J . Org. Chem. 2002, 67, 1403-1406
1403
macrocycle and hydrogen-bond functionality are juxta-
posed in a side-to-side arrangement.
P or p h yr in Ar ch itectu r es Bea r in g
F u n ction a lized Xa n th en e Sp a cer s
We sought to extend our PCET studies to the multi-
electron activation chemistry of oxygen and other small
molecules.2,5 To this end, we have developed methods for
the facile assembly of symmetric cofacial bisporphyrins
bearing dibenzofuran (DPD)14,15 and xanthene (DPX)16
spacers that exhibit variable pocket sizes with minimal
lateral displacements. In these systems, the face-to-face
arrangement of porphyrin subunits allows for the ef-
ficient delivery of the oxidizing or reducing equivalents
necessary to effect the overall multielectron activation
of small molecule substrates.
Christopher J . Chang, Chen-Yu Yeh, and
Daniel G. Nocera*
Department of Chemistry, 6-335, Massachusetts Institute of
Technology, 77 Massachusetts Avenue,
Cambridge, Massachusetts 02139
nocera@mit.edu
Received September 6, 2001
Abstr a ct: A modular synthetic strategy for the construction
of cofacial porphyrin architectures bearing hydrogen-bond
synthons on a xanthene platform is presented. The conver-
gent approach is based on a xanthene aldehyde-ester build-
ing block that is easily obtainable on a multigram scale with
minimal purification. Treatment of this xanthene derivative
with a variety of aryl aldehydes and pyrrole under standard
Lindsey conditions affords a family of meso-substituted
porphyrins bearing a single functionalized xanthene spacer.
Direct modification of the hydrogen-bond synthon after
macrocyclization proceeds smoothly to furnish porphyrin
systems with a variety of cofacial functionalities (e.g.,
carboxylic acid, ester, amide). Porphyrins bearing two trans-
functionalized xanthene spacers are prepared by the Mac-
Donald [2 + 2] condensation of the xanthene aldehyde-ester
with readily available 5-aryl-substituted dipyrromethanes
such as 5-mesityldipyrromethane to afford the pure R,R- and
R,â-porphyrin atropisomers after chromatographic separa-
tion. The versatility of this synthetic method offers intrigu-
ing opportunities for the use of these and related templates
for the study of proton-coupled activation of small molecules.
A complement to both these approaches is the con-
struction of chemical architectures containing porphyrins
and hydrogen-bond synthons in a face-to-face arrange-
ment.17-32 To achieve this goal, we recently introduced
asymmetric cofacial platforms in which the rigid xan-
thene anchor is used to “hang” a hydrogen-bond func-
tionality over the porphyrin macrocycle (HPX ) hanging
porphyrin xanthene).33 Remarkably, the monomeric iron-
(III) hydroxide derivative of this “Hangman” porphyrin
has the unprecedented ability to orient exogeneous water
via hydrogen bonding, affording a minimalist model for
the heme/water channel assemblies found in the oxygen-
activating cytochrome P450 enzymes. In this report, we
describe the design and synthetic details for preparing
this novel HPX porphyrin and expand this approach to
afford a modular and facile methodology for the synthesis
(11) Deng, Y.; Roberts, J . A.; Peng, S.-M.; Chang, C. K.; Nocera, D.
G. Angew. Chem., Int. Ed. Engl. 1997, 36, 2124-2127.
(12) Roberts, J . A.; Kirby, J . P.; Wall, S. T.; Nocera, D. G. Inorg.
Chim. Acta 1997, 263, 395-405.
(13) Yeh, C.-Y.; Miller, S. E.; Carpenter, S. D.; Nocera, D. G. Inorg.
Chem. 2001, 40, 3643-3646.
(14) Deng, Y.; Chang, C. J .; Nocera, D. G. J . Am. Chem. Soc. 2000,
122, 410-411.
(15) Chang, C. J .; Deng, Y.; Shi, C.; Chang, C. K.; Anson, F. C.;
Nocera, D. G. Chem. Commun. 2000, 1355-1356.
(16) Chang, C. J .; Deng, Y.; Heyduk, A. F.; Chang, C. K.; Nocera,
D. G. Inorg. Chem. 2000, 39, 959-966.
(17) Chang, C. K.; Kondylis, M. P. Chem. Commun. 1986, 316-318.
(18) Chang, C. K.; Liang, Y.; Aviles, G.; Peng, S.-M. J . Am. Chem.
Soc. 1995, 117, 4191-4192.
(19) Liang, Y.; Chang, C. K. Tetrahedron Lett. 1995, 36, 3817-3820.
(20) Momenteau, M.; Reed, C. A. Chem. Rev. 1994, 94, 659-698.
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Y. Angew. Chem., Int. Ed. 2000, 39, 1989-1991.
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6825.
Porphyrins functionalized with hydrogen-bond syn-
thons offer attractive building blocks for the efficient
construction of supramolecular assemblies with appeal-
ing structural and electronic properties.1 Of particular
interest is the use of such systems toward unraveling the
effect of hydrogen bonding on energy and electron-
transfer reactions.2-4 We have exploited this approach
in the development of hydrogen-bond networks for the
study of proton-coupled electron transfer (PCET)
reactions.2,5-13 In particular, our work has focused on
porphyrins modified with an amidinium group;9,11,13 these
porphyrins associate with carboxylates to form stable,
directional salt bridge complexes where the porphyrin
(1) Kadish, K. M.; Smith, K. M.; Guilard, R. In The Porphyrin
Handbook; Academic Press: San Diego, 2000.
(24) Zhang, X.-X.; Fuhrmann, P.; Lippard, S. J . J . Am. Chem. Soc.
1998, 120, 10260-10261.
(2) Chang, C. J .; Brown, J . D. K.; Chang, M. C. Y.; Baker, E. A.;
Nocera, D. G. In Electron Transfer in Chemistry; Balzani, V., Ed.;
Wiley-VCH: Weinheim, Germany, 2000; Vol. 3.2.4, pp 409-461.
(3) Sessler, J . L.; Wang, B.; Springs, S. L.; Brown, C. T. In
Comprehensive Supramolecular Chemistry; Murakami, Y., Ed.; Per-
gamon: Oxford, 1997; Vol. 4, pp 311-336.
(25) Zhang, X.-X.; Lippard, S. J . J . Org. Chem. 2000, 65, 5298-5305.
(26) Harmjanz, M.; Scott, M. J . Chem. Commun. 2000, 397-398.
(27) Harmjanz, M.; Gill, H. S.; Scott, M. J . J . Am. Chem. Soc. 2000,
122, 10476-10477.
(28) Harmjanz, M. S., Michael, J . Inorg. Chem. 2000, 39, 5428-
5429.
(4) Hayashi, T.; Ogoshi, H. Chem. Soc. Rev. 1997, 26, 355-364.
(5) Cukier, R. I.; Nocera, D. G. Annu. Rev. Phys. Chem. 1998, 49,
337-369.
(29) Harmjanz, M.; Gill, H. S.; Scott, M. J . J . Org. Chem. 2001, 66,
5374-5383.
(6) Zaleski, J . M.; Turro´, C.; Mussell, R. D.; Nocera, D. G. Coord.
Chem. Rev. 1994, 132, 249-258.
(30) Harmjanz, M.; Bozidarevic, I.; Scott, M. J . Org. Lett. 2001, 3,
2281-2284.
(7) Turro´, C.; Chang, C. K.; Leroi, G. E.; Cukier, R. I.; Nocera, D. G.
J . Am. Chem. Soc. 1992, 114, 4013-4015.
(31) Walker, F. A.; Bowen, J . J . Am. Chem. Soc. 1985, 107, 7632-
7635.
(8) Roberts, J . A.; Kirby, J . P.; Nocera, D. G. J . Am. Chem. Soc. 1995,
117, 8051-8052.
(32) For examples of hydrogen-bonded cavities in non-heme environ-
ments, see: MacBeth, C. E.; Golombek, A. P.; Young, V. G., J r.; Tang,
C.; Kuczera, K.; Hendrich, M. P.; Borovik, A. S. Science 2000, 289,
938-941 and references therein.
(33) Yeh, C.-Y.; Chang, C. J .; Nocera, D. G. J . Am. Chem. Soc. 2001,
123, 1513-1514.
(9) Kirby, J . P.; van Dantzig, N. A.; Chang, C. K.; Nocera, D. G.
Tetrahedron Lett. 1995, 36, 3477-3480.
(10) Kirby, J . P.; Roberts, J . A.; Nocera, D. G. J . Am. Chem. Soc.
1997, 119, 9230-9236.
10.1021/jo016095k CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/30/2002