α-fused dithienyl BODIPYs synthesized by oxidative ring closure

Article abstract of DOI:10.1021/ol500572t

Both symmetrical and unsymmetrical α-fused dithienyl-BODIPY dyes have been prepared by oxidative ring closure induced by anhydrous FeCl₃. Extension of the π-system in the fused BODIPY leads to a progressive shift to 579 and 665 nm respectively

Full text of DOI:10.1021/ol500572t

Letter
pubs.acs.org/OrgLett
α‑Fused Dithienyl BODIPYs Synthesized by Oxidative Ring Closure
Elodie Heyer,† Pascal Retailleau,‡ and Raymond Ziessel*,†
†Laboratoire de Chimie Organique et de Spectroscopies Avancee
Strasbourg Cedex 2, France
́
s (ICPEES-LCOSA), UMR 7515 CNRS, 25 rue Becquerel, 67087
‡Institut de Chimie des Substances Naturelles (ICSN), CNRS, Avenue de la Terrasse, 91198 Gif Sur Yvette Cedex, France
S
* Supporting Information
ABSTRACT: Both symmetrical and unsymmetrical α-fused dithienyl-
BODIPY dyes have been prepared by oxidative ring closure induced by
anhydrous FeCl3. Extension of the π-system in the fused BODIPY leads
to a progressive shift to 579 and 665 nm respectively for the absorption
wavelength maxima of the mono- and difused dyes relative to the unfused
species (λabs = 502 nm). Linking such dyes to an NIR emitting module
provides a panchromatic chromophore with a large absorption cross
section in the visible range associated with efficient intramolecular
cascade energy transfer.
4,4′-Difluoro-4-bora-3a,4a-diaza-s-indacene dyes, more com-
monly known as BODIPY dyes, have gained tremendous
attention over the past two decades due to the diversity of
applications based on their spectacular optical properties.1
Their absorption bands are sharp with high extinction
coefficients, and their intense fluorescence is attributed to
the chelation of B(III), which rigidifies the structure and
consequently reduces the number of nonradiative decay
channels. The facility of their chemical modification enables
ready tuning of both their spectroscopic and physical
properties including solubility in diverse solvents, ease of
film formation, crystallinity, and mesogenicity. Ongoing
research is directed toward shifting the spectroscopic
properties toward the near-IR region by increasing the
electronic density on the BODIPY core through the
connection of electron-rich modules to the pyrrolic units.2
There are, however, only a few instances known of the use to
this end of α- or β-fused aromatic units derived from, e.g.,
benzene,3 phenanthrene,4 naphthalene,5 porphyrin,6a BODI-
PY,6b furan,7 or thiophene.8 These fused BODIPY dyes have
been obtained by synthesizing fused pyrrolic building blocks
or by oxidative ring closure, but only one paper describes the
use of oxidative ring closure to give intramolecular fusion of
phenyl-BODIPY dyes.4b
in this work was synthesized in three steps according to
reported procedures for similar species (Scheme S1).9 The
unsubstituted tolyl-BODIPY 4 was prepared using a standard
two-step procedure.10 Monoiodination on the 2-position of
compound 4 was achieved at 55 °C with ICl,11 limiting
undesired polyhalogenation in the 1- and 6-positions (Scheme
1). At 35 °C, in the presence of the P(tBu)3 and Pd, the
monoiodinated BODIPY 5 and the dithienyl unit 3a were
coupled in excellent yield (2T-1, 81%), via a Suzuki
reaction.12 From previous work on oxidative reactions of
BODIPY dyes, it was known that the BODIPY 6-position13
and the α-position of the dithienyl moiety have to be
blocked14 in order to obtain intra- rather than intermolecular
Scholl-type reactions. Thus, these positions were substituted
selectively via electrophilic aromatic reactions: first on the
dithienyl moiety using NBS at 0 °C (2T-2, 83%) and then
with ICl on the BODIPY 6-position (2T-3, 85%). The final
oxidative coupling step was achieved using anhydrous FeCl3 as
a reagent giving inappreciable side reactions compared to
other oxidants tested (DDQ, PIFA).
In principle, it is possible that the coupling to give 2T-4
could occur to give either the α- or γ-fused species (Scheme
1). The 1H NMR spectrum of 2T-4 clearly showed the
absence of one singlet of the BODIPY unit around 6.90 ppm
corresponding to the proton in position 1 or γ of the parent
and the simplification of the doublets from the dithienyl unit
(6.71 and 6.89 ppm). Only one singlet, corresponding to the
meso tolyl group and integrating for 3H, was observed at 2.52
Here, we discuss first the formation and oxidative ring
closure reactions of singly substituted (unsymmetrical)
BODIPYs to illustrate the procedures before considering the
analogous reactions of disubstituted (symmetrical) derivatives.
The unsymmetrical α-fused dithienyl-BODIPYs (2T) were
obtained by a multistep protocol, using a convergent synthesis
to link, via a Pd cross-coupling reaction, the BODIPY dye and
the alkylated dithienyl unit and in a final step oxidative ring
closure mediated by anhydrous FeCl3. The dithienyl unit used
Received: February 21, 2014
© XXXX American Chemical Society
A
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Scheme 1
1
Figure 2. (Left) ORTEP view for 2-T4 showing the atom-labeling
scheme. Thermal ellipsoids are plotted at the 30% level. B1−N1,
B1−N2, B1−F1, B1−F2, N1−C1, N2−C8, N1−C4, and N2−C5
bond lengths are 1.552(7), 1.534(7), 1.395(7), 1.382(7), 1.384(6),
1.392(6), 1.340(6), and 1.370(5) Å, respectively. (Right) Views
orthogonal to the previous one to highlight the planarity of the
molecule and the projection of the hexyl chain out of the mean
plane.
Figure 1. H NMR superposition of 4, 5, 2T-1, 2T-2, 2T-3, and 2T-
4. * Stands for the residual peak of the solvent (CDCl3).
ppm, indicating that the intramolecular oxidative reaction had
given the γ-fused form of 2T-4 (Figure 1).
This deduction was, however, contradicted by the fact that
the 13C NMR spectrum of 2T-4 showed a through-space
coupling of 8.8 Hz, previously ascribed to C−F coupling,15 for
the peak near 123.0 ppm, indicating that the reaction may
have involved position 3 or α to give the α-fused form of 2T-
4.
results prompted us to review our synthetic strategy to obtain
the dyad 2T-8 (Scheme 2). First, the bromine on 2T-2 was
substituted using a standard Suzuki coupling with p-benzoyl
boronic acid, leading to 2T-5 in 79% yield. Next, oxidative
ring closure afforded 2T-6 (52%) which could be halogenated
with ICl (2T-7, 47%). Sonogashira cross-coupling between
2T-7 and BODIPY 9 afforded the deep-green dyad 2T-8 in
an acceptable yield (36%).
The preparation of the bis-thienyl BODIPY 4T-3 was
preferentially achieved by Suzuki coupling using the bis-
bromo derivatives 6b and 3a, affording 4T-1 in 77% yield.
Bromine “stoppers” were inserted quasi-quantitatively using
NBS at 0 °C on the α-position of the bis-thiophene moieties,
giving 4T-2, before performing cyclization with FeCl3 to
afford 4T-3 in excellent yields (Scheme 3).
Fortunately, single crystals of 2T-4 could be obtained, and
an X-ray structure determination showed that indeed it was at
the α-pyrrolic position of the BODIPY that the ring closure
occurred, confirming that the α-position of the BODIPY dyes
is the most reactive site toward oxidative coupling reactions
(Figure 2). As usual, the meso substituent and the BODIPY
core are twisted (52.2°) away from coplanarity, consistent
with the absence of electronic delocalization. The BODIPY
core together with the α-fused dithienyl unit comprises a
nearly flat 22-atom entity (albeit slightly concave; see Figure
2) with an rms deviation of 0.086 Å, the maximum deviation
concerning the iodinated carbon (>0.17 Å). The boron atom
lies within the mean plane and has the usual tetrahedral
geometry (N−B−N from 106.5° to 112.4°) while the
disordered hexyl group extends out of the plane (Figure 2).
Some efforts were made to selectively substitute the
halogen centers on 2T-4 via Pd cross-coupling reactions
under mild conditions, but neither Sonogashira nor Suzuki
coupling gave significant chemoselectivity. These unsatisfying
The NMR spectra of 4T-3 were similar to those of the
unsymmetrical compound 2T-4, showing a triplet at 123.6
ppm (8.4 Hz) in the 13C spectrum and the same low field
shifts of the γ-pyrrolic protons from 6.83 to 8.23 ppm (Figure
3) in the 1H. Again, cyclization afforded the bis α-fused
BODIPY.
B
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Scheme 2
1
Figure 3. H NMR superposition of 4, 6b, 4T-1, 4T-2, and 4T-3. *
Stands for the residual peak of the solvent (CDCl3).
Scheme 3
The electronic absorption spectra in toluene for key dyes
are shown in Figure 4. BODIPY 4 and 6b exhibit standard
absorption spectra with high extinction coefficients, and
narrow bands with a shoulder on the high energy side due
to vibronic coupling with the C−C frame vibration of 1300
cm−1 typical of dipyrromethenes. On grafting two flexible
dithienyl modules, the shape of the main absorption transition
is broader (fwhm ≈ 2600 cm−1) and bathochromically shifted
with a significant decrease of the extinction coefficient (Table
S1).
This may be a reflection of the conformational flexibility of
the dithienyl side chains. After ring closure, the shape of the
S0 → S1 main transition for 4T-3 (Figure 4) is similar to that
of those for the unsubstituted derivatives 4 and 6b, but the
extinction coefficient increases to 163 000 M−1 cm−1 and the
absorption is shifted by 163 nm to lower energy. This is
mainly due to the rigidification of the structure and the
additional bathochromic shift to the increase of the
delocalization pathway. The fluorescence of the nonfused
BODIPY is weak (less than 10%) probably due to the free
rotation of the tolyl group (Table S1). No fluorescence was
observed for 4T-3 in solution at rt due to intersystem
crossing (ISC) to a low lying triplet state favored by the
presence of sulfur atoms. Preliminary results with 4T-3 in
degassed and frozen methyl-THF showed a triplet emitting
state around 990 nm, revealing the existence of a pronounced
ISC.
Figure 4. Normalized absorption of 4, 6b, 4T-1, 4T-2, and 4T-3 in
toluene at 25 °C.
fluorescent module such as in the hybrid BODIPY molecule
2T-8. This compound exhibits several absorption bands
between 320 and 720 nm due to the linear combination of
the absorption of the individual fragments 9 and 2T-7
(Figures 5 and S1). In fact, selective irradiation at 580 nm in
the α-fused BODIPY showed the unique emission of the 2T-8
module at 764 nm (Figure 5), therefore creating a virtual
Stokes shift of approximately 3500 cm−1. The quantum yield
Despite the weak luminescence at rt, we were able to show
that these dyes could be used as input centers for an
intramolecular cascade energy transfer when linked to a
Figure 5. Absorption (blue trace), normalized emission (green
trace), and excitation spectra (red trace) of 2T-8 in toluene at 25 °C.
C
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module has a QY of 4%, allowing the conclusion that that
more than 70% of the excitonic energy is transferred from
fragment 2T-7 to fragment 9 in the dyad 2T-8.
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In short, we have shown here a means of access to new
families of near-IR dyes using an innovative approach
consisting in the oxidative coupling induced by FeCl3 of
prepositioned lateral arms. Cyclization occurs exclusively in
the α,α′-position of the BODIPY core and is compatible with
reactive functional groups on the thiophene residues. The
convenience of this method is also due to the possibility to
selectively anchor energy donor and acceptor or reactive
fragments at precise positions. Fusion of the lateral moieties is
useful to shift the absorption to the red, to markedly enhance
the extinction coefficient, and to sharpen the absorption
bands. The presence of thiophene rings in the fused
framework renders the dyes weakly fluorescent or non-
fluorescent possibly due to deactivation in a triplet state by
intersystem crossing. Characterization and exploitation of the
triplet state are currently under investigation.
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ASSOCIATED CONTENT
* Supporting Information
■
(11) (a) Ortiz, M. J.; Agarrabeitia, A. R.; Duran-Sampedro, G.;
S
Banuelos Prieto, J.; Arbeloa Lopez, T.; Massad, W. A.; Montejano,
̃
Materials and instrumentation, synthetic procedures, NMR
traces, UV−visible spectroscopy, and X-ray data are reported.
This material is available free of charge via the Internet at
http://pubs.acs.org.
H. A.; Garcìa, N. A.; Lopez Arbeloa, I. Tetrahedron 2012, 68, 1153−
1162. (b) Hayashi, Y.; Yamaguchi, S.; Cha, W. Y.; Kim, D.;
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AUTHOR INFORMATION
Corresponding Author
■
Broring, M.; Ahrens, J.; Bard, A. J. J. Am. Chem. Soc. 2011, 133 (48),
̈
19498−19504.
*E-mail: ziessel@unistra.fr.
(14) (a) Poirel, A.; De Nicola, A.; Ziessel, R. Org. Lett. 2012, 14
(22), 5696−5699. (b) Poirel, A.; De Nicola, A.; Retailleau, P.;
Ziessel, R. J. Org. Chem. 2012, 77 (17), 7512−7525.
(15) Chen, J.; Reibenspies, J.; Derecskei-Kovacs, A.; Burgess, K.
Chem. Commun. 1999, 2501−2502.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Reg
■
́
ion Alsace for a fellowship to Elodie Heyer
and the Centre National de la Recherche Scientifique
(CNRS) for financial support of this work. Professor Jack
Harrowfield (ISIS in Strasbourg) is warmly acknowledged for
commenting on this manuscript prior to publication. Dr.
Gilles Ulrich is acknowledged for measuring the triplet
emission of the dyes, Arnaud Poirel for helpful discussion
of the halogenations of dye 4T-1 prior to ring closure, and
Alexandra Sutter for providing a sample of dye 7.
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