Synthesis and stereochemistry of highly unsymmetric β,meso-linked porphyrin arrays

Article abstract of DOI:10.1021/jo901483q

(Chemical Equation Presented) Porphyrin arrays with tailor-made photophysical properties and well-defined three-dimensional geometries constitute attractive synthetic targets in porphyrin chemistry. The paper describes a variable, straightforward syntheti

Full text of DOI:10.1021/jo901483q

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Synthesis and Stereochemistry of Highly Unsymmetric β,Meso-Linked
Porphyrin Arrays
†
Daniel C. G. Gotz, Torsten Bruhn, Mathias O. Senge,* and Gerhard Bringmann*
†
,‡
,†
€
†
€
Institute of Organic Chemistry and Rontgen Research Center for Complex Material Systems,
University of Wu€rzburg, Am Hubland, D-97074 Wu€rzburg, Germany, and ‡School of Chemistry,
SFI Tetrapyrrole Laboratory, Trinity College Dublin, Dublin 2, Ireland
bringman@chemie.uni-wuerzburg.de; sengem@tcd.ie
Received July 10, 2009
Porphyrin arrays with tailor-made photophysical properties and well-defined three-dimensional
geometries constitute attractive synthetic targets in porphyrin chemistry. The paper describes a
variable, straightforward synthetic procedure for the construction of β,meso-linked porphyrin
multichromophores in good to excellent yields. In a Suzuki-type coupling reaction β-borylated
5,10,15,20-tetraarylporphyrins (TAPs) served as versatile building blocks for the preparation of a
plethora of directly linked, unsymmetrically substituted di- and triporphyrins. Besides their inter-
esting photophysical properties, especially the trimeric porphyrin arrays show exciting stereochem-
ical features. The established protocols thus open a convenient entry into the synthesis of achiral and
chiral, unsymmetrically substituted β,meso-linked oligoporphyrins, e.g., for applications in biome-
dicine or nonlinear optics.
Introduction
reflecting the electronic “communication” between the mono-
meric subunits in the array, thus accounting for their potential
applications in chemistry, biology, and physics.
The synthesis and physicochemical characterization of
oligomeric porphyrin assemblies has been the subject of
intense research in recent years.1,2 Porphyrin-derived multi-
chromophores display unique physical and optical properties,3
In nature, tetrapyrroles, as the “pigments of life”,4 play a
number of crucial biological roles, such as, e.g., reaction
catalysis, molecular binding, electron and energy transfer,
*To whom correspondence should be addressed. (G.B.) Fax: þ49 931 888
4755. Tel: þ49 931 318 5323. (M.O.S.) Fax: þ353 1 896 8536. Tel: þ353 1 896
8537.
(1) (a) Burrell, A. K.; Officer, D. L.; Plieger, P. G.; Reid, D. C. W. Chem.
Rev. 2001, 101, 2751–2796 and references cited therein. (b) Vicente, M. G. H.;
Jaquinod, L.; Smith, K. M. Chem. Commun. 1999, 1771–1782 and references
cited therein.
(3) (a) Tsuda, A.; Furuta, H.; Osuka, A. J. Am. Chem. Soc. 2001, 123,
10304–10321. (b) Kim, D.; Osuka, A. J. Phys. Chem. A 2003, 107, 8791–8816.
(c) Kim, D.; Osuka, A. Acc. Chem. Res. 2004, 37, 735–745. (d) Ikeue, T.;
Furukawa, K.; Hata, H.; Aratani, N.; Shinokubo, H.; Kato, T.; Osuka, A.
Angew. Chem., Int. Ed. 2005, 44, 6899–6901. (e) Ahn, T. K.; Kim, K. S.; Kim,
D. Y.; Noh, S. B.; Aratani, N.; Ikeda, C.; Osuka, A.; Kim, D. J. Am. Chem.
Soc. 2006, 128, 1700–1704.
(2) Iengo, E.; Zangrando, E.; Alessio, E. Acc. Chem. Res. 2006, 39, 841–
851 and references cited therein.
(4) (a) Battersby, A. R. Nat. Prod. Rep. 1987, 4, 77–87. (b) Battersby, A.
R. Pure Appl. Chem. 1993, 65, 1113–1122.
DOI: 10.1021/jo901483q
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Published on Web 08/25/2009
J. Org. Chem. 2009, 74, 8005–8020 8005
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Gotz et al.
JOCFeatured Article
and light harvesting.5,6 The importance and diversity of these
functions has inspired many synthetically oriented groups to
design artificial tetrapyrrole systems;among them porphyrin
dimers, trimers, and oligomers with covalent linkages between
the monomeric porphyrin subunits1,2;mimicking their natural
counterparts.7-9As a consequence, oligoporphyrins have gained
significant importance as substrates for molecular sensing10 and
molecular recognition,11 as catalysts in asymmetric synthesis,12
for optical13 or medical14 applications, and as building blocks for
the construction of molecular (nano)materials.15
Because of the rapidly increasing importance of these applica-
tions there is an urgent need for efficient, versatile, and straight-
forward procedures for the construction of unsymmetrically
substituted porphyrin arrays with well-defined three-dimen-
sional geometries and tailor-made chemical, physical, and op-
tical properties. However, the synthesis of suitable assemblies of
tetrapyrrole macrocycles is often time-consuming and requires
the sometimes tedious multistep formation of adequately func-
tionalized monomeric porphyrin precursors.1
(5) Battersby, A. R. Nat. Prod. Rep. 2000, 17, 507–526 and references
cited therein.
(6) Tetrapyrroles: Birth, Life and Death (Molecular Biology Intelligence
Unit); Warren, M. J., Smith, A. G., Eds.; Springer Verlag: New York, 2009
and references cited therein.
According to the two types of reactive sites of a porphyrin
(β- and meso-positions), porphyrin-derived multichromo-
phores can be linked via three different types of direct
(7) For artificial tetrapyrrole systems used in reaction catalysis, see: (a)
Collman, J. P.; Wagenknecht, P. S.; Hutchison, J. E. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1537–1554. (b) Ozaki, S. i.; Matsui, T.; Roach, M. P.;
Watanabe, Y. Coord. Chem. Rev. 2000, 198, 39–59. (c) Vincente, M. G. H.;
Smith, K. M. Curr. Org. Chem. 2000, 4, 139–174. (d) Vinhado, F. S.; Martins,
P. R.; Iamamoto, Y. Curr. Top. Catal. 2002, 3, 199–213. (e) Stephenson, N.
A.; Bell, A. T. J. Mol. Catal. A: Chem. 2007, 275, 54–62. (f) Doyle, M. P.
Angew. Chem., Int. Ed. 2009, 48, 850–852.
(8) For some recent examples of molecular binding properties of artificial
porphyrin systems, see: (a) Zheng, J.-Y.; Konishi, K.; Aida, T. Tetrahedron
1997, 53, 9115–9122. (b) Weiss, J. J. Inclusion Phenom. Macrocycl. Chem.
2001, 40, 1–22. (c) Zhou, H.; Groves, J. T. J. Porphyrins Phthalocyanines
2004, 8, 125–140. (d) Mamardashvili, N. Z.; Maltseva, O. V.; Ivanova, Y. B.;
Mamardashvili, G. M. Tetrahedron Lett. 2008, 49, 3752–3756. (e) Chekme-
neva, E.; Hunter, C. A.; Packer, M. J.; Turega, S. M. J. Am. Chem. Soc. 2008,
130, 17718–17725. (f) Yang, J.; Cho, S.; Yoo, H.; Park, J.; Li, W.-S.; Aida, T.;
Kim, D. J. Phys. Chem. A 2008, 112, 6869–6876. (g) Silva, I.; Sansone, S.;
Brancaleon, L. Protein J. 2009, 28, 1–13.
(9) For recent reviews on artificial photosynthetic model systems derived
from porphyrins, see: (a) Wasielewski, M. R. Chem. Rev. 1992, 92, 435–461.
(b) Gust, D.; Moore, T. A.; Moore, A. L. Acc. Chem. Res. 1993, 26, 198–205.
(c) Gust, D.; Moore, T. A.; Moore, A. L. Acc. Chem. Res. 2001, 34, 40–48. (d)
Fukuzumi, S.; Imahori, H. Electron Transfer Chem. 2001, 2, 927–975. (e)
Imahori, H.; Mori, Y.; Matano, Y. J. Photochem. Photobiol., C 2003, 4, 51–
83. (f) Guldi, D. M. Chem. Soc. Rev. 2002, 31, 22–36. (g) Kobuke, Y.; Ogawa,
K. Bull. Chem. Soc. Jpn. 2003, 76, 689–708. (h) Imahori, H. Org. Biomol.
Chem. 2004, 2, 1425–1433. (i) Imahori, H. J. Phys. Chem. B 2004, 108, 6130–
6143. (j) Fukuzumi, S. Bull. Chem. Soc. Jpn. 2006, 79, 177–195. (k) Satake,
A.; Kobuke, Y. Org. Biomol. Chem. 2007, 5, 1679–1691. (l) Hori, T.;
Nakamura, Y.; Aratani, N.; Osuka, A. J. Organomet. Chem. 2007, 692,
148–155. (m) Jiang, L.; Li, Y. J. Porphyrins Phthalocyanines 2007, 11, 299–
312. (n) Nakamura, Y.; Aratani, N.; Osuka, A. Chem. Soc. Rev. 2007, 36,
831–845.
(10) For selected recent examples of applications of porphyrins in mo-
lecular sensing, see: (a) Konishi, K.; Kimata, S.; Yoshida, K.; Tanaka, M.;
Aida, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 2823–2825. (b) Ashkenasy,
G.; Ivanisevic, A.; Cohen, R.; Felder, C. E.; Cahen, D.; Ellis, A. B.; Shanzer,
A. J. Am. Chem. Soc. 2000, 122, 1116–1122 (O2 sensing). (c) Dooling, C. M.;
Worsfold, O.; Richardson, T. H.; Tregonning, R.; Vysotsky, M. O.; Hunter,
C. A.; Kato, K.; Shinbo, K.; Kaneko, F. J. Mater. Chem. 2001, 11, 392–398
(NO2 sensing). (d) Zhang, X.-B.; Guo, C.-C.; Li, Z.-Z.; Shen, G.-L.; Yu, R.-Q.
Anal. Chem. 2002, 74, 821-825 (sensing of mercury ions). (e) Kim, Y.-H.; Hong,
J.-I. Chem. Commun. 2002, 512-513 (sensing of NaCN). (f) Bucher, C.;
Devillers, C. H.; Moutet, J.-C.; Royal, G.; Saint-Aman, E. Chem. Commun. 2003,
888-889 (sensing of neutral molecules). (g) Zhang, Y.; Yang, R.; Liu, F.; Li, K. A.
Anal. Chem. 2004, 76, 7336-7345 (imidazole sensing). (h) Niu, C.-G.; Gui, X.-
Q.; Zeng, G.-M.; Guan, A.-L.; Gao, P.-F.; Qin, P.-Z. Anal. Bioanal. Chem. 2005,
383, 349-357 (pH sensing). (i) Zhang, H.; Sun, Y.; Ye, K.; Zhang, P.; Wang, Y. J.
Mater. Chem. 2005, 15, 3181-3186 (O2 sensing). (j) Kejik, Z.; Zaruba, K.;
Michalik, D.; Sebek, J.; Dian, J.; Pataridis, S.; Volka, K.; Kral, V. Chem.
Commun. 2006, 1533-1535 (sensing of ATP). (k) Gulino, A.; Mineo, P.;
Scamporrino, E.; Vitalini, D.; Fragala, I. Chem. Mater. 2006, 18, 2404-2410
(pH sensing). (l) Xie, Y.; Hill, J. P.; Charvet, R.; Ariga, K. J. Nanosci.
Nanotechnol. 2007, 7, 2969–2993. (m) Shoji, Y.; Tashiro, K.; Aida, T. Chirality
2008, 20, 420–424.
(13) Data storage: (a) Ao, R.; Kummerl, L.; Haarer, D. Adv. Mater. 1995, 7,
495. Nonlinear optics: (b) Nalwa, H. S. Adv. Mater. 1993, 5, 341.Electrochro-
mism: (c) Mortimer, R. J. Chem. Soc. Rev. 1997, 26, 147. Optical limiting:
(d) Perry, J. W.; Mansour, K.; Lee, I.-Y. S.; Wu, X.-L.; Bedworth, P. V.; Chen,
C.-T.; Ng, D.; Marder, S. R.; Miles, P.; Wada, T.; Tian, M.; Sasabe, H. Science
1996, 273, 1533.
(14) Photodynamic therapy (PDT): (a) Moan, J. Photochem. Photobiol.
1986, 43, 681. (b) Dougherty, T. J. Adv. Photochem. 1992, 17, 275–311. (c)
Dougherty, T. J.; Marcus, S. L. Eur. J. Cancer 1992, 28, 1734–1742. (d)
Bonnett, R. Chem. Soc. Rev. 1995, 24, 19–33. (e) Franck, B.; Nonn, A.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1795–1811. (f) Sternberg, E. D.;
Dolphin, D. Tetrahedron 1998, 54, 4151–4202. (g) MacDonald, I. J.; Dougherty,
T. J. J. Porphyrins Phthalocyanines 2001, 5, 105-129. Boron neutron capture
therapy (BNCT): (h) Barth, R. F.; Soloway, A. H.; Brugger, R. M. Cancer Invest.
1996, 14, 534–550. (i) Kahl, S. B.; Li, J. Inorg. Chem. 1996, 35, 3878. (j) Soloway,
A. H.;Tjarks, W.;Barnum, B. A.;Rong, F.-G.;Barth, R.F.; Codogni, I. M.;Wilson, J.
G. Chem. Rev. 1998, 98, 1515-1562. DNA cleavage: (k) An, J. M.; Yang, S. J.; Yi,
S.-Y.; Jhon, G.-J.; Nam, W. Bull. Korean Chem. Soc. 1997, 18, 117. (l) Mehta, G.;
Muthusamy, S.; Maiya, B. G.; Arounaguiri, S. Tetrahedron Lett. 1997, 38, 7125.
(m) Barth, R. F.; Coderre, J. A.; Vicente, M. G. H.; Blue, T. E. Clin. Cancer Res.
2005, 11, 3987–4002.
(15) For some recent examples, see: (a) Crossley, M. J.; Burn, P. L. J.
Chem. Soc., Chem. Commun. 1991, 1569. (b) Wagner, R. W.; Lindsey, J. S. J.
Am. Chem. Soc. 1994, 116, 9759. (c) Wagner, R. W.; Lindsey, J. S.; Seth, J.;
Palaniappan, V.; Bocian, D. F. J. Am. Chem. Soc. 1996, 118, 3996. (d) Harth,
E. M.; Hecht, S.; Helms, B.; Malmstrom, E. E.; Frechet, J. M. J.; Hawker, C.
J. J. Am. Chem. Soc. 2002, 124, 3926–3938. (e) Murakami, H.; Nomura, T.;
Nakashima, N. Chem. Phys. Lett. 2003, 378, 481–485. (f) Tsuda, M.; Dy, E.
S.; Kasai, H. Eur. Phys. J. D 2006, 38, 139–141. (g) Elemans, J. A. A. W.; van
Hameren, R.; Nolte, R. J. M.; Rowan, A. E. Adv. Mater. 2006, 18, 1251-1266
and references cited therein. (h) Fukuzumi, S.; Kojima, T. J. Mater. Chem. 2008,
18, 1427–1439.
(16) Osuka, A.;Shimidzu, H. Angew. Chem., Int. Ed. Engl. 1997, 36, 135–137.
(17) Yoshida, N.; Osuka, A. Tetrahedron Lett. 2000, 41, 9287–9291.
(18) (a) Susumu, K.; Shimidzu, T.; Tanaka, K.; Segawa, H. Tetrahedron
Lett. 1996, 37, 8399–8402. (b) Senge, M. O.; Feng, X. Tetrahedron Lett. 1999,
40, 4165–4168. (c) Wojaczynski, J.; Latos-Grazynski, L.; Chmielewski, P. J.;
Van Calcar, P.; Balch, A. L. Inorg. Chem. 1999, 38, 3040–3050. (d) Senge, M.
O.; Feng, X. J. Chem. Soc., Perkin Trans. 1 2000, 3615–3621. (e) Miller, M.
A.; Lammi, R. K.; Prathapan, S.; Holten, D.; Lindsey, J. S. J. Org. Chem.
2000, 65, 6634–6649. (f) Hiroto, S.; Osuka, A. J. Org. Chem. 2005, 70, 4054–
4058. (g) Jin, L.-M.; Chen, L.; Yin, J.-J.; Guo, C.-C.; Chen, Q.-Y. Eur. J. Org.
Chem. 2005, 3994–4001. (h) Jin, L.-M.; Yin, J.-J.; Chen, L.; Guo, C.-C.;
Chen, Q.-Y. Synlett 2005, 2893–2898.
(19) Aratani, N.; Osuka, A. Org. Lett. 2001, 3, 4213–4216.
(20) Khoury, R. C.; Jaquinod, L.; Smith, K. M. Chem. Commun. 1997,
1057–1058.
(21) For directly meso,meso-linked dimmers derived from corroloid
systems, see: Sankar, J.; Rath, H.; Prabhuraja, V.; Gokulnath, S.; Chandra-
shekar, T. K.; Purohit, C. S.; Verma, S. Chem.;Eur. J. 2007, 13, 105–114.
€
(22) (a) Bringmann, G.; Gotz, 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, 130, 17812–17825. (b) Bringmann,
(11) For reviews on porphyrins used for chiral recognition, see: (a)
Ogoshi, H.; Mizutani, T. Acc. Chem. Res. 1998, 31, 81–89. (b) Huang, X.;
Nakanishi, K.; Berova, N. Chirality 2000, 12, 237–255. (c) Simonneaux, G.;
Le Maux, P. Coord. Chem. Rev. 2002, 228, 43–60.
€
€
G.; Rudenauer, S.; Gotz, D. C. G.; Gulder, T. A. M.; Reichert, M. Org. Lett.
(12) For selected examples of porphyrins used in asymmetric synthesis,
see: (a) Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I.
Science 1993, 261, 1404–1411. (b) Gross, Z.; Ini, S. J. Org. Chem. 1997, 62,
5514–5521. (c) Rose, E.; Quelquejeu, M.; Pandian, R. P.; Lecas-Nawrocka,
A.; Vilar, A.; Ricart, G.; Collman, J. P.; Wang, Z.; Straumanis, A. Poly-
hedron 2000, 19, 581–586. (d) Zhang, J.-L.; Zhou, H.-B.; Huang, J.-S.; Che,
C.-M. Chem.;Eur. J. 2002, 8, 1554–1562. (e) Ferrand, Y.; Le Maux, P.;
Simonneaux, G. Org. Lett. 2004, 6, 3211–3214. (f) Zhang, R.; Yu, W.-Y.;
Che, C.-M. Tetrahedron: Asymmetry 2005, 16, 3520–3526.
2006, 8, 4743–4746.
(23) For β,β0-bisporphyrins without meso-substituents that might be
axially chiral but have not been stereochemically characterized, see refs 24
and 25.
(24) Deng, Y.; Chang, C. K.; Nocera, D. G. Angew. Chem., Int. Ed. 2000,
39, 1066–1068.
(25) (a) Paine, J. B. III; Dolphin, D. Can. J. Chem. 1978, 56, 1710–1712.
(b) Uno, H.; Kitawaki, Y.; Ono, N. Chem. Commun. 2002, 116–117.
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porphyrin-porphyrin connections: meso,meso0-,16-21 β,β0-,22-27
or β,meso.28-30 The relative energies of the frontier orbitals;
and, thus, also the electron transfer (ET) characteristics of such
systems;are influenced by the chosen substituents of the por-
phyrin backbone and, in particular, by the type of the porphyr-
in-porphyrin linkage.31 Thus, e.g., to gain detailed insight into
the interplay of the monomeric subunits in directly linked
porphyrin arrays in dependence of their connectivities, the avail-
ability of suitable porphyrin systems with different types of
linkages and tunable electronic and optical properties is required.
Osuka and co-workers have pioneered the chemistry of
meso,meso0-linked porphyrin arrays (Figure 1) by greatly
facilitating the synthesis of such systems by introducing their
AgPF6-promoted coupling protocol.16 This procedure is,
however, restricted to the preparation of oligomeric por-
phyrins arising from a homocoupling of two (or more)
constitutionally identical precursors.32,33 While meso-substi-
tuted porphyrin building blocks are usually available more
easily by methods developed by Senge et al.,34 viz. by
regioselective nucleophilic addition of organolithium re-
agents to meso-unsubstituted porphyrin precursors and oxi-
dation of the Meisenheimer-type intermediates, the synthesis
of oligoporphyrins with direct β-linkages has, for a long
time, been hampered by the lack of suitably β-functionalized
tetraarylporphyrins (TAPs). Bringmann et al. have, there-
fore, recently established the synthesis of β-borylated TAPs
from their respective brominated precursors by using a
Miyaura-like transmetalation reaction.22 The synthesized
porphyrinyl boronic acid esters have proven to be valuable
coupling partners in Suzuki couplings leading to the
synthesis of a broad variety of intrinsically axially chiral
(26) For a directly β,β0-linked, yet N-confused bisporphyrin, which has
been stereochemically characterized more recently, see: (a) Siczek, M.;
Chmielewski, P. J. Angew. Chem., Int. Ed. 2007, 46, 7432-7436. For its
synthesis, see: (b) Chmielewski, P. J. Angew. Chem., Int. Ed. 2004, 43, 5655–
5658.
(27) For the synthesis and detailed characterization of directly β,β’-linked
corrole dimers, see: (a) Mahammed, A.; Giladi, I.; Goldberg, I.; Gross, Z.
Chem.;Eur. J. 2001, 7, 4259–4265. (b) Luobeznova, I.; Simkhovich, L.;
Goldberg, I.; Gross, Z. Eur. J. Inorg. Chem. 2004, 1724–1732. (c) Hiroto, S.;
Furukawa, K.; Shinokubo, H.; Osuka, A. J. Am. Chem. Soc. 2006, 128,
12380–12381. (d) Barata, J. F. B.; Silva, A. M. G.; Neves, M. G. P. M. S.;
ꢀ
Tome, A. C.; Silva, A. M. S.; Cavaleiro, J. A. S. Tetrahedron Lett. 2006, 47,
8171–8174. (e) Cho, S.; Lim, J. M.; Hiroto, S.; Kim, P.; Shinokubo, H.;
Osuka, A.; Kim, D. J. Am. Chem. Soc. 2009, 131, 6412–6420.
FIGURE 1. Meso,meso0-linked dimeric porphyrins 1, whose axial
chirality originates from their unsymmetric meso-substitution
pattern as synthesized by Osuka et al.,17 C2-symmetric and
thus intrinsically chiral β,β0-bisporphyrins of type 2 reported by
Bringmann’s group,22 and one of the few literature-known repre-
sentatives of (basically achiral) β,meso-linked porphyrin dimers 3
(Senge et al.).28
€
(28) (a) Wiehe, A.; Senge, M. O.; Schafer, A.; Speck, M.; Tannert, S.;
Kurreck, H.; Roder, B. Tetrahedron 2001, 57, 10089–10110. (b) Senge, M. O.;
€
€
€
Rossler, B.; von Gersdorff, J.; Schafer, A.; Kurreck, H. Tetrahedron Lett.
2004, 45, 3363–3367.
(29) (a) Wasielewski, M. R.; Johnson, D. G.; Niemczyk, M. P.; Gaines, G.
L. III; O’Neil, M. P.; Svec, W. A. J. Am. Chem. Soc. 1990, 112, 6482–6488. (b)
Johnson, D. G.; Niemczyk, M. P.; Minsek, D. W.; Wiederrecht, G. P.; Svec,
W. A.; Gaines, G. L. III; Wasielewski, M. R. J. Am. Chem. Soc. 1993, 115,
5692–5701. (c) Zheng, G.; Pandey, R. K.; Forsyth, T. P.; Kozyrev, A. N.;
Dougherty, T. J.; Smith, K. M. Tetrahedron Lett. 1997, 38, 2409–2412.
(30) Ogawa, T.; Nishimoto, Y.; Yoshida, N.; Ono, N.; Osuka, A. Angew.
Chem., Int. Ed. 1999, 38, 176–179.
(31) (a) Yang, S. I.; Seth, J.; Balasubramanian, T.; Kim, D.; Lindsey, J. S.;
Holten, D.; Bocian, D. F. J. Am. Chem. Soc. 1999, 121, 4008–4018. (b)
Huber, M. Eur. J. Org. Chem. 2001, 4379–4389.
(32) For statistical AgPF6-promoted meso,meso-couplings between two
different porphyrins, see: (a) Wojaczynski, J.; Lotos-Grazynski, L.;
Chmielewski, P. J.; Calcar, P. V.; Balch, A. L. Inorg. Chem. 1999, 38, 3040.
(b) Miller, M. A.; Lammi, R. K.; Prathapan, S.; Holten, D.; Lindsey, J. S. J.
Org. Chem. 2000, 65, 6634.
β,β0-linked bisporphyrins (Figure 1). Although a few repre-
sentatives of β,meso-linked porphyrin dimers or trimers have
been synthesized,35 no methodological study has so far
aimed at the preparation of unsymmetric, directly β,meso-
linked porphyrin arrays (Figure 1).
In this paper, we report on the synthesis of a variety of
β,meso-linked porphyrin multichromophores via simple
convergent reaction sequences in high yields, including
dimeric and trimeric porphyrin arrays with axial chirality.
The novel porphyrin trimers show interesting spectral and
chiroptical properties and, in particular, possess unique
(33) For a more general synthesis of meso,meso-linked bisporphyrins by
Suzuki coupling reactions, see ref 19.
(34) (a) Feng, X.; Senge, M. O. Tetrahedron 2000, 56, 587–590. (b) Senge,
M. O.; Bischoff, I. Eur. J. Org. Chem. 2001, 1735–1751. (c) Ryppa, C.; Senge,
M. O.; Hatscher, S. S.; Kleinpeter, E.; Wacker, P.; Schilde, U.; Wiehe, A.
Chem.;Eur. J. 2005, 11, 3427–3442. (d) Senge, M. O. Acc. Chem. Res. 2005,
38, 733–743.
(35) (a) For the synthesis of β,meso-linked porphyrin dimers or trimers by
mixed condensation reactions, see ref 28. (b) For the synthesis of similar β,meso-
linked porphyrin-chlorin dyads and triads by mixed condensation reactions, see ref
29. (c) For the synthesis of β,meso-linked bisporphyrins by electrochemical
oxidation of metalated porphyrins, see ref 30.
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TABLE 1. Classification of Dimeric and Trimeric β,Meso-Linked Porphyrins by the “ABCD Nomenclature”
substitution pattern
denotation
A3-βTAP type
R1 = R2 = R3 = substituent 1
R1 = R3 = substituent 1, R2 = H
5,15-A2-βTAP type
R1 = R3 = substituent 1, R2 = substituent 2
R1 = substituent 1, R3 = substituent 2, R2 = H
R1 = substituent 1, R2 = substituent 2, R3 = substituent 3
R1 = R3 = substituent 1, R2 = tetraarylporphyrin
R1 = substituent 1, R3 = substituent 2; R2 = tetraarylporphyrin
5,15-A2B-βTAP type
5,15-AB-βTAP type
ABC-βTAP type
βTAP-5,15-A2-βTAP0 type
βTAP-5,15-AB-βTAP0 type
stereochemical features. The established protocols open a
convenient entry into the design of achiral and chiral,
unsymmetrically substituted β,meso-linked oligoporphyrins,
e.g., for applications in biomedicine or nonlinear optics.
literature procedures.40 The desired β-boronic acid esters of
TAPs were synthesized by the Miyaura-like transmetala-
tion protocol recently published.22 Using the coupling con-
ditions previously optimized for the synthesis of β,β0-linked
bisporphyrins,22 a broad variety of β,meso-linked porphyrin
dimers were obtained in yields ranging from 50 up to 84%
(Table 2).
Results and Discussion
Classification of Unsymmetric β,Meso-Linked Oligopor-
phyrins. Besides the IUPAC nomenclature for tetrapyrrolic
macrocyles,36 another more practical denotation for meso-
substituted porphyrins was proposed by Lindsey37 to classify
monomeric porphyrins by their different meso-substitution
patterns. This nomenclature was further developed by Senge
et al. and is now known as the ABCD system.34 In order to
facilitate the classification of the unsymmetrically substi-
tuted oligoporphyrins synthesized in the present work, we
further extended the ABCD system to the unambiguous
denotation of dimeric and trimeric β,meso-linked porphyrins
as shown in Table 1.
Synthesis of β,Meso-Linked Bisporphyrins. The synthesis
of β,meso-linked dimeric porphyrins started with the Suzuki
coupling38 of suitable meso-brominated 5,15-di- or 5,10,15-
trisubstituted porphyrins with β-borylated TAPs.22 The
respective brominated precursors were easily accessible by
simple condensation reactions of dipyrrylmethanes with
aldehydes39 and subsequent functionalization of the gener-
ated 5,15-disubstituted porphyrins by addition of organo-
lithium reagents,34 followed by bromination according to
Starting with 5,10,15-homosubstituted precursors and
porphyrin boronic acid esters as the coupling partners, the
simple Cs-symmetric A3-βTAP-type bisporphyrins 6a-d
bearing three identical aryl or alkyl substituents in the
meso-linked moiety were generated in good yields. Full
metalation of the dimers 6a, 6d, 6e, or rac-6h to give the
respective zinc(II), nickel(II), or copper(II) complexes 6a-
Zn2, 6a-Ni2, 6a-Cu2, 6d-Zn2, 6e-Ni2, and rac-6h-Zn2 was
easily achieved by known methods41 in yields higher than
92%. In contrast to the synthesis of β,β0-bisporphyrins,
where the reaction course depends on the metalation states
of the coupling partners,22 the metal ion did not show a
significant influence on the yields obtained in the case of
the β,meso-linked dimers. Hence, the coupling of precur-
sors differing in their metalation states should permit free
combination of two different metal centers within the
bisporphyrin backbone, thus offering the possibility to
selectively manipulate the properties of the desired dimers
by the rational choice of the two central metals. In addi-
tion, variation of the meso-substituents of the β-borylated
starting material can be expected to further expand the
scope of the established method to most different substitu-
tion patterns of the accessible dimeric porphyrins: As
(36) (a) Moss, G. P. Pure Appl. Chem. 1987, 59, 799–832. (b) Moss, G. P.
Eur. J. Biochem. 1988, 178, 277-573. (c) www.chem.qmul.ac.uk/iupac/
tetrapyrrole/.
(37) For definitions and nomenclature of meso-substituted porphyrins,
see: Lindsey, J. S. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M.,
Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 1, pp 45-118.
(38) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483. (b)
Suzuki, A. Proc. Jpn. Acad. 2004, 80, 359–371.
(39) The MacDonald [2 þ 2]-type co-condensations were carried under
standard Lindsey conditions: (a) Arsenaulte, G. P.; Bullock, E.; MacDonald,
S. F. J. Am. Chem. Soc. 1960, 82, 4384–4389. (b) Lindsey, J. S.; Hsu, H. C.;
Schreimann, I. C. Tetrahedron Lett. 1986, 27, 4969–4970.
(40) For a representative bromination protocol, see: Arnold, D. P.; Bott,
R. C.; Eldridge, H.; Elms, F. M.; Smith, G.; Zojaji, M. Aust. J. Chem. 1997,
50, 495–503.
(41) For the insertion of zinc(II), see: (a) Adler, A. D.; Longo, F. R. J. Inorg.
Nucl. Chem. 1970, 32, 2443-2445. For the insertion of nickel(II), see: (b)
Richeter, S.; Hadj-Aissa, A.; Taffin, C.; van der Leeb, A.; Leclercq, D. Chem.
Commun. 2007, 2148-2150. For the insertion of copper(II), see: (c) Hosseini, A.;
Taylor, S.; Accorsi, G.; Armaroli, N.; Reed, C. A.; Boyd, P. D. W. J. Am. Chem.
Soc. 2006, 128, 15903–15913.
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TABLE 2. Synthesis of β,Meso-Linked Bisporphyrins by Suzuki Coupling of Meso-Brominated Porphyrins with β-Borylated TAPsa
Ar
Ph
Ph
Ph
Ph
Ph
4-ClPh
Ph
Ph
M1
reactant
R1
R2
Ph
Ph
Ph
n-Hex
H
H
Ph
R3
M2
reactant
product (yield (%))c
type
2H
2H
2H
2H
2H
2H
2H
2H
Zn
2H
4a
4a
4a
4a
4a
4b
4a
4a
4c
4a
Ph
Ph
Ph
Ph
Ph
Ph
2H
Zn
Ni
2H
2H
2H
2H
2H
2H
2H
5a
5b
5c
5d
5e
5e
5f
5g
5g
5h
6a (65)
6b (58)
6c (66)
6d (50)
6e (65)
6f (48d)
6g (81)
rac-6h (84)
rac-6i (82)
rac-6j (74)
A3-βTAP
A3-βTAP
A3-βTAP
A3-βTAP
5,15-A2-βTAP
5,15-A2-βTAP
5,15-A2B-βTAP
5,15-AB-βTAP
5,15-AB-βTAP
ABC-βTAP
n-Hex
Ph
n-Hex
Ph
Ph
Ph
3,5-di-t-BuPhe
4-MeOPh
4-MeOPh
4-MeOPh
3,5-di-t-BuPhe
n-Hex
n-Hex
H
H
n-Hex
Ph
Ph
Ph
aReactions were carried out under Ar with porphyrin β-boronic acid ester 4 (1.0 equiv), meso-bromoporphyrin 5 (0.7-2.0 equiv), Ba(OH)2 8H2O (10
3
equiv), and Pd catalyst (20 mol %). bZn(OAc)2 2H2O (10 equiv) or Cu(OAc)2 (1.5 equiv) in CHCl3/MeOH, or Ni(acac) (2.5 equiv) in toluene. cIsolated,
3
nonoptimized yields. d4b was reisolated in 19% yield. e3,5-di-t-BuPh = 3,5-di-tert-butylphenyl.
an example, coupling of the β-boronic acid ester 4b derived
from 5,10,15,20-tetra(4-chlorophenyl)porphyrin42 resulted in
the formation of an 5,15-A2-βTAP-type dimer 6f having
an electron-poor TAP subunit, albeit in a decreased yield
of 48% (along with 19% recovered starting material 4b),
due to the low reactivity of the deactivated borylated
precursor 4b.
Even structurally more complex bisporphyrins were ob-
tained in excellent yields using heterogeneously meso-sub-
stituted precursors such as 5-bromo-10,20-bis(di-tert-butyl-
phenyl)-15-phenylporphyrin (5f), 5-bromo-10-n-hexyl-20-
(4-methoxyphenyl)porphyrin (5g),43 or 5-bromo-10-phenyl-
15-n-hexyl-20-(4-methoxyphenyl)porphyrin (5h)43 as de-
monstrated by the synthesis of the 5,15-A2B-βTAP-, 5,15-
AB-βTAP-, and ABC-βTAP-type bisporphyrins 6g44 and
rac-6h-j (Table 2). Altogether, the synthetic strategy pre-
sented herein provides a modular principle for the generation
of a broad structural diversity of β,meso-linked bisporphyr-
ins suitable for most different applications.
trimer 8a was synthesized in which two identical TAPs were
β-linked to the central porphyrin macrocycle in a linear array
(Table 3). Due to hindered rotation about the porphyrin-
porphyrin axes, 8a exists as a mixture of diastereomers, cis-
8a and trans-8a, which were resolved by column chromatog-
raphy on standard silica gel.45 The product ratios of cis-8a
and trans-8a (cis/trans = 1:2) obtained after isolation reflect
the fact that the cis-geometry, i.e., with the C200 and C2000
aryl moieties being on the same side of the central macro-
cycle, is sterically much more demanding than the trans-
orientation, with its “inner” phenyl rings (i.e., at C200 and
C2000), which point toward the central porphyrin subunit,
being located at opposite sides. A detailed discussion of the
spatial arrangement of 8a is given in the stereochemistry
section.
Similar to the preparation of dimeric porphyrins, structu-
rally even more differentiated trimers were synthesized, this
time starting from 5,15-dibromo-10-n-hexyl-20-(4-methoxy-
phenyl)porphyrin (7b).43 The βTAP-5,15-AB-βTAP triad
8b, which was thus accessible in excellent yields, was again
obtained as a mixture of diastereomers, cis-8b and trans-8b
(product ratio cis/trans = 1:1.5; Table 3). Full metalation41
of trans-8a with zinc(II) was achieved in 94% yield.
Synthesis of Constitutionally Symmetric β,meso-Linked
Porphyrin Triads. Besides the synthesis of β,meso-linked
porphyrin dimers, the established strategy also offers an easy
entry into the design of trimeric porphyrins featuring two
direct porphyrin-porphyrin axes: Starting from dibromi-
nated 5,15-diphenylporphyrin 7a, the βTAP-5,15-A2-βTAP
Triporphyrins of this type had already been synthesized
before, by co-condensation of β-formyl porphyrins and
dipyrrylmethane, yet only in small quantities and poor
combined yields of about 10% (product ratio cis/trans =
1:1).28 The isolated yields using our optimized C-C coupling
(42) For the synthesis of 4b, see ref 22.
(43) This compound has not been described in the literature so far. For its
synthesis, see the Supporting Information.
(44) The fact that two signals are observed for the tert-butyl groups
indicates that both the rotation about the porphyrin-porphyrin and around
the porphyrin-(3,5-di-tert-butylphenyl) axes is restricted. A similar phe-
nomenon had already been observed for meso,meso0-linked bisporphyrins.17
(45) For a meso,meso0-linked porphyrin trimer that was isolated as a
mixture of atropo-diastereomers with relative cis- or trans-orientations, see
ref 17.
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TABLE 3. One-Step Formation of Constitutionally Symmetric β,Meso-Linked Porphyrin Triads by a 2-Fold Suzuki Coupling of 5,15-Dibrominated
Porphyrins with β-Borylated TAPsa
Ar
M1
reactant
R1
R2
Ph
n-Hex
M2
reactant
product (yield (%))b
type
Ph
Ph
2H
2H
4a
4a
Ph
4-MeOPh
2H
2H
7a
7b
cis-8a (27) trans-8a (52)
cis-8b (29) trans-8b (42)
βTAP-5,15-A2-βTAP
βTAP-5,15-AB-βTAP
aReactions were carried out under Ar with porphyrin β-boronic acid ester 4 (2.5 equiv), meso-bromoporphyrin 5 (1.0 equiv), Ba(OH)2 8H2O (10-20
3
equiv), and Pd catalyst (20 mol %). bIsolated, nonoptimized yields.
procedure22 (combined yields 71-79%), by contrast, are
excellent, proving the efficiency of the method established
here. Thus, for the first time, the desired trimers are now
available in one simple coupling step, e.g., at a 200-mg scale.
Furthermore, coupling of metalated dibromoporphyrins
with β-borylated TAPs bearing a different metal center
should result in the formation of trimers combining two
identical central metals in the peripheral subunits with
another, different one in the central porphyrin core. Thus,
the synthetic procedure elaborated here permits rapid gen-
eration of a large variety of β,meso-linked porphyrin triads,
differing in their substitution pattern, in the metalation states
of the subunits, and, in addition, in the spatial arrangement
(e.g., cis/trans-geometry) of the chromophores. Finally, con-
version of 5,10-diaryl-15,20-dibromoporphyrins will offer
the possibility to synthesize β,meso-linked trimers with an
angular array of the three porphyrin units as yet another
structural modification of the linear arrangement reported in
the present work.46,47
Functionalization of Preformed β,meso-Linked Bisporphyr-
ins. In contrast to the above-described one-step synthesis of
constitutionally symmetric porphyrin triads, the construc-
tion of constitutionally unsymmetric triporphyrins required
the stepwise formation of the trimeric porphyrin backbone,
either by the chemoselective transformation of difunctiona-
lized monomeric porphyrins (e.g., 5-bromo-15-iododiaryl-
porphyrins)48 or by the directed preparation of an initially
meso-free dimer, with subsequent halogenation and renewed
C-C coupling with a suitable monomeric porphyrin. In
order to enable a divergent modification of the precious
dimeric porphyrins at a late stage of the synthesis, the second
alternative seemed preferable. Therefore, adequately func-
tionalized bisporphyrins had to be synthesized to permit
subsequent C-C coupling reactions.
The porphyrin dimers thus prepared can contain a free
meso-position (see, e.g., 6e, 6f, rac-6h, and rac-6i, Table 2)
amenable to further synthetic manipulations. As an example,
the bisporphyrins 6e, 6f, and rac-6i were brominated40 in
good to excellent yields (82-99%, Table 4) giving the
functionalized dimeric porphyrins 9a, 9b, and rac-9c, respec-
tively.
The brominated dimers also permit introduction of an-
other, different meso-substituent by a C-C coupling reac-
tion at a very late stage of the synthesis yielding 5,15-A2B-
βTAP-type porphyrin dyads. Furthermore, a Miyaura trans-
metalation reaction49 might give rise to meso-borylated
bisporphyrins that can serve as versatile building blocks
for the construction of complex porphyrin multichromo-
phores.50
Moreover, the introduction of another meso-substituent
succeeded, through nucleophilic attack of organolithium
reagents34 such as phenyllithium (PhLi) followed by quench-
ing with H2O and oxidation with DDQ in acceptable yields
(rac-9d, 43%, Table 4). It is noteworthy that the reaction
takes place with a good regioselectivity at the free meso-
position, C5. Reaction of the more reactive nucleophile n-
hexyllithium (n-HexLi) with 6e or the fully nickelated bis-
porphyrin 6e-Ni2, however, resulted in a complex, inseparable
(46) The synthesis of such systems is currently under investigation in our
groups.
(47) For meso,meso0-linked triporphyrins displaying such a rectangular
geometry as synthesized by a Suzuki coupling, see ref 19.
(49) Hyslop, A. G.; Kellett, M. A.; Iovine, P. M.; Therien, M. J. J. Am.
Chem. Soc. 1998, 120, 12676–12677.
(48) For a stepwise chemoselective functionalization of 5-bromo-15-
iodo-diarylporphyrins leading to unsymmetric monomeric TAP derivatives,
see: Shanmugathasan, S.; Johnson, C. K.; Edwards, C.; Matthews, K.;
Dolphin, D.; Boyle, R. W. J. Porphyrins Phthalocyanines 2000, 4, 228–232.
(50) For the synthesis of borylated meso,meso0-bisporphyrins and meso,
meso0-linked porphyrin tetramers, see: Hori, T.; Aratani, N.; Takagi, A.;
Matsumoto, T.; Kawai, T.; Yoon, M.-C.; Yoon, Z. S.; Cho, S.; Kim, D.;
Osuka, A. Chem.;Eur. J. 2006, 12, 1319–1327.
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TABLE 4. Further Functionalization of Bisporphyrins Having a Free Meso-Position
R1
R2
Ph
Ph
n-Hex
n-Hex
Ar
Ph
4-ClPh
Ph
Ph
M1
M2
reactant
reaction conditions
X
product (yield (%))a
Ph
Ph
2H
2H
2H
2H
2H
2H
Zn
2H
6e
6f
rac-6i
rac-6h
NBS/pyridine, 0 °C, 15 min
NBS/pyridine, 0 °C, 30 min
NBS/pyridine, 0 °C, 15 min
(1) PhLi, 0 f 40 °C
(2) H2O, 0 °C f rt
(3) DDQ, rt
Br
9a (98)
9b (82)
rac-9c (93)
rac-9d (43)
Br
Br
Ph
4-MeOPh
4-MeOPh
Ph
Ph
Ph
Ph
Ph
Ph
2H
Ni
2H
Ni
6e
(1) HexLi, -5 f 40 °C
(2) H2O, 0 °C f rt
(3) DDQ, rt
(1) HexLi, -78 °C
(2) H2O, -78 °C
(3) DDQ, -78 °C
n-Hex
n-Hex
complex
mixture
6e-Ni2
complex
mixture
aIsolated, nonoptimized yields.
mixture of polyalkylated species and decomposition products
even at -78 °C.
Besides synthetic manipulation at a free meso-position,51
additional functionality can also be introduced by reactions at
the periphery of the bisporphyrins. Some examples of such
transformations are described in the stereochemistry part below.
In summary, the presented strategy will permit access to a
plethora of 5,15-A2B-βTAP-type porphyrin dyads differing
in their substituent B starting from preformed bisporphyrins
by regioselective nucleophilic attack of organolithium re-
agents on a free meso-position.34 In addition, the established
protocols provide useful precursors, such as the brominated
porphyrin dimers 9a, 9b, rac-9c, which, besides their use for
the diverging introduction of meso-substituents at a late
stage of the synthesis, can facilitate the construction of even
larger, superstructured;chiral or achiral;oligoporphyrins,
by simple C-C coupling reactions.
Synthesis of Constitutionally Unsymmetric β,Meso-Linked
Porphyrin Triads. As expected, the functionalized dimers
thus generated were not only useful for the divergent synth-
esis of a broad variety of unsymmetrically substituted bis-
porphyrins but proved to be versatile precursors for the
construction of highly complex porphyrin trimers (βTAP-
5,15-AB-βTAP0 type) incorporating up to three different
metal centers, two different substituents in the positions 10
and 20, and two differently substituted TAP moieties in the
positions 5 or 15, as shown by the synthesis of 10 (Scheme 1).
Directly linked trimeric porphyrins of comparable structural
complexity have not been described in the literature so far.
As compared to the synthesis of the porphyrin triads
cis/trans-8a and cis/trans-8b (cis/trans = 1:2 and 1:1.5,
respectively), the higher portion of trans-configured atro-
FIGURE 2. Typical UV/vis profiles of β,meso-linked dimeric and
trimeric porphyrins in dichloromethane, exemplarily shown for the
dimer 6a and the trimer trans-8a, in comparison with the UV/vis
spectrum of TPP.
po-diastereomer (cis/trans = 1:3.5) and the generally de-
creased yields (71-79% overall yield for 8a/b as compared to
36% for 10) obtained in the synthesis of 10 reflect the
increased steric hindrance of cis-10 due to the para-methyl
group of the C2000 tolyl moiety (see also Figure 4). The
additional formation of traces of trimeric byproducts resulting
from metal scrambling further contributed to the lowered yields.
Spectral Properties of β,Meso-Linked Oligoporphyrins. As
expected, the UV/vis spectra of the free-base multichromo-
phores, 6a-j, cis/trans-8a, cis/trans-8b, 9a-f, and 10 showed
the B band (Soret band) at about 425 nm and the four Q
bands between 480 and 680 nm. In contrast to the UV/vis
spectrum of monomeric TPP, the Soret bands of dimeric and
trimeric porphyrins were broadened and split due to the
exciton coupling between the porphyrin subunits (Figure 2),
in analogy to other β,meso-coupled bisporphyrins and
in perfect accordance with the exciton coupling theory.52
(51) Further synthetic manipulations at a free meso-position of β,meso-
linked bisporphyrins by, e.g., nitration (with subsequent reduction to meso-
amino substituted bisporphyrins) or Vilsmeier formylation are currently
under investigation.
(52) (a) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy: Exciton
Coupling in Organic Stereochemistry; University Science Books: Mill Valley,
ꢀ
CA, 1983. (b) Rodger, A.; Norden, B. Circular Dichroism and Linear Dichro-
ism; University Press: Oxford, 1997.
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SCHEME 1. Synthesis of the Constitutionally Unsymmetric Triporphyrin 10
Consequently, a significant Davydov splitting of the B bands
was observed, with an energy gap ΔE (energetic difference
between the By and the Bx bands) of about 1200 and 1600
cm-1 for the β,meso-linked dimers and trimers, respectively.
In contrast to the dimeric porphyrins, the β,meso-triporphyr-
ins furthermore displayed a slight splitting of the energeti-
cally lower Q bands (ΔE about 650 cm-1).
decreased number of Q bands. The structurally complex
porphyrin trimer 10 shows a UV profile that can be perceived
as the superposition of a metal free and a fully metalated
triporphyrin (see the Supporting Information).
Characteristic NMR Properties. Depending on the proxi-
mity of the four different phenyl groups of the β-coupled
subunits relative to the central porphyrin-porphyrin axis,
1
The ΔE values observed for the β,meso-linked dimers
correlate with typical splittings reported for similar litera-
ture-known systems with a β,meso-linkage30 and, thus, range
between those of β,β0-22,24 and meso,meso0-coupled30 bispor-
phyrins, which show characteristic B-band splittings of
about 800 and 2100 cm-1, respectively. For β,meso-linked
triporphyrins, no exciton coupling energies have so far been
reported. The free-base β,meso-linked triads gave ΔE values
around 1800 cm-1, while slightly increased splitting energies
were observed for the fully metalated derivatives (ΔE value
of trans-8a-Zn3: 1950 cm-1). As compared to zincated meso,
their protons were found to vary largely in H NMR with
respect to the chemical shifts (Figure 3a,b). Especially the
central phenyl residues located above the meso-linked por-
phyrin macrocycle showed signals strongly shifted toward
higher field. Due to a π-stacking interaction between these
phenyl substituents and the adjacent, nearly coplanar-ar-
ranged porphyrin, they exhibited the most pronounced ring
current affected chemical shifts.54
Thus, for all dimeric porphyrins and for the trans-config-
ured trimers, the para-protons of the phenyl moiety at C200
(and C2000 for the trimers, see Scheme 1) appeared around
4.00 ppm (instead of 7.77 ppm in TPP), the meta-protons
were shifted to about 4.70 ppm (instead of resonating at 8.22
ppm as in TPP), and the ortho-protons were found in the
region from 6.75 to 6.95 ppm (instead of 7.77 ppm in TPP).55
However, in the trimers possessing a cis-relationship be-
tween the central phenyl moieties at C200 and C2000, the
protons seemed to be less affected by the ring current as
compared to the corresponding trans-diastereomers: The
respective para-protons resonated around 4.90 ppm, the
meta-protons appeared at 5.40 ppm, and the ortho-protons
were shifted to the region of 7.20 to 7.40 ppm, thus hinting at
a conformation of the cis-configured compounds in which
the central phenyl residues have “slipped” toward the mag-
netically less shielding periphery56,57 of the coplanar por-
phyrin moiety (see also Figures 6 and 8). This may be due to
meso0-linked porphyrin trimers (ΔE=3200 cm-1 19 the peak
)
splitting thus seems to be less significant following the trend
of decreasing splitting energies from the meso,meso0- via the
β,meso- to the β,β0-linkage as observed for differently linked
bisporphyrins. The cis-configured diastereomers cis-8a, cis-
8b, and cis-10 displayed UV profiles nearly identical to those
of the trans-analogues trans-8a, trans-8b, and trans-10.
In comparison to the Soret band of TPP, the By bands of
the novel porphyrin dimers and trimers appeared almost
unchanged regarding their wavelengths, whereas the Bx and
Q bands were red-shifted. In general, the Q-band absorp-
tions showed increased intensities, while the B band inten-
sities were slightly decreased as compared to the respective
bands in TPP.53
As expected, full metalation of the dimeric and trimeric
porphyrins gave rise to a higher molecular symmetry and,
thus, to a degeneration of the Q transitions resulting in a
(54) This characteristic upfield shift for the central phenyl residues had
previously been observed for similar dimeric porphyrin systems.22,28
(55) For a 1H NMR spectrum of TPP, see ref 22b.
(53) Especially for the highly unsymmetric derivatives a more detailed
assignment of electronic transitions and explicit discussion of the excitonic
effects in all multiporphyrins synthesized is hampered by a strong overlap of
multiple B bands, which is caused by the low symmetry of the compounds.
(56) (a) Cross, K. J.; Crossley, M. J. Aust. J. Chem. 1992, 45, 991–1004. (b)
Abraham, R. J.; Smith, K. M. J. Am. Chem. Soc. 1983, 105, 5734–5741.
(57) Iwamoto, H.; Horib, K.; Fukazawaa, Y. Tetrahedron Lett. 2005, 46,
731–734.
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FIGURE 3. Characteristic NMR shifts and selected NOESY cor-
relations of (a) trans-8a/b and (b) cis-8a/b.
additional steric constraints of the two central aryl substit-
uents being located on the same side of the central porphyrin
macrocycle.
A confirmation of this first, preliminary assignment of the
cis- and the trans-configured trimers based on the chemical
shifts of the protons of the C200 and C2000 phenyl moieties by
ROESY correlations was, however, not trivial, because, for
cis-8a and cis-8b, the corresponding ortho-, meta-, or para-
protons of the two phenyl substituents (C200 and C2000) are
chemically equivalent due to their enantiotopic or homo-
topic relationship, thus precluding the observation of any
ROESY interactions, e.g., between the two para-protons
(C2040 and C20400). On the other hand, a possible correlation
between the para- and the meta-protons should result in a
ROESY cross peak, but the “interphenyl” correlation (e.g.,
between the C2040 para-H and the C20300 meta-H) cannot be
distinguished from an “intraphenyl” interaction (e.g., be-
tween the C2040 para-H and the C2030 meta-H), since, again,
FIGURE 4. Characteristic NMR shifts and selected NOESY cor-
relations of (a) trans-10 and (b) cis-10.
As a consequence, due to their close structural similarity,
all trimers with the more downfield-shifted resonances of the
central aryl moieties were assigned to be cis-configured,
while the trimers exhibiting the less downfield shifted signals
have the trans-configuration. These assignments are in line
with the fact that the isomers that have thus been evidenced
to be trans-configured are the main products of the coupling
reactions, in agreement with their sterically less demanding
array.
Stereochemical Characterization of Chiral β,Meso-Linked
Porphyrin Dyads and Triads. The new oligoporphyrins are
interesting not only because of their physicochemical proper-
ties3,28 but also because some of them show, in addition,
rewarding stereochemical features. While the A3-, 5,15-A2-,
and 5,15-A2B-βTAP-type bisporphyrins 6a-g, 9a, and 9b
possess intramolecular mirror planes, which make them Cs-
symmetric, the constitutionally unsymmetric dimers rac-
6h-j, rac-6h-Zn2, and rac-9c-f (5,15-AB-βTAP type or
ABC-βTAP type) are C1-symmetric and, thus, axially chiral
due to their heterogeneous substitution pattern (exemplarily
shown for 6h, 9e, and 9f, Scheme 2).58
3
0
3
the two meta-protons (C20 and C20 00) are chemically
equivalent. ROESY correlations should thus, in principle,
be observed for both, the cis- and the trans-configured
trimers, cis-8a,b and trans-8a,b (Figure 3a,b).
A robust assignment according to 2D NMR correlations
was, however, easily possible for the highly unsymmetric
trimer 10 equipped with two different aryl moieties in the
core region: For the isomer of 10 with the less ring-current
affected chemical shifts, the para-methyl substituent of the
central C2000-tolyl moiety resonating at 0.35 ppm showed a
clear, diagnostically highly significant, ROESY correlation
with the para-proton (4.88 ppm) of the C200-phenyl substi-
tuent (Figure 4b). Thus, this isomer was attributed the cis-
configuration, while the other isomer, which gave no
ROESY correlation between the para-methyl group (-1.31
ppm) of the C2000 residue and any of the five protons of the
C200-phenyl moiety, was evidenced to be trans-configured
(Figure 4a).
The presumably chiral, C1-symmetric, and conformation-
ally stable dimeric porphyrins 6h, 6i, 6h-Zn2, and 9c-f
should exist as racemic mixtures of the two respective
atropo-enantiomers. However, despite many attempts on a
(58) For an example of a meso,meso0-linked bisporphyrin with an achiral
basic structure, which is, however, chiral due to its unsymmetric substitution
pattern, see ref 17.
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SCHEME 2. First Stereochemical Analysis of Axially Chiral β,Meso-Bisporphyrins: (a) Chemical Derivatization of 6h To Deliver 9e and
9f; (b) Comparison of the HPLC-CD Spectra (Measured in the Stopped-Flow Mode on a Chiral Phase) with the CD Curves Calculated
Quantum Chemically (TDPBEO/6-31G*); (c) Assigned Stereostructures of the M- and the P-Configured Atropo-Enantiomers,
Exemplarily for the β,Meso-Linked Bisporphyrin 9e
variety of chiral HPLC phases under different chromato-
graphic conditions, even at 0 °C, none of the bisporphyrins
6h, 6i, 9c, or 9d could be resolved into its expected enantio-
mers. Only for 6h-Zn2 was a slight “peak doubling” ob-
served, but the separation was not sufficient to permit online-
CD measurements. For this reason, a derivative of rac-6h
with a more polar functional group was prepared, viz. the
hydroxy-substituted dimer rac-9e (see Scheme 2): O-de-
This porphyrin dimer rac-9e now indeed gave a satisfy-
ing separation on a Chirex 3010 column (Phenomenex) at
room temperature using n-hexane-dichloromethane (v/v
80:20, isocratic, flow: 0.7 mL/min) as the solvent system
(Scheme 2). The novel dimers rac-6h-j, rac-6h-Zn2, rac-9c,
and rac-9c-f are the first examples of axially chiral β,meso-
linked bisporphyrins described so far.
That the two resulting LC-UV peaks indeed corre-
sponded to the two respective atropo-enantiomers of 9e
was clearly demonstrated by their opposite CD effects, as
measured by LC-CD coupling in the stopped-flow mode,
providing a positive CD signal for the faster eluting peak A
and a negative one for the slower eluting peak B at 485 nm.
For the determination of the absolute configurations of
the two atropo-enantiomers, full online-CD spectra were
59
methylation of the dimer rac-6h-Zn2 with BBr3 gave the
hydroxy derivative rac-9e in 72% yield, accompanied by
complete demetalation. Starting from the free-base bispor-
phyrin rac-6h, rac-9e was obtained in 81% yield.
(59) (a) McOmie, J. F. W.; Watts, M. L.; West, D. E. Tetrahedron 1968,
24, 2289–2292. (b) Milgrom, L. R. J. Chem. Soc., Perkin Trans. I 1983, 2535–
2539.
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FIGURE 5. (a) Stereostructures of the C2h-symmetric triporphyrin trans-8a and (b) of the C2v-symmetric trimer cis-8a.
For this reason and due to the fact that the dimer 9e is highly
unsymmetric (C1-symmetry), attribution of its absolute config-
uration by application of the exciton chirality method52 was not
possible. Likewise excluded was an empirical comparison of its
CD spectra with those of other porphyrin dimers, due to the
unprecedented structure of 9e. For this reason, quantum chemi-
cal CD calculations seemed to be the method of choice, despite
the size of the molecule. Thus, the structure of the dimer 9e was
optimized with RI-PBE/SV(P)61,62 in combination with a dis-
persion correction to take into account π,π-interactions between
the phenyl substituent next to the axis and the adjacent porphyr-
in moiety.63 TDPBEO/6-31G*61,64 calculations involving the
first 45 excitations and a UV correction65 of 50 nm finally yielded
the calculated CD curves, which were then compared with the
experimental ones. Accordingly, the faster peak A was evidenced
to be M-configured while the slower eluting peak B was found to
be P-configured. Thus, in the case of 9e, application of the
exciton chirality method52 or comparison of the CD spectra with
those of related porphyrin dimers would indeed have led to a
wrong configurational assignment.66,67
Coming back to the enantiomeric resolution of rac-9e:
While the chromatographic separation on a chiral phase
succeeded after setting free the phenolic OH-group (see
above), the respective Mosher derivatives68,69 S,M-9f and
(61) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77,
3865–3868.
FIGURE 6. Possible C2-symmetric chiral conformation of cis-8a
that might be stereochemically stable depending on the size of the
“inner” aryl groups.
€
(62) Schafer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571–7.
(63) Such π-stacking interactions had been substantiated for structurally
related bisporphyrins by X-ray diffraction analysis.22
(64) (a) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1997, 78,
1396. (b) Perdew, J. P.; Ernzerhof, M.; Burke, K. J. Chem. Phys. 1996, 105,
9982–9985. (c) Ernzerhof, M.; Scuseria, G. E. J. Chem. Phys. 1999, 110,
5029–5036. (d) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.;
Gordon, M. S.; Defrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654–
3665. (e) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213–22.
(65) Bringmann, G.; Bruhn, T.; Maksimenka, K.; Hemberger, Y. Eur. J.
Org. Chem. 2009, 2717–2727.
recorded, giving mirror-imaged CD curves with a positive
first Cotton effect around 485 nm for the faster and a
negative one for the slower enantiomer.
These CD spectra revealed a remarkable feature: While in
all other literature-known, axially chiral meso,meso0-17 or
β,β0-linked bisporphyrins,22 the inflection points of the
strongest CD effects correlate with the minimum between
the By and the Bx band in the UV spectrum, the CD curves of
9e display their major Cotton effects around 485 nm, i.e.,
red-shifted by about 55 nm.60
(66) For β,β0-bisporphyrins reported previously22 the assignment of the
absolute axial configuration by applying the exciton chirality approach was
in agreement with the result of quantum chemical CD calculations; in
general, however, the interpretation of CD spectra of directly linked dimeric
porphyrins by the exciton chirality method is critical.67
(67) Muranaka, A.; Asano, Y.; Tsuda, A.; Osuka, A.; Kobayashi, N.
ChemPhysChem 2006, 7, 1235–1240.
(68) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543–
2549.
(60) A more detailed discussion of this finding is not possible without in-
depth investigation of the electronic transitions of the bisporphyrin 9e using,
for example, MCD measurements in combination with quantum chemical
calculations. This is currently under investigation.
(69) The free hydroxy function of rac-9e permitted esterification with R-
Mosher’s acid chloride68 on an analytical scale (1 mg) using triethylamine in
dry CH2Cl2 to yield rac-9f in quantitative yield: HRMS (ESI) calcd for
C86H66N8O3F3 [M þ Hþ] 1315.5205, found 1315.5205.
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FIGURE 7. (a) Stereostructure of the chiral, C2-symmetric trimer trans-8b. (b) Cs-symmetric meso-like conformation of cis-8b.
S,P-9f;despite being diastereomers!;could not be re-
solved, not even on a chiral phase.70 Still, the free OH group
of 9e will be useful for other purposes, e.g., for the attach-
ment of such porphyrin dimers to biomolecules71 or dendri-
meric backbones.72
In the case of the porphyrin trimers 8a, 8b, and 10, the
stereochemical analysis becomes more complex: As already
mentioned, all trimers were formed as a diastereomeric
mixture of two atropo-isomers, i.e. the “trans”-isomers with
the two aryl substituents pointing toward the central por-
phyrin being located at opposite sides of the central macro-
cycle and the “cis”-isomers with the aryl moieties being on
the same side (Figures 5 and 7).45 For all porphyrin trimers
synthesized the respective diastereomers were separable by
column chromatography on usual silica gel. The ratios of the
cis-configured isomers as compared to the trans-configured
ones (cis-8a/trans-8a=1:2, cis-8b/trans-8b=1:1.5, and cis-
10/trans-10=1:3.5; Table 3 and Scheme 1) evidenced that the
cis-orientation of the central phenyl rings is sterically more
demanding than the trans-orientation.
(70) In addition, the Mosher derivative of 9e did not give a double set of
signals in 1H NMR, as would have been expected for the two resulting
diastereomers S,M-9f and S,P-9f. Most probably, the position of the
stereocenter is too peripheral to influence, e.g., the protons of the central
C200-phenyl moiety.
(71) For a recent review on porphyrin bioconjugates, see: (a) Hudson, R.;
Boyle, R. W. J. Porphyrins Phthalocyanines 2004, 8, 954-975 and references
cited therein. For some recent, selected publications on porphyrin bioconjugates,
see: (b) Sutton, J. M.; Fernandez, N.; Boyle, R. W. J. Porphyrins Phthalocya-
nines 2000, 4, 655–658. (c) Sutton, J. M.; Clarke, O. J.; Fernandez, N.; Boyle, R.
W. Bioconjugate Chem. 2002, 13, 249–263. (d) Hudson, R.; Carcenac, M.; Smith,
ꢁ
K.; Madden, L.; Clarke, O. J.; Pelegrin, A.; Greenman, J.; Boyle, R. W. Br. J.
FIGURE 8. Chiral conformations of cis-8b with C1 symmetry,
potentially stable depending on the temperature and the size of
the substituent R (here investigated for R = H for cis-8b).
Cancer 2005, 92, 1442–1449. (e) Sibrian-Vazquez, M.; Jensen, T. J.; Fronczek, F.
R.; Hammer, R. P.; Vicente, M. G. H. Bioconjugate Chem. 2005, 16, 852–863. (f)
Borbas, K. E.; Mroz, P.; Hamblin, M. R.; Lindsey, J. S. Bioconjugate Chem. 2006,
17, 638–653. (g) Borbas, K. E.; Kee, H. L.; Holten, D.; Lindsey, J. S. Org. Biomol.
Chem. 2008, 6, 187–194. (h) Jiang, M. Y.; Dolphin, D. J. Am. Chem. Soc. 2008,
130, 4236–4237. (i) Muresan, A. Z.; Lindsey, J. S. Tetrahedron 2008, 64, 11440–
11448. (j) Sibrian-Vazquez, M.; Nesterova, I. V.; Jensen, T. J.; Vicente, M. G. H.
Bioconjugate Chem. 2008, 19, 705–713.
(72) For selected reviews on dendrimeric porphyrins, see: (a) Venturi, M.;
Serroni, S.; Juris, A.; Campagna, S.; Balzani, V. Top. Curr. Chem. 1998, 197,
193–228. (b) Jiang, D.-L.; Sadamoto, R.; Tomioka, N.; Aida, T. In Hyper-Struct.
Mol. I; Sasabe, H., Ed.; Taylor & Francis, CRC Press: Boca Raton, FL, 1999; pp
63-73. (c) Aida, T.; Jiang, D.-L. In The Porphyrin Handbook; Kadishi, R. K.,
Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 3, pp
369-384. (d) Balzani, V.; Ceroni, P.; Juris, A.; Venturi, M.; Campagna, S.;
Puntoriero, F.; Serroni, S. Coord. Chem. Rev. 2001, 219-221, 545–572. (e) Jang,
W.-D.; Nishiyama, N.; Kataoka, K. Supramol. Chem. 2007, 19, 309–314.
Due to their intramolecular mirror planes, the C2h-sym-
metric βTAP-A2-βTAP triporphyrin trans-8a (Figure 4a)
and, in particular, the C2v-symmetric trimer cis-8a
(Figure 5b) should be achiral meso-compounds. This is
indeed the case for trans-8a (Figure 5a). The cis-configured
diastereomer cis-8a, however, although, at first sight, even
possessing two planes of symmetry, actually still might be
chiral depending on steric factors (Figure 6): Thus, if the size
of the para-substituents R (R = H for cis-8a) was sufficiently
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FIGURE 9. (a) Stereostructure of the chiral, C1-symmetric trimer trans-10. (b) Chiral, C1-symmetric porphyrin triad cis-10.
large to prevent the two central aryl moieties from passing
each other, cis-8a should adopt a C2-symmetric conforma-
tion and, as a consequence, exist in the form of two enantio-
mers, cis-8a* and ent-cis-8a* (Figure 6). In addition, π-
stacking interactions between the phenyl substituents and
the central porphyrin (as already substantiated by X-ray
diffraction analysis for similar systems)22,28 might contribute
to the activation energy of the racemization process inter-
converting cis-8a* and ent-cis-8a*. At least in the case of
sterically more demanding substituents R (like, e.g., for
methyl or larger substituents), the rotational barrier should
be high enough to guarantee conformational stability of such
enantiomers. This stereochemical feature would be unique
since, in contrast to all other axially chiral dimers reported so
far, the chirality would not result from an intrinsically chiral
β,β0-coupling22 or (as required in the case of β,meso-28-30 or
meso,meso0-linked16-20 dimers) from an unsymmetric sub-
stitution pattern but would arise from a stable chiral con-
formation of the otherwise symmetric porphyrin backbone
itself, again independent from further unsymmetrically lo-
cated substituents.
In contrast to trans-8a, the constitutionally unsymmetric
porphyrin trimer trans-8b lacks an intramolecular plane of
symmetry due to the heterogeneous 5,15-AB substitution
pattern of the central porphyrin subunit (Figure 7a). Thus,
the C2-symmetric trimer trans-8b should exist as a racemic
mixture of its two atropo-enantiomers, P,P-8b and M,M-8b
(i.e., both with the same relative like-configuration). Unfor-
tunately, despite intensive efforts, we did not succeed in
resolving trans-8b into its atropo-enantiomers P,P-8b and
M,M-8b by HPLC using different chiral stationary phases
with various chromatographic conditions.
least on the NMR time scale. These VT-NMR investigations
are discussed in detail below.
Due to its C1 symmetry, the structurally complex porphyr-
in triad 10 lacks any intramolecular mirror planes, for the
trans-configuration (trans-10), and;in contrast to the
above-discussed trimers cis-8a and cis-8b;also for the cis-
configured isomer, cis-10. Consequently, besides trans-10
(like-configuration, Figure 9a) even the cis-configured tri-
porphyrin cis-10 should be chiral, existing as a racemic
mixture of two atropo-enantiomers, M,P-10 and P,M-10
(both with a relative unlike-configuration, Figure 9b). It is
noteworthy that this chirality of cis-10 is, in contrast to that
of cis-8a/b, independent from the spatial arrangement of the
central phenyl residues because it is C1-symmetric and can,
thus, never adopt a meso-like conformation.
The chirality of cis-10 per se is combined with the addi-
tional chiral element resulting from the central aryl moieties
(viz. the C2000-tolyl and the C200-phenyl group), which might
again adopt stable;now additionally diastereomeric;con-
formations, with these inner aryl residues “slipped” toward
the periphery of the central porphyrin core. This constella-
tion would, thus, give rise to the existence of now even four
stereoisomers of cis-10, namely M,P-10, P,M-10, M,P-100,
and P,M-100 (Figure 10).
Resolution of the supposed stereoisomers did, however,
not succeed by HPLC on a chiral phase. In analogy to the
VT-NMR measurements performed for cis-8b (see the fol-
lowing text), further investigations of the highly unsym-
metric triporphyrin cis-10 by VT-NMR will shed light on
the proposed existence of additional chiral stereogenic ele-
ments of such porphyrin trimers (besides the β,meso-axes)
that are more or less stable on the NMR time scale. This
work is in progress.
1
Variable-Temperature H NMR Investigations of the Tri-
As already discussed in detail for cis-8a, the existence of
stereochemically stable conformational enantiomers of cis-
8b (i.e., with unlike-configuration, Figure 6b) should again
depend on the sterical demand of the aryl residues that point
toward the center of the triporphyrin and, thus, on the
question whether, at a given temperature, cis-8b adopts an
achiral, meso-like, Cs-symmetric conformation (averaged
over time) or a stable chiral C1-symmetric array (Figure 8).
Although no chromatographic resolution of the supposed
atropo-enantiomers succeeded as yet, clear hints at a chiral
conformation of cis-8b at low temperatures were obtained, at
porphyrin cis-8b. To gain further insight into the dynamic
behavior and, thus, into the chiral nature of the triporphyrins
synthesized, low-temperature NMR measurements were
performed, exemplarily for the unlike-configured trimer
cis-8b.
1
As expected, the H NMR of cis-8b showed five signals
for the 10 protons of the central phenyl residues at C200
and C2000 at room temperature (Figure 11).73 Due to the
3
(73) At room temperature the signals of the ortho-protons (20 /20 - and
5
0
0
20300/20500-H) are partially covered by the CDCl3 signal.
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FIGURE 10. Four possible stereoisomers of cis-10 based on the assumption that;besides the two chiral axes;the conformational twisting of
the central aryl moieties may constitute an additional stereogenic element.
FIGURE 11. Variable-temperature NMR spectra of cis-8b showing 10 distinct signals for the protons of the “inner” phenyl substituents (one
meta-H is covered by a hexyl resonance) at low temperatures.
Cs-symmetric “average conformation” of cis-8b the corre-
sponding ortho-, meta-, and para-protons (integrals 2:2:2:
2:2) are pairwise homotopic, thus resulting in two equivalent
ABMNX spin systems. Upon cooling, the resonances of the
meta- and para-protons appeared broadened and finally split
into a total of 10 distinct signals (including the resonances of
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the ortho-protons) at -60 °C. Thus, from the resulting two
separated ABMNX spin systems for the two central phenyl
moieties, all protons of the “inner” phenyl substituents are
nonequivalent under these conditions, and the molecule
must have adopted a C1-symmetric structure! This corrobo-
rates the assumption that the central aryl moieties (viz. the
C2000-tolyl and the C200-phenyl group) can attain stable
conformations with these aryl residues “slipped” toward
the periphery of the central porphyrin core, thus;besides
the two chiral axes;providing an additional and different
element of chirality which had not been recognized so far!
The NH protons of the “outer” porphyrin macrocycles
were broadened, decreased in intensity, and split into two
signals, surprisingly integrating in a ratio of 1:4.2. We
attribute this finding to the existence of two “frozen” main
NH-tautomers, differing in their relative stabilities.74
trimer 10 possessing two direct porphyrin-porphyrin axes,
three different metal centers, two different substituents at
C10 and C20, and two differently substituted TAP moieties
in positions 5 and 10. Porphyrin trimers with a comparable
structural complexity had not yet been described in the
literature.
The novel compounds show remarkable stereochemical
features. Thus, the bisporphyrins 6h, 6i, 6h-Zn2, and 9c-f
were shown to exist as racemic mixtures as demonstrated by
enantiomeric resolution of rac-9e by HPLC on a chiral phase
in combination with online LC-CD measurements. Axially
chiral β,meso-linked bisporphyrins had not been reported
before. The synthesized porphyrin trimers, by contrast, were
even isolated as two configurationally stable atropo-diaster-
eomers, the trans-isomers, with the two “inner” aryl substit-
uents (i.e., those that point toward the central porphyrin)
being located at opposite sides of the central macrocycle, and
the cis-isomers, with the aryl moieties being on the same side.
The novel C2-symmetric porphyrin triads trans-8b, trans-10,
and cis-10 presented in this paper constitute the first exam-
ples of axially chiral β,meso-linked triporphyrins. And even
the cis-configured trimeric porphyrins cis-8a and cis-8b,
although being meso-like;and thus achiral at first sight;
are stereochemically intriguing, since they can, depending on
the steric constraints, also adopt C1-symmetric (and thus
chiral) conformations, as proven by detailed VT-NMR
investigations of the triporphyrins. To the best of our knowl-
edge, chirality originating from a similar phenomenon has
not been observed so far. This makes the synthesis of related,
but sterically more congested, cis-configured porphyrin tri-
mers possibly existing as two configurationally stable enan-
tiomers already at room temperature, a rewarding task. This
work is currently in progress.
Conclusion
In summary, a variable and straightforward procedure for
the synthetic construction of achiral and chiral β,meso-
linked porphyrin arrays has been established. The key step
of the synthesis was an optimized Suzuki coupling of β-
borylated tetraarylporphyrins as previously synthesized for
the first time by some of us.22 Using an optimized C-C
coupling protocol, several constitutionally symmetric and
unsymmetric β,meso-bisporphyrins;differing in their sub-
stitution pattern and in their metalation states;were effi-
ciently prepared.
Furthermore, novel β,meso-linked porphyrin trimers pos-
sessing two direct porphyrin-porphyrin axes have become
available by the presented strategy in good yields and at a
200-mg scale. Thus, a broad structural diversity of β,meso-
linked porphyrin triads has been synthesized, again differing
in their substitution pattern, in the metalation states of the
subunits, and, in addition, in the spatial arrangement (cis- vs
trans-geometry) of the chromophores.
The generated porphyrin dimers can contain a free meso-
position amenable to further synthetic manipulations as
shown, e.g., by the synthesis of the brominated dimers 9a,
9b, and rac-9c. These brominated bisporphyrins constitute
valuable precursors for the synthesis of meso-borylated
porphyrin dimers, which can serve as versatile building
blocks for the construction of complex porphyrin multi-
chromophores.50 Moreover the introduction of another
meso-substituent into a bisporphyrin with a free meso-posi-
tion was achieved by addition of organolithium reagents
followed by oxidation with DDQ,34 as demonstrated by the
successful synthesis of rac-9d. The reaction regioselectively
takes place at the free meso-position of the bisporphyrin
starting material. Thus, time-consuming multistep syntheses
of highly functionalized bisporphyrins can be avoided by the
late-stage divergent modification of preformed porphyrin
dimers.
The synthetic results show that the presented protocols
permit a rapid generation of a plethora of structurally
diverse, constitutionally unsymmetric oligoporphyrins with
enhanced optical properties and unexpected stereochemical
features. Moreover, the introduced synthetic strategy is
applicable to the construction of amphiphilic porphyrin
dimers and trimers for use in photodynamic therapy and
for the synthesis of push-pull chromophores for optical
applications, and it can provide useful precursors for the
preparation of larger, superstructured porphyrin assemblies.
Experimental Section
Synthesis of β,meso-Linked Bisporphyrins 6 (Typical Procedure).
5,10,15-Triphenyl-20-(50,100,150,200-tetraphenylporphyrin-20-yl)-
porphyrin (6a). A Schlenk flask filled with 5-bromo-10,15,20-
triphenylporphyrin (5a, 164 mg, 266 μmol, 1 equiv), β-borylated
TPP 4a (295 mg, 398 μmol, 1.5 equiv), and Ba(OH)2 8H2O (839
3
mg, 2.66 mmol, 10 equiv) was evacuated and flushed with nitrogen
three times. Toluene (50 mL) and deionized H2O (10 mL) were
added, and the solution was degassed by a nitrogen stream in an
ultrasonic bath for 15 min. Pd(PPh3)4 (61.5 mg, 53.2 μmol, 20 mol
%) was added, and the resulting mixture was refluxed for 20 h
with vigorous stirring. The crude mixture was cooled to room
temperature and passed through a short plug of silica gel eluting
with CH2Cl2. Concentration of the filtrate and purification of
the resulting residue by column chromatography on silica gel
using CH2Cl2/n-hexane (1:1, v/v) as the eluent afforded 6a as
a purple solid (199 mg, 173 μmol, 65%): Rf = 0.14 (CH2Cl2/
hexane, 1:1, v/v); mp (CH2Cl2/MeOH): >300 °C; IR (ATR)
ν~=3313 (w), 3053 (m), 2920 (m), 2851 (w), 1595 (m), 1556 (w),
The broad applicability and the efficiency of the estab-
lished procedures was finally demonstrated by the successful
synthesis of the highly unsymmetric, axially chiral porphyrin
(74) This assumption is affirmed by the fact that, in the course of our
investigations, RI-PBE-D/SV(P) calculations of a dimeric model system
predicted the existence of two main tautomers (regarding the NH protons
of the β-linked porphyrin macrocycle) in a ratio of 1:2.8 in the gas phase.
Detailed investigations on this phenomenon are in progress.
J. Org. Chem. Vol. 74, No. 21, 2009 8019

€
Gotz et al.
JOCFeatured Article
1471 (m), 1439 (m), 1347 (m), 1173 (m), 1071 (m), 1001 (m), 979
Hz, 2H, β-pyrrole-H), 8.98 (d, 3J=4.8 Hz, 2H, β-pyrrole-H), 9.03
(d, 3J=4.8 Hz, 2H, β-pyrrole-H), 9.83 (s, 1H, 30-β-pyrrole-H/1H,
300-β-pyrrole-H) ppm; 13C NMR (150 MHz, CDCl3) δ= 116.1,
120.2, 120.3, 120.4, 120.7, 122.1, 122.2 (two peaks), 124.0,
126.6 (two peaks), 126.7, 126.8, 127.5, 127.6, 127.7 (two peaks),
127.8, 131.9, 134.5 (two peaks), 134.7, 134.8, 138.7, 142.0, 142.2,
142.4, 142.6 ppm; HRMS (ESI) calcd for C120H79N12 [M þ
Hþ] 1686.6545, found 1686.6545; UV-vis (CH2Cl2) λmax
(log ε) = 419 (5.57), 455 (5.50), 522 (4.85), 574sh (4.43), 594
(4.49), 650 (4.10), 666 (4.10) nm. Compound cis-8a:
Rf = 0.09 (CH2Cl2/hexane, 1:1, v/v); mp (CH2Cl2/MeOH) >
300 °C; IR (ATR) ν~=3315 (w), 3054 (w), 2920 (m), 2850 (w),
1596 (m), 1559 (w), 1472 (m), 1440 (m), 1347 (m), 1259 (m), 1176
(m), 962 (s), 796 (s) cm-1; 1H NMR (400 MHz, CDCl3) δ= -2.80
(bs, 2H, NH), -2.34 (bs, 2H, NH), 4.05 (app t, appJ (H,H) ≈ 7.6
Hz, 1H, p-20 -Ar-H), 4.75 (app t, appJ (H,H) ≈ 7.6 Hz, 1H, m-
4
0
3
5
20 -Ar-H/1H, m-20 -Ar-H), 6.89 (app d, appJ (H,H) ≈ 7.6 Hz,
0
0
2
6
0
0
1H, o-20 -Ar-H/1H, o-20 -Ar-H), 7.62-7.85 (m, 18H, Ar-H),
8.14-8.18 (m, 2H, Ar-H), 8.19-8.24 (m, 3H, Ar-H/1H, β-pyr-
role-H), 8.29-8.36 (m, 4H, Ar-H), 8.37-8.42 (m, 1H, Ar-H),
8.44-8.49 (m, 2H, Ar-H), 8.59 (d, 3J=4.8 Hz, 2H, β-pyrrole-H),
8.63 (d, 3J=4.8 Hz, 1H, β-pyrrole-H), 8.66 (d, 3J=4.8 Hz, 1H, β-
pyrrole-H), 8.83-8.89 (m, 5H, β-pyrrole-H), 8.90 (d, 3J= 4.8 Hz,
1H, β-pyrrole-H), 8.98 (d, 3J=4.8 Hz, 1H, β-pyrrole-H), 9.01 (d, 3J
=4.8 Hz, 1H, β-pyrrole-H), 9.69 (s, 1H, 30-β-pyrrole-H) ppm; 13C
NMR (100 MHz, CDCl3): δ=120.2, 120.4 (two peaks), 120.5,
122.2, 122.4, 124.1, 126.8, 126.9 (two peaks), 127.0, 127.7, 127.8
(two peaks), 127.9, 128.0, 132.2, 134.5, 134.6, 134.7, 134.8 (two
peaks), 134.9 (two peaks), 139.1, 142.1, 142.3, 142.4, 142.6 (two
peaks) ppm; HRMS (ESI) calcd for C82H54N8 [Mþ] 1150.4466,
found 1150.4466; UV-vis (CH2Cl2) λmax (log ε) = 422 (5.72), 441
(5.73), 522 (4.79), 559 (4.31), 597 (4.15), 654 (3.61) nm.
(m), 1071 (m), 1030 (w), 1001 (m), 979 (m), 962 (s), 796 (s) cm-1
;
1H NMR (600 MHz, CDCl3) δ=-2.86 (bs, 2H, “inner” NH),
-2.29 (bs, 4H, “outer” NH), 4.85 (app t, appJ (H,H) ≈ 7.7 Hz, 1H,
4
0
4
3
0
p-20 -Ar-H/1H, p-20 00-Ar-H), 5.26-5.38 (m, 1H, m-20 -Ar-H/
5
0
3
5
1H, m-20 -Ar-H/1H, m-20 00-Ar-H/1H, m-20 00-Ar-H), 7.24 (app
d, appJ (H,H) ≈ 6.8 Hz, 1H, o-20 -Ar-H/1H, o-20 -Ar-H/1H, o-
2
0
6
0
20200-Ar-H/1H, o-20600-Ar-H), 7.58-7.70 (m, 10H, Ar-H),
3
Synthesis of β,Meso-Linked Triporphyrins
8
(Typical
7.71-7.80 (m, 8H, Ar-H), 7.81-7.86 (m, 6H, Ar-H), 8.15 (d, J
Procedure). 5,15-Diphenyl-10,20-bis-(50,100,150,200-tetraphenyl-
porphyrin-20-yl)porphyrin (8a). A Schlenk flask filled with 5,15-
dibromo-10,20-diphenylporphyrin (7a, 84 mg, 135 μmol, 1
equiv), β-borylated TPP 4a (250 mg, 338 μmol, 2.5 equiv), and
=7.4 Hz, 2H, Ar-H), 8.22-8.29 (m, 4H, Ar-H), 8.30-8.36 (m,
4H, Ar-H), 8.37-8.46 (m, 6H, Ar-H/2H, β-pyrrole-H), 8.58 (d, 3J
=4.8 Hz, 4H, β-pyrrole-H), 8.64 (d, 3J=4.8 Hz, 4H, β-pyrrole-H),
8.73 (d, 3J=4.8 Hz, 2H, β-pyrrole-H), 8.90 (d, 3J= 4.8 Hz, 2H, β-
pyrrole-H), 8.93 (d, 3J = 4.8 Hz, 2H, β-pyrrole-H), 8.98 (d, 3J=
4.8 Hz, 2H, β-pyrrole-H), 9.01 (d, 3J=4.8 Hz, 2H, β-pyrrole-H),
9.61 (s, 1H, 30-β-pyrrole-H/1H, 300-β-pyrrole-H) ppm; 13C NMR
(150 MHz, CDCl3) δ=116.1, 120.4, 120.5, 121.0, 122.1, 122.8,
124.3, 126.7, 126.8, 126.9 (two peaks), 127.0, 127.7, 127.9 (two
peaks), 128.0, 133.0, 134.7, 134.8, 134.9, 139.8, 142.1, 142.4, 142.5
(two peaks) ppm; HRMS (ESI) calcd for C120H79N12 [M þ Hþ]
1686.6545, found 1686.6546; UV-vis (CH2Cl2) λmax (log ε) = 419
(5.54), 454 (5.45), 521 (4.79), 574sh (4.36), 595 (4.52), 650 (4.01),
664 (4.02) nm.
Ba(OH)2 8H2O (852 mg, 2.70 mmol, 20 equiv) was evacuated and
3
flushed with nitrogen three times. Toluene (50 mL) and deionized
H2O (10 mL) were added, and the solution was degassed by a
nitrogen stream in an ultrasonic bath for 15 min. Pd(PPh3)4 (31.2
mg, 27.0 μmol, 20 mol %) was added, and the resulting mixture
was refluxed for 24 h with vigorous stirring. The crude mixture
was cooled to room temperature and passed through a short plug
of silica gel eluting with CH2Cl2. Concentration of the filtrate
afforded 8a as a mixture of diastereomers that were isolated in
pure form after column chromatography on silica gel using n-
hexane/CH2Cl2 (1:1, v/v) as the eluent: The first eluting tripor-
phyrin band yielded the trans-isomer trans-8a (purple solid, 118
mg, 70.2 μmol, 52%) while the second eluting band contained the
respective cis-isomer cis-8a (purple solid, 60.9 mg, 36.1 μmol,
27%). Compound trans-8a: Rf = 0.19 (CH2Cl2/hexane, 1:1,
v/v); mp (CH2Cl2/MeOH) >300 °C; IR (ATR)
ν~=3310 (w), 3054 (m), 2922 (m), 1597 (m), 1559 (w), 1472 (m),
1439 (m), 1347 (m), 1244 (m), 1172 (m), 1072 (m), 1032 (m), 1001
(m), 979 (m), 962 (s), 793 (s) cm-1; 1H NMR (600 MHz, CDCl3) δ
=-2.83 (bs, 2H, “inner” NH), -2.33 (bs, 4H, “outer” NH), 4.00
Acknowledgment. The authors gratefully acknowledge
Carina Grimmer and Dr. Sabine Horn for preparing
several of the monomeric porphyrin precursors, and
Dr. Matthias Grune for carrying out the VT-NMR measure-
ments. This work was supported by the Degussa-Stiftung,
the Studienstiftung des deutschen Volkes e.V. (fellowships to
€
€
D. C. G. Gotz), and the Science Foundation Ireland
(Research Professorship Award o4/RP1/B482 to MOS).
4
(app t, appJ (H,H)
≈
7.6 Hz, 1H, p-20 -Ar-H/1H,
0
p-20400-Ar-H), 4.68 (app t, J (H,H) ≈ 7.4 Hz, 1H, m-20 -Ar-
app
3
0
5
0
3
5
H/1H, m-20 -Ar-H/1H, m-20 00-Ar-H/1H, m-20 00-Ar-H), 6.86
Supporting Information Available: General experimental
details, all experimental procedures at full length, detailed
2D NMR correlations, copies of the 1H, 13C, COSY, and
ROESY NMR spectra, CD spectra, chromatographic
conditions for the resolution of the atropisomers, and infor-
mation concerning the computational methods. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(app d, appJ (H,H) ≈ 6.9 Hz, 1H, o-20 -Ar-H/1H, o-20 -Ar-H/
1H, o-20200-Ar-H/1H, o-20600-Ar-H), 7.65-7.78 (m, 18H, Ar-H),
7.80-7.86 (m, 6H, Ar-H), 8.18-8.23 (m, 4H, Ar-H/2H, β-pyr-
role-H), 8.24-8.28 (m, 4H, Ar-H), 8.30-8.35 (m, 4H, Ar-H),
8.49-8.53 (m, 4H, Ar-H), 8.59 (d, 3J=4.8 Hz, 4H, β-pyrrole-H),
8.63 (d, 3J=4.8 Hz, 2H, β-pyrrole-H), 8.66 (d, 3J=4.8 Hz, 4H, β-
pyrrole-H), 8.86 (d, 3J=4.8 Hz, 2H, β-pyrrole-H), 8.90 (d, 3J=4.8
2
0
6
0
8020 J. Org. Chem. Vol. 74, No. 21, 2009