Functionalized macrocyclic ligands for use in supramolecular chemistry

Article abstract of DOI:10.1021/jo0159744

The synthesis of three cross-conjugated macrocycles bearing pyridine functionality is described. The ability of two of these molecules, 5a and 5c, to behave as 4,4′-bipyridine mimics in self-assembly reactions is demonstrated by axial coordination to a me

Full text of DOI:10.1021/jo0159744

J . Org. Chem. 2002, 67, 1133-1140
1133
F u n ction a lized Ma cr ocyclic Liga n d s for Use in Su p r a m olecu la r
Ch em istr y
Katie Campbell, Robert McDonald, and Rik R. Tykwinski*
Department of Chemistry, University of Alberta, Edmonton AB T6G 2G2, Canada
rik.tykwinski@ualberta.ca
Received J uly 27, 2001
The synthesis of three cross-conjugated macrocycles bearing pyridine functionality is described.
The ability of two of these molecules, 5a and 5c, to behave as 4,4′-bipyridine mimics in self-assembly
reactions is demonstrated by axial coordination to a metalloporphyrin. The directed coordinative
ability of the pyridine rings ensures predictable self-assembly into well-ordered nanoscale systems,
1
both in solution and the solid state. H, 13C, and HMQC NMR spectroscopic experiments and ESI
MS have been used to characterize the supramolecular complexes in solution. X-ray crystallographic
analysis of solid-state assemblies 7a and 7c provides insight into the scope and flexibility of these
macrocyclic ligands as supramolecular building blocks. UV-vis and fluorescence spectroscopies
provide a description of their electronic characteristics.
In tr od u ction
of a cross-conjugated macrocycle, could also participate
in self-assembly reactions.4,5 Such a ligand could provide
a variety of new hybrid architectures that feature metal
atoms linked by a conjugated, porous macrocycle. Ex-
amination of recent literature reveals that bipyridines
and related molecules are among the most widely used
constituents6 of supramolecular assemblies, due in part
to their rigidity and directed coordinative ability. This
is particularly true of 4,4′-bipyridine,7 which is frequently
employed toward the realization of discrete, highly
ordered nanostructures based on transition metal coor-
dination. Ligands 5a -c, based on a 3,5-diethynyl pyri-
dine building block, were therefore designed with the
expectation that they could function as 4,4′-bipyridine
analogues. The directed, exocyclic orientation of the
pyridyl nitrogens ensures their predictable assembly into
well-defined supramolecular scaffolds. Unlike bipy-
ridines, however, the targeted macrocycles could poten-
tially provide for the formation of porous solid-state
structures (Figure 1).8
Carbon-rich, conjugated macrocycles are of consider-
able interest due to their potential as new materials with
shape persistent structures and desirable physical prop-
erties. Particularly appealing is the “tunability” of the
physical characteristics of these highly conjugated scaf-
folds.1 Through the covalent incorporation of functional
groups, their structures can be manipulated to provide
desirable physical properties tailored for specific applica-
tions. For example, coordinative functionality such as the
nitrogen(s) of pyridine or bipyridine, directed toward the
interior of macrocycles has been used in the design of
artificial receptors2 and ion sensors.3
We became intrigued by the idea of introducing func-
tionality into a macrocyclic framework to provide a
system capable of binding to metals and/or metal ions.
Specifically, the incorporation of pyridine(s) such that the
nitrogen(s) are directed away from the cyclic core could
afford a ligand that, while still possessing the attributes
We demonstrate the coordinative ability of macrocycles
5a -c via axial coordination to metalloporphyrin 6a to
give the corresponding assemblies 7a -c.9 These struc-
tures were targeted due to the widespread interest in
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10.1021/jo0159744 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/26/2002

1134 J . Org. Chem., Vol. 67, No. 4, 2002
Campbell et al.
Sch em e 1
F igu r e 1. Schematic comparison of 4,4′-bipyridine and the
targeted macrocycle as supramolecular building blocks.
multiporphyrin architectures, in addition to the well-
established photophysical features of porphyrins.10 X-ray
crystallographic analysis of 7a verifies the ability of these
macrocycles to form highly ordered crystalline materials,
whereas single-crystal X-ray analysis of 7c establishes
the flexibility of these macrocyclic ligands. The ability of
the macrocyclic core to assume both a planar (7a ) and
chair (7c) conformation nicely demonstrates the ability
to tune the conformational nature of these synthons via
changes in pendant functionality.
Resu lts a n d Discu ssion
Syn th esis. Initial synthetic efforts focused on the
construction of the desired macrocycles based on isopro-
pylidene subunits, as outlined in Scheme 1. 3,5-Diethynyl
pyridine11 was cross-coupled12 via palladium-catalysis
with 2 equiv of the readily available building block vinyl
triflate 2a 13 to give the product 3a in 79% yield. Depro-
tection of the trimethylsilyl-protected acetylenes of 3a
was achieved by treating with methanolic K2CO3. The
resulting tetrayne 4a was then carried on, after an
aqueous workup, to an intermolecular oxidative acety-
lenic homocoupling reaction14 via treatment with CuI and
TMEDA at high dilution in CH2Cl2 in the presence of air
(Scheme 2).15 The reaction was stirred at room temper-
ature until TLC analysis indicated the absence of all of
the starting tetrayne 4a (ca. 1.5 h).
Following aqueous workup, the solvent volume was
reduced to afford a solid mixture containing 5a and what
was presumed to be oligomeric byproducts. This mixture
was extremely insoluble in organic solvents, making
column chromatography impractical. As well, all at-
tempts to selectively extract 5a from this mixture were
unsuccessful. When the mixture was treated with 2 equiv
of porphyrin 6a (based on 3a ), however, TLC analysis
(alumina) clearly indicated the formation of only one
product. Furthermore, coordination to the porphyrin
resulted in vastly increased solubility. This allowed for
the isolation of assembly 7a as a dark red solid, in 39%
yield (from 3a ), via column chromatography on neutral
alumina. Excess porphyrin remaining from the reaction
can be easily recovered by flushing the column with
EtOH/CH2Cl2, following the isolation of 7a . While pure
7a shows limited stability under ambient conditions, it
can be stored indefinitely under refrigeration. Thermally,
the assembly 7a decomposes at 132 °C.
(9) Maiya, B. G.; Bampos, N.; Kumar, A. A.; Feeder, N.; Sanders, J .
K. M. New J . Chem. 2001, 797-800. Chichak, K.; Branda, N. R. Chem.
Commun. 2000, 1211-1212. Haycock, R. A.; Hunter, C. A.; J ames, D.
A.; Michelsen, U.; Sutton, L. R. Org. Lett. 2000, 2, 2435-2438. 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) Mongin, O.; Hoyler, N.; Gossauer, A. Eur. J . Org. Chem. 2000,
1193-1197. Ogawa, K.; Kobuke, Y. Angew. Chem., Int. Ed. 2000, 39,
4070-4073. Anderson, H. L. Chem. Commun. 1999, 2323-2330.
Vicente, M. G. H.; J aquinod, 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. Drain,
C. M.; Nifiatis, F.; Vasenko, A.; Batteas, J . D. Angew. Chem., Int. Ed.
1998, 37, 2344-2347. 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.
We then focused on modifying the vinylidene substitu-
tion, intending to improve both the solubility and stability
of the macrocyclic ligand. Adamantylidene-substituted
vinyl triflate 2b16 was cross-coupled to 1 to give tetrayne
3b in 67% yield. Following deprotection, the product 4b
(11) Ng, S. C.; Novak, I.; You, X.; Huang, W. J . Phys. Chem. A 1998,
102, 904-908.
(12) (a) Zhao, Y.; Tykwinski, R. R. J . Am. Chem. Soc. 1999, 121,
458-459. (b) Zhao, Y.; Campbell, K.; Tykwinski, R. R. J . Org. Chem.
2002, 67, 336-344.
(13) Stang, P. J .; Fisk, T. E. Synthesis 1979, 438-440.
(14) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int.
Ed. 2000, 39, 2632-2657.
(15) Hay, A. S. J . Org. Chem. 1962, 27, 3320-3321.
(16) Stang, P. J .; White, M. R.; Maas, G. Organometallics 1983, 2,
720-725.

Functionalized Macrocyclic Ligands
J . Org. Chem., Vol. 67, No. 4, 2002 1135
Sch em e 2
As oxidative coupling reactions are often favored by a
strong base and rigorously anhydrous reaction condi-
tions,14 our strategy was again modified. Oxygen was
vigorously bubbled through a solution of 4b, CuCl, and
DBU in pyridine over molecular sieves for 14 h. After
aqueous workup, 1H NMR and mass spectral analysis of
the crude product revealed the presence of the protonated
macrocyclic product 5b. Unfortunately, all attempts to
isolate the pure, deprotonated macrocyclic product 5b
were unsuccessful. As a result, porphyrin 6a was added
to the crude reaction mixture, following treatment with
base, in an attempt to mediate the purification process.
ESI MS revealed the presence of the desired assembly
product 7b, but all efforts to purify 7b via recrystalliza-
tion and chromatography were unsuccessful. While fur-
ther efforts would likely allow for the isolation of 5b and
the corresponding assembly 7b, this synthesis produced
such low yields of the desired product that such efforts
were considered to be impractical.
The next modification to the synthesis was to incor-
porate diphenyl vinylidene functionality, accessible from
vinyl triflate 2c. It was anticipated that the diphenyl
vinylidene substitution would impart greater solubility
and stability to the system,17 facilitating purification and
characterization. Diethynyl pyridine 1 was cross-coupled
to 2c to give the polyyne 3c in 61% yield. In contrast to
2a ,b, the chemically more robust triethylsilyl protecting
group was necessary to ensure the stability of vinyl
triflate 2c during synthesis and purification. Desilylation
of 3c was effected by treatment with TBAF in wet THF.
This afforded the deprotected tetrayne 4c, which was
subjected to intermolecular homocoupling conditions
(CuI/TMEDA in CH2Cl2, in the presence of air). After the
addition of ether to the reaction mixture, washing with
saturated aqueous NH4Cl, and drying, the solvent was
reduced by about 80%, leading to the formation of a
bright yellow precipitate. This solid was filtered and dried
to give pure 5c in 51% yield. It is worth noting that pure
5c has been accessible by this method alone. All attempts
to isolate 5c from the crude reaction mixture after
evaporation of the solvent have been unsuccessful. As
with macrocycle 5a , the crude reaction mixture is quite
insoluble and, therefore, difficult to purify by column
chromatography. Likewise, attempts to resolvate the
crude reaction mixture and then recrystallize 5c have
been equally unsuccessful. While the ligand 5c is only
marginally soluble (<2 mg/mL in CH2Cl2), it is quite
stable to air, heat, and light, and may be stored for
months under refrigeration without observable degrada-
tion. It decomposes thermally at temperatures exceeding
170 °C.
was subjected to standard oxidative coupling conditions.
Surprisingly, none of the anticipated macrocyclic product
5b was observed. Instead, the only isolated product was
the iodinated oligomer, 8 (eq 1). This product is presum-
ably formed via reductive elimination across a Cu(II)
species to yield the alkynyl iodide. Attempts to perform
the analogous homocoupling reaction of 4b using CuCl
catalyst were then targeted. After monitoring the reac-
tion for 5 days, however, TLC analysis still revealed the
presence of a significant amount of the starting material,
4b, even after bubbling O2 through the reaction mixture.
The self-assembly reaction of 5c with porphyrin 6a was
performed in CH2Cl2. The addition of 2 equiv of porphyrin
6a , followed by recrystallization from CH2Cl2, allowed for
(17) Decomposition of 5a and 7a likely results from an oxygen ene
reaction at the isopropylidene protons; see ref 12b.

1136 J . Org. Chem., Vol. 67, No. 4, 2002
Campbell et al.
F igu r e 3. ESI MS (nitromethane) for supramolecular complex
7a .
tively, on the F1 axis of the spectrum, consistent with
the chemical shifts expected for these pyridyl carbons.
The solution-state presence of complexes 7a and 7c is
also supported by MS analysis. In the ESI mass spectrum
of 7a (nitromethane), a cluster of signals centered at m/z
2160 (3% intensity) is observed (Figure 3). Comparison
of the calculated and observed isotopic distribution
patterns for 7a suggests that these signals are consistent
with a combination of protonated [M + H]+ and radical
cation species [M]+•. A fragment peak of greater intensity
(21%) is observed at m/z 1361, resulting from the loss of
one porphyrin unit. The isotopic distribution of this peak
also suggests the presence of both the radical cationic
and protonated species. Other significant fragments
include peaks at m/z 798 (100% intensity, radical cation)
corresponding to the porphyrin and at m/z 563 (92%)
representing the protonated macrocyclic ligand [5a +
H]+. Numerous attempts were made to improve the
intensity of the [M + H]+ and/or [M]+• peaks, including
varying the applied voltage, using different combinations
of solvents, and acquiring the spectra at lower temper-
atures. All strategies resulted in a loss of sensitivity with
no significant gains in intensity.
F igu r e 2. gHMQC NMR spectrum for 7c (in CD2Cl2) showing
correlations for the ortho and para pyridyl protons.
isolation of the desired assembly 7c, a bright red solid,
in 60% yield. The progress of the assembly reaction was
1
also monitored by H NMR spectroscopy. Aliquots of 6a
were slowly added to a dilute solution of 5c in CD2Cl2,
resulting in the formation of the assembly product 7c.
While the reaction appears to proceed quantitatively on
the basis of NMR analysis, the moderate isolated yield
is apparently due to the weaker association of complex
7c in solution (in comparison to the isopropylidene-
functionalized analogue, 7a ). Unlike 7a , the macrocyclic
portion of 7c dissociates from the Ru-porphyrins when
the complex is subjected to chromatography, with either
alumina or silica, regardless of the solvent employed.
Attempts to precipitate complex 7c from a CH2Cl2 solu-
tion via the addition of other solvents (e.g., hexanes,
ether, and toluene) have been unsuccessful. These efforts
resulted only in the precipitation of macrocycle 5c from
the solution as a result of dissociation of the axially bound
porphyrins from the complex. This behavior of 7c is in
stark contrast to that of complex 7a , which is stable to
chromatography and can be precipitated intact from
solution. In the solid state, the complex 7c is thermally
quite stable, decomposing only at >250 °C.
For the less robust assembly, 7c, an [M + H]+ signal
is not found in the ESI MS. A signal at m/z 1856 (3%) is
observed, corresponding to the fragment resulting from
the loss of one porphyrin moiety. MALDI-TOF analysis
has also been employed for 7c, with 1,8,9-trihydroxyan-
thracene as the matrix and irradiation at 337 nm. As
shown in Figure 4, the most diagnostic signal is found
at m/z 1829, corresponding to assembly 7c with the loss
of one complete porphyrin moiety as well as the second
porphyrinic CO group. As the photochemical dissociation
of CO from ruthenium porphyrins is well-known,18 this
fragmentation is not unexpected considering the irradia-
tion wavelength. In addition to the protonated macrocycle
at m/z 1059.9, signals corresponding to the porphyrin
radical cation (m/z 770.4) and a porphyrin dimer (m/z
1535.2) (where both species are decarbonylated) are also
clearly present in the spectrum.
Ch a r a cter iza tion . The most convincing evidence for
the formation of assemblies 7a and 7c in solution comes
primarily from NMR spectroscopic analysis. In the 1H
NMR spectrum of 5c, the ortho and para pyridyl protons
give rise to signals at 8.13 and 7.83 ppm, respectively.
Upon assembly with the tetratolylporphyrin 6a , however,
these protons are significantly shielded to δ 1.12 and 6.08,
respectively, due to the diamagnetic anisotropy of the
porphyrin ring. This effect is quite dramatic for the ortho
protons due to their proximity to the porphyrin ring.
Solid -Sta te Ch a r a cter iza tion . Single crystals of 7a
suitable for X-ray crystallographic analysis were obtained
from a crude reaction mixture containing 7a and excess
porphyrin 6a in CH2Cl2. The complex 7a cocrystallized
1
Similarly, the H NMR spectrum of assembly 7a shows
the ortho and para pyridyl proton signals at 1.30 and 6.04
ppm, respectively. Two-dimensional gHMQC NMR analy-
ses for both 7a and 7c provided confirmation of these
proton assignments. As shown in Figure 2, the signals
ascribed to the ortho and para pyridyl protons of 7c
correlate to signals at ca. 145.2 and 139.6 ppm, respec-
(18) Saito, M.; Endo, A.; Shimizu, K.; Satoˆ, G. P. Electrochim. Acta
2000, 45, 3021-3028. Funatsu, K.; Kimura, A.; Imamura, T.; Ichimura,
A.; Sasaki, Y. Inorg. Chem. 1997, 36, 1625-1635.

Functionalized Macrocyclic Ligands
J . Org. Chem., Vol. 67, No. 4, 2002 1137
F igu r e 4. MALDI-TOF spectrum for 7c.
with 1 equiv of 6a such that the excess porphyrin is
captured between the layers of the assembly product. An
ORTEP of 7a is shown in Figure 5, and the internal
dimensions of the macrocycle circumscribed by the enyne
scaffold provide a cavity of 0.64 × 1.0 nm. The framework
of the macrocyclic core is virtually planar. It also appears
to be nearly free from strain, as all alkyne angles are
within 8.2° of the expected value of 180° with a mean
deviation of 3.6°. Furthermore, the vinylidene bond
angles C(77)-C(78)-C(82) and C(85)-C(86)-C(90) at
115.5 and 113.7° are quite similar to those found for
analogous acyclic systems.12
When the crystal packing for 7a is viewed along the
b-axis (Figure 5, bottom), stacking of the macrocyclic
portion of the assembly in the solid state can be observed.
The majority of the cavity created by organization of the
macrocycles is occupied the tolyl groups of two of the
offset porphyrin cocrystallites, which are shown in gray
(Figure 5). The void space remaining within the unit cell,
at 751.6 Å3, is still rather large and represents 17.4% of
the total unit cell volume. This so-called void space is
likely to be occupied by solvent, but the final electron
density difference map is ambiguous as to the location
and/or the identity of the solvent molecules. The layers
of the macrocyclic assemblies are separated by ap-
proximately 9 Å to accommodate the cocrystallized por-
phyrin molecules. While single crystals are also available
from a CH2Cl2 solution of pure 7a , to date, all attempts
at X-ray crystallographic analysis have been hindered by
the rapid desolvation of these crystals. Likewise, at-
tempts to cocrystallize 7a with small molecules that
might be suitable for inclusion in the pores of 7a have
also been unsuccessful.
F igu r e 5. Top: ORTEP drawing of supramolecular assembly
7a (20% probability level). Bottom: View down the crystal-
lographic b-axis showing order within the crystal lattice
(cocrystallite porphyrin 6a shown in gray). Primed atoms are
related to unprimed ones by a crystallographic inversion
center.
as found for 7a but instead adopts a chairlike conforma-
tion. The degree of distortion can be approximated by
measuring the dihedral angles of the three chairs gener-
ated in this conformation. Using a dummy atom at the
center of the pyridine ring as one vertex (centroid) of the
hexagon, and the alkylidene carbons C(78) and C(96) as
the others, the following dihedral angles are obtained:
(1) 59.3° [(centroid)-C(78)-C(96)-(centroid)′], (2) 61.8°
[C(78)-C(96)-(centroid)′-C(78)′], and (3) 64.5° [C(96)-
(centroid)′-C(78)′-C(96)′]. This gives an average value
of 61.9°, considerably larger than that of cyclohexane at
55.1°.19 The distortion from planarity is also greater than
that of a recently reported expanded radialene, which has
an average dihedral angle of 57.2°.1m The macrocyclic
portion of assembly 7a , by the same comparison, pos-
sesses a mean dihedral angle of only 3.2°. The chair
conformation of 7c results in a reduction of the alkylidene
bond angles C(77)-C(78)-C(92) and C(95)-C(96)-
C(110), which at 113.6 and 112.3°, respectively, are
smaller by 1.8° than those found for precursor 3c.20 The
remarkable puckering of the macrocyclic core likely
Single crystals of 7c suitable for X-ray analysis were
formed from a CH2Cl2 solution of the pure assembly in
the presence of n-hexadecane. The structure of 7c incor-
porates one hexadecane molecule in the unit cell, the
presence of which hampered data refinement. Figure 6
shows the ORTEP of the centrosymmetrical 7c and
confirms the coordination of 5c to the porphyrin in the
solid state. Analysis of this solid-state structure reveals
that the enyne core of the macrocycle is no longer planar
(19) Kahn, R.; Fourme, R.; Andre´, D.; Renaud, M. Acta Crystallogr.
Sect. B 1973, 29, 131-138.
(20) Campbell, K.; Tykwinski, R. R. Unpublished results.

1138 J . Org. Chem., Vol. 67, No. 4, 2002
Campbell et al.
F igu r e 7. Absorption (solid lines) and emission (broken lines)
spectra for 3c and 5c (in CH2Cl2).
F igu r e 8. Absorption (solid line) and emission (broken line)
spectra for complex 7c (in CH2Cl2).
F igu r e 6. Top: ORTEP drawing of supramolecular complex
7c (20% probability level, hexadecane removed). Bottom:
Alternate view emphasizing the chair conformation of the
macrocyclic core. Primed atoms are related to unprimed ones
by a crystallographic inversion center.
components, were analyzed by UV-vis and fluorescence
spectroscopies. Whereas structures with dimethyl vi-
nylidene substitution do not show significant fluores-
cence, the diphenyl vinylidene moiety greatly enhances
emissive behavior. As seen in Figure 7, the absorption
spectrum for 5c shows a longer wavelength absorption
band, the shoulder centered near 401 nm, as a result of
the extended conjugated framework in comparison to
precursor 3c (λmax ) 348 nm). The lower energy HOMO-
LUMO gap for 5c is also reflected in the emission
spectrum, where the emission maximum for 5c, centered
at 491 nm (excitation at 362 nm), is red-shifted by 45
nm from that of 3c at 446 nm (excitation at 340 nm).
The absorption spectrum of 7c is, for the most part,
the sum of its component parts, i.e., 5c + 2 equiv of 6a .
The Soret Band for both complexes 7a and 7c is found
at 413 nm, identical to the energy of 6a .21 The two
Q-Band absorptions for complexes 7a and 7c found at
569 and 534 nm, however, are slightly red-shifted versus
those of 6a (562 and 530 nm). Assembly 7c shows an
emission at 489 nm (excitation at 364 nm) situated in
the region of low molar absorptivity for the porphyrin
(Figure 8). Although the emission energy for 7c is nearly
identical to that of the pure macrocycle 5c, the relative
results from increased steric interactions between the
diphenyl vinylidene substitution and the attached por-
phyrin ring(s). This observation also helps to account for
the observed fragility of assembly 7c in solution in
comparison to 7a . Somewhat surprisingly, however, is
that the disparity in chemical stability between 7a and
7c is not reflected in N-Ru bond lengths, which are
identical within 0.001 Å for both molecules at 2.218 Å.
The apparent flexibility of the macrocyclic ligand of 7c
in the solid state discussed above suggested that, in
solution, the interconversion between two degenerate
chair conformations (via a twisted or planar intermedi-
ate) or between a chair and planar conformation might
be feasible. Attempts to explore this possibility have,
however, been inconclusive due to the lack of a suitable
spectroscopic signature that would indicate a planar or
twisted conformation. Variable-temperature 1H NMR
spectra obtained over a temperature range of 30 to -80
°C for 7c showed no significant chemical shift change for
any resonance that would suggest that two conformations
were in equilibrium in solution.
Electr on ic Ch a r a cter istics. The electronic charac-
teristics of assemblies 7a and 7c, as well as their
(21) These spectra are provided as Supporting Information.

Functionalized Macrocyclic Ligands
J . Org. Chem., Vol. 67, No. 4, 2002 1139
analysis no longer indicated the presence of the polyyne
starting material. Ether was added, and the resulting solution
was washed with saturated aqueous NH4Cl (2 × 25 mL) and
dried; the solvent was removed in vacuo. Chromatography and/
or recrystallization from acetone gave the desired oligomer.
Gen er a l Hom ocou p lin g P r oced u r e. A mixture of the
appropriate trimethylsilyl- or triethylsilyl-protected polyyne
and K2CO3 (ca. 0.2 equiv) or TBAF (ca. 2.2 equiv) in wet THF/
MeOH (1:1, 25 mL) or THF (25 mL), respectively, was stirred
at room temperature until TLC analysis revealed the disap-
pearance of all trialkylsilyl-protected species. Ether was added,
and the resulting solution was washed with saturated aqueous
NH4Cl (2 × 25 mL) and dried. The solvent was reduced to ca.
1 mL, and dry CH2Cl2 was added. A solution of CuI (ca. 7
equiv) and TMEDA (ca. 20 equiv) in ca. 10 mL of dry CH2Cl2
was prepared and added slowly to the solution containing the
deprotected polyyne. The reaction mixture was stirred at the
temperature indicated until TLC analysis no longer showed
the presence of the deprotected polyyne. Ether was added, and
the resulting solution was washed with saturated aqueous
NH4Cl (6 × 75 mL) and dried.
emission intensity is greater for 7c. This fact supports
emission from the macrocyclic core of 7c rather than
emission from free 5c generated from a dissociation
equilibrium established in solution. A very weak emission
from 7c can also be observed at ca. 725 nm (not shown).
This emission is characteristic of both porphyrin 6a and
6b in solution.22 It is unknown, therefore, whether this
low-energy emission results from the porphyrin com-
plexed in 7c, or from a small concentration of free
porphyrin generated via dissociation of 7c (or from both).
Con clu sion s
We have described a synthetic route to functionalized
macrocycles based on a simple 3,5-diethynyl pyridine
building block. The ability of these macrocycles to func-
tion as ligands and to participate in self-assembly reac-
tions has been demonstrated, yielding nanoscale assem-
blies 7a and 7c. These assemblies were characterized
both in solution as well as in the solid state. Analysis of
the solid-state structure of 7a reveals the ability of these
ligands to form highly ordered, channel-like materials.
A similar analysis of 7c reveals that steric interactions
impede planarity as the size of the vinylidene substitu-
tion is increased from methyl to phenyl. These steric
constraints lead to a chairlike conformation for 7c in the
solid state that demonstrates the flexibility of these
macrocycles as supramolecular synthons. Future efforts
will focus on further exploring the utility of these
molecules as ligands in other self-assembly reactions,
using less sterically demanding metal fragments.
3,5-Bis(1-tr im eth ylsilyl-3-pr opyliden e-1,4-pen tadiyn yl)-
p yr id in e (3a ). Diethynyl pyridine 1 (0.13 g, 1.0 mmol) was
cross-coupled with vinyl triflate 2a (0.63 g, 2.1 mmol) in dry,
degassed THF (80 mL) in the presence of Pd(PPh3)4 (50 mg,
0.040 mmol), CuI (25 mg, 0.13 mmol), and Et2NH (4 mL) at
room temperature for 30 min as described in the general
procedure. Flash chromatography on alumina (hexanes/CH2-
Cl2, 2:1) yielded 3a (0.36 g, 79%) as a colorless solid: mp 71-
72 °C; Rf ) 0.40 (hexanes/CH2Cl2, 2:1); UV-vis (CH2Cl2) 297
(30700) nm; IR (µscope) 2959, 2904, 2210, 2151, 1577 cm-1
;
1H NMR (300 MHz, CDCl3) δ 8.54 (br s, 2H), 7.78 (br s, 1H),
2.08 (s, 12H), 0.21 (s, 18H); 13C NMR (75.5 MHz, APT, CD2-
Cl2) δ 158.3, 150.9, 140.3, 120.4, 101.2, 101.2, 97.1, 90.2, 87.5,
23.1, 23.0, 0.0; ESI MS (MeOH/toluene) m/z (rel intensity):
428.2 ([M + H]+, 100); ESI HRMS calcd for C27H34NSi2 ([M +
H]+) 428.2230, found 428.2226.
Exp er im en ta l Section
3,5-Bis(1-tr im eth ylsilyl-3-adam an tyliden e-1,4-pen tadiy-
n yl)p yr id in e (3b). Compound 1 (35 mg, 0.28 mmol) was cross-
coupled with 2b (0.19 g, 0.47 mmol) in dry, degassed THF (20
mL) in the presence of Pd(PPh3)4 (25 mg, 0.020 mmol), CuI
(12 mg, 0.060 mmol), and Et2NH (2 mL) at room temperature
for 1 h as described in the general procedure. Purification by
column chromatography on alumina (hexanes/CH2Cl2 1:1)
afforded 3b (113 mg, 67%) as an off-white solid: mp 181-183
°C; Rf ) 0.65 (hexanes/CH2Cl2 1:1); UV-vis (CH2Cl2) 250
(35600), 305 (32900) nm; IR (µscope) 3037, 2850, 2203, 2152,
1448 cm-1; 1H NMR (300 MHz, CD2Cl2) δ 8.53 (d, J ) 2.1 Hz,
2H), 7.78 (t, J ) 2.0, 1H), 3.30 (s br, 4H), 2.02-1.80 (m, 24
H), 0.22 (s, 18H); 13C NMR (75 MHz, CD2Cl2, APT) δ 173.3,
150.7, 140.3, 120.5, 100.7, 96.4, 93.4, 89.8, 87.0, 39.7, 39.6, 37.2,
37.1, 37.0, 28.4, 0.1 (one coincident peak not observed); ESIMS
(MeOH/tol 3:1) m/z 612.3 ([M + H]+, 100); ESI HRMS calcd
for C41H50NSi2 ([M + H]+) 612.3482, found 612.3482.
Gen er a l Meth od s. Reagents were purchased reagent grade
from commercial suppliers and used without further purifica-
tion. 3,5-Diethynyl pyridine,11 2a ,c,12 and 2b16 were prepared
as previously reported. Evaporation and concentration in vacuo
was achieved at H2O-aspirator pressure. Drying was done over
anhydrous MgSO4. All Pd-catalyzed coupling reactions were
performed in standard, dry glassware under an inert atmo-
sphere of N2. A positive pressure of N2 was essential to the
success of all Pd-catalyzed reactions. Degassing of solvents was
accomplished by vigorously bubbling N2 through the solutions
for greater than 45 min. Column chromatography was per-
formed on aluminum oxide, neutral Brockman 1, or silica gel.
X-ray crystal data for 7a (Figure 5): (C191H144N14O4Ru3); M
) 3002.41, triclinic space group P1h (No. 2), Fcalcd ) 1.157 g/cm3,
Z ) 1, 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)°,
3,5-Bis(1-t r iet h ylsilyl-3-d ip h en ylvin ylid en e-1,4-p en -
ta d iyn yl)p yr id in e (3c). Compound 1 (70 mg, 0.55 mmol) was
cross-coupled with vinyl triflate 2c (0.50 g, 1.1 mmol) in dry,
degassed THF (65 mL) in the presence of Pd(PPh3)4 (35 mg,
0.030 mmol), CuI (20 mg, 0.10 mmol), and Et2NH (1.5 mL).
The reaction flask was sealed under N2 and stirred for 24 h at
55 °C. Evaporation of the solvent and flash chromatography
on alumina (hexanes/CH2Cl2, 2:1) yielded 3c (254 mg, 61%)
as a colorless solid: mp 118-121 °C; Rf ) 0.40 (hexanes/CH2-
Cl2, 2:1); UV-vis (CH2Cl2) 259 (48800), 348 (41700) nm; IR
V ) 4308.0 (5) Å3, µ ) 0.316 mm-1. Final R(F) ) 0.0887, wR2
2
(F2) ) 0.2941 for 960 variables and 17506 data with Fo
g
-3σ(Fo2) (10363 observations [Fo g 2σ(Fo2)]). Full details can
2
be found in Supporting Information and in ref 4.
X-ray crystal data for 7c (Figure 6): (C180H118N10O2Ru2‚
C
16H34); M ) 2881.42, triclinic space group P1h (No. 2), Fcalcd )
1.022 g/cm3, Z ) 1, a ) 13.9983(16) Å, b ) 17.099(2) Å, c )
22.220(3) Å, R ) 100.949 (2)°, â ) 96.942 (2)°, γ ) 113.311
(2)°, V ) 4680.6 (9) Å3, µ ) 0.211 mm-1. Final R(F) ) 0.1079,
wR2 (F2) ) 0.3587 for 958 variables and 18770 data with Fo
2
(µscope) 3081, 2910, 2205, 2151, 1536 cm-1 1H NMR (300
;
g -3σ(Fo2) (8613 observations [Fo2 g 2σ(Fo2)]). Full details can
be found in Supporting Information.
MHz, CD2Cl2) δ 8.30 (d, J ) 2.0 Hz, 2H), 7.33-7.51 (m, 21H),
0.95 (t, J ) 7.8 Hz, 18H), 0.60 (q, J ) 7.8 Hz, 12H); 13C NMR
(75.5 MHz, APT, CD2Cl2) δ 158.6, 151.0, 140.6, 140.2, 140.0,
130.7, 130.6, 129.3, 129.2, 128.2, 128.1 (2×), 104.0, 101.8, 96.7,
92.8, 87.7, 7.6, 4.5; ESI MS (MeOH/toluene) m/z (rel intensity)
760.4 ([M + H]+, 100); ESI HRMS calcd for C53H54NSi2 ([M +
H]+) 760.3795, found 760.3792.
Gen er a l Cr oss-Cou p lin g P r oced u r e. Two equivalents of
the appropriate vinyl triflate, 2a -c, were added to a dry,
degassed solution of diethynyl pyridine 1 in THF. Ph(PPh3)4
(ca. 0.05 equiv) and Et2NH were added, and the solution was
stirred for 5 min. CuI (ca. 0.15 equiv) was added, and the
solution was stirred at the temperature indicated until TLC
3,5-Bis(1-iod o-3-a d a m a n tylid en e-1,4-p en ta d iyn yl)p yr i-
d in e (8). Compound 3b (0.10 g, 0.16 mmol) was desilylated
by treatment with methanolic K2CO3 for 1 h as described in
(22) Chichak, K.; Branda, N. R. Chem. Commun. 1999, 523-524.

1140 J . Org. Chem., Vol. 67, No. 4, 2002
Campbell et al.
the general procedure. After aqueous workup, the deprotected
polyyne 4b was treated with CuI (0.20 g, 1.1 mmol) and
TMEDA (0.40 mL, 2.6 mmol) in dry CH2Cl2 (350 mL) in the
presence of air. The reaction mixture was stirred at room
temperature for 2 h. Ether was added, and the resulting
solution was washed with saturated aqueous NH4Cl (6 × 75
mL) and dried; the solvent was removed in vacuo. Purification
by column chromatography on silica gel (neat CH2Cl2) yielded
4d (49 mg, 42%) as an off-white solid: Rf ) 0.35 (silica, CH2-
solution of Ru porphyrin 6a (0.20 g, 0.25 mmol, 2 equiv on
the basis of 3a ) in CH2Cl2 (2 mL). Flash chromatography on
alumina (hexanes/CH2Cl2, 1:1) yielded 7a (0.15 g, 39% overall
from 3a ) as a burgundy solid: mp 132 °C dec; UV-vis (CH2-
Cl2) 295 (130900), 414 (519400), 534 (42800); IR (µscope) 3126,
1
2866, 2210, 1916, 1806, 1575 cm-1; H NMR (300 MHz, CD2-
Cl2) δ 8.64 (s, 16H), 8.11 (dd, J ) 7.8, 1.9 Hz, 8H), 7.90 (dd, J
) 7.8, 1.9 Hz, 8H), 7.57 (d, J ) 7.8 Hz, 8H), 7.46 (d, J ) 7.8
Hz, 8H), 6.04 (t, J ) 1.7 Hz, 2H), 2.70 (s, 24H), 2.00 (s, 12H),
1.84 (s, 12H), 1.30 (d, J ) 1.9 Hz, 4H); 13C NMR (125.3 MHz,
CD2Cl2) δ 181.1 (CtO), 161.0, 145.1, 144.0, 139.8, 137.8, 137.4,
134.4 (2×), 132.1, 127.6, 127.3, 122.0, 118.1, 99.7, 88.8, 85.5,
78.1, 75.7, 23.5, 23.2, 21.5; ESI MS (nitromethane) m/z (rel
intensity) 2160 ([M + H]+, 3), 1361 ([M - porphyrin]+, 21),
798 ([porphyrin]+, 100), 563 ([5a + H]+, 92).
1
Cl2); IR (µscope) 2921, 2851, 2205, 1703, 1575 cm-1; H NMR
(300 MHz, CD2Cl2) δ 8.53 (d, J ) 2.1 Hz, 2H), 7.78 (t, J ) 2.1
Hz, 1H), 3.28 (br s, 4H), 1.80-2.03 (m, 24H); 13C NMR (125
MHz, APT, CD2Cl2) δ 174.2, 150.6, 140.2, 120.3, 93.6, 89.9,
89.5, 87.3, 39.8, 39.7, 37.1, 37.0, 28.4, 7.8 (two coincident sp3
peaks not observed); ESI MS (nitromethane) m/z (rel inten-
sity): 720.1 ([M + H]+, 100); ESI HRMS calcd for C35H32NI2
([M + H]+) 720.0624, found 720.0635.
Ma cr ocyclic P or p h yr in Assem bly 7c. Macrocycle 5c (10
mg, 0.0090 mmol) was added to a solution of Ru porphyrin 6a
(15 mg, 0.019 mmol) in CH2Cl2 (2 mL), and the assembly
product crystallized upon concentration to give 7c (15 mg, 60%)
as a bright red solid; mp 266 °C dec; UV-vis (CH2Cl2) 363
(101200), 413 (493200), 533 (36000), 568 (9200) nm; IR (µscope)
Ma cr ocycle 5a . Oligomer 3a (0.15 g, 0.36 mmol) was
desilylated by treating with methanolic K2CO3 for 1 h as
described in the general procedure. Deprotected polyyne 4a
was then oxidatively homocoupled in the presence of CuI (0.52
g, 2.7 mmol), TMEDA (1.0 mL, 6.6 mmol), and air in dry CH2-
Cl2 (350 mL) for 90 min at room temperature. After aqueous
workup, the solvent was removed under reduced pressure to
yield an off-white solid. Macrocycle 5a was not isolated due to
the extremely limited solubility of this crude reaction product.
Ma cr ocycle 5b. Oligomer 3b (30 mg, 0.049 mmol) was
desilylated by treatment with TBAF for 30 min as described
in the general procedure. The deprotected polyyne 4b was then
oxidatively coupled in the presence of CuCl (50 mg. 0.51 mmol),
DBU (0.50 mL), and O2 in pyridine (75 mL). The mixture was
stirred for 14 h at room temperature. Ether was added, and
the resulting solution was washed with saturated aqueous
NH4Cl (4 × 50 mL) and dried. Removal of the solvent yielded
the crude macrocycle 5b that could not be further purified.
Ma cr ocycle 5c. Compound 3c (82 mg, 0.12 mmol) was
desilylated by treatment with TBAF for 30 min as described
in the general procedure. Deprotected polyyne 4c was oxida-
tively coupled in the presence of CuI (0.18 g, 0.92 mmol),
TMEDA (0.35 mL, 2.3 mmol), and air in dry CH2Cl2 (220 mL)
for 3 h at room temperature followed by 12 h at 4 °C. Following
aqueous workup, the solvent was reduced by approximately
80%, resulting in the formation of a bright yellow precipitate.
Isolation of the precipitate afforded 5c (29 mg, 51%) as a bright
yellow solid that was not sufficiently soluble for meaningful
13C NMR analysis; mp 172 °C dec; UV-vis (CH2Cl2) 260
(72600), 362 (88900), 401 (sh, 43400) nm; IR (µscope) 3052,
2210, 1583, 1513 cm-1; 1H NMR (300 MHz, CD2Cl2) δ 8.13 (d,
J ) 1.9 Hz, 4H), 7.83 (t, J ) 1.9 Hz, 2H), 7.31-7.48 (m, 40H);
ESI MS (MeOH/toluene) m/z (rel intensity) 1059.4 ([M + H]+,
43); ESI HRMS calcd for C82H47N2 ([M + H]+) 1059.3734, found
1059.3738.
1
3021, 1949, 1529, 1512, 1493 cm-1; H NMR (300 MHz, CD2-
Cl2) δ 8.58 (s, 16H), 8.05 (d, J ) 7.7 Hz, 8H), 7.76 (d, J ) 7.7
Hz, 8H), 7.53 (d, J ) 7.7 Hz, 8H), 7.02-7.43 (m, 48H), 6.08
(br s, 2H), 2.65 (s, 24H), 1.12 (br s, 4H); 13C NMR (125.3 MHz,
APT, CD2Cl2) δ CO peak not observed, 160.4, 145.3, 143.9,
139.8, 139.6, 139.0, 137.3, 134.5, 134.4, 132.1, 130.5, 130.1,
129.7, 128.3, 128.2, 127.6, 127.5, 117.6, 99.2, 90.5, 85.4, 81.3,
76.4, 21.5 (one broad sp2 CH not observed, one coincident sp2
CH not observed); ESI MS (nitromethane) m/z (rel intensity):
1856 ([M + H - porphyrin]+, 4), 1059 ([5b + H]+, 34), 770
([6a - CO]+, 100); MALDI MS: 1829 ([M + H - porphyrin -
CO ]+).
Ack n ow led gm en t. Financial support for this work
has been provided by the University of Alberta, the
Alberta Science, Research and Technology Authority,
and NSERC. We would like to thank Dr. Angelina
Morales-Izquierdo for help with the ESI MS and Dr.
Tom Nakashima for help with all two-dimensional NMR
analyses. We also appreciate helpful discussions with
Dr. Neil R. Branda.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
1
spectra for compounds 3a -c, 4d , and 7a ,c, H NMR spectra
of 5c and 6, gHMQC spectra of compounds 7a ,c, ESI MS
spectra of compounds 7a , UV-vis analysis for compound 7c
versus (5c + 2 equiv 6a ) and compound 7a versus 7c, and
X-ray crystallographic data for compounds 7a and 7c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Ma cr ocyclic P or p h yr in Assem bly 7a . The crude product
mixture containing macrocycle 5a (0.16 g) was added to a
J O0159744