Apical functionalization of chiral heterohelicenes

Article abstract of DOI:10.1021/jo202623u

We describe a synthetic protocol to selectively functionalize chiral bridged triarylamines at the apical position using regioselective copper-catalyzed amination reaction. This protocol allows the coupling of diphenylamines with a sterically hindered but

Full text of DOI:10.1021/jo202623u

Note
pubs.acs.org/joc
Apical Functionalization of Chiral Heterohelicenes
Sravan K. Surampudi, G. Nagarjuna, Daiki Okamoto, Piyali D. Chaudhuri, and D. Venkataraman*
Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts 01003, United
States
S
* Supporting Information
ABSTRACT: We describe a synthetic protocol to selectively functionalize chiral bridged triarylamines at the apical position
using regioselective copper-catalyzed amination reaction. This protocol allows the coupling of diphenylamines with a sterically
hindered but electronically activated aryl−Br bond in the presence of a sterically unhindered but electronically unactivated aryl−
Br bond. The unactivated aryl−Br bond was utilized further to synthesize a chiral heterohelicene homodimer using Stille
coupling.
ridged triarylamines are a class of π-conjugated molecules
tolerate a variety of functional groups, at this site, thereby vastly
expanding the scope of chiral bridged triarylamines. Moreover,
this would allow us to use resolved molecules, which bear a
camphanate moiety such as (M)-1 or (P)-1 as building blocks
for functional chiral materials. A straightforward way to install a
halogen moiety at the apical position is to replace dimethyl 2-
bromo-5-(tert-butyl)isophthalate with dimethyl 2,5-dibromoi-
sophthalate in the synthetic scheme (Scheme 1). The key step
is the first step, which involves the regioselective coupling of 2-
methoxy-N-phenylaniline and dimethyl 2,5-dibromoisophtha-
late.
B
that exhibit axial chirality.1−3 The combination of chirality
and extended conjugation make these molecules interesting
from the standpoints of fundamental science and technological
applications.4−13 For example, bridged triarylamines have been
used as chromophores for single molecule chiroptical studies to
understand the interaction between light and chiral mole-
cules.5−8 They have also been used as active materials in various
optoelectronic devices.9−13 However, in order to use bridged
triarylamines as building blocks for functional materials, it is
important that these molecules can be suitably functionalized at
appropriate positions. Among the various positions, functional
groups at the apical position can provide access to a broad
range of molecules and macromolecules without compromising
the symmetry of the building block. Selective apical
functionalization of achiral bridge triarylamines have been
reported by blocking the two nonapical positions para to the
nitrogen with tert-butyl groups.9,12 However, this method
cannot be employed to obtain apically functionalized chiral
bridged triarylamines from easily accessible starting materials.14
To the best of our knowledge, there is no literature precedence
to selectively obtain apically functionalized chiral bridged
triarylamines. Here in we report a protocol, based on copper-
catalyzed amination, to synthesize apically functionalized chiral
bridged triarylamines by the selective coupling of a sterically
hindered but electronically activated C−Br bond over a
sterically unhindered, electronically unactivated C−Br bond.
Previously, we reported the synthesis of chiral bridged
triarylamines with a tert-butyl group at the apical position.14 We
reasoned that installing a halogen moiety at the apical position
instead of a tert-butyl group would allow us to perform metal-
mediated cross-coupling reactions, which are often mild and
Synthesis of 1 began with Sandmeyer reaction of 4-bromo-
2,6-dimethylaniline in the presence of CuBr to obtain 2,5-
dibromo-1,3-dimethylbenzene (3) as reported previously.15
3
was oxidized in the presence of KMnO4 to afford 2,5-
dibromoisophthalic acid (4) in 70% yield. Esterification of 4
in the presence of methanol and sulfuric acid resulted in
dimethyl 2,5-dibromoisophthalate (5) in 90% yield (Scheme
2).
2-Methoxy-N-phenylamine (6) was prepared using a
previously reported synthetic procedure.14 The regioselective
coupling of 5 with 6 required a judicious choice of the catalyst
and conditions, since the coupling was required to occur with a
C−Br bond that was strerically hindered but electronically
activated (due to the presence of two ortho-ester function-
alities) instead of a C−Br bond that was sterically unhindered
but electronically unactivated. On the basis of the work
published previously by our group and others for the synthesis
Received: December 19, 2011
Published: January 19, 2012
© 2012 American Chemical Society
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Scheme 1. Synthetic Strategy for the Exclusive Formation of Apically Functionalized Chiral Bridged Triarylamine
Scheme 2. Synthesis of Dimethyl 2,5-dibromoisophthalate 5
Scheme 3. Synthesis of 7 by Regioselective Copper-Catalyzed Coupling
Scheme 4. Synthesis of Apically Functionalized (M)-1 and (P)-1
of triphenylamines from diphenylamines, copper was chosen as
the choice of catalyst for the coupling.16,17 Furthermore, it is
known that coupling of ortho-bromobenzoic acids with aniline
proceeds with high regioselectivity due to the accelerating effect
of the ortho-carboxylate group in homogeneous copper-
catalyzed reactions.18 Therefore, we hypothesized that
copper-mediated coupling of 5 with 6 may proceed
regioselectively because of the presence of two ortho-
carboxylate ester groups in 5. Gratifyingly, regioselective
coupling of 5 with 6 was achieved in the presence of Cu/CuI
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Scheme 5. Synthesis of Acetylene Bridged Homodimer (M)-2
Figure 1. (a) Normalized UV−vis absorption spectra (solid line) and emission spectra (dotted line) of (M)-1 and (M)-2 in dichloromethane. (b)
Normalized CD spectra of (M)-1 and (M)-2 in dichloromethane.
to afford triarylamine 7 in 70% yield (Scheme 3). In addition to
properties of (M)-1 by extending the conjugation. This led us
to the synthesis of acetylene bridged chiral bridged triarylamine
homodimer (M)-2 from (M)-1 via palladium(0)-catalyzed Stille
coupling reaction. Two equivalents of (M)-1 were coupled to
bis(tributylstannyl)acetylene in the presence of Pd(PPh3)4 in
toluene to yield homodimer (M)-2 in 37% yield (Scheme 5).
The low yield of (M)-2 is consistent with previously reported
palladium(0)-catalyzed Stille coupling of similar bridged
triarylamines with bis(tributylstannyl)acetylene.9 1H NMR
spectrum of (M)-2 showed a similar peak pattern with respect
to (M)-1, which indicates the presence of a homodimer. 13C
NMR spectrum of (M)-2 showed an additional peak at δ 89.03
with respect to (M)-1, which is attributed to the additional
acetylenic carbons in (M)-2.
Single crystals suitable for X-ray diffraction of (M)-1 and
(M)-2 were obtained in a binary solvent mixture of hexanes and
ethylacetate. The structures displayed in Figure S1 in the
Supporting Information show the absolute stereochemistry of
(M)-1 and (M)-2. Both (M)-1 (168.53°) and (M)-2 (167.03°
and 170.99°) showed OCCO camphanate dihedral
angles similar to previously reported camphanate dihedral
angles for (M)-[7]helicenes, consistent with an M-configu-
ration (Figure S1 in the Supporting Information).20
Diastereomers (M)-1 and (P)-1 showed identical UV−vis
absorption and emission spectra with absorption maxima at 443
nm, and the emission maxima at 472 nm (when excited at 443
nm). However, the absorption spectrum of (M)-2 showed an
additional peak at 350 nm. The emission spectra (M)-2 showed
no significant change compared to (M)-1, with the emission
maxima occurring at 473 nm (when excited at 446 nm) (Figure
1a). The CD spectrum of (M)-2 showed a similar sign and peak
pattern with respect to (M)-1, confirming the M-configuration
in (M)-2 (Figure 1b). Furthermore, the CD spectrum of (M)-2
also showed the presence of an additional peak at 350 nm,
similar to its absorption spectrum.
1H and 13C NMR, the key evidence for the formation of the
regioisomer 7 was obtained from the single crystal X-ray
diffraction analysis (Figure S1 in the Supporting Information).
Subsequent ester hydrolysis of 7 in the presence of NaOH
gave diacid 8 in 91% yield. The diacid 8 was converted to the
corresponding acid chloride with SOCl2 in dichloromethane,
followed by an in situ intramolecular cyclization in the presence
of SnCl4 to yield racemic bridged triarylamine 9 in 86% yield.
The methyl ether in 9 was then cleaved in the presence of
AlBr3/NaI in dichloromethane to give phenol 10 in 80% yield.
As reported previously by our group, esterification of racemic
phenol 10 with (1S)-camphanic chloride and 4-dimethylami-
nopyridine (DMAP) resulted in atropdiastereomers (M)-1 and
(P)-1 in 92% combined yield (Scheme 4).14
1H NMR spectra of both (M)-1 and (P)-1 showed the
presence of two doublets at 8.76 and 8.72 ppm with a coupling
constant J = 2.4 Hz, consistent with a meta coupling, which
indicates the presence of apical functionality. High-resolution
ESI mass spectra of (M)-1 and (P)-1 showed the presence of
two M + H ion peaks with a ratio of 1:1 at m/z 572.1 and
574.1, consistent with the presence of bromine at the apical
position. The 1H NMR spectra of (M)-1 and (P)-1 differ in the
chemical shifts of camphanate methyl protons Ha and aromatic
proton Hj (Figure S2 in the Supporting Information). As
reported previously, this is due to the difference in ring currents
caused by a change in the preferred conformation of the
camphanate group in (M)-1 and (P)-1.14,19 The circular
dichroism (CD) spectra of (M)-1 and (P)-1 showed an
identical peak pattern with opposite sign, thus confirming the
enantiomeric nature of the bridged triarylamine helicene
chromophore, since the configuration of the camphanate
group is identical in both the diastereomers (Figure S3 in the
Supporting Information). Once we had accomplished the
synthesis of (M)-1 and (P)-1, we wanted to further study if a
significant change is caused in the optical and electronic
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Figure 2. HOMO and LUMO surface plots for (M)-1 and (M)-2.
Toluene was redistilled under argon atmosphere over sodium-
benzophenone ketyl. Flash chromatography was performed using
silica gel (standard grade, 60 Å, 230−400 mesh). Analytical thin layer
chromatography was performed on precoated silica gel glass plates
with visualization under UV light. Chemical shifts (δ) and coupling
constants are reported in parts per million and Hertz, respectively. The
abbreviations for splitting patterns are s, singlet; br s, broad singlet; d,
doublet; t, triplet; q, quartet; and combinations therein (i.e., dd,
doublet of doublets). X-ray data were collected with Mo Kα (λ =
0.71072 Å) as the incident radiation. Diffraction data were collected at
ambient temperature unless otherwise stated. The raw data were
integrated, refined, scaled, and corrected for Lorentz polarization and
absorption effects, if necessary, using the programs DENZO and
Cyclic voltammograms (CV) of (M)-1 and (M)-2 were
recorded in acetonitrile solutions at 1 × 10−3 M concentrations.
(M)-1 shows quasireversible oxidation and reduction peaks at
1.48, −1.43 V (vs Ag/Ag+), respectively,21 whereas (M)-2
shows two quasireversible oxidation peaks at 1.33 and 1.54 V
and a reduction peak at −1.41 V (vs Ag/Ag+) (Figure S4 in the
Supporting Information). Lower oxidation potential for (M)-2
compared to (M)-1 might be because of the enhanced
conjugation via ethyne linker. The redox values for (M)-1 are
consistent for three repeated cycles, indicating that (M)-1
dimerization was hindered because of the presence of bromine
functionality at the apical position.22 Frontier orbital energies
were obtained using established procedures from CV.23 The
calculated HOMO and LUMO energy levels are −6.19 and
−3.28 eV for (M)-1 and −6.04 and −3.3 eV for (M)-2. Frontier
orbital surface plots for (M)-1 and (M)-2 were estimated from
optimized geometry using B3LYP level of theory with 6-
311g(d,p) as the basis set. The frontier molecular orbitals
(FMO) of (M)-2 are evenly distributed on both the helicenes
(Figure 2).
In conclusion, we have established a straightforward route for
the synthesis of apically functionalized chiral bridged triaryl-
amines (M)-1 and (P)-1. The chemistry allowed us to
synthesize a chiral helicene homodimer (M)-2 via palladi-
um(0)-catalyzed Stille coupling. The single crystal X-ray
diffraction analysis and CD of both (M)-1 and (M)-2 show a
chiral signature consistent with an M-configuration. FMO of
(M)-2 is symmetrically distributed on both the helicenes. (M)-
2 was easier to oxidize and also has an additional absorption
peak at 350 nm compared to the (M)-1. This might be because
of the extended conjugation in (M)-2 compared to (M)-1.
Single molecule spectroscopy measurements on these mole-
cules will be reported in due course.
2
SCALEPAK. Structure solutions and refinements were done (on Fo )
using a suite of crystal structure solution and refinement programs.
Data scans for CD were taken from 300 to 550 nm at a rate of 50 nm/
min, with a 0.2 nm data pitch and a 4 s response. Two scans were
taken for each sample at a constant temperature of 23 °C. Data
obtained with a high tension voltage over 600 V were not included in
the analysis. Fluorescence spectra were recorded with excitation and
emission bandwidth kept at 1 nm. Scanning speed was set at 50 nm/
min. CV was recorded with tetrabutylammonium hexafluorophosphate
as a supporting electrolyte (0.1 M) in acetonitrile with platinum as the
working electrode. The redox potentials were determined versus an
Ag/Ag+ reference electrode. The working and auxiliary electrodes were
cleaned after each run. In these conditions, the redox potential of Fc/
Fc+ (Fc = ferrocene) was +0.09 V versus Ag/Ag+. It is assumed that
the redox potential of Fc/Fc+ has an absolute energy level of −4.80 eV
to vacuum. HOMO and LUMO values were calculated using Fc/Fc+
as a reference.
Experimental Procedures. 2,5-Dibromoisophthalic Acid (4).
In a 100 mL round-bottom flask equipped with a magnetic stir bar and
a reflux condenser was added 2,5-dibromo-1,3-dimethylbenzene (3)
(6.45 g, 24.44 mmol), dispersed in 80 mL of a 1:1 mixture of t-butanol
and water. KMnO4 (8.5 g, 53.76 mmol) was added, and the reaction
mixture was heated to reflux for 1 h. After cooling to room
temperature, more KMnO4 (8.5 g, 53.76 mmol) was added, and the
reaction mixture was refluxed for an additional 18 h. After cooling to
room temperature, the reaction was filtered through Celite, and the
filtrate was reduced by 1/3. The solution was acidified with
concentrated HCl. The resulting white precipitate was collected by
vacuum filtration and dissolved in aqueous NaHCO3. The aqueous
layer was washed with ether to remove any residual organics. The
aqueous layer was then acidified with concentrated HCl, and the
EXPERIMENTAL SECTION
■
General Experimental Methods. All reactions were carried out
in oven-dried glassware (160 °C). The chemicals were purchased from
major chemical suppliers and were used without further purification
unless otherwise noted. Dichloromethane was redistilled over calcium
hydride under argon atmosphere and stored over 4 Å molecular sieves.
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precipitate was collected and oven-dried (∼80 °C) overnight to give
5.5 g (70% yield) of the title compound: 1H NMR (400 MHz, DMSO-
d6) δ 13.88 (br s, 2H), 7.91 (s, 2H); 13C NMR (400 MHz, DMSO-d6)
δ 166.9, 139.1, 133.4, 121.1, 115.9; HRMS (ESI) m/z For
C8H4O4Br2Na calculated 344.8374, found 344.8380.
124.8, 124.6, 121.0, 119.6, 117.3, 116.6, 55.6; HRMS (ESI) m/z For
C21H13BrNO3 [M + H]+ calculated 406.0079, found 406.0080.
Synthesis of (10). 9 (0.580 g, 1.43 mmol) and NaI (0.215 g, 1.43
mmol) were dispersed in 25 mL of dry dichloromethane in a 50 mL, 3-
neck round-bottom flask equipped with a magnetic stir bar. The
reaction mixture was then cooled in an ice bath. AlBr3 (2.3 g. 8.6
mmol) was then added in one portion to the reaction mixture. After 20
min, the ice bath was removed, and the reaction was stirred for 16 h at
room temperature. The reaction mixture was then cooled in an ice
bath; methanol, 1 M HCl, and water were added. The aqueous layer
was washed with several portions of dichloromethane, the combined
organic layers were dried over sodium sulfate and filtered, and the
solvent was removed by rotary evaporation. The residue was then
purified by flash chromatography using 9:1 dichloromethane/
diethylether as the eluent to give 0.450 g of 10 (80% yield): 1H
NMR (DMSO-d6, 400 MHz) δ 7.35−7.4 (m, 2H), 7.44- 7.52 (m, 2H),
7.7−7.75 (m, 1H), 7.8 (dd, J = 7.7 and 1.4 Hz, 1H), 8.17 (dd, J = 8
and 1.4 Hz, 1H), 8.52 (d, J = 2.5 Hz, 1H), 8.58 (d, J = 2.5 Hz, 1H),
10.89 (br s, 1H); 13C NMR (DMSO-d6, 400 MHz) δ 177.9, 177.8,
149.5, 140.0, 139.4, 134.0, 133.9, 132.7, 128.9, 127.4, 127.2, 125.7,
125.2, 125.0, 124.8, 124.3, 122.8, 122.1, 117.5, 116.3; HRMS (ESI) m/
z For C20H11BrNO3 [M + H]+ calculated 391.9922, found 391.9921.
Synthesis of (M)-1 and (P)-1. Compound 10 (0.365 g, 0.93
mmol) and DMAP (0.171 g, 1.4 mmol) were dissolved in 20 mL of
dry dichloromethane. (1S)-camphanic chloride (0.405 g, 1.9 mmol)
was added, and the reaction was heated to reflux under argon for 12 h.
Dichloromethane was then removed under vacuum, and the residue
was purified by flash chromatography using 1:1 hexane/ethyl acetate as
the eluent to give 0.250 g of (M)-1 and 0.240 g of (P)-1 (92%
combined yield).
Dimethyl 2,5-Dibromoisophthalate (5). In a 100 mL round-
bottom flask equipped with a magnetic stir bar and a reflux condenser
was added 4 (5.5 g, 17 mmol), in 60 mL of methanol and 4.5 mL of
H2SO4. The reaction mixture was heated to reflux for 18 h and poured
into water (∼20 mL). The reaction was neutralized with NaHCO3,
and aqueous solution was washed several times with ether. The
combined organic layers were dried over sodium sulfate, filtered, and
concentrated. The crude product was then purified by flash
chromatography using 4:1 hexane/ethyl acetate as the eluent to give
1
5.3 g (90% yield) of 5: H NMR (400 MHz, CDCl3) δ 7.84 (s, 2H),
3.95 (s, 6H); 13C NMR (400 MHz, CDCl3) δ 165.6, 136.7, 135.1,
120.9, 118.1, 53.1; HRMS (ESI) m/z For C10H9Br2O4 [M + H]+
calculated 350.8868, found 350.8867.
Synthesis of (7). 2-Methoxy-N-phenylaniline (6) (2.0 g, 10.00
mmol), dimethyl 2,5-dibromoisophthalate (5) (3.50 g, 10.0 mmol),
copper (0.064 g, 1.0 mmol), copper(I) iodide (0.133 g, 0.7 mmol),
and potassium carbonate (2.06 g, 15.0 mmol) were combined in a 50
mL round-bottom flask equipped with a magnetic stir bar and reflux
condenser. Thirty milliliters of di-n-butylether was added, and the
reaction was heated to 150 °C under argon for 60 h. The solvent was
removed under dynamic vacuum, and the residue was filtered using
dichloromethane as a wash solvent. The filtrate was reduced by rotary
evaporation, and the residue was then purified by flash chromatog-
raphy using 4:1 hexane/ethyl acetate as the eluent to give 3.2 g (70%
yield) of 7: 1H NMR (CDCl3, 400 MHz) δ 3.40 (s, 6H), 3.55 (s, 3H),
6.81 (d, J = 8 Hz, 2H), 6.84−6.91 (m, 3H), 7.00 (d, J = 8 Hz, 1H),
7.06 (t, J = 8 Hz, 1H), 7.15 (t, J = 8 Hz, 2H), 7.76 (s, 2H); 13C NMR
(CDCl3, 400 MHz) δ 166.5, 153.5, 147.60, 144.0, 135.7, 134.7, 133.0,
128.5, 127.1, 125.2, 121.7, 121.1, 121.0, 116.5, 113.0, 55.7, 52.2;
HRMS (ESI) m/z For C23H21BrNO5 [M + H]+ calculated 470.0603,
found 470.0598.
Synthesis of (8). Compound 7 (4.40 g, 9.36 mmol) and NaOH
(3.75 g, 93.6 mmol) was heated to reflux in 50 mL of 1:1 ethanol/
water for 24 h. Ethanol was removed by rotary evaporation, diluted
with 10 mL of water, and acidified with concentrated hydrochloric
acid. The resulting precipitate was collected by vacuum filtration and
washed with copious portions of distilled water. The solid was dried in
an 80 °C oven for 12 h to give 3.7 g (91% yield) of the diacid of 8.
Recrystallization from ethanol/water mixture gave crystals suitable for
single crystal X-ray diffraction: 1H NMR (DMSO-d6, 400 MHz) δ 3.47
(s, 3H), 6.57 (d, J = 8.6 Hz, 2H), 6.77−6.82 (m, 2H), 6.9−6.97 (m,
2H), 7.07−7.1 (m, 3H), 7.81 (s, 2H), 12.84 (br s, 2H); 13C NMR
(DMSO-d6, 400 MHz) δ 166.8, 153.8, 147.8, 143.4, 135.9, 135.2,
134.5, 128.4, 127.3, 125.3, 121.0, 120.8, 120.2, 117.2, 113.6, 56.0;
HRMS (ESI) m/z For C21H17BrNO5 [M + H]+ calculated 442.0290,
found 442.0287.
For (M)-1: 1H NMR (CDCl3, 400 MHz) δ 0.79 (s, 3H), 0.89−0.92
(m, 1H), 0.94 (s, 3H), 1.04 (s, 3H), 1.45−1.51 (m, 1H), 1.62−1.75
(m, 2H), 7.42−7.55 (m, 3H), 7.6 (t, J = 7.8 Hz, 1H), 7.72−7.76 (m,
1H), 8.35 (dd, J = 7.8 and 1.6 Hz, 1H), 8.44 (dd, J = 7.8 and 1.6 Hz,
1H), 8.72 (d, J = 2.4 Hz, 1H), 8.76 (d, J = 2.4 Hz, 1H); 13C NMR
(CDCl3, 400 MHz) δ 177.9, 177.4, 177.4, 164.2, 140.3, 139.1, 138.7,
135.3, 134.8, 133.6, 132.0, 129.2, 128.2, 127.0, 126.3, 125.6, 125.1,
124.9, 120.4, 117.9, 89.9, 54.9, 54.6, 29.9, 28.7, 16.6, 16.5, 9.5; HRMS
(ESI) m/z For C30H23BrNO6 [M + H]+ calculated 572.0709, found
572.0714.
1
For (P)-1: H NMR (CDCl3, 400 MHz) δ 0.62 (s, 3H), 0.95 (s,
3H), 1.02 (s, 3H), 1.62−1.65 (m, 2H), 1.75−1.9 (m, 2H), 7.45−7.53
(m, 3H), 7.61 (t, J = 7.8, 1H), 7.65−7.7 (m, 1H), 8.33 (dd, J = 7.8 and
1.6 Hz, 1H), 8.43 (dd, J = 7.8 and 1.6 Hz, 1H), 8.71 (d, J = 2.4 Hz,
1H), 8.75 (d, J = 2.4 Hz, 1H); 13C NMR (CDCl3, 400 MHz) δ 177.7,
177.3, 176.8, 164.9, 140.7, 139.8, 138.9, 135.4, 134.7, 133.6, 133.1,
132.0, 129.3, 128.4, 127.3, 127.0, 126.2, 125.7, 125.5, 125.3, 124.9,
120.4, 120.4, 119.9, 117.9, 89.9, 54.5, 54.4, 30.5, 28.7, 16.7, 16.5, 9.5;
HRMS (ESI) m/z For C30H23BrNO6 [M + H]+ calculated 572.0709,
found 572.0710.
Synthesis of (9). The diacid 8 (1.2 g, 2.71 mmol) was dispersed in
25 mL of dry dichloromethane in a 50 mL, 3-neck round-bottom flask
equipped with a magnetic stir bar and reflux condenser. Under an
argon atmosphere, a few drops of DMF were added, followed by
thionyl chloride (1.2 mL, 16.3 mmol). The reaction was heated to
reflux for 2 h and cooled slightly, and SnCl4 (2.0 mL, 16.3 mmol) was
added. The reaction was heated to reflux for an additional 18 h, cooled
to room temperature, and added dropwise to 50 mL of a 1 M aqueous
solution of NaOH. The aqueous layer was washed with several
portions of dichloromethane. The combined organic layers were dried
over sodium sulfate and filtered, and the solvent was removed by
rotary evaporation. The residue was then purified by flash
chromatography using dichloromethane as the eluent to give 0.940 g
Synthesis of (M)-2. In a 50 mL Schlenk flask equipped with a
magnetic stir bar, a solution of (M)-1 (250 mg, 0.44 mmol) and
Pd(PPh3)4 (51 mg, 0.044 mmol) in dry toluene (15 mL) was bubbled
with argon for 1 h. 1,2-Bis(tributylstannyl)ethyne (0.132 mg, 0.22
mmol) was added, and the reaction was heated to 100 °C for a period
of 12 h. Toluene was then removed under vacuum to yield a black
residue, which was purified by flash chromatography using 3:7 hexane/
1
ethyl acetate as the eluent to give 80 mg of (M)-2 (37% yield): H
NMR (CDCl3, 400 MHz) δ 0.81 (s, 3H), 0.88−0.92 (m, 1H), 0.95 (s,
3H), 1.05 (s, 3H), 1.47−1.51 (m, 1H), 1.67−1.74 (m, 2H), 7.45−7.56
(m, 3H), 7.63 (t, J = 7.7 Hz, 1H), 7.73−7.77 (m, 1H), 8.39 (dd, J = 7.8
and 1.5 Hz, 1H), 8.48 (dd, J = 7.8 and 1.6 Hz, 1H), 8.81 (d, J = 2 Hz,
1H), 8.85 (d, J = 2 Hz, 1H); 13C NMR (CDCl3, 400 MHz) δ 178.3,
177.7, 177.5, 164.3, 140.4, 139.5, 139.2, 135.6, 135.2, 133.5, 131.9,
129.4, 128.1, 127.9, 127.0, 126.3, 125.7, 125.2, 124.3, 123.7, 120.4,
119.0, 90.0, 89.0, 54.9, 54.6, 29.6, 28.7, 16.7, 16.5, 9.6; HRMS m/z For
C62H45N2O12 [M + H]+ calculated 1009.2972, found 1009.2986.
1
of 9 (86% yield): H NMR (CDCl3, 400 MHz) δ 3.74 (s, 3H), 7.23
(d, J = 8.35 Hz, 1H), 7.32 (dd, J = 8 and 1.3 Hz, 1H), 7.4 (t, J = 7.9
Hz, 1H), 7.51−7.6 (m, 2H), 8.1 (dd, J = 8 and 1.4 Hz, 1H), 8.34 (dd, J
= 7.9 and 1.6 Hz, 1H), 8.7 (d, J = 2.5 Hz, 1H), 8.76 (d, J = 2.5 Hz,
1H); 13C NMR (CDCl3, 400 MHz) δ 178.5, 178.2, 150.9, 140.7,
139.3, 135.1, 134.6, 131.6, 129.0, 128.9, 126.5, 126.4, 125.8, 125.0,
2078
dx.doi.org/10.1021/jo202623u | J. Org. Chem. 2012, 77, 2074−2079

The Journal of Organic Chemistry
Note
(22) Seo, E. T.; Nelson, R. F.; Fritsch, J. M.; Marcoux, L. S.; Leedy,
D. W.; Adams, R. N. J. Am. Chem. Soc. 1966, 88, 3498−3503.
(23) Nagarjuna, G.; Kumar, A.; Kokil, A.; Jadhav, K. G.; Yurt, S.;
Kumar, J.; Venkataraman, D. J. Mater. Chem. 2011, 21, 16597−16602.
ASSOCIATED CONTENT
■
S
* Supporting Information
Characterization data and copies of H and 13C NMR spectra
1
of all compounds synthesized and crystallographic information
files (CIF) for 4, 7, 8, (M)-1, and (M)-2. This information is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: dv@chem.umass.edu. Fax: +1-413-545-4490.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge financial support from the National Science
Foundation (NSF CHE-0848596). We thank Ms. Andrea M.
Della Pelle for her assistance with the frontier molecular orbital
calculations and Dr. A. Chandrasekaran for his assistance in
collecting the single crystal X-ray diffraction data.
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