One-step template-directed synthesis of a macrocyclic tetraarylporphyrin hexamer based on supramolecular interactions with a C3-symmetric tetraarylporphyrin trimer

Article abstract of DOI:10.1021/ja057117d

Taking into consideration the model geometry of the macrocyclic hexaporphyrin 1 as a host molecule, the structure of a benzene-centered porphyrin trimer bearing pyridine rings at the apical positions has been designed with the aim to use the latter as a t

Full text of DOI:10.1021/ja057117d

Published on Web 02/17/2006
One-Step Template-Directed Synthesis of a Macrocyclic
Tetraarylporphyrin Hexamer Based on Supramolecular
Interactions with a C3-Symmetric Tetraarylporphyrin Trimer
Simona Rucareanu,† Anne Schuwey, and Albert Gossauer*
Contribution from the Department of Chemistry, UniVersity of Fribourg, chemin du Muse´e 9,
CH-1700 Fribourg, Switzerland
Received October 19, 2005; E-mail: albert.gossauer@unifr.ch
Abstract: Taking into consideration the model geometry of the macrocyclic hexaporphyrin 1 as a host
molecule, the structure of a benzene-centered porphyrin trimer bearing pyridine rings at the apical positions
has been designed with the aim to use the latter as a template for the synthesis of its own host. Indeed,
in the presence of the porphyrin trimer 5, the yield of the cyclization of a linear porphyrin hexamer, as a
precursor of 1, could be improved from 8 to 30% (variable yield) to 50% (reproducible yield). Even the
condensation of equimolecular amounts of porphyrin monomers 20b and 21b in the presence of 5 leds
probably through a loose preorganized complex between the latter and the Zn(II) chelate 20bsto the
formation of 1 in only five steps from 19, as compared with 13 steps of the synthesis via linear porphyrin
hexamer in the absence of template. As evidenced by 1H NMR spectroscopic analysis of the supramolecular
complex between 5 and an analogue of 1b in which all H-atoms at the pyrrole rings have been replaced
by deuterium, in the presence of unlabeled 1b, a rapid dissociation and recombination of the host and
guest molecules forming the supramolecular complex takes place even at low temperature (-40 °C). As
at 55 °C all six Zn(II) porphyrinate rings of the complex 1b + 5 become magnetically equivalent in the 500
1
MHz H NMR time scale, approximate kinetic data for the ligand exchange process could be obtained.
Introduction
at least one equivalent of template has to be present in the
reaction mixture in order to ensure the completion of the
Control of molecular self-assembly to form supramolecular
structures possessing characteristic functional properties is one
of the primordial goals in modern preparative chemistry. Such
kind of process, which is very common in molecular biology,
has been until now rarely reproduced successfully in the
laboratory. Thus, the synthesis of catalysts showing a specific
substrate affinity1 as well as the development of highly ordered
networks using metal-ligand bonding,2 hydrogen bonding,3 and
π-π interactions4 has been only recently exploited, thus opening
new perspectives to the future development of chemistry.5
Characteristic for both a template6 and a catalytic effect is a
preorganization of the reacting molecules which reduces the
entropy content of the transition state of the reaction. In contrast
to a catalyst, however, a template possesses usually a higher
affinity for the reaction product(s) than for the substrate, so that
reaction. On the other hand, the interactions of a template with
the substrate molecules are often more specific with respect to
the geometry of the transition complex. Enzymes combine the
advantages of a catalyst and a template in that they change their
conformation after the transformation of the substrate into the
product(s), thus diminishing the affinity of the latter for the
enzyme.
Linstead’s discovery that phthalocyanine synthesis takes place
in the presence of metal ions7 as well as Helberger’s first
synthesis of tetrabenzoporphyrin8 belong to the earlier observed
template effects in preparative organic chemistry. Even the role
of metals in the biosynthesis of natural occurring tetrapyrrolic
pigments was at that time a matter of speculation.9 In the
porphyrin series, Calvin and co-workers10 reported in 1946 that
the addition of zinc acetate to a reaction mixture of pyrrole and
benzaldehyde doubled the yield from 4 to 5% to 10-11% of
Rothemund’s tetraphenylporphyrin synthesis.11 Although at
present meso-tetraarylporphyrins can be prepared in 30-40%
yields without adding metal ions,12 the favorable influence of
† Present address: McGill University, Chemistry Department, Montreal,
Canada.
(1) Bonar-Law, R. P.; Mackay, L. G.; Walter, C. J.; Marvaud, V.; Sanders, J.
K. M.; Pure Appl. Chem. 1994, 66, 803-810.
(2) Holliday, B. J.; Mirkin, C. A. Angew. Chem. 2001, 113, 2076-2097; Angew.
Chem., Int. Ed. 2001, 40, 2022-2043.
(3) Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto, C. T.; Chin, D.
N.; Mammen, M.; Gordon, D. M. Acc. Chem. Res. 1995, 28, 37-44.
(4) Hoss, R.; Vo¨tgle, F. Angew. Chem. 1994, 106, 389-398; Angew. Chem.,
Int. Ed. Engl. 1994, 33, 375-384.
(7) (a) Byrne, G. T.; Linstead, R. P.; Lowe, A. R. J. Chem. Soc. 1934, 1017-
1022. (b) Linstead, R. P.; Lowe, A. R. J. Chem. Soc. 1934, 1022-1027.
(c) Dent, C. E.; Linstead, R. P. J. Chem. Soc. 1934, 1027-1031.
(8) Helberger, J. H.; von Rebay, A.; Heve´r, D. B. Liebigs Ann. Chem. 1938,
533, 197-215 and references given therein.
(9) Helberger, J. H. Liebigs Ann. Chem. 1937, 525, 205-218.
(10) Ball, R. H.; Dorough, G. D.; Calvin, M. J. Am. Chem. Soc. 1946, 68, 2278-
2281.
(11) Rothemund, P.; Menotti, A. R. J. Am. Chem. Soc. 1941, 63, 267-270.
(5) (a) Furlan, R. L. E.; Otto, S.; Sanders, J. K. M. Proc. Natl. Acad. Sci.
U.S.A. 2002, 99, 4801-4804. (b) Sanders, J. K. M Philos. Trans. R. Soc.
London A 2004, 362, 1239-1245.
(6) Thomson, M. C.; Busch, D. H. J. Am. Chem. Soc. 1962, 84, 1762-1763;
1964, 86, 213-217.
9
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J. AM. CHEM. SOC. 2006, 128, 3396-3413
10.1021/ja057117d CCC: $33.50 © 2006 American Chemical Society

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
metal ions, such as copper(I)13 and cobalt(II),14 on the synthesis
of functionalized porphyrin derivatives, in general, is well
documented in the literature.
More recently, the principle of ligand metal coordination has
been extended by J. K. M. Sanders and co-workers15 as well as
in J. S. Lindsey’s group16 to the template syntheses of a series
of macrocyclic porphyrin polymers (up to tetramers and
hexamers, respectively) using the appropriate monomeric por-
phyrin metal chelates and pyridine-containing bi-, tri-, and
tetradentate ligands as templates. In most cases, the template
effect was determined by comparison of the yields obtained in
absence and in the presence of the template, taking into account
that cyclizations of linear precursors to yield macrocycles
containing the same number of monomeric units are often
promoted by the so-called “structure contribution”,16a which is
given by the yield of the cyclization obtained in the absence of
template.
Template Synthesis of the Macrocyclic Porphyrin Hex-
amer 1. Within the scope of an ongoing research project on
nanometer-sized polyporphyrin arrays, we reported not long ago
the synthesis of a macrocyclic porphyrin hexamer (1b) by
cyclization of the corresponding linear hexamer.17 By this
procedure, variable yields of the desired product between 8 and
30% were obtained. Later on, the synthesis of a supramolecular
assembly between 1b and a niphaphyrin (2)18 composed of six
10-(pyridin-4-yl)porphyrin subunits attached to the C atoms of
a benzene core through linkers consisting of collinear repetitive
phenylethynyl units was achieved in our laboratory.19 Owing
to the high binding constant (3.5 × 109 mol-1) of this complex,
it became obvious to attempt a template synthesis of 1b from
the appropriate monomer in the presence of the above nipha-
phyrin. Unfortunately, however, no cyclic hexamer could be
detected in the reaction mixture using the same conditions which
served to cyclize the linear hexamer in absence of template.
Figure 1. Different metal complexes of a toroid-like hexaporphyrin array
with an internal diameter of the cavity of ca. 4.6 nm.
standard bond lengths for C-C bonds and the benzene ring. In
the supramolecular complex, the length of the Zn-N(pyridine)
bond is supposed to be 2.14 Å, corresponding to the value
determined by X-ray diffraction analysis of pyridinato Zn(II)
complexes of meso-substituted porphyrins.22 Moreover, as the
metal ion in porphyrin Zn(II) chelates can be pulled toward the
ligand by about 0.33 Å on coordination with pyridine in an
apical position,22,23 this distance has to be added to the length
of the Zn-N(pyridine) bond in order to estimate the distance
between the N atom of the pyridine ring of the template, as the
“guest”, and the center of the plane of the porphyrin ring which
complexes the Zn(II) ion in the host. The result from this
estimate (2.47 Å) agrees with the corresponding distance (2.49
Å) in a tetrameric zinc porphyrin complex, as determined by
X-ray diffraction analysis.24 Thus, among the structurally related
templates represented in Figure 2, templates 5 and 6, with a
radius of about 19 Å, should fit the best with the distance of
22.8 Å from the center of the cavity to the center of the
porphyrin rings of 1 since 19 + 2.47 ) 21.47 Å, whereas trimer
3 slightly exceeds the cavity dimensions (20.90 + 2.47 ) 23.37
Å) and trimer 4 is too small to fit well inside the macrocycle
(16.63 + 2.47 ) 19.10 Å).
At that point, a careful assessment of the molecular dimen-
sions of both the final “host” molecule 1 and the most
appropriate template was made using as segments (i) the
diameter of the tetraphenylporphyrin molecule20 and (ii) the
distance between the C4 and C4′ atoms of tolane (9.65 Å)21s
both known from X-ray diffraction studiessas well as (iii)
(12) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.; Marguerettaz,
A. M. J. Org. Chem. 1987, 52, 7-836.
(13) Corwin, A. H.; Sydow, V. L. J. Am. Chem. Soc. 1953, 75, 4484-4486.
(14) Johnson, A. W.; Kay, I. T.; Markham, E.; Price, R.; Shaw, K. B. J. Chem.
Soc. 1959, 3416-3419.
(15) (a) Anderson, H. L.; Sanders, J. K. M. Angew. Chem. 1990, 102, 1478-
1480; Angew. Chem., Int. Ed. Engl. 1990, 29, 1400-1403. (b) Anderson,
S.; Anderson, H. L.; Sanders, J. K. M. Acc. Chem. Res. 1993, 26, 469-
475. (c) Vidal-Ferran, A.; Mu¨ller, C. M.; Sanders, J. K. M. J. Chem. Soc.,
Chem. Commun. 1994, 2657-2658. (d) Anderson, S.; Anderson, H. L.;
Sanders, J. K. M. J. Chem. Soc., Perkin Trans. 1 1995, 2247-2254. (e)
Anderson, S.; Anderson, H. L.; Sanders, J. K. M. J. Chem. Soc., Perkin
Trans. 1 1995, 2255-2267. (f) McCallien, D. W. J.; Sanders, J. K. M. J.
Am. Chem. Soc. 1995, 117, 6611-6612. (g) Marvaud, V.; Vidal-Ferran,
A.; Webb, S. J.; Sanders, J. K. M. J. Chem. Soc., Dalton Trans. 1997,
985-990. (h) Vidal-Ferran, A.; Bampos, N.; Sanders, J. K. M. Inorg. Chem.
1997, 36, 6117-6126. (i) Marvaud, V.; Vidal-Ferran, A.; Webb, S. J.;
Sanders, J. K. M. J. Chem. Soc., Dalton Trans. 1997, 985-990.
(16) (a) Li, J.; Ambroise, A.; Yang, S. I.; Diers, J. R.; Seth, J.; Wack, C. R.;
Bocian, D. F.; Holten, D.; Lindsey, J. S. J. Am. Chem. Soc. 1999, 121,
8927-8940. (b) Yu, L.; Lindsey, J. S. J. Org. Chem. 2001, 66, 7402-
7419. (c) Tomizaki, K.; Yu, L.; Wei, L.; Bocian, D. F.; Lindsey, J. S. J.
Org. Chem. 2003, 68, 8199-8207.
On the basis of the experience of other laboratories, pyridine
rings were placed at the apical positions of the templates to
provide the coordination sites for the central ions of the
porphyrin rings of the macrocycle precursor. Accordingly,
porphyrinato zinc(II) ligands were used owing to their property
of forming stable five-coordinate 1:1 complexes with nitrogen-
(20) (a) Hamor, M. J.; Hamor, T. A.; Hoard, J. L. J. Am. Chem. Soc. 1964, 86,
1938-1942. (b) Silvers, S. J.; Tulinsky, A. J. Am. Chem. Soc. 1967, 89,
3331-3337.
(21) Zanin, I. E.; Antipin, M. Yu.; Struchkov, Yu. T. Kristallografiya 1991,
36, 411-419 [SoV. Phys. Crystallogr. 1991, 36, 219-224].
(22) Collins, D. M.; Hoard, J. L. J. Am. Chem. Soc. 1970, 92, 3761-3771.
(23) Cullen, D. L.; Meyer, E. F., Jr. Acta Crystallogr. 1976, B32, 2259-2269.
(24) Anderson, S.; Anderson, H. L.; Bashall, A.; McPartlin, M.; Sanders, J. K.
M. Angew. Chem. 1995, 107, 1196-1200; Angew. Chem., Int. Ed. Engl.
1995, 34, 1096.
(17) Mongin, O.; Schuwey, A.; Vallot, M.-A.; Gossauer, A. Tetrahedron Lett.
1999, 40, 8347-8350.
(18) Mongin, O.; Hoyler, N.; Gossauer, A. Eur. J. Org. Chem. 2000, 1193-
1197.
(19) Rucareanu, S.; Mongin, O.; Schuwey, A.; Hoyler, N.; Gossauer, A.; Amrein,
W.; Hediger, H.-U. J. Org. Chem. 2001, 66, 4973-4988.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3397

A R T I C L E S
Rucareanu et al.
Figure 2. Ligands designed for the template-directed synthesis of macrocycles 1a-c.
containing ligands. Other metal ions, such as Ru(II) and Mg-
(II), which also form five-coordinate complexes, seemed to be
less appropriate. Actually, Ru(II) porphyrin complexes afford
much more stable pyridine complexes than Zn(II), but they
cannot be demetalated without destroying the porphyrin ring.15g
Mg(II) complexes, on the other hand, which efficiently coor-
dinate nitrogen-containing ligands,25,26 are very sensitive to acids
and are difficult to purify. Furthermore, using tridentate ligands
as templates, no more than three (porphyrinato)zinc(II) rings
can be ligated at once in the macrocycle precursor. Therefore,
our first experiments were carried out with ligands in which
Zn(II) porphyrin complexes alternate with their corresponding
porphyrin free bases (e.g., 1c) or with porphyrin Ni(II)
complexes (e.g., 1a), which coordinate nitrogen bases much less
strongly than Zn(II).27 In this way, the structure of the
macrocycle precursor should be unequivocally predetermined
before closing the macrocycle.
Figure 3. Different approaches to the template-directed synthesis of
macrocycles 1.
Strategies and Design. As tridentate ligands are used as
templates, different strategies, three of them are represented in
Figure 3, may be envisaged in order to carry out the template-
directed synthesis of the macrocyclic hexamers 1. The most
obvious approach (Figure 3a) consists of the cyclization of the
corresponding linear hexamers 23 (cf. Scheme 4) in the presence
of the template, which by ligation to three (porphyrinato)zinc
rings is supposed to hold the linear hexamer in a conformation
favorable to the ring closure by intramolecular coupling, thus
(25) Storm, C. B.; Corwin, A. H. J. Org. Chem. 1964, 29, 3700-3702.
(26) (a) Leicknam, J. P.; Anitoff, O. E.; Gallice, M. J.; Henry, M.; Tayeb, A. E.
K. J. Chim. Phys. Phys.-Chim. Biol. 1981, 78, 587-596. (b) Leicknam, J.
P.; Anitoff, O. E.; Gallice, M. J.; Henry, M.; Rutledge, D.; Tayeb, A. E.
K. J. Chim. Phys. Phys.-Chim. Biol. 1982, 79, 171-180.
(27) (a) Cole, S. J.; Curthoys, G. C.; Magnusson, E. A.; Phillips, J. N. Inorg.
Chem. 1972, 11, 1024-1028. (b) Jia, S. L.; Jentzen, W.; Shang, M.; Song,
X.-Z.; Ma, J.-G.; Scheidt, W. R.; Shelnutt, J. A. Inorg. Chem. 1998, 37,
4402-4412.
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3398 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
Scheme 1a
a Reagents and conditions: (a) TFA, CH2Cl2/EtOH (95:5), then DDQ; (b) 1,3,5-triethynylbenzene, in toluene/Et3N (5:1), Pd2dba3/P(o-tol)3, 35 °C; (c)
CH2Cl2/Et3N (1:1), TBAF, 25 °C; (d) same as (b) but with 1,3,5-triiodobenzene as reagent.
suppressing intermolecular reactions that presumably lead to
chain-like products of high molecular weight. On the other hand,
a more straightforward strategy consists in the coupling of three
porphyrin rings (as free bases or Ni(II) chelates) with three
(porphyrinato)zinc rings, which are held together in an ap-
propriate arrangement by previous complexation with the
template (Figure 3c). A modification of the latter approach is
represented in Figure 3b, in which three identical angular
building blocks, consisting of a (porphyrinato)zinc ring co-
valently bound to a porphyrin ring (as free base or Ni(II) chelate)
through a meta-phenylene unit as cornerstone of the macrocycle,
are linked together head-to-tail after coordination with the
template. A further possibility of constructing the macrocycle,
namely, a [3 + 3] coupling, was not taken into consideration
because, using a tridentate ligand, two different complementary
building blocks would be required.
star-shaped trimers reported earlier19 gave the expected trimer
3 in low yield (18%), probably due to the poor solubility of the
starting porphyrin in DMF. Using toluene instead of DMF and
the more active catalyst Pd[P(o-tol)3]2,33 higher yields (35%)
were obtained and no more attempts were made for optimizing
the reaction, as the trimer 3 was a less efficient template for
the synthesis of 1.
Porphyrin 9a, which was used as a building block for the
synthesis of the smaller trimer 4, was obtained under the same
conditions as porphyrin 8 but after a shorter reaction time (5
instead of 12 h). Deprotection of 9a with fluoride ions afforded
porphyrin 9b in high yield (91%), which was subsequently
transformed into the trimer 4 (59%) by cross-coupling with
triiodobenzene (cf. Scheme 1).
The synthetic pathway to the template molecule 5 is depicted
in Scheme 2. Both the synthesis of 5,15-bisaryl-10,20-biseth-
ynylporphyrins (such as 11) and 5,10,15,20-tetraethynylpor-
phyrins (which are known as chlorphyrins because of their green
color)34 deserve great interest due to their applications in the
field of conjugated electronic materials with nonlinear optical
properties.35 Variable yields of these compounds are obtained
by reacting propynals either with pyrrole itself36,37 or with
dipyrrylmethanes29,36,38 (cf. 7 f 10-12). Higher yields have
been obtained by protection of the alkynal group with dicobalt
octacarbonyl, prior to the porphyrin formation step, followed
Results and Discussion
Synthesis of the Templates. As a common starting material
for the synthesis of templates 3-5, dipyrrylmethane 7 was used,
which was obtained in 82% yield through reaction of 3,5-di-
tert-butylbenzaldehyde with excess pyrrole as described in the
literature.28,29 As usual, the tert-butyl substituents in the
templates should prevent cofacial aggregation (i.e., π-π-
stacking) of the porphyrin rings, thus improving the solubility
of the corresponding polycyclic derivatives.
(31) (a) W. Hu¨bel, W.; Mere´nyi, R. Angew. Chem. 1962, 74, 781-782. (b)
Weber, E.; Hecker, M.; Koepp, E.; Orlia, W.; Czugler, M.; Cso¨regh, I. J.
Chem. Soc., Perkin Trans. 1988, 2, 1251-1257.
The benzene-centered trimers 3 and 4 were synthesized
following procedures previously described19 (cf. Scheme 1). As
a precursor of 3, porphyrin 8 was obtained in 6% yield by
condensation of dipyrrylmethane 7 with an equimolecular
mixture of 4-pyridinecarboxaldehyde and 4-iodobenzaldehyde,30
in the presence of TFA, and subsequent oxidation with DDQ.
As expected, the two corresponding symmetrically substituted
(32) Mongin, O.; Papamica¨el, C.; Hoyler, N.; Gossauer, A. J. Org. Chem. 1998,
63, 5568-5580.
(33) (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030-3039.
(b) Wagner, R. W.; Ciringh, Y.; Clausen, C.; Lindsey, J. S. Chem. Mater.
1999, 11, 2974-2983. (c) Wan, W. B.; Haley, M. M. J. Org. Chem. 2001,
66, 3893-3901.
(34) Milgrom, L. R.; Yahioglu, G. Tetrahedron Lett. 1995, 36, 9061-9064.
(35) (a) Anderson, H. L.; Martin, S. J.; Bradley, D. D. C. Angew. Chem. 1994,
106, 711-713; Angew. Chem., Int. Ed. Engl. 1994, 33, 655-659. (b)
McEwan, K. J.; Robertson, J. M.; Wylie, A. P.; Anderson, H. L. Mater.
Res. Soc. Symp. Proc. 1997, 479, 29. (c) Krivokapic, A.; Anderson, H. L.;
Bourhill, G.; Ives, R.; Clark, S.; McEwan, K. J. AdV. Mater. 2001, 13,
652-656. (d) Screen, T. E. O.; Thorne, J. R. G.; Denning, R. G.; Bucknall,
D. G.; Anderson, H. L. J. Am. Chem. Soc. 2002, 124, 9712-9713.
(36) Anderson, H. L. Tetrahedron Lett. 1992, 33, 1101-1104.
(37) (a) Proess, G.; Pankert, D.; Hevesi, L. Tetrahedron Lett. 1992, 33, 269-
272. (b) Anderson, H. L.; Wylie, A. P.; Prout, K. J. Chem. Soc., Perkin
Trans. 1 1998, 1607-1611.
porphyrins,
[5,15-bis(3,5-di-tert-butylphenyl)-10,20-bis(4-
iodophenyl)]porphine and [5,15-bis(3,5-di-tert-butylphenyl)-
10,20-di(pyrid-4-yl)]porphine, were obtained as byproducts,
which were separated by chromatography of the reaction
mixture. Reaction of 8 with 1,3,5-triethynylbenzene31,32 using
the same conditions as those for the similar alkyl-substituted
(28) (a) Beavington, R.; Burn, P. L. J. Chem. Soc., Perkin Trans. 1 1999, 583-
592. (b) Imahori, H.; Ozawa, S.; Ushida, K.; Takahashi, M.; Azuma, T.;
Ajavakom, A.; Akiyama, T.; Hasegawa, M.; Taniguchi, S.; Okada, T.;
Sakata, Y. Bull. Chem. Soc. Jpn. 1999, 72, 485-502.
(29) Plater, M. J.; Aiken, S.; Bourhill, G. Tetrahedron 2002, 58, 2415-2422.
(30) Paciorek, K.; Masuda, S.; Shih, J.; Nakahara, J. J. Fluorine Chem. 1991,
53, 233-248.
(38) (a) Wilson, G. S.; Anderson, H. L. Synlett 1996, 1039-1040. (b) Milgrom,
L. R.; Yahioglu, C. Tetrahedron Lett. 1996, 37, 4069-4072. (c) Jiang, B.;
Yang, S.-W.; Barbini, D. C.; Jones, W. E., Jr. J. Chem. Soc., Chem.
Commun. 1998, 213-214. (d) Taylor, P. N.; Wylie, A. P.; Huuskonen, J.;
Anderson, H. L. Angew. Chem. 1998, 110, 1033-1037; Angew. Chem.,
Int. Ed. 1998, 37, 986-989. (e) Wilson, G. S.; Anderson, H. L. Chem.
Commun. 1999, 1539-1540.
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A R T I C L E S
Scheme 2a
Rucareanu et al.
a Reagents and conditions: (a) TFA, CHCl3/EtOH (95:5), 5 h, then DDQ; (b) NaOH (1 N), 2 h at 25 °C; (c) 4-iodopyridine in toluene/Et3N (5:1),
Pd2dba3/P(o-tol)3, 60 °C; (d) CH2Cl2/Et3N (1:1), TBAF; (e) 1,3,5-triiodobenzene in toluene/Et3N (5:1), Pd2dba3/P(o-tol)3, 35 °C.
by oxidative deprotection of the triple bond.39 An alternative
pathway is the coupling of meso-haloporphyrins with mono-
substituted alkynes.40,41 Thus, while this work was in progress,
Plater et al.42 reported the synthesis of 13 (as Zn chelate) by
Sonogashira coupling of 5,15-dibromobis-10,20-(3,5-di-tert-
butyl)porphine with trimethylsilylacetylene, subsequent depro-
tection of both ethynyl groups with fluoride ions, and selective
reprotection of one ethynyl group with triisopropylsilyl chloride.
The procedure described in the present work afforded the
desired porphyrin 11 in a one-pot, two-step reaction via mixed
condensation of meso-(3,5-di-tert-butylphenyl)-2,2′-dipyrryl-
methane (7) with 3-trimethylsilylprop-2-ynal43 and 3-triisopro-
pylsilylprop-2-ynal,44 in the presence of trifluoroacetic acid,
followed by oxidation of the porphyrinogen intermediate with
DDQ (Scheme 2). As expected, the reaction mixture contained
porphyrins 10 (4%) and 12 (8%) in addition to 11, which was
readily isolated by column chromatography as the main product
(12%), despite the close resemblance of the two protecting
groups (TMS and TIPS) used for the ethynyl functions. It is
worth mentioning that no scrambling byproducts were detected,
despite a long reaction time (5 h), though some side products
resulting from acid-catalyzed rearrangements have been isolated
in similar cases.29,38a Moreover, the reaction could be carried
out on a larger scale, affording batches of more than 300 mg of
porphyrin without affecting the yield. The above procedure was
found to afford better yields than the alternative reaction of 3,5-
di-tert-butylbenzaldehyde with the corresponding meso-al-
kynyldipyrrylmethanes, the latter being too electron-deficient
to react efficiently with aromatic aldehydes.38a
The selective cleavage of the TMS protecting group of 11
was readily achieved with aqueous NaOH, affording the
ethynylporphyrin 13 in 95% yield. At this point, two alternative
routes to 5 are available starting from the same compound
depending on whether step c in Scheme 2 precedes step e or
vice versa. In our hands, however, only the pathway outlined
in Scheme 2 proved to be successful. Thus, coupling of 13 with
4-iodopyridine45 in the presence of Pd2dba3 and P(o-tol)3 as
catalyst afforded the ethynylpyridylporphyrin 14a in 50% yield,
which could be improved to 75% by adding a second portion
of catalyst 6 h after the beginning of the reaction. Although
4-iodopyridine can be replaced by 4-bromopyridine hydrochlo-
ride, which is commercially available, the Pd-catalyzed coupling
with the latter proved to not be reproducible, in our hands, as
the yields fluctuated between 12 and 50%, compared with 75%
in the case of 4-iodopyridine. Also, important amounts (up to
50%) of a porphyrin dimer formed by homocoupling of 13 were
obtained when 4-bromopyridine hydrochloride was used, whereas
only traces of homocoupling products could be isolated in the
case of 4-iodopyridine. The fluctuating yields obtained with
4-bromopyridine hydrochloride are probably related to the low
solubility and/or instability of the latter.46
Initial attempts to remove the triisopropylsilyl group of 14a
with TBAF failed to give any porphyrin. The decomposition
of the product was avoided by carrying out the reaction in a
mixture of CH2Cl2/Et3N (1:1) instead of neat CH2Cl2, and
quenching the reaction, after 10 min stirring at 25 °C by addition
of CaCl2. The deprotected porphyrin 14b was thus isolated in
fair yield (85%) and coupled further with 1,3,5-triiodobenzene
(39) Milgrom, L. R.; Rees, R. D.; Yahioglu, C. Tetrahedron Lett. 1997, 38,
4905-4908.
(40) Suter, J. M.; Boyle, R. W. Chem. Commun. 2001, 2014-2015.
(41) Fletcher, J. T.; Therien, M. J. Inorg. Chem. 2002, 41, 331-341.
(42) (a) Plater, M. J.; Aiken, S.; Bourhill, G. Tetrahedron Lett. 2001, 2225-
2229. (b) Plater, M. J.; Aiken, S.; Bourhill G. Tetrahedron 2002, 58, 2405-
2413.
(43) Kruithof, K. J. H.; Schmitz, R. F.; Klumpp, G. W. Tetrahedron 1983, 39,
3073-3081.
(44) Lange, T.; van Loon, J.-D.; Tykwinsky, R. R.; Schreiber, M.; Diedrich, F.
Synthesis 1996, 4, 537-550.
(45) Coudret, C. Synth. Commun. 1996, 26, 3543-3547.
(46) (a) Roe, A.; Hawkins, G. F. J. Am. Chem. Soc. 1947, 69, 2443-2444. (b)
Murray, A.; Langham, W. H. J. Am. Chem. Soc. 1952, 74, 6289-6290.
(c) Albers, W. M.; Canters, G. W.; Reedijk, J. Tetrahedron 1995, 51, 3895-
3904.
9
3400 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
Scheme 3a
alternative synthesis of 6 involved the trimer 18a, which was
obtained in 85% yield through reaction of 16b with triiodo-
benzene at -20 °C using Pd2dba3 in the presence of tris(2,4,6-
trimethylphenyl)phosphine as catalyst.49 Desilylation of 18a with
TBAF afforded the deprotected product 18b (97%), which was
subsequently reacted with an excess of 4-iodopyridine to gave
the trimer 6 in 56% yield.
Preparation of the Substrates for the Template-Directed
Synthesis of 1. As mentioned before, the template-directed
synthesis of 1 was attempted using the porphyrin monomers
20b and 21b as well as the porphyrin dimer 22b and the linear
hexaporphyrin 23 as substrates (cf. Scheme 4). All of them were
prepared from 1950 as the starting material. The deuterated
derivative of the latter (19-d8), containing 90% 2H at all
â-positions of the pyrrole rings, was synthesized from pyrrole-
a Reagents and conditions: (a) TMSA in THF/i-Pr2NH, Pd(PPh3)2Cl2,
CuI, 50 °C (33%); (b) same as in (a) but with TIPSA as reagent (62%); (c)
1 N NaOH in THF, 25 °C, 2 h (95%); (d) 4-iodopyridine in toluene/Et3N
(5:1), Pd2dba3/P(o-tol)3, 80 °C (66%); (e) CH2Cl2/Et3N (1:1), TBAF; (f)
1,3,5-triiodobenzene in DMF/i-Pr2NEt (20:1), TBAI, CuI, Pd2dba3/tris(2,4,6-
trimethylphenyl)phosphine 50 °C (59%); (g) same as (f) but at -20 °C
(85%); (h) 4-iodopyridine in THF/Et3N (5:1), Pd(PPh3)2Cl2/PPh3, 60 °C
(56%).
2
d5 (98% H)51 via the corresponding meso-(mesityl)dipyrryl-
methane-d6 (cf. ref 50) following the procedure given in ref 52
(cf. Experimental Section). Transformation of 19 into 20a, 22a,
and the linear porphyrin hexamer 23 has been reported
elsewhere.19 Deprotection of the ethynyl group of 22a (M )
2H or Ni(II)) with aq NaOH (1 N) led to 22b (M ) 2H or Ni)
in 84 and 97% yield, respectively. Intermediate 20a, which had
been previously obtained as a byproduct (30%) of the reaction
of 19 with an equimolecular amount of 1-(3-tert-butyl-5-
ethynylphenyl)-3,3-diethyltriaz-1-ene,19 was obtained in 73%
yield by reacting 2 equiv of the latter with 19 in the presence
of Pd(PPh3)2Cl2/CuI as a catalyst (cf. Experimental Section).
Subsequent reaction of 20a with iodomethane at 135 °C yielded
20b almost quantitatively (98%). On the other hand, intermediate
21a was obtained in 68% yield by reacting 19 with trimethyl-
silylacetylene in the presence of Pd(PPh3)2Cl2/CuI as a catalyst.
Thereafter, the Zn(II) ion was removed by treatment with TFA,
and the triple bonds were deprotected by stirring with aq NaOH
in THF to give 21b (M ) 2H). The total yield after purification
by column chromatography amounts to 99%. Thereon, Ni(II)
was inserted by reacting 21b (M ) 2H) with nickel acetate to
afford 21b (M ) Ni) in 65% yield.
Template Synthesis Starting from the Linear Hexamer
23 (M ) Ni). In our previous work, the macrocycle 1 was
prepared by an iterative divergent-convergent approach involv-
ing 17 steps, the less satisfactory of which being the intramo-
lecular cyclization of the linear hexamer intermediate 2317,19
(cf. Scheme 4). This stepwise procedure is cumbersome as it
begins with a monomeric porphyrinic building block, which
yields eventually the linear hexamer by successive functional
group transformations. Moreover, the ring closure, which is the
last step of the procedure, was not reproducible, as the yield
obtained after laborious chromatographic purification varied in
a large range (8-31%) without an apparent reason. As most
attempts to optimize the cyclization step had been carried out
with hexamer 23 in which Zn(II) and Ni(II) porphyrinate rings
alternate (cf. Table 1), the effect of trimers 3-6 on the
cyclization of this linear hexamer was investigated first.
It was observed in the course of these experiments that when
Pd2dba3 together with P(o-tol)332 was employed as the catalyst
the hexameric macrocycle could be much more easily separated
in toluene at 35 °C using, as before, Pd2dba3 and P(o-tol)3 as
catalysts (cf. ref 32). The purification of the crude reaction
mixture afforded, after chromatography on silica gel, some traces
of homocoupling dimer as the first migrating component and
trimer 5, which was eluted as the second green fraction in 87%
yield.
When compared with 5, template 6 results from the replace-
ment of three porphyrin rings by p,p′-biphenylene units, thus
leaving the external diameter of the molecule almost unchanged.
Trimer 6 was prepared from commercial 4,4′-dibromobiphenyl
as starting material, following the pathway outlined in Scheme
3.
Intermediate 16a was prepared either in one step by a mixed
cross-coupling between 4,4′-dibromobiphenyl and an equimo-
lecular mixture of trimethylsilylacetylene and triisopropylsilyl-
acetylene or in two steps by reacting 4,4′-dibromobiphenyl first
with trimethylsilylacetylene and then the obtained product 15
with triisopropylsilyl acetylene. The mixed coupling afforded
16a in 16% yield along with 12% of 4-bromo-4′-(trimethyl-
silylethynyl)biphenyl (15), which, in its turn, was subsequently
reacted with triisopropylsilylacetylene. On the other hand, the
coupling of 4,4′-dibromobiphenyl with trimethylsilylacetylene
led to a mixture of 15 (33%), starting material (14%), and small
amounts of symmetrically 4,4′-disubstituted product, which were
separated by column chromatography. The monosubstituted
product 15 was reacted thereafter with triisopropylsilylacetylene
to give 16a in 62% yield. Thereon, the TMS protecting group
of 16a was cleaved under mild conditions (1 N aq NaOH) to
afford the terminal alkyne intermediate 16b in 95% yield.
48
Alternative syntheses of intermediates 15,47 16a,48 and 16b
from 4-bromo-4′-iodobiphenyl as starting material have been
previously reported in the literature.
Reaction of 16b with an excess (2.5 equiv) of 4-iodopyridine
under the conditions of the Sonogashira coupling, as described
above for 14a, afforded 17a in 66% yield (cf. Scheme 3).
Finally, removal of the remaining protecting group of 17a with
TBAF and reaction of the obtained product 17b with triiodo-
benzene afforded the desired trimer 6 in 34% overall yield. An
(49) Nakamura, K.; Okubo, H.; Yamaguchi, M. Synlett 1999, 5, 549-550.
(50) Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427-11440.
(51) Fajer, J.; Borg, D. C.; Forman, A.; Felton, R. H.; Vegh, L.; Dolphin, D.
Ann. NY Acad. Sci. 1973, 206, 349-364.
(47) Nitschke, J. R.; Tilley, T.; Don, J. Am. Chem. Soc. 2001, 123, 10183-
10190.
(48) Cheng, Y.-J.; Luh, T.-Y. Chem.sEur. J. 2004, 10, 5361-5368.
(52) Gross, Z.; Kaustov, L. Tetrahedron Lett. 1995, 36, 3735-3736.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3401

A R T I C L E S
Scheme 4a
Rucareanu et al.
a Reagents and conditions: (a) 1-[3-(1,1-dimethylethyl)-5-ethynylphenyl]-3,3-diethyltriaz-1-ene in DMF/Et3N (5:1), Pd(PPh3)2Cl2/CuI, 35 °C, 14 h, (30%);
(b) same as in (a) but with ethynyltrimethylsilane as a reagent (68%); (c) ICH3, 135 °C, 2 h, (98%); (d) TFA in CHCl3, 25 °C, 2 h, then aq. NaOH in THF,
25 °C, 3 h (100%); (e) 1 M aq. NaOH in THF, 25 °C, 3 h (84%).
Table 1. Dependence of the Yield of 1a, Obtained by Cyclization
of 23 in the Absence of Template, on the Reaction Conditions
the concentration of triethylamine in the solvent (toluene) was
reduced to 20% (v/v). The amine cannot be completely excluded,
as the coupling reaction does not take place in the absence of
base.
entry
catalyst
solvent
yield (%)
1
2
3
4
Pd(PPh3)4
Pd(PPh3)4
Pd2dba3/P(o-tol)3
Pd2dba3/P(o-tol)3
DMF/Et3N
toluene/Et3N
toluene/Et3N
DMF/Et3N
8-30a
21
20-30
17
On the other hand, triethylamine was used instead of a
secondary amine (e.g., diethylamine) in order to avoid side
reactions such as addition to the acetylenic bonds (cf. ref 36).
Also, high temperatures must be avoided in order to prevent
dissociation of the kinetically labile substrate-template complex.
These mild conditions also prevent the use of the copper
reagents, afford coupling in dilute solution, and preserve the
metalation state. Interestingly, although an excess of catalyst
(60 mol % of Pd per I atom) was required to complete the
reaction, the addition of a second batch of catalyst, a few hours
after the beginning of the reaction, did not significantly increase
the yield but facilitated substantially the separation of the cyclic
hexamer by column chromatography. Presumably, some oligo-
mers, which otherwise would be eluted closely to the cyclic
hexamer, are converted in the presence of an excess of catalyst
to less soluble compounds of high molecular weight.
a From refs 17 and 19.
Table 2. Yield of Macrocycle 1a, Obtained by Pd2dba3/
P(o-tol)3-Catalyzed Cyclization of 23 in Toluene/(C2H3)3N (5:1) as
Solvent, in the Presence of Template
template
yield (%)
3
4
c
5
5a
6
48
45b
59d
41b
a In this run, only 30% Pd per I atom was added in two portions (cf.
Experimental Section). b The isolated product was 95% pure. c No pure
fraction could be isolated. d Maximal yield; mostly the yield varied between
52 and 55%.
from the reaction mixture. Therefore, the reaction in the presence
of template was performed under the conditions specified in
Table 2. Tetrahydrofuran cannot be used as a solvent because
it competes with the pyridine ligands of the template for the
porphyrin binding sites of the substrate. For the same reason,
After completion of the cyclization reaction, the usual
procedure to remove the template from the host cavity consists
in decomposition of the porphyrin zinc chelates by treatment
9
3402 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
Table 3. Yields of Macrocycle 1c, Obtained from Monomeric
Porphyrins 20b and 21b (M ) 2H), in the Presence of 5 as
Template
geometry of the assembly, as a whole, is not anymore favorable
to intramolecular coupling. In light of these experiments, we
can conclude that the appropriate template for the linear 23 (M
) Zn) hexamer should be a star-shaped hexamer (niphaphyrin)
that bears the same arms as template 5. Until now, unfortunately,
our efforts to synthesize such a template were unsuccessful.
Presently, a synthesis of a similar star-like hexamer whose arms
are those used for the trimer 6 is underway.
run
1
2
3
4
5
6
7a
7.1
yield (%)
6.3
7.5
5.2
5.4
6.3
4.8
a In this run, macrocycle 1a was synthesized from 20b and 21b (M )
Ni).
with acid. In the present case, however, no additional demeta-
lation step was necessary before separation of the reaction
mixture by column chromatography since the complex between
the cyclic hexamer and the trimer template dissociates on
dissolving the crude product in THF before its isolation. Thus,
the cyclic hexamer was eluted first with a CHCl3/hexane mixture
and purified further by preparative TLC. Thereon, about 50%
of the template was retrieved eluting with a CHCl3/MeOH
mixture. The loss of the trimer template is probably related to
the considerable precipitation observed during the template-
directed syntheses, and it may be due to the inclusion of the
template in the insoluble polymers formed as byproducts.
As expected, the best yields of macrocycle were obtained in
the case of trimer 5, whose dimensions fit the best into the inner
cavity of the macrocycle (Table 2). The high yield obtained
reflected a significant “template-directed” contribution to the
ring closure reaction.
Trimer 3 proved to be a less efficient template. The lengths
of its “arms” slightly exceed the cavity radius of 1b, and even
though the macrocycle is apparently flexible enough to accom-
modate the trimer, giving a very stable host-guest complex
(the measured binding constant amounts to K ) 1.4 × 109 M-1),
the reactive ends of the linear precursor complexed with 3 may
be not close enough to favor intramolecular coupling against
intermolecular reactions. Thus, polymers are presumably formed,
which make the separation of the desired product more difficult.
Actually, after repeated chromatographic separation, the purity
of the macrocycle obtained in the presence of 3 as a template
did not exceed 95%.
In the presence of the smaller trimer 4 as a template, only
complex mixtures of products were obtained, and even if the
presence of 1b was detected, no pure fraction could be isolated.
This was not surprising, as the arms of the trimer are too short
to fit inside the cavity of the macrocyclic hexamer, so that
probably not all three (porphyrinato)zinc(II) rings of the same
linear precursor are complexed with one molecule of the
template, thus disfavoring intramolecular coupling.
Trimer 6, in which biphenyl moieties replace the porphyrin
rings, has dimensions similar to those of 5. Therefore, it forms
a stable complex with 1b (cf. Table 4) and serves also as an
efficient template for the synthesis of the latter (cf. Tables 2
and 3).
Templated Synthesis Starting from Porphyrin Monomers.
Encouraged by the above results, we attempted next the
template-directed synthesis of 1a using 5 as the template and
porphyrins 20b and 21b (M ) Ni) as the substrates (cf. Figure
3c). In this approach, the (porphyrinato)zinc(II) building blocks
should ligate first to the pyridine rings at the apical positions
of the template, thus forming a loose complex, in which three
porphyrin rings are held in the appropriate positions to yield
the macrocyclic porphyrin hexamer on reaction with 21b (M
) Ni) as the complementary building blocks. Thus, the
cyclization step involves six coupling reactions, without isolation
of any intermediate (cf. Figure 3c). Since pyridine ligands do
not efficiently coordinate with the Ni(II) ions in porphyrin
complexes,27 they should not compete with the ligated (por-
phyrinato)zinc(II) rings for the apical positions in the above-
mentioned loose complex. However, as suggested by Sanders
and co-workers for a similar template-directed synthesis of a
cyclic porphyrin tetramer,15d,g an alternative mechanism could
consist in the trapping of linear intermediates by the template,
while a preassembly of monomeric components around the
ligand, before any chemical reaction takes place, is most likely
if the porphyrin complexes (e.g., Ru(II) porphyrinates15g or Zn-
(II)-dioxoporphyrinates53) strongly bind the pyridine ligands.
Actually, in the course of our experiments carried out to optimize
the yield of the macrocyclic porphyrin hexamer 1a, it was
observed that if smaller amounts of catalyst than 2 × 30 mol
% Pd per I atom were used, no pure macrocycle could be
isolated. Instead, several fractions containing linear trimers to
octamers were identified by ESI mass spectrometry. Evidently,
therefore, linear polymerization of the building blocks 20b and
21b (M ) Ni) compete with the reaction of the latter with a
preorganized complex between 20b and the template. Moreover,
some components identified by ESI mass spectrometry lack the
iodine atom, so that hydrodeiodination of the substrates,54,55
which interrupts the polymerization process, seems to be an
important side reaction under the employed conditions.
As templates normally bind too strongly to the product of
the reaction to act catalytically, stoichiometric quantities of
template and substrates are at least needed for an efficient
cyclization. In the present case, the best results were obtained
under these conditions. In our hands, no pure macrocycle could
be isolated using a 1:1:1 ratio of reagents, although sometimes
better yields have been reported using an excess of template.15d
Replacement of the free base monomer 21b (M ) 2H) for the
corresponding Ni(II) complex did not affect the outcome of the
reaction (Table 3). The thus obtained macrocycle 1c can be
either transformed into the corresponding complex with six Zn-
(II) ions upon treatment with zinc acetate or completely
The data collected along this work show that the template-
directed synthesis of 1a is reproducible under the employed
conditions, the yields obtained in five runs ranging between 52
and 59% (Table 2). Not unexpectedly, the template-directed
cyclization of the linear hexamer 23 (M ) Zn) in the presence
of 5 led to a very complex mixture of products, and no pure
fraction could be isolated, even after repeated chromatography.
This result may be explained by the circumstance that upon
complexation of 23 (M ) Zn) with the template there are still
three unligated Zn-porphyrin rings, which are available for
complexation with other molecules of the trimer, so that the
(53) McCallien, D. W. J.; Sanders, J. K. M. J. Am. Chem. Soc. 1995, 117, 6611-
6612 and references given therein.
(54) Nguyen, P.; Yuan, Z.; Agocs, L.; Lesley, G.; Marder, T. B. Inorg. Chim.
Acta 1994, 220, 289-296.
(55) Chou, M.-Y.; Mandal, A. B.; Leung, M. J. Org. Chem. 2002, 67, 1501-
1505.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3403

A R T I C L E S
Rucareanu et al.
however, that such values are at the limit of the accuracy of
direct measurements from UV-vis titration curves,56,58 so that
the margin of error of the values quoted in Table 4 cannot be
neglected.
Apparently, the macrocycle of hexamers 1a and 1b is flexible
enough to accommodate the trimers 3, 4, and 5 without
noticeable distortion of the molecule that obviously would result
in lower values of the binding constant. Although trimer 6 is
bound about 4 times less strongly than 5, the supramolecular
complex is stable enough for a template-directed synthesis. On
the other hand, the guest affinity toward Zn porphyrinates is
directly dependent on the ligand basicity,59-61 that is, the more
basic the ligands are, the stronger they bind. As the binding
constants for all trimers are situated in the same range, their
quality as templates depends rather on the geometry of the
complex with the substrates which, in the end, is determined
by the length of the arms of the template.
Figure 4. Unfavorable geometries of the substrate ligand complex may
thwart the synthesis of macrocycles 1a-c starting from porphyrin dimers.
demetalated by treatment with TFA. Subsequently, the metal-
free macrocycle can be transformed into a complex with six
metal ions of the same element, other than Zn(II). Despite its
modest yield (∼5%), the above-described templated synthesis
starting from porphyrin monomers is more advantageous than
the cyclization of the linear hexamer 23 (M ) Zn) since the
synthesis of the latter implies more than 13 time-consuming
steps with an overall yield of only 1%.
As in the case of previously described molecular complexes
of 1a with homologues of 5 (cf. ref 19), 1H NMR spectroscopy
proved to be a useful tool for the structure determination of the
corresponding supramolecular assemblies. The assignment of
the resonance signals of both the host and guest molecule in
the complex was carried out by a combination of COSY and
NOE experiments, which, in the case of complex 1a + 5, clearly
show that the tridentate ligand binds inside the cavity of the
hexaporphyrin macrocycle, the pyridine rings being bound to
the Zn(II) ions and not to the Ni(II) ions, as a consequence of
the low affinity of Ni(II) ions for nitrogen-containing ligands.27
Templated Synthesis Starting from Porphyrin Dimers.
Should the mechanism of the above-described synthesis of 1a
imply the trapping of linear intermediates by the template, it
would be conceivable that starting from a porphyrin dimer as
the substrate the yield of the reaction could be improved since
the cyclization process involves only three coupling reactions
instead of six, as required in the one-pot synthesis starting from
monomers (cf. Figure 3). Unexpectedly, however, attempted
coupling of three molecules of 22b in the presence of template
5 yielded a complex reaction mixture, from which no pure cyclic
hexamer could be isolated. This result may reflect the higher
disorder in a loose complex, in which three (porphyrinato)zinc-
(II) rings are ligated to the apical pyridine residues, but the other
three nonligated rings may adopt conformations which are
unfavorable for intramolecular ring closing (cf. Figure 4).
Structure of the Supramolecular Complexes. The com-
plexation behavior of the macrocyclic porphyrin hexamers 1a
and 1b (as hosts) against the trimer templates 3-6 (as guests)
was examined, and corresponding binding parameters were
obtained by UV-vis spectroscopic titration experiments. Ti-
trations were carried out at constant cyclic hexamer concentra-
tion in CH2Cl2 solutions at 20 °C.
The changes in absorption were monitored as a function of
concentration of template in a range where maximum change
in absorption was observed during the titration (cf. Figure 6).
So, two sets of data were obtained: one for the decreasing
absorption near λmax of the free host and the second one for the
rising absorption near λmax of the newly formed complex (cf.
ref 56). The simulation analysis of the resulting data was carried
out by subtracting one data set from another using a least-squares
curve-fitting program. The experimental points match well with
a set of theoretical equations for a plain 1:1 complexation
isotherm using the nonlinear least-squares optimization. Thus,
values of binding constants for complexes between 1a and 1b
and the star-shaped trimers 3-6 were obtained (Table 4), which
are in agreement with an efficient three-point bonding57 ranging
between 108-109 mol dm-3 (cf. ref 19). It must be pointed out,
1
Accordingly, the H NMR spectrum at 500 MHz of complex
1b + 5 shows, at 20 °C, two sets of resonance signals
corresponding to the Zn(II) porphyrinate rings which are bound
to the pyridine moieties of the guest molecule and those in which
the Zn(II) ions are devoid of axial ligands (cf. Figure 5).
Interestingly, however, at 55 °C, all six Zn(II) porphyrinate rings
become magnetically equivalent, as evidenced by the fact that
1
only a set of signals is observed in the H NMR spectrum of
1b + 5 at this temperature (see below). As in the case of
complex 1a + 5, the resonance signals at δ 2.79 and 6.10 ppm,
assigned to the R- and â-H atoms, respectively, of the complexed
pyridine rings are upfield shifted by ∆δ ) - 6.06 and - 1.81
ppm, respectively, with respect to the corresponding signals of
the free ligand. The observed upfield displacements are in the
same range as those observed in similar complexes with
tridentate ligands, thus confirming that all three pyridine ligands
are bound simultaneously.15g,62 Moreover, the structure of the
molecular complex depicted in Figure 5 is consistent with the
insignificant changes of chemical shift observed for the protons
at the 1,3-phenylene rings serving as cornerstones of the
macrocycle as well as the (porphyrinato)zinc(II) rings which
are not involved in intermolecular bonding.
Additional support for the proposed structure of complexes
1a + 5 and 1b + 5 was supplied by the MALDI-TOF MS
(57) Anderson, H. L.; Walter, C. J.; Vidal-Ferran, A.; Hay, R. A.; Lowden, P.
A.; Sanders, J. K. M. J. Chem. Soc., Perkin Trans. 1 1995, 2275-2279.
(58) Anderson, H. L.; Sanders, J. K. M. J. Chem. Soc., Chem. Commun. 1989,
1714-1715.
(59) Kirksey, C. H.; Hambright, P.; Storm, C. B. Inorg. Chem. 1969, 8, 2141-
2144.
(60) Borovkov, V. V.; Lintuluoto, J. M.; Sugeta, H.; Fujiki, M.; Arakava, R.;
Inoue, Y. J. Am. Chem. Soc. 2002, 124, 2993-3006.
(61) Anderson, H. L. Inorg. Chem. 1994, 33, 972-981.
(62) Clyde-Watson, Z.; Bampos, N.; Sanders, J. K. M. New J. Chem. 1998,
1135-1138.
(56) Anderson, H. L.; Anderson, S.; Sanders, J. K. M. J. Chem. Soc., Perkin
Trans. 1 1995, 2231-2245.
9
3404 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
Figure 5. 1H NMR resonance signals of the complex 1b + 5 at 0 °C, as assigned by COSY and NOE experiments. Chemical shifts (in ppm) point to the
corresponding atoms (f), and NOE connectivities are indicated by dashed lines (- - -). Mesityl groups at one of the meso positions of the (porphyrinato)-
zinc(II) rings have been omitted for clarity.
besides the two peaks belonging to the individual ligand 5 (m/z
) 2507.14) and cyclic hexamer 1a (m/z ) 5619.94), the
expected molecular peak pattern of the corresponding supramo-
lecular complex (m/z ) 8126.06). Similar results were obtained
for the complex 1b + 5 (m/z ) 8147.7) and its components 1b
(m/z ) 5638.62) and 5.
Dynamics of Supramolecular Assembly. A solution of the
host macrocycle 1a in CDCl3 was titrated at 20 °C against the
Figure 6. UV-vis titration spectra showing the decrease of the intensity
tridentate ligand 5, and 1H NMR spectra were recorded at 360
of the Soret band of 1b (5.19 × 10-8 M in CH2Cl2) and the increase of the
MHz. On adding 5, the intensity of the sharp resonance signals
of 1a decreased, while new sharp signals belonging to the
complex arose and gradually increased until only signals of the
intensity of the Soret band of the complex 1b + 5 upon addition of ligand
5 (1.29 × 10-6 M in CH2Cl2).
Table 4. Binding Constants (K) in CH2Cl2 at 20 °C between
complex were present when 1 equiv of 5 had been added.
Integration of the signal intensities reveals a guest/host ratio of
1:1 according to a structure analogous to those depicted in Figure
5. In the presence of an excess of 5, the signals of the bound
ligand broaden slightly, and broad signals of free 5 appear which
are slightly shifted upfield. Presumably, they are broadened as
a result of the weak binding to the external faces of the
macrocycle via six-coordinate zinc(II) (cf. ref 15e).
Macrocycle 1a and 1b and Ligands 3-6
1
macrocycle
ligand
K (M-
)
1a
1a
1a
1a
1b
3
4
5
6
5
1.4 × 109
3.4 × 109
2.8 × 109
6.5 × 108
2.7 × 109
On the other hand, when the host macrocycle 1b was titrated
against the same ligand (5) at 20 °C, slightly broadened
resonance signals of both the complex and the host molecules
technique that proved to be a valuable tool for analyzing
complexes consisting of noncovalent interactions. The mass
spectrum (DCTB matrix) of the complex 1a + 5 revealed,
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3405

A R T I C L E S
Rucareanu et al.
As mentioned before, at 55 °C, only a set of signals is
1
observed for the six Zn(II) porphyrinate rings in the H NMR
spectrum of the complex 1b + 5 (cf. Figure 7). When the host
macrocycle 1b was titrated against the ligand 5 at 55 °C, the
1H resonance frequencies of both reactants at 500 MHz remained
unchanged, and no shift or broadening of the resonance signals
was observed until 1 equiv of ligand has been added. The
intensity of the signals belonging to the newly formed complex
increased progressively with the amount of trimer added, while
the signals of the free host gradually disappeared. On addition
of ligand to a solution of the complex 1b + 5 at 55 °C, the
resonance signals of the former became progressively broader
and shifted gradually downfield on increasing the amount of
ligand added.
In principle, the magnetic equivalence of all Zn(II) porphy-
rinate rings of complex 1b + 5 can be explained either by
intramolecular rotation of the ligand inside the cavity of the
host molecule or by rapid dissociation and recombination of
the host and guest molecules forming the complex. Actually,
both mechanisms would agree with the observed broadening
1
of the H NMR signals at about 35 °C as the coalescence
1
Figure 7. Detail of the 500 MHz H NMR spectrum of complex 1b + 5
in the δ ) 8.70-9.05 ppm range showing the temperature dependence
between 0 and +55 °C of the signals assigned to the H-atoms at (a) C8
and C12 of the porphyrin rings of the ligand; (b) even-numbered â-positions
of the unligated Zn(II) porphyrinate rings of the macrocycle; (c) even-
numbered â-positions of the ligated Zn(II) porphyrinate rings of the
macrocycle; (d) odd-numbered â-positions of the unligated Zn(II) porphy-
rinate rings of the macrocycle; and (e) odd-numbered â-positions of the
ligated Zn(II) porphyrinate rings of the macrocycle (cf. Figure 5).
temperature (cf. Figure 7). Although the mechanism involving
intramolecular ligand exchange, which drives the guest molecule
to rapidly walk around the inside of the cavity, has been
suggested by Sanders and co-workers in order to explain that
only a set of porphyrin signals is seen, at room temperature, in
the 1H NMR spectrum of molecular complexes in which
bidentate ligands are inside the cavity of a cyclic porphyrin
trimer,15c,56 an alternative mechanism involving the break of
only one N-Zn bond followed by rotation of the (bidentate)
ligand around the other N-Zn bond may also operate in their
case (cf. ref 62b). In the case of 1b + 5, the interpretation of
the 1H NMR spectrum at 55 °C was hampered by the fact that,
at this temperature, the resonance signals of the (uncomplexed)
host macrocycle are shifted upfield by 0.026 ppm so that they
largely overlapseven at 700 MHzswith the corresponding
signals of the complex in the relevant range between δ 8.70
and 9.05 ppm.
were observed. Contrarily, progressive addition of the ligand
to a solution of the host macrocycle at 0 °C allows one to clearly
differentiate the resonance signals of the complex and the host
macrocycle present in excess at the beginning (cf. Figure 5).
Interestingly, the proton resonances of both the free and bound
ligand are slightly broader at 0 °C than at 20 °C (cf. Figure 7),
probably due to restricted rotation of the porphyrin rings around
the axis of the acetylenic bonds.63 Moreover, the resonance
signals of both the complex and free host molecules do not
broaden or shift until 1 equiv of ligand is added to the solution
of the macrocycle, thus indicating that a distinct complex is
formed,61 since a dynamic equilibrium between a variety of
complexes would result in broad, concentration-dependent
signals (cf. refs 64 and 65). This is in agreement with the
presence of a single isosbestic point at 428.2 nm for the family
of curves obtained on progressive addition of ligand 5 to a
solution of macrocycle 1b, as monitored by UV-vis spectros-
copy (cf. Figure 6). At 0 °C, addition of an excess of ligand 5
to the solution of the complex 1b + 5 resulted in broadening
of the resonance signals either as a result of ligation to the outer
faces of the three Zn(II) porphyrinate rings, which are devoid
of axial ligands inside the cavity of the macrocycle, or to
exchange free and complexed ligand molecules, which is
presumably accelerated in the presence of an excess of ligand
by an associative SN2-like mechanism via a six-coordinate Zn-
(II) intermediate66 (cf. ref 67).
Therefore, to get an insight into the kinetic stability of the
complex 1b + 5, 1 equiv of the host molecule was added at
-40 °C to a solution of the complex 1b-d48 + 5, in which the
H-atoms at all â-positions of the porphyrin rings forming the
macrocycle had been replaced by deuterium. Actually, if ligand
exchange between labeled and unlabeled molecules of the host
1
takes place slowly on the H NMR time scale (at 500 MHz),
the proton resonance signals corresponding to Zn(II) porphy-
rinate rings, which are ligated to the pyridine moieties of the
ligand, should gradually appear on increasing the temperature.
In an extreme case, ligand exchange does not take place at all,
thus leading to the conclusion that the porphyrin rings of
complex 1b + 5 become equivalent at 55 °C as a result of
intramolecular ligand exchange which drives the guest molecule
to rapidly walk around inside the cavity. As a matter of fact,
however, even after rapid addition of 1b to the solution of the
deuterated complex 1b-d48 + 5 at -40 °C, the 1H NMR
spectrum of the mixture, which was recorded at -30 °C, reveals
the presence of the resonance signals of the unlabeled complex
(cf. Figure 8c). As the difference of chemical shifts of
(63) Middel, O.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem. 2001, 66, 3998-
4005.
(64) Tsuda, A.; Nakamura, T.; Sakamoto, S.; Yamaguchi, K.; Osuka, A. Angew.
Chem. 2002, 114, 2941-2945; Angew. Chem., Int. Ed. 2002, 41, 2817-
2821.
(65) Stultz, E.; Ng, Y.-F.; Scott, S. M.; Sanders, J. K. M. J. Chem. Soc., Chem.
Commun. 2002, 524-525.
(66) Walker, F. A.; Benson, M. J. Am. Chem. Soc. 1980, 102, 5530-5538.
(67) Mackay, L. G.; Anderson, H. L.; Sanders, J. K. M. J. Chem. Soc., Perkin
Trans. 1 1995, 2269-2273.
9
3406 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
mol-1. Accordingly, the free energy of activation for the
dissociation of the complex at 20 °C (293 K) and at -30 °C
(243 K) amounts to ∆Gq ≈ 67 and 74 kJ mol-1, respectively.
The corresponding rate constants for dissociation are k293 ) 6.5
and k243 ) 7.4 × 10-4 s-1, respectively. The latter figure, which
corresponds to a half-time of the reaction of about τ1/2 ) 15
min at 243 K, is in good agreement with the observation that
even at low temperature exchange of the guest molecule of the
1
complex was almost complete before measurements of the H
NMR spectrum could be started. On the other hand, a maximum
rate constant for the dissociation of the supramolecular complex
at 293 K can be calculated from the experimentally determined
equilibrium constant K ) 2.7 × 109 (cf. Table 4), assuming
that the maximum possible association rate constant is diffusion
controlled, and therefore it cannot exceed the value 1010 M-1
s-1 (cf. refs 15f and 69). Therefore, as the equilibrium constant
equals the quotient of this maximum on-rate divided by the off-
rate, an upper limit of the latter should be k ) 3.7 s-1, a value
which, within the margin of error, is close to the rate constant
(k293 ) 6.5 s-1) derived from the kinetic experiment as explained
above. Even though the large size and steric restrictions of the
molecules involved in the formation of the complex may reduce
the above diffusion limit, the above-mentioned inaccuracy of
the experimental determination of the equilibrium constant, on
the other hand, may result in a too high value for the latter, so
that the correspondence between the rate constants estimated
from the kinetic and thermodynamic data is quite satisfactory.
Therefore, although intramolecular rotation of the guest molecule
inside of the cavity of the host cannot be excluded unequivocally
on the basis of the presently available data, these strongly
suggest that intermolecular ligand exchange alone accounts for
the equivalence of all porphyrin rings observed in the 1H NMR
spectrum of 1b + 5 at 55 °C.
Conclusions
The template-directed synthesis of the macrocyclic hexapor-
phyrins 1a and 1c described in this work exemplifies a
straightforward approach for the preparation of such macrocycles
starting from monomeric porphyrin building blocks. The work
emphasizes the importance of the molecular dimensions of both
the host and guest molecules for the formation of a complex
with the appropriate geometry required for the cyclization
process. Unexpectedly, in contrast to the low dissociation
constant (Kdiss ≈ 10-9) of the supramolecular complex between
1
Figure 8. Detail from the H NMR spectrum at -30 °C of (a) unlabeled
1b and (b) complex 1b-d48 + 5, showing the signals of residual H-atoms
at the â-positions of the porphyrin rings of 1b-d48. (c-i): Temperature
dependence of the 500 MHz 1H NMR spectrum of complex 1b-d48 + 5
observed between -30 and +55 °C in the δ ) 8.70-9.05 ppm range, after
addition of 1 equiv of unlabeled 1b (for assignments, see Figures 5 and 7).
1
corresponding â-H-atoms at the Zn(II) porphyrinate rings, which
are ligated to pyridine, and those which are devoid of the axial
ligand amounts to 0.05 ppm (i.e., 25 Hz at 500 MHz), the first-
order rate constant for the dissociation of the complex at a
temperature of approximately 35 °C (308 K), at which the
resonance signals of the H-atoms at the â-positions of the pyrrole
rings of the unlabeled host molecule coalesce (cf. Figure 8g,h),
may be estimated at kc ) 56 s-1 according to kc ) (π/x2)∆ν.68
The corresponding free energy of activation can be calculated
to be ∆Gq308 ≈ 65.2 kJ mol-1 using Eyring’s equation. As the
entropy of binding is unlikely to be greater than 130 J mol-1
K-1 (cf. ref 56), the activation enthalpy for the formation of
the supramolecular complex will not exceed ∆Hq ) 105 kJ
the tridentate ligand 5 and the macrocycles 1a-c, H NMR
spectroscopic analysis of the macrocyclic hexaporphyrin 1b in
the presence of its analogue, in which all H-atoms at the pyrrole
rings have been replaced by deuterium, revealed that even at
low temperature (-40 °C) a rapid dissociation and recombina-
tion of the host and guest molecules forming the supramolecular
complex takes place.
Experimental Section
General. All air- or water-sensitive reactions were carried out under
argon. Solvents were generally dried and distilled prior to use. Reactions
were monitored by thin-layer chromatography (TLC) on Merck silica
gel 60 F254 (0.2 mm) precoated aluminum foils. Reaction products were
separated by flash chromatography (FC) on Merck silica gel 60 (0.040-
0.063 mm, 230-400 mesh), except otherwise noted, and/or on
preparative TLC plates (20 × 20 cm, silica gel 60 F254, 1 mm). Melting
(68) Kost, D.; Carlson, E. H.; Raban, M. Chem. Commun.1971, 656-657.
(69) Storm, C. B.; Turner, A. H.; Swann, M. B. Inorg. Chem. 1984, 23, 2743-
2746.
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A R T I C L E S
Rucareanu et al.
points (mp) were determined with a hot stage apparatus (Thermovar,
C. Reichert AG, Vienna) equipped with a digital thermometer. UV/vis
spectra were recorded on a Hewlett-Packard 8452A diode-array or a
Perkin-Elmer Lambda 40 spectrometer; λmax (logꢀ) in nm. NMR:
Bruker Avance DPX360 (1H, 360.14 MHz, 13C, 90.56 MHz), or Bruker
Avance DRX500 (1H, 500.13 MHz, 13C, 125.76 MHz) in CDCl3
P(o-tol)3 (15.5 mg, 50.88 µmol) following the procedure described
above for the synthesis in the absence of template. Separation of the
reaction product by FC using successively CHCl3/n-hexane (7:3),
CHCl3, and CHCl3/MeOH (9:1) as eluants was followed by preparative
TLC (n-hexane/CHCl3/EtOAc 4:1:1), yielding 1.4 mg (7%) of 1a,
identical with the above samples.
1
solutions unless otherwise stated; H and 13C chemical shifts (δ) are
Macrocyclic Hexaporphyrin 1c from Monomers 20b and 21b
(M ) 2H) in the Presence of Template. A mixture of 20b (14.1 mg,
10.6 µmol), 21b (M ) 2H) (7.9 mg, 10.6 µmol), and 5 (8.9 mg, 3.54
µmol) was reacted as described above for 1a to yield 1.0 mg (5%) of
1c, as the component with the lowest Rf. Its analytical data are identical
to those previously reported.17
given in parts per million relative to Si(CH3)4 as internal standard, and
J values are in hertz. Assignments are based on homonuclear COSY-
1
45, H{1H} NOE difference correlations, and/or chemical shifts. 13C
signal multiplicities were determined by attached proton test (APT)
experiments. Mass spectra: Vacuum Generators Micromass 7070E
instrument equipped with a data system DS 11-250. EI (electron
ionization): acceleration voltage 70 eV; FAB (fast atom bombardment)
in 3-nitrobenzyl alcohol with Ar at 8 kV; ES+-MS (electrospray
ionization, positive mode) and MALDI-MS (Matrix Assisted Laser
Desorption Ionization) using dithranol as matrix; FT mass spectrometer
Bruker 4.7T BioAPEX II; MALDI-TOF, Bruker Reflex-II (delayed
extraction, 20 kV acc. voltage, positive reflection mode) using DCTB
(2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene] malonitrile)19
dissolved in CHCl3 (0.05 M) as matrix (dried droplet method) and
averaging 200-1100 shots. Elemental analyses were carried out by
Ilse Beetz Microanalytical Laboratory, Kronach, Germany.
1
Complex 1a + 5. The complex formation was monitored by H
NMR spectroscopy adding gradually 1 equiv of 5 (in concentrated
CDCl3 solution) to a solution of 1a in CDCl3 and recording a 1H NMR
spectrum after each addition. Signal integration indicates that a new
species was formed between 1a and 5 in a ratio of 1:1; the proton
chemical shifts in the guest porphyrins are upfield shifted due to the
ring currents of the porphyrin rings in the macrocycle. 1H NMR (500.13
MHz): δ -2.16 (br, 6H, NH), 1.42 (s, 108H, t-Bu on 5), 1.49 (s, 54H,
t-Bu on 1a), 1.84 (s, 36H, o-CH3 on Ni porphyrinate), 1.88 (s, 36H,
o-CH3 on Zn porphyrinate), 2.58 (s, 18H, p-CH3 on Ni porphyrinate),
2.63 (s, 18H, p-CH3 on Zn porphyrinate), 2.76 and 6.06 (2 × apparent
d, J ) 5.99 Hz, 12H, C6H4N), 7.23 (s, 12H, phenyl-m-H on Ni
porphyrinate), 7.29 (s, 12H, phenyl-m-H on Zn porphyrinate), 7.70 (t,
J ) 1.71 Hz, 6H, p-H on di-t-Bu-phenyl), 7.73 (app. s, 6H, o-H on
t-Bu-phenyl), 7.66 (app. s, 6H, o-H on t-Bu-phenyl), 7.84 (app. s, 6H,
p-H on t-Bu-phenyl), 7.89 (d, J ) 1.71 Hz, 12H, o-H on di-t-Bu-
phenyl), 7.92 and 8.10 (AA′XX′ apparent J ) 8.07 Hz, 24H, phenylene
on Ni porphyrinate), 7.98 and 8.33 (AA′XX′ apparent J ) 8.07 Hz,
24H, phenylene on Zn porphyrinate), 8.62 (s, 3H, benzenetriyl), 8.63
and 9.00 (2 × d, J ) 4.64 Hz, 12H, â-H on porphyrin trimer), 8.65
and 8.76 (2 × d, J ) 4.9 Hz, 24H, â-H on Ni porphyrinate), 8.78 and
8.89 (2 × d, J ) 4.64 Hz, 24H, â-H on Zn porphyrinate), 8.83 and
9.77 (2 × d, J ) 4.64 Hz, 12H, â-H on porphyrin trimer). MALDI-
TOF-MS (DCTB): 8126.063, 5619.941, 2507.143; calcd average mass
for C561H471N39Ni3Zn3 (complex 1a + 5), C384H300N24Ni3Zn3 (5), and
Tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) was purchased
from Acros Organics (B-2440 Geel); tris(dibenzylideneacetone)di-
palladium (Pd2dba3), tri-o-tolylphosphine (P(o-tol)3), tetrabutylammo-
nium fluoride (TBAF), tetrabutylammonium iodide (TBAI), dimeth-
ylformamide (DMF), and N,N-diisopropylethylamine (iso-Pr2NEt) were
purchased from Aldrich Chemie (CH-9471 Buchs); trifluoroacetic acid
(TFA), tetrahydrofuran (THF), trimethylsilylacetylene (TMSA), triiso-
propylsilylacetylene (TIPSA), and other reagents were from Fluka
Chemie AG (CH-9471 Buchs).
Macrocyclic Hexaporphyrin 1a from Linear Hexamer 23 (M )
Ni) in the Absence of Template. A solution of 23 (M ) Ni) (3 mg,
0.52 µmol) in 5 mL of toluene was purged of air by passing Ar for 5
min before triethylamine (1 mL) was added. Then, the mixture was
degassed by three freezing/thaw cycles in vacuo before Pd2dba3 (0.14
mg, 0.156 µmol) and P(o-tol)3 (0.38 mg, 1.248 µmol) were added at
25 °C under Ar. Thereon, the reaction mixture was stirred at 35 °C for
8 h under an Ar stream, protected from light, before a second portion
of catalyst was added, and stirring was continued overnight. The solvent
was removed under reduced pressure, and the solid residue was purified
twice by FC, using CHCl3/hexane (7:3) as eluant, to yield a main violet
product which was washed with MeOH and n-hexane. The maximal
yield of 1a obtained by this procedure amounted to 0.6 mg (21%). Its
analytical data were identical to those previously reported.19
C177H171N15 (1a) ) 8131.50, 5622.99, and 2508.4, respectively.
Complex 1b + 5 was characterized as described above for the
1
complex 1a + 5. H NMR (500.13 MHz, 0 °C): δ -2.24 (br, 6H,
NH), 1.42 (s, 108H, t-Bu on 5), 1.50 (s, 54H, t-Bu on 1b), 1.87 (s,
36H, o-CH3 on unligated Zn porphyrinate), 1.89 (s, 36H, o-CH3 on
ligated Zn porphyrinate), 2.64 (s, 18H, p-CH3 on ligated Zn porphy-
rinate), 2.65 (s, 18H, p-CH3 on unligated Zn porphyrinate), 2.79 and
6.10 (2 × apparent d, J ) 5.4 Hz, 12H, -C6H4N), 7.31 (s, 12H, m-H
on ligated Zn porphyrinate), 7.32 (s, 12H, m-H on unligated Zn
porphyrinate), 7.68 (app. s, 6H, p-Ph), 7.76 (app. s, 6H), 7.77 (app. s,
6H), 7.89 (app. s, 6H), 7.91 (app. s, 12H, o-Ph), 8.00 and 8.30 (AA′XX′
on unligated Zn porphyrinate, apparent J ) 7.7 Hz, 24H), 8.00 and
8.34 (AA′XX′ on ligated Zn porphyrinate, apparent J ) 7.7 Hz, 24H),
8.62 (s, 3H, benzenetriyl), 8.67 and 9.02 (2 × br, 12H, â-H on porphyrin
trimer), 8.80 and 8.90 (2 × d, J ) 4.3 Hz, 24H, â-H on ligated Zn
porphyrinate), 8.84 and 8.95 (2 × d, J ) 4.2 Hz, 24H, â-H on unligated
Zn porphyrinate), 8.84 and 9.78 (2 × br, 12H, â-H on porphyrin trimer).
NMR (500.13 MHz, 55 °C): δ -2.11 (br, 6H, NH), 1.39 (s, 108H,
t-Bu on trimer), 1.50 (s, 54H, t-Bu on hexamer), 1.87 (s, 72H, o-CH3
on Zn porphyrinate), 2.62 (s, 36H, p-CH3 on Zn porphyrinate), 2.65
(s, 18H, p-CH3 on unligated Zn porphyrinate), 2.82 and 6.04 (2 × br,
12H, -C6H4N), 7.28 (s, 24H, m-H on Zn porphyrinate), 7.68 (app. s,
6H, p-Ph), 7.74 (app. s, 12H), 7.87 (app. s, 18H), 7.97 and 8.29
(AA′XX′ on Zn porphyrinate, apparent J ) 8.0 Hz, 48H), 8.58 (s, 3H,
benzenetriyl), 8.60 and 8.98 (2 × d, J ) 4.5 Hz, 12H, â-H on porphyrin
trimer), 8.79 and 8.90 (2 × d, J ) 4.4 Hz, 48H, â-H on Zn
porphyrinate), 8.78 and 9.72 (2 × d, J ) 4.3 Hz, 12H, â-H on porphyrin
trimer). MALDI-TOF-MS: 8147.735, 5638.619, 2507.072; calcd
Macrocyclic Hexaporphyrin 1a from Linear Hexamer 23 (M )
Ni) in the Presence of Template. A mixture of 23 (M ) Ni) (3 mg,
0.52 µmol) and 5 (1.3 mg, 0.52 µmol) was reacted under the same
conditions as described above for the synthesis in the absence of
template. FC of the reaction product afforded two main components:
a violet band, which contained the desired product, was eluted first
with CHCl3/hexane (7:3), then the column was eluted successively with
CHCl3 and CHCl3/MeOH (9:1) to afford a green fraction from which
0.6 mg (46%) of 5 was retrieved. Crude 1a was dissolved in CHCl3
and purified by TLC using n-hexane/CHCl3/EtOAc (4:1:1) as eluant.
Acyclic oligomers moved with the solvent front. The band with the
lowest Rf was scraped off from the TCL plate, extracted with CHCl3,
and the solvent was evaporated under reduced pressure. The violet solid
obtained was washed with MeOH and n-hexane and dried in vacuo to
yield 1.6 mg (55%) of 1a.
Macrocyclic Hexaporphyrin 1a from Monomers 20b and 21b
(M ) Ni) in the Presence of Template. A mixture of 20b (14.1 mg,
10.6 µmol), 21b (M ) Ni) (8.5 mg, 10.6 µmol), and the template 5
(8.9 mg, 3.54 µmol) was dissolved in 20 mL of toluene/triethylamine
(5:1) and reacted in the presence of Pd2dba3 (5.8 mg, 6.36 µmol) and
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Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
average mass for C561H471N39Zn6 (complex 1b + 5), C384H300N24Zn6
(1b), and C177H171N15 (5) ) 8151.6, 5643.2, and 2508.4, respectively.
8.79 (s, 3H, benzenetriyl), 8.98 and 9.70 (2 × d, J ) 4.6 Hz, 12H,
â-H on porphine), 9.03 and 9.94 (2 × d, J ) 4.65 Hz, 12H, â-H on
porphine). ES+-MS (in THF/HCO2H): 1255.28 ([M + 2H]2+), 837.16
([M + 3H]3+); calcd average mass for C177H171N15 ) 2508.4. HRMS
(ESI-MS): 836.46783; calcd for [M + 3H]3+ ) 836.46867.
5,5′,5′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl-4,1-phenylene)]tris-
[10,20-bis(3,5-bis(1,1-dimethylethyl)phenyl)-15-(pyrid-4-yl)-21H,23H-por-
phine] (3). Air was removed from a solution of 8 (7 mg, 7.24 µmol)
and 1,3,5-triethynylbenzene31c (0.27 mg, 1.81 µmol) in 7 mL of toluene/
Et3N (5:1) by blowing argon for 1 h. Then Pd2dba3 (0.7 mg, 0.8145
µmol) and P(o-tol)3 (1.9 mg, 6.516 µmol) were added, and deaeration
was continued for 10 min before heating at 35 °C for 5 h, when an
aliquot of catalyst was added and stirring was continued overnight.
FC of the reaction mixture yielded 1.7 mg pure product 3 (35%) and
1.6 mg (23%) of starting porphyrin 8. UV/vis (CH2Cl2): 296 (4.99),
4,4′,4′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl)]tris[[(4′-(pyrid-4-
yl)ethynyl)]1,1′-biphenyl] (6). Method A: A mixture of 17b (50 mg,
179 µmol), 1,3,5-triiodobenzene70 (22 mg, 48.4 µmol), CuI (8.3 mg,
43.5 µmol), and TBAI (53.6 mg, 145 µmol) was deaerated flushing
with argon for 30 min before DMF/iPr2NEt (10.5 mL, 20:1) followed
by Pd2dba3 (13.3 mg, 14.5 µmol) and tris(2,4,6-trimethylphenyl)-
phosphine (11.3 mg, 29.0 µmol) were added. The mixture was deaerated
for an additional 10 min and then heated at 50 °C overnight. The solvent
was removed under reduced pressure, and the solid residue, dissolved
in CHCl3, was purified by FC using CHCl3/MeOH (9:1) as eluant. The
residue obtained from the main fraction, after evaporation of the solvent,
was washed with MeOH to yield 28.3 mg (59%) of 6. Mp 220 °C
(dec), which was not soluble enough for recording a 13C NMR spectrum.
1H NMR (360.14 MHz): δ 7.41 and 8.63 (AA′XX′, apparent J ) 5.9
Hz, 12H, -C6H5N), 7.65 (d, J ) 3.2 Hz, 24H, phenylene), 7.72 (s,
3H, benzenetriyl). ES+-MS (THF/HCO2H): 909.99 ([M + H]+), 456.10
([M + 2H]2+), 304.38 ([M + 3H]3+); calcd average mass for C69H39N3
1
421 (6.08), 517 (4.72), 552 (4.48), 591 (4.24), 647 (4.19). H NMR
(360.14 MHz): δ -2.74 (br, 6H, NH), 1.54 (s, 108H, t-Bu), 7.82 (t, J
) 1.8 Hz, 6H, p-Ph), 8.03 and 8.30 (AA′XX′, apparent J ) 8.1 Hz,
12H, -C6H4-), 8.05 (s, 3H, benzenetriyl), 8.10 (d, J ) 1.8 Hz, 12H,
o-Ph), 8.19 and 9.02 (2 × apparent d, J ) 5.5 Hz, 12H, -C6H4N),
8.80 and 8.95 (2 × d, J ) 4.8 Hz, 12H, â-H on porphine), 8.92 and
8.96 (2 × d, J ) 4.8 Hz, 12H, â-H on porphine). ES+-MS (in THF/
HCO2H): 889.18 ([M + 3H]3+); calcd average mass for C189H183N15
) 2664.62. HRMS (ESI-MS): 888.50060; calcd for [M + 3H]3+
)
888.49997.
) 910.10. HRMS (ESI-MS): 910.32138; calcd for [M + H]+
)
5,5′,5′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl)]tris[10,20-bis(3,5-
bis(1,1-dimethylethyl)phenyl)-15-(pyrid-4-yl)-21H,23H-porphine] (4).
Deprotected porphyrin 9b (7 mg, 8.88 µmol) and 1,3,5-triiodobenzene70
(1.0 mg, 2.22 µmol) were dissolved in 7 mL of toluene/Et3N (5:1),
and the solution was deaerated by bubbling argon for 45 min. Then,
Pd2dba3 (0.9 mg, 0.99 µmol) and P(o-tol)3 (2.4 mg, 7.99 µmol) were
added, and the mixture was flushed with argon for an additional 10
min before it was heated at 35 °C for 4 h, when an aliquot of catalyst
was added and stirring was continued overnight. The product (3.2 mg,
59%) was isolated by FC on silica gel using successively CHCl3 and
CHCl3/MeOH (9:1) as eluants. UV/vis (CH2Cl2): 302 (4.84), 439 (6.02),
535 (4.56), 580 (5.06), 610 (4.31), 670 (4.75). 1H NMR (360.14
MHz): δ -2.24 (br, 6H, NH), 1.56 (s, 108H, t-Bu), 7.85 (app. s, 6H,
p-Ph), 8.12 (d, J ) 1.8 Hz, 12H, o-Ph), 8.18 and 9.04 (AA′XX′,
apparent J ) 5.4 Hz, 12H, -C6H4N), 8.75 and 8.90 (2 × d, J ) 4.5
Hz, 12H, â-H on porphine), 8.81 (s, 3H, benzenetriyl), 9.10 and 10.01
(2 × d, J ) 4.5 Hz, 12H, â-H on porphine). ES+-MS (in THF/
HCO2H): 1219.04 ([M + 2H]2+), 813.08 ([M + 3H]3+); calcd average
mass for C171H171N15 ) 2436.33. HRMS (ESI-MS): 812.46382; calcd
for [M + 3H]3+ ) 812.46867.
5,5′,5′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl)]tris[10,20-bis(3,5-
bis(1,1-dimethylethyl)phenyl)-15-[(pyrid-4-yl)ethynyl]-21H,23H-
porphine] (5). A solution of 14b (34 mg, 41.86 µmol) and 1,3,5-
triiodobenzene70 (4.77 mg, 10.46 µmol) in toluene (11.7 mL) was
flushed with argon for 5 min before triethylamine (2.3 mL) was added.
The mixture was deaerated by three freezing/thaw cycles in vacuo and
then allowed to reach room temperature under Ar atmosphere before
Pd2dba3 (4.3 mg, 4.7 µmol) and P(o-tol)3 (11.5 mg, 37.65 µmol) were
added. Thereon, the reaction mixture was stirred under an Ar stream,
protected against light, at 35 °C for 8 h before an aliquot of catalyst
was added and stirring was continued overnight. The solvent was
removed under reduced pressure, and the crude product was purified
by FC. A first fraction, which contained a porphyrin dimer formed by
homocoupling of 14b, was eluted with CHCl3/EtOAc (5:1); the second
green-colored fraction, which contained 5, was eluted with CHCl3/
MeOH (9:1). The residue obtained after evaporation of the solvent was
washed with MeOH and hexane to yield 22.8 mg (87%) of the product.
UV/vis (CH2Cl2): 447 (5.97), 519 (4.31), 558 (4.38), 604 (4.11), 693
(4.95). 1H NMR (500.13 MHz, 30 °C): δ -1.88 (br, 6H, NH), 1.59 (s,
108H, t-Bu), 7.86 (t, J ) 1.8 Hz, 6H, p-Ph), 7.89 and 8.84 (AA′XX′,
apparent J ) 5.9 Hz, 12H, -C6H4N), 8.12 (d, J ) 1.8 Hz, 12H, o-Ph),
910.32167.
Method B: A solution of 18b (15 mg, 22 µmol) and 4-iodopyridine45
(40.8 mg, 199 µmol) in 12 mL of THF/Et3N (5:1) was deaerated by
blowing argon for 45 min. Then, Pd2(PPh3)2Cl2 (7.0 mg, 9.94 µmol)
and PPh3 (5.2 mg, 19.88 µmol) were added, and deaeration was
continued for 10 min before heating at 60 °C for 5 h, when an aliquot
of catalyst was added and stirring was continued overnight. The solid
residue obtained after evaporation of the solvent under reduced pressure
was purified by FC using successively CHCl3, CHCl3/EtOAc (1:1),
and CHCl3/MeOH (1:1) as eluants to yield 11.2 mg (56%) of 6.
5,15-Bis[3,5-bis(1,1-dimethylethyl)phenyl]-10-(4-iodophenyl)-20-
(pyrid-4-yl)-21H,23H-porphine (8). To a deaerated solution of meso-
(3,5-di-tert-butylphenyl)-2,2′-dipyrrylmethane (7)29 (167 mg, 0.5 mmol)
in 50 mL of CH2Cl2/EtOH (95:5) were successively added 4-iodoben-
zaldehyde30 (116 mg, 0.5 mmol), 4-pyridine carboxaldehyde (48 µL,
0.5 mmol), and TFA (100 µL, 1.27 mmol). The solution was protected
from light and stirred, under Ar, at 25 °C overnight. Thereafter, a
saturated solution of DDQ (170 mg, 0.75 mmol) in THF was added,
and stirring was continued for an additional 1 h. The solid residue
obtained after removal of the solvent under reduced pressure was
washed with methanol, then dissolved in CH2Cl2, and purified by FC.
A first fraction consisting of 5,15-bis(4-iodophenyl)-10,20-bis(3,5-bis-
(1,1-dimethylethyl)phenyl)porphyrin was eluted with CH2Cl2, then the
column was eluted with CH2Cl2 /EtOAc (95:5) or, alternatively, CH2-
Cl2 /EtOH (97:3) to afford a second fraction which contained 14.7 mg
(6%) of the desired product 8. UV/vis (CH2Cl2): 419 (5.59), 516 (4.21),
1
551 (3.92), 591 (3.74), 646 (3.66). H NMR (360.14 MHz): δ -2.78
(br, 2H, NH), 1.54 (s, 36H, t-Bu), 7.82 (t, J ) 1.8 Hz, 2H, p-Ph), 7.96
and 8.10 (AA′XX′, apparent J ) 7.7 Hz, 4H, -C6H4I), 8.08 (d, J )
1.5 Hz, 4H, o-Ph), 8.18 and 9.02 (AA′XX′, apparent J ) 5.9 Hz, 4H,
-C6H4N), 8.80 and 8.92 (2 × d, J ) 4.8 Hz, 4H, â-H on porphine),
8.84 and 8.94 (2 × d, J ) 4.8 Hz, 4H, â-H on porphine). ES+-MS (in
THF/HCO2H): 967.10 ([M + H]+), 483.98 ([M + 2H]2+); calcd
average mass for C59H60N5I ) 966.10. HRMS (ESI-MS): 966.39599;
calcd for [M + H]+ ) 966.39662. Anal. Calcd C 73.35, H 6.26, N
7.25; found C 73.34, H 6.21, N 7.18.
5,15-Bis[3,5-bis(1,1-dimethylethyl)phenyl]-10-(pyrid-4-yl)-20-
[(trimethylsilyl)ethynyl]-21H,23H-porphine (9a). A solution of meso-
(3,5-di-tert-butylphenyl)-2,2′-dipyrrylmethane (7)29 (334.5 mg, 1 mmol),
3-trimethylsilylprop-2-ynal43 (126 mg, 1 mmol), and 4-pyridinecar-
boxaldehyde (96 µL, 1 mmol) in CH2Cl2/EtOH (100 mL, 95:5) was
deaerated by bubbling Ar for 30 min. Then, TFA (120 µL, 1.52 mmol)
was added, and the reaction mixture was stirred for 4 h at room
(70) Ozasa, S.; Fujiota, Y.; Hashino, H.; Kimura, N.; Ibuki, E. Chem. Pharm.
Bull. 1983, 31, 2313-2320.
9
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A R T I C L E S
Rucareanu et al.
temperature, protected from light. Thereafter, a saturated solution of
DDQ (340 mg, 1.5 mmol) in THF was added, and stirring was continued
for an additional 1 h. The reaction mixture was filtered through a silica
and alumina pad, which was subsequently washed with CHCl3 until
the filtrate was colorless. The solvent was removed under reduced
pressure, and the solid residue was dissolved in CH2Cl2/hexane (1:1)
and purified by FC, eluting successively with CH2Cl2/hexane (1:1),
CH2Cl2, CHCl3, and CHCl3/EtOAc (9:1). The first eluted fraction
contained 5,15-bis(3,5-bis(1,1-dimethylethyl)phenyl)-10,20-bis[(tri-
methylsilyl)ethynyl)]porphyrin (33.4 mg, 8%) followed by the desired
product 9a (22.7 mg, 5%). UV/vis (CH2Cl2): 428 (5.57), 529 (4.17),
5-Ethynyl-10,20-bis[3,5-bis(1,1-dimethylethyl)phenyl]-15-[(triiso-
propylsilyl)ethynyl] -21H,23H-porphine (13). To a solution of 11
(143.6 mg, 149 µmol) in 20 mL of THF was added 5 mL of 1 N aq.
NaOH, and the mixture was stirred for 2 h at 25 °C. Thereon, the solid
residue obtained after evaporation of the solvent under reduced pressure
was dissolved in CH2Cl2/n-hexane (4:1) and purified by column
chromatography on silica gel using CH2Cl2/n-hexane (4:1) as eluant to
afford 126 mg (95%) of 13. UV/vis (CH2Cl2): 430 (5.47), 538 (4.12),
1
579 (4.50), 616 (3.77), 676 (4.15). H NMR (360.14 MHz): δ -2.18
(br, 2H, NH), 1.43 (m, 21H, (i-Pr)3Si, 1.55 (s, 36H, t-Bu), 4.18 (s,
1H), 7.82 (t, J ) 1.8 Hz, 2H, p-Ph), 8.03 (d, J ) 1.8 Hz, 4H, o-Ph),
8.89 and 9.66 (2 × d, J ) 4.5 Hz, 4H, â-H on porphine), 8.89 and
9.67 (2 × d, J ) 4.5 Hz, 4H, â-H on porphine). ES+-MS (in THF/
HCO2H): 892.07 ([M + H]+), 446.31 ([M + 2H]2+), 297.3 ([M +
3H]3+), 594.45 ([2M + 3H]3+); calcd average mass for C61H74N4Si )
1
566 (4.31), 605 (3.76), 662 (3.94). H NMR (360.14 MHz): δ -2.43
(br, 2H, NH), 0.61 (s, 9H, TMS), 1.54 (s, 36H, t-Bu), 7.82 (t, J ) 1.8
Hz, 2H, p-Ph), 8.06 (d, J ) 1.8 Hz, 4H, o-Ph), 8.14 and 9.02 (AA′XX′,
apparent J ) 5.9 Hz, 4H, -C6H4N), 8.71 and 8.86 (2 × d, J ) 4.5 Hz,
4H, â-H on porphine), 8.95 and 9.69 (2 × d, J ) 5.0 Hz, 4H, â-H on
porphine). ES+-MS (in THF/HCO2H): 861.03 ([M + H]+), 430.76 ([M
+ 2H]2+); calcd average mass for C58H65N5Si ) 860.30. HRMS (ESI-
MS): 860.50820; calcd for [M + H]+ ) 860.50820. Anal. Calcd C
80.98, H 7.62, N 8.14; found C 80.94, H 7.69, N 8.09.
891.40. HRMS (ESI-MS): 891.57574; calcd for [M + H]+
)
891.57555.
5,15-Bis[3,5-bis(1,1-dimethylethyl)phenyl]-10-[(triisopropylsilyl)-
ethynyl]-20-[(pyrid-4-yl)ethynyl)]-21H, 23H-porphine (14a). A solu-
tion of 13 (60 mg, 67.3 µmol) and 4-iodopyridine45 (34.5 mg, 168.25
µmol) in 15 mL of toluene/Et3N (5:1) was purged of air by blowing
Ar for 45 min before Pd2dba3 (9.2 mg, 10.09 µmol) and P(o-tol)3 (24.6
mg, 80.76 µmol) were added. Deaeration was continued for 10 min,
and then the solution was heated at 60 °C for 6 h. Thereon, the same
amounts of catalyst were added, and stirring was continued overnight.
The crude product obtained after evaporation of the solvent under
reduced pressure was purified by FC. A first fraction, which contained
very small amounts of a porphyrin dimer formed by homocoupling of
13, was eluted with CH2Cl2, then the column was eluted successively
with CHCl3 and CHCl3/EtOAc (5:1) to afford a second fraction
containing the desired product. The solid residue obtained after
evaporation of the eluant was washed with methanol and dried in vacuo
to yield 49.1 mg (75%) of 14a. UV/vis (CH2Cl2): 438 (5.57), 549
(4.05), 592 (4.73), 624 (3.85), 685 (4.45). 1H NMR (360.14 MHz): δ
-2.03 (br, 2H, NH), 1.43 (m, 21H, (i-Pr)3Si), 1.56 (s, 36H, t-Bu), 7.83
(t, 2H, J ) 1.8 Hz, p-Ph), 7.86 and 8.81 (AA′XX′, apparent J ) 5.9
Hz, 4H, -C6H4N), 8.04 (d, J ) 1.8 Hz, 4H, o-Ph), 8.89 and 9.67 (2 ×
d, J ) 4.5 Hz, 4H, â-H on porphine), 8.92 and 9.66 (2 × d, J ) 4.5
Hz, 4H, â-H on porphine). ES+-MS (in THF/HCO2H): 969.42 ([M +
H]+), 484.81 ([M + 2H]2+); calcd average mass for C66H77N5Si )
5-Ethynyl-10,20-bis[3,5-bis(1,1-dimethylethyl)phenyl]-15-(pyrid-
4-yl)-21H,23H-porphine (9b). To a solution of 9a (12.7 mg, 14.76
µmol) in 30 mL of CH2Cl2/Et3N (1:1) was added TBAF (15 µL soln.
1 M in THF, 15.00 µmol), and the mixture was stirred for 10 min at
25 °C. The reaction was quenched by adding ca. 1 g of CaCl2. The
solvent was removed under reduced pressure, and the solid residue was
purified by FC with CHCl3 containing 2% Et3N as eluant to yield 10.6
mg (91%) of 9b. UV/vis (CH2Cl2): 425 (5.56), 524 (4.21), 561 (4.15),
601 (3.73), 658 (3.78). 1H NMR (360.14 MHz): δ -2.49 (br, 2H, NH),
1.54 (s, 36H, t-Bu), 4.21 (s, 1H, ethynyl), 7.83 (t, J ) 1.8 Hz, 2H,
p-Ph), 8.06 (d, J ) 1.8 Hz, 4H, o-Ph), 8.14 and 9.02 (AA′XX′, apparent
J ) 5.9 Hz, 4H, -C6H4N), 8.73 and 8.98 (2 × d, J ) 4.5 Hz, 4H, â-H
on porphine), 8.87 and 9.72 (2 × d, J ) 4.5 Hz, 4H, â-H on porphine).
ES+-MS (in THF/HCO2H): 789.01 ([M + H]+), 394.74 ([M + 2H]2+);
calcd average mass for C55H57N5 ) 788.10. HRMS (ESI-MS):
788.46892; calcd for [M + H]+ ) 788.46867. Anal. Calcd C 83.82, H
7.29, N 8.89; found C 83.74, H 7.32, N 8.79.
5,15-Bis-[3,5-bis(1,1-dimethylethyl)phenyl]-10-[(triisopropylsilyl)-
ethynyl]-20-[(trimethyl silyl)ethynyl]-21H, 23H-porphine (11). A
solution of meso-(3,5-di-tert-butylphenyl)-2,2′-dipyrrylmethane (7)29
(2.0 g, 6 mmol), 3-trimethylsilylprop-2-ynal43 (756 mg, 6 mmol), and
3-triisopropylsilylprop-2-ynal44 (1.27 g, 6 mmol) in 600 mL of CHCl3/
EtOH (95:5) was purged of air by bubbling Ar for 25 min. Then, TFA
(720 µL, 9.12 mmol) was added, and the reaction mixture was stirred
under Ar at 25 °C for 5 h, protected from light. Thereafter, a saturated
solution of DDQ (2.0 g, 8.8 mmol) in THF was added, and stirring
was continued for an additional 1 h. The reaction mixture was filtered
through a silica gel and alumina pad, which was subsequently washed
with CH2Cl2 until the filtrate became colorless. Chromatography of
the solid residue obtained after evaporation of the solvent under reduced
pressure on silica gel using successively a 1:4 and 3:2 mixture of CH2-
Cl2/n-hexane, as eluant, afforded three fractions. The first and third
eluted violet-green bands containing 12 (260.6 mg, 8%) and 10 (100
mg, 4%), respectively, whose analytical data agree with those reported
in ref 37e and refs 25b and 34a, respectively. After evaporation of the
solvent, the component of the second violet-green band was washed
with cold methanol and dried in vacuo to yield 352.4 mg (12%) of the
desired product 11. UV/vis (CH2Cl2): 433 (5.51), 543 (4.06), 584 (4.64),
620 (3.74), 680 (4.28). 1H NMR (360.14 MHz): δ -2.12 (br, 2H, NH),
0.59 (s, 9H, TMS), 1.43 (m, 21H, TIPS), 1.54 (s, 36H, t-Bu), 7.80 (t,
J ) 1.8 Hz, 2H, p-Ph), 8.03 (d, J ) 1.8 Hz, 4H, o-Ph), 8.86 and 9.61
(2 × d, J ) 4.5 Hz, 4H, â-H on porphine), 8.87 and 9.66 (2 × d, J )
4.5 Hz, 4H, â-H on porphine). ES+-MS (in THF/HCO2H): 964.09 ([M
+ H]+), 321.33 ([M + 3H]3+), 642.87 ([2M + 3H]3+); calcd average
mass for C64H82N4Si2 ) 963.60. HRMS (ESI-MS): 963.61641; calcd
for [M + H]+ ) 963.61508.
968.50. HRMS (ESI-MS): 968.60557; calcd for [M + H]+
)
968.60210.
5-Ethynyl-10,20-bis[3,5-bis(1,1-dimethylethyl)phenyl]-15-[(pyrid-
4-yl)ethynyl]-21H,23H-porphine (14b). To a solution of 14a (51.4
mg, 53.07 µmol) in 16 mL of CH2Cl2/Et3N (1:1) was added 63.7 µL
of TBAF solution (1 M in THF), and the mixture was stirred for 10
min at 25 °C. Then, the reaction was quenched by addition of ca. 1 g
of CaCl2, and the solid residue obtained after evaporation of the solvent
under reduced pressure was chromatographed on a silica gel column
using CH2Cl2 as eluant to afford 36.7 mg (85%) of 14b. UV/vis (CH2-
1
Cl2): 436 (5.54), 543 (4.09), 586 (4.62), 620 (3.85), 680 (4.32). H
NMR (360.14 MHz): δ -2.12 (br, 2H, NH), 1.56 (s, 36H, t-Bu), 4.21
(s, 1H), 7.85 (t, J ) 1.8 Hz, 2H, p-Ph), 7.86 and 8.81 (AA′XX′, apparent
J ) 5.9 Hz, 4H, -C6H4N), 8.07 (d, J ) 1.8 Hz, 4H, o-Ph), 8.91 and
9.66 (2 × d, J ) 4.9 Hz, 4H, â-H on porphine), 8.94 and 9.67 (2 × d,
J ) 4.9 Hz, 4H, â-H on porphine). ES+-MS (in THF/HCO2H): 813.02
([M + H]+); calcd average mass for C57H57N5 ) 812.10. HRMS (ESI-
MS): 812.46950; calcd for [M + H]+ ) 812.46867. Anal. Calcd C
84.30, H 7.07, N 8.62; found C 84.32, H 7.28, N 8.60.
4-Bromo-4′-[(trimethylsilyl)ethynyl]-1,1′-biphenyl (15). To a solu-
tion of 4,4′-dibromobiphenyl (1 g, 3.2 mmol) in THF (15 mL)
containing diisopropylamine (4 mL) were added successively, under
Ar, ethynyltrimethylsilane (526 µL, 3.8 mmol), Pd(PPh3)2Cl2 (266.7
mg, 0.38 mmol), and CuI (72.4 mg, 0.38 mmol) before the reaction
mixture was stirred at 50 °C for 24 h. After removal of the solvent
under reduced pressure, the solid residue was dissolved in CH2Cl2 and
9
3410 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
purified twice by FC using n-hexane as eluant to yield 135 mg (14%)
of starting material, as the first eluted component, and 343 mg (33%)
of 15, which was eluted as the second moving band, followed closely
by a small amount of 4,4′-bis[(trimethylsilyl)ethynyl]-1,1′-biphenyl,
which was discarded. The analytical data of 15 are identical to those
reported elsewhere.47
4-[(Triisopropylsilyl)ethynyl]-4′-[(trimethylsilyl)ethynyl]-1,1′-bi-
phenyl (16a). Method A: Reaction of 4,4′-dibromobiphenyl (3.12 g,
10.0 mmol) with a mixture of ethynyltrimethylsilane (1.66 mL, 12
mmol) and ethynyltriisopropylsilane (2.19 mL, 12 mmol) under the
same conditions as described for 15 afforded 16a in 16% yield, as a
viscous oil. Method B: A better yield (62%) was obtained reacting a
solution of 15 (320 mg, 0.97 mmol) in 15 mL of THF with
ethynyltriisopropylsilane (435.9 µL, 1.94 mmol) under the same
conditions as described for 15. Anal. Calcd C 78.07, H 8.89; found C
78.14, H 8.92. The analytical data are identical to those reported
elsewhere.48
4-Ethynyl-4′-[(triisopropylsilyl)ethynyl]-1,1′-biphenyl (16b). To
a solution of 16a (260 mg, 0.6 mmol) in THF (7 mL) was added 3 mL
of aq. NaOH (1 N), and the mixture was vigorously stirred for 2 h at
25 °C. After evaporation of the solvent under reduced pressure, the
obtained oily residue was purified by FC using hexane/CH2Cl2 as eluant
to yield 205.7 mg (95%) of 16b as a light yellow oil which crystallized
upon standing. Mp 42-43 °C (lit.48 41-42 °C). Anal. Calcd C 83.74,
H 8.43; found C 83.55, H 8.32. The spectroscopic data are identical to
those reported in ref 48.
mixture was allowed to reach room temperature, and the resulting dark
brown solution was stirred overnight at 25 °C. The solid residue
obtained after removal of the solvent under reduced pressure was
dissolved in CH2Cl2/hexane (1:5) and purified by FC using CH2Cl2/
hexane (1:5) as eluant. The main fraction was separated and purified
again by FC using CH2Cl2/hexane (1:9) as eluant to yield 73.10 mg
(85%) of 18a, as a solid of mp 125 °C, which is not soluble enough
1
for recording a 13C NMR spectrum. H NMR (360.14 MHz): δ 1.15
(s, 63H, TIPS), 7.56 (br s, 12H, phenylene), 7.61 (br s, 12H, phenylene),
7.70 (s, 3H, benzenetriyl). FAB-MS (matrix, NBA): 1149.0 ([M +
H]+); calcd average mass for C81H90Si3 ) 1148.2. Anal. Calcd C 84.76,
H 7.90; found C 84.08, H 8.00.
4,4′,4′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl)]tris[(4′-ethynyl)-
1,1′-biphenyl] (18b). The ethynyl groups of 18a (64 mg, 55.8 µmol)
were deprotected by treatment with TBAF (1 M in THF, 200 µL) as
described previously for 14b, yielding, after FC using CH2Cl2/hexane
(9:1) as eluant, 36.7 mg (97%) of 18b. Mp 182 °C (dec), which is not
1
soluble enough for recording a 13C NMR spectrum. H NMR (360.14
MHz): δ 3.16 (s, 3H, ethynyl), 7.59 (br s, 12H, phenylene), 7.62 (br
s, 12H, phenylene), 7.70 (s, 3H, benzenetriyl). FAB-MS (matrix,
NBA): 678.00 (M+); calcd average mass for C54H30 ) 678.80. HRMS
(MALDI-MS, dithranol): 678.23222; calcd for M+ ) 678.23420.
[(2,3,7,8,12,13,17,18-2H8)-5,15-Bis(4-iodophenyl)-10,20-bis(2,4,6-
trimethylphenyl)porphyrinato(2-)]zinc(2+) (19-d8). A solution of
mesitylaldehyde71 (1.47 mL, 10 mmol) in pyrrole-d5 (27.8 mL, 400
72
mmol) was purged from air by passing Ar for 30 min before BF3
etherate (0.369 mL, 3.0 mmol) was added. The reaction mixture was
stirred for 30 min at 25 °C and thereon neutralized adding 20 g of
anhydrous K2CO4. After evaporation of the solvent under reduced
pressure, unreacted pyrrole was removed by vacuum distillation, and
the obtained residue was purified twice by FC, using EtOAc/n-hexane
(1:9) as eluant, to yield 1.4 g (55%) of (3,3′,4,4′5,5′-2H6)-meso-(2,4,6-
4-[(Triisopropylsilyl)ethynyl]-4′-[(pyrid-4-yl)ethynyl]-1,′1-biphen-
yl (17a). A solution of 16b (759 mg, 2.12 mmol) and 4-iodopyridine45
(612 mg, 2.98 mmol) in 102 mL of a mixture of toluene and
triethylamine (5:1) was purged of air by passing Ar for 45 min before
Pd2dba3 (291 mg, 317.8 µmol) and P(o-tol)3 (773 mg, 2.54 mmol) were
added, and the mixture was heated at 80 °C for 6 h. Then an aliquot of
catalyst was added, and stirring was continued overnight. Thereafter,
the solution was cooled to 25 °C, and the residue obtained after removal
of the solvent under reduced pressure was purified by FC using CH2-
Cl2 and CHCl3 as eluant to afford 17a contaminated with traces of
4-iodopyridine, which was removed by sublimation in vacuo at 80 °C
2
trimethylphenyl)-2,2′-dipyrrylmethane containing 82-89% H on the
C-atoms. The isotope content was subsequently increased by dissolving
a sample (470 mg, 0.173 mmol) in 10 mL of dry CH2Cl2 and shaking
2
the solution for 12 h at 25 °C with a mixture of H2O (10 mL) and
acetic acid-d1 (5 mL) in the dark. Thereafter, 100 mL of CH2Cl2 was
added, and the aqueous suspension was neutralized by adding 12 g of
anhydrous K2CO3; the organic layer was separated, dried on MgSO4,
filtered, and the solvent was removed under reduced pressure. The thus
obtained dipyrrylmethane-d6, which contained >95 mol % deuterium,
was dissolved together with 401 mg (0.173 mmol) of 4-iodobenzal-
dehyde30 in 175 mL of amylene-stabilized CHCl3 containing 1.75 mL
of ethanol-d. The solution was purged from air passing Ar for 10 min,
and then 235 µL from a 2.5 M stock solution of BF3 etherate in CHCl3
was added. The mixture was stirred for 1 h at 25 °C, and thereafter,
DDQ (298 mg, 1.31 mmol) was added and stirring was continued for
30 min before the solvent was removed. Purification of the residue by
FC using CH2Cl2 as eluant afforded, as the first moving band, 271 mg
(33%) of 5,15-bis(4-iodophenyl)-10,20-bis(2,4,6-trimethylphenyl)por-
phine-d8 containing 90% deuterium on the â-C-atoms of the pyrrole
rings. Finally, the porphyrin was transformed into 19-d8 by reaction
with zinc acetate following the procedure given in ref 28.
[5,15-Bis(4-{[3-(3,3-diethyl-1-triazenyl)-5-(1,1-dimethylethyl)-
phenyl]ethynyl}phenyl)-10,20-bis(2,4,6-trimethylphenyl)porphinato-
(2-)]zinc(2+) (20a). A solution of 1950 (1.5 g, 1.48 mmol) and 1-[3-
(1,1-dimethylethyl)-5-ethynylphenyl]-3,3-diethyl-1-triazene19 (0.952 g,
3.7 mmol) in 260 mL of DMF/Et3N (5:1) was purged of air by passing
Ar for 30 min. Then, Pd(PPh3)2Cl2 (207.8 mg, 0.296 mmol) and CuI
(114.3 mg, 0.6 mmol) were added, and deaeration was continued for
10 min, before the mixture was heated at 35 °C for 14 h. The solvent
was removed under reduced pressure, and the crude product was
purified by FC, using CHCl3/n-hexane/Et3N (gradient from 50:50:0.2
1
during 3 h to yield 604 mg of the product (66%); mp 95-98 °C. H
NMR (360.14 MHz): δ 1.15 (s, 21H, (i-Pr)3Si), 7.40 and 8.62 (AA′XX′,
apparent J ) 5.9 Hz, 4H, C6H4N), 7.54-7.65 (m, 8H, phenylene). 13
C
NMR (90.56 MHz): δ 11.5, 18.8, 87.7, 92.1, 93.9, 106.8, 121.4, 123.2,
125.7, 126.9, 127.2, 131.5, 132.5, 132.7, 139.9, 141.2, 149.9. FAB-
MS (matrix, NBA): 436 (M+); calcd average mass for C30H33NSi )
435.68. HRMS (ESI-MS): 436.24424; calcd for [M + H]+
)
436.244550.
4-Ethynyl-4′-[(pyrid-4-yl)ethynyl)]-1,1′-biphenyl (17b) was ob-
tained reacting 17a (604 mg, 1.39 mmol) with TBAF (1 M in THF,
1.6 mL) under the same conditions as described for 14b. After
evaporation of the solvent, the product separated by FC using
successively CHCl3/EtOAc (8:3) and CHCl3/MeOH (9:1) as eluants
was washed with MeOH to yield 229 mg (59%) of 17b as a solid of
mp 201.5 °C (dec), which is not soluble enough for recording a 13C
NMR spectrum. 1H NMR (360.14 MHz): δ 3.16 (s, 1H, ethynyl), 7.40
and 8.62 (AA′XX′, apparent J ) 5.9 Hz, 4H, C6H4N), 7.54-7.65 (m,
8H, phenylene). ES+-MS (in THF/HCO2H): 280.12 ([M + H]+); calcd
average mass for C21H13N ) 279.30. HRMS (ESI-MS): 280.11233;
calcd for [M + H]+ ) 280.11208.
4,4′,4′′-[1,3,5-Benzenetriyltris(2,1-ethynediyl)]tris[[(4′-triisopro-
pylsilyl) ethynyl]-1,1′-biphenyl (18a). A solution of 1,3,5-triiodoben-
zene70 (34 mg, 75 µmol), TBAI (55.2 mg, 149 µmol), CuI (12.8 mg,
67.2 µmol), and tris(2,4,6-trimethylphenyl)phosphine (17.4 mg, 45
µmol) in 10.5 mL of a mixture of DMF/i-Pr2NEt (20:1) was purged of
air by passing Ar for 30 min before Pd2dba3 (10.3 mg, 11.2 µmol) was
added, and the mixture was stirred at 20 °C for 5 min. Thereon, the
yellow mixture was cooled to -20 °C before 16b (100 mg, 279 µmol)
was added, and stirring was continued for 1 h. Thereafter, the reaction
(71) Newmann, M. S.; Lee, L. F. J. Org. Chem. 1972, 37, 4468-4469.
(72) (a) Bean, G. P. Chem. Commun. 1971, 421. (b) Fajer, J. Ann. NY Acad.
Sci. 1973, 349-364.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3411

A R T I C L E S
Rucareanu et al.
to 80:20:0.2) as eluant to yield 1.38 g (73%) of 20a. UV-vis (CH2-
Cl2): 294 (4.92), 423 (5.74), 550 (4.43), 591 (3.83). 1H NMR (360.14
MHz): δ 1.32 (t, J ) 7.3 Hz, 12H, Et), 1.42 (s, 18H, t-Bu), 1.84 (s,
12H, o-Me), 2.64 (s, 6H, p-Me), 3.82 (q, J ) 7.0 Hz, 8H, Et), 7.49 (d,
J ) 1.7 Hz, 4H), 7.59 (t, J ) 1.7 Hz, 2H), 7.93 and 8.23 (AA′XX′,
apparent J ) 8.5 Hz, 8H, Ph), 8.80 and 8.90 (2 × d, J ) 4.9 Hz, 8H,
â-H on porphine). ES+-MS (in THF/HCO2H): 1274.05 ([M + H]+),
637.46 ([M + 2H]2+); calcd average mass for C82H82N10Zn ) 1273.0.
HRMS (ESI-MS): 1271.60803, 636.30800; calcd for [M + H]+ and
[M + 2H]2+ ) 1271.60882 and 636.30805, respectively (monoisotopic
peaks corresponding to 64Zn).
ethynyl), 7.28 (s, 4H, m-H), 7.88 and 8.19 (AA′XX′, apparent J ) 8.1
Hz, 8H), 8.70 and 8.77 (2 × d, J ) 4.5 Hz, 8H, â-H on porphine).
ES+-MS (in CHCl3/MeOH): 747.35 ([M + H]+), 374.18 ([M + 2H]2+);
calcd average mass for C54H42N4 ) 746.95. HRMS (ESI-MS):
747.34781; calcd for ([M + H]+) ) 747.34822. Anal. Calcd C 86.83,
H 5.67, N 7.50; found C 86.49, H 5.58, N 7.49.
By the same procedure, 21b-d8 (M ) 2H) was prepared from 21a-
d8.
[5,15-Bis(4-ethynylphenyl)-10,20-bis(2,4,6-trimethylphenyl)por-
phinato(2-)] nickel (21b, M ) Ni). To a solution of 21b (M ) 2H)
(100 mg, 134 µmol) in 10 mL of CHCl3/AcOH (9:1) was added nickel
acetate tetrahydrate (600 mg, 2.4 mmol), and the mixture was refluxed
for 48 h. Thereafter, the solvent was removed under reduced pressure,
and the obtained solid residue was purified twice by FC on silica gel
eluting with a 40:60 and a 30:70 mixture of CHCl3/n-hexane,
respectively. The yield of 21b (M ) Ni) amounts to 70 mg (65%).
UV-vis (CH2Cl2): 294 (4.22), 414 (5.36), 527 (4.23). 1H NMR (360.14
MHz): δ 1.80 (s, 12H, o-Me), 2.57 (s, 6H, p-Me), 3.28 (s, 2H, ethynyl),
7.27 (s, 4H, m-H), 7.81 and 8.00 (AA′XX′, apparent J ) 8.2 Hz, 8H),
8.60 and 8.67 (2 × d, J ) 5.0 Hz, 8H, â-H on porphine). ES+-MS (in
THF/HCO2H): 803.72 (M+); calcd average mass for C54H40N4Ni )
803.64. HRMS (ESI-MS): 803.26788, 802.26014; calcd for [M + H]+)
and M+ ) 803.26792 and 802.26010, respectively (monoisotopic peaks
corresponding to 58Ni).
By the same procedure, 20a-d8 was prepared from 19-d8.
[5,15-Bis[4-[[3-(1,1-dimethylethyl)-5-iodophenyl]ethynyl]phenyl]-
10,20-bis(2,4,6-trimethylphenyl)porphinato(2-)]zinc(2+) (20b). A
solution of 20a (100 mg, 78.6 µmol) in iodomethane (20 mL) contained
in a thick-walled screw cap tube was flushed with argon before the
tube was sealed and the mixture heated to 135 °C for 2 h. The mixture
was then cooled to 25 °C, and the crude product obtained after
evaporation of the solvent under reduced pressure was purified by FC
using CHCl3/hexane/Et3N (50:50:0.1) as eluant to yield 102 mg (98%)
of 20b. UV-vis (CH2Cl2): 288 (4.76), 422 (5.72), 549 (4.39), 591
1
(3.82). H NMR (360.14 MHz): δ 1.38 (s, 18H, t-Bu), 1.83 (s, 12H,
o-Me), 2.64 (s, 6H, p-Me), 7.29 (s, 4H, m-H), 7.66 (t, J ) 1.4 Hz),
7.75 (t, J ) 1.4.Hz, 2H), 7.86 (t, J ) 1.4 Hz, 2H), 7.92 and 8.24
(AA′XX′, apparent J ) 8.1 Hz, 8H), 8.80 and 8.89 (2 × d, J ) 4.8
Hz, 8H, â-H on porphine). ES+-MS (in THF/HCO2H): 1326.23 ([M
+ H]+), 1264.33 ([M - Zn + 2H]+), 632.16 ([M - Zn + 2H]2+);
calcd average mass for C74H62I2N4Zn ) 1326.52. HRMS (ESI-MS):
5-[4-[3-[[4-[10,20-Bis(2,4,6-trimethylphenyl)-15-(4-ethynylphenyl)-
21H,23H-porphin-5-yl]phenyl]ethynyl]-5-(1,1-dimethylethyl)phenyl]-
ethynyl]phenyl]-15-[4-[[3-(1,1-dimethylethyl)-5-iodophenyl]ethynyl]-
phenyl]-10,20-bis(2,4,6-trimethylphenyl)-21H,23H-porphinato(2-
)-N21,N22,N23,N24]zinc(2+) (22b, M ) 2H). To a solution of 22a (M
) 2H)19 (48 mg, 24 µmol) in 4.0 mL of THF was added 2.9 mL of aq.
NaOH (1 N), and the mixture was stirred vigorously for 3 h at 25 °C.
Thereafter, the mixture was diluted with 15 mL of CH2Cl2 before 15
mL of water was added, and the organic layer was separated, washed
with water, and dried (MgSO4). The residue obtained after evaporation
of the solvent under reduced pressure was purified by FC using CHCl3/
n-hexane (60:40) as eluant to yield 39 mg (84%) of 22b (M ) 2H) as
a violet solid. UV-vis (CH2Cl2): 288 (4.86), 422 (5.89), 516 (4.37),
1324.23931, 1263.32980; calcd for M+ and [M - Zn + 3H]+
)
1324.23498 and 1263.32931, respectively (monoisotopic peaks corre-
sponding to 64Zn).
By the same procedure, 20b-d8 was prepared from 20a-d8.
[5,15-Bis(2,4,6-trimethylphenyl)-10,20-bis[4-[(trimethylsilyl)eth-
ynyl] phenyl] porphinato(2-)]zinc(2+) (21a). Air was removed from
a solution of 1950 (64 mg, 63.1 µmol) in 12 mL of DMF/Et3N (5:1) by
blowing Ar for 30 min. Then, Pd(PPh3)2Cl2 (4.4 mg, 6.3 µmol) and
CuI (2.4 mg, 12.6 µmol) were added, and the mixture was flushed
with argon for an additional 10 min before ethynyltrimethylsilane (52
µL, 379µmol) was added and the mixture was heated at 35 °C for 15
h. The solid residue obtained after evaporation of the solvent under
reduced pressure was purified by FC eluting with CHCl3/n-hexane (1:
1) to yield 41 mg (68%) of 21a. UV-vis (CH2Cl2): 305 (4.14), 421
(5.49), 549 (4.12), 588 (3.40). 1H NMR (360.14 MHz): δ 0.37 (s, 18H,
Me3Si), 1.82 (s, 12H, o-Me), 2.63 (s, 6H, p-Me), 7.28 (s, 4H, m-H),
7.86 and 8.18 (AA′XX′, apparent J ) 8.1 Hz, 8H), 8.78 and 8.84 (2 ×
d, J ) 4.8 Hz, 8H, â-H on porphine). ES+-MS (in THF/HCO2H):
955.34 ([M + H]+), 892.43 ([M - Zn + 3H]+); calcd average mass
for C60H56N4Si2Zn ) 954.34. HRMS (ESI-MS): 952.33155, 891.42663;
calcd for M+ and [M - Zn + 3H]+ ) 952.33295 and 891.42728,
respectively (monoisotopic peaks corresponding to 64Zn).
1
550 (4.50), 590 (4.06), 646 (3.81). H NMR (360.14 MHz): δ -2.63
(br, 2H, NH), 1.38 (s, 9H, t-Bu), 1.49 (s, 9H, t-Bu), 1.84 (s, 24H, o-Me),
2.64 (s, 12H, p-Me), 3.32 (s, 1H, ethynyl), 7.29 (s, 8H, m-H), 7.66 (t,
J ) 1.5 Hz, 1H), 7.75 (t, J ) 1.5 Hz, 2H), 7.76 (t, J ) 1.5 Hz, 1H),
7.84 (t, J ) 1.5 Hz, 1H), 7.86 (t, J ) 1.5 Hz, 1H), 7.88 and 8.20
(AA′XX′, apparent J ) 8.4 Hz, 4H), 7.92 and 8.25 (AA′XX, apparent
J ) 8.4 Hz, 8H), 7.98 and 8.24 (AA′XX, apparent J ) 8.4 Hz, 4H),
7.98 and 8.27 (AA′XX, apparent J ) 8.4 Hz, 4H), 8.71 and 8.77 (2 ×
d, J ) 4.8 Hz, 4H, â-H on porphine), 8.73 and 8.84 (2 × d, J ) 4.8
Hz, 4H, â-H on porphine), 8.80 and 8.89 (2 × d, J ) 4.8 Hz, 4H, â-H
on porphine), 8.81 and 8.92 (2 × d, J ) 4.8 Hz, 4H, â-H on porphine).
ES+-MS (in THF): 1946.54 ([M + H]+), MALDI-MS (matrix,
dithranol) 1945.6 (M+); calcd average mass for C128H103IN8Zn )
1945.55. HRMS (MALDI): 1942.66652; calcd for M+ ) 1942.66418
(monoisotopic peak corresponding to 64Zn).
By the same procedure, 21a-d8 was prepared from 19-d8.
5,15-Bis(4-ethynylphenyl)-10,20-bis(2,4,6-trimethylphenyl)-21H,-
23H-porphine (21b, M ) 2H). To a solution of 21a (729 mg, 0.76
mmol) in CHCl3 (230 mL) was added TFA (23 mL), and the mixture
was stirred at 25 °C for 2 h. The solution was then neutralized with
saturated aq. NaHCO3, and the aqueous residue obtained after evapora-
tion of the organic solvent under reduced pressure was diluted with
102 mL of THF. NaOH (2.28 g) was added, and the mixture was
vigorously stirred for 3 h at 25 °C. Then, the mixture was diluted with
CH2Cl2 (300 mL), the organic layer was separated, washed with water,
and dried (MgSO4) before the solvent was evaporated. The obtained
solid residue was purified by FC using successively a 55:45 and a 70:
30 mixture of CHCl3/hexane as eluant to afford 21b in quantitative
yield (569 mg). UV-vis (CH2Cl2): 303 (4.26), 419 (5.68), 515 (4.30),
{µ{5-{4-[3-[[4-[10,20-Bis(2,4,6-trimethylphenyl)-15-(4-ethynyl-
phenyl)-21H,23H-porphin-5-yl-KN21,KN22,KN23,KN24]phenyl]eth-
ynyl]-5-(1,1-dimethylethyl)phenyl]ethynyl]phenyl}-15-[4-[[3-(1,1-di-
methylethyl)-5-iodophenyl]ethynyl]phenyl]-10,20-bis(2,4,6-trimethyl-
phenyl)-21H,23H-porphinato(4-)-KN21,KN22,KN23,KN24}}(nickel(2+))-
zinc(2+) (22b, M ) Ni) was obtained from 22a (M ) Ni)19 (83 mg,
40 µmol) as described for 22b (M ) 2H). After purification by FC
using CHCl3/hexane (50:50) as eluant, 22b (M ) Ni) was obtained as
a violet solid in 97% yield (78 mg). UV-vis (CH2Cl2): 289 (4.87),
1
422 (5.76), 536 (4.32), 549 (4.41), 590 (3.75). H NMR (360.14 M
Hz): δ 1.38 (s, 9H, t-Bu), 1.47 (s, 9H, t-Bu), 1.81 (s, 12H, o-Me),
1.84 (s, 12H, o-Me), 2.57 (s, 6H, p-Me), 2.63 (s, 6H, p-Me), 3.26 (s,
1H, ethynyl), 7.21 (s, 4H, m-H), 7.28 (s, 4H, m-H), 7.66 (t, J ) 1.5
Hz, 1H), 7.72 (t, J ) 1.5 Hz, 1H), 7.75 (t, J ) 1.5 Hz, 2H), 7.80 and
1
550 (3.93), 591 (3.76), 646 (3.64). H NMR (360.14 MHz): δ -2.66
(br, 2H, NH), 1.83 (s, 12H, o-Me), 2.63 (s, 6H, p-Me), 3.31 (s, 2H,
9
3412 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Template-Directed Synthesis of a Tetraarylporphyrin Hexamer
A R T I C L E S
8.01 (AA′XX′, apparent J ) 8.2 Hz, 4H), 7.82 (t, J ) 1.5 Hz, 1H),
7.86 (t, J ) 1.5 Hz, 1H), 7.89 and 8.07 (AA′XX′, apparent J ) 8.2
Hz, 4H), 7.91 and 8.24 (AA′XX′, apparent J ) 8.2 Hz, 4H), 7.96 and
8.26 (AA′XX′, apparent J ) 8.2 Hz, 4H), 8.60 and 8.68 (2 × d, J )
4.8 Hz, 4H, â-H on porphine), 8.62 and 8.74 (2 × d, J ) 4.8 Hz, 4H,
â-H on porphine), 8.80 and 8.89 (2 × d, J ) 4.8 Hz, 4H, â-H on
porphine), 8.81 and 8.92 (2 × d, J ) 4.8 Hz, 4H, â-H on porphine).
MALDI-MS (matrix, dithranol): 2001.97 (M+); calcd average mass
for C128H101IN8NiZn ) 2002.23. HRMS (MALDI): 1998.58544; calcd
ETH Zu¨rich) for recording MALDI-TOF mass spectra of the
supramolecular complexes, as well as Dr. Detlef Moskau
(Bruker Biospin A.G., Fa¨llanden, Switzerland) for 700 MHz
1H NMR spectra of complex 1b + 5. We are also deeply
indebted to Dr. Habil Teodor Silvu Balaban (Institut fu¨r
Nanotechnologie des Forschungszentrums Karlsruhe, Germany)
for the generous gift of samples of 5,15-bis-(3,5-di-tert-butyl)-
porphine and derivatives therefrom.
Supporting Information Available: Copies of 1H NMR and
mass spectra (MS, MALDI-MS, MALDI-TOF) for all new
compounds as well as copies of the UV-vis spectra of all new
porphyrinic compounds and of the 13C NMR spectra of
compounds 17a,b and 18a,b. This material is available free of
charge via the Internet at http://pubs.acs.org.
for M+
) 1998.58386 (monoisotopic peak corresponding to
58Ni64Zn).
Acknowledgment. Financial support of this work by the
Swiss National Science Foundation (Project No. 2000-065091.01)
is gratefully acknowledged. NMR spectra were performed by
Felix Fehr, and mass spectra by Fre´dy Nydegger. We thank
Oliver Scheidegger (Laboratorium fu¨r Organische Chemie der
JA057117D
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3413