Exo- and Endo-Receptors in One. A Novel Class of Supramolecular Structures Housing Transition-Metal-Binding Bi- and Terpyridine Units alongside Lithium Ion-Selective Trispirotetrahydrofuranyl Components

Article abstract of DOI:10.1021/jo030373t

The preparation of bipyridine and terpyridine ligands covalently linked via acetylenic and alkoxy tethers to rigid inositol orthoformate platforms is described. The constitution of compounds 3-6 is such that latent exo- and endo-receptor properties are si

Full text of DOI:10.1021/jo030373t

Exo- a n d En d o-Recep tor s in On e. A Novel Cla ss of Su p r a m olecu la r
Str u ctu r es Hou sin g Tr a n sition -Meta l-Bin d in g Bi- a n d Ter p yr id in e
Un its a lon gsid e Lith iu m Ion -Selective Tr isp ir otetr a h yd r ofu r a n yl
Com p on en ts
David G. Hilmey and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210
paquette.1@osu.edu
Received December 5, 2003
The preparation of bipyridine and terpyridine ligands covalently linked via acetylenic and alkoxy
tethers to rigid inositol orthoformate platforms is described. The constitution of compounds 3-6 is
such that latent exo- and endo-receptor properties are simultaneously present with specific binding
sites for Li+ and transition-metal ions. The 2-fold complexation in different regions is not dependent
on prior molecular association. To gauge this unprecedented property, the model systems 11-14
were synthesized and their response to CuCl and FeCl2 probed by UV-vis and MS techniques. In
a similar fashion, the ability of 3-6 to ligate lithium ions chemoselectively was evaluated by
electrospray methods. The introduction of controlled amounts of both types of cation followed, and
conversion to insoluble oligomeric products presumed to result from integral incorporation of the
different metal ions in the expected fashion was achieved.
The past 30 years have been witness to the develop-
ment of chemosensors for potential use in many applica-
tions, including most notably those of relevance to
biology, medicine, materials chemistry, and environmen-
tal science.1 These conceptually fascinating advances
have centered around a considerable array of ions rang-
ing from those in the alkali metal family to the many
transition-metal candidates. Supramolecular chemistry
has emerged as the defining descriptor for the operation
of noncovalent interactions in chemical entities where
two or more intermolecular forces operate.2 Current
trends in this field suggest that the proper integration
of multiple binding sites offers the potential for providing
more powerful sensing capabilities than those available
to single receptor systems.3 Although there has been
extensive work carried out in connection with multiple
cationic binding,4 little research has been dedicated to a
ligand’s ability to selectively bind two different metal ions
predictably in dissimilar regions of the same molecule.5
The concept of multiple heterocationic binding without
cooperativity is of significant interest as it represents a
new consideration in metalloreceptor chemistry and has
biological relevance, for example, in the co-transport of
dissimilar cations across liquid membranes.
We have recently described the synthesis and com-
plexation properties of 1 and its homoditopic dimer 2.6
The rigid inositol ortho ester platform is particularly well
suited to strong ionophoric interaction with the lithium
ion. This property, and particularly the demonstrated
preference of 1 for formation of a 2:1 complex with Li+,
is shared by 2, which readily forms a rodlike ionic
polymer upon treatment with LiClO4 or LiBF4. The
spirotetrahydrofuran triad is particularly conducive to
lithium ion affinity. Smaller ring sizes bind less ef-
fectively, presumably because of the differing polariz-
abilities of the nonbonded electron pairs.7
(1) (a) Ellis, A. B., Walt, D. R. Chem. Rev. 2000, 100, 2477. (b) Ricco,
A. J .; Crooks, R. M. Acc. Chem. Res. 1998, 31, 200. (c) De Silva, A. P.;
Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J . M.; McCoy, C.
P.; Rademacher, J . T.; Rice, T. E. Chem. Rev. 1997, 97, 1515. (d)
Czarnik, A. W. Chem. Biol. 1995, 2, 423.
(2) Lehn, J .-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89.
(3) (a) White, J .; Kauer, J . S.; Dickinson, T. A.; Walt, D. R. Anal.
Chem. 1996, 68, 2191. (b) Dickinson, T. A.; White, J .; Kauer, J . S.;
Walt, D. R. Nature 1996, 382, 697.
(4) (a) Bruce, J . I.; Chanbron, J .-C.; Koll, P.; Sauvage, J .-P. J . Chem.
Soc., Perkin Trans. 1 2002, 1226. (b) Kaes, C.; Hosseini, M. W.; De
Cian, A.; Fischer, J . Tetrahedron Lett. 1997, 38, 3901. (c) Mendoza, J .;
Mesa, E.; Rodriguez-Ubis, J .; Vasquez, P.; Vogtle, F.; Windschief, P.;
Rissanen, K.; Lehn, J .-M.; Lilienbaum, P.; Ziessel, R. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1331. (d) Romero, F. M.; Ziessel, R. Tetrahedron
Lett. 1994, 35, 9203. (e) Baxter, P. N. M. J . Org. Chem. 2000, 65, 1257.
Herein, we describe synthetic approaches to the four
supramolecular ligands 3-6 and their behavior regarding
co-complexation with Li+ and several transition-metal
ions. One site is the stereodefined and conformationally
constrained spiro ether structural arrangement related
directly to 1 and 2. The second locale consists of a bi- or
terpyridine building block, for which ample precedent is
10.1021/jo030373t CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/26/2004
3262
J . Org. Chem. 2004, 69, 3262-3270

Exo- and Endo-Receptors in One
SCHEME 1
SCHEME 2
the binding of one metal ion is not necessary to achieve
the second binding.9 Our analysis of the chemical events
in operation is derived from mass spectroscopy and UV-
vis analysis of simplified versions of the anticipated
supramolecular structures.10
available regarding their heightened capacity for binding
to Cu+ and Fe2+ ions.8 Complexation of the transition
metals occurs selectively on the “inside” portion of the
molecule, thereby generating “endoreceptor” character-
istics akin to the binding pocket of a protein.2 When the
lithium ion binds specifically to the inositol site, it
protrudes out from the ionophoric region, thus giving rise
to an “exoreceptor” arrangement.5-7 The two distinctive
regions of molecular association are interlinked by acety-
lenic or ether bridges.
Resu lts a n d Discu ssion
The synthesis of 3-6 was achieved by two reaction
types. Initial attempts at effecting the Sonagashira coup-
ling of the previously reported alkyne 76 with the dibro-
mides 811 and 912 were uniformly unsuccessful at first.
Since parallel palladium-catalyzed reactions13 involving
phenylacetylene proceeded smoothly (see below), the
major complication was obviously derived from 7. Ulti-
mately, the Vasella protocol,14 which involves the co-
addition of triphenylphosphine, triethylamine, copper(I)
iodide, and the dichloropalladium bistriphenylphosphine
complex, gave indication of very modest levels of coupling
(Scheme 1). Further improvisation was necessary to
achieve reasonable yields of 3 and 5. These reactions
must be performed at reflux temperature under a septum-
capped condenser while blanketed with N2 and with total
exclusion of oxygen. Under these conditions, 9 is trans-
formed into 5 (22%) and the monosubstitution product
(47%). Alternative heating in a sealed tube resulted in
no conversion to product and limited recovery of 7.
Although both 7 and the dibromide of choice are essen-
tially insoluble in triethylamine, decomposition ensues
The present investigation provides a unique look into
heterometallic-specific binding under conditions where
(5) (a) Kocian, O.; Mortimer, R. J .; Beer, P. D. Tetrahedron Lett.
1990, 31, 5069. (b) Nabeshima, T.; Inaba, T.; Furukawa, N.; Hosoya,
T.; Yano, Y. Inorg. Chem. 1993, 32, 1407. (c) Kobuke, Y.; Sumida, Y.;
Hayashi, M.; Ogoshi, H. Angew. Chem., Int. Ed. Engl. 1991, 30, 1496.
(d) Nabeshima, T.; Inaba, T.; Furukawa, N. Tetrahedron Lett. 1987,
28, 6211. (e) Habata, Y.; Bradshaw, J . S.; Zhang, X. X.; Izatt, R. M. J .
Am. Chem. Soc. 1997, 119, 7145.
(6) (a) Tae, J .; Rogers, R. D.; Paquette, L. A. Org. Lett. 2000, 2, 139.
(b) Paquette, L. A.; Tae, J .; Gallucci, J . C. Org. Lett. 2000, 2, 143. (c)
Paquette, L A.; Tae, J . J . Am. Chem. Soc. 2001, 123, 4974.
(7) Paquette, L. A.; Ra, C. S.; Gallucci, J . C.; Kang, H.-J .; Ohmori,
N.; Arrington, M. P.; David, W.; Brodbelt, J . S. J . Org. Chem. 2001,
66, 8629.
(8) (a) Constable, E. C. Adv. Inorg. Chem. 1989, 34, 1. (b) Sleiman,
H.; Baxter, P.; Lehn, J .-M.; Rissanen, K. J . Chem. Soc., Chem.
Commun. 1995, 715. (c) Harriman, A.; Ziessel, R.; Moutet, J .-C.; Saint-
Amon, E. Phys. Chem. Chem. Phys. 2003, 5, 1593.
(9) (a) Pfeil, A.; Lehn, J . M. J . Chem. Soc., Chem. Commun. 1992,
838. (b) Kobuke, Y.; Satoh, Y. J . Am. Chem. Soc. 1992, 114, 789.
J . Org. Chem, Vol. 69, No. 10, 2004 3263

Hilmey and Paquette
F IGURE 1. Titration curves for 11, 13, and 14 as monitored by UV-vis spectroscopy.
if a cosolvent such as acetonitrile or dimethylformamide
is added. Finally, during the course of the aqueous work-
up, it is imperative that potassium cyanide be introduced
to free the product from its complex with cuprous ion.
Nucleophilic aromatic substitution involving the same
pair of dibromides and the potassium alkoxide of carbinol
106 gave 4 and 6 (Scheme 2). The use of Li+ as a
counterion was avoided so as to skirt complexation of the
spiro ether oxygens and loss of product upon aqueous
workup. Despite these precautions, the yields of 4 and 6
approximated only 30%. No means for enhancing the
efficiency of these conversions was found.
For this reason, simpler prototypes were also secured for
use in probing the site selectivity behavior of those metal
ions selected for investigation. Although we viewed as
intuitive the fact that lithium ions would exhibit little
or no tendency to bind to the available bipyridine or
terpyridine endoreceptor subunits, examples of such
binding to bipyridines accompanied by large shifts in the
UV-vis spectrum have been reported.15 Consequently,
(10) Romero, F. M.; Ziessel, R.; Dupont-Gervais, A.; Dorsselaer, A.
V. J . Chem. Soc., Chem. Commun. 1996, 551.
(11) Parks, J . E.; Wagner, B. E.; Holm, R. H. J . Organomet. Chem.
1973, 56, 53.
(12) Constable, E. C.; Lewis, J . Polyhedron 1982, 1, 303.
(13) Ziessel, R. J . Org. Chem. 1996, 61, 6535.
Although the four targeted compounds were now in
hand, each was available only in milligram quantities.
3264 J . Org. Chem., Vol. 69, No. 10, 2004

Exo- and Endo-Receptors in One
F IGURE 2. Titration curves for 3, 5, and 6 as monitored by UV-vis spectroscopy.
CHART 1
the phenylated analogues 11-14 (Chart 1) were prepared
and subjected to binding studies with LiClO4, CuCl, and
FeCl2. Arrival at 1116 and 12 was likewise realized by
Sonagashira coupling; however, it was not necessary to
apply stringently controlled experimental conditions in
these cases. This fact and the higher yields observed (75-
85%) lend credence to the working principle that the spiro
ether triad is a root cause of our difficulties. The acquisi-
tion of 13 and 14 was also met with enhanced yields
(70%).
In a series of titration experiments, solutions of the
Li+, Fe2+, and Cu+ salts were added in 0.25, 0.50, and
1.0 equiv amounts to solutions of 11-14 in 1:1 CH3CN/
CHCl3. The response of each ligand to such treatment
was monitored by UV-vis spectroscopy as shown in
Figure 1. The presence of LiClO4 clearly has no effect,
and no coordinative interaction develops. In contrast, the
progressive addition of a copper(I) or iron(II) salt induces
(14) Burli, R.; Vasella, A. Helv. Chim. Acta 1999, 82, 485.
(15) Ogawa, S.; Uchida, T.; Uchiya, T.; Hirano, T.; Saburi, M.;
Uchida, Y. J . Chem. Soc., Perkin Trans. 1 1990, 1649.
(16) Butler, I. R.; Soucy-Breau, C. Can. J . Chem. 1991, 69, 1117.
J . Org. Chem, Vol. 69, No. 10, 2004 3265

Hilmey and Paquette
SCHEME 3
appreciable absorption shifts toward the visible region
in at least three of the examples. The generation of 15-
17 is presumably responsible for these phenomena, as
confirmed by electrospray mass spectral analysis of the
solids obtained following introduction of 0.5 equiv of the
transition metal salt (Scheme 3). The results recorded
for 12 are regarded to be inconclusive. Extensive efforts
to record 1H NMR spectra for 15-17 were to no avail
because of substantial line broadening.
Following upon these calibration experiments, ligands
3, 5, and 6 were examined for their binding preferences
(Figure 2). Particularly notable was the response of 3 and
5 to the presence of CuCl (0.5 equiv). Confirmation that
conversion to 18 and 19 had materialized was again
derived from spectroscopic and mass spectral measure-
ments. While the complexation of terpyridine 6 to FeCl2
(0.5 equiv) was met with the same reactivity pattern to
give 20, the response of bipyridine 4 was less definitive
and therefore probed no further (Scheme 4).
first step was accompanied with the customary color
change from water-white to red-orange. The second stage
induced the slow precipitation of a gelatinous-like mate-
rial from the 1:1 CH3CN/CHCl3 medium, which ulti-
mately gave rise to a pale orange-brown solid in quan-
titative yield following solvent evaporation. No phenomeno-
logical differences were noted if the proportion of LiClO4
was increased to 2.0 equiv. The sequence in which the
metal ions were introduced was reversed for 5. Im-
mediately following admixture with 0.5 equiv of LiClO4,
a comparable level of CuCl was introduced. In this
instance, colloid formation was initially observed with
concomitant orange coloration. However, after solvent
removal under reduced pressure, an orange solid again
resulted (100%). As expected, both end products proved
to be highly insoluble in a variety of solvents, thus
precluding their more definitive characterization by mass
spectral methods (particularly MALDI).
These results correlate well with the generation of dis-
persed oligomeric supramolecular structures under these
circumstances. There are no options other than ligation
of the Cu+ ions in endo receptor fashion to the bi- and
terpyridine nitrogen atoms with concurrent strong coordin-
ation of the lithium ions to the spirocyclic oxygen triads.
The exo receptor quality of the binding to this alkali
metal ion, as rigorously demonstrated in a number of
We next addressed the admixture of 3-6 with 0.5 equiv
of LiClO4 in the same solvent system. The solids produced
from these experiments were identified as 21-24 by
electrospray mass spectroscopy (Chart 2). In light of these
observations, double-complexation experiments were per-
formed with 3 and 5. In the first instance, 0.5 equiv of
CuCl was added in advance of 1.0 equiv of LiClO4. The
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Exo- and Endo-Receptors in One
SCHEME 4
triethylamine (0.4 mL) and deoxygenated. Alkyne 7 (40 mg,
0.12 mmol) was introduced, and heating at the reflux tempera-
ture under an attached condenser with N2 blanketing was
maintained for 48 h. After cooling, the solvent was evaporated
and the residue was chromatographed on silica gel. Elution with
5% methanol in CH2Cl2 afforded a small amount of 3. Passage
of aqueous KCN solution (Caution!) through the column freed
the remainder of 3, which was isolated upon resumption of the
chromatography. A total of 30 mg (64%) of 3 was isolated as a
white solid: mp > 270 °C; IR (neat, cm-1) 2950, 2875, 1062;
1H NMR (500 MHz, CDCl3) δ 8.52 (d, J ) 7.0 Hz, 2 H), 7.83 (t,
simpler prototypes, is considered to be operative here as
well. In keeping with these trends, the resulting polymers
are viewed to result from multiple heterocationic binding
in dissimilar regions of the same molecule. Since chain
length is not a controllable option, the materials generated
here are necessarily nonhomogeneous in molecular weight.
Exp er im en ta l Section
Bip yr id in e 3. A mixture of dibromide 8 (17.8 mg, 0.057
mmol), PdCl2(PPh3)2 (2.4 mg, 3 mol %), CuI (3 mg, 14 mol %),
and triphenylphosphine (2.4 mg, 8 mol %) was treated with
J . Org. Chem, Vol. 69, No. 10, 2004 3267

Hilmey and Paquette
CHART 2
J ) 7.8 Hz, 2 H), 7.56 (d, J ) 7.8 Hz, 2 H), 4.01 (t, J ) 6.8 Hz,
12 H), 3.72 (s, 6 H), 2.41 (t, J ) 7.8 Hz, 12 H), 1.95 (quintet,
J ) 7.3 Hz, 12 H); 13C NMR (125 MHz, CDCl3) δ 156.1, 140.9,
137.4, 128.6, 122.3, 103.1, 81.6, 81.0, 80.1, 78.0, 70.1, 37.0, 24.4;
ES HRMS m/z (M + Na)+ calcd 843.3099, obsd 843.3124.
Ter p yr id in e 5. A mixture of dibromide 9 (28 mg, 0.060
mmol), PdCl2(PPh3)2 (2.4 mg, 3 mol %), CuI (3 mg, 14 mol %),
and triphenylphosphine (2.4 mg, 8 mol %) was treated with
triethylamine (0.4 mL) and deoxygenated. Alkyne 7 (40 mg,
0.12 mmol) was introduced and heating at the reflux temper-
ature under an attached septum-capped condenser with N2
blanketing was maintained for 48 h. After cooling, the above
workup was applied to provide 13 mg (22%) of 5 alongside 20
mg (47%) of the monosubstitution product.
For 5: white solid; mp 207-210 °C; IR (neat, cm-1) 2940,
1
1340, 1065; H NMR (500 MHz, CDCl3) δ 8.78 (s, 2 H), 8.63
3268 J . Org. Chem., Vol. 69, No. 10, 2004

Exo- and Endo-Receptors in One
(d, J ) 8.0 Hz, 2 H), 7.90 (d, J ) 7.8 Hz, 2 H), 7.84 (t, J ) 7.8
Hz, 2 H), 7.58 (m, 5 H), 4.00 (t, J ) 6.8 Hz, 12 H), 3.70 (s, 6
H), 2.42 (t, J ) 7.4 Hz, 12 H), 1.93 (quintet, J ) 7.0 Hz, 12 H);
13C NMR (125 MHz, CDCl3) δ 156.6, 154.9, 150.8, 142.0, 136.9,
129.1, 128.9, 128.1, 127.6, 126.2, 121.6, 120.0, 102.7, 81.2, 80.7,
79.7, 77.5, 69.7, 36.6, 24.0; ES HRMS m/z (M + Na)+ calcd
996.3678, obsd 996.3604.
Bip yr id in e 4. A solution of 10 (40 mg, 0.12 mmol) in dry
THF (2 mL) was treated at rt with potassium hexamethyldisila-
zide (0.25 mL of 0.5 M in toluene). After 10 min, dibromide 8
(19 mg, 0.06 mmol) was introduced, and the reaction mixture
was refluxed overnight, cooled, quenched with water, and ex-
tracted with CH2Cl2 (5×). The volume of the combined organic
phases was reduced to the 10% level by evaporation under
reduced pressure, and the residue was chromatographed on
silica gel (elution with 5% methanol in CH2Cl2) followed by
recrystallization from CH2Cl2 gave 4 as a white solid: mp >
270 °C (15 mg, 30%); IR (neat, cm-1) 2946, 1072; 1H NMR (500
MHz, CDCl3) δ 7.98 (d, J ) 7.4 Hz, 2 H), 7.67 (t, J ) 7.8 Hz,
2 H), 6.84 (d, J ) 8.1 Hz, 2 H), 4.45 (s, 4 H), 4.00 (t, J ) 6.9
Hz, 12 H), 3.65 (s, 6 H), 2.35 (t, J ) 7.3 Hz, 12 H), 1.91 (quintet,
J ) 7.5 Hz, 12 H); 13C NMR (125 MHz, CDCl3) δ 162.2, 152.9,
139.3, 114.2, 111.4, 107.0, 80.0, 76.3, 69.6, 66.2, 36.3, 23.9; ES
HRMS m/z (M + Na)+ calcd 855.3311, obsd 855.3271.
CH2Cl2, and the combined organic phases were dried and
evaporated. The residue was chromatographed on silica gel
(elution with 1:1 CH2Cl2/hexanes) to furnish 0.17 g (72%) of
13 as a white solid: mp 174-175 °C; IR (neat, cm-1) 1574,
1
1435; H NMR (300 MHz, CDCl3) δ 8.02 (d, J ) 7.3 Hz, 2 H),
7.72 (t, J ) 7.5 Hz, 2 H), 7.53 (d, J ) 6.8 Hz, 4 H), 7.39 (m, 6
H), 6.82 (d, J ) 8.2 Hz, 2 H), 5.53 (s, 4 H); 13C NMR (75 MHz,
CDCl3) δ 162.8, 153.3, 139.4, 137.6, 128.5, 128.1, 127.8, 113.9,
111.3, 67.4; ES HRMS m/z (M + Na)+ calcd 391.1417, obsd
391.1418.
Ter p yr id in e 14. Reaction of 9 (0.20 g, 0.43 mmol) with
benzyl alcohol (0.18 mL, 1.7 mmol) according to the pre-
described protocol resulted in the isolation of 0.11 g (50%) of
14 as a white solid: mp 158-159 °C; IR (neat, cm-1) 3064,
1
1582, 1266; H NMR (300 MHz, CDCl3) δ 8.58 (s, 2 H), 8.27
(d, J ) 7.5 Hz, 2 H), 7.79 (m, 4 H), 7.55 (m, 7 H), 7.39 (m, 6
H), 6.88 (d, J ) 8.2 Hz, 2 H), 5.56 (s, 4 H); 13C NMR (75 MHz,
CDCl3) δ 162.9, 155.8, 153,6, 150.0, 141.0, 139.5, 137.8, 129.1,
129.0, 128.5, 128.0, 127.8, 127.3, 118.8, 114.3, 111.6, 67.7; ES
HRMS m/z (M + Na)+ calcd 544.1995, obsd 544.2013.
Gen er a l P r oced u r e for Com p lexa tion Exp er im en ts
In volvin g 11, 13, or 14 w ith Cu Cl or F eCl2. Approximately
1.0 mg of the ligand was dissolved in ∼0.5 mL of a 1:1 mixture
of CH3CN and CHCl3. To this solution was added the proper
quantity of a 0.04 or 0.08 M solution of CuCl in the same
solvent system or of FeCl2 in methanol. After the addition, the
red or yellow solutions were evaporated in a stream of N2 to
furnish the complex in quantitative yield.
Ter p yr id in e 6. Reaction of 10 (50 mg, 0.15 mmol) in dry
THF (2.5 mL) sequentially with potassium hexamethyldisi-
lazide (0.30 mL of 0.5 M in toluene) and dibromide 9 (34.4
mg, 0.073 mmol) in a manner paralleling that described above
furnished 21 mg (30%) of 6 as a white solid: mp 191-193 °C;
For 15: orange solid; ES HRMS m/z (M+) calcd 775.2017,
obsd 775. 2015.
1
IR (neat, cm-1) 2944, 2874, 1581, 1074; H NMR (500 MHz,
For 16: pale orange solid; ES HRMS m/z (M+) calcd
1081.3174, obsd 1081.3180.
CDCl3) δ 8.60 (s, 2 H), 8.32 (d, J ) 7.4 Hz, 2 H), 7.85 (d, J )
7.2 Hz, 2 H), 7.80 (t, J ) 7.9 Hz, 2 H), 7.60 (t, J ) 7.2 Hz, 2
H), 7.53 (t, J ) 7.4 Hz, 1 H), 6.94 (d, J ) 8.1 Hz, 2 H), 4.56 (s,
4 H), 4.01 (t, J ) 6.4 Hz, 12 H), 3.67 (s, 6 H), 2.37 (t, J ) 7.4
Hz, 12 H), 1.91 (quintet, J ) 7.4 Hz, 12 H); 13C NMR (125
MHz, CDCl3) δ 162.9, 156.0, 153.8, 150.9, 139.9, 139.8, 129.5,
129.2, 127.9, 119.4, 115.2, 112.1, 107.6, 80.4, 76.8, 70.0, 66.5,
36.7, 24.4; ES HRMS m/z (M + Na)+ calcd 1008.3889, obsd
1008.3842.
For 17: red solid; ES HRMS m/z (M+2/2) calcd 549.1772,
obsd 549.1778.
Gen er a l P r oced u r e for Com p lexa tion Exp er im en ts
In volvin g 3, 5, a n d 6 w ith Cu Cl or F eCl2. Approximately
1.0 mg of the ligand was dissolved in ∼0.5 mL of a 1:1 mixture
of CH3CN and CHCl3. To this was added the proper µL
quantity of a 0.04 or 0.08 M CuCl in the same solvent system
or of FeCl2 in methanol. Subsequently, the red or yellow
solutions were freed of solvent under a stream of N2 to give
the complex in quantitative yield.
Bip yr id in e 11. To a mixture of 8 (0.25 g, 0.80 mmol), CuI
(18 mg, 12 mol %), and PdCl2(PPh3)2 (37 mg, 6 mol %) was
added triethylamine (10 mL) under N2. Phenylacetylene (0.18
mL, 1.67 mmol) was introduced dropwise, and overnight
stirring was maintained prior to quenching with water. The
aqueous layer was extracted with CH2Cl2, and the combined
organic phases were dried and concentrated. The residue was
chromatographed on silica gel (elution with 1:1 CH2Cl2/
hexanes) to provide 210 mg (74%) of 11 as a white solid: mp
194-195 °C (lit.16 mp 195.8-196.2 °C); IR (neat, cm-1) 2357,
For 18: orange solid; ES HRMS m/z (M+) calcd 1704.5839,
obsd 1704.5736.
For 19: orange solid; ES HRMS m/z (M+) calcd 2010.6996,
obsd 2010.7003.
For 20: red solid; ES HRMS m/z (M+2/2) calcd 1013.8683,
obsd 1013.8723.
Gen er a l P r oced u r e for Recor d in g UV-vis Absor p tion
Cu r ves. A specific weight of 1-5 mg of the ligand was
dissolved in 1:1 CH2CN/CHCl3 (1-5 mL). These solutions were
scanned in the region from 190 to 890 nm. These solutions
were individually treated with 0.25, 0.50, and 1.0 equiv of
LiClO4, CuCl, or FeCl2 solutions defined above. Scanning was
repeated at every stage.
Gen er a l P r oced u r e for Com p lexa tion Exp er im en ts
In volvin g 3-6 w ith LiClO4. Approximately 1.0 mg of ligands
3-6 was dissolved in ∼0.5 mL of a 1:1 mixture of CH3CN and
CHCl3. To each solution was added the proper microliter
quantity of 0.235 or 0.176 M LiClO4 in the same solvent
system. After the addition, either the solid that precipitates
or the resulting solution was freed of solvent under a stream
of N2 to provide the complex in quantitative yield.
For 21: obtained from 3 as a white solid that precipitates
immediately; ES HRMS m/z for C92H96LiN4O24+ calcd 1648.6603,
obsd 1648.6749.
1
1567; H NMR (300 MHz, CDCl3) δ 8.48 (d, J ) 7.9 Hz, 2 H),
7.81 (t, J ) 7.8 Hz, 2 H), 7.64 (m, 4 H), 7.56 (d, J ) 7.7 Hz, 2
H), 7.39 (m, 6 H); 13C NMR (75 MHz, CDCl3) δ 155.9, 142.8,
137.1, 132.0, 128.9, 128.3, 127.5, 122.3, 120.8, 89.0, 88.9.
Ter p yr id in e 12. To a mixture of 9 (0.25 g, 0.54 mmol), CuI
(12 mg, 12 mol %), and PdCl2(PPh3)2 (23 mg, 6 mol %) was
added triethylamine (10 mL) under N2. After the dropwise
introduction of phenylacetylene (0.29 mL, 2.6 mmol), the
reaction mixture was processed in the above manner to give
190 mg (70%) of 12 as a white solid: mp 219-220 °C; IR (neat,
1
cm-1) 3060, 2360, 1575, 1400; H NMR (300 MHz, CDCl3) δ
8.82 (s, 2 H), 8.62 (d, J ) 7.9 Hz, 2 H), 7.93 (d, J ) 7.1 Hz, 2
H), 7.87 (t, J ) 7.8 Hz, 2 H), 7.67 (m, 4 H), 7.59 (d, J ) 7.4 Hz,
2 H), 7.45 (m, 3 H), 7.39 (m, 6 H); 13C NMR (75 MHz, CDCl3)
δ 156.7, 155.0, 150.7, 146.9, 142.8, 138.1, 137.0, 132.1, 129.0,
128.9, 128.4, 127.5, 127.4, 122.4, 120.6, 119.7, 89.1, 89.0; ES
HRMS m/z (M + Na)+ calcd 532.1784, obsd 532.1782.
For 22: obtained as a white solid after solvent evaporation;
ES HRMS m/z for C114H110LiN6O24Na+2 calcd 988.8826, obsd
988.8888.
For 23: obtained as a white solid after solvent evaporation;
ES HRMS m/z for C88H104LiN4O28Na+2 calcd 847.3442, obsd
847.3429.
Bip yr id in e 13. A cold (0 °C) solution of 8 (0.20 g, 0.64
mmol) in dry THF (15 mL) was treated with potassium
hexamethyldisilazide (5.1 mL of 0.5 M in toluene) and stirred
for 20 min prior to the introduction of benzyl alcohol (0.26 mL,
2.55 mmol). The reaction mixture was heated to reflux for 3 h
and quenched with water. The product was extracted into
J . Org. Chem, Vol. 69, No. 10, 2004 3269

Hilmey and Paquette
For 24: obtained as a white solid after solvent evaporation;
ES HRMS m/z for C110H118LiN6O28Na+2 calcd 1000.9037, obsd
1000.9046.
equiv of LiClO4 from a 0.176 M solution in the same solvent.
Immediately thereafter, 0.5 equiv of CuCl from a 0.0535 M
solution of 1:1 CH3CN/CHCl3 was introduced. No precipitation
was evident. However, subsequent solvent removal gave rise
in quantitative yield to an orange solid that proved totally
insoluble in all solvents examined.
Dou b le Com p lexa t ion E xp er im en t s. A. In volvin g
Liga n d 3. To a solution of 3 (1.0 mg, 1.2 µmol) in 1:1 CH3CN/
CHCl3 (0.5 mL) was added a solution of CuCl in the same
solvent system (9.3 µL of 0.0652 M). Following the color change
to orange, 1.0 equiv of LiClO4 (3.5 µL of 0.176 M in the same
solvent) was introduced. The precipitation of a gelatinous-like
material ensued. Solvent evaporation gave in quantitative
yield a light orange solid that proved totally insoluble in all
solvents examined.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR and 13C NMR spectra of compounds 3-6 and 12-14.
This material is available free of charge via the Internet at
http://pubs.acs.org.
B. In volvin g Liga n d 5. To a solution of 5 (1.0 mg, 1.03
µmol) in 0.5 mL of 1:1 CH3CN/CHCl3 was added 0.5 molar
J O030373T
3270 J . Org. Chem., Vol. 69, No. 10, 2004