Regioselective and Stepwise Syntheses of Functionalized BODIPY Dyes through Palladium-Catalyzed Cross-Coupling Reactions and Direct C-H Arylations

Article abstract of DOI:10.1021/acs.joc.6b00858

Regioselective and stepwise syntheses of a series of functionalized BODIPY dyes through palladium-catalyzed cross-coupling reactions and direct C-H arylations have been developed. In particular, this method allows the straightforward synthesis of 2,6-dibr

Full text of DOI:10.1021/acs.joc.6b00858

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Article
Regioselective and Stepwise Syntheses of Functional
BODIPY Dyes through Palladium-Catalyzed Cross-
coupling Reactions and Direct C-H Arylations
Zeya Feng, Lijuan Jiao, Yuanmei Feng, Changjiang Yu, Na Chen, Yun Wei, Xiaolong Mu, and Erhong Hao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00858 • Publication Date (Web): 30 Jun 2016
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Regioselective and Stepwise Syntheses of
Functionalized BODIPY Dyes through
Palladium-Catalyzed Cross-coupling Reactions
and Direct C-H Arylations
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Zeya Feng, Lijuan Jiao,* Yuanmei Feng, Changjiang Yu, Na Chen, Yun Wei, Xiaolong Mu and
Erhong Hao*
The Key Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Laboratory of
Molecule-Based Materials; School of Chemistry and Materials Science, Anhui Normal University,
Wuhu, China 241000.
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*To whom correspondence should be addressed.
E-mail: haoehong@ahnu.edu.cn, jiao421@ahnu.edu.cn
Abstract Graphic
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Abstract: Regioselective and stepwise syntheses of a series of functionalized BODIPY dyes
through palladium-catalyzed cross-coupling reactions and direct C-H arylations have been developed.
In particular, this method allows the straightforward synthesis of 2,6-dibromo-3,5-diarylBODIPYs
and 2-bromo-3-arylBODIPYs from polybrominated BODIPYs. The X-ray structure of intermediates
5a-c indicated that the palladium was first inserted into the C-Br bonds at 3,5-positions of
brominated BODIPYs. The resulting 2,6-dibromo-substituted BODIPYs are potential long
wavelength photosensitizers which are not easily accessible using previous methods.
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Introduction
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BODIPYs, or 4,4’-difluoro-4-bora-3a,4a-diaza-s-indacenes, are valuable fluorophores due to their
many excellent properties, such as high stability, strong absorption/emission in the visible spectral
range.1 In recent years, there has been increasing interest in the use of BODIPYs as fluorescent
labels and probes,2 organic electronics/photovoltaics,3 and photodynamic therapy (PDT) agents.4 To
meet the diverse applications, much investigation is ongoing on the synthesis and functionalization
of BODIPYs for fine tuning their photophysical properties such as high fluorescence quantum
yields, red/NIR emission, and singlet oxygen quantum yields.1-5
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Comparing to the total synthesis from functionalized pyrroles, the development of efficient
synthetic methods for the facile functionalization of the BODIPY chromophore has thus attracted
intense research interests lately6,7 and modification at α- or β-positions of the BODIPY core is an
effective strategy to tune photophysical properties of resulting dyes. Among those, the direct
introduction of a variety of functionalities on the BODIPY core through nucleophilic substitutions
and metal-catalyzed cross-coupling reactions of the easily accessible core-halogenated BODIPYs8-11
is particularly attractive. For example, 3- and/or 5-halo-BODIPYs (Scheme 1a) have been used to
prepare a series of 3- and/or 5-aryl-, alkenyl- and alkynyl-functionalized BODIPYs through
SNAr9b,9f,9h and palladium-catalyzed cross-coupling reactions (e.g. Stille, Negishi, Heck, Suzuki and
Sonogashira).9-11
Another more efficient method for late-stage modification of BODIPY is the direct C-H
activation of which currently only a few examples were reported.12,13 Direct alkenylation by Burgess
et. al12a and direct regioselective palladium-catalyzed C-H arylation12c,f and recent radical C-H
arylation/alkylation13 at 3- and 3,5-positions of BODIPY by Boens, Dehaen and us were reported
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(Scheme 1a), while Wu and You12g reported regioselective palladium-catalyzd decarboxylative direct
C-H arylation at 2,6-positions of BODIPY (Scheme 1a).
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Scheme 1. Summary of synthetic pathways toward arylated BODIPYs
Alternatively, very recently, while we were working in this project, direct C-H arylation on
3,4-ethlenedioxythiophene (EDOT) derivatives with 1,3,5,7,8-pentamethyl-2,6-dibromoBODIPY
was recently reported by Yu and coworkers14a (Scheme 1b). Previously, our group developed
regioselective stepwise brominations of BODIPYs8a from which polybrominated BODIPYs, like 2a
in Scheme 2, are easily available. Since the 3,5-positions of BODIPY contain partial positive charge
and are subject to nucleophilic addition,14b we rationalized that C-Br bonds at the 3,5-position would
be highly reactive toward metal catalyzed reactions.
Herein, we report regioselective and stepwise syntheses of a series of functional BODIPY dyes
from polybrominated BODIPYs through palladium-catalyzed cross-coupling reactions and direct
C-H arylations on thiophene and furans. Previous results by Ortiz and coworkers8d on iodinated
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BODIPYs showed that the introduction of iodine atoms at 2 and/or 6 positions were critical for the
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efficiency of O2 generation, while iodine atoms at 3 and/or 5 positions did not produce a
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significant impact.8d,4b Our resulting regioselective cross-coupling products (BODIPYs with bromo
atoms at 2,6-positions and aryl groups at 3,5-positions) also showed efficient singlet oxygen
generation properties due to the enhanced intersystem crossing (ISC) as a result of heavy atom
effect. These novel dyes join to the previously reported bromo- and iodo-containing BODIPYs4,8,15,16
(PS1-3 in Scheme 1d), orthogonal BODIPY dimers17 and BODIPY-C60 complexes (via
intramolecular spin converter)18 as a new type of potential photosensitizers.
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Results and Discussions
Synthesis:
2,3,5,6-Tetrabromo-substituted BODIPYs 2a14b and 2b8a (Scheme 2) were regioselectively
synthesized in over 90% yields using bromine in dichloromethane from the corresponding BODIPYs
1a and 1b in one step. We first tested the reaction between 2a/2b and 5 equiv thiophene in toluene
using Pd(OAc)2 as catalyst, PPh3 as ligand, and K2CO3 as base (method b in Scheme 2). The
reactions turned bluish quickly and gave mainly one bluish spot on TLC. To our delight, in contrast
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to many direct C-H arylations which use expensive ligands, such as PCy3·HBF4 or P(o-Anisyl)3,14a
this economical reaction conditions were efficient for the arylations of BODIPYs and
3,5-dithiophene-2,6-dibromoBODIPYs 3a or 3b in 39% and 52% yields, respectively. The
regioselectivity of this reaction was confirmed by the X-ray structure of 3b (Figure 1) and by the
pronounced red-shifted absorption of the resulting thienyl BODIPYs, similar to those reported by
Ziessel19 through total synthesis. Although excess thiophene (5 equiv) was used, no product with
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thienyl group at 2,6-positions was isolated. Increasing the reaction temperature to 110 C, trithienyl
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substituted BODIPYs were detected in small amount and no isolation was attempted. Using pivalic
acid instead of PPh3 (method a in Scheme 2) gave similar result.
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To demonstrate the generality of this C-H arylation protocol, BODIPY 2a was further reacted with
3,4-ethylenedioxythiophene (EDOT) and 2-methylfuran, giving 3c and 3d in 40% and 42% yields,
respectively (Scheme 2). 2,3-Dibromo-substituted BODIPY 2c was also reacted with 2.5 equiv
thiophene, EDOT, 2,2’-bithiophene and 2-methylfuran, respectively, giving α-arylated BODIPYs
4a, 4b, 4c and 4d in 47-50% yields (Scheme 2).
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Scheme 2. Regioselective direct C-H arylations on thiophenes and furan with BODIPYs 2.
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Figure 1. X-Ray structure of 3b (top) and 3e (bottom): top (a, d), front (b, e) views and crystal
packing (c, f). C, light gray; N, blue; B, dark yellow; F, bright green; Br, green; O, red; S, yellow.
Hydrogen atoms were omitted for clarity
The crystals of 2,6-dibromo-substituted BODIPY 3b suitable for X-ray analysis were obtained
by slow evaporation of its dichloromethane solution and confirmed the regioselectivity of the above
reaction. The average deviation of the twelve atoms from the mean plane of BODIPY core is only
0.0051 Å and the maximum deviation is 0.1759 Å, indicating that 3b has an almost planar boron
complexed dipyrrin core. The dihedral angle between the idealized meso-phenyl ring and the
BODIPY core in 3b is around 62o. The two thienyl rings at the 3,5-positions in 3b both tilted to the
same direction and the dihedral angles between the idealized thienyl rings and the BODIPY core in
3b are 45o and 46o, respectively. The crystal packing diagram of 3b in Figure 1c showed that two
neighboring molecules form π-stacked dimer structures in a head-to-head arrangement with an
intermolecular distance of 4.08 Å between the π-conjugated planes of the neighboring molecules,
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where the molecules are longitudinally arranged in a slightly offset fashion to avoid steric repulsion
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between the meso-phenyl rings.
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Scheme 3. Regioselective synthesis complexes 5a-c from the reaction of BODIPYs 2 and
Pd(PPh3)4.
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Since the initial step of the palladium-catalyzed C-H arylation is the palladium insertion to the
C-Br bond, we isolated the intermediates 5a-c (Scheme 3) which may further prove the origin of the
high regioselectivity at the 3,5-position. Mixing 2,3,5,6-tetrabromo-substituted BODIPY 2a and 2,3
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-dibromo-substituted BODIPY 2c with 2 equiv or 1 equiv Pd(PPh3)4 at 70 C regioselectively gave
the palladium complexes 5a-c (Scheme 3) in 81%, 60% and 65% yields after silica gel column
purification, respectively. No complexes with palladium substituted at 2,6-positions of BODIPY
were detected or isolated. Interestingly, the palladium complexes 5a-c are highly stable during the
purification, characterization in various solvents with no sign of decomposition.
X-Ray structures of 5a, 5b and 5c are shown in Figure 2. The average and maximum deviations
of the twelve atoms from the mean plane of BODIPY core are 0.0059 Å and 0.2857 Å for BODIPY
5a, 0.0006 Å and 0.0335 Å for BODIPY 5b, 0.0010 Å and 0.0441 Å for BODIPY 5c. These results
indicate no major deformations of the BODIPY cores due to the presence of Pd(PPh3)2Br at
3/5-positons. The Pd-C, Pd-Br and Pd-P distances were found to be respectively, 1.9895(37),
2.4911(7), and 2.3267(12)/2.3353(12)
Å
for 5a, and 1.9704(45), 2.4827(8), and
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2.3311(17)/2.3405(17)
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for 5c, and 1.9913(32)/1.9851(34), 2.4949(6)/2.4975(7), and
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2.3178(11)-2.3559(12) Å for 5b.
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Figure 2. X-Ray structure of 5a, 5c and 5b: top (a, c, e) and front (b, d, f) views; C, light gray; N,
blue; B, dark yellow; F, bright green; Br, green; Pd, brown; P, red. Hydrogen atoms were omitted for
clarity
Scheme 4. The Suzuki cross-coupling reactions of complexes 5a and 5c.
The reactivity of these intermediates 5a and 5c was studied. The Suzuki reaction between 5a
and 5 equiv (4-methoxyphenyl)boronic acid gave tetraarylBODIPY 6a in 92% yield without the
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need of additional catalyst (Scheme 4). Notably, 5c was a good and air-stable catalyst for
palladium-catalyzed coupling reactions. For example, 2c reacted with (4-tert-butylphenyl)boronic
acid in the presence of only 1.7% mmol 5c, regioselectively giving BODIPY 4e in 41% yield
(Scheme 4).
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Along with this finding, we further extended the palladium catalyzed regioselective reaction to
various palladium-catalyzed cross-coupling reactions. Although various palladium-catalyzed
coupling reactions have been reported on halogenated BODIPYs, only very recently a few
regioselective coupling reactions on polybrominated BODIPYs were reported.10d,10g,11f We first tested
the Stille coupling reaction on these 2,3,5,6-tetrabromo-substituted BODIPYs since the Stille
coupling reaction is highly reactive and does not need base. BODIPYs 2a or 2b in toluene with 2
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equiv 2-(tributylstannyl)thiophene in the presence of Pd(PPh3)4 were stirred at 80 C. The reactions
turned bluish quickly and gave mainly 3,5-dithiophene-2,6-dibromoBODIPYs 3a or 3b in over 40%
yields. Increasing the amount of 2-(tributylstannyl)thiophene to 4 equiv, this Stille coupling reaction
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at 90 C gave exclusively 2,3,5,6-tetrathiopheneBODIPYs 6b or 6c in around 50% yields (Scheme
5).
Scheme 5. Regioselective Stille coupling reactions of BODIPYs 2.
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To further investigate this regioselectivity between the 3/5 and 1/7 positions,
1,2,3-tribromo-substituted BODIPY 2d was synthesized from bromination of BODIPY 1d in 85%
yield using 4 equiv Br2, and was applied to the above Stille coupling reaction using with 1 equiv
2-(tributylstannyl)thiophene at 80 oC (Scheme 5). BODIPY 4f was observed as a major product and
was isolated from this reaction in 43% yield. 1H-NMR, 13C-NMR and HRMS all indicate that 4f only
has one thiophene ring as expected. In order to further confirm its structure, crystals suitable for
X-ray structure analysis were obtained by slow diffusion of hexane into its dichloromethane solution.
Surprisingly, X-ray structure of 4f (Figure 3) indicated the above Stille coupling reaction
regioselectively occurred at 1-position instead of 3-position of BODIPY core. The thiophene ring is
tilted by 35o relative to the BODIPY core. The average root-mean-square deviation of the BODIPY
core is 0.0067 Å, indicating that 4f adopts an almost planar conformation.
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Figure 3. X-Ray structure of 4f: top (a) and front (b) views. C, light gray; N, blue; B, dark yellow; F,
bright green; Br, green, S, yellow. Hydrogen atoms were omitted for clarity
The Suzuki coupling of 2a with different amount of (4-methoxyphenyl)boronic acid in the
presence of Pd(PPh3)4 and Na2CO3 also regioselectively gave 3,5-diarylated BODIPY 3e (confirmed
by the X-ray structure in Figure 1) and 2,3,5,6-tetraarylated BODIPY 6a in 45% and 76% yields,
respectively (Scheme 6). Further Suzuki coupling of 2,6-dibromo-3,5-diarylBODIPY 3e with 5
equiv (4-tert-butylphenyl)boronic acid under the above Suzuki coupling gave
2,3,5,6-tetraarylBODIPY 6d having two different sets of substituents at the 3,5- and 2,6-positions,
respectively, in 78% yield.
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Scheme 6. Regioselective Suzuki cross-coupling reactions of BODIPY 2a.
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Scheme 7. Regioselective Heck and Sonogashira cross-coupling of BODIPY 2a.
Similarly, the Heck reaction between 2a and 10 equiv methyl acrylate in the presence of
Pd(OAc)2, PPh3 and Na2CO3 at 80 oC gave mainly 2,6-dibromo-substituted BODIPY 3f in 47% yield
after 1.5 h (Scheme 7). Extending the reaction time to 10 h, the same reaction gave 2,3,5-trialkenyl
substituted BODIPY 7 in 51% yield as the major product. Increasing the amount of methyl acrylate
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to 50 equiv and the reaction temperature to 110 C, gave exclusively the 2,3,5,6-tetraalkenyl
substituted BODIPY 6e in 51% yield. The palladium-catalyzed regioselective cross-coupling
reaction was further extended to the Sonogashira coupling reaction. 2,6-Dibromo-substituted
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BODIPYs 3g and 3h were thus regioselectively synthesized in 31% and 38% yields under standard
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condition from 5 equiv 2-ethynylthiophene and 4-ethynylanisole, respectively (Scheme 7).
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Similar to BODIPY 3b, BODIPY 3e also show an almost planar structure for the BODIPY core
since the average and maximum deviations of the twelve atoms from the mean plane of BODIPY
core are 0.0014 Å and 0.1142 Å. The dihedral angle between the two idealized pyrrole rings in the
dipyrrin is 1.9 o and B-N bond lengths are both around 1.57 Å. The dihedral angle between the
meso-mesityl group and the BODIPY core in 3e is around 83o due to the steric hindrance of the
methyl groups on the meso-mesityl group, while the dihedral angles between the 3,5-phenyl rings
and the BODIPY core are around 60o. The crystal packing diagram of 3e in Figure 1f showed that
two neighboring molecules form π-stacked dimer structures in a head-to-tail arrangement with an
intermolecular distance of 4.48 Å between the π-conjugated planes of the neighboring molecules.
The π-stacked dimer further packed with another dimer in a head-to-tail arrangement with an
intermolecular distance of 5.11 Å.
Spectroscopic properties
These palladium catalyzed reactions provided a set of dyes with a variety of substituents at the
2,3,5,6,8-positions of the BODIPY nucleus. The absorption and fluorescence emission spectra of
these dyes cover a broad range of visible spectrum (Figure 4) and their optical properties are
summarized in Table 1. The α-arylated BODIPYs 3, 4, 6 and 7 all have red-shifted absorption and
emission spectra in relation to BODIPYs 1 and 2. Electron-rich 2-methylfuran and large
π-conjugated 2-ethynylthiophene and 4-ethynylanisole groups, which gave absorption maxima
around 670 nm (3d, 3g and 3f), introduced larger red shifts than those BODIPYs with thiophene and
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phenyl groups at 3,5-positions (Figure 4). The thienyl BODIPYs 3a-c and 4a-c have larger Stokes
6
7
shift (1304-2257 cm-1) than most of other dyes which have classical small Stokes shift of BODIPYs
8
9
(Tables 1 and S3).
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Table 1. Photophysical properties of BODIPYs 1-7 in dichloromethane at room temperature.
max
max
λabs
λem
ε
dyes
1ac
2a
3a
3b
3c
Φb
Stokes shift (cm-1)
729
(nm)
501
(nm)
520
(cm-1M-1)a
77600
0.99
556
606
605
606
667
582
612
667
667
523
529
560
580
534
532
553
593
559
616
577
658
662
649
689
630
628
706
697
583
588
641
609
567
596
584
608
575
672
92300
53500
40300
37000
50100
66100
86700
72800
81900
35000
32200
32200
34500
43500
29500
49100
79700
83500
49000
655
0.08±0.006
0.37±0.02
0.57±0.02
0.58±0.03
0.43±0.01
0.34±0.02
0.64±0.03
0.64±0.03
0.48±0.02
0.51±0.02
0.60±0.03
0.60±0.02
0.58±0.02
0.51±0.01
0.04±0.004
0.45±0.01
0.30±0.01
0.44±0.02
0.42±0.02
1304
1423
1093
479
3d
3e
1309
416
3f
3g
3h
4a
4b
4c
828
645
1968
1897
2257
821
4d
4e
1090
2018
960
4f
5a
5b
5c
416
498
6a
1353
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6b
6c
6d
6e
7
632
633
604
634
622
662
662
666
669
655
48000
43400
63700
80700
83500
717
692
1541
825
810
0.10±0.01
0.19±0.01
0.62±0.02
0.79±0.04
0.26±0.02
﹣
﹣
aData corresponding to the strongest absorption maximum, the unit for ε is M cm . The standard
errors are less than 10% from three independent measurements. Fluorescence quantum yields of 2a,
1
1
b
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1.0
(a)
2a
4a-b，4e and 5a-c were calculated using Rhodamine B (φ = 0.49 in ethanol) as the reference.
3a
3d
f
Fluorescence quantum yields of 3a-h, 4c-d, 6a-e and 7 were calculated using Cresyl violet
3e
3g
3h
c
14b
perchlorate (φf = 0.54 in methanol) as the reference. Data taken from the reference .
0.5
0.0
300
400
500
600
700
Wavelength (nm)
1.0
2a
3a
3d
3e
3g
3h
(b)
0.5
0.0
600
700
800
Wavelength (nm)
Figure 4. Normalized absorption (left) and emission (right) spectra of dyes 2a, 3a, 3d, 3e, 3f, 3g and
3h in dichloromethane.
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The solvatochromic effects on most of these new dyes were investigated in hexane, toluene,
dichloromethane, tetrahydrofuran, acetonitrile and methanol (Figures S1-S21, Supporting
information) and were summarized in Table S3 (Supporting information). The influence of the
solvent on λabs(max) and λem(max) is minimal. BODIPYs 3a-h, 4a-e and 6a-e showed upto 20 nm
shifts of both their λabs(max) and λem(max) in these different solvents which were often red-shifted
with increasing solvent polarizability, similar to previously reported 3,5-diaryl substituted
BODIPYs.12g For example, λabs(max) of 3a moves only 18 nm among these different solvents
tested (from 596 nm in acetonitrile to 618 nm in toluene), at the same time as a 14 nm change of
λem(max) is observed (from 652 nm in acetonitrile to 666 nm in toluene).
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Although these α-arylated BODIPYs dyes 3, 4 and 6 have lower fluorescence quantum yields
that those of corresponding nonbrominated BODIPYs,12a they still showed surprisingly good
fluorescence quantum yields in these five solvents (Tables 1 and S3). Only slight variations of
fluorescence quantum yields were observed for most of these dyes, except for BODIPY 3c
containing EDOT group and 2,3,5,6-tetrathiopheneBODIPYs 6b or 6c. The later three dyes showed
a gradual decrease of the fluorescence quantum yields with the increase of the polarity of the
solvents. For example, the fluorescence quantum yields for 6b were 0.42 in hexane, which was
gradually reduced to 0.25 (in toluene), 0.10 (in dichloromethane), 0.09 (in tetrahydrofuran) and
0.03 (in acetonitrile).
Interestingly, the palladium complexes 5a-c all showed good fluorescence quantum yields
ranging from 0.30 to 0.60 in different solvents as well as good solid state fluorescence due to the
presence of bulky substituents (Figure S26 in the Supporting information).
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Since BODIPY dyes possess a set of ideal optical properties, including high molar absorption
coefficients, low dark toxicities, efficient cellular uptake and excellent photostability that are
characteristics of photosensitizers,4 several halogenated BODIPYs have been reported as
photosensitizers.15,16 However, currently only limited types of them show strong near infrared (NIR)
absorption. Representative examples are PS2 (Figure 1) one by Akkaya and others15b,c and PS3
(Figure 1) by You15d and Shen15e. With a series of 2,6-dibromo-substituted BODIPYs in hand, the
singlet oxygen generation properties of representative 2,6-dibromo-substituted BODIPYs 3d, 3f and
3g with long wavelength absorption maxima above 600 nm were selected and studied. A
comparative study of the relative singlet oxygen generating efficiency of these dyes (1 × 10-5 M) was
performed in air-saturated dichloromethane under broad band light (> 590 nm, at 2 mw/cm2)
irradiation condition using 1,3-diphenylisobenzofuran (DPBF, 8 × 10-5 M) as a trap molecule. A
well-known photosensitizer methylene blue (1 × 10-5 M) was used as reference, which has a singlet
oxygen quantum yield of 0.57 in air-saturated dichloromethane.20 The decrease of the absorbance
band of DPBF at 415 nm was monitored (Figure 5). The calculated singlet oxygen quantum yields in
dichloromethane are 0.14, 0.35 and 0.19 for 3d, 3f and 3g, respectively, using methylene blue as the
reference. Nevertheless, the singlet oxygen quantum yields of 3d, 3g and 3h in dichloromethane are
lower than those known BODIPY based photosensitizers PS1-3 (Figure 1).15
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1.6
1.4
1.2
1.0
(b)
(a)
1.5
1.0
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0.0
time (s )
0
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D P B F control
Methylene B lue
3d
3f
3g
400
500
600
700
0
10
20
30
40
T ime (s )
Wavelength (nm)
Figure 5. (a) Absorption spectra of DPBF (8 × 10-5 M) upon irradiation in the presence of BODIPY
3f (1 × 10-5 M) in dichloromethane. (b) Comparative DPBF degradation profiles (absorbance
changes at 415 nm) in dichloromethane by BODIPYs 3d, 3f and 3g (1 × 10-5 M). Methylene Blue (1
× 10-5 M) was used as reference. Filtered light > 590 nm was used at 2 mw/cm2.
Conclusion
In conclusion, a versatile, general method for regioselective functionalization of brominated
BODIPYs using palladium-catalyzed direct C-H arylations on furans and thiophenes as well as
cross-coupling reactions was developed. The resulting dyes showed strong bathochromically shifted
absorption and emission compared to the starting BODIPYs. With this fast and efficient reaction,
new fluorophores with interesting photophysical properties can be synthesized, avoiding the tedious
total synthesis of pyrrole precursors and unstable intermediates.
Experimental Section
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General. Reagents and solvents were used as received from commercial suppliers unless noted
otherwise. All reactions were performed in oven-dried or flame-dried glassware unless otherwise
stated, and were monitored by TLC using 0.25 mm silica gel plates with UV indicator (HSGF 254)
for thin-layer chromatography (TLC). Flash column chromatography was performed using silica gel
(200−400 mesh). 1H and 13C NMR were recorded on a 300 MHz or 500 MHz NMR spectrometer at
room temperature. Chemical shifts (δ) are given in ppm relative to CDCl3 or DMSO-d6 (7.26 ppm
for 1H, 77 ppm and 40 ppm for 13C) or to internal TMS. High-resolution mass spectra (HRMS) were
obtained using APCI (or ESI)-TOF in positive mode.
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Photophysical Measurements. UV-visible absorption and fluorescence emission spectra were
recorded on commercial spectrophotometers (190-870 nm scan range) at room temperature (10 mm
quartz cuvette). Relative fluorescence quantum efficienciesof BODIPY derivatives were obtained by
comparing the areas under the corrected emission spectrum of the test sample in various organic
solvents with with Rhodamine B (Φ= 0.49 in ethanol)21a and Cresyl violet perchlorate (Φ= 0.54 in
methanol)21b. Non-degassed, spectroscopic grade solvents and a 10 mm quartz cuvette were used.
Dilute solutions (0.01<A<0.05) were used to minimize the reabsorption effects. Quantum yields
were determined using the equation (1)22:
)
Fx 1−10− A (λ
nx2
nr2
r
ex
ex
(1)
Φx = Φr ×
×
×
)
1−10−A (λ
x
F
r
Where the subscripts x and r refer respectively to our sample x and reference (standard) fluorophore
r with known quantum yield Φr in a specific solvent, F stands for the spectrally corrected, integrated
fluorescence spectra, A(λex) denotes the absorbance at the used excitation wavelength λex, and n
represents the refractive index of the solvent (in principle at the average emission wavelength).
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Singlet oxygen quantum yield (Φ) determinations were carried out using the chemical trapping
method20. Typically, a 3 mL portion of the respective photosensitizer solutions (1 × 10-5 M) that
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contained 8 × 10-5 M diphenylisobenzofuran (DPBF) was irradiated at > 590 nm (2.0 mW/cm3) in
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air saturated dichloromethane. ΦΔ value was obtained by the relative method using methylene blue as
the reference equation (2):
750 Aref
K
Kref
∫
ref
ΦΔ
590
Φ =
(2)
Δ
750 A
∫
590
ref is the singlet oxygen quantum yield for the standard (methylene blue = 0.57)20a,20c, K and Kref
ΦΔ
are the DPBF photo-bleaching rate constants in the presence of the respective samples and standard,
750
750A
respectively;
and
ref are the integration of light absorption at the irradiation wavelength
A
∫
∫
590
590
from 590 nm to 750 nm by the samples and standard, respectively.
Crystallography. Crystals of 3b, 3e, 4f, 5a, 5b and 5c suitable for X-ray analysis were obtained by
slow diffusion of hexane into their dichloromethane solutions or slow evaporation of their
dichloromethane solutions. The vial containing this solution was placed, loosely capped, to promote
the crystallization. A suitable crystal was chosen and mounted on a glass fiber using grease. Crystal
diffraction suitable for X-ray analysis was performed on a CCD diffractometer using
graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å) at 293(2) K, with φ and ω scan
techniques. An empirical absorption correction was applied using the SADABS program.23 All
structures were solved by direct methods, completed by subsequent difference Fourier syntheses, and
refined anisotropically for all non-hydrogen atoms by full-matrix least-squares calculations based on
F2 using the SHELXTL program package.24 The hydrogen atom coordinates were calculated with
SHELXTL by using an appropriate riding model with varied thermal parameters. The residual
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electron densities were of no chemical significance. CCDC-1431320 (3b), CCDC-1431321 (3e),
CCDC-1485940 (4f), CCDC-1431322 (5a), CCDC-1443083 (5b) and CCDC-1431323 (5c) contain
the supplementary crystallographic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Synthesis. BODIPYs 1a and 1b25, 2a,8a 2b,14b and 2d8a were synthesized according to literatures.
Synthesis of BODIPY 2c: To compound 4,5-dibromo-1H-pyrrole-2-carbaldehyde (1 mmol, 253 mg)
in 50 mL of CH2Cl2 was added 3-ethyl-2,4-dimethyl-1H-pyrrole (1.2 mmol) in 1 mL of CH2Cl2 and
POCl3 (50 µL, 0.5 mmol), respectively, at ice-cold condition under argon. The reaction mixture was
stirred at ice-cold condition for 3 h, and Et3N (1.5 mL) was added into the reaction mixture. The
mixture was further stirred for 10 mins, then BF3·OEt2 (1.8 mL) was added through a syringe. The
reaction mixture was left stirring for 10 h, poured into 50 mL of water, and extracted with 30 mL of
CH2Cl2. Organic layers were combined, and solvent was removed under vacuum. The crude product
was purified by chromatography (silica gel, petroleum ether / dichloromethane = 3/1, v/v) to give the
desired compound 2c as a brown powder in 52% yield (211 mg). mp 140-141 ℃. 1H NMR (300
MHz, CDCl3) δ 6.87 (s, 1H), 6.73 (s, 1H), 2.57 (s, 3H), 2.40 (q, J = 7.5 Hz, 2H), 2.15 (s, 3H), 1.08 (t,
J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 166.7, 142.1, 137.0, 136.4, 132.3, 124.6, 123.1, 121.0,
106.3, 17.3, 14.0, 13.6, 9.5. HRMS (APCI) calcd. for C13H13BBr2FN2 [M-F]+ 386.9502, found
386.9505.
Synthesis of BODIPY 2d: To 1,3-dimethyl-2-ethylBODIPY 1d (49 mg, 0.2 mmol) in 16 mL of dry
CH2Cl2 was added liquid bromine (45 µL, 0.8 mmol) in CH2Cl2 (4 mL). The mixture was left stirring
for 30 min at room temperature, then poured into an aqueous solution of sodium thiosulfate, and
extracted by CH2Cl2. Organic layers were combined, dried over anhydrous Na2SO4, and evaporated
to dryness under vacuum. The crude product was purified by chromatography (silica gel,
dichloromethane as eluent) to give the desired 2d as brown solids in 85% yield (82 mg). mp
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185-189 ℃. H NMR (300 MHz, CDCl3) δ 7.01 (s, 1H), 2.58 (s, 3H), 2.42 (q, J = 7.0 Hz, 2H),
5
6
7
13
2.21(s, 3H), 1.10 (t, 7.5 Hz, 3H). C NMR (75 MHz, CDCl3) δ 167.8, 142.5, 137.5, 137.0, 131.1,
8
9
122.2, 119.0, 114,1, 108.9, 17.3, 13.9, 13.8, 9.6. HRMS (APCI) calcd. for C13H14Br3N2
[M-BF2+2H]+ 436.8687, found 436.8719.
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Direct C-H arylation on thiophenes and furan
Syntheses of BODIPY 3a:
Method a: To a dry round-bottom flask loaded with compound 2a (0.1 mmol, 62 mg),
trimethylacetic acid (0.12 mmol, 12 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3
mg) and thiophene (1 mmol, 82 mg) in 3 mL of toluene were added through a syringe into the
mixture. Freeze-pump-thaw cycle was carried out three times. After that, the mixture was warmed
to 80 oC under argon and stirred for 10 h. After cooling to room temperature, the reaction mixture
was extracted with CH2Cl2 and dried over anhydrous Na2SO4. Then the solvent was removed
under vacuum. The crude product was purified by chromatography (silica gel, petroleum
ether/dichloromethane = 4/1, v/v) to give the desired compound 3a as brown solid in 35% yield
(23 mg). mp 213-215 ℃. 1H NMR (300 MHz, CDCl3) δ 7.86 (d, J = 3.4 Hz, 2H), 7.60 (d, J = 5.0
Hz, 2H), 7.23 – 7.14 (m, 2H), 6.99 (s, 2H), 6.75 (s, 2H), 2.38 (s, 3H), 2.19 (s, 6H). 13C NMR (126
MHz, CDCl3) δ 157.4, 149.1, 142.3, 139.3, 136.7, 135.0, 133.3, 130.6, 130.4, 129.9, 129.1, 128.4,
127.4, 110.1, 21.2, 20.2. HRMS (APCI) calcd. for C26H20BF2N2S2Br2 [M+H]+ 632.9475, found
632.9464.
Method b: To a dry round-bottom flask loaded with compound 2a (0.1 mmol, 62 mg), K2CO3
(0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10 mg) and thiophene (1
mmol, 84 mg) in 3 mL of toluene were added through a syringe into the mixture.
Freeze-pump-thaw cycle was carried out three times. After that, the mixture was warmed to 80 oC
under argon and stirred for 10 h. After cooling to room temperature, the reaction mixture was
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extracted with CH2Cl2 and dried over anhydrous Na2SO4. Then the solvent was removed under
vacuum. The crude product was purified by chromatography (silica gel, petroleum
ether/dichloromethane = 4/1, v/v) to give the desired compound 3a as brown solid in 39% yield
(26 mg).
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BODIPY 3b was obtained as brown solid in 51% yield (31 mg) using method b from compound
2b (0.1 mmol, 58 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04
1
mmol, 10 mg) and thiophene (0.5 mmol, 42 mg) in 3 mL of toluene. mp 236-238 ℃. H NMR
(300 MHz, CDCl3) δ 7.84 (d, J = 3.6 Hz, 2H), 7.64 – 7.52 (m, 7H), 7.17– 7.20 (m, 2H), 6.99 (s,
2H). 13C NMR (126 MHz, CDCl3) δ 149.2, 142.3, 134.7, 133.4, 133.3, 133.3, 132.1, 130.8, 130.4,
129.9, 128.7, 127.5, 117.0, 110.0. HRMS (APCI) calcd. for C23H14BF2N2S2Br2 [M+H]+ 590.9000,
found 590.8991.
BODIPY 3c was obtained as brown solid in 40% yield (30 mg) using method b from compound 2a
(0.1 mmol, 62 mg), K2CO3 (0.25 mmol, 35 mg) , Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10
mg) and EDOT (0.5 mmol, 71 mg) in 3 mL of toluene. mp 231-232 ℃. 1H NMR (300 MHz, CDCl3)
δ 6.97 (s, 2H), 6.71 (s, 2H), 6.62 (s, 2H), 4.22 – 4.27 (m, 8H), 2.37 (s, 3H), 2.16 (s, 6H). 13C NMR
(75 MHz, CDCl3) δ 148.2, 143.2, 142.3, 140.9, 139.2, 136.7, 135.4, 129.9, 129.0, 128.3, 128.2,
111.7, 104.6, 64.7, 64.3, 21.1, 20.2. HRMS (APCI) calcd. for C30H23BBr2FN2O4S2 [M-F]+ 728.9523,
found 728.9515.
BODIPY 3d was obtained as brown solid in 42% yield (26 mg) using method b from compound 2a
(0.1 mmol, 62 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10
mg) and 2-methylfuran (0.5 mmol, 41 mg) in 3 mL of toluene . mp 200-202 ℃. 1H NMR (300 MHz,
CDCl3) δ 7.61 (d, J = 3.4 Hz, 2H), 6.95 (s, 2H), 6.62 (s, 2H), 6.27 (d, J = 3.0 Hz, 2H), 2.47 (s, 6H),
2.36 (s, 3H), 2.13 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 156.3, 143.3, 142.9, 138.9, 136.9, 135.0,
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130.5, 129.6, 128.3, 119.6, 119.5, 119.4, 109.6, 21.1, 20.0, 14.0. HRMS (APCI) calcd. for
C28H23BBr2FN2O2 [M-F]+ 609.0183, found 609.0181.
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BODIPY 4a was obtained as brown solid in 47% yield (19 mg) using method b from 2c (0.1 mmol,
40 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10 mg) and
thiophene (0.25 mmol, 21 mg) in 3 mL of toluene. mp 158-160 ℃. 1H NMR (300 MHz, CDCl3) δ
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7.66 (d, J = 3.3 Hz, 1H), 7.51 (d, J = 4.2 Hz, 2H), 7.17 (d, J = 3.9 Hz, 1H), 7.00 (s, 1H), 6.92 (s,
1H), 2.53 (s, 3H), 2.40 (q, J = 15.0 Hz, 2H), 2.19 (s, 3H), 1.08 (t, J = 9.0 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 140.9, 135.9, 132.2, 131.3, 131.2, 131.2, 131.1, 128.3, 126.9, 126.3, 124.7, 121.6,
121.0, 17.3, 14.0, 13.5, 9.5. HRMS (APCI) calcd. for C17H16BFN2SBr [M-F]+ 389.0295, found
389.0300.
BODIPY 4b was obtained as brown solid in 48% yield (22 mg) using method b from compound 2c
(0.1 mmol, 40 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10
1
mg) and EDOT (0.25 mmol, 36 mg) in 5 mL of toluene. mp 258-260 ℃. H NMR (300 MHz,
CDCl3) δ 6.99 (s, 1H), 6.89 (s, 1H), 6.55 (s, 1H), 2.53 (s, 3H), 2.39 (q, J = 15.0 Hz, 2H), 2.19 (s, 3H),
1.07 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) δ 153.7, 143.0, 141.7, 141.2, 141.0, 132.7,
132.6, 126.5, 125.5, 123.89, 123.9, 123.8, 102.6, 64.8, 64.6, 17.1, 14.3, 13.7, 9.7. HRMS (APCI)
calcd. for C19H19BF2N2O2SBr [M+H]+ 467.0412, found 467.0411.
BODIPY 4c was obtained as brown solid in 50% yield (25 mg) using method b from compound 2c
(0.1 mmol, 40 mg), K2CO3 (0.25 mmol, 35 mg), Pd(OAc)2 (0.01 mmol, 3 mg), PPh3(0.04 mmol, 10
1
mg) and 2,2’-bithiophene (0.5 mmol, 83 mg) in 5 mL of toluene. mp 104-105 ℃. H NMR (300
MHz, CDCl3) δ 7.67 (d, J = 3.9 Hz, 2H), 7.23 (d, J = 3.9 Hz, 1H), 6.98 – 7.04 (m, 3H), 6.92 (s, 1H),
2.55 (s, 3H), 2.40 (q, J = 15 Hz, 2H), 2.19 (s, 3H), 1.08 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 140.2, 137.1, 132.5, 132.3, 132.2, 130.7, 127.9, 127.8, 126.6, 125.0, 124.8, 124.2, 124.0,
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123.8, 121.4, 121.2, 17.3, 14.1, 13.5, 9.5. HRMS (APCI) calcd. for C21H18BFN2S2Br [M-F]+
471.0172, found 471.0172.
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BODIPY 4d was obtained as brown solid in 48% yield (20 mg) using method b from compound 2c
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(0.1 mmol, 40 mg), K2CO3 (0.25 mmol, 35 mg) , Pd(OAc)2 (0.01 mmol, 3 mg), PPh3 (0.04 mmol, 10
1
mg) and 2-methylfuran (0.25 mmol, 21 mg) in 3 mL of toluene. mp 108-109 ℃. H NMR (300
MHz, CDCl3) δ 7.31 (d, J = 3.3 Hz, 1H), 6.93 (s, 1H), 6.89 (s, 1H), 6.18 (d, J = 3.3 Hz, 1H), 2.57 (s,
3H), 2.48 – 2.34 (m, 5H), 2.17 (s, 3H), 1.08 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 154.3,
139.9, 127.9, 127.3, 121.2, 120.9, 116.1, 116.1, 116.0, 115.1, 109.7, 109.6, 108.6, 17.3, 14.1, 13.9,
13.3, 9.4. HRMS (APCI) calcd. for C18H18BBrFN2O [M-F]+ 387.0680, found 387.0682.
Intermediates 5a, 5b and 5c from BODIPYs 2 and Pd(PPh3)4.
Syntheses of BODIPY 5a: To a dry round-bottom flask loaded with compound 2a (0.05 mmol, 31
mg) and Pd(PPh3)4 (0.05 mmol, 55.0 mg) were added toluene (5.0 mL). Freeze-pump-thaw cycle
was carried out three times. After that, the mixture was heated to 60 oC under argon and stirred for 8
h. After cooling to room temperature, the mixture was evaporated under vacuum. The residue was
purified through column chromatography (silica, petroleum ether/ethyl acetate = 2/1, v/v) to afford 6
as orange crystals in 81% yield (51 mg). mp 162-164 ℃. 1H NMR (300 MHz, CDCl3) δ 7.81 (s,
13H), 7.33 (s, 17H), 6.80 (s, 2H), 6.04 (s, 1H), 5.85 (s, 1H), 2.26 (s, 3H), 1.87 (s, 6H). HRMS (APCI)
+
calcd. for C54H43BBr3F2N2P2Pd [M-Br] : 1176. 9507, found 1176.9525.
BODIPY 5b was obtained as purple crystals in 60% yield (31 mg) using the above method from
1
compound 2a (0.03 mmol, 18 mg) and Pd(PPh3)4 (0.06 mmol, 66 mg). mp 243-244 ℃. H NMR
(300 MHz, CDCl3) δ 8.07 – 8.15 (s, 15H), 7.44 (s, 18H), 7.26 – 7.29 (m, 7H), 6.89 (s, 5H), 6.79 (s,
2H), 6.70 (s, 8H), 6.49 (s, 7H), 5.58 (s, 2H), 2.26 (s, 3H), 1.95 (s, 6H). HRMS calcd. for
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C54H43BBr3F2N2P2Pd [M-Pd(PPh3)2Br] : 1176.9507, found 1176.9490. HRMS (APCI) calcd. for
5
6
7
+
C54H44BBr2F2N2P2Pd [M-Pd(PPh3)2-2Br+H] : 1097.0422, found 1097.0422.
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BODIPY 5c was obtained as orange crystals in 65% yield (47 mg) using the above method from
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compound 2c (0.05 mmol, 20 mg) and Pd(PPh3)4 (0.05 mmol, 55 mg). mp 228-230 ℃. H NMR
(300 MHz, CDCl3) δ 7.71 (s, 13H), 7.28 (s, 17H), 6.33 (s, 1H), 5.82 (s, 1H), 2.27 – 2.35 (m, 5H),
+
2.04 (s, 3H), 1.02 (t, J = 7.5 Hz, 3H). HRMS (APCI) calcd. for C49H42BBr2F2N2P2Pd [M-H] :
1035.0265, found 1035.0267.
The Suzuki coupling reaction for 4e catalyzed by BODIPY 5c. To a dry round-bottom flask
loaded with compound 2c (0.28 mmol, 112 mg), BODIPY 5c (5 mg, 0.0048 mmol),
(4-tert-butylphenyl)boronic acid (0.4 mmol, 60 mg), Na2CO3 (0.6 mmol, 63 mg) were added
toluene (5 mL). Freeze-pump-thaw cycle was carried out three times. After that, the mixture was
o
heated to 80 C under argon and stirred for 15 h. After cooling to room temperature, the reaction
mixture was extracted with CH2Cl2 and dried over anhydrous Na2SO4. The organic layers were
combined and evaporated under vacuum. The residue was purified through column
chromatography (silica, petroleum ether/ethyl acetate = 5/1, v/v) to afford purple powder 4e in
41% yield (53 mg). mp 196-198 ℃. 1H NMR (300 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 7.47
(d, J = 8.3 Hz, 2H), 7.03 (s, 1H), 6.94 (s, 1H), 2.49 (s, 3H), 2.39 (q, J = 7.6 Hz, 2H), 2.19 (s, 3H),
1.37 (s, 9H), 1.07 (t, J = 7.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 163.9, 151.8, 150.2, 140.7,
136.0, 135.3, 131.9, 130.1, 128.1, 126.3, 125.2, 124.6, 122.1, 34.8, 31.3, 17.3, 14.1, 13.4, 9.4.
HRMS (APCI) calcd. for C23H26BBrFN2 [M-F]+ 439.1356, found 439.1346.
The Suzuki coupling reaction for 6a from BODIPY 5a. To a dry round-bottom flask loaded
with compound 5a (0.02 mmol 25 mg), (4-methoxyphenyl)boronic acid (0.1 mmol, 15 mg),
Na2CO3 (0.04 mmol, 4 mg) were added toluene (5 mL). Freeze-pump-thaw cycle was carried out
o
three times. After that, the mixture was heated to 80 C under argon and stirred for 8 h. After
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cooling to room temperature, the reaction mixture was extracted with CH2Cl2 and dried over
anhydrous Na2SO4. The organic layers were combined and evaporated under vacuum. The residue
was purified through column chromatography (silica, petroleum ether/ethyl acetate = 6/1, v/v) to
afford purple powder in 92% yield (17 mg). mp 264-265 ℃. 1H NMR (300 MHz, CDCl3) δ 7.47
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(d, J = 7.9 Hz, 4H), 7.00 (s, 2H), 6.91 (d, J = 8.0 Hz, 4H), 6.85 (d, J = 7.9 Hz, 4H), 6.69 (d, J = 7.9
13
Hz, 4H), 6.64 (s, 2H), 3.82 (s, 6H), 3.74 (s, 6H), 2.39 (s, 6H), 2.29 (s, 6H). C NMR (75 MHz,
CDCl3) δ 160.1, 158.5, 155.8, 141.9, 138.5, 137.0, 134.7, 134.1, 132.1, 130.6, 129.5, 128.2, 126.7,
126.1, 124.4, 113.6, 113.4, 55.2, 55.1, 21.2, 20.3. HRMS (APCI) calcd. for C46H42BF2N2O4
[M+H]+ 735.3206, found 735.3197.
The Stille coupling reaction
Syntheses of BODIPY 3a: To a dry round-bottom flask loaded with compound 2a (0.1 mmol, 62
mg), 2-(tributylstannyl)thiophene (0.2 mmol, 75 mg) and Pd(PPh3)4 (0.01 mmol, 11 mg) were
added toluene (6 mL). Freeze-pump-thaw cycle was carried out three times. After that, the mixture
was heated to 80
under argon and stirred for 14 h. After cooling to room temperature, the
reaction mixture was extracted with CH2Cl2 and dried over anhydrous Na2SO4. The organic layers
were combined and evaporated under vacuum. The residue was purified through column
chromatography (silica, petroleum ether/dichloromethane = 4/1, v/v) to afford 3a as a brown solid
in 41% yield (26 mg).
BODIPY 3b was obtained as brown solids in 43% yield (25 mg) using the above method from
compound 2b (0.1 mmol, 58 mg), 2-(tributylstannyl)thiophene (0.2 mmol, 75 mg) and Pd(PPh3)4
(0.01 mmol, 11 mg).
BODIPY 6b was obtained as brown crystals in 49% yield (31 mg) using the above method at 90
from compound 2a (0.1 mmol, 62 mg), 2-(tributylstannyl)thiophene (0.4 mmol, 149 mg) and
1
Pd(PPh3)4 (0.015 mmol, 16 mg). mp 267-268 ℃. H NMR (500 MHz, CDCl3) δ 7.55 (d, J = 3.6
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Hz, 2H), 7.50 (d, J = 5.0 Hz, 2H), 7.17 (d, J = 5.0, Hz, 2H), 7.10 (d, J = 5.0 Hz, 2H), 7.01 (s, 2H),
5
6
13
6.89 (d, J = 5.0 Hz, 2H), 6.72 (d, J = 3.6 Hz, 2H), 6.69 (s, 2H), 2.40 (s, 3H), 2.26 (s, 6H). C
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NMR (126 MHz, CDCl3) δ 149.0, 143.5, 138.9, 136.8, 135.3, 135.2, 132.3, 130.9, 129.8, 129.6,
129.1, 128.3, 127.2, 127.2, 126.4, 126.3, 125.5, 21.2, 20.3. HRMS (APCI) calcd. for
C34H26BF2N2S4 [M+H]+ 639.1035, found 639.1023.
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BODIPY 6c was obained as brown crystals in 46% yield (27 mg) using the above method at 90
from compound 2b (0.1 mmol, 58 mg), 2-(tributylstannyl)thiophene and (0.4 mmol, 149 mg) and
Pd(PPh3)4 (0.015 mmol, 16 mg). mp 253-255℃. 1H NMR (300 MHz, CDCl3) δ 7.62 (m, 5H), 7.55
(d, J = 3.3 Hz, 2H), 7.53 – 7.48 (m, 2H), 7.20 (d, J = 5.1 Hz, 2H), 7.11 (dd, J = 6 Hz, 2H), 6.95 (s,
2H), 6.92 (d, J = 5.0 Hz, 2H), 6.76 (d, J = 3.5 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 164.3,
159.8, 149.1, 143.4, 135.2, 135.1, 133.9, 132.3, 130.9, 130.6. HRMS (APCI) calcd. for
C31H20BF2N2S4 [M+H]+ 597.0565, found 597.0562.
BODIPY 4f was obtained as brown solids in 43% yield (41 mg) using the above method at 80 ℃
from compound 2d (0.2 mmol, 92 mg), 2-(tributylstannyl)thiophene (0.2 mmol, 75 mg) and
Pd(PPh3)4 (0.02 mmol, 22 mg). mp 189-191 ℃. 1H NMR (300 MHz, CDCl3) δ 7.50 (d, J = 6.0 Hz,
1H), 7.31 (d, 3.0 Hz, 1H), 7.22 (s, 1H), 7.20 (brs,, 1H), 2.60 (s, 3H), 2.42 (q, J = 8.0 Hz, 2H), 2.17
(s, 3H), 1.09 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 165.7, 141.7, 137.1, 136.2, 132.3,
128.7, 127.8, 127.6, 124.6, 120.3, 114.1, 106.7, 17.3, 14.0, 13.5, 9.5. HRMS (APCI) calcd. for
C17H16BBrF2N2S [M-Br+H]+ 408.0279, found 408.0299.
The Suzuki coupling reaction
Syntheses of BODIPY 3e: To a dry round-bottom flask loaded with compound 2a (0.1 mmol, 62
mg), (4-methoxyphenyl)boronic acid (0.2 mmol, 30 mg), Na2CO3 (5 mml, 1 M) and Pd(PPh3)4
(0.01 mmol, 11 mg) were added toluene (5 mL). Freeze-pump-thaw cycle was carried out three
o
times. After that, the mixture was heated to 80 C under argon and stirred for 10 h. After cooling
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to room temperature, the reaction mixture was extracted with CH2Cl2 and dried over anhydrous
Na2SO4. The organic layers were combined and evaporated under vacuum. The residue was
purified through column chromatography (silica, petroleum ether/ethyl acetate = 4/1, v/v) to afford
3e as a blackish green crystal in 45% yield (31 mg). mp 247-248 ℃. 1H NMR (300 MHz, CDCl3)
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δ 7.64 (d, J = 8.7 Hz, 4H), 7.01 – 6.92 (m, 6H), 6.74 (s, 2H), 3.83 (s, 6H), 2.38 (s, 3H), 2.21 (s,
6H). 13C NMR (126 MHz, CDCl3) δ 160.8, 156.0, 143.0, 139.1, 136.7, 134.4, 131.98, 130.1, 129.3,
128.3, 122.3, 113.4, 109.5, 55.2, 21.2, 20.2. HRMS (APCI) calcd. for C32H28BF2N2O2Br2 [M+H]+
681.0553, found 681.0554.
BODIPY 6a was obtained as fuchsia solids in 76% yield (55 mg) using the above method from
compound 2a (0.1 mmol, 62 mg), (4-methoxyphenyl)boronic acid (0.5 mmol, 76 mg), Na2CO3 (5
1
mml, 1 M) and Pd(PPh3)4 (0.01 mmol, 11 mg). mp > 250 ℃ H NMR (300 MHz, CDCl3) δ 7.47
(d, J = 7.9 Hz, 4H), 7.00 (s, 2H), 6.91 (d, J = 8.0 Hz, 4H), 6.85 (d, J = 7.9 Hz, 4H), 6.69 (d, J = 7.9
13
Hz, 4H), 6.64 (s, 2H), 3.82 (s, 6H), 3.74 (s, 6H), 2.39 (s, 6H), 2.29 (s, 6H). C NMR (75 MHz,
CDCl3) δ 160.1, 158.5, 155.8, 141.9, 138.5, 137.0, 134.7, 134.1, 132.1, 130.6, 129.5, 128.2, 126.7,
126.1, 124.4, 113.6, 113.4, 55.2, 55.1, 21.2, 20.3. HRMS (APCI) calcd. for C46H42BF2N2O4
[M+H]+ 735.3206, found 735.3197.
BODIPY 6d was obtained as fuchsia solids in 78% yield (60 mg) using the above method from
compound 3e (0.1 mmol, 68 mg), (4-tert-butylphenyl)boronic acid (0.3 mmol, 45 mg), Na2CO3 (3
mml, 1 M) and Pd(PPh3)4 (0.01 mmol, 11 mg). mp > 300 ℃. 1H NMR (500 MHz, CDCl3) δ 7.49
(d, J = 5.0 Hz, 4H), 7.15 (d, J = 10.0 Hz, 4H), 6.99 (s, 2H), 6.92 (d, J = 10.0 Hz, 4H), 6.86 (d, J =
13
5.0 Hz, 4H), 6.69 (s, 2H), 3.83 (s, 6H), 2.39 (s, 3H), 2.27 (s, 6H), 1.24 (s, 18H). C NMR (125
MHz, CDCl3) δ 160.1, 156.0, 149.7, 138.5, 137.0, 134.8, 134.2, 132.1, 131.2, 128.1, 127.8, 126.7,
125.0, 124.4, 113.4, 55.2, 34.4, 31.3, 21.2, 20.3. HRMS (APCI) calcd. for C52H53BFN2O2 [M-F]+
767.4184, found 767.4190.
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