Convenient synthesis of green diisoindolodithienylpyrromethene-dialkynyl borane dyes

Article abstract of DOI:10.1021/ol0627404

(Graph Presented) Versatile dyes based on diisoindolodithienylpyrromethene substituted at the boron center by alkynylaryl chromophores have been developed that efficiently fluorescence in the near infrared. Fast intramolecular energy transfer from the appended alkynyl units to the central core provides Stokes shifts above 16 000 cm^-1.

Full text of DOI:10.1021/ol0627404

ORGANIC
LETTERS
2007
Vol. 9, No. 5
737-740
Convenient Synthesis of Green
Diisoindolodithienylpyrromethene
Borane Dyes
−Dialkynyl
Se´bastien Goeb and Raymond Ziessel*
Laboratoire de Chimie Mole´culaire, Centre National de la Recherche Scientifique
(CNRS), UniVersite´ Louis Pasteur, Ecole de Chimie, Polyme`res, Mate´riaux de
Strasbourg (ECPM), 25 rue Becquerel, 67087 Strasbourg, Cedex 02, France
ziessel@chimie.u-strasbg.fr
Received November 9, 2006
ABSTRACT
Versatile dyes based on diisoindolodithienylpyrromethene substituted at the boron center by alkynylaryl chromophores have been developed
that efficiently fluorescence in the near infrared. Fast intramolecular energy transfer from the appended alkynyl units to the central core
-1
provides Stokes shifts above 16 000 cm
.
The engineering of light-emitting molecules for practical
applications1 depends upon the achievement of the right
balance between the electronic interactions and their effects
upon the excited-state lifetimes of the chromophoric subunits.
The development of high-performance, environmentally
stable fluorescent probes has been largely a consequence of
efforts to mimic the light-harvesting complexes and reaction
centers of natural photosynthetic systems.2 While highly
fluorescent molecules derived from acridine,3 anthracene,4
phenanthrene,5 pyrene,6 dansyl,7 and indacene8-11 cores
display a rich variety of optical properties, challenges remain
in the control of nonradiative decay pathways and in the
conversion of often fragile organic frameworks to more
robust species. Partial success in enhancing stability has,
however, been achieved by encapsulating dyes within
nanoparticles.12 To overcome the problems of generally low
yields in the synthesis of complex chromophores and rather
(5) Onkelinx, A.; De Schryver, F. C.; Viaene, L.; Van der Aueraer, M.;
Iwai, K.; Yamamoto, M.; Ichikawa, M.; Masuhara, M.; Maus, M.; Rettig,
W. J. Am. Chem. Soc. 1996, 118, 2892.
(6) (a) Herbich, J.; Kapturkiewicz, A. Chem. Phys. 1993, 170, 221. (b)
Harriman, A.; Hissler, M.; Ziessel, R. Phys. Chem. Chem. Phys. 1999, 1,
4203. (c) Hissler, M.; Harriman, A.; Khatyr, A.; Ziessel, R. Chem. Eur. J.
1999, 5, 3366. (d) Shen, Z.; Procha´zka, R.; Daub, J.; Fritz, N.; Acar, N.;
Schneider, S. Phys. Chem. Chem. Phys. 2003, 5, 3257.
(7) Prodi, L.; Bolletta, F.; Montalti, M.; Zaccheroni, N. Eur. J. Inorg.
Chem. 1999, 455.
(1) Valeur, B. In Molecular Fluorescence: Principles and Applications;
Wiley-VCH: Weiheim, Germany, 2002.
(8) Kollmannsberger, M.; Rurack, K.; Resch-Genger, U.; Daub, J. J. Phys.
Chem. 1998, 102, 10211.
(9) Wan, C.-W.; Burghart, A.; Chen, J.; Bergstro¨m, F.; Johanson, L. B.-
A.; Wolford, M. F.; Kim, T. G.; Topp, M. R.; Hochstrasser, R. M.; Burgess,
K. Chem. Eur. J. 2003, 9, 4430.
(10) Yilmaz, M. D.; Bozdemir, O. A.; Akkaya, E. U. Org. Lett. 2006, 8,
2871.
(11) McDonnell, S. O.; O’Shea, D. F. Org. Lett. 2006, 8, 3493.
(2) (a) Olson, J. M. Photochem. Photobiol. 1998, 67, 61. (b) Gust, D.;
Moore, T. A.; Moore, A. L. Acc. Chem. Res. 2001, 34, 40.
(3) Herbich, J.; Kapturkiewicz, A. J. Am. Chem. Soc. 1998, 120, 1014.
(4) (a) Mataga, N.; Nishikawa, S.; Asahi, T.; Okada, T. J. Phys. Chem.
1988, 92, 6233. (b) Wiessner, A.; Hu¨ttmann, G.; Ku¨hnle, W.; Staerk, H. J.
Phys. Chem. 1995, 99, 14923.
10.1021/ol0627404 CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/02/2007

limited possibilities for varying these syntheses, we have
turned our attention to the remarkable family of difluoro-
bora-diaza-s-indacene (“F-Bodipy”) dyes. These are par-
ticularly intriguing molecules for several reasons:8,9,13 (i) they
combine high molar absorptivities with very high fluores-
cence quantum yields; (ii) their optical properties can be
tuned by modifying the pyrrole unit and/or the bridge of the
pyrromethene unit and/or, as shown recently, the boron
substituents; (iii) they are chemically and photochemically
stable in solution and in the solid state; and (iv) they are
redox active both as oxidants and as reductants.
and emits at 780 nm with a quantum yield of 20% when
excited in the lower energy absorption band (Figure 2), thus
The focus of the present work is the issue of whether or
not a range of F-Bodipy derivatives can be obtained showing
both absorption and emission in the near-infrared area (in
particular, 720-780 nm; Figure 1A). To this end, we have
Figure 2. Absorption, emission spectra of starting material 1
(green) and pivotal intermediate 5 (black) in CH2Cl2, at rt.
largely satisfying the demands specified above for a near-
infrared active material. Its excitation and absorption spectra
match precisely, indicating that the emission results from
the S1fS0 transition. The Stokes’ shift, however, as expected
for an organic singlet emitter, is relatively small (∆ν ) 930
cm-1), but slightly larger than in dipyrromethene dyes.17
The promising characteristics of 1 prompted us to examine
further functionalization involving attachment of arylalkynide
fragments at boron, the aryl substituents involving both metal
ion chelating and luminescent polycyclic aromatic units. Our
earlier observation was that 1 was not resistant to substitution
using 4-lithioethynyltoluene or 1-lithioethynylpyrene, prob-
ably as a result of deprotonation of the relatively acidic meso-
proton. This problem could be readily circumvented, how-
ever, by using alkynyl-Grignard reagents in place of the
lithium species, enabling 2 to be obtained readily and in good
yield (Scheme 1).
Figure 1. General formulas for F-Bodipy and E-Bodipy.
explored the substitution of the fluoride ligands on boron
by polyaryl-alkynide ligands (Figure 1B), the aryl substitu-
ents being designed to produce large virtual Stokes’ shifts
by virtue of intramolecular energy transfer.
While trigonal alkynylboranes14 are well-characterized
species, much less is known of tetrahedral alkynylborates15,16
and thus we have explored their synthesis in some detail.
The systems developed significantly extend the scope of
available indacene-dye derivatives and provide photo- and
electroactive materials with potential applications in both
biological analysis and various light-emitting devices.
Our earlier work involving introduction of oligopyridine
substituents onto the meso position of F-Bodipy’s demon-
strated that this could produce highly luminescent materials,
soluble in polymeric matrices, of considerable promise in
sensors17 and electroluminescent devices.18 The pivotal
building block 119 absorbs at 727 nm (ꢀ ) 90 000 M-1 cm-1)
Scheme 1
(12) Montalti, M.; Prodi, L.; Zaccheroni, N.; Zattoni, A.; Reschiglian,
P.; Falini, G. Langmuir 2004, 20, 2989.
(13) (a) Ulrich, G.; Ziessel, R. Synlet. 2004, 439. (b) Ulrich, G.; Ziessel,
R. J. Org. Chem. 2004, 69, 2070. (c) Ulrich, G.; Ziessel, R. Tetrahedron
Lett. 2004, 45, 1949.
Thus, our present target became the substitution of the
fluoro ligands by sophisticated arylalkynyl entities. Crucial
to the success of the strategy adopted was the unsymmetrical
functionalization of 1,4-diiodobenzene with acetylenic units
bearing different protecting groups (Scheme 2).
Our earlier work on bipyridine derivatives provided
appropriate inspiration.20 Thus, compound 6 could be
selectively deprotected on the 2-hydroxyprop-2-yl side by
using an alkali metal hydroxide under anhydrous conditions.
(14) (a) Yamaguchi, S.; Akiyama, S.; Tamao, K. J. Am. Chem. Soc. 2000,
122, 6335. (b) Jia, W.-L.; Saong, D.; Wang, S. J. Org. Chem. 2003, 68,
701. (c) Kubo, Y.; Yamamoto, M.; Ikeda, M.; Takeuchi, M.; Shinkai, S.;
Yamaguchi, S.; Tamao, K. Angew. Chem., Int. Ed 2003, 42, 2036.
(15) (a) Qian, B.; Baek, S. W.; Smith, M. R., III Polyhedron 1999, 18,
2405. (b) Ding, L.; Ma, K.; Du¨rner, G.; Bolte, M.; Fabrizi de Biani, F.;
Zanello, P.; Wagner M. J. Chem. Soc., Dalton Trans. 2002, 1566.
(16) Ulrich, G.; Goze, C.; Guardigli, M.; Roda, A.; Ziessel, R. Angew.
Chem., Int. Ed. 2005, 44, 3694.
(17) Goze, C.; Ulrich, G.; Charbonnie`re, L.; Ziessel, R. Chem. Eur. J.
2003, 9, 3748.
(18) Hepp, A.; Ulrich, G.; Schmechel, R.; von Seggern, H.; Ziessel, R.
Synth. Met. 2004, 146, 11.
(19) Kang, H. C.; Haugland, R. P. U.S. Patent 5,433,896, July 18, 1995.
(20) Goeb, S.; De Nicola, A.; Ziessel, R. J. Org. Chem. 2005, 70, 1518.
738
Org. Lett., Vol. 9, No. 5, 2007

is not deactivated and an excess of triphenylphosphine is
not required. Despite their low solubility, both 1-ethynyl-
pyrene and 1-ethynylperylene also reacted efficiently. In-
terestingly, the mixed species 14 was obtained in 43%
isolated yield by using two different ethynyl derivatives
mixed immediately, the resulting three components of the
product mixture being easily separated by column chroma-
tography (Scheme 4). This design opens up the possibility
Scheme 2
Scheme 4
The Grignard derivatives were prepared by reactions of 4
and 7 with EtMgBr in THF at 50 °C and their reactions with
1 at room temperature provided the target alkynylboron
derivatives 5 (78%) and 8 (80%). Note that the conversion
of 5 to 8 is also possible by using standard Pd-catalyzed
cross-coupling (Scheme 2).
While deprotection of 8 with K2CO3 in a protic solvent
does produce the terminal alkyne, this was too reactive to
be conveniently isolated. Further, in situ deprotection and
cross-coupling with 4′-{[(trifluoromethyl)sulfonyl]oxy}-
2,2′;6′,2′′-terpyridine21 results only in an intractable mixture
of products, so that, to bypass such problems, we developed
a cross-coupling reaction of the bis-iodo compound 5 and a
stable terminal alkyne. An outline of the reactions involved
is given in Scheme 3.
of preparing new dyes bearing an activated function suitable
for protein labeling. The approach is unique in that it uses
an easy access to dissymmetric fluorescent dyes.
All the new dyes are deep emerald-green crystalline solids
which show a metallic luster. The electronic absorption
spectra all exhibit a structureless maximum near 708 nm with
a molar absorptivity of ∼80 000 M-1 cm-1. A higher energy
absorption found near 350 nm in 12 and near 450 nm in 13
can be assigned to spin-allowed π-π* transitions centered
on the pyrene and perylene fragments, respectively. Note
that in some cases the absorption in the near-UV is very
strong (Table 1) due to an overlapping of these absorption
Scheme 3
Table 1. Optical Properties in CH2Cl2, at Room Temperature
compd λabs (nm) ꢀ (M-1 cm-1
)
λem (nm) ∆Sa (cm-1
)
Φb (%)
1
2
5
8
9
727
709
709
707
709
335
708
335
708
342
708
399
708
474
708
399
344
90 000
86 000
84 000
81 000
86 000
130 000
80 000
123 000
81 000
95 000
83 000
135 000
84 000
122 000
80 000
71 000
76 000
780
750
750
750
750
750
750
750
750
750
750
750
750
750
750
750
750
930
771
771
790
771
20
42
45
43
22
8
21
9
19
9
40
23
40
15
34
18
15
16 500
790
16 600
790
16 000
790
11 800
790
7 800
790
11 800
15 700
10
11
12
13
14
With use of known terminal alkynes,22 reaction occurs
under mild conditions and no decomposition of the dyes was
observed. Despite the presence of a chelating unit, the catalyst
a Stokes shifts calculated from the absorption and emission energies.
b Relative quantum yields ((20%) determined with use of Cresyl violet as
reference23 (Φ ) 0.51%, λ exc ) 578 nm). Concentration range 0.9 × 10-8
to 1.2 × 10-7 M.
(21) Potts, K. T.; Konwar, D. J. Org. Chem. 1991, 56, 4815.
(22) Grosshenny, V.; Romero, F. M.; Ziessel, R. J. Org. Chem. 1997,
62, 1491.
Org. Lett., Vol. 9, No. 5, 2007
739

bands with the one localized on the di-isoindolodithienyl-
pyrromethene skeleton (see Figure 2). In the bipyridine and
terpyridine derivatives 9, 10, and 11, absorptions assigned
to π-π* and n-π* transitions are observed between 290
and 350 nm. In all cases, irradiation in the band near 708
nm gives rise to a broad emission at 780 nm, with quantum
yields between 18% and 45%. Selected data are gathered in
Table 1.
Intriguing observations were made on irradiating com-
pound 12 in the pyrene band (399 nm) and compound 13 in
the perylene band (474 nm). Some very weak residual
emission (<1%) from the polyaromatic entities was detect-
able but far more efficient emission occurred through the
bis-isoindolemethene unit near 750 nm (Figure 3). This
shows aggregate formation, which perturbs the optical
behavior.
The substitution of both fluoro ligands by polyaromatic
or polypyridine units in the previously described di-iso-
indolodipyrromethene frameworks19 is a nice tool to engender
light-emission in the near-infrared region. The virtual Stoke
shifts obtained by irradiation in the imported fragments
around 400 nm are very high, >16 000 cm-1 in some cases
due to an efficient intramolecular singlet energy transfer
process. For comparison, recently reported work involving
the modification of an F-Bodipy by a conformationally
restricted substituent with less extended conjugation resulted
in displacement of the fluorescence only between 630 and
680 nm with Stokes’ shifts lying between 240 and 800 cm-1.
An added advantage of the presently described compounds
is the variation in characteristics associated with the substi-
tuted alkynyl ligands on boron. Compounds 12 and 13 have
particularly useful characteristics in regard to application as
fluorescent labels. They absorb and emit at exceptionally long
wavelengths when compared to known Bodipy species and
the quantum yields remain satisfactory given the low energy
of the emission. We contend that the present work paves
the way for the development of a new generation of stable,
functionalized luminophores.
Acknowledgment. This work was supported by the
CNRS, the Ministe`re de la recherche et de l’Enseignement
Supe´rieur. We thank Dr. Gilles Ulrich and Dr. Antoinette
de Nicola from the LCM for their comments and criticisms
concerning the present work.
Figure 3. Absorption, emission spectra of 12 (red) and 13 (blue)
in CH2Cl2, at rt.
Supporting Information Available: Experimental pro-
cedure and characterization and proton, carbon, and boron
NMR spectra for all compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
corresponds to virtual Stokes’ shifts of 11 800 and 7 800
cm-1, respectively. Consideration of the quantum yields
indicates that intramolecular energy transfer must occur with
58% and 38% efficiency respectively for compounds 12 and
13. Provided only very dilute solutions (about 1 10-7 M)
are considered, the absorption and excitation spectra match
perfectly, indicating that a single excited state is the source
of the observed emission. The use of higher concentration
OL0627404
(23) Olmsted, J., III J. Phys. Chem. 1979, 83, 2581.
(24) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.; Burgess, K. J. Org.
Chem. 2000, 65, 2900.
740
Org. Lett., Vol. 9, No. 5, 2007