Synthesis of diazo-bridged bodipy dimer and tetramer by oxidative coupling of β-amino-substituted BODIPYs

Article abstract of DOI:10.1021/ol501131j

A diazo-bridged BODIPY dimer and tetramer were prepared by the oxidative coupling reaction of β-amino-substituted BODIPYs. The structure of the dimer was elucidated by X-ray diffraction analysis, showing its coplanar orientation of two BODIPY units. Effective extension of π-conjugation was confirmed by optical and electrochemical investigations.

Full text of DOI:10.1021/ol501131j

Letter
pubs.acs.org/OrgLett
Synthesis of Diazo-Bridged BODIPY Dimer and Tetramer by
Oxidative Coupling of β‑Amino-Substituted BODIPYs
Hiroki Yokoi, Satoru Hiroto,* and Hiroshi Shinokubo*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya, 464-8603, Japan
S
* Supporting Information
ABSTRACT: A diazo-bridged BODIPY dimer and tetramer
were prepared by the oxidative coupling reaction of β-amino-
substituted BODIPYs. The structure of the dimer was
elucidated by X-ray diffraction analysis, showing its coplanar
orientation of two BODIPY units. Effective extension of π-
conjugation was confirmed by optical and electrochemical
investigations.
ODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, has
treatment of 1 with 1.1 equiv of NBS. The palladium-catalyzed
B
been one of the most important functional dyes in a
cross-coupling reaction of 2 with benzophenone imine followed
by acidic hydrolysis furnished 4 in good yield. Compound 4
was stable enough for handling under air and concentrated
conditions. This is in sharp contrast to 2-amino BODIPYs
without α-substituents, which decomposed during concen-
tration by rotary evaporator.5j We next attempted oxidative
coupling of 4 with several oxidizing reagents.8 A copper-
mediated oxidative coupling resulted in the formation of a
complex mixture. On the other hand, oxidation of 4 with DDQ
in chloroform provided a diazo-linked BODIPY dimer 5 in 8%
yield (Table 1). In this reaction, we also observed the formation
of DDQ adducts as side products. Accordingly, we further
optimized the reaction conditions with other oxidants.
Oxidation of 4 with p-chloranil improved the yield to 12%.
However, a large amount of the starting material remained
unreacted. The use of MnO2 as the oxidant furnished 5 in 17%
yield. tBuOI, recently reported by Minakata et al.,9a worked well
wide area of material science due to its high thermal and
photochemical stability as well as strong absorption and
emission in the visible region.1 A number of BODIPY-based
molecules have been extensively explored for bioimaging
probes,2 photodynamic therapy,3 and light emitting devices.4
Recently, BODIPY oligomers with covalent linkages have
attracted much interest for their near-IR light absorbing
property.5 Although a number of BODIPY oligomers have
been reported, there is no example of diazo-bridged ones.
Diazo-bridged π-conjugated materials represented by azo-
benzene are photoactive materials, exhibiting photochromic
behavior through cis−trans isomerization.6 The diazo linkage
also enables effective π-conjugation due to its less sterically
demanding nature in comparison to ethylene and imino
linkages.7 In addition, the electron-withdrawing feature of
diazo groups effectively stabilizes π-conjugated systems to
prevent decomposition by air oxidation. Here, we describe the
synthesis of a diazo-bridged BODIPY dimer and tetramer as
novel covalently linked BODIPYs through oxidative dimeriza-
tion of amino-substituted BODIPYs.
Table 1. Oxidative Dimerization of 4
We prepared 3,5-diphenyl-2-amino BODIPY 4 as a starting
substrate from 3,5-diphenyl BODIPY 1 in three steps (Scheme
1). 2-Bromo BODIPY 2 was obtained in 94% yield by
Scheme 1. Synthesis of 2-Amino Substituted BODIPY 4
entry
oxidant (equiv)
DDQ (2.1)
time (h)
1
solvent
yield (%)
1
2
3
4
5
CHCl3
CHCl3
CHCl3
DME
8
12
17
33
34
a
p-chloranil (2.1)
23
MnO2 (26)
tBuOCl (2.0) + NaI (2.0)
24
13
2
PhI(OCOCF3)2 (2.1)
CHCl3
a
The reaction was conducted at rt for 17 h and at 60 °C for an
additional 6 h.
Received: April 19, 2014
© XXXX American Chemical Society
A
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Letter
to provide 5 in 33%, but inseparable chlorinated byproducts
were formed. Oxidation with bis(trifluoroacetoxy)iodobenzene
(PIFA) afforded the desired product 5 in 34% yield without
formation of chlorinated byproducts.9b,c In this case, the
starting material 4 was completely consumed. Recently, we
have reported the formation of pyrazine-fused BODIPY trimers
through oxidation of 2-amino BODIPYs without α-substi-
tuents.5j However, none of the pyrazine-fused products were
detected in the oxidation of 4.
Scheme 2. Synthesis of 2-Amino Substituted BODIPY
The product 5 was assigned by spectroscopic methods. The
parent mass ion peak observed at m/z = 951.4119 (calcd for
(C60H49B2F4N6)+ = 951.4154 [(M + H)+]) indicated its
1
dimeric structure. In its H NMR spectrum, peaks for pyrrole
protons of 5 were shifted in the lower field as compared to 4
and the broad NH2 signal of 4 disappeared after oxidation. This
spectral change indicates conversion of the electron-donating
NH2 group to the electron-withdrawing diazo linkage. Finally,
the structure of 5 was unambiguously elucidated by X-ray
diffraction analysis.9 Figure 1 displays the X-ray crystal structure
prospective utility of the diazo linkage to obtain stable and
highly conjugated BODIPY oligomers.
Figure 2a shows the UV/vis absorption spectra of 1, 5, and 7
in dichloromethane. The lowest energy bands were substan-
Figure 1. X-ray crystal structure of 5. (a) Top view and (b) side view.
The thermal ellipsoids are scaled at 50% probability level. The mesityl
and phenyl groups in (b) are omitted for clarity.
of 5, revealing its highly planar structure including the diazo
linkage. The deviation from the mean plane which consisted of
the two BODIPY cores and the diazo moiety is 0.088 Å, and
the dihedral angle between the BODIPY unit and the diazo
linkage is only 1.1°. The length of the C(2)−N(3) bond is 1.40
2
2
Å, which is shorter than the standard Csp −Nsp single bond
length. These structural features indicate the presence of
effective conjugation between two BODIPY cores through the
diazo linkage.
We then attempted to obtain higher oligomers. Bromination
of 5 with NBS proceeded regioselectively. Amino-substituted
BODIPY dimer 6 was prepared in a similar manner as 4.
Oxidation of 6 with MnO2 furnished tetramer 7 in 4% yield.
The yield was improved to 24% with PIFA as an oxidant
(Scheme 2). The formation of 7 was confirmed by mass and
NMR spectroscopic analyses. The high-resolution mass
spectrum of 7 exhibits the parent mass ion peak at m/z =
Figure 2. (a) UV/vis absorption and (b) emission spectra of 1 (red), 5
(blue), and 7 (black) in dichloromethane.
1
1927.8142, indicating its tetrameric structure. The H NMR
tially shifted to the low energy region in the order of 7 > 5 > 1,
indicating effective expansion of π-conjugation upon oligome-
rization. The splitting absorption band at 690 nm for 5 also
indicates strong π-conjugation, showing an anisotropic
transition over the BODIPY plane.11 Tetramer 7 exhibited an
intense absorption band in the near-infrared region at 802 nm.
The intense emission was observed for 1 with a fluorescence
spectrum of 7 showed a C2 symmetric feature. Singlet signals
for pyrrole protons of 6 at 6.51, 6.36, and 5.87 ppm were
shifted further downfield to 6.58, 6.57, and 6.52 ppm in 7,
suggesting the formation of a new diazo group. Although the
yield of the oxidative coupling reaction was not high, tetramer 7
was stable under the aerobic conditions, demonstrating the
B
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Organic Letters
Letter
quantum yield of 0.88, while dimer 5 exhibited weak and red-
shifted emission (Φf = 0.02) at 743 nm (Figure 2b). The
quenching of fluorescence might be due to cis−trans isomer-
ization dynamics at the excited state.12 However, no isomer-
ization product was detected upon irradiation.
To investigate the electronic structure of oligomers 5 and 7,
electrochemical analysis was performed by cyclic voltammetry
(Figures 3, S19). Dimer 5 exhibited three reversible oxidation
ASSOCIATED CONTENT
* Supporting Information
Experimental details and spectral data for all new compounds.
Crystallographic data (CIF file) for 5. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: hshino@apchem.nagoya-u.ac.jp.
*E-mail: hiroto@apchem.nagoya-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “New Polymeric Materials Based
on Element-Blocks (No. 2401)” (25102514) and Program for
Leading Graduate Schools “Integrative Graduate Education and
Research in Green Natural Sciences”, MEXT, Japan. S.H.
acknowledges The Sumitomo Foundation for financial support.
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