyridine) (Ga(tpfc)(pyr), 4)
are provided in previous publications.3,8
Hydroformylation of 4, the Gallium Complex of 1. (a) Conditions
for Monosubstitution. DMF (0.16 mL) was cooled to 5-10 °C, POCl3
(0.12 mL, 1.16 mmol) was added under N2, and the mixture was stirred
for 15 min. The ice bath was removed, and the solution was stirred for
another 15 min. Dry dichloromethane (4 mL) was then added, and the
reagent was cooled to 0-5 °C. A limited amount of the reagent (0.428
mL) was added dropwise to a solution of 4 (100 mg, 0.106 mmol) in
8 mL of CH2Cl2. During addition, the solution turned from red to deep
green, and after 3-5 min, TLC (silica, CH2Cl2:hexane, 2:1, and some
drops of pyridine) showed no starting material. A saturated solution of
Na2CO3 (50 mL) was added, and the mixture was stirred overnight,
after which the organic phase was separated. The water phase was
extracted by CH2Cl2 three times, the organic phases were combined,
washed by brine, dried by Na2SO4, and the solvents were evaporated.
Column chromatography on silica (eluent, CH2Cl2:hexane:pyridine,
which was gradually changed from 100:20:0.2 to 60:100:0.4) afforded
3-formyl-5,10,15-tris(pentafluorophenyl)corrolato gallium(III)(pyridine)
(9) as green-blue crystals (yield 0.091 g, 87% after recrystallization
from CH2Cl2, hexane, and some drops of pyridine). 1H NMR (CDCl3):
Nitration of 4, the Gallium Complex of 1. (a) Conditions for
Mononitration. 4 (40 mg, 0.043 mmol), sodium nitrite (290 mg, 4
mmol), and dry acetonitrile (5 mL) were placed in a two-necked flask,
and the suspension was stirred for 10 min under Ar. Tris(4-bromo-
phenyl)aminium hexachloroantimonate (5, 24 mg, 0.03 mmol, 75 mol
%) was added, and stirring was continued for 1 h at room temperature,
after which the solvent was evaporated to dryness. The crude material
was separated and purified on a silica gel column eluted with 20%
ethyl acetate in hexane, as to provide two fractions (Rf ) 0.43 (major)
and Rf ) 0.26 (minor) on silica with hexane:ethyl acetate/3:2).
Recrystallization from dichloromethane/hexane of the two fractions
afforded 38 mg (84% yield) of 3-nitro-5,10,15-tris(pentafluorophen-
yl)corrolato gallium(III)(bis-pyridine) (6) and 4 mg (8.9% yield) of
3,17-dinitro-5,10,15-tris(pentafluorophenyl)corrolato gallium(III)(bis-
pyridine) (7).
3
3
6.1H NMR (CDCl3): δ ) 9.69 (s, 1H), 8.71 (d, J(H,H) ) 4.1 Hz,
δ 10.52 (s, 1H, CHO), 9.65 (s, 1H, R-CHO), 9.11 (d, J(H,H) ) 4.1
3
3
3
3
Hz, 1H), 8.76 (d, J(H,H) ) 4.7 Hz, 1H), 8.73 (d, J(H,H) ) 4.1 Hz,
1H), 8.67 (d, 3J(H,H) ) 4.8 Hz, 1H), 8.52 (d, 3J(H,H) ) 4.8 Hz, 1H),
8.48 (d, 3J(H,H) ) 4.7 Hz, 1H), 6.77 (tt, 3J(H,H) ) 7.7 Hz, 4J(H,H) )
1.5 Hz, 1H), 6.00 (td, 3J(H,H) ) 6.6 Hz, 4J(H,H) ) 1.24 Hz, 2H), 3.29
(d, 3J(H,H) ) 5.0 Hz, 2H). 19F NMR (CDCl3): δ -138.1 (m
1H), 8.61 (t, J(H,H) ) 5.1 Hz, 2H), 8.45 (d, J(H,H) ) 4.1 Hz, 1H),
3
3
8.32 (d, J(H,H) ) 4.6 Hz, 2H), 6.01 (t, J(H,H) ) 7.7 Hz, 2H), 5.89
(m, 4H), 5.55 (t, J(H,H) ) 6.2 Hz, 4H). 19F NMR (CDCl3): δ )
3
3
3
-139.07 (t, J(F,F) ) 12.6 Hz, 4F), -140.38 (dd, J(F,F) ) 24.6 Hz,
4J(F,F) ) 6.7 Hz, 2F), -152.15 (td, J(F,F) ) 21.9 Hz, 4J(F,F) ) 5.2
3
3
4
Hz, 2F), -153.59 (t, 3J(F,F) ) 21.4 Hz, 1F), -161.95 (m, 4F), -163.5
(overlapping doublet), 4F), -138.96 (dd, J(F,F) ) 24.16 Hz, J(F,F)
3
3
4
) 8.27 Hz, 2F), -153.02 (t, J(F,F) ) 20.34 Hz, 1F), -153.05 (t,
(td, J(F,F) ) 23.1 Hz, J(F,F) ) 6.9 Hz, 2F). UV/vis (EtOAc): λmax
442 nm (ꢀ 101 000), 612 (30 000). MS (DCI-): m/z 906.9 [M - 2
pyridine]-.
7. H NMR (CDCl3): δ ) 9.54 (s, 2H), 8.61 (d, J(H,H) ) 4.57
Hz, 2H), 8.35 (d, 3J(H,H) ) 4.6 Hz, 2H), 7.35 (t, 3J(H,H) ) 7.62 Hz,
2H), 6.60 (t, 3J(H,H) ) 6.06 Hz, 4H), 6.3 (br s, 4H). 19F NMR
(CDCl3): δ ) -139.04 (dd, 3J(F,F) ) 19.9 Hz, 4J(F,F) ) 6.7 Hz, 2F),
-140.53 (dd, J(F,F) ) 18.0 Hz, J(F,F) ) 6.7 Hz, 4F), -150.86 (t,
3J(F,F) ) 21.4 Hz, 1F), -152.06 (t, 3J(F,F) ) 21.2 Hz, 2F), -161.37
(td, 3J(F,F) ) 22.1 Hz, 4J(F,F) ) 6.2 Hz, 2F), -162.58 (td, 3J(F,F) )
22.1 Hz, 4J(F,F) ) 6.5 Hz, 4F). UV/vis (EtOAc): λmax 324 nm (ꢀ
26 500), 380 (17 000), 460 (46 200), 644 (31 000). MS (DCI-): m/z
951 [M - 2 pyridine]-.
3J(F,F) ) 20.68 Hz, 1F), -153.38 (t, 3J(F,F) ) 21.24 Hz, 1F), -162.4
(m, 6F). UV/vis (CH2Cl2): λmax (ꢀ (M-1 cm-1)) ) 410 nm (41 300),
432 (171 500), 602 (24 600), 620 (28 600). IR (CHCl3, cm-1): 1653
(CO). MS (DCI+): m/z (%) 891 ([MH+], 100). MS (DCI-): m/z (%)
890 ([M-], 100), 862 ([M -CO], 20). Rf ) 0.18 (CH2Cl2:hexane, 2:1,
and some drops of pyridine). Further elution by CH2Cl2:pyridine (100:
0.5) gives 2,17-bis-formyl-5,10,15-tris(pentafluorophenyl)corrolato gal-
lium(III)(bis-pyridine) (10) (yield 0.004 g, 3.5% after recrystallization
from CH2Cl2, hexane, and some drops of pyridine). 1H NMR (CDCl3):
δ 11.13 (s, 1H, CHO), 10.57 (s, 1H, CHO), 10.03 (s, 1H, R-CHO),
9.01 (s, 1H, R-CHO), 8.67 (d, 3J(H,H) ) 4.76 Hz, 1H), 8.60 (d, 3J(H,H)-
) 4.78 Hz, 1H), 8.38 & 8.37 (overlapping doublets, 2H), 7.04 (td,
3J(H,H) ) 7.68, 4J(H,H) ) 1.6 Hz, 2H), 6.33 (t, 3J(H,H) ) 7.06, 4H),
4.33 (br s, 4H). 19F NMR (CDCl3): δ -138.08 (m, 4F), -139.57 (dd,
3J(F,F) ) 23.97, 4J(F,F) ) 8.08 Hz, 2F), -152.15 (t, 3J(F,F) ) 42.49
Hz, 1F), -152.74 (t, 3J(F,F) ) 42.11 Hz), -153.05 (t, 3J(F,F) ) 42.11
1
3
3
4
(b) Conditions for Bis-nitration. The same reaction conditions as
above were utilized, but with more tris(4-bromophenyl)aminium
hexachloroantimonate (68.8 mg, 0.08 mmol, 200 mol %). The crude
material was separated and purified on a silica gel column eluted with
20% ethyl acetate in hexane, as to provide three fractions: 6 (2%), 7
(94%), and traces of 3,17,18-trinitro-5,10,15-tris(pentafluorophenyl)-
corrolato gallium(III)(bis-pyridine) 8 (Rf ) 0.12 on silica with hexane:
ethyl acetate/3:2).
3
4
Hz, 1F), -161.48 (dt, J(F,F) ) 43.43 Hz, J(F,F) ) 7.33 Hz, 2F),
3
4
-161.87 (dt, J(F,F) ) 44.46 Hz, J(F,F) ) 7.52 Hz, 2F), -162.71
3
4
(dt, J(F,F) ) 44.84 Hz, J(F,F) ) 7.33 Hz, 2F). UV/vis (CH2Cl2):
λmax (ꢀ (M-1 cm-1)) ) 416 nm (20 700), 436 (57 100), 612 (16 400),
636 (12 600). IR (CHCl3, cm-1): 1674 (CO). MS (DCI+): m/z (%)
919 ([MH+], 100). MS (DCI-): m/z (%) 918 ([M-], 100), 890 ([M-
- CO], 40). Rf ) 0.11 (CH2Cl2:hexane, 2:1, and some drops of
pyridine).
(c) Conditions for Tris-nitration. Using identical reaction condi-
tions as above, but with 300 mol % tris(4-bromophenyl)aminium
hexachloroantimonate (103 mg, 0.12 mmol), we separated the crude
material and purified it on a silica gel column eluted with 20% ethyl
acetate in hexane, as to provide three fractions: traces of 6, 7 (58%),
and 8 (27%).
(b) Conditions for Bis-substitution. DMF (1.6 mL) was cooled to
5-10 °C, POCl3 (1.22 mL, 11.6 mmol) was added under N2, and the
mixture was stirred for 15 min. The ice bath was removed, and the
solution was stirred for another 15 min. Dry dichloromethane (2 mL)
was then added, and the reagent was cooled to 0-5 °C. This solution
was added dropwise to a solution of 4 (100 mg, 0.106 mmol) in 2 mL
of CH2Cl2. During addition, the solution turned from red to deep green,
and after 3-5 min, TLC (silica, CH2Cl2:hexane, 2:1, and some drops
of pyridine) showed no starting material. A saturated solution of
Na2CO3 was added, and the mixture was stirred overnight, after which
the organic phase was separated. The aqueous phase was extracted by
CH2Cl2, the organic phases were collected and washed by brine, dried
by Na2SO4, and solvents were evaporated. Column chromatography
on silica (eluent:CH2Cl2:hexane:pyridine, which was gradually changed
from 100:20:0.2 to 60:100:0.4) afforded 9 as green-blue crystals (yield
1
8. H NMR (CDCl3): δ ) 9.84 (s, 1H), 8.44 & 8.39 (overlapping
doublets, 2H), 8.18 & 8.14 (overlapping doublets, 2H), 7.36 (t, 3J(H,H)
) 7.6 Hz, 2H), 6.81 (br s, 4H), 6.08 (br s, 4H). 19F NMR (CDCl3): δ
) -138.23 (m, 4F), -139.95 (d, 3J(F,F) ) 16.1 Hz, 2F), -149.24 (t,
3J(F,F) ) 20.4 Hz, 1F), -150.93 (t, 3J(F,F) ) 20.8 Hz, 1F), -152.04
(t, 3J(F,F) ) 20.7 Hz, 1F), -160.65 (t, 3J(F,F) ) 20.4 Hz, 4F), -161.98
3
(t, J(F,F) ) 20.6 Hz, 2F). UV/vis (EtOAc): λmax 326 nm (ꢀ 25 000),
416 (42 000), 456 (31 000), 616 (29 000), 668 (28 000). MS (DCI-):
m/z 997 [M - 2 pyridine]-.
The X-ray quality crystals of complexes 6, 7, and 8 were obtained
via slow crystallization from mixtures of benzene/heptane, CHCl3/
heptane, and CH2Cl2/hexane, respectively, with small amounts of
pyridine present in all cases.
9
J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7413

A R T I C L E S
Saltsman et al.
0.015 g, 15% after recrystallization from CH2Cl2, hexane, and some
drops of pyridine). Further elution by CH2Cl2:pyridine (100:0.5)
provides 10 (yield 0.075 g, 64% after recrystallization from CH2Cl2,
hexane, and some drops of pyridine).
Insertion of Cobalt(III). A 10 mL EtOH solution of 3 (10 mg, 10
µmol) and NaOAc (30 mg, 0.37 mmol) was mixed for 5 min at 25 °C,
after which PPh3 (20 mg, 76 µmol) and Co(OAc)2‚4H2O (20 mg, 80
µmol) were added, and the solution was mixed for another 30 min.
Following solvent evaporation, column chromatography on silica with
CH2Cl2 as eluent was used to remove the excess of PPh3 and EtOH to
free the product from inorganic salts, as to afford 12 mg (9 µmol, 90%
yield) of the (triphenylphosphine)cobalt(III) complex of 3.
Chlorosulfonation of 1 (Preparation of 2 and 3). Eighty milligrams
of 1 (100 µmol) and 2 mL of chlorosulfonic acid (30 mmol) were stirred
at 25 °C for 5 min, after which the reaction mixture was cooled by an
ice bath and treated with small ice chips (5-10 g, caution!). The product
was obtained via the addition of 20 mL of distilled water and CH2Cl2
(the CH2Cl2 solution was washed three times with distilled water) and
evaporation. On the basis of NMR spectroscopy, 2 was obtained in
1H NMR (CD3OD): δ ) 9.40 (s, 1H), 8.40 (m, 5H), 7.05 (t, 3J(H,H)
3
3
) 8.0 Hz, 3H), 6.70 (t, J(H,H) ) 7.7 Hz, 6H), 4.60 (dd, J(H,H) )
7.8 Hz, J(P,H) ) 11.3 Hz, 6H). 19F NMR (CD3OD): δ ) -134.9
3
(dd, 3J(F,F) ) 24.0 Hz, 4J(F,F) ) 7.0 Hz, 1F), -135.2 (dd, 3J(F,F) )
24.0 Hz, 4J(F,F) ) 7.0 Hz, 1F), -135.7 (dd, 3J(F,F) ) 24.0 Hz, 4J(F,F)
) 7.0 Hz, 1F), -136.7 (dd, 3J(F,F) ) 24.0 Hz, 4J(F,F) ) 7.0 Hz, 1F),
-137.0 (m, 2F), -152.7 (t, 3J(F,F) ) 20.0 Hz, 1F), -153.0 (t, 3J(F,F)
1
quantitative yield. H NMR (200 MHz, CDCl3): δ ) 9.44 (s, 1H),
8.95 (s, 1H), 8.60 (d, J ) 5.0 Hz, 1H), 8.50 (d, J ) 5.0 Hz, 1H), 8.41
(d, J ) 5.0 Hz, 1H), 8.18 (d, J ) 5.0 Hz, 1H). 19F NMR (188 MHz,
CDCl3): δ ) -137.5 (d, J ) 21.1 Hz, 4F), -138.3 (d, J ) 18.1 Hz,
2F), -149.6 (t, J ) 21.31, 1F), -150.1 (t, J ) 21.21, 2F), -160.0 (m,
4F), -161.6 (m, 2F). MS (DCI-): m/z (%) 991.8 (5) [M-], 892 (20)
[M- - SO2Cl].
3
) 20.0 Hz, 1F), -155.5 (t, J(F,F) ) 20.0 Hz, 1F), -161.4 (m, 4F),
-164.7 (m, 2F). UV/vis (MeOH): λmax (ꢀ) 378 nm (32 000), 410
(33 000), 558 (8600), 594 (9000).
Insertion of Tin(IV). A 10 mL DMF solution of 3 (12 mg, 13 µmol)
and SnCl2‚2H2O (12 mg, 53 µmol) was heated to reflux for 30 min,
followed by evaporation of the solvent. Addition of CH2Cl2 to the
residue, filtration, and solvent evaporation afforded 13 mg (12 µmol,
92% yield) of the (chloro)tin(IV) complex of 3 after evaporation.
1H NMR (CD3OD): δ ) 10.04 (s, 1H), 9.04 (d, 3J(H,H) ) 4.8 Hz,
1H), 8.96 (s, 1H), 8.94 (d, 3J(H,H) ) 5.2 Hz, 1H), 8.84 (d, 3J(H,H) )
4.3 Hz, 2H). 19F NMR (CD3OD): δ ) -135.1 (m, 2F), -136.8 (m,
4F), -151.8 (t, 3J(F,F) ) 20.2 Hz, 1F), -152.4 (t, 3J(F,F) ) 20.0 Hz,
A suspension of 2 in 20 mL of water was refluxed for 12 h. The
solution was filtered and evaporated to dryness as to provide 3 in 71%
yield based on 1 (68 mg, 71 µmol). 1H NMR (CD3OD): δ ) 9.68 (br
s, 1H), 9.14 (d, J ) 4.8 Hz, 1H), 8.98 (d, J ) 4.8 Hz, 1H), 8.90 (br s,
1H), 8.86 (d, J ) 4.8 Hz, 1H), 8.84 (d, J ) 4.8 Hz, 1H). 19F NMR
(188 MHz, CD3OD): δ ) -137.5 (d, J ) 20.3 Hz, 2F), -137.8 (d, J
) 19.6 Hz, 4F), -149.8 (t, J ) 20.3, 1F), -150.8 (t, J ) 20.1, 1F),
-152.1 (t, J ) 19.4, 1F), -160.3 (m, 2F), -160.8 (m, 2F), -163.1
(m, 2F). UV/vis (buffer solution, pH 7.00): λmax (ꢀ (M-1 cm-1)) )
414 (71 000), 430 (62 000), 588 (15 000), 620 (27 000). MS (MALDI-
TOF): m/z 956.6 [M+].
3
1F), -154.7 (t, J(F,F) ) 20.0 Hz, 1F), -161.2 (m, 4F), -164.3 (m,
2F). UV/vis (MeOH): λmax (ꢀ) 424 nm (140 000), 582 (16 000), 602
(18 000). MS (FAB-): m/z 1107.38 [M-].
Chlorosulfonation of 1, Followed by Amidation and Insertion
of Cobalt (Preparation of 13 and 14). As described in our previous
publication,15 the successive treatment of complex 2, obtained as
described above, with piperidine, cobalt(II) acetate, and triphenylphos-
phine allows the isolation of 2,17-substituted complex 13 in 72% yield
via recrystallization from benzene/heptane, while the 3,17-substituted
isomer 14 is obtained in 3% yield from chromatographic treatment of
the mother liquor. X-ray quality crystals of complex 14 were obtained
from benzene/heptane.
Insertion of Chromium(III). One portion of CrCl2 (40 mg, 0.33
mmol) was added at once to a 10 mL pyridine solution of 3 (14 mg,
15 µmol), and the mixture was heated immediately to reflux for 30
min. The solvent was evaporated, and inorganic salts were removed
via column chromatography on silica (eluent, MeOH:pyridine ) 20:
1). Dissolving the dried product in CH2Cl2, filtration, and solvent
evaporation afforded 16 mg (14 µmol, 93% yield) of the (bis-pyridine)-
chromium(III) complex of 3.
UV/vis (MeOH/pyridine 5%): λmax (ꢀ) 320 nm (11 000), 420
(19 000), 434 (22 000), 476 (6300), 542 (3700), 586 (5100), 614 (6300),
648 (7300).
Metalation of 3. Insertion of Gallium(III). A solution of 3 (20
mg, 21 µmol) in pyridine (10 mL) was added to a flask that contains
a large excess (about 0.2 g) of flame-dried GaCl3, and the reaction
mixture was heated to reflux for 30 min under argon, followed by
evaporation of the solvent. The inorganic salts were separated by
column chromatography on silica (eluent, MeOH:pyridine ) 20:1),
affording 21 mg (19 µmol, 90% yield) of the (pyridine)gallium(III)
complex of 3.
Crystallography. The crystalline samples of 6 and 8 were covered
with a thin layer of light oil and cooled to 110-115 K to minimize the
escape of volatile crystallization solvents and minimize thermal motion/
structural disorder effects. Crystal structures of 7 and 14 were analyzed
at room temperature. The intensity data were corrected for absorption.
The structures were solved by direct methods (SHELXS-86 and SIR-
92),16 and refined by full-matrix least-squares on F 2 (SHELXL-97).17
All non-hydrogen atoms of the corroles were refined anisotropically.
The hydrogens were located in idealized positions, and were refined
using a riding model with fixed thermal parameters [Uij ) 1.2Uij (equiv)
for the atom to which they are bonded]. The four corrole compounds
cocrystallized with additional guest/solvent components trapped, and
severely disordered, in the lattice. In addition, partial rotational disorder
characterizes some of the pentafluorophenyl rings of the corroles (as it
is demonstrated, in particular, by excessively large thermal displacement
parameters of the corresponding atoms), affecting to some extent
(particularly in 7 and 8) the precision of the crystallographic determi-
nation. Yet, in all cases the crystallographic analysis provided an
unequivocal description of the respective molecular structures, adding
confidence to the conclusions based on the spectroscopic analyses.
1H NMR (CD3OD): δ ) 9.77 (s, 1H), 8.77 (s, 1H), 8.70 (d, 3J(H,H)
3
3
) 4.8 Hz, 1H), 8.57 (d, J(H,H) ) 4.8 Hz, 1H), 8.48 (t, J(H,H) )
4.3 Hz, 2H), 8.27 (br s, 2H), 7.71 (t, 1H), 7.30 (br s, 2H). 19F NMR
(CD3OD): δ ) -135.2 (d, 3J(F,F) ) 23.0 Hz, 2F), -136.8 (d, 3J(F,F)
) 23.5 Hz, 4F), -153.5 (t, 3J(F,F) ) 20.1 Hz, 1F), -154.1 (t, 3J(F,F)
) 20.5 Hz, 1F), -156.2 (t, 3J(F,F) ) 20.3 Hz, 1FF), -162.2 (m, 4F),
-165.1 (m, 2F). UV/vis (buffer solution, pH 7.30): λmax 424 nm (ꢀ
75 000), 588 (13 600), 610 (17 300). MS (MALDI-TOF): m/z 1022.2
[M+ - pyridine, 100%] and a characteristic isotopic pattern of 1023.2
(55%), 1024.2 (92%), 1025.2 (58%).
Insertion of Manganese(III). A flask loaded with a 10 mL of DMF
solution of 3 (15 mg, 16 µmol) and Mn(OAc)2‚4H2O (15 mg, 61 µmol)
was heated to reflux for 15 min, followed by evaporation of the solvent.
The inorganic salts were separated by column chromatography on silica
(eluent: EtOH), affording 15 mg (15 µmol, 94% yield) of the
manganese(III) complex of 3.
(16) Sheldrick, G. M. SHELXS-86. Acta Crystallogr. 1990, A46, 467. Altomare,
A.; Burla, M. C.; Camalli, M.; Cascarano, M.; Giacovazzo, C.; Guagliardi,
A.; Polidori, G. SIR-92. J. Appl. Crystallogr. 1994, 27, 435.
(17) Sheldrick, G. M. SHELXL-97. Program for the Refinement of Crystal
Structures from Diffraction Data; University of Goettingen: Germany, 1997.
UV/vis (buffer solution, pH 7.30): λmax 392 nm (ꢀ 19 000), 422
(21 000), 480 (17 000), 644 (11 500), 610 (9500), 576 (9000). MS
(MALDI-TOF): m/z 1007.9 [M+, 100%], 108.9 [MH+, 85%].
9
7414 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Selective Substitution of Corroles
A R T I C L E S
Scheme 3. Selective Nitration of 4
Crystal Data. 6. C42H12F15GaN6O2‚(C6H6), M ) 1065.4, ortho-
rhombic, space group P212121, a ) 12.0410(2), b ) 18.2040(3), c )
18.5900(3) Å, V ) 4074.8(1) Å3, Z ) 4, T ) 110(2) K, Dc ) 1.737 g
Complex 4 was previously shown to be a pentacoordinated
complex both in solution and in the solid phase.8 The NMR
examinations show that the same holds for complex 9, while 6,
7, 8, and 10 were obtained as hexacoordinated (bis-pyridine)
complexes. This factor was taken into consideration for calcula-
tion of the chemical yield. The lability of the sixth ligand8b is
responsible for the fact that the X-ray quality crystals of
complexes 6 and 8 contain only a single pyridine ligand.
Nitration. The nitration of 4 was performed by its mixing
with a suspension of NaNO2 in CH3CN (no reaction) and at-
once addition of a limited amount of the one-electron oxidant
tris(4-bromophenyl)aminium hexachloroantimonate (5). With 75
mol % oxidant, the major product was the mononitro corrole 6
(isolated yield: 84%), with 200 mol % oxidant, the bis-nitro
complex 7 was isolated in 94% yield, and with 300 mol % of
5, the trinitrocorrole 8 and 7 were isolated in 27 and 58% yield,
respectively (Scheme 3). Most important, all three products were
obtained as single isomers, that is, only one out of four possible
mono-, one out of 16 bis-, and one out of 28 tris-nitro corroles.
This was elucidated by NMR spectroscopy and further sub-
stantiated by X-ray crystallography of all three nitro-substituted
corroles.
cm-3, µ(Mo KR) ) 0.80 mm-1, 5283 unique reflections to 2θmax
)
55.7°, 662 refined parameters, R1 ) 0.046 for 4374 observations with
I > 2σ(I), R1 ) 0.064 (wR2 ) 0.113) for all unique data. Molecules of
the benzene solvent exhibit an in-plane rotational disorder, which was
modeled by two possible orientations with occupancy factors of
0.71(3) for the major site and 0.29 for the minor one. This compound
crystallized as a racemic twin.
7. C47H16F15GaN8O4‚NaNO3, M ) 1196.4, monoclinic, space group
P21/c, a ) 17.9080(4), b ) 12.5160(2), c ) 25.1330(5) Å, â ) 122.650-
(2)°, V ) 4743.1(2) Å3, Z ) 4, T ) 293(2) K, Dc ) 1.675 g cm-3
,
µ(Mo KR) ) 0.71 mm-1, 8117 unique reflections to 2θmax ) 50.0°,
738 refined parameters, R1 ) 0.069 for 2987 observations with I >
2σ(I), R1 ) 0.158 (wR2 ) 0.181) for all unique data. The experimental
measurements were carried out in this case at room temperature, at
which the analyzed crystal exhibited somewhat poor diffraction because
of the considerable disordered guest species. Thus, the structure of the
sodium nitrate could not be precisely modeled.
8. C42H10F15GaN8O6‚CH2Cl2‚C6H12, M ) 1246.4, monoclinic, space
group P21/c, a ) 11.3990(3), b ) 19.0230(4), c ) 22.7610(6) Å, â )
104.564(1)°, V ) 4777.0(2) Å3, Z ) 4, T ) 110(2) K, Dc ) 1.733 g
cm-3, µ(Mo KR) ) 0.81 mm-1, 10 262 unique reflections to 2θmax
)
55.7°, 799 refined parameters, R1 ) 0.101 for 6276 observations with
I > 2σ(I), R1 ) 0.160 (wR2 ) 0.312) for all unique data. The crystals
turned out to be partly twinned. Moreover, the dichloromethane and
hexane solvent species are severely disordered in the crystal lattice even
at the low temperature and could not be reliably modeled and refined.
The pentafluorophenyl rings also exhibit large-amplitude thermal motion
about axes connecting them to the main corrole ring, hence, the
relatively high R factors.
14. C65H41CoF15N6O4PS2‚C6H6, M ) 1487.2, triclinic, space group
P-1, a ) 13.827(3), b ) 13.815(3), c ) 18.209(4) Å, R ) 76.76(2), â
) 79.18, γ ) 70.13(2)°, V ) 3161.2(12) Å3, Z ) 2, T ) 293(2) K, Dc
) 1.562 g cm-3, µ(Mo KR) ) 0.46 mm-1, 8592 unique reflections to
2θmax ) 46.0°, 799 refined parameters, R1 ) 0.105 for 5128 observa-
tions with I > 2σ(I), R1 ) 0.167 (wR2 ) 0.270) for all unique data.
The crystals of this compound were diffracting poorly because of wide-
amplitude thermal motion of the included solvent and the various
substituents on the corrole ring.
Hydroformylation. For the synthesis of the monosubstituted
corrole, a limited amount of the Vielsmeier reagent was used,
and the desired product (9) was obtained in 87% yield as a single
isomer, accompanied by a small amount of the bis-substituted
product (10). On the other hand, the reaction does not proceed
further than bis-substitution even with a 100-fold excess of
reagent, and 10 can be isolated in 64% yield without any indica-
tion for other isomers. On the basis of a spectral comparison
(1H and 19F NMR) with the nitro-substituted products, the sub-
stitution patterns are identical for the mononitro and the mono-
formyl corroles, but different for the bis-substituted products.
Chlorosulfonation. This reaction was only performed with
excess reagent, which served as solvent as well. Only bis-
substituted products were obtained, in a ratio of 96:4 in favor
of the 2,17- relative to the 3,17-substituted isomer. Upon
hydrolysis, the bis-sulfonate corrole 3 was obtained in 71%
relative to 1. Interestingly, applying the same reaction conditions
for either the gallium complex 4 or the metal-free 5,10,15-tris-
(2,6-difluorophenyl)corrole resulted in much lower selectivities
(no attempts were made to separate the products or to find
alternative reaction conditions).
Results
Initially, all three reactions were attempted on the metal-free
corrole 1. Chlorosulfonation proceeded very well, but poor
results were obtained for hydroformylation and nitration.
Accordingly, the two latter reactions were performed on the
gallium(III) complex of 1 (4), similar to the well-documented
approach of using zinc(II) and other metals in porphyrins.
Metalation of 3. Gallium(III), chromium(III), manganese-
(III), cobalt(III), and tin(IV) were inserted in the inner core of
9
J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7415

A R T I C L E S
Saltsman et al.
Scheme 4. Selective Hydroformylation of 4
3, using the methods that were developed for metal insertion
into 1.6,8,18 In all of the cases, the reactions proceeded
quantitatively, and the products were identified via comparison
to the corresponding metal complexes of 1.
Discussion
The most remarkable result of these studies is the high
selectivity that is displayed by corrole 1 and its gallium(III)
complex 4 in their reactions with all three systems. However,
a prerequisite for elucidating possible reasons for this phenom-
enon is to discuss the synthetic and possibly mechanistic aspects
and the way that the structures were determined.
findings: the reaction conditions employed for corroles are
milder, the meso positions are more reactive than the â-pyrroles
in both macrocycles, and there is no selectivity in the very few
cases that proceed beyond monosubstitution. In contrast, in the
reaction of 4 with 110 mol % of reagent at room temperature,
only one out of the four possible monosubstituted products
was obtained (9, Scheme 4), together with small amounts of
the 2,17 bis-substituted corrole (10). The latter was the main
product (64% yield) when up to 1000 mol % of reagent was
used, and there were no indications for any of the other 15
different bis-formyl corroles that could have been formed in
principle. Although both 9 and 10 were stable compounds, we
were not able to grow X-ray quality crystals. Fortunately, the
presence of the formyl groups allowed for quite straightforward
identification of the products’ structures.
Syntheses. (a) Nitration. The nitration of 4 was first
attempted with a variety of reagents that were previously used
with zinc(II) and other metal porphyrins: HNO3/H2SO4, HNO3/
AcOH, N2O4, cerium(IV) ammonium nitrate (CAN), and
AgNO2/I2.19 Yet, all of these conditions led to significant
decomposition of the corrole ring and to mixtures of products
resulting from polynitration. During these attempts, we noted
the reports that in many cases (particularly with the AgNO2/I2
system) the porphyrin is first oxidized to its π-cation radical
which subsequently reacts with NO2 .
- 20 Accordingly, we have
prepared the already reported π-cation radical of 4, obtained
via oxidation with tris(4-bromophenyl)aminium hexachloroan-
timonate (5),8a and reacted it with NO2-. To our surprise, while
addition of 5 prior to the nucleophile gave negative results, the
opposite order of addition was very successful. In addition, it
was easy to control the extent of substitution by adjusting the
amount of 5 (Scheme 3). Importantly, even with only 75 mol
% of 5, the starting material was fully consumed, and the mono-
and dinitro corroles 6 and 7 were isolated in 84 and 9% yield,
respectively, clearly indicative of a chain reaction. Accordingly,
we suggest that under these reaction conditions (very large
excess of NaNO2 relative to 4), 5 oxidizes NO2- to NO2, rather
than 4 to its π-cation radical. Supporting evidence for this
hypothesis is provided by the following observations: the best
results with all previous mentioned methods were obtained with
N2O4, selective nitration (to the C3-position) by the 5/NaNO2
system was obtained even with a corrole metal complex that is
not oxidizable by 5 (the tin complex (tpfc)SnCl),6c and the
regioisomer of the bis-substituted product in the 5/NaNO2
system is different from that obtained with the clearly electro-
philic reagents (the Vielsmeier reagent and chlorosulfonic acid).
(b) Hydroformylation. The obvious choice for this reaction
was the Vielsmeier reagent, which was previously used for the
substitution of both the meso- and the â-pyrrole carbon atoms
of porphyrins and the meso-carbon atoms of octa-alkyl cor-
roles.12,21 These literature reports reveal several important
(c) Chlorosulfonation. The two major advantages of chlo-
rosulfonation relative to direct sulfonation are the much milder
reaction conditions (0-25 °C vs >100 °C) and the larger
synthetic utility of the product (RSO2Cl vs RSO3H). On the
other hand, the large reactivity of chlorosulfonic acid (CSA)
presents a problem in reactants with multiple reactive sites; the
preferred sites for substitution reactions of tetraarylporphyrins
with CSA are the aryls, and the various available positions in
phthalocyanines are substituted with very low selectivity.22 In
sharp contrast, the reaction of 1 with excess CSA displays very
high selectivity for the 2,17-bis-substituted corrole 2. The only
other product (11, )3%) was the 3,17-isomer, which was
isolated after amidation of 2 by piperidine and subsequent
metalation by cobalt (Scheme 2). Both the 2,17- and the 3,17-
regioisomers were fully characterized by NMR spectroscopy
and X-ray crystallography of their (triphenylphosphine)cobalt-
(III) complexes, 13 and 14, respectively.
(d) Metalation. The most variable compounds obtained in
this study are 2 and 3, because of the easy substitution of the
chloride in the -SO2Cl functions of 2 and the large variety of
metal ions that can be inserted into either 2 or 3. As the first
option was already demonstrated in our previous publication,15
we turned our attention to the metalation of 3. Generally, the
same methods that were developed for corrole 1 worked for 3
(18) Meier-Callahan, A. E.; Simkhovich, L.; DiBilio, A. J.; Gray, H. B.;
Goldberg, I.; Gross, Z. Inorg. Chem. 2001, 40, 6788-6793. Mahammed,
A.; Giladi, I.; Goldberg, I.; Gross, Z. Chem.-Eur. J. 2001, 7, 4259. Meier-
Callahan, A. E.; Gray, H. B.; Gross, Z. Inorg. Chem. 2000, 39, 3605-
3607. Simkhovich, L.; Galili, N.; Saltsman, I.; Goldberg, I.; Gross, Z. Inorg.
Chem. 2000, 39, 2704-5.
(19) Catalano, M. M.; Crossley, M. J.; Harding, M. M.; King, L. G. J. Chem.
Soc., Chem. Commun. 1984, 1535. Palacio, M.; Mansuy-Mouries, V.; Loire,
G.; Le Barch-Ozette, K.; Leduc, P.; Barkigia, K. M.; Fajer, J.; Battioni, P.;
Mansuy, D. Chem. Commun. 2000, 1907. Siri, O.; Jaquinod, L.; Smith, K.
M. Tetrahedron Lett. 2000, 41, 3583. Wickramasinghe, A.; Jaquinod, L.;
Nurco, D. J.; Smith, K. M. Tetrahedron 2001, 57, 4261. Evans, B.; Smith,
K. M.; Cavaleiro, J. A. S. J. Chem. Soc., Perkin Trans. 1 1978, 768.
(20) Malek, A.; Latos-Grazynski, L.; Bartczak, T. J.; Zadlo, A. Inorg. Chem.
1991, 30, 3222. Barnett, G. H.; Smith, K. M. J. Chem. Soc., Chem.
Commun. 1974, 772. Baldwin, J. E.; Crossley, M. J.; De Bernandis, J.
Tetrahedron 1982, 38, 685.
(21) (a) Inhoffen, H. H.; Fuhrhop, J.-H.; Voigt, H.; Brockmmann, H. Liebigs
Ann. Chem. 1966, 695, 133. (b) Brockmmann, H.; Bliesener, K.-M.;
Inhoffen, H. H. Liebigs Ann. Chem. 1968, 718, 148. (c) Schlozer, R.;
Fuhrhop, J.-H. Angew. Chem., Int. Ed. Engl. 1975, 14, 363. (d) Momenteau,
M.; Loock, B.; Bisagni, E. Can. J. Chem. 1979, 57, 1804. (e) Henrick, K.;
Owston, P. G.; Peters, R.; Tasker, P. A. Inorg. Chim. Acta 1980, 45, L161.
(f) Smith, K. M.; Bisset, G. M. F.; Tabba, H. D. J. Chem. Soc., Perkin
Trans. 1 1982, 581. (g) Buchler, J. W.; Dreher, C.; Herget, G. Liebigs
Ann. Chem. 1988, 43. (h) Montforts, F.-P.; Scheurich, G.; Meier, A.; Haake,
G.; Hoper, F. Tetrahedron Lett. 1991, 32, 3477.
(22) Rocha Gonsalves, A. M. A.; Johnson, R. A. W.; Pereira, M. M.; SantAna,
A. M. P.; Serra, A. C.; Sobral, A. J. F. N. Heterocycles 1996, 43, 829. (b)
Vinagradov, S. A.; Wilson, D. F. J. Chem. Soc., Perkin Trans. 2 1995,
103. (c) Bishop, S. M.; Khoo, B. J.; MacRobert, A. J.; Simpson, M. S. C.;
Phillips, D.; Beeby, A. J. Chromatogr. 1993, 646, 345.
9
7416 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Selective Substitution of Corroles
A R T I C L E S
smaller than those of C7H, C8H, C12H, C13H remains conserved
in the substituted corroles allows for a straightforward structural
assignment of the products, especially when aided by symmetry
considerations.
The products from the nitration reactions were assigned as
follows. First, there are four CH protons with large J-coupling
constants (>4.5 Hz) in the mono- and bis-nitro products (6, 7,
Table 1), indicating that C7H, C8H, C12H, C13H are not
substituted therein. Second, the observation of only one singlet
for two CH protons in the bis-nitro complex 7 enforces the
conservation of C2V-symmetry. Third, the sole singlet in the tris-
nitro complex 8 can only be explained by double substitution
of one of the double bonds. This reduces the number of possible
isomers for each product to only two: 2- or 3-nitro for 6, 2,18-
or 3,17-dinitro for 7, and 2,3,17- or 2,3,18-trinitro for 8. The
differentiation between the remaining possibilities requires
arguments based on chemical shifts, which although being less
reliable, were found to be applicable in the present cases. Thus,
the singlet at 9.69 ppm for 6 is more consistent with the effect
of a single â-nitro group on the chemical shift of C2H (9.15
ppm in 4) than of C3H (8.70 ppm in 4), suggesting the location
of the nitro group on C3. This conclusion, together with the
C2V-symmetry indicated by the observation of only one singlet
for 7 (at 9.54 ppm), leads to its assignment as a 3,17- rather
than a 2,18-bis-nitro corrole. Finally, the observation of only
one singlet (at 9.84 pmm) for 8 can only be explained if two of
its three nitro groups are located on the same carbon-carbon
bond, leaving no doubts for its assignment as the 2,3,17-
trinitrocorrole.
Figure 1. Drawing and numbering system of 4, the 1H NMR chemical
shifts of its â-pyrrole protons (in C6D6), and the calculated HOMO electron
density on the â-pyrrole carbon atoms (numbers in parentheses are for the
close-in-energy HOMO-1).
as well: Co(OAc)2/PPh3/EtOH for obtaining the (triphenylphos-
phine)cobalt(III) complex of 3, CrCl2/pyridine for the (bis-
pyridine)chromium(III) complex, Mn(OAc)2/DMF for the man-
ganese(III) complex, SnCl2‚2H2O/DMF for the (chloro)tin(IV)
complex, and GaCl3/pyridine for the gallium(III) complex. Both
3 and its metal complexes were soluble in water, and at the
low concentrations that are relevant for UV-vis measurements
(10-4-10-6 M), the linear plots obtained for elucidating the ꢀ
values indicate the absence of aggregation.
Structural Elucidation. (a) NMR Spectroscopy. A prereq-
uisite for determining the structures of the reaction products of
1 and 4 with the various reagents via NMR spectroscopy is the
assignment of the CH protons in the starting materials. However,
a rigorous spectral analysis was never performed for any corrole,
including the long-known alkyl-substituted derivatives such as
octaethylcorrole. Accordingly, we have addressed this issue by
examining 1 and a large range of its diamagnetic metal
complexes (CoIII, RhIII, Fe(NO), AlIII, GaIII, GeIV, SnIV, and PV)
by a combination of advanced NMR techniques and isotopic
labeling.23 The main findings of these studies were that in all
cases the four expected doublets (C2HdC18H, C3HdC17H,
C7HdC13H, C8HdC12H, see Figure 1 for 4) are divided into
two groups that differ significantly in their J-coupling con-
stants. The J ) 5.1-4.4 Hz and J ) 3.9-4.3 Hz were assigned
as reflecting C7H-C8H (dC12H-C13H) and C2H-C3H
(dC17H-C18H) coupling, respectively. In addition, we noted
that the C2-C3 and C17-C18 bonds (1.376, 1.383 Å for 4) are
significantly longer than C7-C8 and C12-C13 (1.358, 1.358 Å
for 4). These two trends corroborate each other, as an inverse
correlation between CdC bond lengths and CHdCH coupling
constants has been observed in other five-membered rings.24
The differentiation between C2H (dC18H) and C3H (dC17H)
was less obvious, but we found that the former protons always
appear at lower field. This outcome is reasonable, considering
the chemical shifts of the relevant protons in directly joined
R-R′-bypyrroles.25 We have also observed that the signal of C2H
is sharper than that of C3H, probably because of the absence of
remote coupling by fluorine atoms from meso-C6F5 in the
former. The most difficult task is the differentiation between
C7H and C8H, but this is not required for the present purposes
(vide infra). To conclude, the chemical shifts and coupling
constants of 4 are shown in Figure 1. Thus, assuming that the
trend of the coupling constants of C2H, C3H, C17H, C18H being
The spectroscopic analysis of 6-8 is confirmed via the X-ray
structures of the complexes (Figures 2-4). This adds confidence
to the assignment of 9 and 10, which failed to provide X-ray
quality crystals. For 9, the presence of only one doublet with a
small J-coupling constant (4.1 Hz) is consistent with substitution
at either C2 or C3. Support for the latter option is provided by
the chemical shift of the singlet (9.65 ppm) and its comparison
to that of the C2H in the nonsubstituted 4 (9.15 ppm) and the
3-nitrocorrole 6 (9.69 ppm). In addition, NOE experiments show
that the C2H is in proximity with both C18H (at 9.11 ppm) and
the formyl proton, while the sole interaction of the latter proton
is with C2H. This rules out substitution at C2, because in such
a case the formyl proton should experience NOE interactions
with both C3H and C18H. As for 10, the observation of two
singlets (10.03 and 9.01 ppm) enforces asymmetric substitution,
and the absence of small J-coupling constants for the remaining
doublets leads to the conclusion that the formyl groups are
located on C3 and C18 (dC2 and C17).
1
The H NMR inspection of the crude reaction product from
the chlorosulfonation of 1 revealed that it contains, in addition
to the previously described 3,18-bis-chlorosulfonato corrole 2,15
a minor product ()3%, 11) that displaced only one singlet at
9.06 ppm. This limited information was inadequate for a reliable
assignment of the substitution pattern in 11, especially because
the resonances of its other protons were hidden by the major
isomer. Yet, the sequence of amidation, cobalt insertion, and
chromatography allowed the separation of the main and minor
(triphenylphosphine)cobalt(III) complexes (13 and 14, respec-
tively, in Scheme 2) and the comparison of chemical shifts
therein with the corresponding complex of 1 (12, Table 1). The
observation of only one singlet served to confirm the C2V
(23) Saltsman, I.; Balazs, Y.; Mahammed, A.; Tkachenko, E.; Golubkov, G.;
Gross, Z., manuscript in preparation.
(24) Gu¨nther, Harald. NMR Spectroscopy, 2nd ed.; John Wiley and Sons Ltd.:
England, 1995.
(25) Farnier, M.; Soth, S.; Fournari, P. Can. J. Chem. 1976, 54, 1083. Cavaleiro,
J. A. S.; Condesso, M.; Olmstead, M. M.; Oram, D. E.; Snow, K. M.;
Smith, K. M. J. Org. Chem. 1988, 53, 5847.
9
J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7417

A R T I C L E S
Saltsman et al.
Table 1. Chemical Shifts (in CDCl3 for Compounds 1-11 and in C6D6 for 12-14) and J-Coupling Constants (Hz, in Parentheses) of the
Protons in All Compounds Described in This Work
substituted carbon atom(s)
C2H
C3H
C17H
C18H
C7H, C13H
C8H, C12H
1
none
3,17-(SO2Cl)2
3,18-(SO2Cl)2
9.10 (4.4)
9.06 (s)
9.44 (s)
8.57 (4.4)
8.57 (4.4)
9.10 (4.4)
9.06 (s)
8.75 (4.4)
a
8.57 (4.4)
a
11
2b
8.95 (s)
8.08 (4.6)
8.68 (s)
8.60 (5.0)
8.50 (5.0)
8.42 (5.0)
8.34 (4.9)
8.37 (5.0)
8.15 (4.7)
8.83 (4.5)
8.32 (4.6)
8.61 (4.6)
8.14, 8.18
8.76 (4.7)
8.67 (4.8)
8.67 (4.8)
8.38
8.41 (5.0)
8.18 (5.0)
8.28 (5.0)
8.20 (4.9)
8.24 (5.0)
8.13 (4.7)
8.61 (4.5)
8.61 (5.1)
8.35 (4.6)
8.39, 8.44
8.48 (4.7)
8.52 (4.8)
8.60 (4.8)
8.37
12
none
3,17-(SO2pip)2
3,18-(SO2pip)2
8.66 (4.6)
9.05 (s)
9.64 (s)
8.08 (4.6)
8.70 (4.0)
8.66 (4.6)
9.05 (s)
14
13b
4
6
none
3-NO2
3,17-(NO2)2
2,3,17-(NO2)3
3-CHO
9.15 (4.0)
9.69 (s)
9.54 (s)
8.70 (4.0)
8.71 (4.1)
9.15 (4.0)
8.45 (4.1)
9.54 (s)
9.84 (s)
9.11 (4.1)
7
8c
9
9.65 (s)
8.73 (4.1)
9.01 (s)
10b,c
3,18-(CHO)2
10.03 (s)
a Could not be determined because they are hidden by the main isomer 2. b For easier comparison, the isomers are named 3,18- in the table, rather than
the correct nomenclature of 2,17- that is used in the text. c Some of the coupling constants were not determined because of too closely spaced chemical
shifts.
and C17 (a shift of 0.39 ppm of C2H relative to 12) rather than
on C2 and C18 (a shift of 0.97 ppm of C3H relative to 12).
This conclusion is further strengthened by the data of 13, which
show that it requires two proximate sulfamido groups for
affecting a shift of 0.98 ppm for its C2H relative to 12.
(b) X-ray Crystallography. X-ray quality crystals were
obtained for all three nitration products (6, 7, and 8, Figures
2-4) and the (triphenylphosphine)cobalt(III) complexes of the
amidated chlorosulfonation products (13 (previously reported)
Figure 2. Molecular structure of 6. The observed Ga-N coordination
and 14, Figure 5). The comparison between the molecular
structures of 13 and 14 suggests that steric factors do not play
a major role in the large selectivity obtained by chlosulfona-
tion reaction of 1 in favor of the 3,18- ()2,17) relative to the
3,17-isomer (96:4). In fact, Figure 5 shows a marked similarity
between 13 and 14 (apart from the different disposition of the
sulfonate substituents). In both structures, the corrole macrocycle
is roughly planar, and the cobalt ion deviates about 0.3 Å from
the mean corrole plane toward the axial triphenylphosphine
ligand. The 1-piperidinesulfonate groups reside in sterically
unhindered areas away from the triphenylphosphine ligand, and
can adapt different orientations with respect to the corrole
framework even at the supposedly more crowded positions at
C3/C17, as is evident in Figure 5.
The mononitro- and trinitro-substituted complexes 6 (Figure
2) and 8 (Figure 4) are five coordinate with a single pyridine
species as an axial ligand. In these two corroles, the Ga ion
deviates by 0.376 Å (in 6) and 0.301 Å (in 8) from the plane of
the four pyrrole nitrogens, assuming a square-pyramidal coor-
dination environment and imparting to the complexes a domed
conformation. This involves also a slight upward rotation of
the pyrrole rings with respect to the mean plane of the corrole
macrocycle toward the metal. Thus, in the resulting domed
structures, the inner N-atoms lie 0.3-0.4 Å above the plane of
the eight peripheral carbon atoms (i.e., the four outer C-C bonds
of the pyrrole rings) that compose the outer rim of the corrole
framework. On the other hand, the dinitro-substituted complex
7 (Figure 3) is six-coordinate with two pyridyl axial ligands
bound to the Ga ion from opposite sides (at a slightly longer
coordination distance than in the five-coordinate complexes).
This coordination number is apparently unique to the trianionic
corroles; that is, we are not aware of hexacoordinated gallium-
distances to the four pyrrole and the pyridyl nitrogens are 1.972, 1.926,
1.942, 1.938, and 2.039(4) Å, respectively.
Figure 3. Molecular structure of 7. The observed Ga-N coordination
distances to the four pyrrole and the two pyridyl nitrogens are 1.924, 1.909,
1.913, 1.940, 2.234, and 2.284(6) Å, respectively.
Figure 4. Molecular structure of 8. The observed Ga-N coordination
distances to the four pyrrole and the pyridyl nitrogens are 1.954, 1.918,
1.909, 1.958, and 2.055(5) Å, respectively.
symmetry in 14 (also holds for its precursor, 11), and the large
J-coupling constant (4.9 Hz) ruled out substitution at either C7
and C13 or C8 and C12. In addition, the chemical shift of the
singlet in 14 (9.05 ppm) is consistent with substitution at C3
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7418 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Selective Substitution of Corroles
A R T I C L E S
C7-C8 and C12-C13 ones are 1.341 and 1.358 Å in 6, 1.329
and 1.337 Å in 7, and 1.337 and 1.327 Å in 8.
Source of Selectivity. The results show that the first
substitution on both 1 and 4 is invariably directed to C3 and
that the second substitution occurs at C17 for nitration and on
C18 for hydroformylation and chlorosulfonation (together with
a small amount on C17). In addition, the third nitration takes
place at C18 rather than in any of the other positions that are
much more remote from the first two nitro groups. This clearly
demonstrates the vast difference between the carbon atoms
located on the directly joined A and D pyrrole rings (C2, C3,
C17, C18) and the meso-carbon bridged B and C rings (C7,
C8, C12, C13). The crystallographic and spectroscopic data
show that the relevant CdC bonds in rings A and D are
relatively long, thus suggesting that their larger reactivity is
because of the less aromatic character therein. As for the C3
versus C2 selectivity, the crystallographic results suggest that
it is not because of steric forces. Accordingly, it almost enforces
the conclusion that this position is much more electron-rich than
all others. A verification of this hypothesis is provided in Fig-
ure 1, which shows the π-electron density at all â-pyrrole
carbon atoms obtained from the recently published DFT
calculations on 4.8a Apparently, the differences are large enough
for complete direction of electrophilic reagents to C3. In
addition, the deactivating effect of the first substituent in each
case (-SO2Cl, -[CHdNMe2], NO2) is expected to be more
significant at C2 and C17 than on C18 because of alternation.
This explains the selective formation of 3,18-bis-substituted
products in the reactions with CSA and the Vielsmeier reagent.
Figure 5. Comparison of the molecular structures of (top) 13 (shown with
50% probability ellipsoids at 110 K)15 and (bottom) 14 (35% ellipsoids at
273 K). The observed Co-N and Co-P coordination distances are 1.867-
1.874(3) and 2.225(1) Å in 13, and 1.852-1.867(7) and 2.217(3) Å in 14.
The C-S bond lengths of the sulfonate substituents to the corrole ring are
C3-S 1.760(3) and C18-S 1.737(3) Å in 13, and C3-S 1.738(10) and C17-S
1.724(10) Å in 14.
In the synthetic part, we have already provided indications
that suggest that nitration of 4 by the 5/NaNO2 system proceeds
via NO2, that is, a radical rather than an electrophilic reagent.
This hypothesis is further supported by the following observa-
tions. The selectivity for nitration (3,17-bis-nitro in 7) is
different, only this reaction proceeds behind bis-substitution
(2,3,17-tris-nitro in 8), and the third nitration occurs on an
already nitrated pyrrole ring (D) rather than on the yet non-
reacted B or C rings. All together, these results provide strong
evidence for a radical rather than electrophilic reaction pathway.
(III) complexes with dianionic porphyrin or phthalocyanine
ligands.
Correspondingly, in this structure, the corrole ring is es-
sentially planar with an octahedral coordination environment
around the metal. The two pyridyls are roughly parallel to each
other, with a twist angle between their planes of approximately
14°. It is interesting to note that, whenever possible, the nitro
substituents are nearly coplanar with the adjacent pyrrole rings
to enhance electron delocalization. The dihedral angles between
the plane of the nitro groups and the pyrrole rings they are
attached to are within 9-25° in 6, 7, and for two out of the
three substituents in 8. Only the third NO2 group on the doubly
substituted pyrrole in 8 (bound to C17) is aligned in a
perpendicular manner (the corresponding dihedral angle is 84°)
to minimize steric hindrance as well as electrostatic repulsion
with the neighboring nitro and pentafluorophenyl fragments. In
all three complexes, the pentafluorophenyl rings are oriented
in an almost perpendicular manner with respect to corrole ring,
all the corresponding dihedral angles being within 71-86°.
Moreover, in perfect agreement with the NMR data for 6-8
and earlier structural observations in 4, these three structures
show systematically that the peripheral C-C bond lengths in
pyrrole rings A and D are longer than those in rings B and C.
These findings are consistent with the higher reactivity of the
former sites toward chemical substitution, as well with the
analysis of the J-coupling constants. The corresponding
C2-C3 and C17-C18 bond distances are 1.389 and 1.381 Å in
6, 1.396 and 1.399 Å in 7, and 1.396 and 1.376 in 8; the
Summary and Conclusions
We have demonstrated in this work the feasibility and
powerfulness of electrophilic substitution on triarylcorroles as
a synthetic tool to new derivatives. The large difference in the
reactivity of the various carbon atoms on the macrocycle was
shown to be of electronic rather than steric origin. A careful
choice of reagents and a delicate control of reaction conditions
allowed the selective syntheses of novel derivatives, in all of
which substitution took place selectively in only one-half of
the macrocycle. This was proven by a combination of X-ray
crystallography of the various products and detailed analysis
of their NMR spectra, the latter of which also paves the way
for future studies of different corroles and different reagents.
All the substituents that were introduced into the corrole’s
skeleton (chlorosulfonyl, formyl, nitro) can, in principle, be
transformed into water-solubilizing groups by routine methods
(hydrolysis, oxidation, reduction), resulting in amphiphilic
corroles. This was demonstrated for the chlorosulfonation
product, which was also shown to chelate a variety of metal
ions. The utilization of these corroles and their metal complexes
9
J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7419

A R T I C L E S
Saltsman et al.
in several applications is the subject of ongoing research in our
laboratories.
Supporting Information Available: Details of the X-ray
crystallographic data collection and structure refinement, tables
of atomic coordinates, bond distances and angles, anisotropic
thermal parameters, and hydrogen atom positions for 6, 7, 8,
and 14 in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. This research (No. 368/001 for Z.G. and
No. 68/01 for I.G.) was supported by The Israel Science
Foundation and the Petroleum Research Fund (Z.G.). Partial
support by “Technion V.P.R. Fund - New York Metropolitan
Research Fund” is acknowledged as well (Z.G.).
JA025851G
9
7420 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002