Facile synthesis of β-derivatized porphyrins - Structural characterization of a β - β-bis-porphyrin

Article abstract of DOI:10.1002/(SICI)1521-3773(20000317)39:6<1066::AID-ANIE1066>3.0.CO;2-G

A generally applicable Suzuki methodology for the synthesis of β- derivatized porphyrins has been developed starting from bromoporphyrin 1, which is converted into an air- and water-stable boronate derivative. Metal- mediated cross-coupling of the latter

Full text of DOI:10.1002/(SICI)1521-3773(20000317)39:6<1066::AID-ANIE1066>3.0.CO;2-G

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Facile Synthesis of b-Derivatized PorphyrinsÐ
Structural Characterization of a b ± b-Bis-
Porphyrin**
Yongqi Deng, C. K. Chang,* and Daniel G. Nocera*
Linked porphyrin complexes have been a popular struc-
tural motif for studies of electron and energy transfer. The
ability to tune the electronic properties of porphyrins by their
catenation is central to controlling the efficiencies and rates of
these transfers,[1±6] engendering applications in areas ranging
from the design of ªmolecular wiresº and optoelectronic
materials to the development of biomimetic models of
photosynthetic reaction centers and light-harvesting antenna
complexes.[7±12] Modification of porphyrins is more common at
the meso-position than at the b-position, which confronts
more lengthy syntheses and lower product yields. This is
especially true for bis-porphyrins where several new emerging
methodologies for direct meso coupling[13±16] contrast a limited
set of approaches for the synthesis of b ± b linked bis-
porphyrins.[16b, 17] Porphyrin coupling chemistry has changed
in recent years with the emergence of metal-catalyzed cross-
coupling methods, which have been employed to link bis-
porphyrins via phenyl and ethynyl spacers at meso ± meso-,
meso ± b- and b ± b-positions.[7, 8] The direct coupling of
porphyrins by such methods, however, has not yet been
achieved. We now show the utility of metal-mediated cross-
coupling for the general synthesis of b-derivatized porphyrins,
including the preparation and first structural characterization
of a bis-porphyrin unit directly linked at the b-position.
Scheme 1 shows the strategy developed for the direct b ± b
coupling of the porphyrin rings. Air- and water-stable 2 was
isolated in 76% yield by applying the method of Miyaura
et al.[18] to couple the pinacol diboronate with bromoporphy-
rin 1.[19] Porphyrin 2 can also be prepared according to
Masudaꢁs method where the pinacol borane is the trans-
metalating reagent.[20, 21] The same boronate has recently been
applied to synthesize porphyrins derivatized at the meso-
position[22] in yields similar to that reported here for b-
derivatization. Cross-coupling 1 and 2 under typical Suzuki
reaction conditions affords the previously reported bis-
porphyrin 3a,[17, 23] but prepared here more conveniently and
in higher yield (62%).
Scheme 1. Synthesis of 3a ± e.
The crystal structure of the porphyrin dimer 3a[24] (Fig-
ure 1) is unique inasmuch as no porphyrin system directly
linked by a carbon ± carbon bond at the b-position of the rings
has been heretofore structurally characterized. Connection
Figure 1. ORTEP representation of 3a with hydrogen atoms omitted for
clarity. Thermal ellipsoids are drawn at the 30% probability level.
at the less sterically encumbered b-position results in a
dihedral angle (51.78) (defined by four Npyrrolyl atoms of each
porphyrin) between the two porphyrin macrocyles that is
considerably smaller than that observed between the phenyl
and porphyrin rings in tetraphenylporphyrin (TPP),[25] other
crystallographically characterized TPP type compounds[26, 27]
and, most pertinently, than two porphyrins directly linked by a
C C bond at their meso-positions (dihedral angle of 65 to
848).[14] The unique bridging C2 C2' bond (1.46 Š) is also
shorter than the C C bond of the meso ± meso coupled bis-
porphyrin (d ˆ 1.51 Š) and the sp3 ± sp3 distance of a recently
reported b ± b linked bis-chlorin (d ˆ 1.61 Š), which is typical
of a single bond.[28] These bond length comparisons suggest
greater electronic conjugation between two porphyrin macro-
cycles when linked at their b-positions.
[*] Prof. D. G. Nocera, Dr. Y. Deng
Department of Chemistry, 6-335
Massachusetts Institute of Technology
Cambridge, MA 02139 (USA)
Fax : (‡ 1)617-253-7670
E-mail: nocera@mit.edu
Prof. C. K. Chang
Department of Chemistry
Michigan State University
East Lansing, MI 48824 (USA)
Fax : (‡ 1)517-353-1793
E-mail: chang@msu.edu
[**] Financial support for this work was provided by the National Institutes
of Health (GM 47274). The authors would like to thank William
Cieslik from Hamamatsu Corporation for providing a C4334-0 Streak
Camera for luminescence lifetime measurements and Alan Heyduk
for assistance with the X-ray crystal structure determination.
Figure 2a compares the electronic absorption spectra of the
monomeric subunit (zinc(ii) etio-I porphyrin) and 3a. The
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in the presence of a catalytic amount (5 ± 10 mol%) of
[PdCl2(dppf)]
(dppf ˆ 1,1'-bis(diphenylphosphanyl)ferro-
cene) and 10 equivalents of aqueous K2CO3 at 808C under
an inert atmosphere to give the corresponding b-substituted
porphyrins in high yields.[30] Reaction of bromobenzene and p-
bromotoluene with 2 affords the phenyl and tolyl b-derivat-
ized porphyrins 3b and 3c, respectively, in yields that are
similar to that obtained for the coupling between 1 and phenyl
boronic acid or p-tolyl boronic acid. Although molecules such
as anthryl porphyrin 3d may be synthesized by reacting water-
sensitive dichlorozinc anthracene reagents with 1,[31] the air
and water stability of 2 makes the approach reported here
superior for preparing this type of compound in high yields.
Furthermore, 2 reacts smoothly with aryl halides bearing
electrophilic functional groups; coupling of 2 with 4-bromo-
benzaldehyde leads to the formation of 3e with the reactive
aldehyde group remaining intact, thus demonstrating the
suitability of 2 for a wide range of substrates. Along these
lines, utilization of b-boronate 2 as a coupling precursor
provides a general alternative to recent methods relying on
arylboronic acids[32] and boronates,[9] with the advantage that
it is more tolerant to base-sensitive functional groups.
A structurally characterized meso ± meso, meso ± b, b ± b
bis-porphyrin series provides a solid foundation from which to
interpret trends in the observed electronic spectra of directly
coupled porphyrins. The ability to differentially perturb
electronic structure by the site of substitution about the
porphyrin periphery has important reactivity issues. As we
have recently shown, substituents at the b-position that are in
direct electronic communication with the porphyrin ring can
profoundly influence the rates of electron transfer.[33] In view
of the rich chemistry of boronic acid esters and borates,[34]
further application of 2 will undoubtedly provide unique
porphyrin architectures that will further advance our under-
standing of the spectroscopic and the electron/energy transfer
properties of catenated porphyrin supermolecules.
Figure 2. a) Absorption and b) emission spectra of 3a (ÐÐ) and zinc(ii)
etio-I porphyrin (monomer) (±±±) in CH2Cl2 at 228C.
Soret (B) and Q band absorptions are clearly perturbed upon
b-catenation of the monomer subunits. The B band maximum
of 3a is red-shifted relative to that of the monomer. A
concomitant broadening and splitting of the B band is
indicative of exciton splitting within the bis-porphyrin super-
structure.[29] A similar splitting is also reflected in the Q band
absorptions to lower energy. The difference in energy (DE) of
539 cm 1 between the two maxima of the split B band (and an
1
analogous DE ˆ 395 cm for the split Q band) is smaller than
that of bis-porphyrins connected by a C C bond at the meso ±
1
1
b- (DE ˆ 1265 cm ) and meso ± meso- (DE ˆ 2100 cm )
positions.[16]
The crystal structure of 3a provides critical insight into the
trend in DE for the three cases. Exciton splittings arise from
allowed transitions (By and Bx) resulting from the constructive
vector sum of transition dipole moments of coplanar bis-
porphyrin subunits in a parallel (my) and in-line (mx) disposi-
tion. For the case of the meso ± meso bis-porphyrin system, the
in-line transition dipoles are always aligned[14] and only the
parallel transition moment varies with rotation about the
connecting C C bond. Conversely, the crystal structure of the
b ± b linked bis-porphyrin 3a shows that the mx and my
transition dipole moments assume an oblique angle due to
the fanning of the two porphyrin subunits from each other. In
the situation of oblique transition dipoles, the exciton splitting
energy will be attenuated owing to the angular dependence of
the transition moment. Although the orientation of the
porphyrin rings in a meso ± b system has not been crystallo-
graphically determined,[16b] the observation that the exciton
splitting energy lies between the b ± b and meso ± meso bis-
porphyrin systems suggests that the two porphyrins are also
obliquely disposed but to a lesser degree than observed for 3a.
Excitation into the absorption manifold of 3a results in the
intense luminescence bands characteristic of Q(0,0) and
Q(0,1) transitions (Figure 2b). As with the absorption profile,
the emission bands are red-shifted with respect to monomer
emission and a splitting of the lowest energy emission band is
Received: September 3, 1999 [Z13961]
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1
clearly evident (DE ˆ 345 cm ). The luminescence red shift,
consistent with increased conjugation of the bis-porphyrin
pair, is reflected in a slightly shorter lifetime than that of
the monomer (tobs(3a) ˆ 1.55(1) ns and tobs(zinc(ii) etio-I
porphyrin) ˆ 1.61(1) ns).
The b-derivatized boronate 2 is a general building block for
modification of porphyrins at the b-position. Cross coupling
between 2 and various aryl halides was carried out in DMF
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Angew. Chem. Int. Ed. 2000, 39, No. 6
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[11] N. S. Hush, J. R. Reimers, L. E. Hall, L. A. Johnston, M. J. Crossley,
Ann. N. Y. Acad. Sci. 1998, 852, 1.
transitions red-shift relative to the B band of the monomer. The same
situation occurs for the meso ± b and the meso ± meso bis-porphyrins of
ref. [16b) ]. These red shifts indicate that the exciton coupling in
porphyrins linked by a single bond is augmented by other factors; one
likely factor is electronic coupling between porphyrin subunits across
the C C bond.
[12] a) C. C. Mak, D. Pomeranc, M. Montalti, L. Prodi, J. K. M. Sanders,
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[30] 3b ± e: 3b, 91% yield. UV/Vis (CH2Cl2): lmax ˆ 402, 530, 570 nm;
1H NMR (300 Hz, CDCl3, 258C): d ˆ 1.73 (m, 9H; CH3), 3.39, 3.41,
3.50, 3.64 (s, 3H each; CH3), 3.86 (m, 6H; CH2), 7.70 ± 8.22 (m, 5H;
Ar H), 9.41, 9.53, 9.74, 9.84 (s, 1H each; meso-H); FAB HRMS for
C36H36N4Zn: calcd: 588.2223; found: 588.2230. 3c, 93% yield. UV/Vis
(CH2Cl2): lmax ˆ 402, 533, 569 nm; 1H NMR (300 Hz, CDCl3, 258C):
d ˆ 1.75 (m, 9H; CH3), 2.72 (s, 3H; CH3), 3.39 (s, 6H; CH3), 3.44, 3.66
(s, 3H each; CH3), 3.86 (m, 6H; CH2), 7.68, 8.08 (dd, 3J(H,H) ˆ
14.5 Hz, 2H; Ar H), 9.40, 9.50, 9.73, 9.84 (s, 1H each; meso-H);
FAB HRMS for C37H36N4OZn: calcd: 602.23879; found: 602.23908.
3d, 88% yield. UV/Vis (CH2Cl2): lmax ˆ 404, 534, 570 nm; 1H NMR
(300 MHz, CDCl3, 258C): d ˆ 1.74 (t, 3J(H,H) ˆ 7.5 Hz, 3H; CH3),
1.85 (t, 3J(H,H) ˆ 7.3 Hz, 3H; CH3), 1.92 (t, 3J(H,H) ˆ 7.5 Hz, 3H;
CH3), 3.07, 3.41, 3.56, 3.65 (s, 3H each; CH3), 4.08 (m, 6H; CH2), 7.17
[13] K. Susumu, T. Shimidzu, K. Tanaka, H. Segawa, Tetrahedron Lett.
1996, 37, 8399.
[14] R. G. Khoury, L. Jaquinod, K. M. Smith, Chem. Commun. 1997, 1057.
[15] M. O. Senge, X. D. Feng, Tetrahedron Lett. 1999, 40, 4165.
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[17] J. B. Paine, III, D. Dolphin, Can. J. Chem. 1978, 56, 1710.
[18] T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem. 1995, 60, 7508.
[19] Compound 1 was obtained as a minor product in the standard
etioporphyrin I synthesis. Apparently an ethyl group was replaced by
bromine during the formation of the dipyrrylmethene precursor under
harsh bromination conditions. Being less basic, 1 can be separated
from etioporphyrin by acid extractions, for example, 20 g of 1 from
3 kg of etioporphyrin. Other Heck reactions with homologous b-
bromoporphyrins have been reported, see H. Ali, J. E. van Lier,
Tetrahedron 1994, 50, 11933.
3
(m, 2H; Ar H), 7.53 (m, 2H; Ar H), 7.81 (d, J(H,H) ˆ 8.8 Hz, 2H;
Ar H), 8.30 (d, 3J(H,H) ˆ 8.9 Hz, 2H; Ar H), 8.86 (s, 1H; Ar H),
9.48, 10.00, 10.06, 10.34 (s, 1H each, meso-H); FAB HRMS for
C44H40N4Zn: calcd: 688.25444; found: 688.25432. 3e, 82% yield. UV/
Vis (CH2Cl2): lmax ˆ 406, 533, 574 nm; 1H NMR (300 MHz, CDCl3,
258C): d ˆ 1.72 (m, 9H; CH3), 3.36 (s, 3H; CH3), 3.40 (s, 6H; CH3),
3.59 (s, 3H; CH3), 3.84 (m, 6H; CH2), 8.34 (dd, 3J(H,H) ˆ 14.9 Hz,
2H; Ar H), 9.43, 9.50 (s, 1H each; meso-H), 9.62 (s, 2H; meso-H),
10.35 (s, 1H; CHO); FAB HRMS for C37H36N4OZn: calcd: 616.21806;
found: 616.21786.
[20] M. Murata, S. Watanabe, Y. Masuda, J. Org. Chem. 1997, 62, 6458.
[21] 2: 76% yield. UV/Vis (CH2Cl2): lmax ˆ 401, 533, 574 nm; 1H NMR
(300 Hz, CDCl3, 258C): d ˆ 1.78 (s, 12H; CH3), 1.80 (m, 9H; CH3),
3.44, 3.50, 3.64, 3.96 (s, 3H each; CH3), 3.98 (m, 6H; CH2), 9.60, 9.64,
9.90, 10.76 (s, 1H each; meso-H); FAB HRMS for C36H43BN4O2Zn:
calcd: 638.27712; found: 638.27705.
[31] S. G. DiMagno, V. S.-Y. Lin, M. J. Therien, J. Org. Chem. 1993, 58,
5983.
[22] A. G. Hyslop, M. A. Kellett, P. M. Iovine, M. J. Therien, J. Am. Chem.
Soc. 1998, 120, 12676.
[32] X. Zhou, M. K. Tse, T. S. M. Wan, K. S. Chan, J. Org. Chem. 1996, 61,
3590.
[33] a) Y. Q. Deng, J. A. Roberts, S. M. Peng, C. K. Chang, D. G. Nocera,
Angew. Chem. 1997, 109, 2216; Angew. Chem. Int. Ed. Engl. 1997, 36,
[23] 3a: 62% yield. UV/Vis (CH2Cl2): lmax ˆ 403, 415, 534, 579 nm; 1H
3
(300 Hz, CDCl3, 258C): d ˆ 1.74 (t, J(H,H) ˆ 7.2 Hz, 6H; CH3), 1.90
(t, 3J(H,H) ˆ 7.2 Hz, 6H; CH3), 2.02 (t, 3J(H,H) ˆ 7.2 Hz, 6H; CH3),
2.88, 3.65, 3.74, 3.92 (s, 6H each; CH3), 4.20 (m, 12H; CH2), 10.06,
10.14, 10.22, 10.50 (s, 2H each; meso-H); FAB HRMS for
C60H62N8Zn2: calcd: 1022.36804; found: 1022.36765; elemental anal-
ysis (%) for C60H62N8Zn: calcd: C 70.24, H 6.09, N 10.92; found: C
70.32, H 6.12, N 11.03.
2124; b) C. Turro, C. K. Chang, G. E. Leroi, R. I. Cukier, D. G.
Â
Nocera, J. Am. Chem. Soc. 1992, 114, 4013.
[34] N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
[24] Crystallographic data: C63H74N8O3Zn2 from CH3OH/CH2Cl2, Mr ˆ
1122.04, monoclinic, space group C2/c, a ˆ 14.58560(10), b ˆ
21.5321(3), c ˆ 19.6353(3) Š, b ˆ 104.5520(10)8, Vˆ 5968.81(13) Š3,
Z ˆ 4, 1calcd ˆ 1.249 gcm 3, F(000) ˆ 2368, l(MoKa) ˆ 0.7107 Š, crystal
dimensions 0.5 Â 0.25 Â 0.10 mm3. A total of 8840 reflections were
collected at 908C using a Siemens diffractometer equipped with a
CCD detector in the q range of 1.72 to 20.008, of which 2788 were
unique (Rint ˆ 0.0570). The structure was solved by the Patterson
heavy atom method in conjunction with standard difference Fourier
techniques. Hydrogen atoms were placed in calculated positions using
a standard riding model and were refined isotropically. A methanol
solvent molecule was found to be disordered and was modeled by
standard procedures. The largest peak and hole in the difference map
were 0.957 and 0.424 eŠ 3, respectively. The least-squares refine-
ment converged normally giving residuals of R ˆ 0.0749 and wR2 ˆ
0.1983. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion no. CCDC-133672. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.
ac.uk).
One-Pot Synthesis of Antigen-Bearing,
Lysine-Based Cluster Mannosides
Using Two Orthogonal Chemoselective
Ligation Reactions**
Cyrille Grandjean,* Corinne Rommens,
 Á
Helene Gras-Masse, and Oleg Melnyk*
Dendritic cells (DCs) are well-recognized for playing a
crucial role in the control of immunity. These professional
antigen-presenting cells act both as initiators and modulators
[*] Dr. C. Grandjean, Dr. O. Melnyk, C. Rommens, Prof. H. Gras-Masse
Á
Â
Laboratoire de Synthese, Structure et Fonction des Biomolecules
Â
UMR 8525 CNRS Universite de Lille II
Institut de Biologie et Institut Pasteur de Lille
Â
1 rue du Professeur Calmette BP447, 59021 Lille Cedex (France)
[25] W. R. Scheidt, M. E. Kastner, K. Hatano, Inorg. Chem. 1978, 3, 706.
[26] K. M. Barkigia, M. D. Berber, J. Fajer, C. J. Medforth, M. W. Renner,
K. M. Smith, J. Am. Chem. Soc. 1990, 112, 8851.
Fax: (‡33)3-20-87-12-33
E-mail: Cyrille.Grandjean@pasteur-lille.fr
[27] X. Zhou, Z. Y. Zhou, T. C. W. Mak, K. S. Chan, J. Chem. Soc. Perkin
Trans. 1 1994, 2519.
[**] This work was financially supported by the ANRS and the Fondation
Â
pour la Recherche Medicale (Sidaction grant to CG). We are grateful
[28] B. Krattinger, D. J. Nurco, K. M. Smith, Chem. Commun. 1998, 757.
[29] Standard exciton considerations predict that By should blue-shift and
Bx should red-shift about the unperturbed B band. In 3a, both
to B. Coddeville and G. Montagne for recording ES-MS and NMR
spectra, respectively, and also to Dr. S. Brooks for proofreading the
manuscript.
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