Tailoring the properties of boron-dipyrromethene dyes with acetylenic functions at the 2,6,8 and 4-B substitution positions

Article abstract of DOI:10.1021/ol800560b

(Chemical Equation Presented) Substitution of F-Bodipy with alkynylaryl residues at boron, at the pyrrolic core or at the meso position, provides unique tri-, tetra-, and pentasubstituted dyes. Substitution at the (pyrrolic) 2,6-positions provides substan

Full text of DOI:10.1021/ol800560b

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2183-2186
Tailoring the Properties of
Boron-Dipyrromethene Dyes with
Acetylenic Functions at the 2,6,8 and
4-B Substitution Positions
Laure Bonardi, Gilles Ulrich,* and Raymond Ziessel*
Laboratoire de Chimie Organique et Spectroscopies AVance´es (LCOSA), 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 March 11, 2008
ABSTRACT
Substitution of F-Bodipy with alkynylaryl residues at boron, at the pyrrolic core or at the meso position, provides unique tri-, tetra-, and
pentasubstituted dyes. Substitution at the (pyrrolic) 2,6-positions provides substantial red shifts with quantum yields in the 40-90% range
and excited-state lifetimes of 3-7 ns. ON/OFF fluorescence switching can be produced by protonation of dibutylamino subunits.
Difluoroboradiaza-s-indacene (F-Bodipy) derivatives are the
subject of intense current research not only as convenient
fluorescent dyes for biochemical labeling1 but also as part
of photonic molecular systems, laser dyes, mesomorphic
materials, organogelators, and dopants in light-emitting
devices.2
Strategies to extend the absorption properties to the near-
infrared3 have been based on (i) substitution of the 3,5-
positions by styryl functions,4 (ii) replacement of the meso
8-carbon by a nitrogen atom leading to aza-Bodipy,5 (iii)
fusing some aromatic rings to the Bodipy core,6 and finally,
(iv) the replacement of pyrrole by isoindole.7 The electronic
absorption and emission profiles are clearly sensitive to the
delocalization over the skeleton, and yellow to deep-green
colors are provided routinely. The substitution of the central
8-position with aryl groups has little effect on the optical
properties except where these groups incorporate electron-
donating substituents like linear or cyclic tertiary amines or
(5) (a) Gorma, A.; Killoran, J.; O’Shea, C.; Kenna, T.; Gallagher, W. M.;
O’Shea, D. F. J. Am. Chem. Soc. 2004, 126, 10619–10631. (b) Zhao, W.;
Carreira, E. M. Chem. Eur. J. 2006, 12, 7254–7263.
(1) The Handbook of Fluorescent Probes and Research Chemicals, 6th
ed.; Molecular Probes: Eugene, OR, 1996.
(6) (a) Chen, J.; Burghart, A.; Derecskei-Kowacs, A.; Burgess, K. J.
Org. Chem. 2000, 65, 2900–2906. (b) Umezawa, K.; Nakamura, Y.; Makino,
H.; Citterio, D.; Suzuki, K. J. Am. Chem. Soc. 2008, 130, 1550–1551.
(7) Ulrich, G.; Goeb, S.; De Nicola, A.; Retailleau, P.; Ziessel, R. Synlett
2007, 1517–1520.
(2) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008,
47, 1184–1201.
(3) Loudet, A.; Burgess, K. Chem. ReV. 2007, 107, 4891–4932.
(4) Saki, N.; Dinc, T.; Akkaya, E. U. Tetrahedron 2006, 62, 2721–2725.
10.1021/ol800560b CCC: $40.75
Published on Web 05/08/2008
2008 American Chemical Society

electron-withdrawing substituents like NO28 or CN.9 In these
cases, photoinduced electron transfer (oxidative and reduc-
tive, respectively) are responsible for luminescence quench-
ing. Otherwise, the orthogonality of the central fragment with
respect to the dipyrromethene core prevents orbital interac-
tion.
Scheme 2
In considering the modification of Bodipy to induce
properties such as high solubility, the capacity for ready
linking to biological substrates, and enhanced absorptivity,
it may be noted that 2,6-substitution has not been utilized
much, probably because of the lack of general synthetic
procedures.10,11 The objective of the present work was
therefore to develop procedures as part of a battery of
methods for introducing these types of functionalities at all
possible sites on the Bodipy molecule.
To this end, we first explored the synthesis of 1 by a
classical route (Scheme 1). Condensation of Kryptopyrrole
Under conventional Pd catalysis, iodophenyl and iodopyr-
role substituents appear to react at similar rates, so that
reactant 5 gives the disubstituted product 9. As anticipated,
the substitution of the ꢀ pyrrolic iodo substituent in 4, 5,
and 6 by ethynyltolyl groups induces a bathochromic shift
in the emission peaks by 64, 62, and 94 nm, respectively,
for 8, 9, and 10 compared to the starting material.
Scheme 1
For attachment of arylalkynyl fragments at boron, selective
functionalization is feasible in the presence of halogenopyr-
role residues: the use of alkynyl-Grignard reagents providing
13-16 in good yield (Scheme 3). The disappearence of the
(2,4-dimethyl-3-ethylpyrrole) with the in situ generated
triethylsilylacetylene acid chloride provided, in 25% yield,
the target compound 1, which could be deprotected to the
corresponding terminal alkyne 2 in 31% yield. Both com-
pounds show an intense S0fS1 absorption at 572 nm, red-
shifted by 30 nm compared to the methyl-substituted
derivative12 due to extension of conjugation. Unfortunately,
owing to the relatively high reactivity of the terminal alkyne,
cross-coupling with various halogenoaryl derivatives failed
under a variety of experimental conditions.
Scheme 3
A strategy based on the Bodipy made from Knorrpyrrole
(2,4-dimethylpyrrole) was more successful (Scheme 2). Here,
the selective electrophilic attack of ICl provided either the
monoiodo 4 and 5 or the bis-iodo derivatives 6 and 7 in
excellent yields under mild conditions when compared to
the previously described procedure.13 Cross-coupling of
p-tolylacetylene or di-n-butylaminophenylacetylene was
straightforward, providing 8 to 11 in acceptable yields
(Scheme 2).
triplet at ca. 3.5 ppm in the 11B NMR spectrum in favor of
a singlet at ca. -9 ppm is good evidence for the substitution
process.14
Our next target became the substitution of the iodo groups
by arylalkynyl entities. Both mono- and double-cross-linking
smoothly afforded the highly fluorescent dyes 17 and 18 in
excellent yields, although the use of solubilizing alkyl groups
on the boron center was crucial to avoid precipitation during
the synthesis of 18 (Scheme 4).
(8) Ziessel, R.; Bonardi, L.; Retailleau, P.; Ulrich, G. J. Org. Chem.
2006, 71, 3093–3102.
(9) Sathyamoorthi, G.; Boyer, J.-H.; Allik, T. H.; Chandra, S. Heteroatom
Chem. 1994, 5, 403–407
(10) Wan, C.-W.; Burghart, A.; Chen, J.; Bergstro¨m, F.; Johansson,
L. B.-A; Wolford, M. F.; Kim, T. G.; Topp, M. R.; Hochstrasser, R. M.;
.
As expected from earlier work on the substitution of fluoro
by alkynyl fragments, no additional wavelength shift was
observed. Thus, due to the absence of heavy atoms in 17
Burgess, K. Chem. Eur. J. 2003, 9, 4430–4441
.
(11) Thivierge, C.; Bandichor, R.; Burgess, K. Org. Lett. 2007, 9, 2135–
2138
.
(12) Boyer, J. H.; Haag, A. M.; Sathyamoorthi, G.; Soong, M. L.;
Thangaraj, K. Heteroatom Chem. 1993, 4, 39–49.
(13) Yogo, T.; Urano, Y; Ishitsuka, Y.; Maniwa, F.; Nagano, T. J. Am.
Chem. Soc. 2005, 127, 12162–12163.
(14) Goze, C.; Ulrich, G.; Ziessel, R. J. Org. Chem. 2007, 72, 313–
322.
2184
Org. Lett., Vol. 10, No. 11, 2008

such as p-tolylacetylene or 1-pyrenylacetylene. The highly
soluble compounds 24 and 25 were easily purified.
Scheme 4
These reactions demonstrated the possibility of preparing
pentasubstituted dyes bearing three different acetylenic
frameworks, each imparting different properties to the final
fluorophore. As a prototypical example, we introduce an
aliphatic alkyne first bearing a dimethyloxazoline group (as
carboxylic acid protection) via Sonogashira coupling to the
meso-iodophenyl subunit (Scheme 6). The compound 26 was
Scheme 6
and 18 compared to 13 and 15, the fluorescence quantum
yields increase to 75 and 72%, respectively, and the excited-
state lifetimes are ∼4 ns.
To perform more sophisticated syntheses, discrimination
between halogen substituents at the ꢀ pyrrolic and meso-
phenyl centers was required. This was achieved as outlined
in Scheme 5. Interestingly, despite the presence of acetylenic
Scheme 5
selectively iodinated by use of ICl in a polar solvent to give
the nonfluorescent compound 27 in fair yield, despite the
presence of an alkyne function. The use of two equivalents
of ethynyl-Grignard allowed the replacement of both fluorine
atoms by two ethynylpyrene units, leading to compound 28
in 67% yield. Triethylsilylacetylene functions were easily
linked to the Bodipy core by standard procedures.
Some of the compounds described here show unusual
photophysical behavior (Table 1). Molecules having a heavy
halogen atom on the 2- or 2,6-positions show low quantum
yields and reduced fluorescence lifetimes. This is largely due
to efficient intersystem crossing leading to a low lying triplet
state.13
Compound 11 is of particular interest in that its absorption
spectrum displays a large and red-shifted band, and an
additional intense band around 330 nm, presumably due to
intramolecular charge transfer (ICT) from the p-dialkylami-
nophenyl-ethynyl residues to the Bodipy. This ICT would
explain the fluorescence quenching, but additional photoin-
duced electron transfer is also possible.
bonds linked to the boron atom in 19 and two phenyl
moieties, the reaction with NBS nonetheless provided the
monobromo compounds 20 and 21 in respectable yields. To
circumvent the selectivity problem observed with 5 between
the phenyl iodo in the 8-position and iodo in the 4-position,
we reacted 20 and 21 under standard conditions with 1 equiv
of p-tolylacetylene. Compound 20 reacted smoothly to give
22 in 81% yield, while 21 gave a mixture of insoluble
derivatives which could not be fully separated by conven-
tional procedures.
After some experimentation, we succeeded in preparing
tetrasubstituted derivatives carrying three different acetylenic
derivatives using a sequence of substitution at boron by
means of C10-Grignard reagents to give high solubility,
followed by cross-coupling with different acetylenic reagents
Protonation of the amino groups induces a drastic change
in the absorption and emission spectra, and restores the
fluorescence. This phenomenon has been observed with other
Bodipy derivatives bearing tertiary amine groups on the 8-15
and 3-positions.2,3
As expected, compound 29 behaves like a known pyrene-
substituted Bodipy:14 an almost quantitative intramolecular
Org. Lett., Vol. 10, No. 11, 2008
2185

to 20% when excited in the Bodipy S0-S1 transition and weak
energy transfer occurs after excitation of the pyrene moiety
(residual quantum yield around 2%).
Table 1. Optical Properties of Selected Compounds in CH2Cl2
at rta
compd
λabs (nm) ꢀ (M-1 cm-1
)
λem (nm) τ (ns) Φb (%)
1
2
4
6
8
571
573
509
527
526
565
599
554
523
557
529
540
531
552
370
57000
54000
90000
90000
72000
83000
40000
65000
73000
89000
50000
62000
64400
66700
86000
593
591
529
548
575
603
700
584
561
588
570
602
549
571
571
5.2
5.1
<1
<1
3.2
3.5
-
3.7
4.2
3.9
4.3
1.8
<1
6.5
20
40
14
6
47
46
<1
53
75
72
55
20
2
10
11
c
11 + 2H+
17
18
24
25
28
29
99
90
a Determined in aerated dichloromethane solution, ca. 5 × 10-7 M. Using
Rhodamine 6G as reference, Φ ) 0.78 in water, λ
) 488 nm. All ΦF
exc
are corrected for changes in refractive index. b Excitation at the corre-
Figure 2. Absorption (blue line) and emission (red line) of 25 in
CH2Cl2 at rt.
sponding λmax wavelength. c By addition of CF3COOH in dichloromethane.
In conclusion, we have developed a new series of
π-conjugated Bodipys based on the selective substitution
either at the dipyrromethene core (2,6-positions), or at the 8
and 4 positions. The electrophilic iodination of the dipyr-
romethene core with ICl is significant even in the presence
of alkyne fragments which remain inert. In comparison with
standards, the obvious red-shift of λmax of their absorption
and PL spectra is in agreement with an increase of the
effective conjugation length. Introduction of multiple sub-
stituents not only suppresses the formation of aggregates but
also modifies the solubility and spectroscopic properties. We
are currently synthesizing a complete library of novel
compounds by adapting these strategies to investigate den-
dritic Bodipy scaffoldings for photon-concentrators.
energy transfer being observed after excitation in the pyrene
absorption bands. This is not the case with derivative 25,
where the ethynylpyrene group is connected to the 2-position
(Figures 1 and 2). Here, the fluorescence of the dye drops
Acknowledgment. We thank CNRS and ULP for funding.
G.U. thanks ANR for support (JC05-42228). We are also
indebted to Professor J. Harrowfield (ISIS in Strasbourg) for
his comments on the manuscript.
Figure 1. Absorption spectra of 11 (blue), 11 with 2 equiv of
Supporting Information Available: Experimental pro-
cedure and characterization; proton and carbon spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
CF3COOH (green), and emission of 11 with TFA (red).
(15) Rurack, K.; Kollmansberger, M.; Resch-Genger, U.; Daub, J. J. Am.
Chem. Soc. 2000, 122, 968–969.
OL800560B
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Org. Lett., Vol. 10, No. 11, 2008