[2-Methylazeteochlorinato]Ni(II): A pyrrole ring-contracted chlorin analogue

Article abstract of DOI:10.1016/j.tetlet.2010.06.096

The formal replacement of one of the pyrrole rings in [meso- tetraphenylporphyrinato]Ni(II) (5Ni) by an azete moiety is reported. Thus, reaction of known chlorophin monoaldehyde 7Ni (made in three steps from 5Ni) with methyl-Grignard, followed by an acid-catalyzed ring-closure reaction, generates the title compound [meso-tetraphenyl-2-methylazeteochlorinato]Ni(II) (10Ni) in a rational and scalable process in good yields. The UV-vis spectroscopic properties of this chromophore are, as expected for this chlorin analogue, red-shifted when compared to the corresponding [porphyrinato]Ni(II) (5Ni) complex. A much improved synthesis of the starting material 7Ni by Vilsmeier-Haack formylation of [meso-tetraphenylchlorophinato]Ni(II) (8Ni) is also reported.

Full text of DOI:10.1016/j.tetlet.2010.06.096

Tetrahedron Letters 51 (2010) 4505–4508
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
[2-Methylazeteochlorinato]Ni(II): a pyrrole ring-contracted chlorin analogue
*
Subhadeep Banerjee , Michael A. Hyland , Christian Brückner
Department of Chemistry, University of Connecticut, Unit 3060, Storrs, CT 06269-3060, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The formal replacement of one of the pyrrole rings in [meso-tetraphenylporphyrinato]Ni(II) (5Ni) by an
azete moiety is reported. Thus, reaction of known chlorophin monoaldehyde 7Ni (made in three steps
from 5Ni) with methyl-Grignard, followed by an acid-catalyzed ring-closure reaction, generates the title
compound [meso-tetraphenyl-2-methylazeteochlorinato]Ni(II) (10Ni) in a rational and scalable process
in good yields. The UV–vis spectroscopic properties of this chromophore are, as expected for this chlorin
analogue, red-shifted when compared to the corresponding [porphyrinato]Ni(II) (5Ni) complex. A much
improved synthesis of the starting material 7Ni by Vilsmeier–Haack formylation of [meso-tetraphenyl-
chlorophinato]Ni(II) (8Ni) is also reported.
Received 20 May 2010
Revised 16 June 2010
Accepted 17 June 2010
Available online 22 June 2010
Keywords:
Porphyrins
Porphyrinoids
Chlorins
Ó 2010 Elsevier Ltd. All rights reserved.
Chlorin analogues
Pyrrole-modified porphyrins
The potential application of porphyrins and chlorins (dihydro-
porphyrins) as dyes in, for instance, light harvesting and photo-
medicine largely drives their study.1 Particularly derivatives with
modulated photophysical properties are of interest. Therefore, por-
phyrin isomers and porphyrin analogues containing non-pyrrolic
heterocycles were synthesized.2 In addition, a host of expanded
porphyrins has become known.3
existence of azeteochlorin alcohol 3Ni which formed as a side
product of the Vilsmeier–Haack formylation of chlorophin (for
more details of this reaction, see below).6 Though its formation
could be rationalized, no realistic synthesis could be presented.
Ph
Ph
M
O
O
H
H
O
H
(i) or
(ii)
N
N
H
N
N
N
N
N
N
N
N
N
N
N
N
N
M
Ph
Ph
Ph
Ph
H
H
H
H
N
1
2
Ph
Ph
Ph
porphyrin
chlorin
M = 2H, NiII, CuII, ZnII
(iii)
+ other
products
Only most recently, however, a contracted porphyrin analogue
containing only three conjugated pyrroles was reported.4 Similarly,
very little has become known about pyrrole-ring-contracted por-
phyrinoids, that is, products in which a pyrrolic moiety in a por-
phyrin is replaced by a four-membered ring, although Crossley
and King showed as early as 1984 that the oxidation of porphyrin
dione 1 leads to the formation of free base azeteoporphyrin ketone
2 (Scheme 1) as a minor product (4%).5 In 2005, we indicated the
Ph
CO2Me
OH
N
N
N
N
N
N
N
N
M
Ph
Ph
Ni
Ph
Ph
3Ni
4
Ph
Ph
* Corresponding author. Tel.: +1 860 486 2743; fax: +1 860 486 2981.
E-mail address: c.bruckner@uconn.edu (C. Brückner).
Contributed equally.
Scheme 1. Reaction and conditions: (i) (1) NaH, O2, CH2Cl2; (2) 3 M aq HCl. (ii)
Excess BSA, chlorobenzene, reflux. (iii) (1) NH2NH-Ts, CH2Cl2; (2) 200 W HgXe lamp
(k >300 nm), CH2Cl2/MeOH.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.096

4506
S. Banerjee et al. / Tetrahedron Letters 51 (2010) 4505–4508
seemingly high reactivity of the
framework toward the synthesis of azeteochlorins.
a-position of the chlorophin
Ph
Ph
Ni
CHO
CHO
To this end, we reacted brown-green monoaldehyde 7Ni with a
stoichiometric excess of methyl-Grignard (Scheme 2; for details,
see Supplementary data). The rapid formation of a more polar
(Rf = 0.42 vs the Rf of 7Ni of 0.50, silica-CH2Cl2/petroleum ether
30-60, 1:1) green product suggested the formation of secondary
alcohol 9Ni. The 1H NMR spectrum of a crude sample of 9Ni
showed the presence of a major product lacking axial symmetry
(e.g., six b-protons signals could be identified), and displaying a
N
N
N
N
N
N
N
N
(i), (ii)
Ni
Ph
Ph
Ph
Ph
5Ni
6Ni
Ph
Ph
Ph
Ph
Route A (iii)
Route A' (iv)
signal corresponding to a single a-position (10.3 ppm; for details,
see Supplementary data). This indicated that no ring closure had
taken place. A broad signal at 5.15 ppm was indicative of an alcohol
moiety. Attempted purification of this compound resulted in its
decomposition. Thus, this product was reacted in crude form with
a stoichiometric excess of TMSOTf to induce an intramolecular Fri-
edel–Crafts reaction by removal of the alcohol and generation of
the corresponding carbocation. As the starting material was con-
sumed, a new green low polarity (Rf = 0.70, silica-CH2Cl2/petro-
leum ether 30–60, 1:1) product was formed. It was isolated by
preparative plate chromatography in, after crystallization by sol-
vent exchange, up to 75% yields.
CHO
N
N
N
N
N
N
N
N
Ni
+
Route B, (v)
Ni
Ph
Ph
Ph
Ph
(7Ni 12% + 60% 8Ni, Route A)
8Ni
Ph
Ph
(7Ni 9% + 45% 8Ni + 7% 3Ni, Route A')
7Ni (25-45%, Route B)
(vi)
The molecular formula of this product was shown by HR-MS
(FAB) to be C44H30N4Ni.15 The composition is commensurate with
an intramolecular electrophilic substitution of the presumably
formed secondary carbocation with the ortho-position of a flanking
phenyl group, forming a fused dehydroindane moiety, or the de-
Me
OH
Ph
Ph
Me
N
N
N
N
N
N
(vii)
sired a
-substitution product 10Ni.12,16 The 1H and 13C NMR spectra
Ni
Ni
Ph
Ph
Ph
Ph
of 10Ni are characteristic for a twofold symmetric product (e.g.,
two d at 8.70 and 8.67 ppm, 3J = 4 Hz, and a s at 8.52 ppm, all 2H
ea, assigned to the b-protons) (Fig. 1). This immediately excludes
the possibility of the phenyl-fused product. Diagnostic peaks for
N
N
Ph
9Ni (not isolated)
Ph
10Ni (60-75%)
Scheme 2. Reaction and conditions: (i) (1) OsO4, pyridine, CHCl3; (2) H2S, CHCl3/
MeOH. (ii) PbIV(acetate)4, THF. (iii) 2–3 equiv (Ph3P)3RhCl, PhCN, reflux. (iv) 2 equiv
(Ph3P)3RhCl added in portions over 2–3 days, PhMe/PhCN, reflux. (v) (1) DMF–
POCl3, CHCl3, reflux, 5 min; (2) aq NaHCO3. (vi) MeMgBr, dry THF. (vii) (1) TMSOTf,
CH2Cl2; (2) aq NaHCO3.
Zaleski and co-workers achieved a breakthrough, in that they
were able to provide two examples of azeteoporphyrins/chlo-
rins:7–10 the synthesis of ketone 2 (as its Ni(II) and Cu(II) com-
plexes) using a benzeneseleninic anhydride oxidation of 1 and
preparation of ester 4 (as its Ni(II), Cu(II), and Zn(II) complexes)
using a photochemically induced Wolff rearrangement of diazo
derivative 3 (Scheme 1). Importantly, their methods are relatively
high yielding and the first proof of the structures of 2Ni, 2Cu,
and 4Ni by X-ray diffractometry was provided by this group.
Mirroring the differences of the oxidation states of porphyrins
and chlorins, we like to refer 2 as an azeteoporphyrin, but like to
name 4 and other derivatives containing sp3-carbon in the azete
moiety as azeteochlorins.
We present herein the expansion of the class of azeteochlorins
by a member that is available through a rational and stepwise syn-
thesis. Their formation highlight a unique reactivity of chlorophins,
and points toward a generalized strategy for the conversion of a
porphyrin to pyrrole ring-contracted derivatives.
We have previously shown the synthetic utility of secochlorin
bisaldehyde 6Ni (and its free base analogue) for the formation of
pyrrole-modified porphyrins,11–13 including its step-wise deformy-
lation to form chlorophin monoaldehyde 7Ni and chlorophin 8Ni
(Scheme 2).6,14 Our earlier observation of (fortuitously formed)
azeteochlorin alcohol derivative 3 could be rationalized by an
intramolecular Friedel–Crafts-type reaction of chlorophin monoal-
dehyde derivative 7Ni.6 This suggested to us the exploitation of the
Figure 1. 1H NMR spectrum (400 MHz, C6D6, 25 °C) of 10Ni.

S. Banerjee et al. / Tetrahedron Letters 51 (2010) 4505–4508
4507
azeteochlorin 10Ni are the signals for the methyl group (d, 1.23, 3H
and 30.0 ppm, respectively) and the sp3-azete position (q, 4.99, 1H
and 45.0 ppm, respectively; see also Supplementary data). The
methyl group located on one face of the porphyrin causes a face
differentiation at the ortho-positions of the flanking phenyl groups.
Evidently, phenyl rotation is slow on the NMR time scale.
its b- or the phenyl positions, particularly as the method used
was firstly reported for the b-formylation of 5Ni.
A comparison of the Electronic absorption spectrum of 10Ni to
that of a typical Ni(II) chlorin [tetraphenyl-2,3-dihydroxychlorina-
to]Ni(II) and that of the metalloporphyrin 5Ni clearly demonstrates
that it is based on the relative intensity of the Q-band with respect
to the Soret band and the Q-band shapes and positions, metallo-
chlorin-like (Fig. 2). However, the Soret band is ꢀ10 nm hypsochro-
mically shifted as compared to the corresponding band of the
chlorin and Ni(II) porphyrin 5Ni. We interpret this blue-shift as a
spectroscopic signature for the (projected)18 planarity of the sys-
tem compared to the ruffled conformation of the chlorin and the
porphyrin.19 As expected, the spectral features of Zaleski’s azeteo-
Although the two-step conversion of monoaldehyde 7Ni to 10Ni
is high yielding and straightforward, the preparation of 7Ni is
fraught with problems: it cannot be prepared efficiently by
mono-deformylation of secochlorin bisaldehyde 6Ni (itself readily
available from the corresponding diol chlorin,6 which itself is avail-
able in gram-scales from the corresponding porphyrin by an OsO4-
mediated dihydroxylation reaction).13 This is because the reaction
of bisaldehyde 6Ni with excess Wilkinson’s catalyst in refluxing
PhCN generates chlorophin 8Ni in 60% isolated yields, but monoal-
dehyde 7Ni in only about 12% yields.6 In other words, the first
deformylation is much slower than the second, greatly inhibiting
the generation of larger quantities (e.g., 25 mg batches) of 7Ni. In
the attempts to optimize the reaction conditions, we varied the
solvents (using mixtures of varying ratios of dry PhCN and PhCH3)
and reduced the stoichiometric ratio of Wilkinson’s catalyst ini-
tially used (down to 1.0 equiv with a batch-wise addition of further
1.0 equiv over the course of 3 days at reflux temperatures; for de-
tails, see Supplementary data). In the best of circumstances, this al-
lowed the isolation of 9% of 7Ni, with up to 30% recovery of the
starting material 6Ni. The extended reaction times also led to the
loss of the brown-green 7Ni as it is converted to the turquoise alco-
hol 3Ni in ꢀ7% yield (this represents an improvement over the pre-
viously described formation,6 but still does not constitute a
practical synthesis).
chlorin ester 4Ni (DSoret = À2 nm,
D
kmax = À3 nm)7,9 and alcohol
3Ni (DSoret = 2 nm,
those of 10Ni.
Dkmax = 9 nm) are overall similar compared to
In summary, an improved Vilsmeier–Haack formylation of chlo-
rophin results in the efficient formation of monoformyl chlorophin
7Ni. This aldehyde is susceptible to a ring-closing reaction using
the addition of methyl-Grignard, followed by an acid-catalyzed
ring-closing step to form azeteochlorin 10Ni. This reaction ex-
plores the high reactivity of the
a-position of the chlorophin to-
ward electrophilic substitution. This work points toward a novel
strategy for the construction of novel pyrrole-contracted porphyri-
noids. The optical properties of 10Ni are suggestive of the presence
of a planar macrocycle, providing an additional evidence for an in-
creased rigidity of the azeteoporphyrin/chlorin chromophore when
compared to the corresponding porphyrins/chlorins.
Acknowledgments
Since we failed to skew the product ratios of the deformylation
reaction toward the monoformyl product 7Ni, we revisited the
Vilsmeier–Haack formylation of 8Ni that, in an earlier report,6
did not proceed satisfactorily (Scheme 2). When we used a much
lower ratio of Vilsmeier reagent (chloroiminium formed from
DMF and POCl3) to substrate than that previously described and
switched the solvent to CHCl3 under reflux conditions for short
periods of time (5–10 min),17 we were able to obtain the mono-
formylated product in up to 45% isolated yields (for details, see
Supplementary data). Despite no 8Ni can be recovered from the
reaction and two minor unidentified side products formed, the
reaction has the advantage of allowing the preparation of 10 mg
This work was supported by the NSF (CHE-0517782 and CMMI-
0730826) and the US Air Force (through a stipend to M.A.H.).
Supplementary data
Supplementary data (procedure for the conversion of 7Ni to
10Ni via 9Ni and for the optimized Vilsmeier–Haak mono-formyla-
tion of 8Ni to provide 7Ni, including corresponding spectroscopic
data of the novel compounds and reproductions of key spectra)
associated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2010.06.096.
batches of 7Ni (using 20 Â 20 cm, 500
lm silica gel preparative
chromatography plates for the isolation of the product). The selec-
References and notes
tivity of the formylation reaction provides another indication for
1. Representative reviews of porphyrins in photomedicine: (a) Sternberg, E. D.;
Dolphin, D.; Brückner, C. Tetrahedron 1998, 54, 4151–4202; (b) O’Connor, A. E.;
Gallagher, W. M.; Byrne, A. T. Photochem. Photobiol. 2009, 85, 1053–1074; Light
harvesting: (c) Aratani, N.; Kim, D.; Osuka, A. Acc. Chem. Res. 2009, 42, 1922–
1934; (d) Gust, D.; Moore, T. A.; Moore, A. L. Acc. Chem. Res. 2009, 42, 1890–
1898.
the high reactivity of the chlorphin a-position when compared to
2. (a) Lash, T. D.. In Kadish, K. M., Smith, K. M., Guilard, R., Eds.; The Porphyrin
Handbook; Academic Press: San Diego, 2000; pp 125–200; (b) Latos-Grazynski,
L.. In Kadish, K. M., Smith, K. M., Guilard, R., Eds.; The Porphyrin Handbook;
Academic Press: San Diego, 2000; pp 361–416.
3. Sessler, J. L.; Weghorn, S. Expanded, Contracted & Isomeric Porphyrins; Pergamon
Press: New York, NY, 1997.
4. The much longer and well known corroles might also be considered ring-
contracted porphyrins: Nardis, S.; Monti, D.; Paolesse, R. Mini-Rev. Org. Chem.
2005, 2, 355–374.
5. Crossley, M. J.; King, L. G. J. Chem. Soc., Chem. Commun. 1984, 920–922.
6. Brückner, C.; Hyland, M. A.; Sternberg, E. D.; MacAlpine, J.; Rettig, S. J.; Patrick,
B. O.; Dolphin, D. Inorg. Chim. Acta 2005, 358, 2943–2953.
7. Köpke, T.; Pink, M.; Zaleski, J. M. J. Am. Chem. Soc. 2008, 130, 15864–15871.
8. Köpke, T.; Pink, M.; Zaleski, J. M. Chem. Commun. 2006, 4940–4942.
9. Köpke, T.; Pink, M.; Zaleski, J. M. Org. Biomol. Chem. 2006, 4, 4059–4062.
10. Köpke, T. Ph.D. Thesis, Department of Chemistry, Indiana University, 2008.
11. (a) Campbell, C. J.; Rusling, J. F.; Brückner, C. J. Am. Chem. Soc. 2000, 122, 6679–
6685; (b) McCarthy, J. R.; Melfi, P. J.; Capetta, S. H.; Brückner, C. Tetrahedron
2003, 59, 9137–9146; (c) Daniell, H. W.; Brückner, C. Angew. Chem., Int. Ed.
2004, 43, 1688–1691; (d) Akhigbe, J.; Ryppa, C.; Zeller, M.; Brückner, C. J. Org.
Chem. 2009, 74, 4927–4933.
Figure 2. UV–vis spectral comparison of [tetraphenylporphyrinato]Ni(II) 5Ni
(dashed trace), [tetraphenyl-2,3-diolchlorininato]Ni(II) (solid trace), and [tetraph-
enylazeteochlorinato]Ni(II) 10Ni (dotted trace), all in CH2Cl2.

4508
S. Banerjee et al. / Tetrahedron Letters 51 (2010) 4505–4508
12. McCarthy, J. R.; Hyland, M. A.; Brückner, C. Org. Biomol. Chem. 2004, 2, 1484–
1491.
13. Brückner, C.; Rettig, S. J.; Dolphin, D. J. Org. Chem. 1998, 63, 2094–2098.
14. Brückner, C.; Sternberg, E. D.; MacAlpine, J. K.; Rettig, S. J.; Dolphin, D. J. Am.
Chem. Soc. 1999, 121, 2609–2610.
16. Fox, S.; Boyle, R. W. Tetrahedron 2006, 62, 10039–10054.
17. Mironov, A. F.; Moskalchuk, T. V.; Shashkov, A. S. Russ. J. Bioorg. Chem. 2004, 30,
261–267.
18. This projection is based on the known crystal structures for 2Ni and 4Ni, Refs.
7–10.
15. In fact, the composition of the product is identical with the composition of
[meso-tetraphenylchlorinato]Ni(II). Thus, 10Ni is formally a chlorin isomer.
19. Wondimagegn, T.; Ghosh, A. J. Phys. Chem. B 2000, 104, 10858–10862.