Synthesis of fluorescent 9-aryl-substituted benzo[b]quinolizinium derivatives

Article abstract of DOI:10.1055/s-0029-1217060

The arylation of readily available benzo[b]quinolizinium-9-boronic acid with carbocyclic or heterocyclic bromoarenes in the presence of a palladium catalyst [Pd(dppf)Cl₂?CH₂Cl₂ or Pd(PPh₃)₂Cl₂

Full text of DOI:10.1055/s-0029-1217060

4226
PAPER
Synthesis of Fluorescent 9-Aryl-Substituted Benzo[b]quinolizinium
Derivatives
9
-Aryl-Substituted Ben
a
zo[
b
]quino
o
lizinium Sal
qun Tian, Heiko Ihmels*
Organische Chemie II, Universität Siegen, Adolf-Reichwein-Straße 2, 57068 Siegen, Germany
Fax +49(271)7404052; E-mail: ihmels@chemie.uni-siegen.de
Received 12 June 2009
reported. Thus, bromoquinolizinium derivatives have
been employed successfully in Stille and Sonogashira
coupling reactions.6,7,8 Considering the latter results, we
proposed that the Suzuki–Miyaura cross-coupling
Abstract: The arylation of readily available benzo[b]quinolizini-
um-9-boronic acid with carbocyclic or heterocyclic bromoarenes in
the presence of a palladium catalyst [Pd(dppf)Cl2·CH2Cl2 or
Pd(PPh3)2Cl2] gives the corresponding cationic biaryl products in
yields of 15–81%. All aryl-substituted benzo[b]quinolizinium reaction9 may be an appropriate reaction for the synthesis
(acridizinium) derivatives exhibit a long-wavelength absorption
of 9-aryl-substituted benzo[b]quinolizinium ions (acridiz-
inium ions),3 i.e., a class of compounds we are interested
maximum between 409 and 422 nm in water, which change margin-
ally in different solvents (Dl <10 nm). As the only exception, the 9-
in because of their potential application as DNA-binding
(N,N-dimethylaminophenyl)benzo[b]quinolizinium exhibits pro-
ligands and as water-soluble fluorescent probes.2e As a
nounced solvatochromic behavior (H2O: labs = 422 nm; MeCN:
starting point, we chose the benzo[b]quinolizinium-9-bo-
ronic acid (1a; Figure 1), because the potential coupling
reagents, namely halogen-substituted arenes, are readily
available with a broad variation of the substitution pattern.
The Suzuki–Miyaura coupling of 9-bromobenzo[b]quino-
lizinium bromide (1b) with arene boronic acids may also
be considered; however, this inverse approach has been
shown to be rather inefficient with bromoquinolizinium
derivatives.6b,8 Herein, we demonstrate that, indeed, the
benzo[b]quinolizinium-9-boronic acid (1a) may be em-
ployed in palladium-mediated coupling reactions and that
the products exhibit promising photophysical properties.
l
abs = 474 nm; CH2Cl2: labs = 507 nm) due to the strong donor–
acceptor interplay in the cationic chromophore. Depending on the
donor strength of the aryl substituent, the benzo[b]quinolizinium
derivatives exhibit fluorescence bands in water with long-wave-
length maxima between lfl = 452 nm (R = phenyl) and 529 nm
(R = 4-methoxyphenyl). The non-fluorescent 9-(N,N-dimethylami-
nophenyl)benzo[b]quinolizinium may be employed as a pH-sensi-
tive light-up probe (pH 2.8–4.8), since its emission intensity
increases by a factor of 130 upon protonation.
Key words: arylations, biaryls, cationic hetarenes, heterocycles,
fluorescent probes
Heterocyclic polyaromatic cations with a quaternary ni-
trogen atom represent attractive and versatile sources for
the design of water-soluble materials; for example, as col-
orimetric or fluorimetric probes.1 Moreover, annelated
azinium and quinolizinium derivatives, i.e. arenes which
contain quaternary bridgehead nitrogen atoms, have been
shown to bind to DNA and may thus be employed as a
central unit in DNA-targeting drugs.2 To explore the pos-
sibilities offered by this particular class of heteroaromatic
compounds in detail and to have efficient access to target
molecules with a definite substitution pattern, synthetic
methods are required that allow the versatile functional-
ization of the heteroaromatic core. Nevertheless, in many
cases the electrophilic aromatic substitution of cationic
heteroarenes is an inefficient and rather unselective reac-
tion; in particular as the substrates are often not persistent
under the reaction conditions.3 On the other hand, nucleo-
philic substitution reactions occasionally give the desired
products,4 but in many cases nucleophilic reagents induce
ring-opening reactions that lead to the destruction of the
substrate.5 Notably, only a few successful transition-
metal-mediated reactions of cationic hetarenes have been
1
11
10
R
2
3
N+
8
Br–
4
6
7
1a: R = B(OH)2
1b: R = Br
Figure 1
The benzo[b]quinoliziniumboronic acid 1a was synthe-
sized from the known (4-bromomethylphenyl)boronic
ester (2),10 which was prepared in two steps from com-
mercially available p-tolylboronic acid (75% overall
yield). The reaction of boronic ester 2 with (1,3-dioxolan-
2-yl)pyridine yielded the N-benzylpyridinium derivative
3
almost quantitatively (Scheme 1). The cyclo-
dehydration3b of the pyridinium salt 3 in refluxing HBr
(48%) gave the benzo[b]quinoliziniumboronic acid 1a in
80% yield. The structure of 1a was confirmed by 1H- and
13C NMR analysis, mass-spectrometric data and elemen-
tal analysis.
The first attempts to achieve an aryl–aryl coupling reac-
tion between the benzo[b]quinoliziniumboronic acid 1a
and bromobenzene were performed under commonly em-
ployed conditions of the Suzuki–Miyaura reaction, i.e.,
with Pd(PPh3)2Cl2 as the catalyst in a refluxing solution of
water and 1,4-dioxane. To avoid the known ring-opening
SYNTHESIS 2009, No. 24, pp 4226–4234
x
x.
x
x
.
2
0
0
9
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217060; Art ID: T11809SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
9-Aryl-Substituted Benzo[b]quinolizinium Salt
4227
O
O
O
O
O
B
OH
O
B
B
O
HBr (48%)
N
O
OH
N+
N+
reflux, 4 h
DMSO, r.t., 7 d
Br–
Br–
Br
1a
80%
3
> 95%
2
Scheme 1 Synthesis of the benzo[b]quinolizinium-9-boronic acid (1a)
reaction of the benzo[b]quinolizinium ion in the presence this catalyst did not improve the yield of the coupling re-
of a strong nucleophile,5a,b potassium fluoride was used as action of the boronic acid 1a with, for example, 3-bromo-
the additive.11 However, only traces of cross-coupling furan (Table 1, entry 9 and 10). Except for product 4a, all
product 4a were generated in the reaction as indicated by products 4b–g are new compounds and were fully charac-
1H NMR spectroscopic analysis of the crude product. The terized. Specifically, the structural assignments were con-
use of potassium phosphate as a rather weak base led to firmed by 1H and 13C NMR analysis, mass-spectrometric
the decomposition of the substrate 1a (monitored by and elemental analysis data. Unfortunately, attempts to
TLC). The optimization of the reaction conditions re- synthesize pyridine-substituted benzo[b]quinolizinium
vealed that an efficient cross-coupling between 1a and derivatives in various catalyst systems such as
bromobenzene may be achieved in a solvent mixture of Pd(PPh3)2Cl2/KF, Pd(dppf)Cl2·CH2Cl2/KF, or Pd2(dba)3/
water, methanol and 1,2-dimethoxyethane (DME) with PCy3/KF, by the reaction of the boronic acid 1a with 2-
Pd(PPh3)2Cl2 as catalyst and potassium fluoride as a base bromo-, 3-bromo- or 4-iodopyridine, i.e. reagents which
(Scheme 2). Under these particular conditions, the reac- are frequently used for Suzuki–Miyaura coupling reac-
tion of the boronic acid 1a with bromobenzene, p-bromo- tions, did not provide the corresponding pyridyl-substitut-
fluorobenzene or p-bromoanisole gave the 9- ed benzo[b]quinolizinium derivatives. So far, it is not
arylbenzo[b]quinolizinium derivatives 4a–c as the main clear why the coupling reaction with bromopyridine de-
products, which were isolated in moderate yields (21– rivatives failed; however, these results are consistent with
44%) by precipitation as tetrafluoroborate or perchlorate the observation that the inverse combination of substrates,
salts upon addition of aqueous sodium tetrafluoroborate i.e., bromoquinolizinium ions and pyridine boronic acids,
or sodium perchlorate solutions (ion metathesis) and sub- do not react in a Suzuki-type coupling reaction either.6b
sequent crystallization (Table 1). In contrast, only traces
of the cross-coupling product 4d were isolated when the
reaction was performed with p-bromo-N,N-dimethyl-
OH
–
B
BF3
OH
KHF2
aniline as substrate. Presumably, the oxidative addition to
the electron-rich bromoarene is not efficient enough to
maintain the catalytic cycle.9a Nevertheless, the use of
Pd(dppf)Cl2·CH2Cl2 as the catalyst increased the yield of
the products 4c and 4d up to 81% and 40%, respectively,
as compared with 21% and 3% with Pd(PPh3)2Cl2
(Table 1, entries 3–6). As this observation indicated that
Pd(dppf)Cl2·CH2Cl2 may be an appropriate catalyst for
the coupling of the boronic acid 1a and electron-rich bro-
moarenes, it was also employed for the reaction with 3-
bromothiophene, 2-bromothiophene, and 3-bromofuran;
however, the corresponding heteroaryl-substituted ben-
zo[b]quinolizinium derivatives 4e–g were isolated only in
low to moderate yields (15–42%). Although Pd2(dba)3/
PCy3 has been demonstrated to catalyze Suzuki cross-
coupling reactions of nitrogen heterocycles efficiently,12
N+
N+
MeOH–H2O
0 °C
2 h
r.t.
Br–
1a
5
~ 85% (purity: 90–95%)
Scheme 3 Synthesis of benzo[b]quinolizinium-9-trifluoroborate 5
As it has been demonstrated that organotrifluoroborates
may be employed in Suzuki–Miyaura coupling reac-
tions,13,14 it was examined whether benzo[b]quinolizini-
umtrifluoroborate derivatives are synthetically available
and whether they may be used for palladium-mediated
coupling reactions with bromoarenes. The boronic acid 1a
was reacted with KHF2 to give the corresponding organ-
1
otrifluoroborate 5 as the main product (Scheme 3). H-,
13C- and 19F NMR spectroscopic data are in agreement
with the proposed structure. In particular, the coupling be-
OH
Ar
B
catalyst, KF
OH
ArBr
+
N+
N+
H2O–MeOH–DME
reflux, 5–24 h
4a–g: Ar = aryl or heteroaryl
1a
(see Table 1)
Scheme 2 Synthesis of 9-aryl-substituted benzo[b]quinolizinium derivatives by Suzuki–Miyaura cross-coupling (for substituent Ar, see
Table 1)
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

4228
M. Tian, H. Ihmels
PAPER
Table 1 Reaction Conditions for the Synthesis of 9-Aryl-Substituted Benzo[b]quinolizinium Derivatives According to Scheme 2
Entry
1
Catalyst
Time (h)
5
Product
Yield (%)a
44b
Pd(PPh3)2Cl2
4a
Ar =
Ar =
Ar =
Ar =
Ar =
Ar =
Ar =
Ar =
2
3
Pd(PPh3)2Cl2
8
8
4b
4c
4c
4d
4d
4e
4f
40b
21c
81c
3c
F
Pd(PPh3)2Cl2
OMe
OMe
NMe2
4
Pd(dppf)Cl2·CH2Cl2
Pd(PPh3)2Cl2
8
5
8
6
Pd(dppf)Cl2·CH2Cl2
Pd(dppf)Cl2·CH2Cl2
Pd(dppf)Cl2·CH2Cl2
Pd(dppf)Cl2·CH2Cl2
Pd2(dba)3/PCy3
8
40c
42c
28c
15c
14c
NMe2
S
7
24
24
24
24
8
S
O
O
9
4g
4g
Ar =
Ar =
10
a Yields are the average of two independent experiments; dppf = 1,1¢-bis(diphenylphosphino)ferrocene.
b Isolated and fully characterized as a tetrafluoroborate salt.
c Isolated and fully characterized as a perchlorate salt.
tween fluorine atoms and C-8 (J = 1 Hz), C-10 (J = 2 Hz) For comparison, the complementary Suzuki–Miyaura re-
along with the chemical shift of the fluoro substituents action between the 9-bromobenzo[b]quinolizinium 1b
(d = –140.8 ppm) are characteristic of the aryltrifluorobo- and potassium phenyltrifluoroborate was examined under
rate structure. Nevertheless, the product could not be iso- established conditions, i.e., Pd(OAc)2/K2CO3/water;8
lated as a pure sample (purity: 90–95% as determined by however, this reaction failed due to extensive decomposi-
1H NMR spectroscopic analysis). The benzo[b]quinoli- tion of the benzo[b]quinolizinium substrate under these
ziniumtrifluoroborate 5 is insoluble in most organic sol- particular reaction conditions. In contrast, the reaction of
vents except for DMF or DMSO, presumably due to its 9-bromobenzo[b]quinolizinium 1b with phenylboronic
zwitterionic nature. Attempts to employ the ben- acid with Pd(dppf)Cl2·CH2Cl2 as catalyst and potassium
zo[b]quinoliziniumtrifluoroborate 5 (90% purity) in fluoride gave the phenylbenzo[b]quinolizinium 1c in 42%
cross-coupling reactions with aryl bromides in the pres- yield (Scheme 4). This observation shows that the synthe-
ence of either potassium fluoride or cesium carbonate as sis of aryl-substituted benzo[b]quinolizinium derivatives
the base were not successful either because no reaction may be accomplished by either possible Suzuki–Miyaura
took place (in the presence of KF) or decomposition of the approach, i.e. starting with the substrates 1a or 1b. Thus,
substrate (in the presence of CsCO3) occurred under these both methods may be used complementarily; however, it
conditions.
should be considered that arylboronic acid derivatives are
not as easily available as the corresponding bromoarenes,
i.e. the boronic acids are usually significantly more expen-
Br
Pd(dppf)Cl2⋅CH2Cl2, KF
+
N+
N+
H2O–MeOH–DME
reflux, 5 h
HO
B
Br–
OH
4a
42%
1b
Scheme 4 Synthesis of 9-phenylbenzo[b]quinolizinium (4a) from the reaction of 9-bromobenzo[b]quinolizinium (1b) with phenylboronic
acid
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

PAPER
9-Aryl-Substituted Benzo[b]quinolizinium Salt
4229
sive or require additional synthetic steps for their prepara- The 9-arylbenzo[b]quinolizinium derivatives 4a–c and
tion.9a In addition, Stille coupling reactions may also offer 4e–g exhibit absorption properties that resemble those of
a possible route to quinolizinium-based biaryl deriva- the benzo[b]quinolizinium chromophore15 (Table 2);
tives;6a,b however, Suzuki coupling reactions are more at- however, depending on the electron-donating character of
tractive from a practical viewpoint because of the low the aryl substituents, red-shifts of the absorption bands are
toxicity and facile removal of the boron-containing side induced as compared with the parent benzo[b]quinolizi-
product and reasonable yields of the coupling products.
nium (long-wavelength maximum: 399 nm in EtOH,
Table 2 Absorption and Emission Properties of Compounds 4a–g
Compound
Solvent
l
abs (nm) (log e)a
lfl (nm)b
ffl
H2Of
MeCN
MeOH
DMF
409 (4.12)
409 (4.11)
411 (4.11)
413 (4.10)
415 (4.15)
431, 452
434, 453
435, 455
437, 458
442, 459
31c
26c
35c
22c
21c
N+
CH2Cl2
4a
H2Of
MeCN
MeOH
DMF
409 (4.17)
409 (4.14)
410 (4.15)
413 (4.06)
414 (4.17)
454
36c
34c
38c
24c
20c
F
437, 455
440, 455
438, 458
451, 459
N+
CH2Cl2
4b
H2Of
MeCN
MeOH
DMF
411 (4.23)
414 (4.27)
416 (4.29)
417 (4.26)
421 (4.30)
529
528
526
531
520
29d
44d
62d
34d
35d
OMe
N+
CH2Cl2
4c
e
e
H2O
422 (4.23)
474 (4.33)
477 (4.38)
476 (4.36)
475 (4.35)
507 (4.39)
–
–
–
–
–
–
–
NMe2
e
e
MeCN
MeOH
DMSO
DMF
–
e
e
–
e
e
–
e
e
N+
–
e
e
CH2Cl2
–
4d
H
+ NMe2
H2O
408 (4.12)
423, 447
14c
N+
4d + H+
H2Of
MeCN
MeOH
DMF
412 (4.22)
413 (4.21)
415 (4.26)
417 (4.24)
420 (4.26)
472
474
476
479
473
23c
26c
28c
22c
18c
S
N+
CH2Cl2
4e
H2Of
MeCN
MeOH
DMF
422 (4.22)
424 (4.28)
426 (4.30)
428 (4.27)
432 (4.31)
495
497
496
502
490
25d
28d
19d
22d
11d
S
N+
CH2Cl2
4f
H2Of
MeCN
MeOH
DMF
408 (4.14)
409 (4.17)
410 (4.16)
411 (4.20)
416 (4.17)
474
474
478
471
467
17c
25c
39c
4c
O
N+
CH2Cl2
14c
4g
a Long-wavelength absorption maximum (c = 50 mM).
b Fluorescence emission maximum (c = 10 mM); excitation wavelength lex = 380 nm.
c Fluorescence quantum yield relative to Coumarin 1.
d Fluorescence quantum yield relative to Coumarin 153.
e Too low to be determined.
f Containing 1% MeCN.
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

4230
M. Tian, H. Ihmels
PAPER
of the absorption spectra of compound 4d in dichlo-
romethane are essentially independent of the concentra-
tion (inset of Figure 2), the bathochromic and
hyperchromic effect is unlikely the result of aggregation.
Similar red-shifted absorption bands have previously
been reported for 9-aminobenzo[b]quinolizinium and 7-
aminoquinolinium derivatives in dichloromethane and ex-
plained by the exceptionally high polarizability of this sol-
vent (a = 6.52 Å3).2e,4b Thus, the influence of this solvent
on the delicate interplay between the vertical electronic
excitation and the immediate vertical conversion to the
solvent-relaxed Franck–Condon excited state of charged
push-pull polyenes18 leads to a decrease of the energy of
the excited state.
The absorption and emission properties of the dimethyl-
aminophenyl-substituted benzo[b]quinolizinium deriva-
tive 4d change significantly upon protonation (Figure 3).
Thus, with decreasing pH value of the solution (pH 6.1–
1.7) the broad long-wavelength absorption disappeared,
along with the development of a new absorption band
(lmax = 388 nm) that resembles that of the 9-phenylben-
zo[b]quinolizinium 4a, which indicates the disruption of
the donor–acceptor system in 4d by the protonation of the
electron-donating amine substituent. On the other hand,
the addition of acid to the weakly fluorescent ben-
zo[b]quinolizinium derivative 4d leads to a significant in-
crease of the emission intensity by a factor of 130. This
increase of the fluorescence intensity is also caused by
protonation of the amino group, which leads to the sup-
pression of the major quenching process in the excited
state of compound 4d, namely the photoinduced electron-
transfer between the excited benzo[b]quinolizinium and
the amine substituent.2e,17,19 The data from the photomet-
ric and fluorimetric titrations were used to determine the
pKa value of the protonated amine 4d in water (insets of
Figure 3) by a numerical fit of the experimental data to the
Henderson–Hasselbalch equation.20 Based on the spectro-
Figure 2 Absorption spectra of compound 4d in different solvents
(c = 50 mM). Inset: Plot of the absorbance of 4d in dichloromethane
at l = 506 nm versus concentration (r2 = 0.9996).
log e = 3.88).15 In particular, the strong donor–acceptor
interplay in the dimethylaminophenyl-substituted ben-
zo[b]quinolizinium derivative 4d results in a pronounced
red-shifted absorption maximum of this compound (477
nm in MeOH). In the case of the thienyl-substituted ben-
zo[b]quinolizinium ions 4e and 4f, the donating effect of
the electron-rich thiophene ring is more effective when it
is connected with its C2 carbon atom to the benzo[b]qui-
nolizinium as indicated by the larger red-shift of the ab-
sorption maximum of compound 4f (424 nm; in MeCN)
as compared with the isomer 4e (413 nm in MeCN).16
Compounds 4a–c and 4e–g show relatively weak solvato-
chromism (Table 2). In contrast, the long-wavelength ab-
sorption bands of 4d show a bathochromic and
hyperchromic effect upon changing the solvent from wa-
ter to polar organic solvents.17 Notably, this effect was
most pronounced in dichloromethane, in which the ab-
sorption maximum is significantly red-shifted (507 nm,
Figure 2). Since the extinction coefficients and the shape
Figure 3 Influence of the pH value on the absorption (a; c = 50 mM) and emission (b; c = 10 mM, lex = 381 nm) properties of 4d in Britton–
Robinson buffer; arrows indicate the development of emission bands upon addition of acid. Insets: spectrophotometric titration curves (a; open
circles: Absorption at 293 nm; filled circles: Absorption at 350 nm) and spectrofluorimetric titration curve (b); numerical fits calculated for the
value pKa = 3.8. Inset: image showing the fluorescence of 4d (c = 10 mM) in Britton–Robinson buffer at pH 7.0 (left) and pH 2.0 (right).
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

PAPER
9-Aryl-Substituted Benzo[b]quinolizinium Salt
4231
and spectrofluorimetric titrations and determination of the pKa val-
ue of compound 4d were performed according to published meth-
ods.2e All spectrophotometric measurements were performed at
least three times to ensure the reproducibility. Solutions for analysis
were prepared by dilution of stock solutions (1.0 × 10–3 M in MeCN
or MeOH) immediately before the experiments.
metric data, the pKa was determined to be 3.8, i.e. it is
comparable to those of 9-(p-amino)phenylacridinium ions
(pKa = 2.5–3.5 in water), which exhibit an increase of the
fluorescence intensity upon protonation or complexation
with metal cations.17,21 Thus, compound 4d represents a
water-soluble pH-sensitive fluorescent probe,22 whose
light-up effect may be used at pH 2.8–4.8 with essentially
no background fluorecence at higher pH values. It should
be noted that the pKa of 4d and its range of performance
may be modified by substitution of the phenyl ring with
electron-donor or electron-acceptor substituents.
2-(1,3-Dioxolan-2-yl)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)benzyl] Pyridinium Bromide (3)
A solution of 2-(1,3-dioxolan-2-yl)pyridine (4.80 g, 31.8 mmol)
and 4-(bromomethyl)benzeneboronic acid pinacol ester (9.40 g,
31.8 mmol) in DMSO (15 mL) was stirred under an argon gas atmo-
sphere at r.t. for 7 d. The reaction mixture was poured into EtOAc
(1 L) and the precipitated white solid was collected, washed thor-
oughly with EtOAc and Et2O, and dried under vacuum to give the
analytically pure product.
In summary, we present one of the rare examples for a
successful palladium-mediated arylation of heteroaromat-
ic cations. Specifically, the Suzuki–Miyaura reaction of
the readily available benzo[b]quinoliziniumboronic acid
1a may be employed to obtain 9-aryl-substituted ben-
zo[b]quinolizinium derivatives. The products exhibit
promising absorption and emission properties and repre-
sent a useful starting point for the design of fluorescent
probes. In particular, it was demonstrated with the di-
methylaminophenyl-substituted benzo[b]quinolizinium
derivative 4d that this method may be generally used to at-
tach functionality to the benzo[b]quinolizinium fluoro-
phore, in this case the pH-sensitive amino substituent,
which allows fluorimetric detection of selected analytes.
Along these lines, it may be proposed that other selective
receptor units may be introduced instead of the aminome-
thyl substituent, thus leading to a significant fluorimetric
response upon complexation of a particular guest mole-
cule.
Yield: 13.5 g (95%); colorless solid; mp 163–164 °C.
1H NMR (400 MHz, DMSO-d6): d = 1.29 (s, 12 H, CH3), 4.11 (s,
4 H, CH2), 6.06 (s, 2 H, CH2), 6.48 (s, 1 H, CH), 7.33 (d, J = 8.0 Hz,
2 H, H-3, H-5), 7.72 (d, J = 8.0 Hz, 2 H, H-2, H-6), 8.20–8.27 (m,
1 H, H-5¢), 8.34 (dd, J = 8.1, 1.3 Hz, 1 H, H-3¢), 8.72–8.79 (m, 1 H,
H-4¢), 9.07 (dd, J = 6.2, 1.0 Hz, 1 H, H-6¢).
13C NMR (100 MHz, DMSO-d6): d = 24.5 (CH3), 59.8 (CH2), 65.6
(CH2), 83.8 (CH), 97.0 (CH), 126.0 (CHAr), 127.4 (CHAr), 128.6
(CHAr), 129.0 (Cq), 134.9 (CHAr) 136.8 (CHAr), 147.2 (CHAr), 147.3
(CHAr), 152.0 (Cq).
MS (ESI+): m/z (%) = 368 (100) [M]+.
Anal. Calcd for C21H27BBrNO4: C, 56.28; H, 6.07; N, 3.13. Found:
C, 56.15; H, 6.11; N, 3.13.
Benzo[b]quinolizinium-9-boronic Acid Bromide (1a)
The pyridinium derivative 3 (1.00 g, 2.23 mmol) was dissolved in
aq HBr (48%, 10 mL) and the reaction mixture was stirred under re-
flux for 4.5 h. After cooling to r.t., the reaction mixture was poured
into THF (500 mL) and the yellow precipitate was collected,
washed with THF and EtOAc and dried to give the product (0.61 g,
All commercially available chemicals were reagent grade and used
without further purification. 9-Bromobenzo[b]quinolizinium bro-
mide (1b) was prepared according to published procedures.23 Melt-
ing points were determined with a melting point apparatus (Büchi
510K) and are uncorrected. Mass spectra (ESI in the positive-ion
mode, source voltage 6 kV) were recorded with a Finnigan LCQ
Deca instrument; only m/z values in the range of 100–2000 units
were analyzed. NMR spectra were measured on a Bruker Avance
400 (1H: 400 MHz, 13C: 100 MHz) and a Varian NMR System 600
(1H: 600 MHz, 13C: 150 MHz, 19F: 564 MHz) at 20 °C. Chemical
shifts of 1H- and 13C NMR spectra are given in ppm (d) relative to
TMS (d = 0.00 ppm). Chemical shifts of 19F NMR spectra are given
in ppm (d) relative to a spectrometer reference based on the 2H-fre-
quency according to IUPAC rules.24 Unambiguous proton NMR as-
signments were established with the help of {1H, 1H}-COSY,
HSQC and HMBC experiments. All couplings given in the 13C
NMR spectroscopic data refer to 13C–19F couplings. Elemental
microanalyses of all new compounds were performed with a
HEKAtech EuroEA combustion analyzer by Mr. H. Bodenstedt
(Organische Chemie I, Universität Siegen). TLC analyses were per-
formed on silica gel sheets (Macherey–Nagel Polygram Sil G/
UV254; eluent: CHCl3–MeOH–AcOH, 90:10:1 v/v). Purified water
with resistivity ≥18 MW cm–1 was used for spectrophotometric mea-
surements. Absorption spectra were recorded on a Varian Cary 100
double-beam spectrophotometer. Emission spectra were recorded
on a Varian Cary Eclipse fluorescence spectrophotometer. All spec-
trophotometric measurements were performed in thermostated
quartz sample cells at 20 °C. The Britton–Robinson buffer
solution25 was prepared from boric acid, phosphoric acid and sodi-
um acetate (0.04 M each) in purified water and neutralized to pH 7.0
by addition of 2 M NaOH solution. Acid–base spectrophotometric
1
91%), which was pure by H NMR. An analytically pure sample
was obtained by two-fold recrystallization from H2O.
Yellow needles; mp 228–230 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.95–8.02 (m, 1 H, H-3), 8.13–
8.05 (m, 1 H, H-2), 8.27 (d, J = 9.3 Hz, 1 H, H-8), 8.42 (d, J = 8.8
Hz, 1 H, H-7), 8.61 (d, J = 8.6 Hz, 1 H, H-1), 8.76 (br s, 3 H, H-10,
2 × OH), 9.28 (s, 1 H, H-11), 9.31 (d, J = 6.8 Hz, 1 H, H-4), 10.45
(s, 1 H, H-6).
13C NMR (100 MHz, DMSO-d6): d = 122.4 (CHAr), 125.1 (CHAr),
126.2 (Cq), 126.2 (CHAr), 126.9 (CHAr), 130.8 (CHAr), 133.5
(CHAr), 134.0 (CHAr), 134.5 (Cq), 134.6 (CHAr), 137.4 (Cq), 139.6
(CHAr), 141.7 (Cq).
MS (ESI+): m/z (%) = 224 (100) [M]+.
Anal. Calcd for C13H11BBrNO2·H2O: C, 48.50; H, 4.07; N, 4.35.
Found: C, 48.71; H, 3.91; N, 4.45.
Suzuki Coupling of Benzo[b]quinolizinium-9-boronic Acid Bro-
mide (1a) and Aryl Bromides; General Procedure
Under an inert gas atmosphere, a solution of benzo[b]quinolizini-
umboronic acid (1a; 303 mg, 1.00 mmol), the corresponding aryl or
heteroaryl bromide (1.50 mmol), Pd(PPh3)2Cl2 (21 mg, 0.03 mmol)
or Pd(dppf)Cl2×CH2Cl2 (40.8 mg, 0.05 mmol) and KF (232 mg,
4.00 mmol) in DME–MeOH–H2O (2:1:1; 12 mL) was stirred under
reflux for 5–24 h (reaction monitored by TLC). After cooling to r.t.,
MeOH (10 mL) was added to the reaction mixture. The precipitated
palladium-black was removed by filtration and sat. aq NaBF4 or
NaClO4 (5 mL) was added to the filtrate until no more precipitation
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

4232
M. Tian, H. Ihmels
PAPER
9-(p-N,N-Dimethylaminophenyl)benzo[b]quinolizinium Per-
chlorate (4d)
Catalyst: Pd(dppf)Cl2·CH2Cl2.
was observed. The yellow precipitate was collected, washed with
H2O, EtOAc, and Et2O. The analytically pure product was separated
by recrystallization of the precipitate from MeCN–EtOAc or by col-
umn chromatography (Al2O3, Activity I; MeCN) and subsequent re-
crystallization from MeCN–EtOAc.
Yield: 160 mg (40%); dark-red powder; mp >300 °C.
1H NMR (600 MHz, DMSO-d6): d = 3.04 (s, 6 H, CH3), 6.89 (d,
J = 8.9 Hz, 2 H, H-2¢, H-6¢), 7.80–7.86 (m, 1 H, H-3), 7.91 (d,
J = 9.3 Hz, 2 H, H-3¢, H-5¢), 7.95–8.02 (m, 1 H, H-2), 8.35–8.50 (m,
3 H, H-1, H-7, H-8), 8.51 (s, 1 H, H-10), 8.99 (s, 1 H, H-11), 9.14
(d, J = 6.9 Hz, 1 H, H-4), 10.24 (s, 1 H, H-6).
9-Phenylbenzo[b]quinolizinium Tetrafluoroborate (4a)
Catalyst: Pd(PPh3)2Cl2.
Yield: 152 mg (44%); yellow prisms; mp 203–204 °C.
1H NMR (600 MHz, DMSO-d6): d = 7.57 (t, J = 7.2 Hz, 1 H, H-4¢),
7.64 (dd, J = 7.9, 7.6 Hz, 2 H, H-3¢, H-5¢), 7.93–7.97 (m, 1 H, H-3),
8.02 (d, J = 7.3 Hz, 2 H, H-2¢, H-6¢), 8.08 (dd, J = 9.0, 7.2 Hz, 1 H,
H-2), 8.40 (dd, J = 9.0, 1.5 Hz, 1 H, H-8), 8.58 (d, J = 9.2 Hz, 1 H,
H-7), 8.60 (d, J = 9.5 Hz, 1 H, H-1), 8.71 (s, 1 H, H-10), 9.20 (s, 1
H, H-11), 9.27 (d, J = 7.0 Hz, 1 H, H-4), 10.42 (s, 1 H, H-6).
13C NMR (150 MHz, DMSO-d6): d = 122.2 (CHAr), 123.6 (CHAr),
124.6 (CHAr), 125.0 (Cq), 126.8 (CHAr), 127.7 (CHAr), 129.0
(CHAr), 129.5 (CHAr), 129.7 (CHAr), 130.5 (CHAr), 131.1 (CHAr),
134.4 (CHAr), 135.8 (Cq), 137.8 (Cq), 137.8 (Cq), 140.0 (CHAr),
145.3 (Cq).
13C NMR (150 MHz, DMSO-d6): d = 39.5 (CH3), 112.2 (CHAr),
119.4 (CHAr), 121.1 (CHAr), 123.0 (CHAr), 123.4 (Cq), 124.2 (Cq),
126.3 (CHAr), 128.2 (CHAr), 128.3 (CHAr), 129.5 (CHAr), 130.4
(CHAr), 133.8 (CHAr), 136.0 (Cq), 137.4 (Cq), 139.0 (CHAr), 145.1
(Cq), 151.0 (Cq).
MS (ESI+): m/z = 299 (100) [M]+.
Anal. Calcd for C21H19ClN2O4: C, 63.24; H, 4.80; N, 7.02. Found:
C, 62.94; H, 4.72; N, 7.07.
9-(3-Thienyl)benzo[b]quinolizinium Perchlorate (4e)
Catalyst: Pd(dppf)Cl2·CH2Cl2.
MS (ESI+): m/z (%) = 256 (100) [M]+.
Yield: 152 mg (42%); yellow needles; mp 238–240 °C (dec.).
Anal. Calcd for C19H14BF4N·0.5H2O: C, 64.81; H, 4.29; N, 3.98.
Found: C, 64.47; H, 4.22; N, 3.79.
1H NMR (600 MHz, DMSO-d6): d = 7.82 (dd, J = 5.2, 2.9 Hz, 1 H,
H-4¢), 7.88–7.93 (m, 2 H, H-3, H-5¢), 8.02–8.07 (m, 1 H, H-2),
8.41–8.45 (m, 2 H, H-8, H-2¢), 8.49 (d, J = 9.0 Hz, 1 H, H-7), 8.55
(d, J = 8.7 Hz, 1 H, H-1), 8.66 (s, 1 H, H-10), 9.06 (s, 1 H, H-11),
9.22 (d, J = 6.9 Hz, 1 H, H-4), 10.31 (s, 1 H, H-6).
9-(p-Fluorophenyl)benzo[b]quinolizinium Tetrafluoroborate
(4b)
Catalyst: Pd(PPh3)2Cl2.
13C NMR (150 MHz, DMSO-d6): d = 121.9 (CHAr), 122.0 (CHAr),
124.0 (CHAr), 124.9 (Cq), 126.3 (CHAr), 126.3 (CHAr), 126.7
(CHAr), 128.5 (CHAr), 128.8 (CHAr), 130.1 (CHAr), 131.1 (CHAr),
134.3 (CHAr), 136.1 (Cq), 137.8 (Cq), 139.3 (CHAr), 139.6 (Cq),
139.9 (Cq).
Yield: 143 mg (40%); yellow prisms; mp 235–237 °C.
1H NMR (600 MHz, DMSO-d6): d = 7.44–7.51 (m, 2 H, H-2¢, H-6¢),
7.92–9.97 (m, 1 H, H-3), 8.05–8.10 (m, 3 H, H-2, H-3¢, H-5¢), 8.38
(dd, J = 9.1, 1.7 Hz, 1 H, H-8), 8.57 (d, J = 8.9 Hz, 1 H, H-7), 8.60
(d, J = 8.8 Hz, 1 H, H-1), 8.68 (s, 1 H, H-10), 9.17 (s, 1 H, H-11),
9.26 (d, J = 6.8 Hz, 1 H, H-4), 10.40 (s, 1 H, H-6).
MS (ESI+): m/z = 262 (100) [M]+.
13C NMR (150 MHz, DMSO-d6): d = 116.3 (d, J = 22 Hz, CHAr),
122.1 (CHAr), 123.4 (d, J = 1 Hz, CHAr), 124.5 (CHAr), 124.8 (Cq),
126.7 (CHAr), 128.9 (CHAr), 129.9 (d, J = 8 Hz, CHAr), 130.2
(CHAr), 131.1 (CHAr), 134.1 (d, J = 3 Hz, Cq), 134.3 (CHAr), 135.6
(Cq), 137.7 (Cq), 139.8 (CHAr), 144.0 (Cq), 163.0 (d, J = 248 Hz,
Cq).
Anal. Calcd for C17H12ClNO4S: C, 56.44; H, 3.34; N, 3.87; S, 8.86.
Found: C, 56.45; H, 3.29; N, 4.09; S, 8.59.
9-(2-Thienyl)benzo[b]quinolizinium Perchlorate (4f)
Catalyst: Pd(dppf)Cl2·CH2Cl2.
Yield: 100 mg (28%); yellow prisms; mp 214–216 °C (dec.).
MS (ESI+): m/z = 274 (100) [M]+.
1H NMR (600 MHz, DMSO-d6): d = 7.32 (dd, J = 4.9, 3.7 Hz, 1 H,
H-4¢), 7.88 (dd, J = 5.0, 0.9 Hz, 1 H, H-3¢), 7.89–7.92 (m, 1 H, H-
3), 8.01 (dd, J = 3.5, 0.9 Hz, 1 H, H-5¢), 8.04 (dd, J = 9.0, 7.4 Hz, 1
H, H-2), 8.36 (dd, J = 8.9, 1.6 Hz, 1 H, H-8), 8.46–8.52 (m, 2 H, H-
1, H-7), 8.55 (s, 1 H, H-10), 9.10 (s, 1 H, H-11), 9.20 (d, J = 7.0 Hz,
1 H, H-4), 10.30 (s, 1 H, H-6).
Anal. Calcd for C19H13BF5N: C, 63.19; H, 3.63; N, 3.88. Found: C,
62.79; H, 3.30; N, 3.89.
9-(p-Methoxyphenyl)benzo[b]quinolizinium Perchlorate (4c)
Catalyst: Pd(dppf)Cl2·CH2Cl2.
13C NMR (150 MHz, DMSO-d6): d = 120.7 (CHAr), 122.0 (CHAr),
124.0 (CHAr), 124.8 (Cq), 126.7 (CHAr), 128.2 (CHAr), 129.0
(CHAr), 129.1 (CHAr), 129.4 (CHAr), 130.1 (CHAr), 131.3 (CHAr),
134.3 (CHAr), 135.9 (Cq), 137.9 (Cq), 138.7 (Cq), 139.6 (CHAr),
141.1 (Cq).
Yield: 312 mg (81%); yellow prisms; mp 218–220 °C.
1H NMR (600 MHz, DMSO-d6): d = 3.88 (s, 3 H, CH3), 7.16–7.22
(m, 2 H, H-2¢, H-6¢), 7.88–7.94 (m, 1 H, H-3), 7.98–8.08 (m, 3 H,
H-2, H-3¢, H-5¢), 8.40 (dd, J = 9.0, 1.6 Hz, 1 H, H-8), 8.53 (d,
J = 9.3 Hz, 1 H, H-7), 8.56 (d, J = 8.8 Hz, 1 H, H-1), 8.64 (s, 1 H,
H-10), 9.12 (s, 1 H, H-11), 9.23 (d, J = 6.9 Hz, 1 H, H-4), 10.36 (s,
1 H, H-6).
13C NMR (150 MHz, DMSO-d6): d = 55.4 (CH3), 114.9 (CHAr),
121.9 (CHAr), 122.0 (CHAr), 124.1 (CHAr), 124.8 (Cq), 126.7
(CHAr), 128.8 (CHAr), 129.1 (CHAr), 129.7 (Cq), 130.2 (CHAr),
131.0 (CHAr), 134.3 (CHAr), 136.0 (Cq), 137.7 (Cq), 139.7 (CHAr),
144.9 (Cq), 160.7 (Cq).
MS (ESI+): m/z = 262 (100) [M]+.
Anal. Calcd for C17H12ClNO4S: C, 56.44; H, 3.34; N, 3.87; S, 8.86.
Found: C, 56.38; H, 3.28; N, 3.83; S, 8.59.
9-(3-Furyl)benzo[b]quinolizinium Perchlorate (4g)
Catalyst: Pd(dppf)Cl2·CH2Cl2.
Yield: 50 mg (15%); yellow powder; mp 234–236 °C (dec.).
MS (ESI+): m/z = 286 (100) [M]+.
1H NMR (600 MHz, DMSO-d6): d = 7.29–7.34 (m, 1 H, H-4¢),
7.88–7.93 (m, 1 H, H-3), 7.93–7.96 (m, 1 H, H-5¢), 8.05 (dd, J = 8.5,
7.0 Hz, 1 H, H-2), 8.32 (dd, J = 9.0, 1.2 Hz, 1 H, H-8), 8.49 (d,
J = 8.9 Hz, 1 H, H-7), 8.56 (s, 1 H, H-2¢), 8.57 (d, J = 9.0 Hz, 1 H,
Anal. Calcd for C20H16ClNO5: C, 62.26; H, 4.18; N, 3.63. Found: C,
62.50; H, 3.86; N, 3.68.
Synthesis 2009, No. 24, 4226–4234 © Thieme Stuttgart · New York

PAPER
9-Aryl-Substituted Benzo[b]quinolizinium Salt
4233
H-1), 8.69 (s, 1 H, H-10), 9.04 (s, 1 H, H-11), 9.23 (d, J = 7.0 Hz, 1
H, H-4), 10.30 (s, 1 H, H-6).
I.; Cuevas, C.; Vaquero, J. J. J. Med. Chem. 2004, 47, 1136.
(b) Molina, A.; Vaquero, J. J.; García-Navío, J. L.; Alvarez-
Builla, J.; Pascual-Teresa, B.; Gago, F.; Rodrigo, M. M.
J. Org. Chem. 1999, 64, 3907. (c) Fontana, A.; Benito, E. J.;
Martín, J. M.; Sánchez, N.; Alajarin, R.; Vaquero, J. J.;
Alvarez-Builla, J.; Lambel-Giraudet, S. L.; Pierre, A.;
Caignard, D. Bioorg. Med. Chem. Lett. 2002, 12, 2611.
(d) Ihmels, H.; Faulhaber, K.; Vedaldi, D.; Dall’Acqua, F.;
Viola, G. Photochem. Photobiol. 2005, 81, 1107.
(e) Granzhan, A.; Ihmels, H.; Viola, G. J. Am. Chem. Soc.
2007, 129, 1254.
13C NMR (150 MHz, DMSO-d6): d = 108.5 (CHAr), 121.1 (CHAr),
122.0 (CHAr), 123.7 (CHAr), 124.8 (Cq), 124.9 (Cq), 126.7 (CHAr),
128.7 (CHAr), 129.6 (CHAr), 131.2 (CHAr), 134.3 (CHAr), 136.1
(Cq), 137.8 (Cq), 137.9 (Cq), 139.6 (CHAr), 143.3 (CHAr), 145.6
(CHAr).
MS (ESI+): m/z = 246 (100) [M]+.
Anal. Calcd for C17H12ClNO5: C, 59.06; H, 3.50; N, 4.05. Found: C,
58.52; H, 3.42; N, 3.95.
(3) (a) Vaquero, J. J.; Alvarez-Builla, J. Advances in Nitrogen
Heterocycles, Vol. 4; Moody, C. J., Ed.; JAI Press: Stamford
CT, 2000. (b) Bradsher, C. K. In Comprehensive
Heterocyclic Chemistry, Vol. 2; Boultier, A. J.; McKillop,
A., Eds.; Pergamon Press: Oxford, 1985, 525.
(4) (a) Granzhan, A.; Ihmels, H. ARKIVOC 2007, (viii), 136.
(b) van den Berg, O.; Jager, W. F.; Picken, S. J. J. Org.
Chem. 2006, 71, 2666. (c) Naruto, S.; Mizuta, H.;
Nishimura, H. Tetrahedron Lett. 1976, 17, 1597.
(5) (a) Deiseroth, H. J.; Granzhan, A.; Ihmels, H.; Schlosser, M.;
Tian, M. Org. Lett. 2008, 10, 757. (b) Krapcho, A. P.;
Cadamuro, S. A.; Macnee, L. ARKIVOC 2007, (ix), 28.
(c) Mörler, D.; Kröhnke, F. Liebigs Ann. Chem. 1971, 744,
65. (d) Arai, S.; Hida, M. Advances in Heterocyclic
Chemistry; Katritzky, A. R., Ed.; Academic Press: Orlando,
1992. (e) Miyadera, T.; Tachikawa, R. Tetrahedron 1969,
25, 837.
9-Phenylbenzo[b]quinolizinium Tetrafluoroborate (4a) from
9-Bromobenzo[b]quinolizinium Bromide (1b)
Under an inert gas atmosphere, a solution of 1b (303 mg, 1.00
mmol), phenyl boronic acid (122 mg, 1.00 mmol), Pd(dp-
pf)Cl2·CH2Cl2 (24.5 mg, 0.03 mmol) and KF (232 mg, 4.00 mmol)
in DME–MeOH–H2O (2:1:1; 12 mL) was stirred under reflux for 5
h (reaction monitored by TLC). After cooling to r.t., MeOH (10 mL)
was added to the reaction mixture and the precipitated palladium-
black was removed by filtration. Sat. aq NaBF4 (5 mL) was added
to the filtrate until no more precipitation was observed. The yellow
precipitate was collected and washed with H2O, EtOAc, and Et2O.
The analytically pure product was separated by recrystallization of
the precipitate from MeCN–EtOAc (145 mg, 42%). The spectro-
scopic data and melting point are identical with those of the product
from the Pd-catalyzed reaction of benzo[b]quinolizinium-9-boronic
acid bromide (1a) and bromobenzene (see above).
(6) (a) Barchín, B. M.; Valenciano, J.; Cuadro, A. M.; Alvarez-
Builla, J.; Vaquero, J. J. Org. Lett. 1999, 1, 545. (b) García-
Cuadrado, D.; Cuadro, A. M.; Barchín, B. M.; Nuñez, A.;
Cañeque, T.; Alvarez-Builla, J.; Vaquero, J. J. J. Org. Chem.
2006, 71, 7989. (c) García, D.; Cuadro, A. M.; Alvarez-
Builla, J.; Vaquero, J. J. Org. Lett. 2004, 6, 4175.
(7) García-Cuadrado, D.; Cuadro, A. M.; Alvarez-Builla, J.;
Vaquero, J. J. Synlett 2002, 1904.
Benzo[b]quinolizinium-9-trifluoroborate (5)
Under an inert gas atmosphere, a solution of benzo[b]quinolizini-
um-9-boronic acid (1a; 303 mg, 1.00 mmol) and KHF2 (234 mg,
3.00 mmol) in MeOH (5 mL) was stirred at 0 °C. H2O (5 mL) was
added dropwise to the solution at 0 °C, and the reaction mixture was
stirred at r.t. for 2 h. The solvent was evaporated in vacuo and the
resulting solid was collected and washed thoroughly with H2O and
MeOH, and dried to give the crude product with 90–95% purity (de-
(8) Caneque, T.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J.
1
J. Tetrahedron Lett. 2009, 50, 1419.
termined by H NMR spectroscopic analysis) as pale-yellow solid
(9) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11.
(c) Suzuki, A. Chem. Commun. 2005, 4759. (d)Miyaura, N.
In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F.; de Meijere, A., Eds.; Wiley-VCH: New York, 2004,
Chap. 2. (e) Martin, R.; Buchwald, S. L. Acc. Chem. Res.
2008, 41, 1461.
(10) (a) Nicolas, M.; Fabre, B.; Marchand, G.; Simonet, J. Eur. J.
Org. Chem. 2000, 1703. (b) Zhang, C.; Zheng, G.; Fang, L.;
Li, Y. Synlett 2006, 475.
(233 mg, 85%). The crude product was used for the coupling reac-
tion without further purification.
1H NMR (600 MHz, DMSO-d6): d = 7.78–7.86 (m, 1 H, H-3), 7.90–
7.98 (m, 1 H, H-2), 8.04 (d, J = 8.5 Hz, 1 H, H-8), 8.19–8.27 (m, 2
H, H-7, H-10), 8.44 (d, J = 8.8 Hz, 1 H, H-1), 9.05 (s, 1 H, H-11),
9.16 (d, J = 7.0 Hz, 1 H, H-4), 10.27 (s, 1 H, H-6).
13C NMR (150 MHz, DMSO-d6): d = 121.2 (CHAr), 123.3 (CHAr),
125.1 (CHAr), 125.4 (Cq), 126.6 (CHAr), 127.7 (q, J = 2 Hz, CHAr),
129.7 (CHAr), 133.7 (CHAr), 135.4 (Cq), 136.1 (q, J = 1 Hz, CHAr),
136.9 (Cq), 139.2 (CHAr).
(11) Wright, S. W.; Hageman, D. L.; McClure, L. D. J. Org.
Chem. 1994, 59, 6095.
(12) Kudo, N.; Perseghini, M.; Fu, G. C. Angew. Chem. Int. Ed.
2006, 45, 1282.
19F NMR (564 MHz, DMSO-d6): d = –140.8.
(13) Molander, G. A.; Petrillo, D. E. Org. Lett. 2008, 10, 1795.
(14) Molander, G. A.; Canturk, B.; Kennedy, L. E. J. Org. Chem.
2009, 74, 973.
(15) Saraf, S. U. D. Heterocycles 1981, 16, 987.
(16) A similar effect has been observed in other chromophores,
see: (a) Choi, S. H.; Kim, K.; Lee, J.; Do, Y.; Churchill, D.
G. J. Chem. Crystallogr. 2007, 37, 315. (b) Baraldi, I.;
Ginocchietti, G.; Mazzucato, U.; Spalletti, A. Chem. Phys.
2007, 337, 168.
(17) A similar effect was observed for 9-[(4-dimethyl-
amino)phenyl]-10-methylacridinium perchlorate, see:
Ariese, F.; Verhoeven, J. W. Recl. Trav. Chim. Pays-Bas
1989, 108, 109.
Acknowledgment
Generous support by the Deutsche Forschungsgemeinschaft is
gratefully acknowledged. We thank Mr. Marco Primerano, Univer-
sity of Padova, Italy, for technical assistance.
References
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(19) (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnalaugsson, T.;
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