Carbazole-Based Boron Dipyrromethenes (BODIPYs): Facile Synthesis, Structures, and Fine-Tunable Optical Properties

Article abstract of DOI:10.1021/acs.orglett.5b01363

Carbazole-based BODIPYs were synthesized in three steps using an organometallic approach consisting of sequential Ir-catalyzed borylation, Suzuki-Miyaura coupling, and boron complexation. Various substituents were introduced into the carbazole moiety, and

Full text of DOI:10.1021/acs.orglett.5b01363

Letter
pubs.acs.org/OrgLett
Carbazole-Based Boron Dipyrromethenes (BODIPYs): Facile
Synthesis, Structures, and Fine-Tunable Optical Properties
Chihiro Maeda,* Takumi Todaka, and Tadashi Ema*
Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Tsushima,
Okayama 700-8530, Japan
S
* Supporting Information
ABSTRACT: Carbazole-based BODIPYs were synthesized in
three steps using an organometallic approach consisting of
sequential Ir-catalyzed borylation, Suzuki−Miyaura coupling,
and boron complexation. Various substituents were introduced
into the carbazole moiety, and large substituent effects were
confirmed by means of absorption spectroscopy, cyclic
voltammetry, and DFT calculations. Dibenzocarbazoles were
also converted into the corresponding BODIPYs.
We decided to use Ir-catalyzed direct borylation to
functionalize the 1-position of the carbazole because of the
high selectivity and functionality tolerance of this method.7
Borylation of the carbazole occurred selectively at the 1,8-
positions because the NH moiety acted as a directing group.8
Initially, we optimized the reaction of 3,6-di-tert-butylcarbazole
(1a) (Scheme 2 and Table 1). Using 0.5 and 1.0 equiv of
oron dipyrromethene (BODIPY) derivatives show prom-
Bise as dyes because of their high extinction coefficients and
fluorescent quantum yields and since they are also chemically,
thermally, and photostable.1 These properties suggest that
BODIPYs will have applications in fluorescent sensors,
biological labeling, photodynamic therapies, and photovoltaic
cells. To date, a number of BODIPYs, including fused,2 aza,3
and oligomeric4 varieties, have been developed. Such BODIPYs
have often been synthesized by acid-catalyzed condensation,
and their functionalization has been extensively studied.
However, the design of novel BODIPY derivatives by
alternative synthetic protocols has rarely been reported.
Scheme 2. Ir-Catalyzed Borylation of Carbazole 1a (cod =
1,5-cyclooctadiene, dtbpy = 4,4′-di-tert-butyl-2,2′-bipyridyl)
Carbazole derivatives have also been studied as potential
electron conductors, catalysts, and sensors. Recently, we
reported the synthesis of carbazole-based porphyrinoids5 and
found that the incorporation of carbazole units into the
porphyrin core generated some interesting properties. BODIPY
is known as porphyrin’s little sister, and so we assessed the
feasibility of incorporating a carbazole unit into a BODIPY
framework (Scheme 1).6 Herein we report the synthesis of
carbazole-based BODIPYs based on an organometallic
approach. In this method, a pyrrolic skeleton is attached to
the 1-position of the carbazole via Ir-catalyzed borylation and
Suzuki−Miyaura coupling. Boron complexation of the resulting
dipyrrin affords the carbazole-based BODIPY.
(Bpin)2, the monoborylated carbazole 2 and the bis-borylated
carbazole 3 were produced as the major product, respectively
a
Table 1. Ir-Catalyzed Borylation of Carbazole 1a
b
entry
(Bpin)2 (equiv)
yield (1a/2/3)
1
2
3
4
5
6
0.50
0.60
0.65
0.75
1.0
30/62/8
26/62/12
14/65/21
11/61/28
13/20/67
Scheme 1. Schematic Representation of the Construction of
a Carbazole-Based BODIPY
c
d
2.0
10/− /90(79 )
a
Conditions: 1a (1.0 mmol), [Ir(OMe)(cod)]2 (10 μmol), dtbpy (20
b
c
d
μmol), and THF (1.0 mL). NMR yield. Not detected. Isolated
yield after recrystallization.
Received: May 10, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01363
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Letter
(entries 1 and 5). Further increases in the amount of (Bpin)2
selectively provided 3 in 79% isolated yield (entry 6). To
maximize the yield of 2, we carefully optimized the reaction
conditions while using from 0.5 to 1.0 equiv of (Bpin)2. As a
result, 0.65 equiv was found to be the optimal amount (entries
2−4).
Following the borylation of 1a, the carbazole-based BODIPY
was synthesized by the Suzuki−Miyaura coupling reaction and
subsequent boron complexation (Scheme 3). We selected 1-(3-
Scheme 3. Synthesis of 5a−5h
Figure 1. X-ray crystal structures of (a) 5b, (b) 5c, (c) 5d, and (d) 5f.
Hydrogen atoms are omitted for clarity. The thermal ellipsoids are
drawn at the 50% probability level.
chloro-1H-isoindol-1-ylidene)-N,N-dimethylmethanamine (4)
as the coupling partner because 4 contains a benzo fusion
moiety and is easily prepared.9 Following the borylation (Table
1, entry 3), a mixture of 1a, 2, and 3 was subjected to the
Suzuki−Miyaura coupling reaction with 4 using Pd(OAc)2 and
XPhos as the catalytic system.10 The subsequent complexation
with BF3·OEt2 afforded the carbazole-based BODIPY 5a from
1a in 24% yield. The high-resolution mass spectrum of 5a
exhibited a parent ion peak at an m/z value of 497.2833 (calcd
for C31H34N3BF2 497.2814 [M]+). Various substituents,
including electron-donating and -withdrawing, aryl and ethynyl,
groups were subsequently attached to the 3,6-positions of the
carbazole moiety. Importantly, nonsubstituted 5c and phenyl-
substituted 5f were also obtained in acceptable yields, indicating
that selective borylation occurred. Single crystals of 5b, 5c, 5d,
5f, and 5g were obtained by the slow diffusion of methanol
vapor into their dichloromethane or toluene solutions. The
resulting X-ray crystal structures unambiguously demonstrated
BODIPY skeletons (Figure 1 and Figures S17−23 in
Supporting Information), in which the dimethylamino group
is oriented outside of the structure. The 1H−1H NOESY
spectra of these compounds confirmed a correlation between
the NMe2 moiety and the benzo-proton, which also supports
the E-conformer (see Figure S2). Because 4 was determined to
exist as the Z-conformer9b and the excess amount of 4 was
recovered without isomerization after the Suzuki−Miyaura
reaction, this isomerization is thought to have occurred during
the boron complexation, likely due to the repulsion between
the dimethylamino group and the BF2 moiety.
Figure 2. UV/vis absorption spectra of 5a−5h in CH2Cl2.
Table 2. Photophysical Data in CH2Cl2
compd
λA (nm)
λF (nm)
ΔνSt (cm−1
)
5a
5b
5c
5d
5e
5f
292, 398, 493
304, 409, 508
292, 390, 482
291, 375, 448, 475
278, 296, 381, 472
287, 401, 495
293, 398, 492
289, 400, 492
561
650
528
508
519
559
555
571
2460
4300
1810
1370
1920
2310
2310
2810
5g
5h
generated blue and red shifts, respectively, indicating efficient
substituent effects. The fluorescence spectra of the BODIPYs
were also perturbed by the substituents, although the
fluorescence quantum yields were very low. As compared to
general BODIPYs, these dyes show broad spectra and a large
Stokes shift value.11
The oxidation and reduction potentials of the BODIPYs
were measured to examine the effects of the substituents on the
π-networks of the BODIPY frameworks (Table 3 and Figure
S15). Cyclic voltammetry (CV) showed one reduction wave at
ca. −1.8 V regardless of the substituents and two oxidation
waves that were dependent on the substituents. Those
compounds having electron-donating and -withdrawing groups
exhibited lower and higher oxidation potentials, respectively.
The HOMO−LUMO gaps of the molecules with electron-
donating, aryl and ethynyl groups were smaller, whereas the
compounds with electron-withdrawing groups had larger gaps,
which is in good agreement with the optical gap data obtained
from absorption spectroscopy and also with the calculated gaps.
The UV/vis absorption spectra of these compounds are
shown in Figure 2, and the corresponding data are summarized
in Table 2. All the compounds show three bands at
approximately 300, 400, and 500 nm, which were effectively
shifted by the substituents. Introduction of electron-with-
drawing groups, and of electron-donating groups or aryl groups,
B
DOI: 10.1021/acs.orglett.5b01363
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a
Table 3. Electrochemical Results
Scheme 4. Synthesis of 7a−7d
b
compd
Ered (V)
Eox (V)
ΔECV
ΔEopt
ΔEDFT
5a
5b
5c
5d
5e
5f
−1.850
−1.823
−1.849
−1.739
−1.760
−1.809
−1.813
−1.779
0.429, 0.770
0.302, 0.717
0.485, 0.663
0.681, 1.044
0.640, 0.940
0.462, 0.848
0.472, 0.808
0.536, 0.861
2.279
2.125
2.334
2.421
2.400
2.271
2.285
2.315
2.52
2.44
2.57
2.61
2.63
2.51
2.52
2.52
2.76
2.57
2.86
3.02
3.00
2.72
2.67
2.73
5g
5h
a
Determined by cyclic voltammetry. Solvent: CH2Cl2. Supporting
electrolyte: Bu4NPF6 (0.10 M). Reference electrode: Ag/Ag+. Scan
rate: 0.1 V/s. Calculated at the B3LYP/6-31G* level.
b
Thus, efficient substituent effects were also observed in the
electrochemical studies.
In order to better understand the electronic and electro-
chemical properties, DFT calculations were performed.12 The
HOMOs and LUMOs of 5b, 5c, and 5d are shown in Figure 3.
Figure 4. X-ray crystal structures of (a) 7a and (b) 7c. Hydrogen
atoms are omitted for clarity. The thermal ellipsoids are drawn at the
50% probability level.
borylation, Suzuki−Miyaura coupling, and boron complexation.
The structures of these compounds have been elucidated by
NMR and X-ray diffraction analyses. Various substituents were
attached to the 3,6-positions of the carbazole moiety, and the
resulting substituent effects were confirmed by means of UV/
vis absorption spectroscopy, CV, and DFT calculations. We
were also able to apply Ir-catalyzed borylation to dibenzo-
carbazoles and consequently succeeded in the synthesis of the
corresponding BODIPYs. Further investigations of the develop-
ment of carbazole-based materials are currently underway.
Figure 3. HOMO (bottom) and LUMO (top) of (a) 5b, (b) 5c, and
(c) 5d calculated at the B3LYP/6-31G* level.
The HOMOs exhibit large electronic coefficients on the
carbazole moiety, especially in the case of 5b. In contrast, the
LUMOs are almost the same and exhibit electronic coefficients
primarily on the isoindole moieties. These results strongly
suggest that the observed fluorescence quenching resulted from
intramolecular charge transfer (ICT) from the carbazole moiety
to the isoindole moiety.13 TD DFT calculations were also
performed to assign the absorption bands: The bands at 500
and 400 nm are related to the transition from the HOMO to
the LUMO and that from the HOMO−2 to the LUMO,
respectively (Figure S14).
Finally, we applied this reaction to dibenzocarbazole
derivatives 6a−6d (Scheme 4) and found that these
compounds also underwent conversion to the corresponding
BODIPYs 7a−7d by a similar process. The structures of 7a and
7c were confirmed by X-ray diffraction analyses (Figure 4).
Although the HOMO and LUMO of dibenzocarbazole exhibit
large electronic coefficients at the 5,9-positions (see Figure
S16) and these positions are reactive,14 the Ir-catalyzed
borylation took place selectively at the 6-position due to the
steric properties and the directing group. Therefore, this
method was found to be suitable for functionalization at the
6,8-positions of the dibenzocarbazoles. The UV/vis absorption
spectra of 7a−7d show similar broad bands in the visible
region, exhibiting slight substituent effects (Figure S14).
In summary, we have synthesized novel BODIPY dyes based
on carbazole skeletons through sequential Ir-catalyzed
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, compound data, and crystallographic
data in CIF format. The Supporting Information is available
free of charge on the ACS Publications website at DOI:
10.1021/acs.orglett.5b01363.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: cmaeda@okayama-u.ac.jp.
*E-mail: ema@cc.okayama-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Young
Scientists (No. 25810027 (B)) from JSPS KAKENHI, Japan.
We thank Prof. A. Osuka and Dr. T. Tanaka (Kyoto University)
C
DOI: 10.1021/acs.orglett.5b01363
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Letter
5691. (b) Maeda, C.; Yoshioka, N. Org. Lett. 2012, 14, 2122.
(c) Maeda, C.; Yoshioka, N. Org. Biomol. Chem. 2012, 10, 5153.
(d) Masuda, M.; Maeda, C. Chem.−Eur. J. 2013, 19, 2971. (e) Masuda,
M.; Maeda, C.; Yoshioka, N. Org. Lett. 2013, 15, 578. (f) Maeda, C.;
Masuda, M.; Yoshioka, N. Org. Lett. 2013, 15, 3566. (g) Maeda, C.;
Masuda, M.; Yoshioka, N. Org. Biomol. Chem. 2014, 12, 2656.
(6) Boron complexes of pyridyl carbazoles were reported; see:
(a) Araneda, J. F.; Piers, W. E.; Heyne, B.; Parvez, M.; McDonald, R.
Angew. Chem., Int. Ed. 2011, 50, 12214. (b) Hao, Q.; Yu, S.; Li, S.;
Chen, J.; Zeng, Y.; Yu, T.; Yang, G.; Li, Y. J. Org. Chem. 2014, 79, 459.
(7) (a) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2003, 680, 3.
(b) Ishiyama, T.; Miyaura, N. Pure Appl. Chem. 2006, 78, 1369.
(c) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890. (d) Hartwig, J. F. Acc. Chem.
Res. 2012, 45, 864.
(8) (a) Paul, S.; Chotana, G. A.; Holmes, D.; Reichle, R. C.;
Maleczka, R. E., Jr.; Smith, M. R., III J. Am. Chem. Soc. 2006, 128,
15552. (b) Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 4068.
(9) (a) Diana, P.; Martorana, A.; Barraja, P.; Montalbano, A.;
Carbone, A.; Cirrincione, G. Tetrahedron 2011, 67, 2072. (b) Wang,
Z.-Y.; Yu, C.-J. Acta Crystallogr. 2013, E69, o448.
(10) Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2006, 45, 3484.
(11) Such broad absorption peaks and/or low fluorescence quantum
yields are observed in some β-benzo-fused BODIPYs2g,r,t or BODIPY
analogues with unsymmetrical structures.1e,3k
(12) Frisch, M. J. et al.. GAUSSIAN 9, Revision C.01; Gaussian, Inc.:
Wallingford, CT; Pittsburgh, PA, 2009. The full reference is in the SI.
(13) We measured absorption and fluorescence spectra in the
presence of TFA. Although the absorption spectra were red-shifted,
fluorescence was not observed. These results also suggest that the
fluorescence quenching is mainly due to ICT.
for MS measurements and X-ray diffraction analysis, and Prof.
S. Suga and Prof. K. Mitsudo (Okayama University) for CV
measurements.
REFERENCES
■
(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) Boens, N.; Leen, V.; Dehaen, W. Chem. Soc. Rev. 2012,
41, 1130. (d) Bessette, A.; Hanan, G. S. Chem. Soc. Rev. 2014, 43,
3342. (e) Frath, D.; Massue, J.; Ulrich, G.; Ziessel, R. Angew. Chem.,
Int. Ed. 2014, 53, 2290.
(2) (a) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.; Burgess, K. J.
Org. Chem. 2000, 65, 2900. (b) Shen, Z.; Rohr, H.; Rurack, K.; Uno,
̈
H.; Spieles, M.; Schulz, B.; Reck, G.; Ono, N. Chem.−Eur. J. 2004, 10,
4853. (c) Goeb, S.; Ziessel, R. Org. Lett. 2007, 9, 737. (d) Umezawa,
K.; Nakamura, Y.; Makino, H.; Citterio, D.; Suzuki, K. J. Am. Chem.
Soc. 2008, 130, 1550. (e) Descalzo, A. B.; Xu, H.-J.; Xue, Z.-L.;
Hoffmann, K.; Shen, Z.; Weller, M. G.; You, X.-Z.; Rurack, K. Org.
Lett. 2008, 10, 1581. (f) Umezawa, K.; Matsui, A.; Nakamura, Y.;
Citterio, D.; Suzuki, K. Chem.Eur. J. 2009, 15, 1096. (g) Jiao, L.; Yu,
C.; Liu, M.; Wu, Y.; Cong, K.; Meng, T.; Wang, Y.; Hao, E. J. Org.
Chem. 2010, 75, 6035. (h) Okujima, T.; Tomimori, Y.; Nakamura, J.;
Yamada, H.; Uno, H.; Ono, N. Tetrahedron 2010, 66, 6895. (i) Ulrich,
G.; Goeb, S.; Nicola, A. D.; Retailleau, P.; Ziessel, R. J. Org. Chem.
2011, 76, 4489. (j) Jiao, C.; Huang, K.-W.; Wu, J. Org. Lett. 2011, 13,
632. (k) Awuah, S. G.; Polreis, J.; Biradar, V.; You, Y. Org. Lett. 2011,
13, 3884. (l) Zeng, L.; Jiao, C.; Huang, X.; Huang, K.-W.; Chin, W.-S.;
Wu, J. Org. Lett. 2011, 13, 6026. (m) Hayashi, Y.; Obata, N.; Tamaru,
M.; Yamaguchi, S.; Matsuo, Y.; Saeki, A.; Seki, S.; Kureishi, Y.; Saito,
S.; Yamaguchi, S.; Shinokubo, H. Org. Lett. 2012, 14, 866. (n) Jiang,
X.-D.; Zhang, H.; Zhang, Y.; Zhao, W. Tetrahedron 2012, 68, 9795.
(o) Uppal, T.; Hu, X.; Fronczek, F. R.; Maschek, S.; Bobadova-
Parvanova, P.; Vicente, M. G. H. Chem.Eur. J. 2012, 18, 3893.
(p) Yu, C.; Xu, Y.; Jiao, L.; Zhou, J.; Wang, Z.; Hao, E. Chem.Eur. J.
2012, 18, 6437. (q) Ni, Y.; Zeng, W.; Huang, K.-W.; Wu, J. Chem.
Commun. 2013, 49, 1217. (r) Wakamiya, A.; Murakami, T.;
Yamaguchi, S. Chem. Sci. 2013, 4, 1002. (s) Bochkov, A. Y.;
Akchurin, I. O.; Dyachenko, O. A.; Traven, V. F. Chem. Commun.
2013, 49, 11653. (t) Shimogawa, H.; Mori, H.; Wakamiya, A.; Murata,
Y. Chem. Lett. 2013, 42, 986.
(14) Xue, W.; LaDow, K.; Warshawsky, D. Chem. Res. Toxicol. 1997,
10, 432.
(3) (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.;
O’Shea, D. F. Chem. Commun. 2002, 1862. (b) Gorman, A.; Killoran,
J.; O’Shea, C.; Kenna, T.; Gallagher, W. M.; O’Shea, D. F. J. Am. Chem.
Soc. 2004, 126, 10619. (c) Zhao, W.; Carreira, E. M. Angew. Chem., Int.
Ed. 2005, 44, 1677. (d) McDonnell, S. O.; O’Shea, D. F. Org. Lett.
2006, 8, 3493. (e) Coskun, A.; Yilmaz, M. D.; Akkaya, E. U. Org. Lett.
2007, 9, 607. (f) Gresser, R.; Hummert, M.; Hartmann, H.; Leo, K.;
Riede, M. Chem.Eur. J. 2011, 17, 2939. (g) Zhang, X.; Yu, H.; Xiao,
Y. J. Org. Chem. 2012, 77, 669. (h) Shimizu, S.; Iino, T.; Araki, Y.;
Kobayashi, N. Chem. Commun. 2013, 49, 1621. (i) Wang, Y.; Chen, L.;
El-Shishtawy, R. M.; Aziz, S. G.; Mullen, K. Chem. Commun. 2014, 50,
̈
11540. (j) Díaz-Moscoso, A.; Emond, E.; Hughes, D. L.; Tizzard, G. J.;
Coles, S. J.; Cammidge, A. N. J. Org. Chem. 2014, 79, 8932. (k) Cheng,
C.; Gao, N.; Yu, C.; Wang, Z.; Wang, J.; Hao, E.; Wei, Y.; Mu, X.;
Tian, Y.; Ran, C.; Jiao, L. Org. Lett. 2015, 17, 278.
(4) (a) Cakmak, Y.; Akkaya, E. U. Org. Lett. 2009, 11, 85. (b) Rihn,
S.; Erdem, M.; Nicola, A. D.; Retailleau, P.; Ziessel, R. Org. Lett. 2011,
13, 1916. (c) Nepomnyashchii, A. B.; Broring, M.; Ahrens, J.; Bard, A.
̈
J. J. Am. Chem. Soc. 2011, 133, 8633. (d) Hayashi, Y.; Yamaguchi, S.;
Cha, W. Y.; Kim, D.; Shinokubo, H. Org. Lett. 2011, 13, 2992.
(e) Maeda, H.; Nishimura, Y.; Hiroto, S.; Shinokubo, H. Dalton Trans.
2013, 42, 15885. (f) Sakamoto, N.; Ikeda, C.; Yamamura, M.;
Nabeshima, T. Chem. Commun. 2012, 48, 4818. (g) Ahrens, J.; Boker,
̈
B.; Brandhorst, K.; Funk, M.; Broring, M. Chem.Eur. J. 2013, 19,
̈
11382. (h) Kolemen, S.; Cakmak, Y.; Kostereli, Z.; Akkaya, E. U. Org.
Lett. 2014, 16, 660.
(5) (a) Maeda, C.; Yoneda, T.; Aratani, N.; Yoon, M.-C.; Lim, J. M.;
Kim, D.; Yoshioka, N.; Osuka, A. Angew. Chem., Int. Ed. 2011, 50,
D
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