Design, synthesis and redox properties of a fluorene platform linking two different Bodipy dyes

Article abstract of DOI:10.1016/j.tetlet.2010.03.095

Several new fluorophores have been prepared by grafting boradiazaindacene (red absorbing) and/or styrylboradiazaindacene (blue absorbing) units as terminal energy acceptors onto a fluorene-derived platform. In one case, an amino-bis(bipyridine) pocket has been attached to enable strong binding of transition metal ions. The stepwise syntheses were largely based on Pd-catalysed cross-coupling reactions. The electrochemistry of the dyes has been analysed by reference to the properties of the various synthetic intermediates, protonation of the tertiary amine site present in the bis(bipyridine) species enabling processes involving this centre to be distinguished from those associated with the boradiazaindacene (Bodipy) unit.

Full text of DOI:10.1016/j.tetlet.2010.03.095

Tetrahedron Letters 51 (2010) 2875–2879
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Design, synthesis and redox properties of a fluorene platform linking two
different Bodipy dyes
*
Thomas Bura, Raymond Ziessel
Laboratoire de Chimie Organique et Spectroscopies Avancées (LCOSA), Ecole Chimie Polymères, Matériaux (ECPM), 25 rue Becquerel, 67087 Strasbourg Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Several new fluorophores have been prepared by grafting boradiazaindacene (red absorbing) and/or sty-
rylboradiazaindacene (blue absorbing) units as terminal energy acceptors onto a fluorene-derived plat-
form. In one case, an amino-bis(bipyridine) pocket has been attached to enable strong binding of
transition metal ions. The stepwise syntheses were largely based on Pd-catalysed cross-coupling reac-
tions. The electrochemistry of the dyes has been analysed by reference to the properties of the various
synthetic intermediates, protonation of the tertiary amine site present in the bis(bipyridine) species
enabling processes involving this centre to be distinguished from those associated with the boradiaza-
indacene (Bodipy) unit.
Received 11 February 2010
Revised 18 March 2010
Accepted 22 March 2010
Available online 27 March 2010
Keywords:
Bodipys’
Fluorene
Bipyridine
Styryl
Ó 2010 Elsevier Ltd. All rights reserved.
Formylation
Electrochemistry
Control of energy and electron transfer processes and high
luminescence efficiency are fundamental aspects of natural photo-
synthesis,1 and are crucial to the development of light emitting
materials for opto-electronic technologies.2 Concerning the latter,
particularly significant observations have been reported concern-
ing molecular photonic wires built around porphyrins using a dip-
yrromethene dye as the primary light harvester.3,4 Upon excitation,
this dye injects photons into a linear array of metallo-porphyrins
along which the photon is transferred rapidly until being trapped
by a low-energy acceptor. Careful balancing of the rates of forward
and reverse energy transfer allows energy migration to proceed
with almost 100% efficiency.5 This use of a dipyrromethene chro-
mophore pioneered the application of such dyes as energy donors.
Since then, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (F-Bodipy)
dyes, which are dipyrromethene derivatives, have become very
popular as a result of their valuable optical properties.6 Amongst
these are pronounced stability, high absorption coefficients
(ꢀ80,000–200,000 Mꢁ1 cmꢁ1) in the visible portion of the electro-
magnetic spectrum, narrow emission profiles and outstanding
emission quantum yields reaching 100% for the best cases.7
The numerous applications since found for Bodipy derivatives
include use in solar concentrators, in molecular wires,8 in multi-
chromophoric scaffoldings dedicated to directional energy trans-
fer,9 in solar cells,10 in fluorescent sensing materials,11 in probes
for bio-labelling,12 as well as in laser applications13 and for grafting
to nanoparticles. In some special instances, two-photon absorbing
dyes dedicated to cell imaging have been produced.14 Recently
new types of liquid crystals,15 fluorescent organogelators16 and
controlled polymers were produced by specific decoration at the
periphery of the dyes.17
In this Letter we describe a modular approach to the rational
synthesis of fluorene-substituted Bodipy dyes. Three fundamental
considerations underlie their design. First, it is known that fluorene
is a fluorescent platform capable of transferring its excitonic
energy when properly excited. Second, the fluorene structure is
readily functionalised on the meta (2,7-positions) and the central
positions (9,90-positions). Third, meso-iodophenyl-substituted Bod-
ipy units, including those with 3-substituents allowing modulation
of the extent of p-conjugation and binding of metal cations, can be
easily prepared for reaction with acetylenic groups on the 2,7-posi-
tions of fluorene.
I
I
N
F
N
F
B
H
H
N
F
N
F
O
O
B
N
N
6
10
11
N
O
O
N
* Corresponding author. Tel.: +33 3 90 24 26 89; fax: +33 3 90 24 27 42.
E-mail addresses: ziessel@unistra.fr, ziessel@chimie.u-strasbg.fr (R. Ziessel).
N
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.095

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T. Bura, R. Ziessel / Tetrahedron Letters 51 (2010) 2875–2879
Access to such platforms first required producing the key reac-
I
Br
N
(i)
N
tants 6, 10 and 11. This, indeed, was complicated by the lack of
general synthetic procedures for the modification of both fluorene
and Bodipy to induce properties such as high solubility and the
capacity for tuning the optical and redox properties, as well as
for the preparation of multi-chromophoric derivatives.
2
+
N
N
(ii)
NH2
(iii)
Encouraged by our success in the large scale preparation of dibro-
mofluorene,11 we attempted to prepare highly soluble unsymmetri-
cal fluorene scaffoldings. To this end, we first explored the synthesis
of compounds 6 and 7 by a routine procedure (Scheme 1) which was
expected to be unselective with regard to product distribution.
Alkylation of 2,7-dibromofluorene with the tosylate derivative 2
was straightforward, leading to compound 3 in 95% yield.18 Palla-
dium(0) promoted cross-coupling with trimethylsilylacetylene
provided a mixture of equimolar quantities of 4 and 5 easily separa-
ble by column chromatography due to the presence of the short
oligoethylene chains. Stepwise deprotection of the TMS group was
feasible by strict control of the reaction time and the separation of
6 and 7 was again easy.
H
O
I
N
N
9
N
N
N
N
(iv)
N
N
N
N
8
Scheme 2. Reagents and conditions: (i) CH3Li, ꢁ78 °C; (ii) NBS, dibenzoyl peroxide,
CCl4; (iii) CH3CN, KI 10 mol %, K2CO3 20 equiv, 80 °C, 5 d, 80%; (iv) [Pd(PPh3)2Cl2]
(10 mol %), HCOONa (1.2 equiv), CO 1 atm, DMF, 100 °C, 3 h, 83%.
4,4difluoro-4bora-3a,4a-diaza-s-indacene 10,23 using Knoevenagel
reaction catalysed under basic conditions and leading to the blue
dye 11 in good yield (Scheme 3). Interestingly, the tetra-bipyridine
derivative 12 could be easily isolated as a side product.
Cross-coupling of the red Bodipy 10 with 2,7-diethynyl-9,9-
bis(2-(2-methoxyethoxy)ethyl)fluorene 6 provided the expected
mixture of the mono- and bis-dyes 14 and 13 in 21% and 29% yield,
respectively (Scheme 4). No degradation was observed and the
unreacted starting material 10 was recycled.
Ultimately, the red-Bodipy 14 was allowed to react with the
blue precursor 11 to provide the dual red-blue compound 15. Puri-
fication was extremely tedious and 15 was always contaminated
with trace amounts of an unidentified species. This was due to
the similar polarities of the target compounds and some side prod-
ucts issued from oxidative homocoupling of the terminal alkyne
derivatives. Previously, we overcame this problem through a long
purification process.24
We next examined a multistep procedure starting from 2-tri-
methylsilylacetylene-7-bromo-9,9-bis(2-(2-methoxy-ethoxy)ethyl)-
fluorene 5 to produce the dual dye 15 by first coupling the red dye
using 8-(4-ethynylphenyl)-1,3,5,7-tetramethyl-4,4difluoro-4bora-
3a,4a-diaza-s-indacene, a synthetic equivalent of 10, and then after
deprotection of the TMS, cross-coupling the blue dye 11 via the
protocol depicted in Scheme 4. Unfortunately, we encountered
the same purification problem as previously observed using the
routine step-by-step cross-coupling reactions.
Our next target became the preparation of the carbaldehyde 9, a
key compound for the preparation of the blue-absorbing Bodipy
11. The design of this complexation pocket was guided by the need
to have a tertiary nitrogen atom in the para position of the
aldehyde and the presence of 2,20-bipyridine units for metal ion
binding.19 Alkylation of 4-iodoaniline with 6-bromomethyl-2,20-
bipyridine,20 itself prepared in two steps from 2,20-bipyridine, pro-
vided compound 8 in fair yield (Scheme 2). Unfortunately, under
conventional Villsmeier formylation reactions compound 9 could
not be isolated in satisfactory yields (<20%) despite the use of var-
ious experimental conditions.21 As anticipated, metallation with a
lithium reagent followed by reaction with anhydrous N-formylpi-
peridine or methylformate failed. After some experimentation,
the only reliable protocol we found was the use of a carboformyla-
tion reaction22 catalysed by Pd(0) under a flux of carbon monoxide
with sodium formate as the hydrogen source.
As expected from earlier work on Bodipy dyes,6 aldehyde 9 was
conveniently reacted with 8-(4-iodophenyl)-1,3,5,7-tetramethyl-
TsO
O
O
Br
Br
2
Br
Br
i)
1
O
O
O
O
After several additional attempts aimed at diminishing the
homocoupling process we succeeded in preparing 15 in an analyt-
ically pure form using the protocol shown in Scheme 5. This ap-
proach was inspired by the selective mono-functionalization of
molecular wires to produce very smart donor–acceptor mole-
cules.25 Using the bis-Bodipy dye 13 and 4-dimethylaminobenzal-
dehyde or the aldehyde 9, selective mono-functionalization was
feasible, providing 15 or 16 in a readily purified form (Scheme 5).
Finally, stable model dye 17 was prepared by cross-coupling
precursors 7 and 11 under our standard conditions (Scheme 6). It
is worth noting that the TMS-deprotected blue dye analogous to
17 is less stable than the protected one, likely due to higher elec-
tronic density imported by the styryl fragment compared to its
red counterpart 14. This excluded use of the protocol devised in
Scheme 4 for the preparation of compound 17.
3
ii)
Br
TMS
TMS
TMS
+
O
O
O
O
O
O
O
O
4
5
iii)
H
H
TMS
H
+
All the Bodipy dyes showed absorption and emissive properties
in keeping with their molecular structures. In all dyes the fluores-
cence of fluorene is quenched, while for the dual dye 15 and 16,
very efficient energy transfer occurs from the high energy donor
(tetramethyl Bodipy kem 510 nm) to the energy acceptor (styryl
Bodipy kabs at 600 nm), which fluoresces at kem 695 nm. Complete
details of these photophysical studies will be disclosed elsewhere.
O
O
O
O
O
O
O
O
6
7
Scheme 1. Reagents and conditions: (i) NaH (3 equiv), DMF, 60 °C, MeO(CH2)2O(-
CH2)2OTs (3 equiv), 12 h, 95%; (ii) trimethylsilylacetylene (3 equiv), [Pd(PPh3)2Cl2]
(10 mol %), CuI (10 mol %), THF/Et3N, 60 °C, 12 h, 40% of 4, 40% of 5; (iii) K2CO3
(1 equiv), MeOH, 30 min, rt, 36% of 7, 58% of 6.

T. Bura, R. Ziessel / Tetrahedron Letters 51 (2010) 2875–2879
2877
I
I
H
O
I
N
F
N
F
B
N
9
(i)
N
F
N
F
N
N
+
B
N
F
N
F
+
N
B
N
N
N
N
N
10
N
N
N
N
N
N
N
N
N
N
N
12
11
Scheme 3. Reagents and conditions: toluene, piperidine, p-TsOH tr., Dean–Stark, 65% for compound 11.
N
F
F
N
F
B
N
F
B
N
O
O
13
O
O
(i)
H
H
+
O
O
H
N
6
F
B
N
F
O
O
O
O
14
O
O
N
N
N
(ii)
N
N
F
N
B
F
N
B
F
N
N
F
O
O
15
O
O
Scheme 4. Reagents and conditions: (i) Dye 10 (1 equiv), [Pd(PPh3)4] (10 mol %), C6H6/Et3N, 60 °C, 15 h, 25% of 13, 21% of 14; (ii) dye 11 (1 equiv), [Pd(PPh3)4] (10 mol %),
C6H6/Et3N, 60 °C, 15 h, 42%.
N
F
N
B
F
N
B
F
N
F
O
O
13
O
O
(i)
N
N
(ii)
F
N
B
F
N
B
F
N
F
O
O
N
16
O
O
N
N
N
N
F
N
B
F
N
B
F
N
N
F
O
O
15
O
O
Scheme 5. Keys: (i) 4-dimethylaminobenzaldehyde, toluene, piperidine, p-TsOH, concentrated, Dean–Stark, 40%; (ii) aldehyde 9, toluene, piperidine, p-TsOH, concentrated,
Dean–Stark, 43%.

2878
T. Bura, R. Ziessel / Tetrahedron Letters 51 (2010) 2875–2879
I
N
F
N
F
H
TMS
B
+
O
O
N
N
O
O
11
7
N
N
N
(i)
N
N
N
Figure 1. Cyclic voltammograms of dye 14 (red trace), dye 15 (black trace) and dye
TMS
N
17 (blue trace) in dichloromethane at rt. The reversible Fc+/Fc redox couple at
N
F
B
N
+0.38 V correspond to genuine ferrocene.
N
F
O
O
17
O
O
assignment of the amino-N oxidation potentials. Protonation also
led to a colour change from blue to magenta associated with an
increase of the energy gap from 2.07 eV to 2.20 eV for compound
15H+ and from 2.02 eV to 2.13 eV for compound 16H+ (Fig. 2).
In short, new borondipyrromethene dyes attached to a func-
tionalised fluorene have been developed and dual-Bodipy species
have been engineered displaying both a red colour (with emission
at 510 nm) and a blue colour (emission at 695 nm). The method
established for the synthesis of new dyads in which red and blue
dyes are linked via a non-innocent spacer has provided families
Scheme 6. Key: (i) [Pd(PPh3)4] (10 mol %), C6H6/Et3N, 60 °C, 15 h, 40%.
We have previously shown that Bodipy dyes exhibit a rich elec-
trochemistry associated with the formation of radical cations and
radical anions depending on the decoration around the central
Bodipy core.26 For both reference compounds 14 and 17 each bear-
ing a single red and blue chromophore, both redox processes are
observed (Table 1). The energy gap between the radical cation
and radical anion, 2.35 eV for the red dye and 2.01 eV for the blue
dye, is in keeping with the steady state emission of the respective
dyes. For the blue dye 17 bearing a tertiary amine an additional
irreversible process was observed at 0.63 V. By addition of a weak
acid this redox process vanished due to protonation and the Bodipy
oxidation potential shifted cathodically by 70 mV due to the
decrease of the electron density on the Bodipy core. This observa-
tion is in keeping with the concomitant colour change of the dye
solution from blue to magenta. For the dual dye the cyclic voltam-
mogram is rich due to the summation of the redox properties of
both subunits (Fig. 1). All potentials could be assigned using the
data for 14 and 17 and noting the effects of protonation. Only very
weak potential shifts resulted from linking both dyes to a common
fluorene unit, indicating that both chromophores remain electron-
ically isolated. This conclusion was confirmed by comparison of the
absorption and emission spectra of the dual dyes with those of the
single dyes.
The dimethylamino fragment in compound 16 is by 70 mV
more easily oxidised than the bis-bipyridylmethyl residue in 15.
Nonetheless, in both cases protonation with HCl confirmed the
Figure 2. Cyclic voltammograms of dye 15 (black trace) and after addition of excess
HCl gas (red trace).
Table 1
Electrochemical data for the hybrid dyes and appropriate reference speciesa
a
Potentials determined by cyclic voltammetry in deoxygenated CH2Cl2 solution, containing 0.1 M TBAPF6, at a solute concentration of ca. 1.5 mM and at rt. Potentials were
Ep = 60 mV) versus SCE. Error in half-wave
standardised versus ferrocene (Fc) as internal reference and converted to the SCE scale assuming that E1/2 (Fc/Fc+) = +0.38 V (
D
potentials is 15 mV and all potentials are for a single electron transfer unless otherwise noted. For irreversible processes the peak potentials (Eap) are quoted. The text colour
denotes the electrochemically active part of the molecule, red for the Knorr-Bodipy, blue for the amino-styryl and magenta for the protonated styryl dye. Black text denotes
the amine oxidation potential.

T. Bura, R. Ziessel / Tetrahedron Letters 51 (2010) 2875–2879
2879
9. Diring, S.; Puntoriero, F.; Nastasi, F.; Campagna, S.; Ziessel, R. J. Am. Chem. Soc.
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of compounds where all redox processes could be assigned in the
light of the electrochemical properties of appropriate reference
species and suitable protonation. This work opens up the possibil-
ity of engineering sophisticated new dyes based on fluorene link-
ers. Preliminary fluorescence measurements revealed efficient
energy transfer between the red and blue species. Interactions with
protons and cations have also been evaluated and more detailed
mechanistic studies are currently in progress.
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Acknowledgements
This work was partially supported by the CNRS providing re-
search facilities. We also warmly thank Professor Jack Harrowfield
(ISIS in Strasbourg) for commenting on the Letter before publication.
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