Rigid, cross-conjugated macrocycles: A cyclic alternative to 4,4′-bipyridines in supramolecular chemistry

Article abstract of DOI:10.1021/ol0156087

(matrix presented) The synthesis of two fully conjugated, rigid macrocyclic analogues to 4,4′-bipyridine is described. The use of these macrocycles in self-assembly processes is demonstrated by axial coordination to metalloporphyrins, and one system (R =

Full text of DOI:10.1021/ol0156087

ORGANIC
LETTERS
2001
Vol. 3, No. 7
1045-1048
Rigid, Cross-Conjugated Macrocycles:
A Cyclic Alternative to 4,4′-Bipyridines
in Supramolecular Chemistry
Katie Campbell, Robert McDonald, Neil R. Branda, and Rik R. Tykwinski*
Department of Chemistry, UniVersity of Alberta, Edmonton, Alberta, T6G 2G2 Canada
rik.tykwinski@ualberta.ca
Received January 24, 2001
ABSTRACT
The synthesis of two fully conjugated, rigid macrocyclic analogues to 4,4′-bipyridine is described. The use of these macrocycles in self-
assembly processes is demonstrated by axial coordination to metalloporphyrins, and one system (R ) Me) has been characterized by single-
crystal X-ray crystallography.
The rigidity and directed coordinative ability of bipyridines
and related molecules make them among the most ubiquitous
constituents of supramolecular assemblies.1-5 This is par-
ticularly true of 4,4′-bipyridines, which have been widely
used for the realization of discrete, highly ordered nano-
structures based on transition metal coordination.6
groups. For example, coordinative functionality, namely the
nitrogen of pyridine(s), directed toward the interior of
macrocycles has been used in the design of artificial
receptors.8
We envisioned that the strategic placement of pyridine(s)
within a macrocyclic framework with nitrogen directed away
Shape-persistent conjugated macrocycles can also provide
a versatile basis for the realization of well-defined materials
with tubular, rigid structures and desirable properties.7
Complementing the rigid framework of these macrocycles
is the fact that their physical attributes can be readily
manipulated by the covalent incorporation of functional
(7) Kro¨mer, J.; Rios-Carreras, I.; Fuhrmann, G.; Musch, C.; Wunderlin,
M.; Debaerdemaeker, T.; Mena-Osteritz, E.; Ba¨uerle, P. Angew. Chem.,
Int. Ed. 2000, 39, 3481-3486. Ge, P. H.; Fu, W.; Herrmann, W. A.;
Herdtweck, E.; Campana, C.; Adams, R. D.; Bunz, U. H. F. Angew. Chem.,
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Lentz, D.; Schlu¨lter, A. D. Chem. Eur. J. 2000, 6, 2362-2367. Ohkita,
M.; Ando, K.; Suzuki, T.; Tsuji, T. J. Org. Chem. 2000, 65, 4385-4390.
Marsella, M. J.; Kim, I. T.; Tham, F. J. Am. Chem. Soc. 2000, 122, 974-
975. Tobe, Y.; Fujii, T.; Matsumoto, H.; Tsumuraya, K.; Noguchi, D.;
Nakagawa, N.; Sonoda, M.; Naemura, K.; Achiba, Y.; Wakabayashi, T. J.
Am. Chem. Soc. 2000, 122, 1762-1775. Eisler, S.; Tykwinski, R. R. Angew.
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Int. Ed. Engl. 1997, 36, 836-838. Anthony, J.; Boldi, A. M.; Boudon, C.;
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10.1021/ol0156087 CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/15/2001

from the cyclic core would combine the desirable attributes
of both conjugated macrocycles and self-assembly. Thus, a
fully conjugated macrocycle based on 3,5-diethynylpyridyl
subunits was designed. It was predicted that these building
blocks (e.g., 5a,b) would readily function as macrocyclic
analogues to 4,4′-bipyridines for creation of highly ordered
assemblies via metal coordination.
Scheme 1
We report herein the realization of these two unprec-
edented macrocycles, 5a,b, based on a cross-conjugated
enyne framework. The rigid skeleton and directed orientation
of the pyridyl nitrogens in 5a and 5b ensure predictable
assembly into well-defined supramolecular scaffolds. This
concept is demonstrated for 5a and 5b by axial coordination
to metalloporphyrins to give 7a and 7b.9 These particular
targets attracted our attention due to the widespread interest
in two- and three-dimensional porphyrinic arrays, in addition
to the well-established photophysical properties of porphy-
rins.10 X-ray crystallographic analysis for 7a confirms the
ability of these macrocycles to afford highly ordered crystal-
line materials.
The synthesis of macrocycles 5a,b and supramolecular
assemblies 7a,b is outlined in Scheme 1. Our efforts began
with the palladium-catalyzed cross-coupling of dimethyl
substituted vinyl triflate 2a11 with 3,5-diethynylpyridine 112
to give 3a in 79% yield.13 Protodesilylation of 3a with
methanolic K2CO3 gave the deprotected tetrayne 4a, which
was carried on to an oxidative acetylenic coupling following
aqueous workup. The coupling of 4a in CH2Cl2, utilizing
CuI and TMEDA in the presence of oxygen,14 afforded a
mixture of 5a and linear oligomers that together showed very
limited solubility in organic solvents.
As a result, purification of 5a by chromatography was
impractical. Selective extraction of the product 5a from
a (a) Pd(PPh3)4, CuI, Et2NH, THF, rt; (b) Pd(PPH3)4, CuI, Et2NH,
THF, 55 °C; (c) K2CO3, wet MeOH/THF, rt; (d) TBAF, THF, rt;
(e) CuI, TMEDA, O2, CH2Cl2, rt; (f) 6 (2 equiv), CH2Cl2, rt.
(8) Tobe, Y.; Nagano, A.; Kawabata, K.; Sonoda, M.; Naemura, K. Org.
Lett. 2000, 2, 3265-3268. Henze, O.; Lentz, D.; Schlu¨ter, A. D. Chem.
Eur. J. 2000, 6, 2362-2367. Nitschke, J.; Zu¨rcher, S.; Tilley, T. D. J. Am.
Chem. Soc. 2000, 122, 10345-10352. Inouye, M.; Miyake, T.; Furusyo,
M.; Nakazumi, H. J. Am. Chem. Soc. 1995, 117, 12416-12425.
(9) Leading references for axial coordination of porphyrins see: Chichak,
K.; Branda, N. R. Chem. Commun. 2000, 1211-1212. Haycock, R. A.;
Hunter, C. A.; James, D. A.; Michelsen, U.; Sutton, L. R. Org. Lett. 2000,
2, 2435-2438. Darling, S. L.; Stulz, E.; Feeder, N.; Bampos, N.; Sanders,
J. K. M. New J. Chem. 2000, 24, 261-264. Taylor, P. N.; Anderson, H. L.
J. Am. Chem. Soc. 1999, 121, 11538-11545. Hunter, C. A.; Hyde, R. K.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1936-1939. Hunter, C. A.; Shannon,
R. J. Chem. Commun. 1996, 1361-1362. Hunter, C. A.; Sarson, L. D.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2313-2316. Fleischer, E. B.;
Shachter, A. M. Inorg. Chem. 1991, 30, 3763-3769.
(10) For examples of porphyrin arrays see: Mongin, O.; Hoyler, N.;
Gossauer, A. Eur. J. Org. Chem. 2000, 1193-1197. Vicente, M. G. H.;
Jaquinod, L.; Smith, K. M. Chem. Commun. 1999, 1771-1782. Fan, J.;
Whiteford, J. A.; Olenyuk, B.; Levin, M. D.; Stang, P. J.; Fleischer, E. B.
J. Am. Chem. Soc. 1999, 121, 2741-2752. Anderson, H. L. Chem. Commun.
1999, 2323-2330. Wagner, R. W.; Seth, J.; Yang, S. I.; Kim, D.; Bocian,
D. F.; Holten, D.; Lindsey, J. S. J. Org. Chem. 1998, 63, 5042-5049. Drain,
C. M.; Nifiatis, F.; Vasenko, A.; Batteas, J. D. Angew. Chem., Int. Ed. 1998,
37, 2344-2347. Anderson, H. L.; Anderson, S.; Sanders, J. K. M. J. Chem.
Soc., Perkin Trans. 1 1995, 2231-2245. Abrahams, B. F.; Hoskins, B. F.;
Robson, R. J. Am. Chem. Soc. 1991, 113, 3606-3607.
byproducts proved equally frustrating, requiring unworkable
amounts of solvent. To circumvent the problems associated
with the separation of 5a from oligomeric impurities, the
combined mixture was treated with 2 equiv (based on 3a)
of porphyrin 6 in CH2Cl2. The self-assembly reaction of 5a
and 6 was monitored by TLC, which clearly showed rapid
formation of the desired assembly 7a. The more limited
solubility of linear oligomers assured that porphyrin coor-
dination occurs almost exclusively with macrocycle 5a.
Following porphyrin complexation, the solubility of the
product, 7a, was greatly improved relative to 5a, and it was
easily purified by column chromatography on neutral alu-
mina. Subsequent crystallization from CH2Cl2 gave 7a as a
deep burgundy solid in 39% yield from 3a. It is worth noting
that the majority (>90%) of the uncoordinated porphyrin 6
could be reclaimed by simply flushing the column with an
EtOH/CH2Cl2 mixture following the isolation of 7a. The
limited solubility of 5a demanded a structural change to the
macrocyclic framework that would facilitate handling and
purification. We thus redesigned the synthetic sequence
described above to use vinyl triflate 2b, incorporating
diphenyl vinylidene substitution that was expected to increase
solubility.15
(11) Zhao, Y.; Tykwinski, R. R. J. Am. Chem. Soc. 1999, 121, 458-
459.
(12) Ng, S. C.; Novak, I.; You, X. M.; Huang, W. J. Phys. Chem. A
1998, 102, 904-908.
(13) The purity and structure of all new compounds (except 5a) were
confirmed by 1H and 13C NMR, IR, and MS. Selected synthetic and
characterization details are provided as Supporting Information.
(14) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int.
Ed. 2000, 39, 2633-2657.
1046
Org. Lett., Vol. 3, No. 7, 2001

Palladium-catalyzed coupling of 1 and 2b gave 3b in 61%
yield. Removal of the triethylsilyl groups by treatment with
TBAF afforded deprotected 4b, which was carried on directly
to the next step, following workup. Oxidative homocoupling
of 4b successfully effected formation of macrocycle 5b,
which was isolated in 51% yield (based on 3b) by crystal-
lization from CH2Cl2. Macrocycle 5b is a bright yellow,
highly fluorescent solid. It is quite stable to heat, light, air,
and moisture, and it can be stored indefinitely under
refrigeration without appreciable decomposition.
Self-assembly of 5b with 2 equiv of porphyrin 6 was
brought about in CH2Cl2, and concentration of the reaction
solution afforded the pure assembly 7b as a burgundy solid
in 60% yield. Attempts to crystallize the readily soluble
complex 7b from, for example, CH2Cl2 by the addition of
hexanes resulted only in selective precipitation of the less
soluble macrocycle 5b and indicated that the axial coordina-
tion within 7b was considerably less robust than that
observed for 7a. The increased steric demands of the
vinylidene phenyl moieties likely account for this behavior.
On the basis of NMR analysis for both 7a and 7b, however,
there is little doubt that the solution-state equilibrium in
CD2Cl2 favors 7b. Specifically, the pyridyl protons at
C1/C5 and C3 for the uncomplexed macrocycle 5b resonate
at 8.13 and 7.83 ppm, respectively.16 For both complexes
7a and 7b, these protons are found upfield as a result of
diamagnetic anisotropy of the porphyrin, and they resonate
at ca. 1.1 and 6.1 ppm, respectively.17
Single crystals of 7a suitable for X-ray crystallographic
analysis were obtained from a crude reaction mixture (CH2-
Cl2) that still contained excess porphyrin 6.18 The complex
7a cocrystallized with 1 equiv of 6 that is sandwiched
between layers of the macrocyclic assembly. The tolyl groups
of two offset porphyrin cocrystallites occupy the majority
of the macrocyclic cavities. An ORTEP of 7a is shown in
Figure 1 and confirms the internal dimensions of the
macrocycle circumscribed by the enyne framework, giving
a cavity of 0.64 by 1.0 nm.19
When the crystal packing for 7a is viewed along the b-axis
(Figure 1, bottom), stacking of the macrocycles in the solid
state can be seen. There is a relatively large separation of
layers of the macrocyclic assemblies of approximately 9 Å
to accommodate the cocrystallized porphyrin molecules.
Large crystals of both 7a and 7b can also be grown from
Figure 1. Top: ORTEP drawing of supramolecular complex 7a.
Bottom: a view down the crystallographic b-axis, showing order
within the crystal lattice (cocrystallite porphyrin shown in gray).
CH2Cl2 solutions in the absence of excess porphyrin. In all
cases to date, however, X-ray analysis of these crystals has
been thwarted by rapid desolvation of these samples.
In conclusion, we have realized the first examples of a
novel class of cross-conjugated macrocycles that function
as macrocyclic analogues of 4,4′-bipyridines. The directed
pyridyl functionality of these building blocks readily allows
for their predictable self-assembly into highly ordered
systems, which has been demonstrated by axial coordination
of the macrocycles to metalloporphyrins.
(15) The incorporation of the triethylsilyl alkyne protecting group was
necessary for a more effective synthesis of 2b.
(16) gHMQC analysis of 7a and 7a was used to unambiguously assign
the pyridyl protons. See Supporting Information for details.
(17) Restricted rotation of the tolyl groups of the porphyrin moiety is
observed for metalloporphyrin 6, as well as for assemblies 7a/7b, and is
evidenced by the splitting of nonequivalent protons in the respective 1H
NMR spectra. The difference in chemical shifts for these protons for 6 and
7a/7b also supports the assignment of a solution state equilibrium that favors
7a and 7b. The 1H spectrum of 6 is provided as Supporting Information
for comparison.
Acknowledgment. Financial support for this work has
been provided by the University of Alberta, the Alberta
Science, Research, and Technology Authority, and NSERC.
We thank Dr. Angelina Morales-Izquierdo for help with the
ESI MS and Dr. Tom Nakashima for help with the two-
dimensional NMR analysis.
(18) Compound 7a (C140H102N10O2Ru2‚C51H42N4O2Ru; Mr ) 3002.41)
crystallized in the triclinic space group P1h with a ) 16.1421(11) Å, b )
17.1025(11) Å, c ) 17.5359(12) Å; R ) 90.3641(14)°, â ) 100.8011-
(13)°, γ ) 114.5012(14)°; V ) 4308.0(5) Å3, Z ) 1; R ) 0.089 (10363
2
2
reflections with Fo g 2σ(Fo )), Rw ) 0.29 for 960 variables and 17506
2
2
unique reflections with Fo g -3σ( Fo ).
(19) For a discussion of channel structures, see: Moore, J. S. Nature
1995, 374, 495-496.
Org. Lett., Vol. 3, No. 7, 2001
1047

Supporting Information Available: Synthetic and char-
acterization details for all new compounds, 1H and 13C NMR
spectra for compounds 5a, 6 (1H spectrum), 7a,b, gHMQC
spectra for 7a,b, X-ray crystallographic details for 7a, and
the ESI MS spectrum for 7a. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL0156087
1048
Org. Lett., Vol. 3, No. 7, 2001