Photochemical preparation of pyrrole ring-contracted chlorins by the Wolff rearrangement

Article abstract of DOI:10.1039/b612776m

Photolysis of the Ni(ii), Cu(ii), and Zn(ii) 2-diazo-3-oxochlorins generates 4-membered rings containing azeteoporphyrins. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b612776m

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
Photochemical preparation of pyrrole ring-contracted chlorins by the Wolff
rearrangement†
Tillmann Ko¨pke, Maren Pink and Jeffrey M. Zaleski*
Received 4th September 2006, Accepted 25th September 2006
First published as an Advance Article on the web 4th October 2006
DOI: 10.1039/b612776m
Photolysis of the Ni(II), Cu(II), and Zn(II) 2-diazo-3-
oxochlorins generates 4-membered rings containing azeteo-
porphyrins.
Porphyrins and chlorins, by virtue of their unique electronic
properties have been evolved as key components of artificial
photosynthetic devices1 and molecular materials,2 as well as
effective agents in medical applications such as photodynamic
therapy (PDT).3 The latter area utilizes low energy photoexcitation
at tissue transparent wavelengths in the near infrared spectral
Scheme 1 Synthesis of 2-diazo-3-oxochlorins.
region to form toxic “diradical-like” species such as 1O2 from 3O2
via annihilation of the photogenerated 3pp* state.
3 with 20 equiv. of p-toluenesulfonylhydrazine under reflux in
In a chemically related arena, valence deficient carbene di-
dichloromethane for 9 h, 6 h, and 3 h, respectively. Separation
radicals produced by loss of dinitrogen from diazoketones are
by column chromatography yielded 4 (60%), 5 (77%), and 6 (74%)
known to undergo H-atom abstraction (triplet) or insertion
in markedly better yields than previously reported.8 Use of Zn(II)
(singlet) reactions with external substrates.4 They also facilitate
as a co-reagent can reduce these reaction times by as much as a
complex internal transformations5 such as the Wolff rearrange-
factor of six.20
ment of the ketocarbene to form a ketene that subsequently
Photolysis of 4 and 5 in a 1 : 1 mixture of CHCl3–MeOH was
reacts with nucleophiles.6 Photochemically, diazoketones are quite
previously reported to yield photoproducts involving substitution
reactive, making them intriguing candidates for chromophore-
on the periphery of the p-electron conjugated macrocycle. These
based photo-therapeutic applications (e.g. PDT), especially in
products are the hydroxy porphyrin (4a, 5a: trace, 25%), the
hypoxic environments. Moreover, since unusual and effective
methoxy porphyrin (Ni(II): 8%, Cu(II): 28%) and two MeOH
chromophore periphery modification2,7 is also important for
insertion oxochlorin products, the methoxy (4b, 5b: 10%, 5%) and
nearly all porphyrinoid-based applications, diazoketone reactivity
dimethoxy (4c, 5c: 14%, 11%) species.21 The latter products suggest
may have considerable potential in this area as well.
involvement by carbene intermediates, the precise natures of which
Current literature provides only one synthetic route to 2-diazo-
were not determined.
3-oxochlorins; the reaction of aminoporphyrins with NaNO2
Carbene intermediates in heterocyclic ring systems can also
in THF.8 This is an established method to diazonium salts,9
undergo the Wolff rearrangement.6,22 To date, only two examples
but in the presence of trace peroxides in THF, it fortuitously
of pyrrole ring-contracted porphyrinoid constructs featuring a
generates the Cu(II) and Ni(II) 2-diazo-3-oxochlorins in 54% and
4-membered azete moiety have been reported, and both were
30% yields, respectively.8 Our previous work on photochemical
obtained by thermal oxidation.23,24 We postulated that such an
diradical generating systems,10–12 and those conjugated to strong
azeteoporphyrin should be accessible via the photoinduced Wolff
chromophores,13,14 prompted our interest in the syntheses and
rearrangement. One may also expect other periphery modification
photoreactivities of 2-diazo-3-oxochlorins.
such as radical or nucleophile addition products resulting from
The accessibility of 2,3-dioxochlorins15,16 and the well known
unimolecular or bimolecular reactions.
conversion of a-dioxo functionalities to a-diazo-oxo systems in
Toward these goals, a 0.7 mM solution of 4 in a 1.67 : 1
high yields by reaction with p-toluenesulfonylhydrazine,17–19 espe-
solution of dried, degassed CH2Cl2 : MeOH (40 mL) was irradiated
cially in p-electron conjugated backbones,18 inspired our synthetic
with a 200 W HgXe lamp in a Pyrex vessel (k > 300 nm)
approach to these targets (Scheme 1). The 2,3-dioxochlorins pre-
under nitrogen for 6 h at 10 ◦C. The photoreaction generated
cursors (1–3)15,16 are readily prepared by a literature procedure.15
two major and two minor molecular products that were com-
The desired (2-diazo-3-oxochlorinato)nickel(II) (4), copper(II) (5),
pletely characterized, as well as black residue that is insolu-
and zinc(II) (6) compounds are then obtained by reaction of 1–
ble in standard organic solvents. Analogous to the previous
report, we also obtain (2-hydroxy-5,10,15,20-tetraphenylporphy-
Department of Chemistry, Indiana University, Bloomington, IN, USA.
E-mail: zaleski@indiana.edu; Fax: +1 (812) 855 8300; Tel: +1 (812) 855
2134
† Electronic supplementary information (ESI) available: Synthesis and
characterization of 4, 4a–e, 5, 5a–d, 6, and 6a–d, as well as X-ray
crystallographic data for 4d, 4e, and 5d. See DOI: 10.1039/b612776m
rinato)nickel(II) 4a (3%) and (2-methoxy-3-oxo-5,10,15,20-
tetraphenylchlorinato)nickel(II), 4b (5%), but in low yields. We ob-
serve in much better yield, the dimethoxychlorin (2,2-dimethoxy-
3-oxo-5,10,15,20-tetraphenyl-chlorinato)nickel(II) 4c (32%), as
well as the unusual pyrrole ring-contracted target azeteoporphyrin
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4059–4062 | 4059
©

View Article Online
compound 4d25 (16%) derived from the Wolff rearrangement and
quenching by MeOH (Fig. 1).
traverse similar reaction pathways, which are analogous to the one
proposed by Meinwald27 where methanol addition to the ketene
generates a methoxy ester.
Due to multiple product formation, a single quantum yield for
the overall photoreaction was obtained by monitoring the photo-
bleaching of the Soret band at kmax = 430 nm.28 The quantum yield
for the decay of 5 in CH2Cl2 at k = 365 nm irradiation wavelength
was measured to be U365 = 0.13, which is in accordance with
published values for UV-excitation of diazoketones.29
One additional photoproduct was also detected in trace
amounts; the dimerization product of two Ni(II) 2-diazo-3-
oxochlorins, which are fused at the 2-position upon loss of N2
4e30 (Fig. 2). The X-ray structure of the dimer also reveals
formation of an exocyclic ring, suggesting that the mechanism
for dimerization first involves radical addition to the meso-phenyl
ring.14 Although mechanistically speculative, the dimer is a glimpse
into the nature of the black residue formed upon photolysis of 4
and 5, suggesting formation of high molecular weight species.
Efforts to reduce the yield of that material by dilution have thus
far been unsuccessful, indicating that the bimolecular aggregation
kinetics compete favorably with substrate addition and the Wolff
rearrangement.
Fig. 1 X-Ray structure of photoproduct 4d. Upper: front view, Lower:
side view along N2–Ni1–N4 axis; Thermal ellipsoids are illustrated at 50%
probability; H-atoms are omitted for clarity.
Photolysis of the Cu(II) 2-diazo-3-oxochlorin 5 under the same
conditions generates chemically similar photoproducts, including
the 4-membered ring-containing Cu(II) azeteoporphyrin, 5d26 (7%)
(Scheme 2). Isolation of 4d and 5d led us to conclude that 4 and 5
Fig. 2 X-Ray structure of photoproduct 4e. Thermal ellipsoids are
illustrated at 50% probability; H-Atoms and spectator phenyl rings are
omitted for clarity.
To determine whether the unfilled d-shell of the central metal
influences the photochemical reactivity and product yields, (2-
diazo-3-oxochlorinato)zinc(II) 6 was prepared using the synthetic
method described above. When a 0.7 mM solution of 6 in a 1.6 : 1
solution of dried, degassed CH2Cl2 : MeOH was irradiated (200 W
HgXe, k > 300 nm) for 6 h at 10 ◦C, the analogous products (6a–
d) to those isolated upon photoreaction of 4 and 5 were obtained
in similar quantities. This indicates limited influence of charge
transfer or ligand field excited states in the excited state reaction
dynamics.
The unique X-ray structures of 4d and 5d are isomorphous
and reveal that the macrocycles are both planar with remarkably
˚
˚
short M–Nazete distances (4d: 1.83 A, 5d: 1.89 A). Typically, metal
ions with small radii compensate for the larger porphyrin core size
by drawing in the pyrrole nitrogens, resulting in puckering of the
backbone.31,32 For 4d and 5d this is not the case as the rigidity
of the smaller macrocycle enforces a planar structure, despite the
short M–Nazete bonds. The result is unusual considering the highly
ruffled/saddled nature of many Ni(II) porphyrins.13,33
Scheme 2 Photoreaction products obtained upon irradiation of 4, 5,
and 6.
4060 | Org. Biomol. Chem., 2006, 4, 4059–4062
This journal is
The Royal Society of Chemistry 2006
©

View Article Online
The Wolff photoproducts 4d and 5d can be considered as a
type of chlorin since they possess an electronic structure with the
requisite 20p electron macrocycle. This assumption is supported by
the chlorin-like electronic absorption spectra of these compounds
(e.g. 4d, Fig. 3), which show a prominent Qx band as the lowest
energy feature. Relative to the starting diazo-oxochlorin 4, the
absorption profile of 4d exhibits a modest blue-shift, likely due to
reduction of the conjugation length and pronounced planarity of
the macrocycle.33
The authors wish to thank Dr Mahendra Nath and David F. Dye
for technical assistance, as well as Indiana University for funding
of this work.
References
1 H. Imahori, Y. Mori and Y. Matano, J. Photochem. Photobiol., C, 2003,
4, 51.
2 M. J. Crossley, L. J. Govenlock and J. K. Prashar, J. Chem. Soc., Chem.
Commun., 1995, 2379.
3 A. Jasat and D. Dolphin, Chem. Rev., 1997, 97, 2267.
4 T. Ye and M. A. McKervey, Chem. Rev., 1994, 94, 1091.
5 L. Horner, E. Spietschka and E. Becker, Chem. Ber., 1955, 88,
934.
6 W. Kirmse, Eur. J. Org. Chem., 2002, 2193.
7 J. L. Sessler and D. Seidel, Angew. Chem., Int. Ed., 2003, 42, 5134.
8 J. A. S. Cavaleiro, V. M. Gerdan, H. K. Hombrecher, M. G. P. M. S.
Neves and A. M. S. Silva, Heterocycl. Commun., 1997, 3, 253.
9 D. F. DeTar and D. I. Relyea, J. Am. Chem. Soc., 1954, 76, 1680.
10 H. J. Eppley, S. M. Lato, J. M. Zaleski and A. D. Ellington, Chem.
Commun., 1999, 2405.
11 B. J. Kraft, H. J. Eppley, J. C. Huffman and J. M. Zaleski, J. Am. Chem.
Soc., 2002, 124, 272.
12 T. D. Maurer, B. J. Kraft, S. M. Lato, J. M. Zaleski and A. D. Ellington,
Chem. Commun., 2000, 69.
13 T. Chandra, B. J. Kraft, J. C. Huffman and J. M. Zaleski, Inorg. Chem.,
2003, 42, 5158.
14 M. Nath, M. Pink and J. M. Zaleski, J. Am. Chem. Soc., 2005, 127,
478.
Fig. 3 Electronic absorption spectra for 4 and 4d in CH2Cl2.
15 M. J. Crossley, P. L. Burn, S. J. Langford, S. M. Pyke and A. G. Stark,
J. Chem. Soc., Chem. Commun., 1991, 1567.
16 H. W. Daniell, S. C. Williams, H. A. Jenkins and C. Bru¨ckner,
Tetrahedron Lett., 2003, 44, 4045.
17 J. Meinwald and J. K. Crandall, J. Am. Chem. Soc., 1966, 88, 1292.
18 B. M. Trost and P. L. Kinson, J. Am. Chem. Soc., 1975, 97, 2438.
19 K. B. Wiberg, B. R. Lowry and T. H. Colby, J. Am. Chem. Soc., 1961,
83, 3998.
20 T. Ko¨pke, M. Pink and J. M. Zaleski, Synlett, 2006, 2183.
21 H. K. Hombrecher, V. M. Gerdan, J. A. S. Cavaleiro and M. G. P. M. S.
Neves, Heterocycl. Commun., 1997, 3, 453.
22 Y. Chiang, M. Gaplovsky, A. J. Kresge, K. H. Leung, C. Ley, M. Mac,
G. Persy, D. L. Phillips, V. V. Popik, C. Roedig, J. Wirz and Y. Zhu,
J. Am. Chem. Soc., 2003, 125, 12872.
To probe whether visible region photolysis could generate the
Wolff product, 4 and 5 were irradiated with a HgXe lamp (200 W,
◦
k ≥ 395 nm) for 48 h at 10 C in a Pyrex vessel under nitrogen.
Although the photolysis times were increased, Wolff products 4d
and 5d are still obtained in 6% and 8% isolated yields, respectively,
due to conjugation of the diazo unit into the visible region pp*
transitions of the macrocycle.
The formation of Wolff products 4d–6d and C–C bond coupling
species 4e derive from carbene insertion, suggesting formation of
a singlet carbene intermediate. Indeed, photolysis (Hg arc lamp;
100 W, 5 h) of a frozen solution of 4 and 5 at 5 K within an
EPR cavity (X-band) yields no new EPR signals between 500–
7000 G characteristic of a triplet carbene, despite detection of
photoproduct by TLC upon thawing. Our experience in detecting
carbene and triplet diradical intermediates by frozen solution
photolysis/EPR at 5 K11,34 leads us to conclude that the carbene
intermediates of both 4 and 5 are likely singlet in nature. This is
consistent with their ability to effectively participate in the Wolff
rearrangement and C–C bond coupling rather than olefin or azine
formation.35 Herein we demonstrate a new synthetic approach
to 2-diazo-3-oxochlorins and the unprecedented photochemical
formation of azeteoporphyrins via the Wolff ring contraction.
Photoproduct analysis and low-temperature EPR measurements
suggest that singlet carbene intermediates are formed, leading to
insertion reactions, as well as formation of the ketene intermediate
of the Wolff pathway. In a general sense, our synthetic strategy
allows selective installation of a photo-labile fragment on the
periphery of a chlorin macrocycle and can therefore be seen as
a synthetic tool for future periphery modifications on porphyrinic
heterocycles. Overall, both carbene and ketene intermediates of
this type may find potential as in situ alkylating agents in photo-
therapeutic applications in hypoxic environments.
23 C. Bru¨ckner, M. A. Hyland, E. D. Sternberg, J. K. MacAlpine, S. J.
Rettig, B. O. Patrick and D. Dolphin, Inorg. Chim. Acta, 2005, 358,
2943.
24 M. J. Crossley and L. G. King, J. Chem. Soc., Chem. Commun., 1984,
920.
25 CCDC reference numbers 605756 (4d), 605758 (4e), and 605757
(5d). For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b612776m. Crystal data for 4d: brown block, 0.25 ×
0.23 × 0.18 mm3, C45H30N4NiO2, M = 717.44, orthorhombic, a =
3
˚
˚
˚
˚
17.0768(12) A, b = 14.1377(10) A, c = 27.7514(19) A, V = 6699.9(8) A ,
T = 130(2) K, space group Pbcn, Z = 8, qcalcd = 1.423 Mg m−3
,
l = 0.627 mm−1, 2hmax = 50◦, MoKa (k = 0.71073). A total of 78224
reflections were measured, of which 5956 (Rint = 0.0526) were unique.
Final residuals were R = 0.0441 and wR2 = 0.1025 (for 5104 observed
reflections with I > 2r(I), 500 parameters) with GOF 1.231 and largest
residual peak 0.322 e A and hole −0.405 e A−3. R1 = 0.0533 and
−3
˚
˚
wR2 = 0.1073 for all data.
26 Crystal data for 5d: dark blue block, 0.15 × 0.11 × 0.10 mm3,
˚
C45H30CuN4O2, M = 722.27, orthorhombic, a = 17.074(3) A, b =
3
˚
˚
˚
14.209(2) A, c = 27.882(4) A, V = 6764.3(19) A , T = 130(2) K, space
group Pbcn, Z = 8, qcalcd = 1.418 Mg m−3, l = 0.693 mm−1, 2hmax
=
52◦, MoKa (k = 0.71073). A total of 72376 reflections were measured,
of which 6870 (Rint = 0.1183) were unique. Final residuals were R =
0.0522 and wR2 = 0.1064 (for 4587 observed reflections with I >
2r(I), 470 parameters) with GOF 1.047 and largest residual peak 0.306
e A and hole −0.572 e A−3. R1 = 0.0926 and wR2 = 0.1233 for all
−3
˚
˚
data.
27 J. Meinwald and P. G. Gassman, J. Am. Chem. Soc., 1960, 82, 2857.
28 J. G. Calvert and J. N. Pitts, Jr., Photochemistry, Wiley, New York,
1966, p. 783.
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4059–4062 | 4061
©

View Article Online
−3
residual peak 1.545 e A and hole −1.013 e A−3. R1 = 0.1465 and
˚
˚
29 N. K. Urdabayev and V. V. Popik, J. Am. Chem. Soc., 2004, 126,
4058.
wR2 = 0.2276 for all data.
30 Crystal data for 4e: brown plate, 0.10
×
0.10
×
0.02 mm3,
˚
31 A. J. Golder, K. B. Nolan, D. C. Povey and L. R. Milgrom, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1988, 44, 1916.
32 W. R. Scheidt, J. U. Mondal, C. W. Eigenbrot, A. Adler, L. J.
Radonovich and J. L. Hoard, Inorg. Chem., 1986, 25, 795.
33 J. A. Shelnutt, C. J. Medforth, M. D. Berber, K. M. Barkigia and K. M.
Smith, J. Am. Chem. Soc., 1991, 113, 4077.
C91H58Cl6N8Ni2O2, M = 1625.57, monoclinic, a◦= 18.111(4) A, b =
3
˚
˚
˚
14.986(4) A, c = 27.852(6) A, b = 102.635(5) , V = 7376(3) A ,
T = 130(2) K, space group P21/n, Z = 4, qcalcd = 1.464 Mg m−3
,
l = 0.787 mm−1, 2hmax = 50◦, MoKa (k = 0.71073). A total of 49219
reflections were measured, of which 13121 (Rint = 0.1224) were unique.
Final residuals were R = 0.0715 and wR2 = 0.1805 (for 7141 observed
reflections with I > 2r(I), 992 parameters) with GOF 1.011 and largest
34 B. J. Kraft and J. M. Zaleski, New J. Chem., 2001, 25, 1281.
35 A. S. Nazran and D. Griller, J. Am. Chem. Soc., 1984, 106, 543.
4062 | Org. Biomol. Chem., 2006, 4, 4059–4062
This journal is
The Royal Society of Chemistry 2006
©