Oxazolochlorins. 2. Intramolecular Cannizzaro reaction of meso-tetraphenylsecochlorin bisaldehyde

Article abstract of DOI:10.1021/jo9006046

(Chemical Equation Presented) Using mildly basic reaction conditions, the periodate-induced diol cleavage of meso-tetraphenyl-2,3-diolchlorin allows for the generation and isolation of the corresponding hitherto elusive free base secochlorin bisaldehyde.

Full text of DOI:10.1021/jo9006046

Oxazolochlorins. 2. Intramolecular Cannizzaro Reaction of
meso-Tetraphenylsecochlorin Bisaldehyde†
Joshua Akhigbe,‡ Claudia Ryppa,‡ Matthias Zeller,§ and Christian Bru¨ckner*,‡
Department of Chemistry, UniVersity of Connecticut, Storrs, Connecticut 06269-3060, and Department of
Chemistry, Youngstown State UniVersity, One UniVersity Plaza, Youngstown, Ohio 44555-3663
c.bruckner@uconn.edu
ReceiVed March 20, 2009
Using mildly basic reaction conditions, the periodate-induced diol cleavage of meso-tetraphenyl-2,3-
diolchlorin allows for the generation and isolation of the corresponding hitherto elusive free base
secochlorin bisaldehyde. An intramolecular Cannizzaro reaction of this porphyrinoid generates three
pyrrole-modified, oxazole-based porphyrins: the known porpholactol (2-oxa-3-hydroxychlorin) as the
major product, known porpholactone (2-oxa-3-oxoporphyrin), and a novel porpholactol dimer that is
linked through an acetal functionality. The structure of the dimer was confirmed by 1H NMR spectroscopy,
X-ray diffractometry, and ESI(+) collision-induced fragmentation mass spectrometry. The chromophores
in the dimer are coupled electronically only to a minor extent. A mechanism to rationalize the formation
of all products is advanced.
Introduction
The synthetic manipulation of the ꢀ,ꢀ′-bonds of porphyrins
offers also many options to convert one (or more) pyrrole to a
nonpyrrolic heterocycle, generating chlorin-like chromophores
or, more generally, pyrrole-modified porphyrins. Early examples
of pyrrole-modified porphyrins using this synthetic strategy were
discovered by serendipity,6,7 but work by the groups of Callot,8
The development of novel synthetic methodologies toward
chlorins and related oligopyrrolic macrocycles constitutes a
significant portion of current porphyrin research. Two principal
approaches can be pursued:1 total synthesis or the conversion
of a porphyrin. Particularly owing to the recent efforts by the
group of Lindsey, the total synthesis and derivatization of
chlorins (and bacteriochlorins) has recently become very ef-
ficient,2 but methods that induce the conversion of a porphyrin
to a chlorin promise also to be versatile and scaleable as the
readily synthesized meso-tetraarylporphyrins3 or octaalkylpor-
phyrin4 can be used as starting materials.5
(2) For recent leading examples, see: (a) Muthiah, C.; Bhaumik, J.; Lindsey,
J. S. J. Org. Chem. 2007, 72, 5839–5842. (b) Ptaszek, M.; McDowell, B. E.;
Taniguchi, M.; Kim, H.-J.; Lindsey, J. S. Tetrahedron 2007, 63, 3826–3839. (c)
Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Lindsey, J. S. Tetrahedron 2007,
63, 3840–3849. (d) Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Boyle, P. D.;
Lindsey, J. S. Tetrahedron 2007, 63, 3850–3863. (e) O’Neal, W. G.; Jacobi,
P. A. J. Am. Chem. Soc. 2008, 130, 1102–1108. (f) Borbas, K. E.; Ruzie´, C.;
Lindsey, J. S. Org. Lett. 2008, 10, 1931–1934. (g) Muthiah, C.; Ptaszek, M.;
Nguyen, T. M.; Flack, K. M.; Lindsey, J. S. J. Org. Chem. 2007, 72, 7736–
7749. (h) Ruzie´, C.; Krayer, M.; Balasubramanian, T.; Lindsey, J. S. J. Org.
Chem. 2008, 73, 5806–5820, and references therein.
(3) Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher, J.; Assour, J.;
Korsakoff, L. J. Org. Chem. 1967, 32, 476.
(4) Sessler, J. L.; Mozaffari, A.; Johnson, M. R. Org. Synth. 1992, 70, 68–
78.
(5) For reviews covering chlorin syntheses, see: (a) Flitsch, W. AdV.
Heterocycl. Chem. 1988, 43, 73–126. (b) Sternberg, E. D.; Dolphin, D.; Bru¨ckner,
C. Tetrahedron 1998, 54, 4151–4202. (c) Galezowski, M.; Gryko, D. T. Curr.
Org. Chem. 2007, 11, 1310–1338.
(6) Chang, C. K.; Wu, W.; Chern, S.-S.; Peng, S.-M. Angew. Chem., Int.
Ed. Engl. 1992, 31, 70–72.
* To whom correspondence should be addressed. Tel: (+1) 860 486-2743.
Fax: (+1) 860 486-2981.
† Oxazolochlorins. 1. See: McCarthy, J. R.; Melfi, P. J.; Capetta, S. H.;
Bru¨ckner, C. Tetrahedron 2003, 59, 9137-9146.
‡ University of Connecticut.
§ Youngstown State University.
(1) (a) Sessler, J. L.; Gebauer, A.; Vogel, E. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego,
2000; Vol. 2, pp 1-54. (b) Sessler, J. L.; Gebauer, A.; Weghorn, S. J. In The
Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: San Diego, 2000; Vol. 2, pp 55-124. (c) Lash, T. D. In The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press:
San Diego, 2000; Vol. 2, pp 125-200.
10.1021/jo9006046 CCC: $40.75  2009 American Chemical Society
Published on Web 06/02/2009
J. Org. Chem. 2009, 74, 4927–4933 4927

Akhigbe et al.
SCHEME 1. Synthesis of Morpholinochlorins13,14
We report here a method toward the synthesis and isolation
of free base secochlorin bisaldehyde 2H2. Furthermore, we
introduce an intramolecular Cannizzaro reaction of 2H2. This
new synthetic methodology generates known monomeric and a
new dimeric oxazolochlorins, pyrrole-modified porphyrins in
which one of the pyrroles was formally replaced by an oxazole
moiety.
Results and Discussion
Synthesis of Free Base meso-Tetraphenylsecochlorin Bis-
aldehyde (2H2). We previously explored the in situ prepara-
tion14 and reactivity17 of 2H2 under acidic reaction conditions
and realized its high reactivity. We therefore decided to test its
formation and reactivity using Lewis and Brønsted basic reaction
conditions. Thus, reaction of the purple, polar (Rf ) 0.12,
silica-CH2Cl2) diolchlorin 3H2 in THF containing 1-2 vol %
Et3N with IO4-, heterogenized onto silica gel, converts it in
essentially quantitative yields into a brown, nonpolar pigment
(Rf ) 0.61, silica-CH2Cl2) (Scheme 2).
Column chromatography (silica gel, CH2Cl2-0.1% Et3N)
allows the isolation of a reactive compound with the spectro-
scopic properties that characterize it as bisaldehyde 2H2.
Notably, its nonchlorin-like UV-vis spectrum displays a split
Soret band and broad side bands that also have been observed
to be diagnostic features for the Ni(II) complex of secochlorin
bisaldehydes (2Ni) and related compounds (Figure 1).15,16 The
NMR spectra of 2H2 reflect its 2-fold symmetry and show the
signals for an aldehyde group (δ ) 9.64 ppm for CHO and 188
ppm for CHO, respectively) that is also evident in its IR
spectrum (neat, νCdO ) 1675 cm-1). In solution, particularly in
acidic and/or wet solvents or on silica gel, this bisaldehyde tends
to decompose within several hours.22 Evaporated to dryness and
kept in a freezer at -18 °C, 2H2 is stable over several months.
Filtration of the crude reaction mixture to remove the oxidant
(with or without being followed by a removal of the solvent by
rotary evaporation) produces suitably pure secochlorin bisal-
dehyde 2H2 for subsequent transformations. For instance,
morpholinochlorin 1H2 is formed upon reaction with an alcohol
and catalytic amounts of acid (HCl fumes).14
Crossley,9 Bonnett,10 Pandey,11 Zaleski,12 and us13-20 point
toward the wide potential of a controlled, stepwise transforma-
tion of a porphyrinic ꢀ,ꢀ′-bond.
We demonstrated the synthesis of meso-tetraphenylmorpholi-
nochlorin (1Ni) and noticed a profound metal-templating
effect.13,14 While the Pb(OAc)4- or IO4--mediated oxidations
of [meso-tetraaryl-2,3-diolchlorinato]Ni(II) generate the stable
and crystallographically characterized bisaldehyde 2Ni,15,16 and
in a subsequent reaction 1Ni,13 the high reactivity of free base
2H2 allowed only its in situ preparation, whereby it can be
trapped in high yields as a stable double-acetal, free base
morpholinochlorin 1H2 (Scheme 1).14
Another area of interest in current porphyrin research is the
synthesis and photophysical characterization of porphyrinoid
dimers and oligomers. Typically, two or more tetrapyrrolic
macrocycles, such as porphyrins, chlorins, or corroles, are linked
directly or via a spacer of various lengths.21 The study of the
energy-transfer processes in these models promises to lead to a
better understanding of photosynthetic pigment assemblies.
(7) Gouterman, M.; Hall, R. J.; Khalil, G.-E.; Martin, P. C.; Shankland, E. G.;
Cerny, R. L. J. Am. Chem. Soc. 1989, 111, 3702–3707.
(8) (a) Callot, H. Bull. Chem. Soc. Chim. Fr. 1972, 11, 4387–4391. (b) Callot,
H. J.; Schaeffer, E. Tetrahedron 1978, 34, 2295–2300. (c) Callot, H. J. Dalton
Trans. 2008, 6346–6357.
(9) Crossley, M. J.; King, L. G. J. Chem. Soc., Chem. Commun. 1984, 920–
922.
(10) (a) Adams, K. R.; Bonnett, R.; Burke, P. J.; Salgado, A.; Valle´s, M. A.
J. Chem. Soc., Chem. Commun. 1993, 1860–1861. (b) Adams, K. R.; Bonnett,
R.; Burke, P. J.; Salgado, A.; Valle´s, M. A. J. Chem. Soc., Perkin Trans. 1
1997, 1769–1772.
(11) Kozyrev, A. N.; Alderfer, J. L.; Dougherty, T. J.; Pandey, R. K. Angew.
Chem., Int. Ed. 1999, 38, 126–128.
(12) (a) Ko¨pke, T.; Pink, M.; Zaleski, J. M. Org. Biomol. Chem. 2006, 4,
4059–4062. (b) Ko¨pke, T.; Pink, M.; Zaleski, J. M. Chem. Commun. 2006, 4940–
4942.
(13) Bru¨ckner, C.; Rettig, S. J.; Dolphin, D. J. Org. Chem. 1998, 63, 2094–
2098.
(14) McCarthy, J. R.; Jenkins, H. A.; Bru¨ckner, C. Org. Lett. 2003, 5, 19–
22.
(15) Bru¨ckner, C.; Sternberg, E. D.; MacAlpine, J. K.; Rettig, S. J.; Dolphin,
D. J. Am. Chem. Soc. 1999, 121, 2609–2610.
Cannizzaro Reaction of meso-Tetraphenylsecochlorin
Bisaldehyde (2H2). Aldehydes lacking R-hydrogens are sus-
ceptible to a Cannizzaro reaction, a Brønsted base-induced
disproportionation reaction of 2 equiv of, for instance, benzal-
dehyde, to generate 1 equiv each of benzyl alcohol and benzoic
acid.23 Bisaldehyde 2H2 could potentially undergo an intramo-
(22) The decomposition is often accompanied by the forming of a green,
polar (Rf ) 0.10, silica-CH2Cl2), and unstable compound. We tentatively
assigned it, based on its morpholinochlorin-like UV-vis spectrum and mass
(ESI+ HR-MS, 100% MeCN, m/z found 665.2548, corresponding to C44H33N4O3,
expected mass 665.2553), as the hydrate structure 2H2 · H2O. Correspondingly,
it can be converted by addition of EtOH, under acid catalysis, in high yield to
morpholinochlorin 1H2. However, attempts to isolate and fully characterize this
compound failed.
(16) Bru¨ckner, C.; Hyland, M. A.; Sternberg, E. D.; MacAlpine, J.; Rettig,
S. J.; Patrick, B. O.; Dolphin, D. Inorg. Chim. Acta 2005, 358, 2943–2953.
(17) McCarthy, J. R.; Hyland, M. A.; Bru¨ckner, C. Org. Biomol. Chem. 2004,
2, 1484–1491.
(18) Daniell, H. W.; Bru¨ckner, C. Angew. Chem., Int. Ed. 2004, 43, 1688–
1691.
(19) Lara, K. K.; Rinaldo, C. K.; Bru¨ckner, C. Tetrahedron 2005, 61, 2529–
2539.
(20) Ryppa, C.; Niedzwiedzki, D.; Morozowich, N. L.; Rapole, S.; Zeller,
M.; Frank, H. A.; Bru¨ckner, C. Chem.sEur. J. 2009, 15, 5749-5762.
(21) For recent representative examples, see: (a) Matano, Y.; Matsumoto,
K.; Nakao, Y.; Uno, H.; Sakaki, S.; Imahori, H. J. Am. Chem. Soc. 2008, 130,
4588–4589. (b) Hisaki, I.; Hiroto, S.; Kim, K. S.; Noh, S. B.; Kim, D.; Shinokubo,
H.; Osuka, A. Angew. Chem., Int. Ed. 2007, 46, 5125–5128. (c) Kelley, R. F.;
Lee, S. J.; Wilson, T. M.; Nakamura, Y.; Tiede, D. M.; Osuka, A.; Hupp, J. T.;
Wasielewski, M. R. J. Am. Chem. Soc. 2008, 130, 4277–4284. (d) Esdaile, L. J.;
Jensen, P.; McMurtrie, J. C.; Arnold, D. P. Angew. Chem., Int. Ed. 2007, 46,
2090–2093. (e) Lysenko, A. B.; Thamyongkit, P.; Schmidt, I.; Diers, J. R.;
Bocian, D. F.; Lindsey, J. S. J. Porphyrins Phthalocyanines 2006, 10, 22–32.
(f) Song, H.; Kirmaier, C.; Taniguchi, M.; Diers, J. R.; Bocian, D. F.; Lindsey,
J. S.; Holten, D. J. Am. Chem. Soc. 2008, 130, 15636–15648, and references
therein.
(23) (a) Cannizzaro, S. Liebigs Ann. Chem. 1853, 88, 129–130. Intramolecular
Cannizzaro reactions of aromatic Vic-bisaldehydes: (b) McDonald, R. S.; Sibley,
C. E. Can. J. Chem. 1981, 59, 1061–1067. (c) Bowden, K.; El-Kaissi, F. A.;
Ranson, R. J. J. Chem. Soc., Perkin Trans. 2 1990, 2089–2092. (d) Anvia, F.;
Bowden, K. J. Chem. Soc., Perkin Trans. 2 1990, 2093–2098.
4928 J. Org. Chem. Vol. 74, No. 14, 2009

Cannizzaro Reaction of meso-Tetraphenylsecochlorin Bisaldehyde
SCHEME 2. Synthesis and Cannizzaro Reaction Products of Secochlorin Bisaldehyde 2H2
lecular Cannizzaro reaction. When a solution of brown, nonpolar
2H2 in THF is treated with a large molar excess of a 30%
aqueous solution of Et4NOH in THF, three purple products are
formed in varying yields (Scheme 2). The product of intermedi-
ate polarity (Rf ) 0.78, silica-CH2Cl2) could be identified as
known porpholactone 6H2.14,24 Its formation has no diagnostic
value whether a Cannizzaro reaction has taken place, or not, as
we have observed its occurrence in a range of reactions
involving diol 3, secochlorins 2 or other pyrrole-modified
porphyrins.25 It appears that this compound is a thermodynamic
sink in the oxidative ꢀ,ꢀ′-degradation pathways of por-
phyrins.7,9,11,14,25
The most polar compound (Rf ) 0.41, silica-CH2Cl2), formed
in up to 59% isolated yields, showed a chlorin-like UV-vis
spectrum (Figure 1) and could be identified as known por-
pholactol 4H2.24,26 Considering that this oxazolochlorin deriva-
tive 4H2 was previously made by reduction of 6H2, which itself
was made by oxidation of diol 3H2,14,24 the Cannizzaro pathway
to free base porpholactol is more direct. Alas, the overall yields
from diol 3H2 along both methods are comparable.
7H2.25 Of note are the greater chemical stability of the methyl
acetal compared to the hemiacetal and the fact that this
transformation is not reflected in the optical properties of the
compound (Figures 1 and 2).
The third, least polar (Rf ) 0.90, silica-CH2Cl2) compound,
5H2, is isolated in yields up to 11%. Its UV-vis spectrum is
chlorin-like and similar to that of porpholactol 4H2 (or its methyl
acetal 7H2), with the exception of the presence of a 9 nm red-
shifted Soret band that also displays a distinct shoulder at 400
nm (Figure 2).
The NMR spectrum of 5H2 reflects its lack of any plane of
symmetry, rendering, for instance, all six ꢀ-protons nonequiva-
lent. Also, the splitting of the signals assigned to the phenyl
o-protons is suggestive of the lack of a plane of symmetry
parallel to the mean plane of the chromophore and is indicative
of the presence of a chlorin-type sp3-carbon carrying four
1
different substituents. In all of these aspects, the H NMR
spectrum is similar to that of 7H2, but stark differences exist
also. For instance, the signals assigned to one phenyl group are
spread and shifted high field between 4.9 and 7.7 ppm. In
comparison, the corresponding signals for 7H2 are found within
An acid-catalyzed reaction of 4H2 in the presence of MeOH
converts it in high yields to the corresponding methyl acetal
FIGURE 1. UV-vis spectra (CH2Cl2) of 2H2 (dotted trace) and 4H2
(solid trace).
FIGURE 2. Overlay of UV-vis spectra (CHCl3) of 7H2 (broken trace)
and 5H2 (solid trace).
J. Org. Chem. Vol. 74, No. 14, 2009 4929

Akhigbe et al.
1
FIGURE 3. Low-field region of H NMR (500 MHz, CDCl3, rt) of 5H2 and 7H2.
a 0.5 ppm span between 7.6 and 8.1 ppm.27 This type of shift
and spread has been shown to be characteristic for a ꢀ-to-phenyl
ring-closure reaction.17,18,28 However, such reactions are gener-
ally also characterized by a significant bathochromic shift of
λ
max as a result of the increased conjugation of the phenyl group
with the chromophore,18 but this is not observed here (Fig-
ure 2).
Compared to the position of the signals of the corresponding
protons in 7H2, a number of other changes are notable: a 0.6
ppm low-field-shifted signal for the oxazole proton and a 0.5
ppm high-field-shifted ꢀ-proton signal. Dramatic shifts of the
NMR signals can be the result of two interacting aromatic
π-systems, suggestive of a dimeric structure of 7H2.29 In support
of this, reaction of 5H2 with MeOH and catalytic quantities of
acid generated quantitatively acetal 7H2 (Scheme 2), indicative
of the presence of a acetal-type dimer structure of 5H2.
Mass spectrometry also provides a number of clear indications
for the structural assignment of 5H2. The ESI(+) mass spectra
of porpholactol 4H2 and its acetal 7H2 display a minor signal
for [4H2 ·H]+ and [7H2 ·H]+ respectively, and a dominating
signal for 8+, the carbocation resulting from the protonated
parent compound after the loss of H2O or MeOH, respectively
(Figure 4). The high abundance of 8+ corresponds well with
the projected stability of this highly stabilized carbocation. The
ESI(+) mass spectrum of [5H2 ·H]+ indicates a mass that is
nearly twice as high as that for 4H2. Its composition, as
determined by ESI(+) HR-MS, is C86H59O3, i.e., corresponding
to [{(2 × 4H2) - H2O}·H]+. Moreover, another peak corre-
FIGURE 4. Interpreted ESI(+) MS and MS2 data for 4H2 and 5H2
(100% CH3CN, 30 V cone voltage).
sponding to the diprotonated species [5H2 ·2H]2+ (at m/z )
626.3; dicationic charge indicated by the 1/2 amu isotope pattern
separation) is visible, providing further support for the presence
of a structure containing two porphyrinoid moieties. The tandem
ESI(+) mass spectrum of the putative dimer [5H2 ·H]+ (at m/z
) 1251.5) displays one signal corresponding to 8+, whereas
the tandem ESI(+) mass spectrum for the diprotonated species
shows a signal for 8+ and [4H2 ·H]+ (Figure 4), suggestive of
5H2 indeed being the acetal dimer of 4H2.
This interpretation rationalizes also all spectroscopic findings.
The altered UV-vis spectrum of 5H2 compared to that of 4H2/
7H2 reflects only a small exciton coupling between the chro-
mophores, suggestive of the absence of, for instance, a cofacial
dimer and a possible orthogonal relative arrangement of the two
chromophores.30 In fact, since the single sp3-oxygen atom is
linking two sp3-carbons, the two chromophores cannot be
arranged coplanar to each other. The NMR data are reflective
of the short linkage as the diatropic ring current of one
oxazolochlorin affects the shifts of the protons on the other
oxazolochlorin, and particularly those that are in between the
two chromophores (the oxazole hydrogen and one phenyl
group). The presence of both high- and low-field shifted proton
(24) McCarthy, J. R. Ph.D. Thesis, University of Connecticut, 2003.
(25) McCarthy, J. R.; Melfi, P. J.; Capetta, S. H.; Bru¨ckner, C. Tetrahedron
2003, 59, 9137–9146.
(26) Bru¨ckner, C.; McCarthy, J. R.; Daniell, H. W.; Pendon, Z. D.; Ilagan,
R. P.; Francis, T. M.; Ren, L.; Birge, R. R.; Frank, H. A. Chem. Phys. 2003,
294, 285–303.
(27) All the assignments were backed by H,H and H,C-COSY measurements;
see the Supporting Information.
(28) (a) Barloy, L.; Dolphin, D.; Dupre´, D.; Wijesekera, T. P. J. J. Org.
Chem. 1994, 59, 7976–7985. (b) Review article: Fox, S.; Boyle, R. W.
Tetrahedron 2006, 62, 10039–10054.
(29) For an example of a chlorin dimer, see: (a) Jaquinod, L.; Nurco, D. J.;
Medforth, C. J.; Pandey, R. K.; Forsyth, T. P.; Olmstead, M. M.; Smith, K. M.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1013–1016. For examples of the 1H
NMR shifts expressed by directly ꢀ,ꢀ′-linked porphyrin dimers, see: (b)
Bringmann, G.; Go¨tz, D. C. G.; Gulder, T. A. M.; Gehrke, T. H.; Bruhn, T.;
Kupfer, T.; Radacki, K.; Braunschweig, H.; Heckmann, A.; Lambert, C. J. Am.
Chem. Soc. 2008, 133, 17812–17825.
(30) Hunter, C. A.; Sanders, J. K. M.; Stone, A. J. Chem. Phys. 1989, 133,
395–404.
4930 J. Org. Chem. Vol. 74, No. 14, 2009

Cannizzaro Reaction of meso-Tetraphenylsecochlorin Bisaldehyde
FIGURE 6. Lowest frequency normal-coordinate structural decomposi-
tion results for the C19N4O macrocycles of ring A and ring B of 5H2.26
FIGURE 5. Stick representation of the single-crystal structure of 5H2.
All hydrogen atoms were omitted for clarity.
SCHEME 3. Proposed Cannizzaro Reaction Sequence and
Consecutive Fundamental Steps toward the Formation of the
Oxazole-Derived Chromophores
signals is indicative of a relative arrangement of the two
porphyrinoids that exposes one oxazolochlorin moiety to the
shielding and deshielding regions of the other π-system.
Interestingly, the NMRs do not indicate the formation of
diastereomers despite the presence of two chiral carbons in the
dimer.
The synthesis of porphyrin dimers is frequently rather
involved,21 but one other serendipitous, photochemically in-
duced, formation of a (metallo)chlorin-type chromophore was
recently reported,12 as well as chlorin dimers,29a and a directly
linked ꢀ,ꢀ′-porphyrin dimers prepared in one step.29b
Structural Characterization of Dimer 5H2. The ultimate
proof of the spectroscopically derived dimeric structure for 5H2
was provided by single-crystal X-ray diffractometry. Figure 5
shows a stick representation of the result. Indeed, two oxazole-
derived chlorin-like moieties are linked via an acetal-type
oxygen. As a result of the sterics imposed by the sequence of
the three sp3-hybridized atoms making up the linkage and the
large size of the linked moieties, the two mean planes of the
chromophores are nearly perpendicular to each other (79° angle
between the two C19N4O oxazolochlorin mean planes), whereby
the two pairs of meso-phenyl groups flanking the linking oxazole
(PhC3-8/PhC36-41 and PhC47-52/PhC80-85, respectively) are arranged
in a cog-wheeled fashion, allowing the expression of multiple
π-edge-to-π-center interactions. This tight packing mode may
also be suggestive of a low conformational flexibility of the
an overall rms of the C19N4OAg macrocycle of only 0.0551
Å.32 With the caveat that the conformational differences in all
these three oxazolochlorins are relatively small, we believe that
they are nevertheless indicative of a significant structural
flexibility of the free base oxazolochlorin macrocycles.
Dimer 5H2 is chiral, containing two homochiral centers (both
sp3 oxazolochlorin carbons) but crystallizes as a racemic mixture
j
in the (nonchiral) centrosymmetric space group P1. Evidently,
establishment of the chirality of the first chiral center enforces
the homochirality of the second. Molecular models show that a
heterochiral linkage appears to cause more steric inhibition and
does not allow for the observed cog-wheeled arrangement of
the phenyl groups.
Mechanistic Considerations. Are the occurrence of products
4H2 and 5H2 an indication that an intramolecular Cannizzaro
reaction has taken place? We suggest that this question can be
answered in the affirmative. An intramolecular Cannizzaro
reaction of 2H2 generates the benzyl alcohol carboxylic acid
intermediate A (Scheme 3). We suggest that acid A decarboxy-
lates to form putative intermediate B before undergoing an
oxidative ring-closure step to form C. The decarboxylation step
has its parallel in the decarboxylation of the putative diacid
compound formed by MnO4--oxidation of diol 3H2 and that
1
linkage. In fact, low-temperature (-10 °C) H NMR studies
lead to a minor sharpening of a few signals but to no further
shifts.
The solid-state structure is idealized 2-fold symmetric, with
an axis of rotation projecting between the molecules through
the linking acetal oxygen. As demonstrated above, the two
chromophores are equivalent by NMR. However, in the crystal
structure, the conformations of rings A and B differ from each
other. The root-mean-square (rms) deviation from planarity of
the C19N4O moiety of ring A is 0.0617 Å, while it is 0.2073 Å
for the corresponding plane in ring B. However, their modes
of nonplanarity, as analyzed by the normal-coordinate structural
decomposition (NSD) procedure, are not fundamentally different
from each other (Figure 6).31
(31) (a) Shelnutt, J. A. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 7, pp 167-
224. (b) Jentzen, W.; Song, X.-Z.; Shelnutt, J. A. J. Phys. Chem. B. 1997, 101,
1684–1699. (c) Song, L.; Shelnutt, J. A. NSD Engine Version 3.0 (http://
jasheln.unm.edu/jasheln/content/nsd/NSDengine/start.htm).
(32) Zeller, M.; Hunter, A. D.; McCarthy, J. R.; Capetta, S. H.; Bru¨ckner,
C. J. Chem. Crystallogr. 2005, 35, 935–942.
Both rings are predominantly saddled, with some ruffled and
a minor waving (x) contribution. The previously structurally
characterized Ag(II) complex of 7H2 was nearly planar, with
J. Org. Chem. Vol. 74, No. 14, 2009 4931

Akhigbe et al.
SCHEME 4. Results of the Cannizzaro Reaction of the
Ni(II) Complex of Secochlorin Bisaldehyde 2Ni
allowed to react for ∼3 h. Additional oxidant (∼0.2 g) was added
until all starting material, as monitored by TLC, was consumed.
Upon completion, the reaction mixture was passed through a glass
frit (M) containing some neutral alumina, and the filter cake was
washed with THF until the filtrate was nearly colorless. The
combined filtrates were evaporated to dryness by rotary evaporation.
Product 2H2 was generally used immediately without any further
purification. A 100% conversion of 3H2 was assumed (30 mg crude
2H2). Spectroscopic data for 2H2: Rf (silica-CH2Cl2) 0.61; 1H NMR
(400 MHz, CDCl3) 9.81 (s, 1H), 9.0 (br s, 1H), 8.41 (d, 3J ) 4 Hz,
3
1H), 8.2 (d, J ) 4 Hz, 1H), 7.7-7.3 (overlapping signals, 10H),
1.1 (s, 1H); 1H NMR (400 MHz, DMSO) 9.64 (s, 1H), 8.32 (d, 3J
) 4 Hz, 1H), 8.16 (d, 3J ) 4 Hz, 1H), 8.07 (s, 1H), 7.98-7.18 (m,
10H), 0.96 (s, 1H, exchangeable with D2O); 13C NMR (100 MHz,
DMSO) 187.9, 153.7, 151.9, 143.0, 139.8, 139.6, 137.9, 133.8,
133.7, 129.7, 129.4, 128.8, 128.6, 127.8, 127.2, 125.4, 124.5, 120.8;
UV-vis (CHCl3) λmax (rel intens) 407 (0.89), 467 (1.00), 532 (0.21),
596 nm (0.12); MS (ESI, 100% CH3CN, cone voltage 30 eV) m/z
647 ([M · H]+); HR-MS (ESI+, 100% CH3CN) calcd for
C44H31N4O2 ([M·H]+) 647.2442, found 647.2433.
ring closes to generate porpholactone 6H2 (though nothing is
known about the exact mechanism of this reaction).9,24 Previous
results reported by us have also shown that the benzylic position
in the oxazole-derived chromophore C is very sensitive toward
further (air) oxidation.24 Further considering that free base
chlorins are generally good photosensitizers, the formation of
the observed oxidation products is readily rationalized. Cor-
respondingly, the formation of 5H2 can be suppressed signifi-
cantly by running the reaction under anaerobic conditions
(though the workup still took place under regular light and
aerobic conditions).
Cannizzaro Reaction on [meso-Tetraphenylsecochlorina-
to]Ni(II) (1Ni). Exposure of the stable Ni(II) complex of
secochlorin 2Ni to the identical strongly basic conditions
described above (THF, aq Et4NOH) also elicits a Cannizzaro
reaction (Scheme 4). However, next to the hemiacetal ox-
azolochlorin Ni(II) complex 4Ni as the main product (56-65%
isolated yields) and some porpholactone 6Ni (<5%), traces of a
few other products are observed, but none of them could be
assigned a Ni2-dimer structure corresponding to 5H2. This result
again highlights the influence of the central metal on the
outcome of a reaction on the ꢀ-positions of porphyrins.17,33
Hemiacetal 4Ni could be converted in high yields to its
corresponding methyl acetal 7Ni.
Cannizzaro Reaction of 2H2 to Generate meso-Tetraphenyl-2-
hydroxy-3-oxachlorin (4H2), meso-Tetraphenyl-2-oxa-3-oxochlo-
rinato (6H2), and (meso-Tetraphenyl-3-oxa-2-yl-chlorin)2O (5H2).
Crude bisaldehyde (30 mg, 4.64 × 10-5 mol) was dissolved in THF
(10 mL) in a round-bottom flask equipped with a magnetic stirring
bar and a N2 inlet/bubbler. Et4NOH (1.0 mL of a 30 wt % solution
in H2O) was added and the mixture stirred at ambient temperature
for 10-15 min. When the starting material was consumed (reaction
control by UV-vis and TLC), the reaction mixture was washed
with water (2 × 10 mL), dried over anhyd Na2SO4, and evaporated
to dryness by rotary evaporation. The resulting mixture was
separated on a preparative TLC plate (silica, CH2Cl2-petroleum
ether 1:1). Isolated yields for 4H2 ranged from 36 to 59% yield
(10.5 to 17.8 mg), for 5H2 from 5 to 11% (3.0 to 6.5 mg; note: the
more rigorously oxygen was excluded, the lower the yield of this
products), and for 6H2 from 10 to 25% (3.0 to 7.4 mg).
1
Spectroscopic data for 5H2: Rf (silica-CH2Cl2) 0.90; H NMR
3
3
(500 MHz, CDCl3) 8.73 (d, J ) 5.0 Hz, 1H), 8.57 (d, J ) 4.5
Hz, 1H), 8.42 (d, 3J ) 4.5 Hz, 1H), 8.38 (d, 3J ) 4.5 Hz, 1H), 8.32
3
3
(d, J ) 4.5 Hz, 1H), 8.18-8.22 (m, 3H), 8.02-8.00 (d, J ) 7.5
Hz, 2H), 7.80-7.74 (m, 6H), 7.67-7.56 (m, 5H), 7.53 (br s, 1H),
3
3
7.50 (t, J ) 7.5 Hz, 1H), 7.33 (br s, 1H), 6.83 (d, J ) 7.5 Hz,
3
3
1H), 6.72 (t, J ) 7.5 Hz, 1H), 4.95 (t, J ) 7.5 HZ, 1H), -0.79
(s, 1H, exchangeable with D2O), -1.06 (s, 1H, exchangeable with
D2O); 13C NMR (125 MHz, CDCl3) 164.0, 154.9, 151.6, 149.9,
142.6, 141.7, 141.6, 140.8, 138.5, 138.2, 136.7, 134.4, 134.1, 133.9,
133.6, 133.5, 133.4, 132.1, 131.7, 129.6, 127.7, 127.5, 127.3, 127.2,
126.9, 126.7, 126.6, 125.9, 125.8, 125.1, 122.0, 121.1, 112.0, 100.5,
99.7; for FT-IR (neat) see the Supporting Information; UV-vis
(CHCl2) λmax (log Σ) 425 (5.42), 516 (4.32), 552 (4.35), 593 (4.06),
646 (4.68) nm; Fl (CH2Cl2, λexcitation ) 418 nm) λmax (rel intensity):
651 (1.0), 709 (0.07) nm; HR-MS (ESI+, 100% CH3CN) m/e calcd
for C86H59N8O3 ([M ·H]+) 1251.4710, found 1251.4888 (∆ ) 14
ppm); HR-MS (FAB, PEG) m/e calcd for C86H58N8NaO3 ([M ·Na]+)
1273.4530, found 1273.4590.
Conclusions
We have demonstrated that free base secochlorin 2H2 can
be prepared. Secochlorin bisaldehydes are susceptible to an
intramolecular Cannizzaro reaction, a novel pathway toward
the generation of pyrrole-modified porphyrins. This method
represents an alternative to the established syntheses of
monomeric porpholactol 4H2 but offers also an all together
novel pathway toward chiral dimeric chlorin-type chro-
mophores (5H2).
Spectroscopic data for 4H2 and 6H2 were identical to those
reported in the literature.20,22,24
Experimental Section
meso-Tetraphenyl-2-methoxy-3-oxachlorin (7H2). Excess MeOH
(1 mL) was added to a stirring solution of 4H2 (100 mg, 15.7 mmol)
in CH2Cl2 (20 mL). Traces of TFA vapors (from a TFA bottle head
space, delivered via pipet) were added, and the reaction was
monitored by TLC for completion. The acid was then neutralized
with Et3N (1 drop) and the solution washed, dried over anhyd
MgSO4, evaporated to dryness, purified by column or preparative
plate chromatography, and recrystallized by slow solvent exchange
from CH2Cl2 to MeOH to provide 90% (92 mg) isolated yield: Rf
) 0.91 (silica-CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 8.60 (dd,
X-ray Single-Crystal Diffractometry of 5H2. All experimental
details are provided in the Supporting Information.
meso-Tetraphenylsecochlorin Bisaldehyde (2H2). meso-Tetraphe-
nyl-2,3-dihydroxychlorin (3H2) (30 mg, 4.62 × 10-5 mol) was
dissolved in THF (10 mL) containing Et3N (5 drops) at rt in a round-
bottom flask equipped with a magnetic stirring bar. The flask was
shielded from ambient light with aluminum foil. Silica gel-supported
NaIO4 (∼0.9 g) was added to the stirring reaction mixture and
4
3
4
3J ) 5.0, J ) 1.6 Hz, 1H), 8.52 (dd, J ) 4.6, J ) 1.8 Hz, 1H),
(33) Buchler, J. W.; Dreher, C.; Herget, G. Liebigs Ann. Chem. 1988, 43–
3
4
3
54.
8.45 (dd, J ) 5.0, J ) 1.6 Hz, 1H), 8.43 (d, J ) 4.6 Hz, 1H),
4932 J. Org. Chem. Vol. 74, No. 14, 2009

Cannizzaro Reaction of meso-Tetraphenylsecochlorin Bisaldehyde
3
3
4
8.35 (d, J ) 4.4 Hz, 1H), 8.21 (dd, J ) 4.6, J ) 1.8 Hz, 1H),
8.07 (br s, 3H), 8.14 (m, 3H), 7.95 (br s,1H), 7.85 (m, 1H), 7.71
(m, 12H), 7.56 (s, 1H), 3.28 (s, 3H), -0.73 (s, 1H), -1.11 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 165.0, 155.1, 152.0, 150.0, 142.0,
136.8, 134.8, 134.0, 133.9, 133.6, 131.9, 131.3, 129.8, 128.1, 128.0,
128.0, 127.9, 127.7, 127.6, 127.1, 126.9, 125.2, 122.1, 112.3, 106.5,
100.3, 54.9; for FT-IR (neat), see the Supporting Information;
UV-vis (CH2Cl2) λmax (log ε): 418 (5.20), 515 (4.00), 550 (4.07),
592 (3.83), 646 (4.38) nm; Fl (CH2Cl2, λexcitation ) 420 nm) λmax
(rel intensity): 653 (1.0), 705 (0.08) nm; HR-MS (FAB+, PEG)
m/z calcd for C44H33O2N4 ([M·H]+) 649.2604, found 649.2629.
[meso-Tetraphenyl-2-hydroxy-2-oxachlorinato]Ni(II) (4Ni). Pre-
pared, next to porpholactone Ni(II) complex 6Ni, according to the
general Cannizzaro procedure. The reaction mixture was separated
by preparative TLC (silica, CH2Cl2-petroleum ether 90:10). At a
4.2 × 10-5 mol scale: 5% of 6Ni and 4Ni in 56 to 65% isolated
127.4, 127.0, 126.9, 124.9, 121.2, 120.3, 100.7; UV-vis (CHCl2)
λ
max (log ε) 415 (5.24), 543 (3.96), 586 (4.49) nm; HR-MS (ESI+,
100% CH3CN) m/z calcd for C43H27N4NiO2 ([M ·H]+) 689.1487,
found 689.1536.
[meso-Tetraphenyl-2-methoxy-2-oxachlorinato]Ni(II) (7Ni). Pre-
pared from 4Ni (30 mg, 4.33 × 10-2 mmol) as described for the
preparation of 7H2 from 4H2. Yield after recrystallization by slow
solvent exchange from CH2Cl2 to MeOH, 94% (28.6 mg): Rf
1
3
(silica-CH2Cl2) 0.86; H NMR (500 MHz, CDCl3) δ 8.32 (d, J
3
3
) 5.0 Hz, 1H), 8.31 (d, J ) 5.0 Hz, 1H), 8.23 (d, J ) 5.0 Hz,
1H), 8.16 (d, 3J ) 5.0 Hz, 1H), 8.08 (d, 3J ) 5.0 Hz, 1H), 8.01 (d,
3J ) 5.0 Hz, 1H), 7.99-7.72 (br, 5H), 7.71-7.45 (m, 15H), 7.31
(s, 1H), 3.28 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 157.0, 151.6,
146.9, 142.9, 140.5, 140.1, 139.7, 138.5, 138.2, 137.4, 136.4, 133.3,
133.1, 132.8, 131.8, 129.8, 129.2, 128.2, 127.9, 127.8, 127.7, 127.6,
127.3, 127.0, 126.9, 125.8, 125.5, 121.4, 112.6, 105.4, 96.6, 54.7;
UV-vis (CH2Cl2) λmax (log ε) 408 (5.02), 499 (3.58), 567 (3.80),
607 (4.47) nm; MS (ESI+, 100% CH3CN) m/z 704.2 (M ·H+), 673.2
(M - OMe)+; HR-MS (ESI+, 100% CH3CN) m/z calcd for
C43H27N4NiO ([M - OMe]+) 673.1538, found 673.1611.
1
yields: Rf (silica-CH2Cl2) 0.69; H NMR (500 MHz, CDCl3) δ
8.33 (d, 3J ) 5.0 Hz, 1H), 8.31 (d, 3J ) 4.5 Hz, 1H), 8.24 (d, 3J )
4.8 Hz, 1H), 8.17 (d, 3J ) 4.4 Hz, 1H), 8.10 (d, 3J ) 4.8 Hz, 1H),
7.98 (d, 3J ) 4.8 Hz, 1H), 7.82-7.81 (m, 5H), 7.68-7.54 (m, 16H),
3.47 (d,3J ) 7.6 Hz, 1H, exchangeable with D2O); 13C NMR (100
MHz, CDCl3/10% CD3OD) δ 160.3, 154.9, 150.2, 146.2, 143.7,
143.4, 143.0, 141.8, 141.5, 140.6, 139.7, 136.5, 136.3, 136.1, 135.1,
133.1, 132.4, 131.5, 131.1, 130.9, 130.6, 130.3, 130.2, 129.1, 128.9,
124.7, 115.9, 108.6, 100.0; UV-vis (CH2Cl2) λmax (log ε) 408
(4.93), 499 (3.53), 567 (3.74), 607 (4.39) nm; HR-MS (ESI+, 100%
CH3CN) m/z calcd for C43H28N4NiO2 ([M]+) 690.1566, found
690.1582.
Acknowledgment. This work was supported by the US
National Science Foundation under Grant Nos. 0517782 and
0730826 (to C.B.). The diffractometer was funded by NSF Grant
No. 0087210, by the Ohio Board of Regents Grant No. CAP-
491, and by YSU.
1
Supporting Information Available: H, 13C NMR, and IR
[meso-Tetraphenyl-2-oxa-3-oxoporphyrinato]Ni(II) ([meso-tet-
raphenylporpholactonato]Ni(II), 6Ni): Rf (silica-CH2Cl2) 0.74; 1H
NMR (400 MHz, CDCl3/10% MeOD) δ 8.55 (d, 3J ) 4.0 Hz, 1H),
8.51-8.47 (two overlapping d, 3J ) 4.0 Hz, 2H), 8.45-8.41 (two
overlapping d, 3J ) 4.0 Hz, 2H), 8.33 (d, 3J ) 4.0 Hz, 1H),
7.90-7.85 (m, 6H), 7.75-7.73 (d, 2H), 7.66-7.60 (m, 12H); 13C
NMR (100 MHz, CDCl3/10% MeOD) δ 149.3, 144.9, 144.5, 141.4,
140.9, 139.9, 137.1, 136.0, 133.5, 133.3, 133.0, 131.8, 128.1, 127.7,
spectra of all novel compounds obtained, (tandem) ESI(+)
spectra for select compounds, and experimental details for the
crystal structure determination of 5H2, including the CIF file.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO9006046
J. Org. Chem. Vol. 74, No. 14, 2009 4933