Effects of electronics, aromaticity, and solvent polarity on the rate of azaquinone-methide-mediated depolymerization of aromatic carbamate oligomers

Article abstract of DOI:10.1021/jo400105m

This paper uses physical-organic studies on well-defined oligomers to establish design principles for creating aromatic poly(carbamates) that depolymerize from head-to-tail in low dielectric constant environments when exposed to specific applied signals. We show that either increasing electron density or decreasing the aromaticity of aromatic repeating units in poly(carbamates) increase the overall depolymerization rate. For example, a methoxybenzene-based repeating unit provides depolymerization rates that are 143× faster than oligomers that contain a benzene-based repeating unit. Furthermore, the rate of depolymerization in the methoxybenzene-based system is tolerant to low dielectric environments, whereas the benzene-based oligomers are not.

Full text of DOI:10.1021/jo400105m

Article
pubs.acs.org/joc
Effects of Electronics, Aromaticity, and Solvent Polarity on the Rate
of Azaquinone−Methide-Mediated Depolymerization of Aromatic
Carbamate Oligomers
Jessica S. Robbins,† Kyle M. Schmid,† and Scott T. Phillips*
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States
S
* Supporting Information
ABSTRACT: This paper uses physical-organic studies on
well-defined oligomers to establish design principles for
creating aromatic poly(carbamates) that depolymerize from
head-to-tail in low dielectric constant environments when
exposed to specific applied signals. We show that either
increasing electron density or decreasing the aromaticity of
aromatic repeating units in poly(carbamates) increase the
overall depolymerization rate. For example, a methoxyben-
zene-based repeating unit provides depolymerization rates that
are 143× faster than oligomers that contain a benzene-based
repeating unit. Furthermore, the rate of depolymerization in
the methoxybenzene-based system is tolerant to low dielectric
environments, whereas the benzene-based oligomers are not.
Currently, there are four classes of these polymers that
depolymerize from head-to-tail, including those that (i)
depolymerize via formation of quinone or azaquinone
methide,5,9,14 (ii) depolymerize via cyclization reactions,10
(iii) combine (i) and (ii) to depolymerize via alternating
cyclization and quinone or azaquinone methide elimination
reactions,11,12,17 and (iv) depolymerize via acetal chemistry.16
This paper addresses a major limitation of the benzene-based
depolymerizable polymers that proceed through azaquinone
methide elimination pathways (Figure 1); these polymers
exhibit slow rates of depolymerization (i.e., hours) in polar
environments and exceedingly slow rates (i.e., days or even not
at all) in environments that have relatively low dielectric
constants compared with that of water (e.g., in plastics, films, or
capsule shell walls).14 In order for these polymers to be useful
in applications that require rapid and tunable responses, we
seek to develop methods both to increase the rate of
depolymerization of this class of polymers and to tune the
ability of the polymers to depolymerize in a variety of
environments.
INTRODUCTION
■
An emerging strategy in polymer chemistry involves designing
polymers and dendrimers that depolymerize continuously from
head to tail in response to a single, specific chemical or physical
signal (Figure 1).1−4 Macromolecules with this capability have
been demonstrated for signal amplification schemes5−8 and
have been configured to create responsive micelles and
nanoparticles for drug delivery,9−13 responsive capsules for
self-healing applications,14 autonomous analyte-responsive
pumps,15 and shape-shifting/reconfigurable plastic materials.16
Depolymerizable aromatic poly(carbamates) contain two
components (Figure 1): (i) a reaction-based detection unit and
(ii) aromatic repeating units. In response to a specific chemical
signal, the reaction-based detection unit is cleaved, revealing an
aniline at the terminus of the polymer, which initiates release of
the next aromatic repeating unit via a presumed azaquinone
methide intermediate. This release process is continuous along
the length of the polymer until the entire polymer
Figure 1. General mechanism of analyte-induced depolymerization in
an aromatic poly(carbamate). Once the reaction-based detection unit
is cleaved by reaction with a specific analyte, the repeating units of the
polymer are released through successive azaquinone methide
elimination reactions. Release of the reporter molecule is used to
determine the kinetics of the depolymerization process.
Received: January 16, 2013
Published: February 18, 2013
© 2013 American Chemical Society
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depolymerizes. A reporter molecule (e.g, a chromophore, such
as p-nitroaniline, Figure 1) often is tethered to the terminus
opposite the reaction-based detection unit as a means to
monitor the kinetics of depolymerization (e.g., by UV/vis
spectroscopy).
The proposed mechanism of azaquinone methide elimi-
nation in these polymers suggests that the release of each
repeating unit proceeds through a less aromatic transition state
(i.e., azaquinone methide) than the aromatic repeating unit.
Proceeding through this less aromatic transition state
presumably results in a large energetic penalty for depolyme-
rization and a slow rate for azaquinone methide-mediated
depolymerization. We reasoned that tuning the electronics and
aromaticity of the aromatic portion of the polymer backbone
could offset the energy penalty associated with the depolyme-
rization reaction. Specifically, we envisaged two different
approaches (Figure 2) that would lower the activation energy
Figure 2. Three repeating units employed in the present study. The
benzene-based repeating unit (a) serves as a reference point, while the
m-methoxybenzene-based unit in (b) tests the effects of electron-
donating groups on the rate of depolymerization.18 The naphthalene-
based unit in (c) tests the effects of aromaticity on the rate of
depolymerization. Naphthalene is less aromatic than benzene as
indicated by the relative aromaticity values of 0.91 and 1.0,
respectively.19
Figure 3. Two oligomeric systems consisting of an aryl boronate
acting as a reaction-based detection unit, one or two repeating units,
and a p-nitroaniline terminus, which when released, will serve as a
reporter molecule. R represents −H, −OMe, or a second aromatic
ring. The difference in half-life between an oligomer containing one
repeating unit (B) and an oligomer containing two repeating units (A)
gives the half-life for the release of a single repeating unit (C).
for the depolymerization reaction either by (i) raising the
HOMO of each repeating unit by addition of electron density
into the aromatic ring (Figure 2b) or (ii) reducing the aromatic
character of the repeating unit (Figure 2c).
Herein we describe a physical organic study to determine the
effects of these hypotheses on the rate of depolymerization of
aromatic poly(carbamates). We designed, synthesized, and
studied several poly(carbamate) oligomers and determined the
rate of release for a single repeating unit in each system.
Furthermore, we studied the effect of environment polarity on
the depolymerization rate of the altered polymer backbones to
quantify the relationship between environment polarity and the
rate of depolymerization. We anticipate that these studies will
help guide future efforts to design poly(carbamate) polymers
that depolymerize quickly in nearly any environment when
exposed to a specific signal.
subsequently proceeds through a quinone methide intermediate
to release the first repeating unit. The last repeating unit will
release p-nitroaniline, which absorbs strongly at 385 nm and
provides a spectroscopic signature of depolymerization that can
be quantified easily using UV/vis spectroscopy.
Hydrogen peroxide was used in 20-fold excess so that the
depolymerization reaction would operate under pseudo-first-
order kinetics. To obtain the rate of release of a single repeating
unit from the data, we measured the half-lives for oligomers
containing one repeating unit (Figure 3, B) and two repeating
units (Figure 3, A). The difference in the half-lives between
these two oligomers provides the half-life for release of a single
repeating unit (Figure 3, C) without complication from the rate
of oxidative cleavage or the rate for release of p-nitroaniline.
Synthesis of the Oligomers. Scheme 1 depicts the
synthetic route to the benzene-based oligomers. The reaction-
based detection unit 2 was synthesized by Miyaura borylation
of 4-bromo-2-methoxybenzyl alcohol. The resulting alcohol was
linked through a trans-carbamation to compound 4, which was
synthesized in two steps from 4-aminobenzyl alcohol.
Deprotection of the resulting carbamate gave 5, which was
linked with p-nitrophenyl isocyanate to afford oligomer 6. To
synthesize oligomer 7, 5 was resubjected to the trans-
RESULTS AND DISCUSSION
■
Design of the Experiments. The oligomeric systems
shown in Figure 3 were designed with the goal of determining
the release time for a single repeating unit from the polymer
backbone. Each oligomer consists of a reaction-based detection
unit (blue), one or two repeating units, and a reporter
(orange). An aryl boronate ester was used as the reaction-based
detection unit. The anticipated mechanism of response is as
follows: the boronate ester reacts selectively with hydrogen
peroxide under mild conditions to reveal a phenol,20 which
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Scheme 1. Synthesis of Benzene-Based Carbamate
Oligomers 6 and 7
Scheme 2. Synthesis of Methoxybenzene-Based Carbamate
Oligomers 12 and 13
a
a
a
Reagents and conditions: (a) NaBH4; (b) TBS-Cl, DMAP, imidazole
(99% over two steps); (c) Pd/C, H2 (93%); (d) PhOCOCl, NaHCO3
(100%); (e) 2, DBTL, toluene, 110 °C (81%); (f) TsOH, THF/H2O
(27% for 11, 66% toward 13); (g) 4-nitrophenyl isocyanate, 80 °C
(77% for 12, 63% for 13); (h) 10, DBTL, dioxanes, 100 °C (37%).
Scheme 3. Synthesis of Naphthalene-Based Carbamate
Oligomer 17 with a Single Repeating Unit
a
Reagents and conditions: (a) bis(pinacolato)diboron, PdCl2dppf,
a
KOAc, 80 °C (85%); (b) PhOCOCl, NaHCO3 (100%); (c) TBS-Cl,
DMAP, imidazole (100%); (d) DBTL, toluene, 110 °C (96%); (e)
TsOH, THF/H2O (58% for 5, 76% toward 7); (f) 4-nitrophenyl
isocyanate, 80 °C (58% for 6, 98% for 7); (g) 4, DBTL, dioxanes, 110
°C (78%).
carbamation reaction, the product was deprotected, and the
deprotected material was labeled with p-nitrophenyl isocyanate.
Oligomer 6 could have been accessed in fewer steps by a tail-to-
head approach, however, the synthesis would have required the
development of two synthetic routes rather than one.
Scheme 2 depicts the synthetic route to the methoxyben-
zene-based oligomers 12 and 13. Compound 10 was made in
four steps from 2-methoxy-4-nitrobenzaldehyde and subjected
to reaction conditions similar to those used to synthesize the
benzene-based oligomers. The poor yields for the silyl ether
deprotection steps were caused by hydrolysis of the pinacol
boronate ester under the aqueous, acidic conditions. Fluoride
could not be used in place of the acid in this step because it
binds to boron and complicates purification steps. To
circumvent these low-yielding steps, an alternative, but similar
route to that depicted in Scheme 2 was carried out using 4-
bromo-2-methoxybenzyl alcohol (compound 1) instead of the
boronate ester (compound 2). Attempts to install the boronate
ester through a Miyaura coupling as a final step, however, led to
decomposition of the oligomers.
a
Reagents and conditions: (a) CaCO3, water, 110 °C; (b) TBS-Cl,
imidazole (84% over two steps); (c) n-BuLi, DMF, −78 °C (97%);
(d) NaClO2, NaH2PO4, 2-methyl-2-butene; (e) DPPA, TEA, 2, 90 °C
(82% over two steps); (f) TsOH, THF−water (79%); (g) 4-
nitrophenyl isocyanate, TEA (54%).
A better solution to the problem of boronate hydrolysis was
employed in the synthesis of the naphthalene-based oligomers
17 and 20 (Schemes 3 and 4). After acid-mediated
deprotection, the acid was neutralized with triethylamine, and
an excess of pinacol was added. This mixture was stirred for 24
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Scheme 4. Synthesis of Naphthalene-Based Carbamate
a
Oligomer 20 with Two Repeating Units
a
Reagents and conditions: (a) DPPA, TEA, 4-(hydroxymethyl)-1-
naphthalenecarboxaldehyde), 90 °C (79% over two steps from (d) in
Scheme 3); (b) NaClO2, NaH2PO4, 2-methyl-2-butene; (c) DPPA,
TEA, 2, 90 °C (55% over two steps); (d) TsOH, THF−water (91%);
(e) 4-nitrophenyl isocyanate, TEA, DMF (40%)
h to convert the boronic acid back to the pinacol ester,
providing yields of 79−91%. These oligomers were accessed by
routes that differed from those of the benzene- and
methoxybenzene-based oligomers because functionalized naph-
thalene starting materials (such as amino- or nitro-function-
alized naphthalene) were not available commercially. There-
fore, the carbamates were installed using Curtius rearrange-
ments.
Demonstration that the Oligomers Depolymerize
When Exposed to H2O2. Oligomer 12 was exposed to 20
equiv of hydrogen peroxide in a 200 μM solution of 5:4:1 p-
dioxanes−DMSO−water (0.01 M phosphate buffer, pH 7.1).
The absorbance values from 250−450 nm were monitored
every 5 min for 1 h (Figure 4a); the λmax for p-nitroaniline in
this solvent composition is 385 nm. The two distinct isosbestic
points in Figure 4a suggest clean conversion from the parent
oligomer to the released p-nitroaniline.
The depolymerization reaction also was followed using
LCMS (Figure 4b). Oligomer 13 was exposed to 20 equiv of
hydrogen peroxide in a 1 mg/mL (1.27 M) solution of 9:1
acetonitrile−water (0.01 M phosphate buffer, pH 7.1). After 30
min, the oligomer had converted completely into the expected
small molecules products 4-hydroxybenzyl alcohol, 4-amino-
benzyl alcohol, and p-nitroaniline (see Figure S1 (Supporting
Information) for representative mass spectra). The presence of
these products suggests that the oligomer depolymerizes from
head-to-tail upon exposure to hydrogen peroxide.
Analysis of the Depolymerization Kinetics of Aro-
matic Poly(carbamate) Oligomers. The rate of release of p-
nitroaniline from oligomers 6, 7, 12, 13, 17, and 20 was
determined from UV/vis absorbance data acquired over time
after exposure to hydrogen peroxide. A 200 μM solution of
each oligomer in a 5:4:1 mixture of p-dioxanes−DMSO−water
(0.01 M phosphate buffer, pH 7.1) was treated with excess of
hydrogen peroxide (20 equiv) (Figure 5a). The release of p-
Figure 4. (a) Wavelength scans over time for oligomer 12 when
treated with 20 equiv of hydrogen peroxide. (b) LCMS spectra at 254
nm for oligomer 13 before and 60 min after exposure to 20 equiv of
hydrogen peroxide. The oligomer depolymerizes into 4-hydroxybenzyl
alcohol, 4-aminobenzyl alcohol, and p-nitroaniline. See Figure S1
(Supporting Information) for representative mass spectra.
nitroaniline was monitored by UV/vis spectroscopy at 385 nm.
The rate constants for release of p-nitroaniline were converted
to half-lives for each oligomer and further comparisons (e.g.,
Figure 3) provided half-lives per repeating unit (Figure 5). For
example, the half-lives for the benzene-based oligomers were
found to be 39.5 2.1 min for oligomer 6 (one repeating unit)
and 639 3.8 min for oligomer 7 (two repeating units). By
subtracting the half-life for the one-unit oligomer (6) from the
half-life of the two-unit oligomer (7), we obtained the half-life
for release of a single repeating unit, which is 599.5 4.3 min.
Figure 5 reveals that the naphthalene-based repeating unit
depolymerizes 113× faster than the benzene-based system,
whereas the methoxybenzene-based system is 1.3× faster still.
These results suggest that both hypotheses of (i) adding
electron density into the benzene ring and (ii) decreasing the
aromaticity of the ring improve the rate of depolymerization
substantially over the parent benzene-based oligomer.
Adding electron density and/or decreasing the aromaticity of
each repeating unit also increases the occurrence of background
depolymerization due to hydrolysis reactions, but this increase
is offset substantially by the rapid rate of depolymerization
when exposed to the desired signal. For example, exposure of
oligomers 7, 13, and 20 to the same solvent conditions as in
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Figure 5. Half-lives for release of each repeating unit during a depolymerization reaction. (a) The release of p-nitroaniline from the oligomers via
depolymerization in response to excess hydrogen peroxide was measured by UV/vis spectroscopy. (b) Comparison of the half-lives for the release of
one repeating unit. The values are the average of three measurements and the error bars represent the standard deviations from these averages.
Figure 5a, but in the absence of hydrogen peroxide, over 10 h
(a long exposure time given the depolymerization half-life of
4.2 1.1 min and 5.3 0.8 min for a single unit in 13 and 20,
respectively) revealed that the methoxybenzene- and naph-
thalene-based oligomers decomposed nonspecifically 4× and
14× more than the benzene-based oligomer (Figure S3,
Supporting Information). The magnitude of nonspecific
depolymerization under this long exposure time is equally
telling: i.e., the benzene-based oligomer decomposed by 1.7%
while the methoxybenzene- and naphthalene-based oligomers
decomposed 7.5% and 24%, respectively. Consequently, the
rate of background reaction must be taken into account when
designing functional materials from these types of oligomers/
polymers when the material will remain exposed to an aqueous
environment for prolonged periods.
Solvent Effects on the Depolymerization Rate. The
polarity of the environment in which the aromatic-based
oligomers/polymers depolymerize should have a substantial
effect on the rate of depolymerization.18 To test this idea, we
measured the half-life for release of a single repeating unit in
solvent systems that varied in polarity (Figure 6).
The reaction conditions and subtraction procedure shown in
Figure 5a were used in this experiment as well, with the
exception that the solvent system was varied by altering the
percentage of dioxanes in the p-dioxanes−DMSO−water (0.01
M phosphate buffer, pH 7.1) mixture. For example, the
experiment corresponding to 30% dioxanes used a solvent
system consisting of 30% dioxanes and 70% 4:1 DMSO−water.
The ratio of DMSO to buffered H2O was kept constant at 4:1
in all experiments.
For the benzene-based oligomers, the half-life is prohibitively
long, even in the highest polarity solvents in which it is soluble,
yet increases further as the polarity of the solvent decreases.
The methoxybenzene- and naphthalene-based systems, in
contrast, show slight increases in half-life as the polarity of
the solvent decreases up to a solvent composition containing
50% dioxanes. Even in 70% dioxanes, the half-life for one
repeating unit increases by only 22 min for the methoxy-
benzene-based system and 15 min for the naphthalene-based
system relative to the half-lives in 10% dioxanes. These new
oligomers not only depolymerize faster than the benzene-based
Figure 6. Solvent effects on the rate for releasing a single repeating
unit using the general conditions described in Figure 3. The color of
the data points reflects the composition of the repeating unit as
follows: the benzene-based repeating unit is green, the methoxy-
benzene-based repeating unit is black, and the naphthalene-based
repeating unit is blue. The inset shows the data for just the
methoxybenzene- and naphthalene-based repeating units. The solvent
polarity reflects the percentage of dioxanes in the solvent system. The
half-lives are the average of three trials (N = 3); most of the error bars
are smaller than the data points.
system, they also depolymerize quickly in substantially more
nonpolar environments than the benzene-based system.
CONCLUSIONS
■
In conclusion, our fundamental studies show that the rate of
depolymerization of stimuli-responsive poly(carbamates) can
be increased both by altering the electron density and
decreasing the overall aromatic character of the repeating
units. Implementation of these strategies is especially useful in
low polarity environments where the rate of depolymerization
(i.e., formation of azaquinone methide) is slow. We expect that
this work will provide guidance for modifying depolymerizable
poly(carbamates) rationally, which will make this class of
depolymerizable polymers more suitable to a diverse range of
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applications, including those involving responses in the solid
state, such as in stimuli-responsive materials and smart coatings.
EXPERIMENTAL PROCEDURES
■
Materials. All reactions were performed in flame-dried glassware
under a positive pressure of argon unless otherwise noted. Air- and
moisture-sensitive liquids were transferred via syringe or stainless steel
cannula. Organic solutions were concentrated by rotary evaporation
(25−40 mmHg) at 30 °C. All reagents were purchased commercially
and were used as received. Acetonitrile, benzene, dichloromethane,
N,N-dimethylformamide, tetrahydrofuran, toluene, and triethylamine
were purified by the method of Pangborn et al.21 Flash column
chromatography was performed as described by Still et al.,22
employing silica gel (60 Å pore size, 32−63 μm, standard grade).
Thin-layer chromatography was carried out on silica gel TLC plates
(20 × 20 cm w/h, F-254, 250 μm). Deionized water was purified by
filtration and irradiation with UV light.
Methods. Proton nuclear magnetic resonance (1H NMR) spectra
and carbon nuclear magnetic resonance spectra (13C NMR) were
recorded using either a 300, 360, or 400 MHz NMR spectrometer at
25 °C, as indicated. Proton chemical shifts are expressed in parts per
million (ppm) and are referenced to residual protium in the NMR
solvent (CHCl3 δ 7.26 ppm or CO(CH3)2 δ 2.05 ppm).23 Data are
represented as follows: chemical shift, multiplicity (s = singlet, bs =
broad singlet, d = doublet, dd = doublet of doublets, t = triplet, m =
multiplet, and/or multiple resonances), integration, and coupling
constant (J) in hertz. Carbon chemical shifts are expressed in parts per
million and are referenced to the carbon resonances of the NMR
solvent (CDCl3 δ 77.0 ppm or CO(CH3)2 δ 29.8 and 206.3 ppm).
UV/vis spectroscopic data were obtained using a six-cell spectrometer.
LCMS data was obtained using an HPLC with a UV detector, a
quadrupole mass spectrometer equipped with an atmospheric-pressure
chemical ionization chamber, and a 150 mm ×2.1 mm Betasil diphenyl
column. Preparative-scale HPLC was performed using an HPLC with
a UV detector and a 150 mm × 30 mm preparative C18 column. Low-
and high-resolution mass spectra were acquired using mobile phases
containing 5 mM ammonium formate.
Figure 7. (a) Plot of “extent of reaction” vs “time” for oligomer 13 and
compound 21. For the oligomer, the extent of reaction refers to the
complete release of p-nitroaniline, whereas for compound 21, extent of
reaction refers to complete oxidative cleavage to reveal 2-
methoxyphenol. (b) A plot of “ln(extent of reaction)” vs “time” for
oligomer 13. The linear region, showing first-order kinetics, is
bracketed with blue lines.
determined by dividing ln(2) by the slope of the line obtained from
the first-order plot.
General Conditions for Measuring the Release Kinetics of
Oligomers 6, 7, 12, 13, 17, and 20. p-Dioxanes (250 μL), dimethyl
sulfoxide (190 μL), and phosphate-buffered water (40 μL, 0.01 M, pH
7.1) were added to a 2 mL vial and swirled to mix. Compound 6 (10
μL from a 0.01 M solution in DMSO) was added to the vial, and the
vial was vortexed for 5 s. Hydrogen peroxide (10 μL from a 0.2 M
solution in phosphate-buffered water, 0.01 M, pH 7.1) was added, and
the combined solution was aspirated using a pipet. The solution was
transferred to a quartz cuvette (500 μL, 0.1 cm path length), and the
absorbance value at 385 nm was monitored continuously. (This
example is for the “50% dioxanes” scenario referred to in Figures 5 and
6.)
Methodology for Determining Half-Lives. 3-Methoxyphenyl-
boronic acid pinacol ester, compound 21 (Figure 7), was synthesized
as a model of a reaction-based detection unit to measure the rate of
oxidative cleavage of the boronic ester in the absence of a subsequent
depolymerization. The oxidation of compound 21 to 3-methoxyphenol
was monitored using UV/vis spectroscopy. The absorbance value at
288 nm was measured continuously under the solvent conditions
shown in Figure 5. Figure 7a compares the rate of oxidative cleavage of
21 to the rate of release of p-nitroaniline for oligomer 13. The
oxidative cleavage reaction reaches 90% completion at approximately
20 min; thus, the first 20 min of the oligomer depolymerization
kinetics will be affected by the kinetics of the oxidative cleavage
reaction. Therefore, the first 20 min of the kinetics data for 13 and the
other oligomers were excluded when determining half-lives for
depolymerization.
Preparation of Compound 4. Phenyl chloroformate (1.7 mL, 13
mmol, 1.1 equiv) was added dropwise over 5 min to a solution of 4-
aminobenzyl alcohol (1.5 g, 12 mmol, 1.0 equiv) in a 2:2:1 mixture of
tetrahydrofuran-saturated aqueous sodium bicarbonate−water (60
mL) under an atmosphere of air. The reaction mixture was stirred
for 15 min at 23 °C. Dichloromethane (30 mL) was added in one
portion, followed by saturated aqueous sodium bicarbonate (10 mL)
in one portion, and the organic and aqueous layers were separated.
The organic layer was washed with saturated aqueous sodium
bicarbonate solution (1 × 50 mL) and was dried over sodium sulfate.
The sodium sulfate was removed by filtration, the solvent was removed
by rotary evaporation, and the residue was purified by silica gel flash
column chromatography (10% ethyl acetate in hexanes, increasing to
70% ethyl acetate in hexanes) to afford compound 22 as a white solid
1
(2.8 g, 12 mmol, 95%), which was identical by H NMR with the
known compound.7
tert-Butyldimethylsilyl chloride (0.75 g, 5.0 mmol, 1.2 equiv),
imidazole (0.42 g, 6.2 mmol, 1.5 equiv), and dimethylaminopyridine
(50 mg, 42 μmol, 0.01 equiv) were added to a solution of compound
22 (1.0 g, 4.2 mmol, 1.0 equiv) in dichloromethane (14 mL) at 23 °C.
The reaction mixture was stirred for 1 h at 23 °C and then quenched
by dropwise addition of methanol (5 mL). The solvent was removed
by rotary evaporation, and the residue was purified by silica gel flash
column chromatography (2% ethyl acetate in hexanes, increasing to
20% ethyl acetate in hexanes) to afford compound 4 as a white,
amorphous solid (1.4 g, 4.0 mmol, 96%): IR (cm−1) 3314, 2928, 2856,
1713, 1614, 1543; 1H NMR δ (300 MHz, CDCl3) 7.44−7.20 (m, 9H),
6.97 (bs, 1H), 4.73 (s, 2H), 0.96 (s, 9H), 0.12 (s, 6H); 13C NMR δ
(300 MHz, CDCl3) 150.7, 136.3, 129.6, 127.1, 125.8, 121.8, 118.8,
64.7, 26.1, 18.6, −5.1 (There appear to be overlapping peaks in the
aromatic region of the 13C spectrum); MS (Q MS APCI+) 358.3 (M +
Based on this caveat, the following method was used to calculate the
half-lives for the depolymerization reactions based on the relative
quantity of released p-nitroaniline. The natural log of the extent of the
reaction was plotted against time (Figure 7b). The half-life was
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+
H+); HRMS (TOF MS AP+) calcd for C20H31N2O3Si (M + NH4 )
375.2104, found 375.2125.
oligomer 6 as an off-white, amorphous solid (0.11 g, 0.19 mmol, 58%):
IR (cm−1) 3308, 2976, 1708, 1598, 1534, 1508; 1H NMR δ (300 MHz,
CO(CD3)2) 9.31 (bs, 1H), 8.81 (bs, 1H), 8.16 (d, 2H, J = 5.0 Hz),
7.76 (d, 2H, J = 5.0 Hz), 7.56 (d, 2H, J = 8.6 Hz), 7.36−7.30 (m, 5H),
5.18 (s, 2H), 5.12 (s, 2H), 3.83 (s, 3H), 1.29 (s, 12H); 13C NMR δ
(300 MHz, CO(CD3)2) 157.3, 154.0, 153.8, 146.1, 143.1, 140.1, 131.0,
129.9, 128.7, 128.7, 127.5, 125.4, 118.8, 118.3, 118.2, 116.1, 84.3, 67.2,
62.0, 55.5, 24.9; MS (Q MS APCI−) 576.2 (M − H+); HRMS (TOF
MS AP−) calcd for C29H31BN3O9 (M − H+) 576.2153, found
576.2130.
Preparation of Compound 2. 4-Bromo-2-methoxybenzyl alcohol
(1.0 g, 4.6 mmol, 1 equiv), bis(pinacolato)diboron (1.4 g, 5.5 mmol,
1.2 equiv), PdCl2(dppf)·CH2Cl2 (0.19 g, 0.23 mmol, 0.05 equiv), 1,1′-
bis(diphenylphosphino)ferrocene (0.13 g, 0.23 mmol, 0.05 equiv), and
KOAc (1.4 g, 13.8 mmol, 3 equiv) were sealed in a two-neck round-
bottom flask equipped with a coldfinger and placed under vacuum for
1 h. The flask was purged with argon, and p-dioxanes (35 mL) was
added. The reaction mixture was heated to 80 °C and stirred for 48 h.
The reaction mixture was cooled to 23 °C, diluted with ethyl acetate
(35 mL), and filtered through a pad of alternating layers of Celite and
silica gel (with silica gel as the bottom layer, 6 layers in total). The
filtrate was concentrated by rotary evaporation, and the residue was
purified using preparative, centrifugally accelerated radial thin-layer
chromatography (10% ethyl acetate in hexanes on a 4 cm silica gel
plate) to afford compound 2 as a white, amorphous solid (1.1 g, 3.9
Preparation of Oligomer 7. Dibutyltin dilaurate (0.15 mL, 0.26
mmol, 0.2 equiv) was added dropwise to a solution of compounds 5
(0.53 g, 1.3 mmol, 1.0 equiv) and 4 (0.50 g, 1.4 mmol, 1.1 equiv) in
toluene (6.4 mL) at 110 °C. The reaction mixture was stirred for 2 h at
110 °C and then cooled to 23 °C. The solution was concentrated by
rotary evaporation, and the residue was purified by silica gel flash
chromatography (10% ethyl acetate in hexanes increasing to 30% ethyl
acetate in hexanes) to afford 24 as a yellow oil (0.68 g, 1.1 mmol,
1
mmol, 85%): IR (cm−1) 3505, 2984; H NMR δ (300 MHz, CDCl3)
1
7.45 (d, 1H, J = 7.2 Hz), 7.32−7.30 (m, 2H), 4.71 (d, 2H, J = 5.1 Hz),
3.92 (s, 3H), 2.53 (bs, 1H), 1.37 (s, 12H); 13C NMR δ (300 MHz,
CDCl3) 156.8, 132.2, 127.9, 127.5, 115.5, 83.8, 62.1, 55.3, 24.9 (there
appear to be overlapping peaks in the aromatic region of the 13C
spectrum); MS (Q MS APCI+) 247.1 (M − OH−); HRMS (TOF MS
AP+) calcd for C14H20O3B (M − OH−) 247.1506, found 247.1504.
Preparation of Oligomer 6. Dibutyltin dilaurate (25 μL, 43
μmol, 0.2 equiv) was added dropwise to a solution of compounds 2
(63 mg, 0.24 mmol, 1.1 equiv) and 4 (77 mg, 0.22 mmol, 1.0 equiv) in
toluene (2.2 mL) at 110 °C. The reaction mixture was stirred for 2 h at
110 °C, then cooled to 23 °C. The solution was concentrated by
rotary evaporation and the residue was purified by silica gel flash
chromatography (5% ethyl acetate in hexanes, increasing to 15% ethyl
acetate in hexanes) to afford 23 as a yellow oil (110 mg, 0.21 mmol,
78%): IR (cm−1) 3314, 2929, 2856, 1709, 1600, 1528; H NMR δ
(400 MHz, CO(CD3)2) 8.84 (bs, 1H), 8.67 (bs, 1H), 7.62 (d, 2H, J =
8.3 Hz), 7.55 (d, 2H, J = 8.3 Hz), 7.42−7.36 (m, 4H), 7.30−7.26 (m,
3H), 5.22 (s, 2H), 5.11 (s, 2H), 4.71 (s, 2H), 3.89 (s, 3H), 1.34 (s,
12H), 0.93 (s, 9H), 0.10 (s, 6H); 13C NMR δ (400 MHz, CO(CD3)2)
157.6, 154.4, 154.4, 140.2, 139.1, 136.7, 132.0, 130.0, 129.1, 129.0,
127.9, 127.7, 119.0, 116.5, 84.7, 66.7, 65.3, 62.3, 55.8, 26.4, 18.9, 17.5,
−5.0 (there appear to be overlapping peaks in the aromatic region of
the 13C spectrum); MS (Q MS APCI−) 675.3 (M − H+); HRMS
(TOF MS AP−) calcd for C36H48BN2O8Si (M − H+) 675.3273, found
675.3254.
p-Toluenesulfonic acid monohydrate (57 mg, 0.30 mmol, 0.3 equiv)
was added in one portion to a solution of compound 24 (0.68 g, 1.0
mmol, 1.0 equiv) in a 9:1 mixture of tetrahydrofuran−water (10 mL).
The reaction mixture was stirred at 23 °C under an atmosphere of air
for 5 h. Ethyl acetate (5 mL) was added in one portion, followed by
saturated aqueous sodium bicarbonate (5 mL) in one portion, and the
organic and aqueous layers were separated. The organic layer was
washed with saturated aqueous sodium bicarbonate solution (1 × 10
mL) and was dried over sodium sulfate. The sodium sulfate was
removed by filtration, the solvent was removed by rotary evaporation,
and the residue was purified by silica gel flash column chromatography
(30% ethyl acetate in hexanes increasing to 50% ethyl acetate in
hexanes) to afford compound 25 as a white, amorphous solid (0.43 g,
0.76 mmol, 76%): IR (cm−1) 3302, 2976, 1705, 1601, 1530; 1H NMR
δ (300 MHz, CO(CD3)2) 8.85 (bs, 1H), 8.66 (bs, 1H), 7.60 (d, 2H, J
= 8.5 Hz), 7.52 (d, 2H, J = 8.3 Hz), 7.41−7.26 (m, 7H), 5.21 (s, 2H),
5.10 (s, 2H), 4.55 (s, 2H), 4.00 (bs, 1H), 3.88 (s, 3H), 1.33 (s, 12H);
13C NMR δ (300 MHz, CO(CD3)2) 157.7, 154.5, 154.4, 140.3, 139.1,
137.8, 132.1, 130.1, 129.1, 128.2, 127.9, 119.1, 116.6, 84.8, 66.8, 64.5,
62.4, 55.9, 25.3 (there appear to be overlapping peaks in the aromatic
region of the 13C spectrum); MS (Q MS APCI−) 561.3 (M − H+);
HRMS (TOF MS AP−) calcd for C30H34BN2O8 (M − H+) 561.2408,
found 561.2406.
A solution of compound 25 (0.10 g, 0.18 mmol, 1.0 equiv) and 4-
nitrophenyl isocyanate (35 mg, 0.21 mmol, 1.2 equiv) in toluene (1.8
mL) was heated to 80 °C. The reaction mixture was stirred for 2.5 h at
80 °C and then cooled to 23 °C. The solvent was removed by rotary
evaporation, and the residue was purified by preparative scale HPLC
(C18 column, 30% acetonitrile in water increasing to 90% over 10
min, maintaining 90% acetonitrile in water for 15 min) to afford
oligomer 7 as an off-white, amorphous solid (130 mg, 0.17 mmol,
98%): IR (cm−1) 3307, 2976, 2148, 1705, 1598, 1529, 1508; 1H NMR
δ (300 MHz, CO(CD3)2) 9.37 (bs, 1H), 8.85 (bs, 1H), 8.79 (bs, 1H),
8.22 (d, 2H, J = 9.3 Hz), 7.82 (d, 2H, J = 9.3 Hz), 7.60 (d, 4H, J = 8.3)
7.40−7.33 (m, 7H), 5.20 (s, 2H), 5.15 (s, 2H), 5.11 (s, 2H), 3.88 (s,
3H), 1.32 (s, 12H); 13C NMR δ (360 MHz, CO(CD3)2) 157.5, 154.3,
154.3, 146.4, 143.4, 140.4, 140.2, 131.8, 131.2, 130.2, 130.0, 129.0,
128.9, 127.8, 125.7, 119.0, 118.6, 118.5, 116.4, 84.6, 67.4, 66.8, 62.2,
55.8, 25.1; MS (Q MS APCI−) 761.2 (M − H+ + 2H2O); HRMS
(TOF MS AP−) calcd for C37H38BN4O11 (M − H+) 725.2630, found
725.2632.
1
96%): IR (cm−1) 3318, 2923, 2852, 1724, 1532; H NMR δ (300
MHz, CDCl3) 7.47−7.27 (m, 7H), 6.98 (bs, 1H), 5.31 (s, 2H), 4.72
(s, 2H), 3.91 (s, 3H), 1.39 (s, 12H), 0.97 (s, 9H), 0.13 (s, 6H); 13C
NMR δ (300 MHz, CDCl3) 159.9, 156.8, 136.7, 132.0, 128.9, 127.5,
127.2, 126.8, 118.5, 115.8, 83.9, 64.6, 62.4, 55.5, 25.9, 24.8, 18.3, −5.3
(There appear to be overlapping peaks in the aromatic region of the
13C spectrum); MS (Q MS APCI−) 526.3 (M − H+); HRMS (TOF
MS AP−) calcd for C28H41BNO6Si (M − H+) 526.2796, found
526.2811.
p-Toluenesulfonic acid monohydrate (32 mg, 0.17 mmol, 0.3 equiv)
was added in one portion to a solution of compound 23 (0.30 g, 0.57
mmol, 1.0 equiv) in a 4:1 mixture of tetrahydrofuran−water (5.7 mL).
The reaction mixture was stirred at 23 °C under an atmosphere of air
for 3 h. Ethyl acetate (10 mL) was added in one portion, followed by
saturated aqueous sodium bicarbonate (10 mL) in one portion, and
the organic and aqueous layers were separated. The organic layer was
washed with saturated aqueous sodium bicarbonate solution (1 × 10
mL) and was dried over sodium sulfate. The sodium sulfate was
removed by filtration, the solvent was removed by rotary evaporation,
and the residue was purified by silica gel flash column chromatography
(100% hexanes increasing to 60% ethyl acetate in hexanes) to afford
compound 5 as a white, amorphous solid (140 mg, 0.33 mmol, 58%):
IR (cm−1) 3493, 3278, 2968, 2918, 2860, 1713, 1604, 1545; 1H NMR
δ (400 MHz, CO(CD3)2) 8.72 (bs, 1H), 7.53 (d, 2H, J = 8.4 Hz), 7.40
(d, 1H, J = 7.4 Hz), 7.36 (d, 1H, J = 7.4 Hz), 7.29−2.27 (m, 3H), 5.21
(s, 2H), 4.56 (s, 2H), 4.08 (bs, 1H), 3.87 (s, 3H), 1.33 (s, 12H); 13C
NMR δ (400 MHz, CO(CD3)2) 157.3, 154.1, 138.7, 137.4, 128.9,
128.7, 127.9, 127.6, 118.7, 116.1, 84.4, 64.2, 61.9, 55.5, 25.0 (There
appear to be overlapping peaks in the aromatic region of the 13C
spectrum); MS (Q MS APCI−) 412.1 (M − H+); HRMS (TOF MS
AP−) calcd for C22H27BNO6 (M − H+) 412.1937, found 412.1935.
A solution of compound 5 (0.14 g, 0.33 mmol, 1.0 equiv) and 4-
nitrophenyl isocyanate (64 mg, 0.39 mmol, 1.2 equiv) in toluene (3.3
mL) was heated to 80 °C. The reaction mixture was stirred for 3 h at
80 °C and then cooled to 23 °C. The solvent was removed by rotary
evaporation and the residue was purified by preparative scale HPLC
(C18 column, 30% acetonitrile in water increasing to 90% over 10
min, maintaining 90% acetonitrile in water for 15 min) to afford
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Preparation of Compound 10. Sodium borohydride (0.69 g, 18
mmol, 1.1 equiv) was added in one portion to a solution of 2-methoxy-
4-nitrobenzaldehyde (3.0 g, 17 mmol, 1.0 equiv) in a 1:1 mixture of
dichloromethane−methanol (56 mL) at 0 °C. The reaction mixture
was stirred for 15 min at 0 °C and then was slowly diluted by dropwise
addition of saturated aqueous ammonium chloride solution (10 mL)
and allowed to warm to 23 °C. Dichloromethane (50 mL) was added
in one portion, followed by saturated aqueous ammonium chloride
solution (50 mL) in one portion, and the organic and aqueous layers
were separated. The organic layer was washed with saturated aqueous
sodium chloride solution (1 × 50 mL) and was dried over sodium
sulfate. The sodium sulfate was removed by filtration, and the solvent
was removed by rotary evaporation to provide compound 26 as a pale
yellow, amorphous solid, which was used without further purification.
tert-Butyldimethylsilyl chloride (3.0 g, 20 mmol, 1.2 equiv),
imidazole (1.7 g, 25 mmol, 1.5 equiv), and dimethylaminopyridine
(20 mg, 0.17 mmol, 0.01 equiv) were added in one portion to a
solution of compound 26 (3.0 g, 17 mmol, 1.0 equiv) in
dichloromethane at 23 °C. The reaction mixture was stirred for 1 h
at 23 °C and then was quenched by dropwise addition of methanol
(10 mL). The solvent was removed by rotary evaporation and the
residue was purified by silica gel flash column chromatography (100%
hexanes followed by 10% ethyl acetate in hexanes) to afford
compound 9 as a light yellow, amorphous solid (4.9 g, 16 mmol,
Preparation of Oligomer 12. Dibutyltin dilaurate (0.10 mL, 0.18
mmol, 0.2 equiv) was added dropwise to a solution of compounds 2
(0.23 g, 0.89 mmol, 1.1 equiv) and 10 (0.31 g, 0.81 mmol, 1.0 equiv)
in toluene (8 mL) at 110 °C. The reaction mixture was stirred for 0.5
h at 110 °C and then cooled to 23 °C. The solution was concentrated
by rotary evaporation, and the residue was purified by silica gel flash
chromatography (10% ethyl acetate in hexanes increasing to 15% ethyl
acetate in hexanes) to afford 28 as a yellow oil (0.36 g, 0.65 mmol,
81%): IR (cm−1) 3318, 2928, 2854, 2361, 1736, 1605, 1535, 1511; 1H
NMR δ (400 MHz, CDCl3) 7.41−7.26 (m, 5H) 6.72−6.69 (m, 2H),
5.27 (s, 2H), 4.70 (s, 2H), 3.89 (s, 3H), 3.80 (s, 3H), 1.35 (s, 12H),
0.94 (s, 9H), 0.09 (s, 6H); 13C NMR δ (300 MHz, CDCl3) 156.8,
156.4, 153.5, 137.7, 128.8, 127.4, 127.1, 127.1, 125.0, 115.8, 109.9,
100.9, 83.9, 62.3, 59.9, 55.4, 55.1, 26.0, 24.8, 18.4, −5.4 (there appear
to be overlapping peaks in the aromatic region of the 13C spectrum);
MS (Q MS APCI−) 556.3 (M − H+). HRMS (TOF MS AP−) calcd
for C29H43BNO7Si (M − H+) 556.2902, found 556.2900.
p-Toluenesulfonic acid monohydrate (37 mg, 0.20 mmol, 0.3 equiv)
was added in one portion to a solution of compound 28 (0.36 g, 0.65
mmol, 1.0 equiv) in a 4:1 mixture of tetrahydrofuran−water (6.5 mL).
The reaction mixture was stirred at 23 °C under an atmosphere of air
for 3.5 h. Ethyl acetate (5 mL) was added in one portion, followed by
saturated aqueous sodium bicarbonate (5 mL) in one portion, and the
organic and aqueous layers were separated. The organic layer was
washed with saturated aqueous sodium bicarbonate solution (1 × 20
mL) and was dried over sodium sulfate. The sodium sulfate was
removed by filtration, the solvent was removed by rotary evaporation,
and the residue was purified by silica gel flash column chromatography
(5% acetone in methylene chloride increasing to 10% acetone in
methylene chloride) to afford compound 11 as a yellow, amorphous
solid (79 mg, 0.18 mmol, 27%): IR (cm−1) 3302, 2974, 2855, 1729,
1
99% over 2 steps): IR (cm−1) 2926, 2855, 1516; H NMR δ (300
MHz, CDCl3) 7.89 (dd, 1H, J = 8.3 Hz, 2.0 Hz), 7.67−7.64 (m, 2H),
4.80 (s, 2H), 3.93 (s, 3H), 0.98 (s, 9H), 0.15 (s, 6H); 13C NMR δ
(300 MHz, CDCl3) 156.0, 147.8, 138.1, 126.6, 116.1, 104.5, 60.1, 55.8,
26.1, 18.5, −5.3. Anal. Calcd for C14H23NO4Si: C, 56.54; H, 7.79; N,
4.71. Found: C, 56.56; H, 7.88; N, 4.65.
Palladium (10% by weight on carbon powder) (0.30 g, 15% by
weight of compound 9) was added in one portion to a solution of
compound 9 (2.0 g, 6.7 mmol, 1.0 equiv) in tetrahydrofuran (34 mL)
under a N2 atmosphere. The flask was evacuated and purged three
times with H2 gas. The reaction mixture was stirred vigorously for 1.5
h at 23 °C under an atmosphere of H2. The flask was evacuated and
purged with argon, and the reaction mixture was filtered through a pad
of Celite. The solvent was removed by rotary evaporation, and the
residue was purified by silica gel flash column chromatography (25%
ethyl acetate in hexanes, increasing to 60% ethyl acetate in hexanes) to
afford compound 27 as a brown, amorphous solid (1.7 g, 6.2 mmol,
1
1606, 1538, 1511; H NMR δ (360 MHz, CO(CD3)2) 8.74 (bs, 1H),
7.40−7.27 (m, 5H), 7.06 (dd, 1H, J = 8.1 Hz, 1.8 Hz), 5.20 (s, 2H),
4.53 (s, 2H), 3.87 (s, 3H), 3.77 (s, 3H), 1.34 (s, 12H); 13C NMR δ
(360 MHz, CO(CD3)2) 157.7, 157.3, 154.0, 140.0, 128.9, 128.6, 128.4,
127.6, 125.3, 116.1, 110.3, 101.6, 84.4, 61.9, 59.5, 55.5, 55.2, 24.9
(There appear to be overlapping peaks in the aromatic and aliphatic
regions of the 13C spectrum); MS (Q MS APCI−) 442.1 (M − H+);
HRMS (TOF MS AP−) calcd for C23H29BNO7 (M − H+) 442.2037,
found 442.2058.
A solution of compound 11 (0.10 g, 0.23 mmol, 1.0 equiv) and 4-
nitrophenyl isocyanate (45 mg, 0.27 mmol, 1.2 equiv) in toluene (1.8
mL) was brought to 80 °C. The reaction mixture was stirred for 1 h at
80 °C, and then the solution was cooled to 23 °C. The solvent was
removed by rotary evaporation and the residue was purified by
preparative scale HPLC (C18 column, 30% acetonitrile in water
increasing to 90% over 10 min, maintaining 90% acetonitrile in water
for 15 min) to afford oligomer 12 as a yellow, amorphous solid (0.11
1
93%): IR (cm−1) 3364, 2928, 2855, 1616, 1511; H NMR δ (400
MHz, CDCl3) 7.21 (d, 1H, J = 8.0 Hz), 6.31 (dd, 1H, J = 8.0, 1.8 Hz),
6.23 (d, 1H, J = 1.6 Hz), 4.69 (s, 2H), 3.78 (s, 3H), 3.65 (bs, 2H), 0.96
(s, 9H), 0.12 (s, 6H); 13C NMR δ (400 MHz, CDCl3) 157.4, 146.7,
128.6, 120.1, 107.0, 98.2, 60.3, 55.2, 26.2, 18.6, −5.1; MS (Q MS APCI
+) 268.2 (M + H+); HRMS (TOF MS AP+) calcd for C14H26NO2Si
(M + H+) 268.1733, found 268.1723.
1
g, 0.18 mmol, 77%): IR (cm−1) 3309, 2975, 1709, 1600, 1509; H
Phenyl chloroformate (0.85 mL, 6.8 mmol, 1.1 equiv) was added
dropwise over 5 min to a solution of compound 27 (1.7 g, 6.2 mmol,
1.0 equiv) in a 2:2:1 mixture of tetrahydrofuran−saturated aqueous
sodium bicarbonate−water (30 mL) under an atmosphere of air. The
reaction mixture was stirred for 15 min at 23 °C. Ethyl acetate (30
mL) was added in one portion, followed by saturated aqueous sodium
bicarbonate (10 mL) in one portion, and the organic and aqueous
layers were separated. The organic layer was washed with saturated
aqueous sodium bicarbonate solution (1 × 50 mL) and was dried over
sodium sulfate. The sodium sulfate was removed by filtration, the
solvent was removed by rotary evaporation, and the residue was
purified by silica gel flash column chromatography (5% ethyl acetate in
hexanes, increasing to 10% ethyl acetate in hexanes) to afford
compound 10 as a white, amorphous solid (2.4 g, 6.2 mmol, 100%):
IR (cm−1) 3272, 2928, 2854, 1712, 1610, 1550; 1H NMR δ (300 MHz,
CDCl3) 7.45−7.21 (m, 8H), 6.81 (d, 1H, J = 8.1 Hz), 4.78 (s, 2H),
3.81 (s, 3H), 1.02 (s, 9H), 0.17 (s, 6H); 13C NMR δ (300 MHz,
CDCl3) 156.9, 151.9, 150.6, 137.3, 129.5, 127.3, 125.8, 125.4, 121.8,
110.3, 101.3, 60.1, 55.2, 26.1, 18.6, −5.2; MS (Q MS APCI+) 256.1
(M − OTBS−); HRMS (TOF MS AP+) calcd for C15H14NO3 (M -
OTBS−) 256.0974, found 256.0963.
NMR δ (400 MHz CO(CD3)2) 9.31 (bs, 1H), 8.86 (bs, 1H), 8.19 (d,
2H, J = 9.2 Hz), 7.80 (d, 2H, J = 9.2 Hz), 7.41−7.29 (m, 5H), 7.10 (d,
1H, J = 8.1 Hz), 5.22 (s, 2H), 5.16 (s, 2H), 3.87 (s, 3H), 3.82 (s, 3H),
1.33 (s, 12H); 13C NMR δ (400 MHz, CO(CD3)2) 158.9, 157.2,
154.0, 153.9, 146.2, 143.0, 141.7, 131.3, 128.6, 127.5, 125.4, 118.7,
118.2, 116.1, 110.3, 101.8, 84.3, 62.5, 62.0, 55.5, 24.9 (there appear to
be overlapping peaks in the aromatic and aliphatic regions of the 13C
spectrum); MS (Q MS APCI−) 606.2 (M − H+); HRMS (TOF MS
AP−) calcd for C30H33BN3O10 (M − H+) 606.2259, found 606.2267.
Preparation of Oligomer 13. Dibutyltin dilaurate (0.10 mL, 0.17
mmol, 0.2 equiv) was added dropwise to a solution of compounds 11
(0.39 g, 0.87 mmol, 1.0 equiv) and 10 (340 mg, 0.87 mmol, 1.0 equiv)
in toluene (8.7 mL) at 110 °C. The reaction mixture was stirred for 2
h at 110 °C and then cooled to 23 °C. The solution was concentrated
by rotary evaporation, and the residue was purified by silica gel flash
chromatography (5% ethyl acetate in hexanes increasing to 10% ethyl
acetate in hexanes) to afford 29 as a yellow, amorphous solid (0.39 g,
0.53 mmol, 61%): IR (cm−1) 3315, 2928, 2853, 2360, 1710, 1604,
1
1513; H NMR δ (300 MHz, CO(CD3)2) 8.83 (bs, 1H), 8.60 (bs,
1H), 7.41−7.28 (m, 7H), 7.12−7.09 (m, 2H), 5.22 (s, 2H), 5.11 (s,
2H), 4.68 (s, 2H), 3.89 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 1.33 (s,
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12H), 0.94 (s, 9H), 0.09 (s, 6H); 13C NMR δ (300 MHz, CO(CD3)2)
158.8, 157.3, 157.2, 154.2, 154.0, 141.6, 140.1, 131.0, 128.8, 127.9,
127.6, 124.2, 119.5, 116.2, 110.4, 101.8, 101.5, 84.4, 67.8, 62.0, 61.9,
60.3, 55.6, 55.2, 26.1, 24.9, 18.7, −5.4 (there appear to be overlapping
peaks in the aromatic region of the 13C spectrum); MS (Q MS
APCI−) 735.3 (M − H+); HRMS (TOF MS AP−) calcd for
C40H56BN2O12Si (M + CH3COO−) 795.3721, found 795.3696.
p-Toluenesulfonic acid monohydrate (12 mg, 65 μmol, 0.2 equiv)
was added in one portion to a solution of compound 29 (0.24 g, 0.32
mmol, 1.0 equiv) in a 4:1 mixture of tetrahydrofuran−water (3.3 mL).
The reaction mixture was stirred at 23 °C under an atmosphere of air
for 8 h. Ethyl acetate (5 mL) was added in one portion, followed by
saturated aqueous sodium bicarbonate (5 mL) in one portion, and the
organic and aqueous layers were separated. The organic layer was
washed with saturated aqueous sodium bicarbonate solution (1 × 10
mL) and dried over sodium sulfate. The sodium sulfate was removed
by filtration, the solvent was removed by rotary evaporation, and the
residue was purified by silica gel flash column chromatography (50%
ethyl acetate in hexanes increasing to 70% ethyl acetate in hexanes) to
afford compound 30 as a yellow, amorphous solid (0.13 g, 0.32 mmol,
sodium chloride solution (1 × 100 mL). The layers were separated,
the organic layer was dried over sodium sulfate, and the sodium sulfate
was removed by filtration. The solvent was removed by rotary
evaporation, and the residue was purified by silica gel flash column
chromatography (1% ethyl acetate in hexanes, increasing to 5% ethyl
acetate in hexanes), yielding compound 32 as a white, amorphous solid
1
(2.3 g, 6.7 mmol, 84% over two steps): IR (cm−1) 2954, 2856; H
NMR δ (300 MHz, CDCl3) 8.28 (d, 1H, J = 8.0 Hz), 7.97 (d, 1H, J =
8.1 Hz), 7.76 (d, 1H, J = 7.7 Hz), 7.61−7.52 (m, 2H), 7.43 (d, 1H, J =
7.7 Hz), 5.14 (s, 2H), 0.94 (s, 9H), 0.11 (s, 6H); 13C NMR δ (360
MHz, CDCl3) 136.8, 131.9, 131.7, 129.5, 127.8, 126.9, 126.6, 124.3,
123.6, 122.1, 63.0, 25.9, 18.4, −5.2; MS (TOF MS ES+, m/z) 351.1
(M + H+); HRMS (TOF MS ES+) calcd for C17H22OSiBr (M − H−)
349.0623. Found: 349.0633.
n-Butyllithium (5.4 mL, 2.5 M in hexanes, 2.0 equiv) was added
dropwise to a solution of compound 32 (2.3 g, 6.7 mmol, 1 equiv) in
tetrahydrofuran (60 mL) at −78 °C, and the resulting mixture was
stirred for 5 min. N,N-Dimethylformamide (2.6 mL, 34 mmol, 5
equiv) was added, the reaction mixture was stirred for 30 min at −78
°C, and then was allowed to warm to 23 °C. After stirring at 23 °C for
1 h, the solution was slowly diluted by dropwise addition of saturated
ammonium chloride solution (5 mL), followed by ethyl acetate (200
mL) in one portion, and then saturated aqueous sodium bicarbonate
solution (200 mL) in one portion. The layers were separated, and the
organic layer was washed with saturated aqueous sodium chloride (1 ×
200 mL). The organic layer was dried over sodium sulfate, and the
sodium sulfate was removed by filtration. The solvent was removed by
rotary evaporation, and the residue was purified by silica gel flash
column chromatography (2.5% ethyl acetate in hexanes, increasing to
10% ethyl acetate in hexanes), yielding compound 33 as a waxy, white
solid (2.0 g, 6.6 mmol, 97%): IR (cm−1) 2931, 2865, 1687; 1H NMR δ
(300 MHz, CDCl3) 10.34 (s, 1H), 9.32 (d, 1H, J = 8.5 Hz), 7.98−7.95
(m, 2H), 7.82 (d, 1H, J = 7.2), 7.69 (t, 1H, J = 7.5), 7.61 (t, 1H, J =
8.0), 5.26 (s, 2H), 0.96 (s, 9H), 0.15 (s, 6H); 13C NMR δ (360 MHz,
CDCl3) 193.5, 144.6, 137.0, 130.7, 130.5, 130.4, 128.6, 127.0, 125.7,
122.9, 122.2, 63.0, 25.9, 18.4, −5.3; MS (TOF MS AP+, m/z) 301.1
(M + H+); HRMS (TOF MS AP+) calcd for C20H28O2SiN (M + H+ +
MeCN) 342.1889, found 342.1857.
A solution of sodium dihydrogen phosphate monohydrate (2.8 g, 20
mmol, 6.0 equiv) and sodium chlorite (1.8 g, 20 mmol, 6.0 equiv) in
water (30 mL) was added dropwise to a solution of compound 33 (1.0
g, 3.4 mmol, 1 equiv) and 2-methyl-2-butene (2.1 mL, 20 mmol, 6.0
equiv) in acetone (30 mL). The suspension was stirred vigorously for
30 min at 23 °C. Acetone was removed by rotary evaporation, and the
aqueous solution was diluted with ethyl acetate (50 mL) in one
portion. The organic and aqueous layers were separated, and the
organic layer was washed sequentially with saturated aqueous
ammonium chloride solution (1 × 30 mL), saturated aqueous sodium
chloride (1 × 50 mL), saturated aqueous sodium thiosulfate (1 × 50
mL), and saturated aqueous sodium chloride (1 × 50 mL). The
organic layer was dried over sodium sulfate, and the sodium sulfate was
removed by filtration. The solvent was removed by rotary evaporation
to afford compound 15 as a white, amorphous solid, which was used
without further purification.
Preparation of Oligomer 17. Triethylamine (0.1 mL, 0.72 mmol,
1.2 equiv) and diphenylphosphoryl azide (0.16 mL, 0.72 mmol, 1.2
equiv) were added sequentially to a solution of compound 15 (0.19 g,
0.60 mmol, 1 equiv) in benzene (3 mL). The solution was heated to
85 °C for 1 h, and then compound 2 (0.17 g, 0.66 mmol, 1.1 equiv)
was added in one portion to the hot solution. The solution was heated
to 85 °C for 3 h, allowed to cool to 23 °C, and concentrated by rotary
evaporation. The residue was purified by silica gel flash column
chromatography (20% ethyl acetate in benzene, increasing to 30%
ethyl acetate in benzene) to afford 34 as a white, amorphous solid
(0.28 g, 0.49 mmol, 82% over two steps): IR (cm−1) 3311, 2930, 2856,
1731, 1715; 1H NMR δ (300 MHz, CDCl3) 8.05−8.01 (m, 1H),
7.90−7.82 (m, 2H), 7.54−7.47 (m, 3H), 7.42−7.00 (m, 4H), 5.32 (s,
2H), 5.14 (s, 2H), 3.90 (s, 3H), 1.34 (s, 12H), 0.93 (s, 9H), 0.10 (s,
6H); 13C NMR δ (360 MHz, CDCl3) 156.9, 133.7, 131.4, 130.0,
128.9, 127.6, 127.2, 126.1, 125.9, 125.8, 124.2, 124.1, 121.2, 120.2,
1
66%): IR (cm−1) 3307, 2923, 2852, 1707, 1604, 1533; H NMR δ
(400 MHz, CO(CD3)2) 8.83 (bs, 1H), 8.59 (bs, 1H), 7.41−7.26 (m,
7H) 7.11−7.07 (m, 2H), 5.22 (s, 2H), 5.11 (s, 2H), 4.55 (s, 2H), 3.88
(s, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 1.33 (s, 12H); 13C NMR δ (400
MHz, CO(CD3)2) 158.8, 157.8, 157.3, 154.2, 154.0, 141.6, 140.1,
131.0, 128.8, 128.5, 127.6, 125.2, 119.5, 116.2, 110.4, 101.9, 84.4, 62.0,
61.9, 59.5, 55.6, 55.5, 55.3, 24.9 (There appear to be overlapping peaks
in the aromatic region of the 13C spectrum); MS (Q MS APCI−)
621.3 (M − H+); HRMS (TOF MS AP−) calcd for C32H38BN2O10
(M − H+) 621.2620, found 621.2620.
A solution of compound 30 (67 mg, 0.11 mmol, 1.0 equiv) and 4-
nitrophenyl isocyanate (23 mg, 0.14 mmol, 1.3 equiv) in toluene (1.1
mL) was brought to 80 °C. The reaction mixture was stirred for 2 h at
80 °C, and then the solution was cooled to 23 °C. The solvent was
removed by rotary evaporation, and the residue was purified by
preparative-scale HPLC (C18 column, 30% acetonitrile in water
increasing to 90% over 10 min, maintaining 90% acetonitrile in water
for 15 min) to afford oligomer 13 as a yellow, amorphous solid (53
1
mg, 68 μmol, 63%): IR (cm−1) 3311, 2974, 1706, 1600, 1509; H
NMR δ (400 MHz, CO(CD3)2) 9.31 (b, 1H), 8.84 (bs, 1H), 8.72 (bs,
1H), 8.19 (dd, 2H, J = 7.3 Hz, 2.0 Hz), 7.80 (dd, 2H, J = 7.2 Hz, 2.0
Hz) 7.40−7.28 (m, 7H) 7.11−7.10 (m, 2H), 5.22 (s, 2H), 5.16 (s,
2H), 5.13 (s, 2H), 3.87 (s, 3H), 3.82 (s, 6H), 1.33 (s, 12H); 13C NMR
δ (400 MHz, CO(CD3)2) 158.9, 158.8, 157.3, 154.2, 154.0, 153.9,
146.3, 143.0, 141.9, 141.6, 131.3, 131.0, 128.7, 127.5, 125.4, 119.3,
118.6, 118.2, 116.1, 110.3, 101.8, 84.4, 62.7, 62.1, 55.5, 24.9 (there
appear to be overlapping peaks in the aromatic and aliphatic regions of
the 13C spectrum); MS (Q MS APCI−) 821.3 (M − H+ + 2H2O);
HRMS (TOF MS AP−) calcd for C39H42BN4O13 (M − H+) 785.2841,
found 785.2844.
Preparation of Compound 15. 1-Bromo-4-(bromomethyl)-
naphthalene (2.4 g, 8.0 mmol, 1 equiv) and calcium carbonate (8.0
g, 80 mmol, 10 equiv) were suspended in p-dioxanes (40 mL) and
water (40 mL). The suspension was heated to 110 °C for 12 h and
allowed to cool to 23 °C, and 1 M HCl was added until the pH of the
solution was 7. The resulting solution was extracted with ethyl acetate
(150 mL), and the combined organics were washed with saturated
aqueous sodium chloride (1 × 150 mL). The organic and aqueous
layers were separated, the organic layer was dried over sodium sulfate,
and the sodium sulfate was removed by filtration. The solvent was
removed by rotary evaporation to afford compound 31 as a white,
amorphous solid, which was used without further purification.
tert-Butyldimethylsilyl chloride (1.4 g, 9.2 mmol, 1.3 equiv) was
added in one portion to a solution of compound 31 (1.7 g, 7.1 mmol,
1 equiv) and imidazole (0.72 g, 10.6 mmol, 1.5 equiv) in
dichloromethane (40 mL) at 23 °C and was stirred for 16 h.
Methanol (3 mL) was added in one portion, and the solution was
stirred for 15 min at 23 °C. Dichloromethane (60 mL) was added in
one portion, and the solution was washed with saturated aqueous
ammonium chloride (1 × 100 mL) followed by saturated aqueous
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120.1, 115.8, 88.9, 63.4, 62.6, 55.5, 25.9, 24.8, 18.4, −5.2; MS (TOF
MS AP−, m/z) 576.3 (M − H+); HRMS (TOF MS AP+) calcd for
to a solution of compound 33 (0.47 g, 1.5 mmol, 1 equiv) in benzene
(7.5 mL). The solution was heated to 85 °C for 1 h, and then
compound 35 (0.31 g, 1.7 mmol, 1.1 equiv) was added to the hot
solution in one portion. The solution was heated to 85 °C for 3 h,
allowed to cool to 23 °C, and concentrated by rotary evaporation. The
residue was purified by silica gel flash column chromatography (10%
ethyl acetate in hexanes, increasing to 30% ethyl acetate in hexanes) to
afford 36 as a white, amorphous solid (0.59 g, 1.2 mmol, 79% over two
+
C32H48BN2O6Si (M + NH4 ) 595.3375, found 595.3370.
A solution of p-toluenesulfonic acid monohydrate (24 mg, 0.13
mmol, 0.3 equiv) in water (0.2 mL) was added dropwise to a solution
of compound 34 (0.25 g, 0.43 mmol, 1 equiv) in tetrahydrofuran (3.8
mL). The resulting solution was stirred at 23 °C for 14 h.
Triethylamine (21 μL, 0.15 mmol, 0.35 equiv) was added dropwise
to the reaction mixture, and the resulting solution was stirred at 23 °C
for 15 min. Pinacol (0.25 g, 2.1 mmol, 5 equiv) was added in one
portion, and the reaction mixture was stirred at 23 °C for 24 h. The
solvent was removed by rotary evaporation and the residue was
dissolved in ethyl acetate (20 mL). The solution was washed with
saturated aqueous ammonium chloride solution (1 × 20 mL) followed
by saturated aqueous sodium chloride (1 × 20 mL). The organic layer
was dried over sodium sulfate, and the sodium sulfate was removed by
filtration. The solvent was removed by rotary evaporation, and the
residue was purified by silica gel flash column chromatography (20%
ethyl acetate in benzene, increasing to 40% ethyl acetate in benzene),
yielding compound 16 as a white, amorphous solid (0.16 g, 0.34
1
steps): IR (cm−1) 3309, 2928, 2855, 1725, 1693; H NMR δ (300
MHz, CDCl3) 10.36, (s, 1H), 9.32 (d, 1H, J = 8.5 Hz), 8.13 (s, 1H),
8.03 (d, 1H, J = 7.3 Hz), 7.96 (d, 1H, J = 6.2 Hz), 7.88 (d, 1H, 7.5
Hz), 7.83−7.60 (m, 4H) 7.55 (d, 1H, J = 7.7 Hz), 7.52−7.48 (m, 2H),
7.02 (s, 1H), 5.76 (s, 2H), 5.14 (s, 2H), 0.93 (s, 9H), 0.10 (s, 6H); 13C
NMR δ (360 MHz, CDCl3) 193.3, 139.0, 136.1, 131.5, 131.4, 128.9,
127.5, 126.1, 125.6, 123.7, 64.9, 63.3, 25.9, 18.4, −5.2; MS (TOF MS
+
AP+, m/z) 517.3 (M + NH4 ); HRMS (TOF MS AP+) calcd for
+
C30H37N2O4Si (M + NH4 ) 517.2523, found 517.2524.
A solution of sodium dihydrogen phosphate monohydrate (0.98 g,
7.2 mmol, 6.0 equiv) and sodium chlorite (0.64 g, 7.2 mmol, 6.0
equiv) in water (12 mL) was added to a solution of compound 36
(0.59 g, 1.2 mmol, 1 equiv) and 2-methyl-2-butene (0.75 mL, 7.2
mmol, 6.0 equiv) in acetone (12 mL). The suspension was stirred
vigorously for 30 min at 23 °C. Acetone was removed by rotary
evaporation, and the aqueous solution was diluted with ethyl acetate
(50 mL) in one portion. The organic and aqueous layers were
separated, and the organic layer was washed sequentially with
saturated aqueous ammonium chloride solution (1 × 30 mL),
saturated aqueous sodium chloride (1 × 50 mL), saturated aqueous
sodium thiosulfate (1 × 50 mL), and saturated aqueous sodium
chloride (1 × 50 mL). The organic layer was dried over sodium sulfate,
and the sodium sulfate was removed by filtration. The solvent was
removed by rotary evaporation to afford compound 18 as a white,
amorphous solid, which was used without further purification.
1
mmol, 79%): IR (cm−1) 3389, 3312, 2977, 1724, 1714; H NMR δ
(300 MHz, CDCl3) 8.12 (d, 1H, J = 6.7 Hz), 7.88 (d, 1H, J = 7.5),
7.78 (s, 1H), 7.54−7.45 (m, 2H), 7.41−7.34 (m, 3H), 7.29 (s, 1H),
7.12 (s, 1H), 5.30 (s, 2H), 5.03 (s, 2H), 3.87 (s, 3H), 2.09 (bs, 1H),
1.33 (s, 12H); 13C NMR δ (360 MHz, CDCl3) 157.3, 133.2, 132.5,
129.5, 128.8, 127.9, 127.6, 126.8, 126.5, 126.0, 125.0, 121.6, 116.3,
84.4, 63.9, 63.1, 56.0, 25.2 (there appear to be overlapping peaks in the
aromatic region of the 13C spectrum); MS (TOF MS AP−, m/z) 462.1
(M − H+); HRMS (TOF MS AP+) calcd for C26H34BN2O6 (M +
+
NH4 ) 481.2510, found 481.2513.
Triethylamine (56 μL, 0.40 mmol, 1.5 equiv) was added dropwise
to a solution of compound 16 (0.12 g, 0.27 mmol, 1 equiv) and 4-
nitrophenyl isocyanate (48 mg, 0.29 mmol, 1.1 equiv) in
tetrahydrofuran (2.5 mL). The reaction mixture was stirred at 23 °C
for 1.5 h and the solvent was removed by rotary evaporation. The
residue was purified by silica gel flash column chromatography (10%
ethyl acetate in benzene, increasing to 30% ethyl acetate in benzene),
yielding oligomer 17 as a pale yellow, amorphous solid (90 mg, 0.14
Triethylamine (0.16 mL, 1.1 mmol, 1.2 equiv) and diphenylphos-
phoryl azide (0.25 mL, 1.1 mmol, 1.2 equiv) were added sequentially
to a solution of compound 18 (0.49 g, 0.95 mmol, 1 equiv) in benzene
(5 mL). The solution was heated to 85 °C for 1 h, and then compound
2 (0.28 g, 1.1 mmol, 1.1 equiv) was added to the hot solution in one
portion. The solution was stirred at 85 °C for 3 h, allowed to cool to
23 °C, and concentrated by rotary evaporation. The residue was
purified by silica gel flash column chromatography (5% ethyl acetate in
benzene, increasing to 30% ethyl acetate in benzene) to afford 37 as a
white, amorphous solid (0.51 g, 0.65 mmol, 65% over two steps): IR
1
mmol, 53%): IR (cm−1) 3312, 2978, 1737, 1714; H NMR δ (300
MHz, CDCl3) 8.13 (d, 2H, J = 9.0 Hz), 8.01 (d, 1H, J = 8.5 Hz), 7.70
(s, 2H), 7.55−7.34 (m, 7H), 7.26 (s, 1H), 5.57 (s, 2H), 5.25 (s, 2H),
3.84 (s, 3H), 1.32 (s, 12H); 13C NMR δ (360 MHz, CDCl3) 152.8,
142.8, 132.1, 128.5, 127.2, 127.1, 126.9, 126.4, 125.1, 117.8, 115.8,
84.0, 65.8, 62.9, 55.5, 24.8; MS (TOF MS AP−, m/z) 626.2 (M −
1
(cm−1) 3309, 2930, 1713 (b); H NMR δ (300 MHz, CDCl3/C6D6)
+
H+); HRMS (TOF MS AP+) calcd for C33H38BN4O9 (M + NH4 )
8.09 (s, 1H), 8.02 (d, 1H, J = 8.2 Hz), 7.87−7.84 (m, 4H), 7.53−7.35,
(m, 9H), 7.14, (s, 2H), 5.63 (s, 2H), 5.33 (s, 2H), 5.14 (s, 2H), 3.89
(S, 3H), 1.34 (s, 12H), 0.94 (s, 9H), 0.11 (s, 6H); 13C NMR δ (360
MHz, CDCl3/C6D6) 156.9, 154.2, 133.6, 132.2, 131.8, 131.4, 130.0,
129.0, 128.3, 128.1, 127.4, 127.2, 126.6, 126.1, 125.9, 125.8, 124.5,
124.1, 121.2, 121.1, 120.2, 120.1, 115.8, 83.9, 65.4, 63.3, 62.7, 55.5,
25.9, 24.8, 18.3, −5.2 (there appear to be overlapping peaks in the
aromatic region of the 13C spectrum); MS (TOF MS AP+, m/z) 794.2
645.2732, found 645.2731.
Preparation of Oligomer 20. A solution of p-toluenesulfonic acid
monohydrate (0.18 g, 1.0 mmol, 0.3 equiv) in water (4.3 mL) was
added dropwise to a solution of compound 33 (0.95 g, 3.2 mmol, 1
equiv) in tetrahydrofuran (26 mL). The resulting solution was stirred
at 23 °C for 14 h. Triethylamine (0.18 mL, 1.3 mmol, 0.4 equiv) was
added dropwise to the reaction mixture, and the solvent was removed
by rotary evaporation. The residue was dissolved in ethyl acetate (50
mL), and the solution was washed with saturated aqueous ammonium
chloride solution (1 × 50 mL) followed by saturated aqueous sodium
chloride (1 × 50 mL). The organic layer was dried over sodium sulfate,
and the sodium sulfate was removed by filtration. The solvent was
removed by rotary evaporation, and the residue was purified by silica
gel flash column chromatography (20% ethyl acetate in hexanes,
increasing to 60% ethyl acetate in hexanes), yielding compound 35 as a
white, amorphous solid (0.58 g, 3.1 mmol, 98%): IR (cm−1) 3391,
+
(M + NH4 ); HRMS (TOF MS AP+) calcd for C44H57BN3O8Si (M +
+
NH4 ) 794.4008, found 794.4013.
A solution of p-toluenesulfonic acid monohydrate (17 mg, 98 μmol,
0.3 equiv) in water (150 μL) was added dropwise to a solution of
compound 37 (0.26 g, 0.33 mmol, 1 equiv) in tetrahydrofuran (2.9
mL). The resulting solution was stirred at 23 °C for 14 h.
Triethylamine (13 μL, 1.3 mmol, 0.4 equiv) was added dropwise to
the reaction mixture, and the resulting solution was stirred at 23 °C for
15 min. Pinacol (0.18 g, 1.7 mmol, 5 equiv) was added in one portion,
and the reaction mixture was stirred at 23 °C for 24 h. The solvent was
removed by rotary evaporation and the residue was dissolved in ethyl
acetate (20 mL). The solution was washed with saturated aqueous
ammonium chloride solution (1 × 20 mL) followed by saturated
aqueous sodium chloride (1 × 20 mL). The organic layer was dried
over sodium sulfate and the sodium sulfate was removed by filtration.
The solvent was removed by rotary evaporation and the residue was
purified by silica gel flash column chromatography (20% ethyl acetate
in benzene, increasing to 50% ethyl acetate in benzene), yielding
1
2860, 1683; H NMR δ (300 MHz, CDCl3) 10.25 (s, 1H), 9.23 (d,
1H, J = 8.4 Hz), 8.01 (d, 1H, J = 8.4 Hz), 7.86 (d, 1H, J = 7.3 Hz),
7.69−7.62 (m, 2H), 7.59 (t, 1H, J = 7.5) 5.17 (s, 2H), 2.54 (s, 1H);
13C NMR δ (360 MHz, CDCl3) 193.6, 144.0, 136.7, 131.0, 130.9,
130.6, 128.8, 127.2, 125.5, 123.4, 123.1, 63.0; MS (TOF MS AP+, m/
z) 187.0 (M + H+); HRMS (TOF MS AP−) calcd for C12H9O2 (M −
H+) 185.0603, found 185.0604.
Triethylamine (0.25 mL, 1.8 mmol, 1.2 equiv) and diphenylphos-
phoryl azide (0.39 mL, 1.8 mmol, 1.2 equiv) were added sequentially
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The Journal of Organic Chemistry
Article
compound 19 as an off-white, amorphous solid (0.2 g, 0.3 mmol,
91%): IR (cm−1) 3430, 3254, 2977, 1707 (b); 1H NMR δ (300 MHz,
CDCl3) 8.07 (d, 2H, J = 8.2 Hz), 7.83−7.63 (m, 4H), 7.52−7.36 (m,
8H), 7.29 (s, 1H), 7.16 (s, 2H), 5.58 (s, 2H), 5.30 (s, 2H), 5.00 (s,
2H), 3.87 (s, 3H), 1.34 (s, 12H); 13C NMR δ (360 MHz, CDCl3)
156.9, 154.2, 133.6, 132.2, 131.7, 128.0, 128.3, 128.1, 127.4, 127.2,
126.6, 126.3, 126.1, 126.0, 125.4, 124.4, 121.2, 115.9, 83.9, 65.4, 63.4,
62.7, 55.5, 24.8 (There appear to be overlapping peaks in the aromatic
region of the 13C spectrum); MS (TOF MS AP+, m/z) 680.3 (M +
Henry Dreyfus Foundation, Mr. Louis Martarano, 3M, and The
Pennsylvania State University.
REFERENCES
■
(1) Esser-Kahn, A. P.; Odom, S. A.; Sottos, N. R.; White, S. R.;
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+
+
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NH4 ). HRMS (TOF MS AP+) calcd for C38H43BN3O8 (M + NH4 )
680.3143, found 680.3169.
Triethylamine (63 μL, 0.45 mmol, 1.5 equiv) was added dropwise
to a solution of compound 19 (0.20 g, 0.30 mmol, 1 equiv) and 4-
nitrophenyl isocyanate (60 mg, 0.36 mmol, 1.2 equiv) in
tetrahydrofuran (3 mL). The reaction mixture was stirred at 23 °C
for 1.5 h, and the solvent was removed by rotary evaporation. The
residue was eluted through a short plug of silica (15% ethyl acetate in
benzene, increasing to 20% ethyl acetate in benzene), and the solvent
was removed by rotary evaporation. The residue was purified by
preparative scale HPLC (C18 column, 40% acetonitrile in water
increasing to 90% over 15 min, maintaining 90% acetonitrile in water
for 10 min) yielding oligomer 20 (0.10 g, 0.12 mmol, 40%) as a pale
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1
yellow, amorphous solid: IR (cm−1) 3300, 2977, 1737, 1713 (b); H
(10) Dewit, M. A.; Beaton, A.; Gillies, E. R. J. Polym. Sci., A: Polym.
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NMR δ (300 MHz, CDCl3/C6D6/ CO(CD3)2) 8.87 (s, 1H), 8.04−
7.92 (m, 9H), 7.70 (bs, 2H), 7.61 (d, 2H, J = 8.9 Hz), 7.47−7.34 (m,
8H), 5.52 (s, 2H), 5.50 (s, 2H), 5.23 (s, 2H), 3.82 (s, 3H), 1.28 (s,
12H); 13C NMR δ (360 MHz, CDCl3/CO(CD3)2) 156.3, 154.2,
152.8, 144.6, 142.1, 133.9, 133.7, 131.8, 128.1, 127.7, 127.4, 127.3,
126.7, 126.2, 125.6, 124.5, 123.7, 121.5, 117.4, 115.4, 83.5, 65.0, 64.9,
62.0, 55.0, 24.4 (there appear to be overlapping peaks in the aromatic
region of the 13C spectrum); MS (TOF MS AP+, m/z) 844.2 (M +
(11) Dewit, M. A.; Gillies, E. R. J. Am. Chem. Soc. 2009, 131, 18327−
18334.
(12) DeWit, M. A.; Nazemi, A.; Karamdoust, S.; Beaton, A.; Gillies,
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(14) Esser-Kahn, A. P.; Sottos, N. R.; White, S. R.; Moore, J. S. J. Am.
Chem. Soc. 2010, 132, 10266−10268.
+
+
NH4 ); HRMS (TOF MS AP+) calcd for C46H48BN4O11 (M + NH4 )
(15) Zhang, H.; Yeung, K.; Robbins, J. S.; Pavlick, R. A.; Wu, M.; Liu,
R.; Sen, A.; Phillips, S. T. Angew. Chem., Int. Ed. 2012, 51, 2400−2404.
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844.3365, found 844.3345.
Preparation of Compound 21. Bis(pinacolato)diboron (0.61 g,
2.4 mmol, 1.2 equiv), PdCl2(dppf)·CH2Cl2 (0.081 g, 0.099 mmol, 0.05
equiv), and KOAc (0.58 g, 5.9 mmol, 3 equiv) were sealed in a two-
neck round-bottom flask equipped with a coldfinger and placed under
vacuum for 1 h. The flask was purged with argon, and p-dioxanes (15
mL) was added in one portion, followed by 3-bromoanisole (0.25 mL,
2.0 mmol, 1 equiv) in one portion. The reaction mixture was brought
to 80 °C and stirred for 18 h. The reaction mixture was cooled to 23
°C, diluted with ethyl acetate (15 mL) in one portion, and filtered
through a thin layer of silica gel covered by a pad of Celite. The filtrate
was concentrated and the residue was purified by silica gel flash
column chromatography (100% hexanes, followed by 2% ethyl acetate
in hexanes) to afford compound 21 as a colorless oil (0.23 g, 0.96
(18) Schmid, K. M.; Jensen, L.; Phillips, S. T. J. Org. Chem. 2012, 77,
4363−4374.
́
(19) Randic, M. Chem. Rev. 2003, 103, 3449−3605.
(20) Chang, M. C. Y.; Pralle, A.; Isacoff, E. Y.; Chang, C. J. J. Am.
Chem. Soc. 2004, 126, 15392−15393.
(21) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518−1520.
(22) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923−
2925.
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Merck Index, 14th ed.; Merck & Co., Inc.: Whitehouse Station, NJ,
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1
mmol, 48%), which was identified by comparison of H NMR data
with literature values.24
(24) Cho, J. Y.; Iverson, C. N.; Smith, M. R. J. Am. Chem. Soc. 2000,
122, 12868−12869.
ASSOCIATED CONTENT
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S
* Supporting Information
Tables of data as well as figures showing H and 13C NMR
1
spectra for intermediates and final compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sphillips@psu.edu.
■
Author Contributions
†These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported in part by the American Chemical
Society (PRF no. 51618-DNI7), DARPA (HR0011-11-1-0007),
the Arnold and Mabel Beckman Foundation, the Camille and
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dx.doi.org/10.1021/jo400105m | J. Org. Chem. 2013, 78, 3159−3169