Synthesis of BF2 complexes of prodigiosin type oligopyrroles

Article abstract of DOI:10.1021/jo201183s

We developed a simple, facile route for the synthesis of BF₂ complexes of prodigiosin type oligopyrroles and their cholesterol conjugates. This route gives an access to synthesize any desired meso-aryl-substituted 3-pyrrolyl BODIPYs which were

Full text of DOI:10.1021/jo201183s

NOTE
pubs.acs.org/joc
Synthesis of BF2 Complexes of Prodigiosin Type Oligopyrroles
M. Rajeswara Rao,† Manu D. Tiwari,‡ Jayesh R. Bellare,‡,§ and M. Ravikanth*,†
†Department of Chemistry, ‡Department of Biosciences and Bioengineering, and §Department of Chemical EngineeringIndian Institute
of Technology, Bombay, Powai, Mumbai 400 076, India
S Supporting Information
b
ABSTRACT: We developed a simple, facile route for the
synthesis of BF2 complexes of prodigiosin type oligopyrroles
and their cholesterol conjugates. This route gives an access to
synthesize any desired meso-aryl-substituted 3-pyrrolyl BODI-
PYs which were not easily accessible earlier.
rodigiosins I, the open-chain pyrrolyldipyrrin type oligopyr-
roles isolated from microorganisms such as Streptomyces
Chart 1
P
and Serratia,1 are red pigments and currently under study for
their potential use as antineoplastic and immunosuppressive
agents.2 Prodigiosins are known to raise the intralysosomal pH
and to stimulate apoptosis; these are proposed to be protona-
tionÀcounteranion-based modes of action. Prodigiosins provided
inspiration to researchers to synthesize and study the anion
recognition properties of several oligopyrrolic systems3 which
are formally related to the naturally occurring prodigiosins. The
coordination of boron to a range of polypyrrole-containing ligands
that includes simple dipyrrins,4 porphyrins,5 corroles,6 and ex-
panded porphyrins7 have received tremendous attention in recent
years. The most widely utilized class of pyrrolyl boron complexes
are dipyrrin-BF2 complexes (4,4-difluoro-4-bora-3a,4a-diaza-s-in-
dacene, BODIPY), which are highly fluorescent dyes and are used
as biolabels, light harvesters, sensitizers for solar cells, fluorescent
sensors, molecular photonic wires, and electron- and energy-
transfer reagents and in laser applications4 due to their remarkable
photophysical properties such as photostability, sharp absorption,
large extinction coefficients, tunable absorption and emission
wavelengths, and high fluorescent quantum yields. BF2 complexes
ofthe prodigiosin types of structuresIIand III (Chart 1) marketed
by Invitrogen (formerly Molecular Probes) have been used as
biological labels because of their excellent photophysical proper-
ties and biocompatibility. However, the BF2 complexes II and III
are very expensive and are only available in small quantities. The
original synthesis of the BF2 complexes of prodigiosins IV and V is
available as patent literature,8 and the synthesis of IV obtained
from a U.S. patent8 is presented in Scheme 1. This route is
applicable only to the synthesis of meso free 3-pyrrolyl BODIPYs
and involves complicated reaction steps and expensive precursors.
In this paper, we report a simple synthetic route for meso-aryl-
Scheme 1. Reported Synthesis of 3-Pyrrolyl BODIPY8
substituted 3-pyrrolyl BODIPYs 1À7 (Chart 2) and biocompa-
tible 3-pyrrolyl BODIPY-cholesterol conjugates 12 and 13.
To synthesize the target compound 3-pyrrolyl meso-phenyl
boron dipyrromethene 1, we first investigated the possibility
of introducing pyrrole at the 3-position of readily available
Received: June 13, 2011
Published: July 29, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201183s J. Org. Chem. 2011, 76, 7263–7268
|

The Journal of Organic Chemistry
NOTE
Chart 2
Scheme 2. Synthesis of 3-Pyrrolyl BODIPY 1
meso-phenyl boron dipyrromethene9 8 by performing nucleophi-
lic substitution with pyrrole under various reaction conditions on
the basis of the recent report by Dehaen and co-workers.10
Addition of pyrrole and DDQ to 8 in chloroform in the presence
or absence of acid catalyst at room temperature or elevated
temperature conditions did not yield the product. We then carried
out the reaction with meso-phenyl dipyrromethene11 10, since the
1-position is susceptible to nucleophilic substitution similarly to
the 3-position in 8 and successfully synthesized 3-pyrrolyl meso-
phenyl boron dipyrromethene 1 as well as other 3-pyrrolyl
BODIPYs 2À7 by adopting a three-step, one-pot reaction
method (Scheme 2). In the first step, the meso-phenyl dipyrro-
methane 9 in CHCl3 was oxidized with 1.5 equiv of DDQ at room
temperature for 30 min. The resultant meso-phenyl dipyrro-
methene 10 without isolation was treated with 1 equiv of pyrrole
at room temperature for 15 min to form the prodigiosin type
of 1-pyrrolyl meso-phenyl dipyrromethene 11. The mechanism
of formation of 11 may be either by oxidative nucleophilic
substitution10 or radical substitution12 (Supporting Information).
However, without isolation of this intermediate 11, the reaction
mixture was treated further with triethylamine and BF3 OEt2 at
3
room temperature for 30 min. TLC analysis indicated the
formation of the desired compound 1 along with BODIPY 8.
Column chromatographic purification on silica gave compound 1
in low yield (2%). We varied the reaction conditions such as
changing the amounts of DDQ and pyrrole and altering the
reaction temperature of the last step. Thebestyield for compound
1 (24%) was obtained when we used 2.5 equiv of DDQ and 3
equiv of pyrrole while maintaining the reaction temperature of
the last step at 50 °C. Under these reaction conditions, we did
not observe any 3,5-disubstituted product. Compounds 2À7
were also prepared under same optimized reaction conditions by
using the corresponding meso-aryl dipyrromethanes (Supporting
Information).
Compounds 1À7 are soluble in common organic solvents and
have been characterized by mass, NMR, absorption, electroche-
mical, and fluorescence techniques. The molecular ion peak in
HR-MS mass spectra confirmed the identity of compounds 1À7.
1
1H, 13C, 19F, and 11B along with 1HÀ H COSY NMR were used
to characterize compounds 1À7 in detail. In 1H NMR spectra,
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NOTE
Figure 2. Comparison of normalized (a) absorption and (b) emission
spectra of compounds 1 and 8 recorded in CHCl3.
Figure 1. Crystal structure of 4 with 50% probability ellipsoids, with
hydrogen bonds denoted by dashed lines: (a) top view; (b) side view.
The cocrystallized water molecule is omitted for clarity.
(∼70À75 nm) compared to the signals for 8, indicating an
enhancement in the π-electron delocalization. Furthermore, in
the absorption spectra, the vibronic transition which appears as a
shoulder in 8 was clearly separated as a band in compound 1. The
absorption and emission spectra of compounds 1À7 were hardly
affected by solvent polarity, the maximum being slightly shifted
bathochromically when the solvent was changed from hexane to
DMSO, which is consistent with the general behavior of BOD-
IPY chromophores.9 The quantum yields of compounds 1À7
were increased by 4À8 times in comparison to that for 8,
indicating that compounds 1À7 are more fluorescent compared
to 8. The cyclic voltammetric studies of compounds 1À7 showed
one reversible reduction and one irreversible reduction along
with an ill-defined oxidation. The reduction potentials of com-
pounds 1À7 were shifted toward less negative potential com-
pared to that of 8 by ∼150À200 mV, indicating that compounds
1À7 were much easier to reduce (Supporting Information).
The use of 3-pyrrolyl BODIPYs for the synthesis of biocom-
patible compounds was demonstrated by synthesizing the 3-pyr-
rolyl BODIPY-cholesterol conjugates 12 and 13 (Scheme 3). The
commercially available cholesterol was reacted with bromoacetic
acid under DCC coupling conditions followed by column chro-
matographic purification, affording the bromo ester of
cholesterol 14. Compound 14 was treated further with either 3
or 6 in the presence of K2CO3 in DMF at room temperature
for 15 min followed by purification on silica, affording 12 and 13,
respectively, in 60À70% yields. Compounds 12 and 13 are
freely soluble in solvents such as n-hexane, CHCl3, CH3OH,
DMF, and DMSO and were characterized by various techniques
(Supporting Information). The fluorescence studies of compounds
12 and 13 indicated that these compounds are more fluorescent
with decent quantum yields (0.3À0.5) compared to those of their
corresponding 3-pyrrolyl BODIPYs 3 and 6, respectively.
Due to their excellent fluorescence properties, the commercially
available as well as synthesized BODIPY-cholesterol conjugates
have found extensive usage in various biological applications,13
especially visualization of sterol trafficking in living cells and
organisms. Since the pyrrolyl BODIPY-cholesterol conjugates
12 and 13 exhibited photophysical properties similar to those of
existing BODIPY-cholesterol conjugates, we carried out prelimin-
ary investigations on their cellular interaction and uptake by
HepG2 cells. The confocal micrographs of HepG2 cells incubated
with 12 for 12 h at 37 °C under 5% CO2 are shown in Figure 3. As
can be seen, the fluorescent molecule dispersed almost uniformly
at the cell boundary by labeling the cell membrane efficiently
without disrupting its architecture, even at a high concentration of
50 mM. This finding concurs with literature reports13 which
showed that the BODIPY-cholesterol molecule partitions itself
into ordered domains in the cell membrane, presumably by
Table 1. Photophysical Data of Compound 1
solvent
λabs (nm)
ε
λem (nm)
Δνst (cmÀ1
)
Φ
hexane
toluene
CHCl3
MeOH
DMSO
542, 579
547, 584
545, 582
540, 575
551, 587
4.55, 4.72
4.45, 4.66
4.43, 4.66
4.27, 4.58
4.37, 4.56
599
608
606
602
619
577
676
681
780
880
0.41
0.35
0.32
0.13
0.07
the eight protons of three pyrrole rings appeared as eight distinct
signals in the 6.3À7.8 ppm region; the meso-aryl protons
appeared as a multiplet at ∼7.50 ppm, and the NH signal of
the pyrrole group appeared as a broad singlet at 10.6 ppm -
(Supporting Information). The pyrrole NH proton appeared
more downfield because of its involvement in intramolecular
hydrogen bonding with the fluoride ion of the BF2 group. The
presence of hydrogen bonding was also clearly evident in 19F
NMR spectra of compounds 1À7, which exhibited a doublet of
quartets at ∼À141.5 ppm. In 11B NMR spectra, compounds
1À7 experienced downfield shifts by 1 ppm compared to the
signals for 8, which is attributed to alteration of π-delocalization
caused by the pyrrole group present at the 3-position of the
BODIPY ring (Supporting Information).
The presence of intramolecular hydrogen bonding between
the pyrrole NH and the fluoride ion of the BF2 group was also
established by the X-ray structure solved for compound 4
(Figure 1). The single crystal of compound 4 was obtained on
slow evaporation of a CHCl3 solution over a period of 2 weeks.
The structure was solved under space group P42/n and showed
the expected chemical composition and connectivity. The dipyr-
rin ring was essentially planar, and the meso-aryl group was
twisted at a 68° dihedral angle relative to the BODIPY core. The
pyrrole group lies almost in the same plane as the BODIPY core,
with a deviation of 9.8°. The NH- - -F distances were 2.15 and
2.33 Å, supporting the existence of intramolecular hydrogen
bonding between the pyrrole NH and the fluoride ions of the
BF2 group.
The absorption and fluorescence properties of compounds
1À7 were studied in five different solvents of varying polarities
(Supporting Information), and the data for compound 1 are
presented in Table 1. A comparison of the absorption and
emission spectra of 1 and 8 is shown in parts a and b of Figure 2,
respectively. As is evident from Figure 2, the absorption and
emission bands of compound 1 experienced a red shift
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Scheme 3. Synthesis of BODIPY-Cholesterol Conjugates 12 and 13
(CV) studies were carried out with an electrochemical system utilizing a
three-electrode configuration consisting of a glassy-carbon working
electrode, platinum-wire auxiliary electrode, and a saturated calomel
reference electrode. The experiments were performed in dry CH2Cl2
using 0.1 M TBAP as the supporting electrolyte. Half-wave potentials
were measured using DPV and also calculated manually by taking the
average of the cathodic and anodic peak potentials.
Materials. Dulbecco’s Modified Eagle’s Medium (DMEM), fetal calf
serum (FCS), trypsin-EDTA, L-glutamine, penicillin (50 U/mL), and
streptomycin (50 μg/mL) were obtained from HiMedia Laboratories.
Culture of HepG2 cells. HepG2 cells were obtained from the
National Centre for Cell Science, Pune, India, and cultured on DMEM
supplemented with 10% FCS, 2 mM L-glutamine, penicillin (50 U/mL),
and streptomycin (50 μg/mL) under an atmosphere of 5% CO2 at
37 °C. At confluence, the cells were passaged by rinsing the cell
monolayer twice with phosphate-buffered saline (pH 7.4) and adding
prewarmed 0.05% trypsin-EDTA solution for 5 min. After detachment
of the cell layer from the surface, complete growth medium was added in
an equal amount to the trypsin-EDTA solution; the cells were then split
1/3 and seeded into fresh complete growth medium.
Visualization of BODIPY-Cholesterol Uptake by Confocal
Microscopy. For confocal microscopy experiments, HepG2 cells were
incubated with BODIPY-cholesterol at concentrations of 5À50 mM
(in DMSO; final volume less than 1% of total medium) and seeded onto
six-well plates containing 3 mL of complete medium with 5 Â 105 cells
per well. The plates were then incubated for 12 h at 37 °C and 5% CO2.
After incubation, cells were washed twice with prewarmed (37 °C)
phosphate-buffered saline (pH 7.4) and visualized under a laser scanning
confocal microscope.
Figure 3. Uptake of BODIPY-cholesterol 12 (50 mM) by HepG2 cells:
(left) confocal micrograph; (right) corresponding overlay picture.
establishing a dynamic equilibrium with the cholesterol moieties of
the cell membrane. Thus, these conjugates can be used as potential
markers to study sterol trafficking in cellular membranes and for
live cell imaging.
In conclusion, we have developed a simple and efficient
synthetic route for the synthesis of BF2 complexes of prodigiosin
type oligopyrroles (3-pyrrolyl BODIPYs). The presence of a
pyrrole group at 3-position resulted in better photophysical
properties. We also showed that the pyrrolyl BODIPYs can be
made suitable for biological studies by covalent attachment to
cholesterol.
’ EXPERIMENTAL SECTION
Synthesis of 3-Pyrrolyl BODIPYs 1À7. A sample of meso-aryl
dipyrromethane (1.35 mmol) was taken up into CHCl3 (30 mL) and
oxidized with DDQ (3.37 mmol) at room temperature for 30 min.
Pyrrole (4.0 mmol) was added and the reaction mixture stirred for an
additional 15 min. During this period, the reaction mixture turned from
General Considerations. All NMR spectra (δ values, ppm) were
recorded using 300 and 400 MHz spectrometers. Tetramethylsilane
(TMS) was used as an external reference for recording 1H (of residual
1
protons; δ 7.26 ppm) and 13C (δ 77.0 ppm) spectra in CDCl3. 1HÀ H
COSY was used to confirm proton assignments. Cyclic voltammetric
yellow to red. Triethylamine (54 mmol) followed by BF3 Et2O (67.5
3
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NOTE
mmol) was added, and the reaction mixture was heated at 50 °C for an
additional 30 min. The reaction mixture was diluted with CH2Cl2 and
washed thoroughly with 0.1 M NaOH solution and water. The organic
layers were combined, dried over Na2SO4, and filtered, and the solvent
was removed on a rotary evaporator under vacuum. The resulting crude
product was purified by column chromatography on silica gel using
petroleum ether/ethyl acetate (92/8) and afforded pure compounds
1À7 as brown solids.
29.6, 30.3, 112.1, 116.3, 119.4, 120.0, 121.8, 123.7, 124.7, 127.2,
128.4, 128.7, 133.1, 133.3, 135.0, 137.0, 138.3, 139.4, 143.1, 151.3,
152.2; HRMS calcd for C19H14N3BOF 330.1214, found 330.1226
[M+ À F].
1
7: yield 18%; mp 236À237 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 5.85 (bs, 1H; ÀOH), 6.42À6.44 (m, 3H; py), 6.74 (d, 1H, 3J(H,
H) = 4.4 Hz; py), 6.90 (d, 1H, 3J(H,H) = 4.0 Hz; py), 6.98À7.00 (m,
1H; py), 7.07À7.08 (m, 1H; Py), 7.18 (d, 1H, 3J(H,H) = 8.4 Hz; Ar),
7.28 (d, 1H, 3J(H,H) = 8.4 Hz; Ar), 7.32À7.36 (m, 1H; Ar), 7.67 (s, 1H;
py), 10.58 (s, 1H, ÀNH); 19F NMR (282.2 MHz, CDCl3, δ in ppm)
À141.2 (dq, J(B,F), J(H,F)); 11B NMR (96.3 MHz, CDCl3, δ in ppm):
1.29 (t); 13C NMR (100 MHz, CDCl3, 25 °C): 111.8, 112.1, 116.2,
116.8, 119.5, 121.8, 123.8, 124.3, 127.3, 128.6, 132.6, 133.1, 135.9, 136.4,
137.1, 138.0, 152.4, 152.9; HRMS calcd for C19H13N3BOFBr 408.0319,
found 408.0324 [M+ À F].
1
1: yield 24%; mp 259À260 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 6.39À6.41 (m, 1H; py), 6.45À6.46 (m, 1H; py), 6.65 (d, 1H,
3J(H,H) = 3.7 Hz; py), 6.90 (d, 1H, 3J(H,H) = 4.7 Hz; py), 6.93 (d, 1H,
3J(H,H) = 4.7 Hz; py), 7.02À7.03 (m, 1H; Py), 7.20À7.21 (m, 1H; Py),
7.51À7.53 (m, 5H; Ar), 7.94 (s, 1H; py), 10.56 (s, 1H, -NH); 19F NMR
(282.2 MHz, CDCl3, δ in ppm) À141.1 (dq, J(B,F), J(H,F)); 11B NMR
(96.3 MHz, CDCl3, δ in ppm) 1.30 (t); 13C NMR (100 MHz, CDCl3,
25 °C) 111.8, 116.1, 118.7, 121.2, 123.7, 125.2, 126.6, 128.4, 130.0,
130.5, 133.3, 133.5, 134.6, 136.8, 137.8, 139.8, 151.7; HRMS calcd for
C19H14N3BF 314.1265, found 314.1260 [M+ À F].
Synthesis of BODIPY-Cholesterol Conjugates 12 and 13. A
mixture of bromo-cholesterol 14 (42 mg, 0.085 mmol), BODIPY 3 or 6
(20 mg, 0.057 mmol), and anhydrous K2CO3 (24 mg, 0.171 mmol) was
stirred in 5 mL of dry DMF for 1 h at room temperature. The DMF was
removed under reduced pressure. The resulting reaction mixture was purified
by column chromatography on silica gel using petroleum ether/ethyl acetate
(96/4) and afforded pure compounds 12 and 13 as brown solids.
1
2: yield 21%; mp 265À267 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 2.11 (s, 6H; ÀCH3), 2.35 (s, 3H; ÀCH3), 6.38À6.40 (m, 3H; py),
6.66 (d, 1H, 3J(H,H) = 4.6 Hz; py), 6.84 (d, 1H, 3J(H,H) = 4.6 Hz; py),
6.95 (s, 2H; Ar), 7.02À7.03 (m, 1H; Py), 7.20À7.21 (m, 1H; Py), 7.65
(s, 1H; py), 10.56 (s, 1H, ÀNH); 19F NMR (282.2 MHz, CDCl3, δ in
ppm) À141.4 (dq, J(B,F), J(H,F)); 11B NMR (96.3 MHz, CDCl3, δ in
ppm) 1.29 (t); 13C NMR (100 MHz, CDCl3, 25 °C) 111.8, 116.1, 118.6,
121.2, 123.8, 123.9, 126.5, 128.2, 130.4, 132.0, 133.5, 136.8, 136.9, 138.1,
138.5, 139.4, 151.8; HRMS calcd for C22H20N3BF 356.1734, found
356.1745 [M+ À F].
1
12: yield 30 mg, (70%); mp 270À271 °C; H NMR (400 MHz,
CDCl3, δ in ppm) 0.6À2.4 (m, 43H; cholesterol), 4.61 (s, 2H; ÀCH2),
6.41À6.44 (m, 2H; py), 6.64 (d, 1H, 3J(H,H) = 4.2 Hz; py), 6.91 (d, 1H,
3J(H,H) = 4.3 Hz; py), 6.96 (d, 1H, 3J(H,H) = 4.3 Hz; py), 7.03 (m, 2H;
py), 7.09 (d, 1H, 3J(H,H) = 7.3 Hz; Ar), 7.14 (d, 1H, 3J(H,H) = 6.9 Hz;
Ar), 7.21 (s, 1H; Ar), 7.40 (t, 1H, 3J(H,H) = 6.9 Hz; Ar), 7.69 (s, 1H;
py), 10.55 (s, 1H, ÀNH); 19F NMR (282.2 MHz, CDCl3, δ in ppm)
À141.3 (dq, J(B,F), J(H,F)); 11B NMR (96.3 MHz, CDCl3, δ in ppm)
1.25 (t); HRMS calcd for C48H61N3O3BF2 776.4729, found 776.4736
[M + 1]+.
1
3: yield 15%; mp 262À263 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 5.46 (bs, 1H; ÀOH), 6.42À6.46 (m, 2H; py), 6.62 (d, 1H; 3J(H,
H) = 3.7 Hz; py), 6.90À6.95 (m, 3H; py), 7.09À7.11 (m, 1H; Py),
7.26À7.28 (m, 2H; Ar), 7.41 (d, 1H, 3J(H,H) = 2.5 Hz; Ar), 7.48À7.51
1
3
3
13: yield 27 mg (59%); mp 267À268 °C; H NMR (400 MHz,
(dd, 1H, J(H,H) = 8.6 Hz, J(H,H) = 4.4 Hz; Ar), 7.67 (s, 1H; py),
10.59 (bs, 1H; ÀNH); 19F NMR (CDCl3) À141.1 (dq, J(B,F), J(H,F));
11B NMR (96.3 MHz, CDCl3, δ in ppm) 1.48 (t); 13C NMR (100 MHz,
CDCl3, 25 °C) 112.1, 116.2, 116.8, 119.4, 120.1, 120.7, 121.6, 123.7,
124.7, 127.1, 131.3, 131.7, 133.3, 134.7, 136.8, 138.3, 152.1, 155.0;
HRMS calcd for C19H14BFON3 330.1214, found 330.1203 [M+ À F].
CDCl3, δ in ppm) 0.6À2.4 (m, 43H; cholesterol), 4.55 (s, 2H; ÀCH2),
6.38À6.39 (m, 2H; py), 6.62 (s, 1H; py), 6.82À6.84 (m, 2H; py),
6.95À6.96 (m, 2H; Py), 7.06 (t, 1H, 3J(H,H) = 7.3 Hz; Ar), 7.18 (s, 1H;
Ar), 7.34 (d, 1H, 3J(H,H) = 7.7 Hz; Ar), 7.42 (t, 1H, 3J(H,H) = 8.1 Hz;
Ar), 7.62 (s, 1H; py), 10.55 (bs, 1H; ÀNH); 19F NMR (CDCl3) À141.1
(dq, J(B,F), J(H,F)); 11B NMR (96.3 MHz, CDCl3, δ in ppm) 1.28 (t);
HRMS calcd for C48H61N3O3BF2 776.4729, found 776.4738 [M + 1]+.
1
4: yield 16%; mp 234À235 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 1.27 (s, 9H; t-Bu), 5.25 (bs, 1H; ÀOH), 6.42À6.46 (m, 2H; py),
6.45À6.46 (m, 1H; py), 6.93À6.97 (m, 3H; py), 7.07À7.08 (m, 1H;
Py), 7.26À7.28 (m, 2H; Ar), 7.40 (d, 1H, 3J(H,H) = 8.2 Hz; Ar), 7.67
(s, 1H; py), 10.58 (s, 1H, ÀNH); 19F NMR (282.2 MHz, CDCl3, δ in
ppm) À141.1(dq, J(B,F), J(H,F)); 11B NMR (96.3 MHz, CDCl3, δ in
ppm) 1.28 (t); 13C NMR (100 MHz, CDCl3, 25 °C) 29.6, 30.3, 112.1,
116.3, 119.4, 120.0, 121.8, 123.7, 124.7, 127.2, 128.4, 128.7, 133.1, 133.3,
135.0, 137.0, 138.3, 139.4, 143.1, 151.3, 152.2; HRMS calcd for
C23H22N3BOF 386.1840, found 386.1826 [M+ À F].
’ ASSOCIATED CONTENT
S
Supporting Information. Tables, figures, and a CIF file
b
giving characterization data for all new compounds and crystal-
lographic data for compound 4. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
5: yield 15%; mp 227À229 °C; H NMR (400 MHz, CDCl3, δ in
’ AUTHOR INFORMATION
ppm) 5.29 (bs, 1H; ÀOH), 6.41À6.44 (m, 2H; py), 6.60 (d, 1H, 3J(H,
H) = 4.4 Hz; py), 6.87À6.93 (m, 3H; py), 7.07 (s, 1H; Py), 7.40À7.51
(m, 3H; Ar), 7.65 (s, 1H; py), 10.55 (s, 1H, ÀNH); 19F NMR (282.2
MHz, CDCl3, δ in ppm) À140.9 (dq, J(B,F), J(H,F)); 11B NMR (96.3
MHz, CDCl3, δ in ppm): 1.26 (t); 13C NMR (100 MHz, CDCl3, 25 °C)
112.4, 112.5, 116.6, 118.6, 120.2, 122.4, 122.5, 123.6, 124.2, 127.9, 131.3,
132.5, 132.7, 133.7, 134.2, 137.3, 138.2, 152.8, 152.9; HRMS calcd for
C19H13N3BOFBr 408.0319, found 408.0303 [M+ À F].
Corresponding Author
*E-mail: ravikanth@chem.iitb.ac.in
’ ACKNOWLEDGMENT
We thank the BRNS, Government of India, for financial
support, and M.R.R. thanks the CSIR for a fellowship. We also
acknowledge SAIF, IIT Bombay, Mumbai, India, for the confocal
laser scanning microscopy facility.
1
6: yield 18%; mp 230À232 °C; H NMR (400 MHz, CDCl3, δ in
ppm) 6.40À6.45 (m, 2H; py), 6.70 (d, 1H, 3J(H,H) = 4.1 Hz; py), 6.91
3
(d, 1H, J(H,H) = 4.0 Hz; py), 6.99À7.08 (m, 3H; py), 7.08 (d, 1H,
3J(H,H) = 7.0 Hz; Ar), 7.22À7.23 (m, 2H; Ar), 7.34 (t, 1H, 3J(H,H) =
7.6 Hz; Ar), 7.67 (s, 1H; py), 10.57 (s, 1H, ÀNH); 19F NMR (282.2
MHz, CDCl3, δ in ppm) À141.0 (dq, J(B,F), J(H,F)); 11B NMR (96.3
MHz, CDCl3, δ in ppm) 1.27 (t); 13C NMR (100 MHz, CDCl3, 25 °C)
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