Synthesis of multi-branched dipyrromethene dyes with soluble diethynylphenyl links

Article abstract of DOI:10.1016/j.tetlet.2008.04.039

Multi-branched dyes were prepared using a convergent step-by-step procedure. The key dibutoxydiethynylphenyl spacing units were first linked to a difluoroboradipyrromethene (yellow fluorophore) dye via the pseudo-meso position and then selectively cross-coupled to a di-(4-phenyliodo)ethynylborodiisoindolomethene (red emitter via the boron). When ethynylpyrene units were connected at the periphery to the boron of the yellow emitter, efficient cascade singlet energy transfer events occurred from the pyrene to the yellow and to the red emitters.

Full text of DOI:10.1016/j.tetlet.2008.04.039

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3716–3721
Synthesis of multi-branched dipyrromethene dyes with soluble
diethynylphenyl links
Alexandre Haefele a, Gilles Ulrich a, Pascal Retailleau b, Raymond Ziessel a,*
a Laboratoire de Chimie Mole´culaire, Centre National de la Recherche Scientifique (CNRS), Universite´ Louis Pasteur, Ecole de Chimie,
`
´
Polymeres, Materiaux de Strasbourg (ECPM), 25 rue Becquerel, 67087 Strasbourg, Cedex 02, France
b
ˆ
Laboratoire de Cristallochimie, ICSN—CNRS, Bat 27—1 avenue de la Terrasse, 91198 Gif-sur-Yvette, Cedex, France
Received 11 March 2008; accepted 7 April 2008
Available online 10 April 2008
Abstract
Multi-branched dyes were prepared using a convergent step-by-step procedure. The key dibutoxydiethynylphenyl spacing units were
first linked to a difluoroboradipyrromethene (yellow fluorophore) dye via the pseudo-meso position and then selectively cross-coupled to
a di-(4-phenyliodo)ethynylborodiisoindolomethene (red emitter via the boron). When ethynylpyrene units were connected at the periph-
ery to the boron of the yellow emitter, efficient cascade singlet energy transfer events occurred from the pyrene to the yellow and to the
red emitters.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Bodipy dyes; Acetylenic spacers; Multi-branched; Pyrene; Energy transfer
Conversion of solar energy into chemical energy, the
basis of natural photosynthesis, is a major contemporary
challenge for chemists. Photosynthetic organisms have
developed efficient antennas that absorb photons through-
out the visible spectrum and funnel energy to the reaction
center where it is used to bring about the fundamental reac-
tions of photosynthesis.1 In Nature, various pigments such
as chlorophylls, carotenes and bilirubins provide absorp-
tions covering most of the solar spectrum. Appropriate
spatial arrangement of the chromophores controls the
energy-funneling processes.1
Artificial systems intended to provide new means for the
utilization of solar energy have been based, for example, on
transition metal complexes2 and semiconductor particles3
but, in most such systems, the efficiency is severely limited
by rapid back reactions and the narrow range of strong
absorption.4 Systems which have provided efficient mimics
of photosynthetic energy transfer events have been based
on ethynyl-bridged porphyrin arrays or dendritic polyphen-
ylacetylene chromophores. In the first case, the energy is
channeled down from a difluoroborondipyrromethene (F-
Bodipy) dye to a low-energy acceptor (metal-free porphy-
rin) which is the energy trap.5 In the second, light is
absorbed by peripheral phenylacetylene moieties and this
energy supply is trapped by a central perylene residue.6
In both cases, the difference in rates of forward and reverse
energy transfer allows energy migration to proceed with
almost 100% efficiency.5,6 Other systems involve unidirec-
tional energy transfer along specific molecular axes,7–9
and we have recently described hybrid systems based on
boradipyrromethene (Bodipy) dyes with ethynylpyrene
and ethynylperylene substituents on boron which involve
ultra-fast, quantitative singlet energy transfer from the aro-
matic fragments to the Bodipy center.10
From a general point of view Bodipys’ are exceptional
fluorescent dyes, easily chemically transformable, and ame-
nable to large quantities and high purities.11
Here, we describe the synthesis of molecular devices
based on two different Bodipy units linked by an increasing
number of dibutoxydiethynylphenyl modules. Thus, a
*
Corresponding author. Tel.: +33 3 90 24 26 89; fax: +33 3 90 24 27 42.
E-mail address: ziessel@chimie.u-strasbg.fr (R. Ziessel).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.039

A. Haefele et al. / Tetrahedron Letters 49 (2008) 3716–3721
3717
boradipyrromethene unit provided a yellow emitting center
and a boraisoindolomethene unit a red emitting dye. The
idea was to extend the excitation wavelengths in order to
study the efficiency of multi-cascade energy transfer events.
The branched arrangement of the final molecules was dic-
tated by the chemistry on the boron of the red emitter
and on the pseudo-meso position 8 of the yellow emitter.
The question of present interest was whether trichromo-
phoric molecules could be assembled using the boron-
functionalization and alkyne-coupling reactions we have
exploited previously. Thus, we first explored the possibility
of functionalizing Bodipy 112 with increasing numbers of
tetrasubstituted-phenylethynyl units (Scheme 1). Pd(0)-cat-
alyzed cross-coupling of 313 with 2,5-dibutoxy-4-iodo-1-
(trimethylsilylethynyl)benzene (obtained in 43% yield by
cross-coupling 1,4-diiodo-2,5-dibutoxybenzene14 with
trimethylsilylacetylene (1 equiv) using Pd(II) catalysts),
followed by deprotection and repetition of the coupling,
provided the target compounds 4, 6, and 8 in an excellent
yield. Optimal conditions involved a mixture of benzene/
triethylamine at 80 °C. Deprotection with KOH afforded
the terminal alkynes 5, 7, and 9.
(kem = 542 nm) measured in dichloromethane from the
Bodipy subunit are almost the same for 4, 6 and 8 as for
the phenyliodo-substituted derivative 1.13 However, both
the absorptivity maximum and its wavelength for the
oligo(phenylene-ethynyl) unit change from
ꢁ1 cmꢁ1, k = 361 nm (n = 1) to 80000
k = 404 nm (n = 3) (Fig. 1).
33000
ꢁ1 cmꢁ1
,
M
M
The pivotal building block 14 was prepared according to
Scheme 2. 4-Methoxybenzohydrazide 10 was readily
prepared from the ester and converted to hydrazone 11
using 2-acetylphenol in n-propanol. The conversion of 11
to diketone 12 with the release of nitrogen15 was achieved
using the stoichiometric amount of Pb(CH3COO)4 under
mild conditions. After some experimentation, we found
that 13 could be isolated in good yield by the reaction of
12 with ammonium acetate with the release of formalde-
hyde. Reaction of 13 with BF3ꢂEt2O in the presence of
the Hunig base readily produced the red emitter 14. The
¨
use of 4-iodo-1-phenylethynylmagnesiumbromide in excess
to substitute both fluoro groups led finally to 15 in an over-
all yield of 17% (Scheme 2). The synthesis of a compound
bearing 4-ethylthiophene in place of p-methoxyphenyl has
recently been reported.16
The promising characteristics of 5, 7, and 9 prompted us
to examine the attachment of these yellow, energy transfer-
ring dyes to the red emitter 15. The use of [Pd(PPh3)4]
(5mol %) enabled the replacement of both iodo substituents
of 15 by a double-coupling reaction and provided the triple
Bodipy molecules 16–19 in acceptable yields (Scheme 3).
Note again that the poor yield for n = 3 may reflect the
instability of the terminal alkyne 9 under the experimental
conditions used.
For n = 3, the yield for the isolation of compound 9 was
poor, perhaps reflecting the instability of the terminal
alkyne. Unfortunately, iterative cross-coupling to generate
larger scaffoldings (n > 3) failed using various experimen-
tal conditions. Interestingly, the intense S0?S1 absorption
(kmax= 526 nm, e ꢀ 68000 Mꢁ1 cmꢁ1) and the fluorescence
X
I
A single crystal X-ray structure was obtained for 15 as
its chloroform solvate (Figs. 2 and 3).17 The boron center
is almost tetrahedral and the bond lengths of the indacene
framework remain characteristic of a fully delocalized cya-
nine unit. The ethyne tethers retain bond lengths typical of
(i)
93%
N
N
B
N
N
B
F
F
˚
F
F
triple bonds (ca. 1.20 A). A slight distortion from planarity
1
is observed for the diisoindolomethene core.15 A ‘butterfly’
conformation is adopted with ‘wings’ consisting of two
planes B–N1–C1–C2–C3–C4–C9 and B–N2–C5–C6–C7–
C8–C9 where the dihedral angle is 9.6°. The tilt angles of
X=TMS,
2
(ii) 90%
X=H,
3
(iii)
65%
X
80000
4
6
OBu
X=TMS,
X=H,
4
6
8
(ii)
8
90%
88%
n=1
BuO
60000
5
(iii)
X=TMS,
X=H,
n
(ii) 80%
40000
20000
0
n=2
n=3
7
(iii)
(ii)
81%
25%
X=TMS,
X=H,
9
N
N
B
F
F
220
320
420
520
620
Scheme 1. Reagents and conditions: (i) TMS-acetylene, [PdCl2(PPh3)2],
CuI; (ii) KOH, methanol; (iii) 2,5-dibutoxy-4-iodo-trimethylsilylethynyl-
phenyl, [Pd(PPh3)4], NEt3, C6H6, 80 °C.
Wavelength (nm)
Fig. 1. Absorption spectra of 4, 6 and 8, in dichloromethane.

3718
A. Haefele et al. / Tetrahedron Letters 49 (2008) 3716–3721
OH
H
N
H
N
O
OEt
O
O
NH2
N
(i)
(ii)
55%
84%
OMe
(iii)
OMe
OMe
88%
10
11
O
O
(iv)
NH
N
77%
13
12
MeO
OMe
MeO
63%
(v)
N
N
B
(vi)
N
N
B
87%
F
F
MeO
OMe
MeO
OMe
14
15
I
I
Scheme 2. Reagents and conditions: (i) NH2–NH2; (ii) 2-acetylphenol; (iii) Pb(OAc)4; (iv) NH4OAc; (v) BF3ꢂEtO2, NEt(iPr)2; (vi) 4-iodo-1-
phenylethynylmagnesium bromide.
N
N
B
H
MeO
OMe
OBu
BuO
2
(i)
N
N
OBu
B
OBu
+
BuO
n
MeO
OMe
BuO
n
I
I
N
N
B
F
F
N
F
N
N
N
B
F
B
F
F
16 , n = 0 , 76%
17 , n = 1 , 60%
18 , n = 2 , 73%
19 , n = 3 , 31%
Scheme 3. Reagents and conditions: (i) [Pd(Ph3)4], NEt3, benzene.
the anisole groups with respect to the indacene mean plane
are 67.9° and 73.5°.
The asymmetric unit of the crystal corresponds to one
molecule of compound 15 and one deuterated chloroform
solvent molecule. The tetrahedral geometry of the solvent
molecule is almost aligned to that of the boron center,
the deuterium atom pointing toward the boron atom at a
of 15, adjacent molecules are linked around a center of
inversion by two reciprocal C–I ꢂ ꢂ ꢂO interactions with a
˚
distance of 3.4 A, implicating I2 of the ethyne tether
oriented parallel to the [5ꢁ13] direction and O1c of the
methoxy group at position (ꢁ1 ꢁ x, ꢁy, ꢁz). Those pairs
of molecules are piling (alternatively) up and down, paral-
lel to the [441] direction, through iodoꢂ ꢂ ꢂp interactions of
˚
˚
˚
distance of 2.93 A, and pushing it by 0.25 A out of the
mean plane of the boradiazaindacene core, along the
B?I1 axis (viz. the [441] direction). In the crystal structure
mean distance of 3.61 A, between the other iodo ethyne
tether and the centroid of an outermost ring of the
indacene core at position (1 + x, 1 + y, z). Another

A. Haefele et al. / Tetrahedron Letters 49 (2008) 3716–3721
3719
Fig. 2. Two ORTEP views of compound 15 (50% probability), with all hydrogen atoms00removed 0for the sake of clarity. B-N1, B-N2, B-C10, B-C100 are
0
00
˚
˚
˚
˚
1.597(6) A, 1.591(5) A, 1.581(6) A, 1.573(7) A, respectively, with angles N1BN2, C1 BC1 , N1BC1 and N2BC1 of 106.7 (3)°, 111.2 (3)°, 108.1 (3)° and
111.8 (4)°, respectively.
˚
3.78 A contact between the methyl group C7c and the
innermost ring (N1, C1–C4) of the indacene core at posi-
tion (ꢁ1 + x, y, z) stabilizes the molecular packing in the
same direction (Fig. 3).
spectra are linear combinations of the absorption features
of the separate modules. Worthwhile noting is the fact that
by increasing the size of the scaffolding, a bathochromic
shift of its absorption is found (Fig. 4). In contrast to this
red-shift of the spacer absorptions, the S0?S1 transitions
of the yellow fluorophore at 520 nm and of the red emitter
at 630 nm remain insensitive to the size of the branched
system.
The orthogonality of the phenyl and the indacene planes
in the yellow fluorophore and the tetrahedral geometry at
boron means that orbital overlap between the different
chromophores is negligible. Consequently, the absorption
Fig. 3. View of the structure of compound 15 surrounded by three neighboring molecules in the crystal at respective positions #1: ꢁ1 ꢁ x, ꢁy, ꢁz, #2:
1 + x, 1 +y, z, #3: ꢁ1 +x, y, z. Intermolecular contacts are indicated by dashed lines in blue. Black arrows highlight the direction of the deuterium atom
of CDCl3.

3720
A. Haefele et al. / Tetrahedron Letters 49 (2008) 3716–3721
400000
400000
300000
200000
100000
0
1
0
350000
16
17
300000
18
19
250000
610
660
710
760
Wavelength (nm)
200000
150000
100000
50000
0
220
320
420
520
620
720
220
320
420
520
620
720
Wavelength (nm)
Wavelength (nm)
Fig. 4. Absorption spectra of 16–19, in dichloromethane.
Fig. 5. Absorption and emission spectra of 23, in dichloromethane.
In order to embed ethynylpyrene subunits in the frame-
work, it was found preferable to substitute the fluoro
ligands of the yellow fluorophore early in the syntheses
rather than after obtaining molecules 16–19. We ultimately
succeeded in preparing the trisubstituted derivatives 21 and
22, carrying two types of different acetylenic derivatives,
through substitution at boron by means of the ethynyl-
pyrene-Grignard reagents,18 followed by cross-coupling
with TMS-acetylene (Scheme 4). The soluble compound
21 was easily purified and was stable over days in solution.
Finally, the tethering of two modules 22 to the red emitter
15 was feasible under mild standard conditions using Pd(0)
as catalyst. The hyperbranched multi-dye 23 was isolated
pure in 50 % yield and characterized by EI-MS (found:
m/z 2297.1, calcd: 2297.0).
As expected from previous work, replacement of fluo-
rine by pyrenylethynyl units on the yellow Bodipy centers
leads to very fast (k > 1010 ꢁ1) and very efficient fluores-
s
cence energy transfer (FRET) from the pyrene to the Bod-
ipy fragment.10 This markedly enhances the possible gap
between the excitation and emission wavelengths.
X
I
(i)
84%
Once more, the absorption spectrum of 23, in dichloro-
methane is a linear combination of those of the precursors
(Fig. 5). The presence of the pyrene does not shift the
S0?S1 absorption of either Bodipy subunit (k. = 522 nm,
e = 207000 Mꢁ1 cmꢁ1 and k. = 641 nm, e = 114000 Mꢁ1
cmꢁ1). The pyrene residue imports its characteristic absorp-
tion between 230 and 370 nm. Excitation of either Bodipy
chromophore produced very strong fluorescence at 670 nm
(Uem = 87%, kex = 641 nm and Uem = 44%, kex = 522 nm).
This result is in keeping with a 50% efficiency of energy
transfer from the yellow to the red emitter with a 4% residual
emission of the yellow Bodipy at 541 nm. For pyrene excita-
tion at 370 nm, the quantum yield for the emission of the
blue Bodipy was still high (Uem = 51%), with a 3% residual
emission of the yellow Bodipy. For excitation at 271 nm, a
quantum yield of 65% of the red emitter was found, consis-
tent with direct excitonic energy transfer from the bridge
to the red emitter without funneling through the yellow
fluorophore.
N
N
N
N
B
B
20
21, X = TMS
22 , X = H
(ii)
98%
(iii)
50%
MeO
N
B
N
N
B
N
N
MeO
B
N
Our design opens up the possibility of engineering new
sophisticated dyes bearing photon absorbers at the periph-
ery and energy transducers in the heart. All photons would
be funneled to a low-energy acceptor before the final emis-
sion. Substitution at boron imports a new dimensionality
for grafting additional chromophores, opening up the pos-
sibility of constructing dendritic scaffoldings in a conver-
gent manner. Work in progress is focused on increasing
23
Scheme 4. Reagents and conditions: (i) TMS-acetylene, [Pd(PPh3)2Cl2]
3 mol %, CuI 10 mol %; (ii) KOH, methanol; (iii) 0.5 equiv compound 15,
[Pd(PPh3)4], NEt3, C6H6, 60 °C.

A. Haefele et al. / Tetrahedron Letters 49 (2008) 3716–3721
3721
Chem. Soc. 2007, 129, 5597; (c) Rohand, T.; Qin, W.; Boens, N.;
Dehaen, W. Eur. J. Org. Chem. 2006, 4658; (d) Yogo, T.; Urano, Y.;
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the dimensionality of these multi-branched systems and
introducing additional energy relays.
Acknowledgments
`
This work was supported by the CNRS, the Ministere
´
de la recherche et de l’Enseignement Superieur for a fellow-
˚
J.; Burgess, K.; Bergstro¨m, F.; Johansson, L. B.-A. J. Org. Chem.
ship to A.H. We are also indebted to Prof. J. Harrowfield
(ISIS in Strasbourg) for his comments on the manuscript.
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15. Ulrich, G.; Goeb, S.; De Nicola, A.; Retailleau, P.; Ziessel, R. Synlett
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˚
ꢀ
space group P1, a = 11.401(1), b = 13.646(1), c = 16.046(2) A, a =
3
˚
95.72(1)°, b = 105.60(2)°, c = 111.69(2)°, V = 2178.8(6) A , Z = 2,
Dc = 1.586 g cmꢁ3, l(MoKa) = 1.669 mmꢁ1, F(0 00) = 1024, pris-
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