Synthesis of dicarboxylate "C-clamp" 1,2-diethynylarene compounds as potential transition-metal ion hosts

Article abstract of DOI:10.1002/ejoc.200700816

We report an efficient convergent synthesis of a new type of C-clamp ligand with a 1,2-diethynylarene scaffold involving a chelate host capable of binding a guest molecule in its endo-dicarboxylate pocket. The chemistry involves a combination of palladium-catalyzed Sonogashira, Heck, and Suzuki cross-coupling reactions. The compounds 2,3-bis[2-(2′-carboxybiphenyl-4-yl)ethynyl] triptycene and 4,5-bis[2-(2′-carboxybiphenyl-4-yl)ethynyl]veratrole and their 2′-carboxy-m-terphenyl-4-yl analogues were designed as dinucleating ligands to assemble carboxylate-bridged transition-metal complexes with a windmill geometry. The X-ray crystal structure of one such C-clamp compound containing co-crystallized water molecules reveals strong hydrogen bonds of the aqua guest to the endo-oriented carboxylic acid entities of the C-clamp host. In addition, two syn-N-donor ligands were prepared as a synthetic scaffold to mimic the geometric arrangement of N-donor atoms in carboxylate-bridged dinuclear proteins. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200700816

FULL PAPER
DOI: 10.1002/ejoc.200700816
Synthesis of Dicarboxylate “C-Clamp” 1,2-Diethynylarene Compounds as
Potential Transition-Metal Ion Hosts
Erwin Reisner[a] and Stephen J. Lippard*[a]
Keywords: Cross-coupling / C–C coupling / Carboxylate ligands / Bridging ligands / Chelates
We report an efficient convergent synthesis of a new type of
C-clamp ligand with a 1,2-diethynylarene scaffold involving
a chelate host capable of binding a guest molecule in its
endo-dicarboxylate pocket. The chemistry involves a combi-
metal complexes with a windmill geometry. The X-ray crystal
structure of one such C-clamp compound containing co-crys-
tallized water molecules reveals strong hydrogen bonds of
the aqua guest to the endo-oriented carboxylic acid entities
nation of palladium-catalyzed Sonogashira, Heck, and Su- of the C-clamp host. In addition, two syn-N-donor ligands
zuki cross-coupling reactions. The compounds 2,3-bis[2-(2Ј-
carboxybiphenyl-4-yl)ethynyl]triptycene and 4,5-bis[2-(2Ј-
carboxybiphenyl-4-yl)ethynyl]veratrole and their 2Ј-carb-
oxy-m-terphenyl-4-yl analogues were designed as dinucle-
ating ligands to assemble carboxylate-bridged transition-
were prepared as a synthetic scaffold to mimic the geometric
arrangement of N-donor atoms in carboxylate-bridged dinu-
clear proteins.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
Methane monooxygenase, a member of the bacterial
multicomponent monooxygenase (BMM) family, catalyzes
the selective oxidation of methane to methanol under ambi-
ent conditions in methanotrophic bacteria.[1] The active site
of the hydroxylase component (MMOH, Figure 1) of solu-
ble methane monooxygenase (sMMO) is embedded in a
four-helix bundle that creates a hydrophobic protein envi-
ronment for O2 activation at a reduced diiron(II) site. Con-
version to a high-valent diiron(IV) intermediate leads to se-
lective oxidation of methane to methanol. The active site
features a non-heme diiron center coordinated by four glu-
tamate and two histidine residues, which coordinate in a
syn disposition with respect to the Fe–Fe axis.[1] Other car-
boxylate-rich diiron enzymes like the stearoyl-acyl carrier
protein ∆9-desaturase and ribonucleotide reductase R2
(RNR-R2, Figure 1) have a similar active site composition
and are responsible for fatty acid desaturation and tyrosyl
radical generation, respectively.[2]
Figure 1. The reduced diiron(II) MMOH (left) and RNR-R2 (cen-
ter) cores and a diiron(II) model complex [Fe2(Et2BCQEBEt)(µ-
O2CArTol)3]+ (right) displaying the N-donors in a syn disposition
with respect to the iron–iron vector. The location of the atoms is
based on X-ray coordinates. The ethyl moieties on the phenyl ring,
and the aromatic carbon atoms of the –O2CArTol ligands (except
the α-carbon atoms) are omitted for clarity in the model com-
pound.
bridges.[5] Coordination of amino or pyridyl N-donor atoms
to such complexes affords diiron complexes that recapitu-
late several salient features of MMOH. For example, these
complexes contain four carboxylate ligands and N-donors
and form reactive intermediates upon exposure to di-
oxygen[6] that display high oxygenation rates[7] and can ox-
idize hydrocarbons,[8] thioethers,[4,9] and phosphanes,[9,10]
particularly when the substrates are held in close proximity
to the diiron core.
However, the current BMM model complexes have sev-
eral limitations, and efforts to prepare biomimetic oxidation
catalysts continue an active area of research. A key con-
sideration for developing functional BMM analogues is to
design a synthetic platform that can stabilize high-valent
(oxido)diiron species. In MMOH, the active oxidant is an
oxido-bridged diiron(IV) unit, which cleaves the C–H bond
To model the structural features of these enzymes, sym-
metric and asymmetric carboxylate ligands, such as 2,6-
bis(p-tolyl)benzoate (–O2CArTol), 2,6-dimesitylbenzoate,
3,5-dimethyl-1,1Ј:3Ј,1ЈЈ-terphenyl-2Ј-carboxylate, and 2-
phenylbenzoate, have been employed.[3,4] These sterically
hindered carboxylates facilitate the isolation of diiron(II)
complexes with double, triple, and quadruple carboxylate
[a] Department of Chemistry, Massachusetts Institute of Technol-
ogy, 18-498,
77 Massachusetts Avenue, Cambridge, Massachusetts 02139,
USA
Fax: +1-617-258-8150
E-mail: lippard@mit.edu
156
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1,2-Diethynylarene Compounds as Potential Transition Metal Ion Hosts
in methane and transfers an oxygen atom from the diiron
core to the substrate to form methanol. DFT calculations
suggest that formation of the diiron(IV) intermediate is fa-
vored when the imidazole ligands of the MMOH active site
are arranged in a syn disposition with respect to the Fe–Fe
vector.[11] In order to mimic more closely the position of the
N-donors in the native enzyme, several dinucleating ligands
containing adjacent N-binding groups were prepared.[12]
These syn-N-donor ligands have enabled the synthesis of
diiron complexes, such as [Fe2(Et2BCQEBEt)(µ-O2CArTol)3]-
(OTf), where Et2BCQEBEt is 1,2-bis{2-[8-(ethoxycarbonyl)-
quinol-3-yl]ethynyl}-4,5-diethylbenzene (Figure 1).[13]
Another consideration in designing synthetic model com-
plexes for diiron enzymes is to provide a scaffold that will
allow for selective binding and activation of external hydro-
carbon substrates. In the native BMM enzymes, several
hydrophobic cavities delineate a pathway from the protein
exterior to the active-site pocket.[15] In order to incorporate
such hydrophobic cavities in a synthetic system, we follow
the strategy of preparing a diiron complex with a two-com-
ponent ligand system. In addition to a syn-N-donor, which
holds the two N-donors in the preferred orientation, a C-
clamp ligand with two endo-oriented dicarboxylate groups
should enforce a doubly bridging motif and allow for sub-
strate access to the diiron core (Figure 2). Molecular re-
cognition and substrate access play pivotal roles for selec-
tive activation of C–H bonds.[16] Here we report the prepa-
ration of syn-N-donor and dinucleating C-clamp ligands for
use in constructing the desired doubly bridged motif. The
synthesis of the latter compounds was achieved through
cross-coupling reactions of a series of suitable and preorga-
nized endo-dicarboxylate compounds with 2,3-diethynyl-
triptycene or 4,5-diethynylveratrole backbones. A retrosyn-
thetic route is depicted in Scheme 1. The preparation of two
new syn-N-donor compounds, according to established
methods,[12] is also described.
Scheme 1. Synthetic route to C-clamp ligands; R = H or Ph and
RЈ2C6H2 = triptycene or veratrole backbone.
Results and Discussion
Structural drawings of the C-clamp and syn-N-donor
molecules are depicted in Figure 3, and the synthetic path
used to construct the former is presented in Scheme 2. The
4,5-diethynylveratrole (DEV) linker (1) was prepared in a
manner analogous to that described for 2,3-diethynyl-
triptycene (DET).[12] Dual Sonogashira coupling of 4,5-di-
bromoveratrole with (trimethylsilyl)acetylene and [Pd-
(PPh4)4]/CuI (2.5 mol-% per coupling) in piperidine at ele-
vated temperature gave the cross-coupled product. Upon
desilylation with K2CO3 in MeOH, 1 was obtained in 67%
overall yield. DEV has two significant advantages over
DET: (i) the starting material 4,5-dibromoveratrole is com-
mercially available in large quantities, whereas 2,3-dibro-
motriptycene is prepared from 1,2,4,5-tetrabromobenzene
and anthracene (2.2 equiv.) in the presence of 1 equiv. of
nBuLi in 62% yield;[17] (ii) C-clamp and syn-N-donor com-
pounds with DEV backbones show improved solubility in
organic solvents such CH2Cl2 and THF, which are com-
monly used for complexation reactions with transition-
metal ions.
Figure 2. The energy-minimized structure[14] of [Fe2{DEV-
(PICMe)2}{DEV(terphCO2)2}] displaying the substrate-access cav- Figure 3. Graphic representation of the C-clamp (4–7) and syn-N-
ity (top) and the exposed diiron center (bottom). donor (8 and 9) ligands.
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E. Reisner, S. J. Lippard
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Scheme 2. Synthetic pathway to diethynylbenzene-based C-clamp ligands; RЈ2C6H2 = triptycene or veratrole backbone. (a) 2 steps, 1:
[Pd(PPh3)4]/CuI, piperidine, 100 °C; 2: K2CO3, MeOH, ref.[12]; (b) [PdCl2(PPh3)2], 1  Na2CO3, THF, 60 °C; (c) [Pd(PPh3)4], Et3N, THF,
70 °C; (d) LiI, pyridine, 110 °C; (e) NaOH, MeOH, 60 °C; (f) NaOTMS, THF, 60 °C.
The aryl halide components for constructing the diethyn- Compounds 4c and 6c can also be prepared in almost quan-
ylbenzene scaffolds were prepared by Suzuki coupling of 4- titative yields directly from 4a and 6a with sodium trimeth-
bromophenylboronic acid with methyl 2-iodobenzoate and ylsilanolate in THF at 60 °C. The syn-N-donor ligands 8
methyl 3-iodobiphenyl-2-carboxylate with a [PdCl2(PPh3)2] and 9 were prepared in a manner similar to that previously
catalyst (5 mol-%) in a mixture of THF and 1  aqueous reported[12] for the compounds DET(PICMe)2 and
Na2CO3 at 50–60 °C to give 2 and 3 in 84 and 76% isolated DET(quinolineCO2Et)2 from methyl 5-bromo-2-picolinate
yields, respectively. A 1.5 equiv. portion of the boronic acid and ethyl 3-[(trifluoromethyl)sulfonyl]quinoline-8-carboxyl-
was used to convert the aryl iodide quantitatively into the ate upon cross-coupling with 1 in 93 and 80% yields,
cross-coupled product, because the product and the aryl io- respectively. The convergent synthetic strategy for the C-
dide are difficult to separate by column chromatography. clamp and syn-N-donor compounds with its satisfying
The Suzuki reaction occurred with remarkable selectivity, overall yields is an important advance that should facilitate
and no major side-products from further coupling of the future study of the coordination chemistry of this family of
boronic acid with the bromoaryl products 2 and 3 were ob- ligands.
served. The X-ray crystal structure of 3 is discussed below.
The solid-state structures of 3 and 4b were determined
A dual Heck alkynylation, i.e. copper-free Sonogashira by X-ray crystallography and are depicted in Figures 4 and
cross-coupling, between the arylalkyne DET or DEV (1) 5. The O(1)–C(1), O(1)–C(2), and O(2)–C(2) bond lengths
and the aryl bromide 2 or 3 with [Pd(PPh4)4] (5 mol-% per of 1.439(2), 1.345(2), and 1.197(2) Å, respectively, and the
coupling) in a mixture of Et3N and THF under warming Br(1)–C(18) distance of 1.892(2) Å in 3 are as expected.
resulted in the formation of C-clamp compounds 4a, 5, 6a Compound 4b crystallizes in the space group I41/a with one
and 7 in good isolated yields (Scheme 2). Compounds 4a half of a molecule in the asymmetric unit. Four water
and 6a were obtained in about 70%, but only modest yields and two methanol molecules co-crystallize per DEV-
(ca. 15%) were achieved for 5 and 7. We do currently not (biphCO2H)2 unit. Two solvent molecules are located be-
have an explanation for why the cross-coupling reaction tween the endo-oriented carboxylate ligands (Figure 5), re-
with 3 results in considerably lower yields than with 2, al- vealing that the C-clamp acid 4b crystallizes preferentially
though steric or conformational factors may play a role. in the desired pre-organized endo conformation, with the
Addition of CuI to the reaction mixture resulted in drasti- two water entities adopting the sites anticipated for poten-
cally reduced yields. An excess of LiI in pyridine in a pres- tial metal–guest binding. Both of these H2O molecules are
sure vessel under an inert gas at 120 °C resulted in saponifi- involved in strong hydrogen bonding with the carboxylate
cation of the C-clamp esters 4a and 6a to give 4b and 6b in oxygen atoms, with O(1)–O(1S) and O(2)–O(2S) distances
73 and 56% yields, respectively. The application of com- of 2.591(6) and 2.647(4) Å, respectively. The O(1)–
monly used bases for the ester hydrolysis, such as KOH or O(1S)–(O1A) and O(2)–O(2S)–(O2A) angles are 142.5(6)
NaOH, did not allow for isolation of the hydrolyzed ester. and 147.7(2)°, respectively, and the dihedral angle
Sodium salts 4c and 6c were isolated quantitatively by heat- ΘO(2)–O(1)–(O1A)–O(2A) is 57.6(3)°. Untwisting the two car-
ing the carboxylic acid in MeOH with 1 equiv. of NaOH. boxylate ligands by rotation around the Ccarboxylate–Cα axis
158
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1,2-Diethynylarene Compounds as Potential Transition Metal Ion Hosts
angles to Θ ≈ 0° results in considerably shorter Ocarboxylate
–
salt of 1,3-bis(aminomethyl)-4,6-diisopropylbenzene.[20] The
Ocarboxylate distances and shows that incorporation of two flexible 1,3-bis(aminomethyl)benzene linker, however, does
metal ions between two endo-oriented carboxylate ligands not allow for convergent preorganization of the carboxylate
would result in M–Ocarboxylate distances of ca. 2.0 Å, the functionalities because of steric repulsions involving the ter-
value required to bind 1st-row transition-metal ions.
phenyl arms, and polymerization can therefore be a major
problem following addition of transition-metal ions.
The non-macrocyclic C-clamp molecules 4–7 feature a
rigid diethynylbenzene linker that assures that both benzo-
ate moieties are oriented in the same direction, avoiding
trans orientation of the carboxylate entities. A hydrogen-
bonding network between the C-clamp acid 4b and guest
water molecules is capable of preorganizing, at least in the
solid state and most likely in solution, the two carboxylates
in an endo configuration. The design of 4–7 allows for a
–
well-positioned endo CO2 –CO2– pair having the proper dis-
tance to accommodate transition-metal guest ions. We are
particularly interested in synthesizing diiron complexes with
one syn-N-donor and one C-clamp ligand allowing for the
two N-donors in syn disposition, and bridging carboxylate
ligands containing an encumbered diiron center with a sub-
strate-access cavity. Molecular modeling studies indicate the
feasibility of preparing such compounds, and an energy-
minimized structure[14] of [Fe2(DEV(PICMe)2)(DEV-
(terphCO2)2)] is shown in Figure 2.
Figure 4. Molecular structure of 3. Thermal ellipsoids are drawn
at 50% probability level. Hydrogen atoms are omitted for clarity.
Conclusions
We have efficiently prepared a series of 1,2-diethynyl-
arene C-clamp and syn-N-donor compounds through
Sonogashira, Heck, and Suzuki palladium cross-coupling
reactions using a convergent synthetic strategy. The dieth-
ynylbenzene linkers DET and DEV orient the N-donor
moieties in a syn configuration, and the two carboxylate
groups of the C-clamp ligands can prevail in an endo orien-
tation when holding small guest molecules in its binding
pocket. Complexation reactions of C-clamp ligands with
transition-metal ions and the preparation of [Fe2(syn-N-do-
nor)(C-clamp)] compounds are underway in our laboratory.
The reported compounds should be of interest as hosts or
ligands for a wide variety of transition-metal ions.
Figure 5. Molecular structure of 4b and two co-crystallized water
molecules at 100% and 50% occupancy for O2S and O1S, respec-
tively, with strong hydrogen bonding (dotted line) between the car-
boxylic acid and the solvent. Thermal ellipsoids are drawn at the
50% probability level. Hydrogen atoms, exo-oriented disordered
carboxylic acid moieties at 33% occupancy, two water molecules
(both 25% occupancy), and two methanol solvent molecules (both
25% occupancy) are omitted for clarity.
Experimental Section
Dicarboxylate-containing molecules with the functional
groups in endo positions are difficult to prepare. The syn,
syn configuration can be achieved when using diphenyl di-
benzofuran-4,6-diylbis(acetate) (Ph4DBA)[18] or the more
rigid “m-xylylenediaminobis(Kemp’s triacid imide)” (XDK)
as a ligand.[19] For endo orientation of the dicarboxylate
groups, macrocycles often are employed.[20,21] Such macro-
cyclic oligocarboxylate compounds have been investigated
for host–guest chemistry because of their strong hydrogen
bonding and coordinative interactions with the guests.
Large chelate rings with sufficient rigidity to allow for pre-
organization are desired to achieve the endo configuration
without the need for a macrocycle. C-clamp ligands have
been prepared previously by reductive amination of 4-
General Considerations: All reagents were obtained from commer-
cial suppliers and used as received, unless otherwise noted. MP-
TMT (macroporous polystyrene-2,4,6-trimercaptotriazine) was ob-
tained from Argonaut Technologies. All cross-coupling reactions
were performed under an inert gas, which was maintained either
by bubbling argon through the solutions or by the freeze-pump-
thaw technique to degas the reaction solutions. 2,3-Diethynyltrip-
tycene[12] and methyl 3-iodobiphenyl-2-carboxylate[22] were pre-
pared as described previously. Compound 1 and the acid of 2 have
been reported previously, but the compounds have been prepared
by different synthetic routes.[23]
1
Physical Methods: H and 13C NMR spectra were measured with
a Varian 300 or 500 spectrometer at the Department of Chemistry
Instrumentation Facility (MIT DCIF). Chemical shifts were refer-
formyl-1,1Ј:3Ј,1ЈЈ-terphenyl-2Ј-carboxylate with the sodium enced to the residual solvent peaks. Melting points were measured
Eur. J. Org. Chem. 2008, 156–163
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159

E. Reisner, S. J. Lippard
FULL PAPER
with an electrothermal Mel-Temp melting-point apparatus. FTIR
spectra were recorded with a Thermo Nicolet Avatar 360 spectrom-
methane, 6:4) to give an off-white powder. Yield 4.05 g (67%). M.p.
122–123 °C. Rf = 0.36 (hexanes/CH2Cl2, 1:1). 1H NMR (300 MHz,
eter outfitted with OMNIC software. ESI-MS data were obtained CDCl3, 20 °C): δ = 6.96 (s, 2 H, HAr), 3.89 (s, 6 H, CH3), 3.28 (s,
with an Agilent 1100 Series LC/MSD mass spectrometer. Spartan
2 H, CϵCH) ppm. 13C NMR (500 MHz, CDCl3, 20 °C): δ = 149.5
04 was employed for molecular modeling.[24]
(MeOCAr), 118.2 (CAr), 114.8 (CAr), 82.2 (CϵC), 79.9 (CϵC), 56.2
(OCH ) ppm. FTIR (KBr): ν = 3277 (s), 3251 (s) [ν(CϵC–H)];
˜
3
X-ray Structure Determination: The X-ray structures of 3 and 4b
were obtained by mounting a single crystal covered in paratone-N
oil on a glass fiber or in a nylon loop cooled under a stream of N2
on a Bruker APEX CCD diffractometer with graphite-monochro-
mated Mo-Kα radiation (λ = 0.71073 Å), controlled by a Pentium-
based PC running the SMART software package.[25] The structures
were collected at 110 and 153 K for 3 and 4b, respectively, solved by
direct methods, and refined on F2 by using the SHELXTL software
package.[26] Empirical absorption corrections were applied with
SADABS,[27] and the structures were validated using the PLATON
software.[28] All non-hydrogen atoms were located and their posi-
tions refined with anisotropic thermal parameters. Hydrogen atoms
were placed at calculated positions and their thermal parameters
assigned as 1.2 times the thermal parameters of the atoms to which
they were attached. Hydrogen atoms were located on difference
Fourier maps for the endo-carboxylic acid protons and the two
water molecules in the C-clamp binding pocket. The MeOH hydro-
gen atom, the H atom of O(3), and the disordered carboxylic acid
proton at 33% occupancy of 4b were not refined. Compound 4b
crystallized with four water molecules, one at 100%, one at 50%,
and two at 25% occupancy, and two methanol molecules, both at
25% occupancy per C-clamp host. In addition, the carboxylic acid
moiety is disordered over two positions, refined in a 2:1 occupancy
ratio. CCDC-658787 (for 3) and -658788 (for 4b) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. 3:
C20H15BrO2, Mr = 367.23 g/mol, Pca21, Z = 4, a = 9.831(4), b =
20.866(9), c = 7.811(3) Å, V = 1602.2(12) Å3, ρcalcd. = 1.522 g/cm3,
size: 0.30ϫ0.25ϫ0.10 mm, total reflections: 23228, independent
reflections: 3936, parameters: 208, Rint = 0.041, completeness:
98.2%, Flack parameter: 0.0135(63), GOF = 1.021, R1 = 0.0238,
wR2 = 0.0565, largest diff. peak and hole: 0.537 and –0.215 Å–3.
4b: C50.5H35O6.5, Mr = 745.79 g/mol, I41/a, Z = 8, a = 12.3624(6),
b = 12.3624(6), c = 51.920(4), V = 7934.9(9) Å3, ρcalcd. = 1.249 g/
cm3, size: 0.35ϫ0.05ϫ0.05 mm, total reflections: 43048, indepen-
dent reflections: 2502, parameters: 317, Rint = 0.039, completeness:
99.9%, GOF = 1.090, R1 = 0.0684, wR2 = 0.1940, largest diff. peak
and hole: 0.356 and –0.344 Å–3.
2973
(m),
2938
(w),
2912
(w)
[ν(C–H)]
cm–1.
ESI-MS (MeOH/CH2Cl2, 2:1): calcd. for [M + Na]+ 209.1; found
208.9. C12H10O2 (186.21): calcd. C 77.40, H 5.41; found C 77.37,
H 5.23.
Methyl 4Ј-Bromobiphenyl-2-carboxylate, BrbiphCO2Me (2): 4-Bro-
mophenylboronic acid (5.00 g, 24.9 mmol) was added to methyl 2-
iodobenzoate (4.35 g, 16.6 mmol) in THF (60 mL) and 1  aque-
ous Na2CO3 (60 mL). The reaction mixture was deoxygenated by
bubbling argon through it with stirring for 30 min, whereupon
[PdCl2(PPh3)2] (0.540 g, 5 mol-%) was added. The reaction mixture
was heated to 60 °C, and the initial orange-red color turned yellow
after ca. 1 h. After 6 h, the dark reaction mixture was cooled to
room temperature. Water (200 mL) was added and the product ex-
tracted with CH2Cl2 (2ϫ150 mL). The combined organic phases
were dried with MgSO4, filtered, and concentrated to dryness. The
product was purified by column chromatography (SiO2; hexanes/
diethyl ether, 95:5) to give a colorless oil. Yield 4.05 g (84%). Rf =
1
0.35 (hexanes/Et2O, 95:5). H NMR (300 MHz, CDCl3, 20 °C): δ
= 7.86 (d, J = 7.5 Hz, 1 H, HAr), 7.53 (d, J = 8.4 Hz, 2 H, HAr),
7.58–7.50 (m, 1 H, HAr), 7.44 (t, J = 7.8 Hz, 1 H, HAr), 7.34 (d, J
= 7.8 Hz, 1 H, HAr), 7.19 (d, J = 8.4 Hz, 2 H, HAr), 3.68 (s, 3 H,
CH3) ppm. 13C NMR (300 MHz, CDCl3, 20 °C): δ = 168.8 (CO2),
141.6 (CAr), 140.5 (CAr), 131.7 (CAr), 131.3 (CAr), 130.8 (CAr),
130.6 (CAr), 130.24 (CAr), 130.17 (CAr), 127.7 (CAr), 121.7 (CAr),
52.2 (CH ) ppm. FTIR (KBr): ν = 3061 (w), 3023 (m), 2993 (w),
˜
3
2948 (m) [ν(C–H)]; 1728 (s) [ν(C=O)] cm–1. ESI-MS (MeOH):
calcd. for [M + Na]+ 313.0; found 312.9. C14H11BrO2 (291.14):
calcd. C 57.76, H 3.81; found C 57.87, H 3.55.
Methyl 4-Bromo-1,1Ј:3Ј,1ЈЈ-terphenyl-2Ј-carboxylate, BrterphCO2-
Me (3): 4-Bromophenylboronic acid (1.78 g, 8.86 mmol) was added
to methyl 3-iodobiphenyl-2-carboxylate (2.00 g, 5.91 mmol) in
THF (20 mL) and 1  aqueous Na2CO3 (15 mL). The reaction
mixture was deoxygenated by bubbling argon through it for 20 min,
after which [PdCl2(PPh3)2] (0.210 g, 5 mol-%) was added. The reac-
tion mixture was heated to 50 °C, and the brownish orange-red
emulsion turned yellow after ca. 1 h. After 6 h, the reaction mixture
was cooled to room temperature. Water (50 mL) was added and the
product extracted with CH2Cl2 (2ϫ50 mL). The combined organic
phases were dried with MgSO4, filtered, and concentrated to dry-
ness. The product was purified by column chromatography (SiO2;
hexanes/diethyl ether, 95:5) to give a white powder. Yield 1.65 g
(76%). M.p. 120–121 °C. Rf = 0.38 (hexanes/Et2O, 95:5). 1H NMR
(300 MHz, CD3OD, 20 °C): δ = 7.56–7.49 (m, 3 H, HAr), 7.40–7.20
(m, 9 H, HAr), 3.32 (s, 3 H, CH3) ppm. 13C NMR (500 MHz,
CDCl3, 20 °C): δ = 169.8 (CO2), 140.6 (CAr), 140.4 (CAr), 139.5
(CAr), 139.2 (CAr), 131.6 (CAr), 130.2 (CAr), 129.5 (CAr), 129.3
(CAr), 128.8 (CAr), 128.3 (CAr), 128.2 (CAr), 127.8 (CAr), 122.1
4,5-Diethynylveratrole (DEV) (1): 4,5-Dibromoveratrole (9.62 g,
32.4 mmol) and (trimethylsilyl)acetylene (15.1 mL, 109 mmol) were
dissolved in piperidine (50 mL), and the solution was deoxygenated
with argon for 40 min. Then [Pd(PPh3)4] (1.87 g, 5 mol-%) and CuI
(0.31 g, 5 mol-%) were added, and the reaction mixture was deoxy-
genated for an additional 10 min. The yellow solution was heated
at 100 °C; after ca. 0.5 h, a dark solution and a precipitate formed.
The next day, the reaction mixture was cooled to room tempera-
ture, poured into H2O (200 mL), and extracted with CH2Cl2
(200 mL). The organic phase was washed with aqueous NH4Cl
(200 mL) and water (200 mL), dried with MgSO4, filtered, and the
solvents were evaporated to dryness. To the crude silylated product
[1H NMR (CDCl3, 20 °C): δ = 6.92 (s, 2 H), 3.89 (s, 6 H), 0.28 (s,
18 H) ppm] was added K2CO3 (12.6 g, 91 mmol) and MeOH
(150 mL), and the suspension was stirred for 3 h. The reaction mix-
ture was then concentrated to dryness, extracted with CH2Cl2
(150 mL), the extract washed with aq. NH4Cl (2ϫ150 mL), dried
with MgSO4, filtered, and concentrated to dryness. The product
was purified by column chromatography (SiO2; hexanes/dichloro-
(CAr), 52.0 (CH ) ppm. FTIR (KBr): ν = 3052 (w), 2947 (m)
˜
3
[ν(C–H)]; 1740 (s) [ν(C=O)] cm–1. ESI-MS (MeOH): calcd. for [M
+ Na]+ 389.0; found 389.0. X-ray diffraction quality single crystals
were grown by slow concentration from a saturated solution of the
compound in CD3OD at room temperature.
2,3-Bis{2-[2Ј-(methoxycarbonyl)biphenyl-4-yl]ethynyl}triptycene,
DET(biphCO2Me)2 (4a): A portion of [Pd(PPh3)4] (0.300 g,
10 mol-%) was added to a solution of 2,3-diethynyltriptycene
(0.780 g,2.56 mmol)andmethyl4Ј-bromobiphenyl-2-carboxylate(2)
160
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 156–163

1,2-Diethynylarene Compounds as Potential Transition Metal Ion Hosts
(1.50 g, 5.15 mmol) in Et3N (4.0 mL) and THF (24 mL) in a sealed
pressure vessel inside a dry box. Then the yellow-orange solution
was heated at 70 °C for 36 h. After cooling to room temperature,
ethyl acetate (200 mL) was added to the very dark orange reaction
mixture, which contained a white precipitate, presumably (Et3NH)-
Br. After extracting twice with aq. NH4Cl (2ϫ100 mL), the or-
ganic phase was dried with MgSO4, filtered, and concentrated to
dryness. The product was purified by column chromatography
(CH2Cl2/hexanes, 8:2), and further purified by stirring in dichloro-
ethane (70 mL) in the presence of the Pd-scavenger MP-TMT
(550 mg) at room temperature for 24 h. The resin was filtered off
the solution, and the filtrate was concentrated to dryness to give a
light yellow product. Yield 1.11 g (60%). M.p. 138–139 °C. Rf =
tion mixture of 4a (0.50 g, 0.69 mmol) and sodium trimethylsilanol-
ate (0.31 g, 2.8 mmol) in THF (30 mL) was heated at 60 °C for
24 h. After cooling the reaction mixture to room temperature, di-
ethyl ether (100 mL) was added and the mixture stirred at room
temperature for an additional 1 h. The tan-colored product was
filtered off, washed with dichloromethane, diethyl ether, and dried
under vacuum at 60 °C overnight. Yield 0.51 g (99 %). M.p.
1
Ͼ300 °C. H NMR (300 MHz, [D6]DMSO, 20 °C): δ = 7.75 (s, 2
H, HAr), 7.58 (d, J = 8.7 Hz, 4 H, HAr), 7.55–7.45 (m, 8 H, HAr),
7.35–7.29 (m, 2 H, HAr), 7.25–7.20 (m, 6 H, HAr), 7.05 (q, 4 H,
HAr), 5.76 (s, 2 H, CH) ppm. 13C NMR (500 MHz, [D6]DMSO,
20 °C): δ = 174.0 (CO2), 146.0 (CAr), 144.4 (CAr), 143.5 (CAr), 142.9
(CAr), 136.4 (CAr), 130.7 (CAr), 128.9 (CAr), 127.3 (CAr), 126.9
(CAr), 126.6 (CAr), 126.5 (CAr), 125.4 (CAr), 123.9 (CAr), 121.9
1
0.44 (hexanes/EtOAc, 7:3). H NMR (300 MHz, CDCl3, 20 °C): δ
= 7.84 (d, J = 6.9 Hz, 2 H, HAr), 7.61 (s, 2 H, HAr), 7.58 (d, J = (CAr), 120.1 (CAr), 93.2 (CϵC), 88.3 (CϵC), 52.0 (CH) ppm. FTIR
8.7 Hz, 4 H, HAr), 7.54 (m, 2 H, HAr), 7.45–7.34 (m, 10 H, HAr), (KBr): ν = 3060 (m), 3018 (m), 2956 (m) [ν(C–H)]; 2203 (w)
˜
7.29 (d, J = 8.4 Hz, 2 H, HAr), 7.05 (dd, J = 2.7, 5.4 Hz, 4 H, HAr),
[ν(CϵC)]; 1601 (m), 1580 (s), 1559 (s) [ν(C=O)] cm–1. ESI-MS
5.45 (s, 2 H, CH), 3.64 (s, 6 H, CH3) ppm. 13C NMR (500 MHz, ( M e O H ) : c a l c d . fo r [ M – N a ] – 7 1 5 . 2 ; f o u n d 7 1 5 . 0 .
[D6]DMSO, 20 °C): δ = 168.2 (CO2), 146.2 (CAr), 144.3 (CAr), 141.1
(CAr), 140.4 (CAr), 131.7 (CAr), 131.2 (CAr), 130.5 (CAr), 130.4
(CAr), 129.5 (CAr), 128.7 (CAr), 127.9 (CAr), 126.8 (CAr), 125.4
(CAr), 123.9 (CAr), 121.6 (CAr), 121.1 (CAr), 92.6 (CϵC), 88.9
(CϵC), 51.97 (CH3 or CH), 51.95 (CH3 or CH) ppm. FTIR (KBr):
C50H28O4Na2·1.25H2O (761.25): calcd. C 78.89, H 4.04; found C
78.86, H 4.07.
2,3-Bis{2-[2Ј-(methoxycarbonyl)-m-terphenyl-4-yl]ethynyl}-
triptycene, DET(terphCO2Me)2 (5): A portion of [Pd(PPh3)4]
(0.040 g, 10 mol-%) was added to a solution of 2,3-diethynyltrip-
tycene (0.103 g, 0.34 mmol) and 3 (0.250 g, 0.68 mmol) in Et3N
(0.50 mL) and THF (5 mL) in a sealed pressure vessel inside a dry
box. The yellow solution was heated at 70 °C for 36 h. After cool-
ing to room temperature, ethyl acetate (30 mL) was added to the
very dark orange reaction mixture, which contained a white pre-
cipitate, presumably (Et3NH)Br. After extracting twice with aq.
NH4Cl (2ϫ25 mL), the organic phase was dried with MgSO4, fil-
ν = 3059 (w), 3020 (w), 2947 (m) [ν(C–H)]; 2207 (w) [ν(CϵC)];
˜
1745 (s) [ν(C=O)] cm–1. ESI-MS (MeOH): calcd. for [M + Na]+
745.2; found 745.2; calcd. for [M + K]+ 761.2; found 761.3.
C52H34O4 (722.82): calcd. C 86.41, H 4.74; found C 85.97, H 4.42.
X-ray diffraction quality single crystals were grown from EtOAc/
hexanes, and the composition of 4a was confirmed by X-ray crys-
tallography. However, the data set was too poor to be published.
2,3-Bis[2-(2Ј-carboxybiphenyl-4-yl)ethynyl]triptycene, DET- tered, and stripped to dryness. The product was purified by column
(biphCO2H)2 (4b): The methyl ester 4a (0.500 g, 0.69 mmol) and
anhydrous lithium iodide (1.39 g, 10.4 mmol) were dissolved in an-
hydrous pyridine (40 mL) in a sealed tube inside a glove box. The
reaction mixture was heated at 110–115 °C in the dark (Al foil)
for 5 d. After cooling to room temperature, the dark solution was
quenched with water (200 mL), CHCl3 (150 mL) was added, and
the aqueous phase acidified with 4  HCl to pH = 1. The acidic
aqueous phase was washed with CHCl3 (100 mL), and the com-
bined organic phases were washed with water (3ϫ150 mL), dried
with MgSO4, filtered, and concentrated to dryness. The residue was
washed with a small amount of cold ethyl acetate and pentane to
give a white powder, which was dried under high vacuum. Yield
chromatography (EtOAc/hexanes, 25:75). The isolated material was
then stirred in dichloroethane with MP-TMT (Pd-scavenger) at
room temperature for 24 h. The resin was filtered off the solution,
and the filtrate was concentrated to dryness to give a light yellow
product. Yield 0.060 g (20%). M.p. 167–168.5 °C. Rf = 0.65 (hex-
anes/EtOAc, 1:1). 1H NMR (300 MHz, [D6]DMSO, 20 °C): δ =
7.84 (s, 2 H), 7.67–7.60 (m, 6 H), 7.51–7.31 (m, 22 H), 7.05 (dd, 4
H), 5.78 (s, 2 H), 3.35 (s, 6 H) ppm. 13C NMR (500 MHz, CDCl3,
20 °C): δ = 169.4 (CO2), 145.6 (CAr), 144.5 (CAr), 140.7 (CAr), 140.6
(CAr), 139.8 (CAr), 132.8 (CAr), 131.7 (CAr), 129.7 (CAr), 129.4
(CAr), 128.9 (CAr), 128.63 (CAr), 128.56 (CAr), 128.53 (CAr), 127.8
(CAr), 127.1 (CAr), 125.8 (CAr), 124.0 (CAr), 122.9 (CAr), 92.7
(CϵC), 89.6 (CϵC), 53.8 (CH or CH3), 52.1 (CH or CH3) ppm.
0.350 g (73%). M.p. 276–277 °C. Rf = 0.47 (hexanes/EtOAc, 2:8 +
1
one drop of acetic acid). H NMR (300 MHz, [D6]DMSO, 20 °C): FTIR (KBr): ν = 3020 (w), 2945 (m) [ν(C–H)]; 2204 (w) [ν(CϵC)];
˜
δ = 12.89 (s, 2 H, CO2), 7.78–7.43 (m, 4 H, HAr), 7.61–7.55 (m, 6
1730(s)[ν(C=O)]cm–1.ESI-MS(MeOH/CH2Cl2,1:1):calcd.for[M+
H, HAr), 7.52–7.44 (m, 6 H, HAr), 7.42–7.37 (m, 6 H, HAr), 7.06 Na]+ 897.3; found 897.3.
(q, 4 H, HAr), 5.77 (s, 2 H, CH) ppm. 13C NMR (500 MHz, [D6]-
4,5-Bis{2-[2Ј-(methoxycarbonyl)biphenyl-4-yl]ethynyl}veratrole,
DMSO, 20 °C): δ = 169.4 (CO2), 146.2 (CAr), 144.3 (CAr), 141.6
(CAr), 140.3 (CAr), 132.1 (CAr), 131.0 (CAr), 130.4 (CAr), 129.4
(CAr), 128.9 (CAr), 127.7 (CAr), 126.9 (CAr), 125.4 (CAr), 123.9
(CAr), 121.5 (CAr), 121.0 (CAr), 92.7 (CϵC), 88.8 (CϵC), 52.0 (CH)
DEV(biphCO2Me)2 (6a): Portions of [Pd(PPh3)4] (0.14 g, 10 mol-
%) and CuI (19 mg, 5 mol-%) were added to a deoxygenated solu-
tion of 4,5-diethynylveratrole (1) (0.370 g, 1.99 mmol) and methyl
4Ј-bromobiphenyl-2-carboxylate (2) (1.27 g, 4.38 mmol) in Et3N
(5.0 mL) and THF (25 mL). The reaction mixture was stirred at
70 °C for 24 h. The product was extracted with CH2Cl2
(2ϫ100 mL) and washed with aq. NH4Cl (100 mL). The organic
phases were dried with Na2SO4, filtered, and the solvents evapo-
rated to dryness. The product was purified by column chromatog-
raphy (CH2Cl2/diethyl ether, 95:5), and further purified with the
ppm. FTIR (KBr): ν = 3061 (m), 3019 (w), 2962 (m) [ν(C–H)]; 2210
˜
(m) [ν(CϵC)]; 1684 (s) [ν(C=O)] cm–1. ESI-MS (MeOH): calcd. for
[M – H]– 693.2; found 693.3; calcd. for [M + Na]+ 717.2; found
717.3. C50H30O4·H2O (712.8): calcd. C 84.25, H 4.52; found C
84.20, H 4.15. Recrystallization from hot MeOH resulted in single
crystals suitable for X-ray diffraction studies.
2,3-Bis[2-(2Ј-carboxybiphenyl-4-yl)ethynyl]triptycene Disodium Salt, Pd-scavenger MP-TMT (0.3 g) in CHCl3 (10 mL). Yield 0.920 g
DET (biphCO2Na)2 (4c). Method A: NaOH (5.8 mg, 0.14 mmol) (76%). Rf = 0.47 (CH2Cl2). 1H NMR (300 MHz, CDCl3, 20 °C): δ
and 4b (50 mg, 72 µmol) were heated in MeOH (7 mL) at 50 °C for
5 h. The solution was concentrated to dryness and dried under high
vacuum at 60 °C overnight. Yield 52 mg (98%). Method B: A reac-
= 7.85 (dd, J = 7.8, 1.2 Hz, 2 H, HAr), 7.63 (d, J = 8.1 Hz, 4 H,
HAr), 7.56 (td, J = 7.8, 1.8 Hz, 2 H, HAr), 7.46–7.38 (m, 4 H, HAr),
7.31 (d, J = 8.7 Hz, 4 H, HAr), 7.07 (s, 2 H, HAr), 3.96 (s, 6 H,
Eur. J. Org. Chem. 2008, 156–163
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
161

E. Reisner, S. J. Lippard
FULL PAPER
OCH3), 3.63 (s, 6 H, CO2CH3) ppm. 13C NMR (300 MHz, CDCl3, 7.53 (t, J = 8.4 Hz, 2 H, HAr), 7.42–7.36 (m, 18 H, HAr), 7.07 (s, 2
20 °C): δ = 169.2 (CO2), 149.2 (CAr), 141.9 (CAr), 141.5 (CAr), 131.6
(CAr), 131.4 (CAr), 130.9 (CAr), 130.7 (CAr), 130.2 (CAr), 128.6
(CAr), 127.7 (CAr), 122.6 (CAr), 119.0 (CAr), 114.1 (CAr), 92.4
H, HAr), 3.96 (s, 6 H, OCH3), 3.40 (s, 6 H, CO2CH3) ppm. 13C
NMR (500 MHz, CDCl3, 20 °C): δ = 169.9 (CO2), 149.3 (CAr),
140.7 (CAr), 140.7 (CAr), 140.6 (CAr), 139.8 (CAr), 132.9 (CAr),
(CϵC), 89.2 (CϵC), 56.2 (OCH3), 52.2 (CO2CH3) ppm. FTIR 131.7 (CAr), 129.7 (CAr), 129.4 (CAr), 128.9 (CAr), 128.7 (CAr),
(KBr): ν = 2941 (m), 2918 (m), 2849 (w) [ν(C–H)]; 2205 (w)
128.6 (CAr), 128.5 (CAr), 127.8 (CAr), 122.9 (CAr), 119.0 (CAr),
˜
[ν(CϵC)]; 1726 (s) [ν(C=O)] cm–1. ESI-MS (MeOH): calcd. for [M
+ Na]+ 629.2; found 629.2. C40H30O6 (606.66): calcd. C 79.19, H
4.98; found C 78.54, H 5.03.
114.2 (CAr), 92.3 (CϵC), 89.4 (CϵC), 56.3 (OCH3), 52.1 (CO2CH3)
ppm. FTIR (KBr): ν = 2961 (m), 2945 (m) [ν(C–H)]; 2206 (w)
˜
[ν(CϵC)]; 1729 (s) [ν(C=O)] cm–1. ESI-MS (MeOH): calcd. for [M
+ Na]+ 781.3; found 781.3.
4,5-Bis[2-(2Ј-carboxybiphenyl-4-yl)ethynyl]veratrole, DEV-
(biphCO2H)2 (6b): A portion of DEV(biphCO2Me)2 (6a) (0.600 g,
0.99 mmol) and anhydrous lithium iodide (2.00 g, 15.0 mmol) were
dissolved in anhydrous pyridine (35 mL) in a sealed pressure tube
inside a glove box. The reaction mixture was heated at 110 °C un-
der protection of light (Al foil) for 6 d. After cooling to room tem-
perature, the dark solution was quenched with water (200 mL).
Then CHCl3 (150 mL) was added and the aqueous phase acidified
with 4  HCl to pH = 1. The acidic aqueous phase was washed
with CHCl3 (100 mL), and the combined organic phases were
washed with water (2ϫ150 mL), dried with MgSO4, filtered, and
the solvents evaporated to dryness. The product was washed with
pentane and dried under high vacuum. Yield 0.320 g (56%). 1H
NMR (300 MHz, CDCl3, 20 °C): δ = 11.11 (br. s, 2 H, CO2), 7.99
(d, J = 8.5 Hz, 2 H, HAr) 7.64–7.57 (m, 6 H, HAr), 7.49–7.44 (m,
4 H, HAr), 7.37 (d, J = 8.4 Hz, 4 H, HAr), 7.08 (s, 2 H, HAr), 3.97
(s, 6 H, OCH3) ppm. 13C NMR (300 MHz, CDCl3, 20 °C): δ =
175.2 (CO2), 149.3 (CAr), 142.6 (CAr), 140.8 (CAr), 132.6 (CAr),
131.7 (CAr), 131.2 (CAr), 131.1 (CAr), 129.7 (CAr), 128.7 (CAr),
127.8 (CAr), 122.7 (CAr), 119.9 (CAr), 113.4 (CAr), 92.6 (CϵC), 88.8
(CϵC), 56.3 (OCH3) ppm.
4,5-Bis{2-[6-(methoxycarbonyl)pyrid-3-yl]ethynyl}veratrole,
DEV(PICMe)2 (8): Solid [Pd(PPh3)4] (0.27 g, 10 mol-%) was added
to a deoxygenated solution of 4,5-diethynylveratrole (1) (0.430 g,
2.31 mmol), and methyl 5-bromo-2-picolinate (1.10 g, 5.09 mmol)
in Et3N (5.0 mL) and THF (25 mL). The yellow solution was
heated at 60 °C for 36 h. The reaction mixture with some yellow
precipitate was cooled to room temperature, concentrated to dry-
ness, and dissolved in CHCl3 (150 mL). The organic phase was
washed with aq. NH4Cl (150 mL), which was dried with Na2SO4,
filtered, and the solvents were evaporated to dryness. The product
was purified by column chromatography (CHCl3/diethyl ether,
97:3). Yield 0.980 g (93%). M.p. 188–189 °C. Rf = 0.42 (CHCl3/
1
Et2O, 95:5). H NMR (300 MHz, CDCl3, 20 °C): δ = 8.87 (d, J =
1.8 Hz, 2 H, HAr), 8.13 (d, J = 8.1 Hz, 2 H, HAr), 7.95 (dd, J =
8.1, 1.8 Hz, 2 H, HAr), 7.09 (s, 2 H, HAr), 4.04 (s, 6 H, CH3), 3.98
(s, 6 H, CH3) ppm. 13C NMR (300 MHz, CDCl3, 20 °C): δ = 165.3
(CO2), 152.0 (CAr), 150.1 (CAr), 146.3 (CAr), 139.1 (CAr), 124.8
(CAr), 124.0 (CAr), 118.1 (CAr), 114.3 (CAr), 94.4 (CϵC), 88.8
(CϵC), 56.3 (OCH ), 53.3 (CO CH ) ppm. FTIR (KBr): ν = 2947
˜
3
2
3
(m) [ν(C–H)]; 2205 (s) [ν(CϵC)]; 1742 (s), 1720 (s) [ν(C=O)] cm–1.
ESI-MS (MeOH): calcd. for [M + Na]+ 479.1; found 479.0.
4,5-Bis[2-(2Ј-carboxybiphenyl-4-yl)ethynyl]veratrole Disodium Salt,
DEV(biphCO2Na)2 (6c): A reaction mixture containing DEV-
(biphCO2Me)2 (6a) (200 mg, 0.33 mmol) and sodium trimethylsil-
anolate (93.0 mg, 0.82 mmol) in THF (50 mL) was stirred at 60 °C
for 3 d. After cooling to room temperature, diethyl ether (70 mL)
was added to the resulting suspension, and the mixture was stirred
at room temperature for an additional 1 h. The white product was
filtered off, washed with diethyl ether, and dried under vacuum at
4,5-Bis{2-[8-(ethoxycarbonyl)quinol-3-yl]ethynyl}veratrole,
DEV(quinolineCO2Et)2 (9): A portion of [PdCl2(PPh3)2] (0.14 g,
10 mol-%) and CuI (19 mg, 5 mol-%) were added to a deoxy-
genated solution of 4,5-diethynylveratrole (1) (0.370 g, 1.97 mmol)
and ethyl 3-[(trifluoromethyl)sulfonyl]quinoline-8-carboxylate
(1.51 g, 4.32 mmol) in Et3N (5.0 mL) and THF (25 mL). The reac-
tion mixture was stirred at room temperature overnight. CH2Cl2
(150 mL) was added to the reaction mixture, which was washed
with aq. NH4Cl (100 mL). The organic phase was dried with
Na2SO4, filtered, and stripped to dryness. The product was purified
by column chromatography (CH2Cl2/diethyl ether, 95:5). Yield
0.920 g (80%). M.p. 168–169 °C. Rf = 0.45 (CHCl3/Et2O, 95:5). 1H
NMR (300 MHz, CDCl3, 20 °C): δ = 9.18 (d, J = 2.1 Hz, 2 H,
HAr), 8.34 (d, J = 1.8 Hz, 2 H, HAr), 8.04 (dd, J = 8.1, 1.2 Hz, 2
H, HAr), 7.88 (dd, J = 7.2, 1.2 Hz, 2 H, HAr), 7.59 (t, J = 7.8 Hz,
2 H, HAr), 7.13 (s, 2 H, HAr), 4.55 (q, J = 6.9 Hz, 4 H, CH2), 4.00
(s, 6 H, OCH3), 1.46 (t, J = 7.2 Hz, 6 H, CH2CH3) ppm. 13C NMR
(500 MHz, CDCl3, 20 °C): δ = 167.6 (CO2), 153.0 (CAr), 149.9
(CAr), 144.2 (CAr), 138.5 (CAr), 132.1 (CAr), 131.2 (CAr), 131.0
(CAr), 127.7 (CAr), 126.7 (CAr), 118.5 (CAr), 118.3 (CAr), 114.4
(CAr), 92.2 (CϵC), 89.6 (CϵC), 61.9 (CO2CH2), 56.4 (OCH3),
1
room temperature. Yield 190 mg (92%). M.p. Ͼ300 °C. H NMR
(300 MHz, [D6]DMSO, 20 °C): δ = 7.61–7.49 (m, 8 H, HAr), 7.34
(m, 2 H, HAr), 7.26 (m, 6 H, HAr), 7.19 (s, 2 H, HAr), 3.86 (s, 6 H,
OCH3) ppm. 13C NMR (500 MHz, [D6]DMSO, 20 °C): δ = 174.2
(CO2), 149.2 (CAr), 143.5 (CAr), 142.5 (CAr), 136.4 (CAr), 130.6
(CAr), 128.9 (CAr), 128.8 (CAr), 127.3 (CAr), 126.8 (CAr), 126.6
(CAr), 120.4 (CAr), 118.1 (CAr), 114.0 (CAr), 92.5 (CϵC), 88.7
(CϵC), 55.8 (OCH ) ppm. FTIR (KBr): ν = 2960 (w) [ν(C–H)];
˜
3
2208 (w) [ν(CϵC)]; 1600 (s), 1578 (s), 1562 (s) [ν(C=O)] cm–1. ESI-
MS (MeOH): calcd. for [M – Na]– 599.1; found 599.0; calcd. for
[M – 2 Na + H]– 577.2; found 577.2.
4,5-Bis{2-[2Ј-(methoxycarbonyl)-m-terphenyl-4-yl]ethynyl}veratrole,
DEV(terCO2Me)2 (7): Solid [Pd(PPh3)4] (0.040 g, 10 mol-%) was
added to a solution of 4,5-diethynylveratrole (1) (0.063 g,
0.34 mmol) and 3 (0.25 g, 0.68 mmol) in Et3N (0.50 mL) and THF
(15 mL) in a sealed pressure vessel inside a dry box. The yellow
solution was heated at 70 °C for ca. 36 h. After cooling to room
temperature, CH2Cl2 (30 mL) was added to the very dark orange
reaction mixture, which contained a white precipitate, presumably
(Et3NH)Br. After washing with aq. NH4Cl (2ϫ25 mL), the or-
ganic phase was dried with MgSO4, filtered, and concentrated to
dryness. The product was purified by column chromatography
(CH2Cl2/hexanes, 28:12). Yield 0.22 g (9%). Rf = 0.58 (CH2Cl2).
14.56 (CH CH ) ppm. FTIR (KBr): ν = 2981 (w), 2960 (m), 2937
˜
2
3
(w), 2902 (w) [ν(C–H)]; 2209 (m) [ν(CϵC)]; 1731 (s) [ν(C=O)] cm–1.
ESI-MS (MeOH): calcd. for [M + Na]+ 607.2; found 607.2.
Acknowledgments
This work was supported by the National Institute of General
Medical Sciences (grant GM032134). E. R. is the recipient of a
1H NMR (300 MHz, CDCl3, 20 °C): δ = 7.64–7.61 (m, 4 H, HAr), Schrödinger fellowship (J2485-B10) from the Austrian Science
162
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1,2-Diethynylarene Compounds as Potential Transition Metal Ion Hosts
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Published Online: October 30, 2007
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