Synthesis of directly connected BODIPY oligomers through Suzuki-Miyaura coupling

Article abstract of DOI:10.1021/ol200799u

Treatment of a meso-arylboron dipyrrin (BODIPY) with NBS provides mono- and dibrominated BODIPYs at the 2- and 6-positions in excellent yields with high regioselectivity. Brominated products can be employed as a nice building block for the synthesis of a

Full text of DOI:10.1021/ol200799u

ORGANIC
LETTERS
2011
Vol. 13, No. 12
2992–2995
Synthesis of Directly Connected BODIPY
Oligomers through SuzukiÀMiyaura
Coupling
Yosuke Hayashi, Shigeru Yamaguchi, Won Young Cha, Dongho Kim,* and
Hiroshi Shinokubo*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University,
Nagoya 464-8603, Japan and Department of Chemistry, Yonsei University,
Seoul 120-749, Korea
hshino@apchem.nagoya-u.ac.jp; dongho@yonsei.ac.kr
Received March 26, 2011
ABSTRACT
Treatment of a meso-arylboron dipyrrin (BODIPY) with NBS provides mono- and dibrominated BODIPYs at the 2- and 6-positions in excellent
yields with high regioselectivity. Brominated products can be employed as a nice building block for the synthesis of a variety of BODIPY
derivatives through SuzukiÀMiyaura coupling. Because of a lack of substituents at the 1,3,5,7-positions, a directly βÀβ-linked BODIPY dimer
exhibits a completely coplanar conformation of BODIPY units, offering effective π-conjugation.
Boron dipyrrins (BODIPY) are currently attracting much
interest in a wide variety of research areas such as labeling
reagents, fluorescent switches, chemosensors, near-IR ab-
sorbing/emitting dyes, nonlinear optical materials, light-
harvester dye-sensitized solar cells, and bulk heterojunc-
tion solar cells owing to their advantageous photophysical
properties such as photostability, large extinction coeffi-
cients, and high luminescence efficiency.1 In addition,
functionalization of BODIPY dyes allows manipulation
of the spectroscopic and electronic properties by introduc-
tion of suitable substituents to the BODIPY peripherals.
Among synthetic precursors for functionalized BODIPYs,
halogenated BODIPYs are one of the most useful build-
ing blocks on the basis of a transition-metal-catalyzed
cross-coupling strategy.2,3 However, regioselective halo-
genation of R-unsubstituted BODIPYs has not been re-
ported. Here we wish to disclose selective and efficient
bromination of 1,3,5,7-unsubstituted BODIPY 1 with N-
bromosuccinimide (NBS) and the use of brominated
BODIPYs in a SuzukiÀMiyaura coupling reaction for
the synthesis of novel BODIPY derivatives including BOD-
IPY oligomers.
We investigated bromination of 1,3,5,7-unsubstituted
BODIPY and found that treatment of 1 with 1.2 equiv of
NBS at room temperature furnished 2 and 3 in 82% and
12% yields, respectively (Scheme 1).4 In addition, the use
of 2.4 equiv of NBS provided dibromo-BODIPY 3 in
excellent yield along with a minor amount of 2. Even with
an excess amount of the brominating agent, none of
regioisomeric products such as R-bromo-BODIPYs were
detected in the reaction mixture.
(1) (a) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891. (b)
Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47,
1184. (c) Loudet, A.; Burgess, K. In Handbook of Porphyrin Science;
Kadish, K. M., Smith, K. M., Guilard, K. R., Eds.; World Scientific:
Hackensack, 2010; Vol. 8 p 1. (d) Ziessel, R.; Ulrich, G.; Harriman New
J. Chem. 2007, 31, 496. (e) Buyukcakir, O.; Bozdemir, O. A.; Kolemen,
S.; Erbas, S.; Akkaya, E. U. Org. Lett. 2009, 11, 4644.
(2) For R-halogenated BODIPYs, see: (a) Rohand, T.; Baruah, M.;
Qin, W.; Boens, N.; Dehaen, W. Chem. Commun. 2006, 266. (b) Rohand,
T.; Qin, W.; Boens, N.; Dehaen, W. Eur. J. Org. Chem. 2006, 4658. (c)
Baruah, M.; Qin, W.; Basaric, N.; De Borggraeve, W. M.; Boens, N.
J. Org. Chem. 2005, 70, 4152.
(3) For β-halogenated BODIPYs, see: (a) Shah, M.; Thangaraj, K.;
Soong, M. L.; Wolford, L. T.; Boyer, J. H.; Politzer, I. R.; Pavlopoulos,
T. G. Heteroatom Chem. 1990, 1, 389. (b) Leen, V.; Braeken, E.;
Luckermans, K.; Jackers, C.; Van der Auweraer, M.; Boens, N.;
Dehaen, W. Chem. Commun. 2009, 4515.
(4) We also found that treatment of BODIPY 1 with a phenyliodine
bis(trifluoroacetate) (PIFA)ÀMe3SiBr combination at À78 °C afforded
2-monobromo-BODIPY 2 in 87% yield along with a minor amount of
2,6-dibromo-BODIPY 3 in 5%. For bromination with PIFAÀMe3SiBr,
see: Dohi, T.; Ito, M.; Yamaoka, N.; Morimoto, K.; Fujioka, H.; Kita,
Y. Tetrahedron 2009, 65, 10797. Bromination with NBS at À78 °C
resulted in much lower conversion.
r
10.1021/ol200799u
Published on Web 05/17/2011
2011 American Chemical Society

Scheme 1. Selective Bromination of BODIPY 1
With the efficient protocol to selectively brominated
BODIPYs 2 and 3 in hand, we then attempted synthesis of
a directly linked BODIPY dimer and trimer (Scheme 2).
Although directly RÀR-linked BODIPY dimers were re-
cently synthesized and investigated,5 directly βÀβ-linked
BODIPY dimers remained unexplored until the very recent
report by Ziessel and De Nicola.6,7 BODIPY 2 was homo-
coupled to the dimer 4 in 81% yield through Pd-catalyzed
borylation8 with bis(pinacolato)diboron (pin2B2) and an in
situ cross-coupling sequence by the use of Cs2CO3 as the
base. The use of potassium acetate instead of cesium carbo-
nate afforded monoboryl BODIPY 59 in 73% yield, which
was then converted to trimer 6 in 71% yield via SuzukiÀ
Miyaura cross-coupling with 2.4 equiv of 2. Unfortunately,
the solubility of the trimer was considerably low and ham-
pered the synthesis of further extended BODIPY oligomers.
Figure 1. X-ray crystal structures of 4 and 11. (a) Top view of 4,
(b) side view of 4, (c) top view of 11, and (d) side view of 11. The
thermal ellipsoids were scaled to the 50% probability level.
Hydrogen atoms and aryl substituents were omitted for clarity.
caused by substituents on 1,3,5,7-positions and is beneficial
for the effective elongation of conjugation. In contrast to
this BODIPY dimer, directly RÀR-linked dimer exhibits
substantially twisted conformation because of steric de-
mands of the proximal positions.5
The UV/vis absorption spectra of 4 and 6 are substan-
tially red-shifted in comparison to monomer 1 due to
effective extension of conjugation caused by highly copla-
nar conformation (Figure 2 and Table 1). Dimer 4 and
trimer 6alsoshow significant red-shiftsin theirfluorescence
Scheme 2. Synthesis of BODIPY Dimer and Trimer via Homo-
and Cross-Coupling Strategy
(5) (a) Broring, M.; Kruger, R.; Link, S.; Kleeberg, C.; Kohler, S.;
Xie, X.; Ventura, B.; Flamigni, L. Chem.;Eur. J. 2008, 14, 2976. (b)
Ventura, B.; Marconi, G.; Broring, M.; Kruger, R.; Flamigni, L. New J.
Chem. 2009, 33, 428.
(6) (a) For βÀβ phenylene ethynylene-bridged BODIPY oligomers,
see: Cakmak, Y.; Akkaya, E. U. Org. Lett. 2009, 11, 85. (b) Zhu, M.;
Jiang, L.; Yuan, M.; Liu, X.; Ouyang, C.; Zheng, H.; Yin, X.; Zuo, Z.;
Liu, H.; Li, Y. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 7401.
(7) During preparation this manuscript, Ziessel and De Nicola have
reported the synthesis of directly βÀβ-linked oligomers of 1,3,5,7-
tetramethyl-BODIPY by oxidative homocoupling with PIFAÀBF3
3
OEt2. Because of steric hindrance around the βÀβ lingkage, these
oligomers take a rather twisted conformation with a large dihedral angle
(64.1°), resulting in smaller electronic interaction between BODIPY
units than our coplanar analogues. See: Rihn, S.; Erdem, M.;
De Nicola, A.; Retailleau, P.; Ziessel, R. Org. Lett. 2011, 13, 1916. We
have presented preparation of 4 and 6 at the 90th Annual Meeting of the
Chemical Society of Japan, Osaka, March 26À29, 2010; 2PA096.
(8) (a) Billingsley, K. L.; Barder, T. E.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2007, 46, 5359. (b) Ishiyama, T.; Itoh, Y.; Kitano, T.;
Miyaura, N. Tetrahedron Lett. 1997, 38, 3447. (c) Ishiyama, T.; Ishida,
K.; Miyaura, N. Tetrahedron 2001, 57, 9813.
Single crystals of BODIPY dimer 4were obtained by slow
vapor diffusion of methanol into a chloroform solution of 4.
X-ray crystallographic analysis of 4 unambiguously eluci-
dated its tapelike structure with a completely flat conforma-
tion (Figure 1). The dihedral angle between two adjacent
pyrrole moiety is only 0.57°. This orientation of the chro-
mophores is clearly due to the lack of steric interaction
(9) β-Borylated BODIPYs have been pareared in low yields via
iridium-catalyzed direct borylation; see: Chen, J.; Mizumura, M.;
Shinokubo, H.; Osuka, A. Chem.;Eur. J. 2009, 15, 5942.
Org. Lett., Vol. 13, No. 12, 2011
2993

for 6 is larger than 4 in the entire spectral region. This
feature indicates that the dipole orientation in the excited
state is predominantly aligned along the long molecular
axis and the difference in the orientation between absorp-
tion and fluorescence dipoles becomes smaller as the
molecule becomes elongated in the long molecular axis like
trimer 3. In addition, as the overall molecular size increases
in going from monomer to dimer 4 and trimer 6, the
rotational diffusion motion becomes slower as demon-
strated by the fluorescence anisotropy decay times (40,
124, and 303 ps for 1, 4, and 6, respectively, Supporting
Information). Nevertheless, the relatively high emission
efficiencyofβÀβ-linked BODIPY oligomers promisestheir
use as near-infrared (NIR) fluorescence dyes.
Brominated BODIPYs 2 and 3 are also useful precursors
for the synthesis of unsymmetrically and symmetrically
substituted BODIPY derivatives. SuzukiÀMiyaura cross-
coupling of dibromo BODIPY 3 with 4-nitrophenyl- and
4-N,N-dimethylaminophenylboronic acids furnished accep-
torÀacceptor- and donorÀdonor-substituted BODIPYs 7
and 8 in good yields (Scheme 3). Monobromo BODIPY 2 is
particularly useful for the synthesis of unsymmetrically
BODIPY derivatives. First, 2 was coupled with 4-nitrophe-
nylboronic acid followed by bromination with NBS pro-
vided BODIPY 7 in 83% yield, which was eventually cross-
coupled with 4-N,N-dimethylaminophenylboronic acid to
furnish donorÀacceptor-substituted BODIPY. X-ray dif-
fraction analysis of these 2,6-diaryl-substituted BODIPY
revealed almost coplanar orientation between the aromatic
groups and the BODIPY core, allowing effective electronic
communication. This is again owing to the lack of steric
hindrance of substituents on 1,3,5,7-positions.
Figure 2. (a) UV/vis absorption spectra of 1, 4, and 6 and (b)
fluorescence spectra of 1, 4, and 6 measured in CH2Cl2.
spectrawithattenuated quantum efficiency(ΦF = 0.15 and
0.25, respectively). To obtain further insight into their
photophysical properties, we have measured the fluores-
cence lifetimes, fluorescence anisotropy decay and spectra
(Supporting Information). Compared with the fluores-
cence lifetime of 6.7 ns for BODIPY monomer 1, dimer 4
and trimer 6 exhibit much reduced fluorescence lifetimes of
1.8 ns. This feature is mainly due to the enhancement of
nonradiative decay processes contributed by the decreased
HOMOÀLUMO gap as well as increased vibrational
relaxation channels including the torsional motions around
the βÀβ linkage in 4 and 6. While both 4 and 6 exhibit the
similar fluorescence lifetime of 1.8 ns, the radiative decay
rate for 6 is larger, but the nonradiative decay rate is larger
for 4, which leads to a larger fluorescence quantum yield for
6 compared with 4. This feature is attributable to an
increase in radiative decay coupling in 6 compared with 4
probably because the molecular rotation around the βÀβ
linkage should experience more restriction from the sur-
rounding solvent molecules. The fluorescence excitation
anisotropy spectra reflect the overall molecular geometry
(Supporting Information). For 1, the anisotropy values are
nearly zero in the entire spectral region, indicating that the
dipole orientation along the long and short molecular axes
is completely mixed in the excited state. On the other hand,
the anisotropy values for 4 and 6 become positive and those
Scheme 3. Synthesis of Donor- and Acceptor-Substituted
BODIPYs
Table 1. Summary of Optical Properties of BODIPYs
compd
λ
max (nm)
ε (MÀ1 cmÀ1
)
λ
em (nm)
Φf
1
2
3
4
5
6
7
8
9
501
518
538
609
502
678
577
686
537
558
644
6.3 Â 104
5.8 Â 104
5.8 Â 104
6.0 Â 104
8.0 Â 104
4.9 Â 104
6.7 Â 104
2.7 Â 104
6.2 Â 104
6.8 Â 104
2.7 Â 104
514
537
577
655
515
731
606
0.92
0.16
0.14
0.15
0.89
0.25
0.78
565
583
0.81
0.35
10
11
2994
Org. Lett., Vol. 13, No. 12, 2011

Figure 3. (a) UV/vis absorption spectra of 1, 7, 8, and 11 and (b)
fluorescence spectra of 1 and 7 in CH2Cl2.
Figure 4. (a) LUMO and (b) HOMO of 8 calculated at the
B3LYP/6-31G(d) level.
In the case of 7, introduction of two 4-nitrophenyl
substituents on the BODIPY core resulted in a consider-
able red-shift and increase of extinction coefficient in the
UV/vis absorption spectra due to effective expansion of
conjugation along with high fluorescence quantum yield
(ΦF = 0.78) (Figure 3 and Table 1). In contrast, 8 and 11
exhibit considerably different shapes of absorption spectra
with much red-shifted and broadened S1ÀS0 transition
band. Furthermore, fluorescence of BODIPYs 8 and 11 is
completely quenched. These photophysical features clearly
indicate intramolecular charge transfer (ICT) owing to the
strongly donating nature of 4-N,N-dimethylamino-
phenyl moiety. DFT calculations at the B3LYP/6-31G(d)
level support charge transfer character in 8 and 11, of
which HOMOs havelarge contribution from the orbitalon
aminophenyl substituents (Figure 4). BODIPY-based ICT
dyes often utilize R-styryl derivatives because of their
favorable coplanar conformation of the styryl groups to
the BODIPY core for ICT interaction.10 However, the
present study clearly demonstrates that β-aryl BODIPYs
without substituents on 1,3-positions are also good
candidates to create BODIPY derivatives bearing strong
ICT character.11
In summary, we have accomplished regioselective bro-
mination of 1,3,5,7-unsubstituted BODIPY with NBS.
Brominated BODIPYs can be used as a versatile synthetic
intermediate for novel BODIPY derivatives, as demon-
strated by expeditious preparation of directly βÀβ-linked
BODIPY oligomers and donorÀacceptor-substituted un-
symmetrical BODIPY. Further direct functionalization of
BODIPYs is currently underway in our group.
Acknowledgment. This work at Nagoya University was
supported by Grant-in-Aids for Scientific Research (Nos.
21685011) from MEXT, Japan, and the Global COE
program in Chemistry of Nagoya University. H.S. ac-
knowledges Asahi Glass Foundation for financial support.
S.Y. appreciatesthe JSPS ResearchFellowshipsfor Young
Scientists. The work at Yonsei University was supported
by the World Class University Program (R32-2010-000-
10217) from the Ministry of Education, Science, and
Technology (MEST) of Korea.
(10) (a) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem.,
Int. Ed. 2001, 40, 385. (b) Deniz, E.; Isbasar, G. C.; Bozdemir, O. A.;
Yildirim, L. T.; Siemiarczuk, A.; Akkaya, E. U. Org. Lett. 2008, 10,
Supporting Information Available.
General proce-
dures, spectral data for compounds, absorption and
fluorescence spectra. X-ray analysis of 4, 7, 8, and 11
(CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
€
3401. (c) Yu, Y.-H.; Descalzo, A. B.; Shen, Z.; Rohr, H.; Liu, Q.; Wang,
Y.-W.; Spieles, M.; Li, Y.-Z.; Rurack, K.; You, X.-Z. Chem. Asian J.
2006, 1, 176. (d) Rurack, K.; Kollmannsberger, M.; Daub, J. New J.
Chem. 2001, 25, 289.
(11) Bonardi, L.; Ulrich, G.; Ziessel, R. Org. Lett. 2008, 10, 2183.
Org. Lett., Vol. 13, No. 12, 2011
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