Highly fluorescent BODIPY dyes modulated with spirofluorene moieties

Article abstract of DOI:10.1021/ol902631d

(Figure presented) A new type of structurally rigid BODIPY dye having spirofluorene moieties has been synthesized. These structurally constrained BODIPY dyes with spirofluorene moieties exhibit an intense bathochromic fluorescence. The solvent dependence of fluorescence ON/OFF switching of a BODIPY dye having an amino moiety was observed.

Full text of DOI:10.1021/ol902631d

ORGANIC
LETTERS
2010
Vol. 12, No. 2
296-299
Highly Fluorescent BODIPY Dyes
Modulated with Spirofluorene Moieties
Toshiyuki Kowada, Shuhei Yamaguchi, and Kouichi Ohe*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto UniVersity, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
ohe@scl.kyoto-u.ac.jp
Received November 14, 2009
ABSTRACT
A new type of structurally rigid BODIPY dye having spirofluorene moieties has been synthesized. These structurally constrained BODIPY dyes
with spirofluorene moieties exhibit an intense bathochromic fluorescence. The solvent dependence of fluorescence ON/OFF switching of a
BODIPY dye having an amino moiety was observed.
The technique of visualizing living cells by labeling proteins
or DNA with fluorescent dyes is widely applicable to early
detection of focus and elucidation of cellular mechanisms.1
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) de-
rivatives are regarded as among the most promising candi-
dates for fluorescent labels and probes.2 In general, BODIPY
dyes are relatively insensitive to the surrounding environment
such as polarity and pH and have large molar absorption
coefficients and high fluorescence quantum yields. Further-
more, their absorption and emission bands are narrow and
sharp, and their photophysical properties are readily tunable
by modification of the BODIPY core.
reported so far, only a limited number of studies have
appeared.4
Herein, we report the synthesis and photophysical proper-
ties of novel BODIPY dyes (sp-BODIPY) derived from
spiro[fluorene-9,4′(1′H)-indeno[1,2-b]pyrrole] (sp-FIP)5 (Fig-
ure 1). To prepare sp-FIP as a key structure, we have
explored the palladium-catalyzed intramolecular direct C-H
arylation of a pyrrole moiety.6-8 This approach enabled us
to obtain a new type of BODIPY dye. Furthermore, their
highly rigid structures reduced nonradiative decay of excited
states, resulting in a high photoluminescence quantum yield.
Extension of π-conjugated systems in general brings about
a bathochromic shift of the emission maxima of fluorophores.
However, free rotation between the BODIPY core and
π-conjugated groups results in a decrease in quantum yields.
Thus, constrained linkage of the BODIPY core with the
π-conjugated moieties is essential to obtain efficient batho-
chromic fluorescence.3 Although structurally constrained
BODIPY dyes with moderate quantum yields have been
(3) Burghart, A.; Kim, H.; Welch, M. B.; Thoresen, L. H.; Reibenspies,
J.; Burgess, K.; Bergstro¨m, F.; Johansson, L. B.-Å. J. Org. Chem. 1999,
64, 7813.
(4) (a) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.; Burgess, K. J.
Org. Chem. 2000, 65, 2900. For aza-BODIPY derivatives, see: (b) Zhao,
W.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44, 1677. (c) Zhao, W.;
Carreira, E. M. Chem.sEur. J. 2006, 12, 7254.
(5) Spiro[fluorene-9,4′-[4H]indeno[1,2-b]thiophene] (sp-FIT) and spiro[f-
luorene-9,4′-[4H]indeno[1,2-b]furan] (sp-FIF) have been already reported
from our laboratory. See: (a) Kowada, T.; Matsuyama, Y.; Ohe, K. Synlett
2008, 1902. (b) Kowada, T.; Ohe, K. Bull. Korean Chem. Soc., in press.
(6) For recent reviews, see: (a) Alberico, D.; Scott, M. K.; Lautens, M.
Chem. ReV. 2007, 107, 174. (b) Satoh, T.; Miura, M. Chem. Lett. 2007, 36,
200. (c) Campeau, L.-C.; Stuart, D. R.; Fagnou, K. Aldrichim. Acta 2007,
(1) Lavis, L. D.; Raines, R. T. ACS Chem. Biol. 2008, 3, 142.
(2) (a) Loudet, A.; Burgess, K. Chem. ReV. 2007, 107, 4891. (b) Ulrich,
G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47, 1184.
40, 35
.
10.1021/ol902631d  2010 American Chemical Society
Published on Web 12/14/2009

Scheme 1. Synthesis of sp-FIP
Figure 1. New approach to structurally constrained BODIPY dyes.
The preparation of sp-FIP is summarized in Scheme 1.
The reaction of 1-bromo-2-iodobenzene with isopropyl
Grignard reagent9 followed by quenching with 9-fluorenone
gave 1 in excellent yield (95%). Friedel-Crafts alkylation
of N-tosylpyrrole with 1 using AlCl3 afforded 2 in 90% yield.
When we carried out the palladium-catalyzed intramolecular
direct C-H arylation of 2, 3a and 3b were isolated in 63%
and 6% yields, respectively. We determined the structures
of both isomers by X-ray crystallography (see the Supporting
Information). Hydrolysis of the tosyl group of 3a proceeded
smoothly to give sp-FIP in quantitative yield (99%).
Scheme 2. Synthesis of BODIPY Dyes 5a-e
We next examined the transformation of sp-FIP to
BODIPY dyes having various aryl substituents at the meso
position (Scheme 2). Several para-substituted aryl aldehydes
were reacted with 2 equiv of sp-FIP in the presence of
catalytic amounts of trifluoroacetic acid to afford the corre-
sponding dipyrromethanes 4a-e in good to excellent yields.
Subsequent DDQ oxidation and complexation with BF3·OEt2
led to the formation of BODIPY dyes 5a-e in good yields.
The structure of 5d was unambiguously determined by X-ray
crystallography (see the Supporting Information).
The absorption and emission spectra of 5a-e were
measured in THF (Table 1). All BODIPY dyes show an
intense, narrow, and sharp absorption band at λabs ) 627-641
nm with ε ) 161060-180700 M-1cm-1. The absorption
maxima of 5a-e were scarcely affected by the electronic
nature of substituents R. Their Stokes shifts are less than 10
nm, while the emission maxima of 5a-e were observed at
(7) For Pd-catalyzed intramolecular direct arylation of a pyrrole, see:
(a) Grigg, R.; Sridharan, V.; Stevenson, P.; Sukirthalingam, S.; Worakun,
T. Tetrahedron 1990, 46, 4003. (b) Smet, M.; Dijk, J. V.; Dehaen, W. Synlett
1999, 495. (c) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Paladino, G.;
Zoni, C. Eur. J. Org. Chem. 2005, 2091. (d) Joucla, L.; Putey, A.; Joseph,
B. Tetrahedron Lett. 2005, 46, 8177. (e) Bowie, A. L., Jr.; Hughes, C. C.;
Trauner, D. Org. Lett. 2005, 7, 5207. (f) Arai, N.; Takahashi, M.; Mitani,
M.; Mori, A. Synlett 2006, 3170. (g) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Synthesis 2008, 136. For Pd-catalyzed
intramolecular direct alkylation of a pyrrole, see: (h) Hwang, S. J.; Cho,
S. H.; Chang, S. J. Am. Chem. Soc. 2008, 130, 16158. (i) Lie´gault, B.;
Fagnou, K. Organometallics 2008, 27, 4841.
636-652 nm. Furthermore, the emission maxima were also
scarcely affected by substituents R. As shown later, it is
noteworthy that all BODIPY dyes except for 5a show higher
quantum yields in comparison with those reported by
Burgess’s group.4a This suggests that the constraint of the
spirofluorene moieties increases the rigidity of the BODIPY
core, thereby reducing the nonradiative decay.
It is noted that the fluorescence quantum yield of 5a having
an N,N-dimethylamino group was exceptionally low relative
to the BODIPY dyes 5b-e. We measured absorption and
emission spectra of 5a in various solvents with different
dielectric constants (Figure 2) because we suspected photo-
induced electron transfer (PeT)10 leading to fluorescence
quenching.11 The positions of the absorption maxima and
the emission maxima in all solvents were scarcely affected
(8) For Pd-catalyzed intermolecular direct arylation of a pyrrole, see:
(a) Filippini, L.; Gusmeroli, M.; Riva, R. Tetrahedron Lett. 1992, 33, 1755.
(b) Reith, R. D.; Mankad, N. P.; Calimano, E.; Sadighi, J. P. Org. Lett.
2004, 6, 3981. (c) Deprez, N. R.; Kalyani, D.; Krause, A.; Sanford, M. S.
J. Am. Chem. Soc. 2006, 128, 4972. (d) Blaszykowski, C.; Aktoudianakis,
E.; Bressy, C.; Alberico, D.; Lautens, M. Org. Lett. 2006, 8, 2043. (e) Toure´,
B. B.; Lane, B. S.; Sames, D. Org. Lett. 2006, 8, 1979. (f) Wang, X.;
Gribkov, D. V.; Sames, D. J. Org. Chem. 2007, 72, 1476.
(9) Boymond, L.; Rottla¨nder, M.; Cahiez, G.; Knochel, P. Angew. Chem.,
Int. Ed. 1998, 37, 1701.
Org. Lett., Vol. 12, No. 2, 2010
297

The feasibility of electron transfer from the electron donor
(N,N-dimethylaminophenyl group) to the electron acceptor
(BODIPY core) was estimated by the Rehm-Weller equa-
tion (eq 1)10,12
Table 1. Optical Properties of 5a-e in THF (c ) 1.00 × 10-6
M)
a
compd λabs (nm) ε (M-1 cm-1
)
λex (nm) λem (nm)
ΦF
∆GET ) E1/2(D+/D)-E1/2(A/A-)-∆E00-wP
(1)
5a
5b
5c
5d
5e
627
632
634
638
641
180700
178570
167210
163890
161060
580
585
585
587
592
636
640
642
648
652
0.16
0.76
0.67
0.73
0.61
where E1/2(D+/D) and E1/2(A/A-) are the ground-state redox
potentials of the donor and acceptor moiety, respectively,
∆E00 is the singlet excited energy of the fluorophore, and
wP is the work term for the charge separation.13 The relative
free energies (∆∆GET) of 5a in various solvents according
to Rehm-Weller equation are summarized in Table 2. The
N,N-dimethylaminophenyl group and BODIPY core are
twisted by 79° and conjugately uncoupled according to the
result of X-ray analysis.14 As shown in Table 2, ∆∆GET in
various solvents indicates that the electron transfer can take
place more easily in following order: in DMF > in THF >
in CHCl3. The emission apparently disappear in THF (ΦF
) 0.16) because fluorescence ON/OFF threshold seems to
exist between CHCl3 and THF (Figure 2c).10
a Determined by using a calibrated integrating sphere system.
by the dielectric constants of the solvents, whereas the
fluorescence quantum yields varied in each solvent. When
we used DMF with a high dielectric constant, the quantum
yield of 5a was very low (ΦF ) 0.06). On the other hand,
CHCl3 and benzene with relatively low dielectric constant
showed high quantum yields (ΦF ) 0.73 and 0.78, respec-
tively). Because the absorption maxima and the emission
maxima of 5a are not changed by varying the solvent, we
deduced that in a more polar solvent, such as DMF, PeT
from the N,N-dimethylaminophenyl group to the BODIPY
core (a-PeT) readily occurred.
Table 2. Relative Free Energies (∆∆GET) of 5a Calculated by
Fitting the Data to the Rehm-Weller Equation
d
e
E1/2(D+/D)a b
E1/2(A/A-)a c
∆E00
∆∆GET
,
,
solvent
(V)
(V)
(eV)
(eV)
DMF
THF
CHCl3
0.34
0.32
0.34
-1.19
-1.44
-1.58
1.79
1.81
1.89
-0.29
-0.08
0
a Measured by CV with 0.1 M n-Bu4NPF6 vs Fc/Fc+ 0.1 V s-1
.
b Oxidation potential of N,N-dimethylaniline. c Reduction potential of 5a.
d Estimated by the absorption edge of the UV-vis spectrum. e Relative ∆GET
values were calculated with respect to the value in CHCl3 as a standard.
To reveal the effect of spirofluorene moieties on photophysi-
cal properties, the absorption and emission spectra of 5b were
compared with those of BODIPY dyes 6, 7, and 8a-c (Table
3). The absorption and emission maxima of 5b showed a
bathochromic shift in comparison with those of 6 and 7. On
the other hand, compared with both maxima of 8a-c, a
hypsochromic shift of 5b was observed. However, the photo-
luminescence quantum yield of 5b was much higher than those
of 6-8. Compared with 6, it is obvious that spirofluorene
(10) Sunahara, H.; Urano, Y.; Kojima, H.; Nagano, T. J. Am. Chem.
Soc. 2007, 129, 5597
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Han, J.; Burgess, K. Chem. ReV. 2009 , DOI: 10.1021/cr900249z
.
.
(12) (a) Kavarnos, G. J. Fundamentals of Photoinduced Electron
Transfer; VCH: New York, 1993. (b) Fahrni, C. J.; Yang, L.; VanDerveer,
D. G. J. Am. Chem. Soc. 2003, 125, 3799. (c) Gabe, Y.; Urano, Y.; Kikuchi,
K.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2004, 126, 3357. (d) Agou,
T.; Kojima, T.; Kobayashi, J.; Kawashima, T. Org. Lett. 2009, 11, 3534.
(e) Kennedy, D. P.; Kormos, C. M.; Burdette, S. C. J. Am. Chem. Soc.
2009, 131, 8578
.
Figure 2. (a) UV-vis absorption and (b) photoluminescence
(13) The work term (wP) is neglected here because this contribution is
relatively small compared to the other parameters.
spectra of 5a in various solvents. (c) Solvent dependence of
fluorescence.
(14) Kollmannsberger, M.; Gareis, T.; Heinl, S.; Breu, J.; Daub, J.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1333.
298
Org. Lett., Vol. 12, No. 2, 2010

Table 3. Comparison of Optical Properties in THF
compd
λabs (nm)
λex (nm)
λem (nm)
ΦF
5b
6
632
623
553
637
658
634
585
579
553
640
629
586
647
673
647
0.76
0.60
0.22
0.34
0.05
0.38
Figure 3. Molecular orbital plots of the HOMO for model
compound 9: (a) structure of 9; (b) front view; (c) top view.
7a
8ab
8bb
8cb
of 9 were mainly delocalized over the indene-fused BODIPY
core. This result implies that an intramolecular charge transfer
process might exist in this system. Furthermore, it is
noteworthy that the HOMO level is slightly delocalized over
the fluorene moieties. This phenomenon is well-known as
spiro conjugation,18 leading to through-space elongation of
the π-system. As a result, it is considered that absorption
and emission maxima of 5b were bathochromically shifted
relative to those of 6.
In conclusion, we have demonstrated that structurally
constrained BODIPY dyes based on spiro[fluorene-9,4′(1′H)-
indeno[1,2-b]pyrrole] exhibit a significant increase in the
fluorescence quantum yield as well as a red shift of the
absorption and emission maxima. Spirofluorene moieties lead
to high rigidity and good planarity of the BODIPY core.
Furthermore, the fluorescence ON/OFF phenomenon was
observed arising from a PeT process from an N,N-dimethyl-
aminophenyl unit to the BODIPY core. DFT calculations
indicate that the π-system of BODIPY derivatives 5a-d was
delocalized over the fluorene moieties as well as the BODIPY
core because of spiro conjugation.
a Reference 15. b Reference 4a, in CHCl3.
moieties effectively affect the red shift of absorption and
emission spectra and increase the quantum yield.
To gain insight into the red shift of absorption and
emission maxima of 5b relative to those of 6, theoretical
calculations of model compound 9 were carried out at the
B3LYP/6-31G(d) level (Figure 3).16,17 A TD-DFT calcula-
tion at the B3LYP/6-31G(d) level indicates that the most
allowed transition is from HOMO to LUMO and HOMO-2
to LUMO, the oscillator strength being 1.04 (see the
Supporting Information). HOMO-2 was mainly delocalized
over the fluorene moieties, whereas the HOMO and LUMO
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Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
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X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
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Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
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Acknowledgment. T.K. gratefully acknowledges the
financial support by the Global COE Program “International
Center for Integrated Research and Advanced Education in
Materials Science” (No. B-09) of MEXT, administered by
the Japan Society for the Promotion of Science.
Supporting Information Available: Experimental pro-
cedures, copies of 1H and 13C NMR spectra for new
compounds, X-ray data of 3a, 3b, and 5d, and DFT
calculation data of 9. This material is available free of charge
via the Internet at http://pubs.acs.org.
Revision B.05; Gaussian, Inc., Pittsburgh, PA, 2003
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of gOpenMol program: Laaksonen, L. J. Mol. Graphics 1992, 10, 33
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5208. (b) Geuenich, D.; Hess, K.; Ko¨hler, F.; Herges, R. Chem. ReV. 2005,
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OL902631D
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