Synthesis of a shape-persistent macrocycle with intraannular carboxylic acid groups

Article abstract of DOI:10.1016/j.tet.2003.09.045

The synthesis of a shape-persistent macrocycle based on the phenylene-ethynylene backbone by the intermolecular oxidative Glaser-coupling of appropriate bisacetylenes is described. The ring contains two intraannular methyl carboxylates that were hydrolyze

Full text of DOI:10.1016/j.tet.2003.09.045

Tetrahedron 59 (2003) 9441–9446
Synthesis of a shape-persistent macrocycle with intraannular
carboxylic acid groups
*
¨
Matthias Fischer and Sigurd Hoger
Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
Received 10 April 2003; revised 8 September 2003; accepted 15 September 2003
Abstract—The synthesis of a shape-persistent macrocycle based on the phenylene–ethynylene backbone by the intermolecular oxidative
Glaser-coupling of appropriate bisacetylenes is described. The ring contains two intraannular methyl carboxylates that were hydrolyzed to
give the free diacid. In order to achieve sufficient solubility it was necessary to attach additional intraannular branched alkyl groups to the
ring.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
annular carboxylic acid groups showed some unexpected
difficulties. Shape-persistent macrocycles are compared to
non-cyclic or flexible analogues much less soluble. That has
its origin in the drastically reduced entropy gain by going
from the bulk phase to the solution. On one hand this
simplifies the isolation and purification of the compounds
which can often be performed by simple recrystallization.
On the other hand it is necessary to attach flexible side
Recently, there has been considerable interest in the design
and study of shape-persistent macrocycles with an interior
in the nanometer regime. Apart from the their organization
in solution, the solid state and at interfaces they offer the
possibility to bind large guest molecules.1–4 The binding of
the guest can be non-specific, or specific if the macrocycle
contains appropriate intraannular binding sites5,6 with a
polarity and arrangement complementary to the guest
molecule.7–11 Our work has focused on shape-persistent
macrocycles based on the phenylene–ethynylene–buta-
dienylene backbone as schematically shown in
Figure 1.12–15
groups to the rings in order to keep the materials tractable.24,
25
Here we describe the synthesis of the macrocycle 1 with two
intraannular carboxylic acid groups (at the positions I,
Fig. 1). 1 contains additionally four intraannular (S)-2-
methylbutoxy groups (at the positions I0, Fig. 1) providing
sufficient solubility of the free diacid. Therefore, 1 might be
a good candidate for the above mentioned investigations.26
Depending on the position where the side groups (which can
also contain functional groups) are attached to the ring they
point either to the inside (intraannular groups I, I0), to the
outside (extraannular groups E, E0), or they can switch their
orientation and point either to the inside or to the outside
(adaptable groups A, A0).16–19 In terms of our ongoing
program towards macrocycles with a highly polar interior
we became interested in structures with two convergently
arranged carboxylic acid groups (at the positions I).20,21
They should be able to recognize organic diamines or might
be in form of their metal salts the basis for new inorganic/
organic hybrid structures. Moreover, attaching oligo-
peptides through their N-terminal sites could lead to new
two-armed peptide receptors.22,23
However, the synthesis of macrocycles with two intra-
Keywords: cyclisation; macrocycles; supramolecular chemistry.
*
¨
Corresponding author. Address: Polymer-Institut, Universitat Karlsruhe
Hertzstr. 16, D-76187 Karlsruhe, Germany. Tel.: þ49-721-608-4465;
fax: þ49-721-608-4421; e-mail: hoeger@chemie.uni-karlsruhe.de
Figure 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.045

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M. Fischer, S. Hoger / Tetrahedron 59 (2003) 9441–9446
9442
2. Results and discussion
36% yield.27 The excess of 7 was nearly quantitatively
recovered and could be used for subsequent coupling
reactions. Coupling of 8 with trimethylsilyl(TMS)-
acetylene yielded 9 (64%), which was desilylated with
K2CO3 to give 10 (96%). The statistical intermolecular
oxidative dimerization of 10 was performed by slow
addition of a solution of 10 in pyridine to a suspension of
CuCl and CuCl2 in the same solvent at 608C, a compromise
between increased coupling rate and decreased product
stability at elevated temperatures.14 The crude cyclization
product was purified by radial chromatography to give pure
11 in 54% isolated yield. Base-catalyzed ester hydrolysis
gave the diacid 1 (65%).
The synthesis of 1 is outlined in Scheme 1.
2,6-Diiodo-4-tert-butylphenol (2) was alkylated with
4-bromo-trimethylorthobutyrate to give the ester 3 in 57%
yield. Palladium-catalyzed Hagihara–Sonogashira coupling
of 3 with the mono-protected bisacetylene 4 and subsequent
desilylation of 5 (94%) by treating with Bu4NF gave the
bisacetylene 6 (84%). As described previously, the basicity
of the fluoride was reduced by adding about 5% of water to
the THF.20 Reaction of 6 with a 4.5-fold excess of the THP-
protected diiodophenol 7 gave the diiodo compound 8 in
Scheme 1. (a) 4-Bromo-trimethylorthobutyrate, K2CO3, DMF (57%); (b) PdCl2(PPh3)2, CuI, THF/NEt3 (94%); (c) Bu4NF, THF/H2O (84%); (d) PdCl2(PPh3)2,
CuI, NEt3/THF (36%); (e) TMS-acetylene, PdCl2(PPh3)2, CuI, piperidine (64%); (f) K2CO3, MeOH/THF (96%); (g) CuCl, CuCl2, pyridine, (54%);
(h) Bu4NOH, MeOH, THF, 65%.

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M. Fischer, S. Hoger / Tetrahedron 59 (2003) 9441–9446
9443
1 is well soluble in a variety of different organic solvents
like CH2Cl2, CHCl3 or THF. In this context it is worth to
mention that the corre0sponding diacid with four methoxy
groups at the position I is nearly insoluble and could not be
characterized by solution NMR spectroscopy.28 Figure 2
displays the 1H NMR spectra of 11 and 1. It show molecules
with a high degree of symmetry, as expected from the
molecular structure. The absence of the methyl signal at
3.5 ppm in 1 is a clear indication for the complete ester
hydrolysis.
under argon, and the glassware was oven-dried (1408C).
THF was distilled from potassium prior to use. Triethyl-
amine and pyridine were distilled over CaH2 and stored
under argon. Commercially available chemicals were used
as received. Compounds 2 and 4 are described elsewhere.20,29
1H NMR and 13C NMR spectra were recorded on a Bruker
DPX 250 or AC 300 spectrometer (250 and 300 MHz for
1H, 62.5 and 75.48 MHz for 13C). Chemical shifts are given
in ppm, referenced to residual proton resonances of the
solvents. Thin-layer chromatography was performed on
aluminum plates precoated with Merck 5735 silica gel 60
F254. Column chromatography was performed with Merck
silica gel 60 (230–400 mesh). The gel permeation
chromatograms were measured in THF (flow rate
1 mL min21) at room temperature, using a combination of
three styragel columns (porosity 103, 105, 106) and an UV
detector operating at l¼254 nm. The molecular weight was
obtained from polystyrene calibrated SEC columns. The
matrix-assisted laser desorption ionization time-of-flight
(MALDI-TOF) mass spectroscopy measurements were
carried out on a Bruker reflex spectrometer (Bruker,
Bremen), which incorporates a 337 nm nitrogen laser with
a 3 ns pulse duration (106–107 W cm21, 100 mm spot
diameter). The instrument was operated in a linear mode
with an accelerating potential of 33.65 kV. The mass scale
was calibrated with polystyrene (Mp¼2300), using a
number of resolved oligomers. Samples were prepared by
dissolving the compounds in THF at a concentration of
1024 mol L21. In all cases, 1,8,9-trihydroxyanthracene was
All in all we have described the synthesis of the first
nanometer size shape-persistent macrocycle with two
intraannular carboxylic acid groups that is soluble enough
to be characterized in solution. Simple intraannular
methoxy groups did not provide enough solubility and
more bulky methylbutoxy groups had to be attached to the
ring. However, this chiral groups inside the macrocycle
might offer additional features for the recognition of guest
molecules of biological origin. In addition, the acid groups
can be further functionalized and the macrocycle can act as
a new template for two-arm peptide receptors.
3. Experimental
3.1. General
Reactions requiring an inert gas atmosphere were conducted
Figure 2. 1H NMR spectra of 11 (bottom) and 12 (top).

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M. Fischer, S. Hoger / Tetrahedron 59 (2003) 9441–9446
9444
used as matrix. Field desorption spectra were recorded on a
VG ZAB 2-SE FPD machine. Microanalyses were
performed by the University of Mainz. Melting points
were measured with a Reichert hot stage apparatus and are
uncorrected.
to 3:1) as the eluent to give an oily product (3.2 g) (Rf
(CH2Cl2/petroleum ether (1:1))¼0.70) that was treated with
MeOH in order to remove the silanol to give 6 as a slightly
yellow solid (2.0 g, 84%). Mp 161–1638C; 1H NMR
(250 MHz, CD2Cl2): d¼7.50 (s, 2H), 7.04 (s, 2H), 7.00 (s,
2H), 4.37 (t, J¼5.9 Hz, 2H), 3.97 (t, J¼6.5 Hz, 4H), 3.96 (t,
J¼6.5 Hz, 4H), 3.52 (s, 3H), 3.39 (s, 2H), 2.66 (t, J¼7.2 Hz,
2H), 2.04–2.16 (m, 2H), 1.75–1.90 (m, 8H), 1.32 (s, 9H),
1.00–1.10 (m, 12H); elemental analysis for C47H54O7
(730.45): calcd C 77.23, H 7.45; found C 76.94, H 7.39; MS
(FD): 730.6 (Mþ).
3.1.1. Methyl 4-(tert-butyl-2,6-diiodophenoxy)-butyrate
3. 4-tert-Butyl-2,6-diiodophenol (2) (15.74 g, 39.0 mmol),
4-bromo-trimethylorthobutyrate
(8.85 g,
39.0 mmol),
K2CO3 (5.5 g, 43.0 mmol) and KI (50 mg) were stirred in
DMF (70 mL) at 608C for 20 h and after cooling to room
temperature poured into ether and water. The organic phase
was separated and extracted with 10% sodium hydroxide
solution, water, and brine. After drying over MgSO4 and
evaporation of the solvent the crude product was chromato-
graphed over silica gel with CH2Cl2/petroleum ether (1:4)
as the eluent (Rf¼0.83) to give 3 as a slightly beige solid
(11.1 g, 57%). The crude product may contain variable
minor amounts of the corresponding orthoester product,
seeing by an extra NMR signal at 3.19 ppm (s). In that case
the crude product was dissolved in CH2Cl2 and extracted
several times with 10% acetic acid, then water, 10%
aqueous sodium hydroxide, water, and brine to complete the
3.1.4. 4-tert-Butyl-2,6-diiodo-1-(2-(S)-methylbutoxy)-
benzene 7. Diethylazodicarboxylate (2.6 g; 15.0 mmol)
were slowly added to a solution of 4-tert-butyl-2,6-
diiodophenol (2) (4.0 g, 10.0 mmol), (S)-2-methyl-1-buta-
nol (0.88 g, 10.0 mmol) and PPh3 (3.9 g, 14.8 mmol) in
THF (20 mL) and the mixture was stirred for 12 h at room
temperature and then poured into ether and water. The
organic phase was separated and extracted with water and
brine. After drying over MgSO4 and evaporation of the
solvent the crude product was chromatographed over silica
gel with petroleum ether as the eluent (Rf¼0.30) to give 7 as
a colorless oil (4.03 g, 85%). 1H NMR (250 MHz, CD2Cl2):
d¼7.80 (s, 2H), 3.60–3.90 (m, 2H), 1.95–2.15 (m, 1H),
1.65–1.80 (m, 1H), 1.25–1.45 (m, 1H), 1.32 (s, 9H), 1.09
(d, J¼5.9 Hz, 3H); 0.98 (t, J¼7.3 Hz, 3H); elemental
analysis for C15H20I2O (472.15): calcd C 38.16, H 4.70;
found C 38.32, H 4.65; MS (FD): 472.2 (Mþ).
1
transformation of the orthoester to 3. Mp 1538C; H NMR
(250 MHz, C2D2Cl4): d¼7.63 (s, 2H), 3.90 (t, J¼6.0 Hz,
2H), 3.61 (s, 3H), 2.61 (t, J¼7.4 Hz, 2H), 2.10–2.25 (m,
2H), 1.17 (s, 9H); elemental analysis for C15H20I2O3
(502.13): calcd C 35.88, H 4.01; found C 35.94, H 3.93;
MS (FD): 502.3 (Mþ).
3.1.2. Methyl 4-(2,6-bis-{2-[2,5-dipropyloxy-4-(2-tri-
isopropylsilylethynyl)phenyl]-ethynyl}-4-tert-butyl-
phenoxy)-butyrate 5. Pd(PPh3)2Cl2 (68 mg) and CuI
(35 mg) were added to a solution of 3 (2.11 g, 4.28 mmol)
and 4 (3.41 g, 8.55 mmol) in triethylamine/THF (5:1)
(120 mL). The solution was stirred for 18 h at room
temperature, for 1 h at 508C and after cooling to room
temperature poured into ether and water. The organic phase
was separated and extracted with water, 10% acetic acid,
water, 10% aqueous sodium hydroxide, water, and brine.
After drying over MgSO4 and evaporation of the solvent the
crude product was chromatographed over silica gel with
CH2Cl2/petroleum ether (slow polarity increase from 1:2 to
1:1) as the eluent (Rf (CH2Cl2/petroleum ether 1:2)¼0.24)
to give 5 as a slightly yellow solid (4.16 g, 94%). Mp 1228C;
1H NMR (250 MHz, CD2Cl2): d¼7.50 (s, 2H), 6.98 (s, 2H),
6.95 (s, 2H), 4.40 (t, J¼6.0 Hz, 2H), 3.86–4.40 (m, 8H),
3.57 (s, 3H), 2.71 (t, J¼7.2 Hz, 2H), 2.05–2.20 (m, 2H),
1.75–1.95 (m, 8H), 1.32 (s, 9H), 1.15 (s, 42H), 1.00–1.15
(m, 12H); elemental analysis for C65H94O7Si2 (1043.64):
calcd C 74.81, H 9.08; found C 74.82, H 9.18; MS (FD):
1044.1 (Mþ).
3.1.5. Methyl 4-{2,6-bis-[2-(2,5-dipropyloxy-4-{2-[2-(2-
(S)-methylbutoxy)-3-iodo-5-tert-butylphenyl]ethynyl}-
phenyl)ethynyl]-4-tert-butylphenoxy}-butyrate
8.
Pd(PPh3)2Cl2 (30 mg) and CuI (15 mg) were added to a
solution of 7 (3.91 g, 8.28 mmol) and 6 (0.92 g, 1.83 mmol)
in triethylamine (15 mL), and the mixture was stirred for
18 h at 608C. Workup was performed as described for
compund 5. The oily crude product was chromatographed
over silica gel with CH2Cl2/petroleum ether (1:2) as the
eluent to recover most of the excess of 7 (2.19 g). Changing
the eluent to CH2Cl2 yielded 8 (Rf¼0.59) as a slightly
yellow solid (0.65 g, 36%). Mp 778C (dec.); 1H NMR
(300 MHz, CD2Cl2): d¼7.79 (d, J¼2.3 Hz, 2H), 7.55 (s,
2H), 7.53 (d, J¼2.3 Hz, 2H), 7.10 (s, 2H), 7.04 (s, 2H), 4.43
(t, J¼6.1 Hz, 2H), 3.95–4.15 (m, 12H), 3.56 (s, 3H), 2.72 (t,
J¼7.2 Hz, 2H), 2.11–2.20 (m, 2H), 1.94–2.09 (m, 2H),
1.80–1.93 (m, 8H), 1.64–1.79 (m, 2H), 1.35 (s, 9H), 1.31
(s, 18H), 1.08–1.18 (m, 18H), 0.98 (t, J¼7.6 Hz, 6H);
elemental analysis for C77H96I2O0 (1419.43): calcd C 65.16,
H 6.82; found C 65.57, H 7.11; MS (FD): 1418.7 (Mþ).
3.1.6. Methyl 4-{2,6-bis-[2-(2,5-dipropyloxy-4-{2-[2-(2-
(S)-methylbutoxy)-3-(2-trimethylsilylethynyl)-5-tert-
butylphenyl]ethynyl}phenyl)ethynyl]-4-tert-butyl-
phenoxy}-butyrate 9. Pd(PPh3)2Cl2 (10 mg) and CuI
(5 mg) were added to a solution of 8 (0.6 g, 0.42 mmol)
and TMS acetylene (0.25 g, 2.54 mmol) in piperidine
(10 mL), and the mixture was stirred for 16 h at 608C.
Workup was performed as described for compund 7.
Column chromatography over silica gel with CH2Cl2/
petroleum ether (2:1) as the eluent (Rf¼0.64) and sub-
sequent radial chromatography over silica gel/gypsum with
CH2Cl2/petroleum ether (8:5) as the eluent gave 9 as a
3.1.3. Methyl 4-{2,6-bis-[2-(2,5-dipropyloxy-4-ethynyl-
phenyl)-ethynyl]-4-tert-butylphenoxy}-butyrate 6.
A
1 M solution of Bu4NF in THF (15.0 mL, 15.0 mmol) was
added to a solution of 5 (3.39 g, 3.25 mmol) in THF (30 mL)
and water (1.5 mL). The mixture was stirred for 2 h at room
temperature and then poured into ether and water. The
organic layer was extracted with water and brine and dried
over MgSO4. After evaporation of the solvent the residue
was purified by chromatography over silica gel with
CH2Cl2/petroleum ether (slow polarity increase from 1:1

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M. Fischer, S. Hoger / Tetrahedron 59 (2003) 9441–9446
9445
slightly yellow oil which slowly solidified (0.37 g, 64%).
1
146.69, 132.02, 131.64, 131.04, 117.68, 117.53, 117.42,
115.89, 114.59, 114.54, 91.72, 91.52, 90.68, 90.40, 79.96,
79.38, 78.01, 73.78, 71.68, 71.60, 36.42, 34.67, 31.33,
31.05, 30.11, 26.60, 26.15, 23.15, 23.09, 16.95, 11.73,
10.70, 10.63; elemental analysis for C162H192O18 (2427.33):
calcd C 80.16, H 7.97; found C 79.78, H 8.16; GPC (PS,
THF): single peak with Mw¼2450, Mn¼2200, PD¼1.02.
MS (MALDI-TOF): 2535.4 (MþAgþ).
Mp 1658C; H NMR (300 MHz, CD2Cl2): d¼7.54 (s, 2H),
7.51 (d, J¼2.3 Hz, 2H), 7.44 (d, J¼2.7 Hz, 2H), 7.09 (s,
2H), 7.04 (s, 2H), 4.43 (t, J¼6.1 Hz, 2H), 4.17 (t, J¼6.8 Hz,
2H), 3.98–4.10 (m, 10H), 3.56 (s, 3H), 2.72 (t, J¼7.2 Hz,
2H), 2.09–2.23 (m, 2H), 1.80–2.00 (m, 10H), 1.63–1.79
(m, 2H), 1.35 (s, 9H), 1.32 (s, 18H), 1.05–1.18 (m, 18H),
0.97 (t, J¼7.3 Hz, 6H), 0.27 (s, 18H); elemental analysis for
C87H114O9Si9 (1360.05): calcd C 76.83, H 8.45; found C
77.01, H 8.38; MS (FD): 1361.2 (Mþ).
3.1.9. Macrocyclic diacid 1. Tetrabutylamonium hydroxide
(0.5 mL, 40% in water) was added to a solution of 11
(30 mg) in THF (10 mL). The mixture was stirred over night
at room temperature and 2 mL of hydrochloric acid was
added (10%) and the solvent removed in vacuum to a small
volume. Methanol (10 mL) and water (2 mL) were added
and the precipitate collected by filtration. Purification was
performed by column chromatography using CH2Cl2 as an
eluent to remove less polar impurities and 1 was eluted with
THF (20 mg, 65%). Mp .2308C (decomp.). 1H NMR
(300 MHz, CD2Cl2): d¼7.53 (d, J¼2.4 Hz, 4H), 7.52 (s,
4H) 7.48 (m, J¼2.4 Hz, 4H), 7.08 (s, 4H), 7.05 (s, 4H), 4.42
(t, J¼6.0 Hz, 4H), 4.15–4.24 (m, 4H), 3.97–4.11 (m, 20H),
3.20 (br.s 4H, H2O), 2.68 (t, J¼7.5 Hz, 4H), 2.06–2.18 (m,
4H), 1.78–2.00 (m, 20H), 1.55–1.79 (m, 8H), 1.32–1.40
(m, 4H), 1.35 (s, 18H), 1.32 (s, 36H), 1.06–1.16 (m, 36H),
0.94 (t, J¼7.2 Hz, 12H); 13C NMR (75 MHz, CD2Cl2):
d¼175.09, 161.48, 159.12, 154.05, 146.91, 146.68, 131.96,
131.58, 131.16, 117.65, 117.45, 115.91, 114.65, 114.55,
91.71, 91.56, 90.68, 90.47, 79.96, 79.42, 78.05. 73.63,
71.70, 36.42, 34.67, 31.35, 30.53, 30.11, 26.60, 25.91,
23.14, 23.10, 16.96, 11.75, 10.69, 10.63; elemental analysis
for C160H188O18 (2399.27): calcd C 80.10, H 7.90; found C
79.81, H 8.02.
3.1.7. Methyl 4-{2,6-bis-[2-(2,5-dipropyloxy-4-{2-[2-(2-
(S)-methylbutoxy)-3-ethynyl-5-tert-butylphenyl]-
ethynyl}phenyl)ethynyl]-4-tert-butylphenoxy}-butyrate
10. A 1 M solution of Bu4NF in THF (1.5 mL, 1.5 mmol)
was added to a solution of 9 (305 mg; 0.22 mmol) in THF
(20 mL) and water (0.5 mL). The mixture was stirred for
1.25 h at room temperature and then poured into ether and
water. The organic layer was extracted with water and brine
and dried over MgSO4. After evaporation of the solvent the
residue was purified by chromatography over silica gel with
CH2Cl2/petroleum ether (1:1) as the eluent (Rf¼0.86) to
give 10 as a slightly yellow solid (261 mg, 96%). Mp 187–
1908C; 1H NMR (300 MHz, CD2Cl2): d¼7.54 (s, 2H), 7.53
(d, J¼2.3 Hz, 2H), 7.48 (d, J¼2.3 Hz, 2H), 7.09 (s, 2H),
7.05 (s, 2H), 4.43 (t, J¼5.7 Hz, 2H), 4.14–4.20 (m, 2H),
3.98–4.12 (m, 10H), 3.56 (s, 3H), 3.31 (s, 2H), 2.72 (t,
J¼7.2 Hz, 2H), 2.12–2.22 (m, 2H), 1.81–1.99 (m, 10H),
1.63–1.78 (m, 2H), 1.35 (s, 9H), 1.32 (s, 18H), 1.23–1.40
(m, 2H), 1.08–1.18 (m, 18H), 0.97 (t, J¼7.3 Hz, 6H); 13C
NMR (75 MHz, CD2Cl2): d¼173.70, 159.66, 158.26,
153.78, 146.61, 146.27, 131.78, 131.71, 131.31, 117.16,
117.04, 116.81, 115.88, 114.31, 114.10, 91.58, 91.53, 90.07,
89.97, 81.06, 80.42, 79.22, 73.42, 71.26, 71.18, 51.31,
36.06, 34.35, 34.27, 31.03, 30.88, 26.23, 25.88, 22.89,
22.84, 16.56, 11.41, 10.48, 10.43 ppm; elemental analysis
for C81H98O9 (1215.68): calcd C 80.03, H 8.13; found C
79.89, H 8.37; MS (FD): 1216.0 (Mþ).
Acknowledgements
Financial Support by the Deutsche Forschungsgemeinschaft
is gratefully acknowledged.
3.1.8. Macrocycle 11. A solution of 10 (260 mg,
0.21 mmol) in pyridine (16 mL) was added to a suspension
of CuCl (1.16 g, 12.0 mmol) and CuCl2 (0.23 g, 1.0 mmol)
in pyridine (30 mL) over 96 h at 608C. After the completion
of the addition, the mixture was allowed to stir for an
additional 24 h at room temperature and then was poured
into CH2Cl2 and water. The organic phase was extracted
with water, 25% NH3 solution (in order to remove the
copper salts), water, 10% acetic acid, water, 10% aqueous
sodium hydroxide, and brine, and dried over MgSO4. After
evaporation of the solvent to a small volume and the
coupling products were precipitated by the addition of
methanol (50 mL) and collected by filtration. Repeated
column chromatography with CH2Cl2/methanol (250:1) and
THF/petroleum ether (1:4) as eluents gave 11 as a slightly
yellow solid (140 mg; 54%) (Rf (THF/petroleum ether
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1
(1:4))¼0.78). Mp .2308C; H NMR (300 MHz, CD2Cl2):
d¼7.54–7.56 (m, 8H), 7.47–7.49 (m, 4H), 7.09 (s, 4H),
7.06 (s, 4H), 4.41 (t, J¼5.7 Hz, 4H), 4.12–4.22 (m, 4H),
3.98–4.10 (m, 20H), 3.51 (s, 6H), 2.64 (t, J¼7.6 Hz, 4H),
2.10–2.20 (m, 4H), 1.80–2.00 (m, 20H), 1.61–1.79 (m,
8H), 1.35 (s, 18H), 1.32 (s, 36H), 1.06–1.16 (m, 36H), 0.97
(t, J¼7.3 Hz, 12H); 13C NMR (75 MHz, CD2Cl2):
d¼173.99, 161.43, 159.35, 154.10, 154.03, 146.88,
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