Direct C-H functionalization of difluoroboron dipyrromethenes (BODIPYs) at β-position by iodonium salts

Article abstract of DOI:10.1039/c7ra13070h

A copper-catalyzed direct C-H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed, which provides facile access to a variety of mono-substituted BODIPY dyes. Interestingly, β-styryl BODIPY compound 9b exhibits apparent cytotoxicity after laser irradiation, which has great potential for photodynamic therapy.

Full text of DOI:10.1039/c7ra13070h

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PAPER
Direct C–H functionalization of difluoroboron
dipyrromethenes (BODIPYs) at b-position by
iodonium salts†
Cite this: RSC Adv., 2018, 8, 5542
Wenming Ren,‡a Huaijiang Xiang,‡b Chengyuan Peng,a Zulipali Musha,ac
b
ac
ac
Jingjing Chen,ac Xin Li,
Ruimin Huang
and Youhong Hu
*
*
Received 5th December 2017
Accepted 27th January 2018
A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the b-position by iodonium salts has
been developed, which provides facile access to a variety of mono-substituted BODIPY dyes. Interestingly,
b-styryl BODIPY compound 9b exhibits apparent cytotoxicity after laser irradiation, which has great
potential for photodynamic therapy.
DOI: 10.1039/c7ra13070h
rsc.li/rsc-advances
Burgess and coworkers reported a few examples of palladium-
catalyzed C–H Heck-type alkenylation at the b-position in 5
days convertion.7 You and coworkers reported decarbox-
Introduction
Diuoroboron dipyrromethenes (BODIPYs) and their deriva-
tives are most widely used as small molecule organic uo-
rophores due to its excellent features, such as high
uorescence quantum yield, narrow emission bandwidth
with high peak intensity, good biocompatibility and high
photophysical stability.1 Modication of the BODIPY frame-
work can tune for their uorescence prole and functionality
for the specic application such as bio-imaging and photo-
dynamic therapy (PDT).2 Besides the meso-derivation for
chemosensors, the extension of BODIPY core by the conju-
gated groups at the a- or b-position of could lead the advan-
tage of red-shied emission band and large Stokes shi.1a,3
Introducing diverse functional groups based on the BODIPY
directly is an efficient way to avoid the use of unstable
intermediate and multiple-steps processes from pyrroles.
Traditionally, the installation of functional conjugated
groups has been proceeded by the coupling reaction from
halogenated BODIPY or the condensation from active carbon
(methyl group at a-position and formyl group at b-position).3,4
Direct C–H functionalization of BODIPY chromophores has
become an attractive alternative due to the economy and
efficiency.5 Several groups successfully developed the C–H a-
arylation of BODIPYs from the different aryl sources.6
However, the conjugated b-derivation is rarely explored.
ylative C–H arylation at the b-position from specic ortho-
substituted ben-zoic acids in the harsh conditions to obtain
the mono-and disubstituted products.8 Herein, we report
a direct C–H arylation or vinylation method for BODIPY
postmodication by iodonium salts at the b-position for the
mono-substitution as the major product, which could fur-
therly result the diversity at a- and b-positions of the BODIPYs
(Scheme 1).
aState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese
Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. E-mail: yhhu@
simm.ac.cn; rmhuang@simm.ac.cn
bCollege of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road,
Hangzhou 310058, China
cUniversity of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 110039, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c7ra13070h
‡ These authors contributed equally.
Scheme 1 Direct arylation or vinylation of BODIPY at b-position.
5542 | RSC Adv., 2018, 8, 5542–5549
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Table
1
Optimization of reaction conditions for b-arylation of
Results and discussion
BODIPYa
Diaryliodonium salts as highly reactive species have been widely
applied to versatile arylation reaction.9 Direct a-selective arylation
of BODIPYs by diaryliodonium salts could be smoothly pro-
ceeded through radical reaction pathway with metal free.6c Since
the b-position of the BODIPY is also potentially electron rich,10 we
hypothesized the direct b-arylation of BODIPYs using diary-
liodonium salt could be proceed by blocking the active a-position
(Scheme 2). We selected the readily available pentamethyl-
substituted BODIPY 1 to investigate the b-arylation reaction
since the methyl group could block the active a-position and be
easily functionalized further. Under the metal-free conditions
reported previously,6c the reaction of BODIPY 1 with diary-
liodonium triates 2a did not happen. Since diaryliodonium salt
could behave as a highly activated aromatic electrophile by Cu
catalyst,11,12 the reaction was carried out in the presence of copper
triuoromethanesulfonate (Cu(OTf)2, 0.1 equiv.) and 2,6-di-tert-
Yieldb (%)
Entry
Solvent
Base
X
3a
4a
ꢀ
butylpyridine (DTBP, 1.2 equiv.) as base in DCM at 70 C for 6
1
2
3
4
5
6
7
8
DCM
DCE
Toluene
1,4-Dioxane
DCM : toluene ¼ 1 : 1
DCM : toluene ¼ 3 : 1
DCM : toluene ¼ 5 : 1
DCM : toluene ¼ 3 : 1
DCM : toluene ¼ 3 : 1
DCM : toluene ¼ 3 : 1
DCM : toluene ¼ 3 : 1
DCM : toluene ¼ 3 : 1
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
—
NaHCO3
DTBP
DTBP
DTBP
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
PF6
Cl
48
43
18
8
6
8
5
—
hours. As expected, the desired mono-arylated product 3a was
obtained in 48% yield with an excellent selectivity. Among the
different solvents (Table 1, entries 1–4), the DCM is best. By the
detailed analysis of the reaction, we found that de-boron
diuoride byproduct was mainly formed in DCM and the start-
ing material 1 could be easily recovered in toluene. Since the
acidic conditions might cause the deboronation of the BODIPY,13
we tried to the mixture solvents of DCM and toluene. The co-
solvents (DCM : toluene ¼ 3 : 1) gave the best yield of 3a with
high selective ratio (ꢁ10 : 1) with the recovered starting material
1. Without base or with inorganic base, the reaction didn't give
the satised results (Table 1, entries 8, 9). In addition, counter
anions of diaryliodonium such as PF6 or Cl were tested (Table 2,
entries 10, 11). The results uncovered the observation that
electron-withdrawing counter anion PF6 afforded the similar
yield and selectivity as OTf. By increasing the equivalents of
iodonium triate salt to 2.4, mono-arylated 3a and diarylated 4a
were obtained in 21% and 50%, respectively.
38
53
39
15
15
52
—
21
4
5
4
3
7
5
—
50
9
10
11
12c
OTf
a
Reaction condition: 1 (0.24 mmol), 2a (0.20 mmol), solvent (2 mL),
Cu(OTf)2 (0.02 mmol), base (0.24 mmol), 70 ꢀC, 6 h, sealed tube under
b
c
N2. Isolated yields. 1 (0.20 mmol), 2a (0.48 mmol), solvent (3 mL),
Cu(OTf)2 (0.04 mmol), base (0.48 mmol), 70 ꢀC, 6 h, sealed tube under N2.
To explore the phenyl substituent scope for this novel Cu(II)-
catalyzed C–H arylation process, various asymmetrical diaryl-
iodonium triates 2 were evaluated to react with 1 under the
optimized conditions (Scheme 3). Gerenally, the results showed
that both electron-withdrawing and electron-donating
substituted diaryliodonium triates 2 were suitable to this
reaction, and desired products 3 were obtained in modest yields
with good selectivity by using the 0.8 equiv. of 2 (condition A).
Unfortunately, methyl group at ortho-position didn't form the
desired product due to the probable steric hindrance of diary-
liodonium salt (Scheme 3, compound 3d). Signicantly, the
bromo substituted diaryliodonium triates performed well
under this reaction conditions, producing compounds 3j and
3k, which could be further modied by coupling reactions.
Increasing the amount of diaryliodonium triates 2 to 2.4
equivalent (condition B), the overall yields of 3 and 4 could be
improved with less selectivity. Since the resultant mono-
substituted BODIPYs could be arylated by the different diary-
liodonium triates to generate the diversity, we applied
compound 3e (Scheme 4A) as the substrate with para-methox-
ycarbonyl group as electron-donor to react with substituted
diaryliodonium triate 2g with electron-acceptor. As expected,
Scheme
2 The possible reaction mechanism for b-arylation of
BODIPY.
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Table 2 Photophysical properties of BODIPY dyes in CH3CN at room temperature
3 (Mꢂ1 cmꢂ1
)
lexb (nm)
lemb (nm)
FF
Stokes shi (nm)
a
a,c
Dyes
labs (nm)
1
492
503
504
504
504
501
504
502
503
502
502
519
509
83 400
86 500
79 500
35 200
78 700
72 000
83 100
81 600
69 600
80 300
85 100
65 400
65 400
491
502
503
503
504
501
502
502
502
502
501
517
510
504
529
535
530
551
523
527
527
527
530
525
574
534
0.98
0.71
0.70
0.78
0.24
0.86
0.91
0.70
0.66
0.77
0.80
0.41
0.67
13
27
32
27
47
22
25
25
25
28
24
57
24
3a
3b
3c
3e
3f
3g
3h
3i
3j
3k
5
7
a
Data were measured in a concentration of 3.0 ꢃ 10ꢂ6 M. b Data were measured in a concentration of 5.0 ꢃ 10ꢂ6 M. c All uorescence quantum
yields (F) were calculated using uorescein in 0.1 N NaOH solution (F ¼ 0.91, excitation ¼ 488 nm) as the standard except 4l using Rhodamine 6G in
anhydrous ethanol (F ¼ 0.95, excitation ¼ 530 nm) as the standard.
the asymmetrical diarylated BODIPY 5 containing D–p–A
(donor–p–acceptor) structure was obtained in 52% yield. In
addition, meso-phenyl BODIPY 6 could react with diary-
liodonium 2a (Scheme 4B) under the condition A to achieve
product 7 in 46% yield.
The photophysical properties of 3a–3k, 5 and 7 were evalu-
ated in different solvents system (Table 2, Fig. S1–5†). As shown
in Table 2, 2-aryl BODIPYs 3a–3k exhibited the absorption
maxima and excitation maxima among 501–504 nm no matter
electron-withdrawing or electron-donating substituents. All 2-
aryl BODIPYs showed high absorption coefficients and relatively
high uorescence quantum yields. Methoxyl substituent 3e
showed a lower uorescence quantum yield (ꢁ24%) corre-
spondingly. On the other hand, 3e exhibited the longest emis-
sion maxima at 551 nm and the largest stokes shi (47 nm)
among 2-aryl BODIPYs. These data indicate that slight modi-
cation of BODIPY could change their photophysical property
signicantly. The asymmetrical diarylated BODIPY 5 containing
D–p–A has the desired properties with red uorescence, high
quantum yield and large Stokes shi.
Next, we explored the reaction of BODIPY 1 with the variety
of styryliodonium triates 8 to generate the different conjugated
Scheme 3 Direct C–H arylation of BODIPY 1 with different diary-
liodonium triflates.a Condition A: 0.8 equiv. of 2 was used; b condition
B: 2.4 equiv. of 2 was used; cisolated yield.
Scheme 4 Extension for b-arylation of BODIPY.
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Fig. 1 Light irradiation (IR)-induced cytotoxicity by compound 9b in
MDA-MB-231 and A-431 cells using SRB assay. *P < 0.0001.
Scheme 5 Scope of the direct C–H vinylation of BODIPY 1 with
different vinyliodonium triflates.aIsolated yield.
systems. Due to the higher reactivity of vinyliodonium than
aryliodonium salts,12b the reaction temperature at 50 ꢀC gave the
ꢀ
similar efficiency at 70 C. To our delight, the different 2-styryl
BODIPYs 9a–9e were delivered (Scheme 5). Additionally, alkyl
vinyliodonium triates can also be successfully applied in this
reaction, maintaining 51% yield of 2-vinyl BODIPY 9f.
Fig. 2 Overlay of fluorescent and differential interference contrast
(DIC) images of MDA-MB-231 cells incubated with of compound 9b or
vehicle control. Blue circles, laser irradiated regions; grey boxes,
regions very near the laser-irradiated areas. Scale bars, 50 mm.
Photophysical properties of 9a–9f were investigated as
shown in Table 3. The 2-vinyl BODIPYs 9 exhibited emission
maxima up to 598–620 nm with large stokes shis. Probably due
to the geometry relaxation of uorophores upon photoexcita-
tion, the quantum yields of those dyes were as low as 0.78%. Dye
with photoproperties such as high extinction coefficient, low
quantum yield and red emission could be used as photosensi-
tizer for photodynamic therapy.2a,2d The BODIPY 9b was thus
chosen to evaluate photocytotoxic activity in vitro. The half
maximal inhibitory concentration (IC50) of compound 9b with
or without light irradiation was assessed in human breast
cancer cell line MDA-MB-231 and epidermoid carcinoma cell
line A-431. Nine different concentrations (ranging from 0.195 to
50 mM) of 9b were applied to cells and 12 h exposure to mercury
lamp decreased the cell viability signicantly in presence of 9b
(P < 0.0001) in both cells (Fig. 1). For example, light irradiation
reduced the IC50 value from 43.9 mM to 4.0 mM (ꢁ88% decline)
in MDA-MB-231 cells. Photophysical property and laser-induced
cytotoxicity of compound 9b were also characterized and visu-
alized by a Leica confocal microscopy. As shown in Fig. 2 and
S7,† high uorescence signals were detected in cytoplasm
within 5 min aer 9b (2.5 mM) feeding. Then the photothermal
treatment was performed by continuous irradiation of the cells
using a 552 nm laser for 10 min, leading to a ꢁ200 mm diameter
irradiation spot. Cell blebbing, a characteristic feature of
injured cells, was only observed in compound 9b-treated cells
but not in the vehicle-treated cells. Similar photothermal effects
were exhibited in 9a- or 9f-treated cells (Fig. S7†). These results
suggest that 2-vinyl BODIPYs could be excellent photosensi-
tizers and have potential for photodynamic therapy of cancer.
Table 3 Photophysical properties of BODIPY dyes in CH3CN at room temperature
3 (Mꢂ1 cmꢂ1
)
lexb (nm)
lemb (nm)
FF
Stokes shi (nm)
a
a,c
Dyes
labs (nm)
9a
9b
9c
9d
9e
9f
523
520
522
520
523
511
50 100
38 100
52 400
70 600
47 700
43 100
517
519
505
518
521
535
608
620
600
610
607
598
0.0080
0.0078
0.0091
0.011
0.010
0.063
91
101
95
92
86
63
a
Data were measured in a concentration of 3.0 ꢃ 10ꢂ6 M. b Data were measured in a concentration of 5.0 ꢃ 10ꢂ6 M. c The uorescence quantum
yields (F) were calculated using rhodamine 6G in anhydrous ethanol (F ¼ 0.95, excitation ¼ 530 nm).
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300 : 100 : 5) to afford crude product. Single and double
substituted products were validated by 400 MHz or 500 MHz
Bruker NMR spectrometer. The residue was puried by TLC silica
gel plate (10 ꢃ 200 ꢃ 200 mm, 10–40 mm, separating solvent and
ratio: dichloromethane/toluene ¼ 1/5) or reversed phase chroma-
tography (separating solvent and ratio: H2O/MeOH ¼ 15/85 to 5/
95) to afford pure products 3a–k, 5, 7 and 9a–g. The yield data
was calculated by diaryliodonium stoichiometric equivalence.
Conclusions
In conclusion, we have developed the Cu-catalyzed direct C–H
arylation and vinylation of BODIPYs at the b-position. This meth-
odology provides a convenient synthetic procedure to prepare
diversied BODIPY derivatives. These reactions exhibited good
selectivity for mono-substituted product to allow the different
modication of BODIPY at 2,6-position. Through the evaluation of
photophysical properties of those dyes, 2-styryl BODIPYs showed
intrinsic large Stokes shi up to 101 nm and low quantum yield,
suggesting the potential for photodynamic therapy of cancer. In
this way, the novel functionality of uorophores with asymmetrical
substitution can be synthesized economically and efficiently.
General procedure for the Cu(II)-catalyzed diarylation of
BODIPYs (reaction condition B)
Copper(II) triuoromethanesulfonate (14.5 mg, 0.04 mmol) was
adequately suspended in 3 mL mixture solution in 10 mL sealed
tube, then 1 (52.4 mg, 0.20 mmol), appropriate diaryliodonium
salt (0.48 mmol) and 2,6-di-tert-butylpyridine (109 mL, 0.48
mmol) were sequentially added to the solution. Seal up the tube
with argon atmosphere. The purication procedures were the
same with reaction condition A to afford 4a–4k. The yield data
was calculated by BODIPY 1 stoichiometric equivalence.
Experimental
General
All reactions were carried out under an atmosphere of argon in
oven-dried glassware with magnetic stirring. All commercially
available reagents were used as received. Chromatographic puri-
cations were performed by ash chromatography with silica gel
(40–63 mm) packed in glass columns. The eluting solvent for the
purication of each compound was determined by thin-layer
chromatography (TLC) on glass plates coated with silica gel 60
Cell viability assay for photocytotoxic effect
Cells were seeded in 96-well plates at a density of 1600–3000
cells per well in triplicate. Twenty-four hours later, the cells were
incubated with fresh medium with compounds at different
concentrations (ranging from 0.195 to 50 mM). The cells were
exposed under the mercury lamp (HXP R120W/45C; Osram,
Germany) for 12 h, and then were kept under normal culture
condition for another 72 h. At the endpoint, the cells were xed
with 10% pre-cooled trichloroacetic acid (Sigma, St Louis, MO,
USA) over 4 h followed by staining with 4 mg mLꢂ1 sulforhod-
amine B (SRB; Sigma) in 1% acetic acid for 15 min. SRB in the
cells was dissolved in 10 mmol Lꢂ1, Tris–HCl and measured at
560 nm using a microplate reader (SpectraMAX190; Molecular
Devices, Sunnyvale, CA, USA). The half maximal inhibitory
concentration (IC50) was decided using (log(inhibitor) vs.
response – variable slope (four parameters)) method in the
GraphPad Prism Soware. The data were presented as the mean
ꢄ SD. Differences were considered statistically signicant at P <
0.0001 by 2 way ANOVA test.
1
F254 and visualized by UV light (254 nm or 365 nM). H NMR
spectra and proton-decoupled 13C NMR spectra were obtained on
1
a 400 MHz or 500 MHz Bruker NMR spectrometer. H chemical
shis (d) are reported in parts per million (ppm) relative to TMS (s,
d 0). 13C NMR chemical shis are reported relative to CDCl3 (t,
d 77.4). High-resolution mass data were obtained on an Agilent
6224 accurate-mass TOF LC/MS (ESI). Absorption spectra were
acquired using a Varian Cary 300 spectrophotometer. Fluores-
cence measurements were carried out on a Horiba FluoroMax-4
spectrometer. Quantum yields were determined in reference to
either uorescein or rhodamine 6G and corrected for solvent
refractive index. The extinction coefficients were determined
through Beer's law plots. All data were measured at room
temperature. Human breast cancer cell line MDA-MB-231 and
human epidermoid carcinoma cell line A-431 were obtained from
the American Type Culture Collection (Manassas, VA, USA) and
were cultured in DMEM (high glucose) and RPMI 1640 medium
respectively, supplemented with 10% fetal bovine serum (Hyclone,
Logan, UT). Cells were incubated at 37 ꢀC in 5% CO2 in air.
Visualization of laser-induced cytotoxicity
Cells were grown on the 8-well chambered coverglass (Thermo
Fisher Scientic, Waltham, MA, USA) for 36 h. Immediately aer
adding the compound with indicated concentrations to cells,
a small region of interest (ROI) was randomly chosen and irra-
diated using the laser line at 552 nm from a confocal microscopy
General procedure for the Cu(II)-catalyzed mono-arylation or
vinylation of BODIPYs (reaction condition A)
Copper(II) triuoromethanesulfonate (7.23 mg, 0.02 mmol) was (Leica TCS SP8 STED, Germany) over 10 min. During that period,
adequately suspended in mL mixture solution the uorescent and differential interference contrast (DIC)
2
ꢀ
(dichloromethane/toluene ¼ 3/1, dried by 4 A molecular sieves) in images were acquired at 0 min, 5 min and 10 min, respectively.
10 mL sealed tube, then 1 (62.91 mg, 0.24 mmol), appropriate The power of the laser was kept at 80% output to ensure the
diaryliodonium salt (0.2 mmol) and 2,6-di-tert-butylpyridine (54 consistent irradiation between experiments.
mL, 0.24 mmol) were sequentially added to the solution. Seal up the
5,5-Diuoro-1,3,7,9,10-pentamethyl-2-phenyl-5H-5l,6l-dipyr-
tube with argon atmosphere. The resulting solution was stirred at rolo[1,2-c:20,10-f][1,3,2]diazaborinine(3a). An orange solid (yield:
50 ꢀC (R ¼ styryl) or 70 ꢀC (R ¼ aryl group) for 6 h. The solution was 35.9 mg, 53%, single substitute: double substitute ¼ 91 : 9), 1H
concentrated and puried by silica gel column chromatography NMR (400 MHz, CDCl3) d 7.43 (t, J ¼ 7.5 Hz, 2H), 7.34 (t, J ¼
(hexane: dichloromethane: acetic ether
¼
300 : 100 : 0 to 7.5 Hz, 1H), 7.21 (d, J ¼ 6.9 Hz, 2H), 6.08 (s, 1H), 2.65 (s, 3H),
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2.54 (s, 3H), 2.47 (s, 3H), 2.44 (s, 3H), 2.32 (s, 3H). 13C NMR (126 orange solid (yield: 29.3 mg, 41%, single substitute: double
MHz, CDCl3) d 153.8, 152.2, 141.6, 141.1, 137.0, 133.9, 133.5, substitute ¼ 95 : 5), 1H NMR (400 MHz, CDCl3) d 7.19–7.09 (m,
132.4, 131.9, 130.4, 128.4, 127.1, 121.4, 17.5, 16.8, 15.4, 14.5, 4H), 6.09 (s, 1H), 2.64 (s, 3H), 2.54 (s, 3H), 2.45 (s, 3H), 2.44 (s,
+
13.2. HRMS (ESI): m/z [M + H]+ calcd for C20H2211BF2N2 : 3H), 2.30 (s, 3H). 13C NMR (126 MHz, CDCl3) d 163.0, 161.1,
339.1839; found: 339.1841, D ¼ ꢂ0.66 ppm.
154.3, 151.7, 141.7, 141.4, 136.9, 132.5, 132.3, 132.0, 130.0,
5,5-Diuoro-1,3,7,9,10-pentamethyl-2-(p-tolyl)-5H-5l,6l-dipyr- 131.7, 129.8, 121.6, 115.5, 17.5, 16.8, 15.3, 14.5, 13.1. HRMS
rolo[1,2-c:20,10-f][1,3,2]diazaborinin (3b). An orange solid (yield: (ESI): m/z [M + H]+ calcd for C20H2211BF3N2+: 357.1744; found:
1
25.9 mg, 37%, single substitute: double substitute ¼ 93 : 7), H 357.1752, D ¼ ꢂ2.01 ppm.
NMR (400 MHz, CDCl3) d 7.24 (d, J ¼ 7.7 Hz, 2H), 7.10 (d, J ¼
2-(4-Chlorophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl-5H-
7.7 Hz, 2H), 6.07 (s, 1H), 2.64 (s, 3H), 2.54 (s, 3H), 2.47 (s, 3H), 5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinine (3i). An
2.43 (s, 3H), 2.41 (s, 3H), 2.32 (s, 3H). 13C NMR (126 MHz, CDCl3) orange solid (yield: 32.3 mg, 43%, single substitute: double
1
d 153.5, 152.4, 141.5, 140.8, 137.2, 136.8, 133.5, 132.3, 131.9, substitute ¼ 94 : 6), H NMR (400 MHz, CDCl3) d 7.40 (d, J ¼
130.8, 130.3, 129.1, 121.3, 21.3, 17.5, 16.8, 15.4, 14.5, 13.3. HRMS 8.3 Hz, 2H), 7.14 (d, J ¼ 8.3 Hz, 2H), 6.10 (s, 1H), 2.64 (s, 3H),
(ESI): m/z [M + H]+ calcd for C21H2411BF2N2 : 353.1995; found: 2.54 (s, 3H), 2.45 (s, 3H), 2.44 (s, 3H), 2.30 (s, 3H). 13C NMR
+
353.1998, D ¼ ꢂ0.78 ppm.
(126 MHz, CDCl3) d 154.5, 151.4, 141.8, 141.6, 136.7, 133.1,
5,5-Diuoro-1,3,7,9,10-pentamethyl-2-(m-tolyl)-5H-5l,6l-dipyr- 132.6, 132.4, 132.0, 131.7, 128.6, 121.7, 17.5, 16.8, 15.3, 14.5,
rolo[1,2-c:20,10-f][1,3,2]diazaborinine (3c). An orange solid (yield: 13.1. HRMS (ESI): m/z [M + H]+ calcd for C20H2111BClF2N2
:
+
1
24.2 mg, 34%, single substitute: double substitute ¼ 91 : 9), H 373.1449; found: 373.1452, D ¼ ꢂ0.33 ppm.
NMR (400 MHz, CDCl3) d 7.31 (t, J ¼ 7.5 Hz, 1H), 7.16 (d, J ¼
2-(4-Bromophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl-5H-
7.6 Hz, 1H), 7.00 (d, J ¼ 11.3 Hz, 2H), 6.08 (s, 1H), 2.65 (s, 3H), 5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2]diazaborinine (3j). An
2.54 (s, 3H), 2.47 (s, 3H), 2.44 (s, 3H), 2.40 (s, 3H), 2.32 (s, 3H). 13
C
orange solid (yield: 28.9 mg, 35%, single substitute: double
1
NMR (126 MHz, CDCl3) d 153.6, 152.4, 141.5, 140.8, 138.0, 137.1, substitute ¼ 93 : 7), H NMR (400 MHz, CDCl3) d 7.55 (d, J ¼
133.8, 132.3, 131.9, 131.0, 128.2, 127.9, 127.5, 121.3, 21.5, 17.4, 8.3 Hz, 2H), 7.07 (d, J ¼ 8.3 Hz, 2H), 6.09 (s, 1H), 2.63 (s, 3H),
16.8, 15.4, 14.5, 13.2. HRMS (ESI): m/z [M + H]+ calcd for 2.54 (s, 3H), 2.45 (s, 3H), 2.43 (s, 3H), 2.30 (s, 3H). 13C NMR
+
C21H2411BF2N2 : 353.1995; found: 353.1992, D ¼ 0.92 ppm.
(126 MHz, CDCl3) d 154.8, 151.5, 142.0, 141.9, 136.9, 133.1,
5,5-Diuoro-2-(4-methoxyphenyl)-1,3,7,9,10-pentamethyl- 132.9, 132.3, 131.9, 131.8, 122.0, 121.5, 17.7, 17.1, 15.5, 14.7,
5H-5l,6l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine (3e). An 13.3. HRMS (ESI): m/z [M + H]+ calcd for C20H2111BClF2N2
orange solid (yield: 36.9 mg, 50%, single substitute: double 373.1449; found: 373.1452, D ¼ ꢂ0.33 ppm.
:
+
substitute ¼ 86 : 14), 1H NMR (400 MHz, CDCl3) d 7.16–7.10 (m,
2-(3-Bromophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl-5H-
2H), 6.99–6.95 (m, 2H), 6.07 (s, 1H), 3.86 (s, 3H), 2.64 (s, 3H), 5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinine (3k). An
2.54 (s, 3H), 2.47 (s, 3H), 2.43 (s, 3H), 2.31 (s, 3H). 13C NMR (126 orange solid (yield: 29.3 mg, 35%, single substitute: double
MHz, CDCl3) d 158.7, 153.5, 152.6, 141.46, 140.8, 137.2, 133.3, substitute ¼ 90 : 10), 1H NMR (400 MHz, CDCl3) d 7.48 (d, J ¼
132.3, 131.9, 131.5, 126.0, 121.2, 113.9, 55.3, 17.4, 16.8, 15.4, 7.9 Hz, 1H), 7.37 (s, 1H), 7.30 (t, J ¼ 7.8 Hz, 1H), 7.14 (d, J ¼
14.5, 13.2. HRMS (ESI): m/z [M + H]+ calcd for [M + H]+ calcd for 7.5 Hz, 1H), 6.11 (s, 1H), 2.65 (s, 3H), 2.55 (s, 3H), 2.47 (s, 3H),
C
21H2411BF2N2O+: 369.1944; found: 369.1941, D ¼ 0.95 ppm.
2.45 (s, 3H), 2.32 (s, 3H). 13C NMR (126 MHz, CDCl3) d 154.8,
5,5-Diuoro-1,3,7,9,10-pentamethyl-2-(4-(triuoromethyl) 151.2, 141.9, 141.8, 136.7, 136.2, 133.3, 132.7, 131.8, 131.6,
phenyl)-5H-5l,6l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine 130.2, 129.9, 129.1, 122.4, 121.8, 17.5, 16.9, 15.3, 14.6, 13.1.
(3f). An orange solid (yield: 29.5 mg, 36%, single substitute: HRMS (ESI): m/z [M + H]+ calcd for C20H2111B79BrF2N2
double substitute ¼ 96 : 4), 1H NMR (400 MHz, CDCl3) d 7.69 (d, 417.0944; found: 417.943, D ¼ ꢂ0.28 ppm.
:
+
J ¼ 8.0 Hz, 2H), 7.33 (d, J ¼ 8.0 Hz, 2H), 6.12 (s, 1H), 2.66 (s, 3H),
5,5-Diuoro-1,3,7,9,10-pentamethyl-2,8-diphenyl-5H-4l,5l-
2.55 (s, 3H), 2.47 (s, 3H), 2.45 (s, 3H), 2.32 (s, 3H). 13C NMR (126 dipyrrolo[1,2-c:20,10-f][1,3,2]diazaborinine (4a). An orange
1
MHz, CDCl3) d 155.1, 150.8, 142.0, 141.9, 137.9, 136.5, 132.8, solid, (yield: 41.4 mg, 50%) H NMR (400 MHz, CDCl3) d 7.47
131.6, 130.7, 129.1, 128.7, 125.3, 123.1, 122.0, 17.5, 16.8, 15.3, (t, J ¼ 7.5 Hz, 4H), 7.38 (t, J ¼ 7.5 Hz, 2H), 7.26 (d, J ¼ 7.0 Hz,
+
14.5, 13.1. HRMS (ESI): m/z [M + H]+ calcd for C21H2111BF5N2 : 4H), 2.75 (s, 3H), 2.53 (s, 6H), 2.38 (s, 6H). 13C NMR (126 MHz,
407.1712; found: 407.1720, D ¼ ꢂ1.97 ppm.
CDCl3) d 152.4, 141.8, 137.1, 133.7, 132.2, 130.4, 128.4, 127.1,
Methyl4-(5,5-diuoro-1,3,7,9,10-pentamethyl-5H-5l,6l-dipyr- 17.3, 15.5, 13.3. HRMS (ESI): m/z [M + H]+ calcd for
rolo[1,2-c:20,10-f][1,3,2]diazaborinin-2-yl)benzoate
orange solid (yield: 44.4 mg, 56%, single substitute: double
(3g).
An
C
26H2611BF2N2+: 415.2152; found: 415.2153, D ¼ ꢂ0.4 ppm.
5,5-Diuoro-1,3,7,9,10-pentamethyl-2,8-di-p-tolyl-5H-4l,5l-
1
substitute ¼ 96 : 4), H NMR (400 MHz, CDCl3) d 8.10 (d, J ¼ dipyrrolo[1,2-c:20,10-f][1,3,2]diazaborinine (4b). An orange
8.1 Hz, 2H), 7.29 (d, J ¼ 8.1 Hz, 2H), 6.11 (s, 1H), 3.95 (s, 3H), solid, (yield: 15.2 mg, 17%) 1H NMR (400 MHz, CDCl3) d 7.25 (d, J
2.65 (s, 3H), 2.55 (s, 3H), 2.48 (s, 3H), 2.45 (s, 3H), 2.33 (s, 3H). ¼ 7.9 Hz, 5H), 7.11 (d, J ¼ 7.9 Hz, 4H), 2.70 (s, 3H), 2.49 (s, 6H),
13C NMR (126 MHz, CDCl3) d 167.0, 154.9, 151.0, 141.9, 139.0, 2.41 (s, 6H), 2.34 (s, 6H). 13C NMR (126 MHz, CDCl3) d 152.4,
136.6, 132.8, 132.1, 131.8, 130.4, 129.6, 128.8, 121.9, 52.2, 17.5, 141.5, 137.0, 136.8, 133.5, 132.2, 130.8, 130.3, 129.1, 77.3, 77.0,
16.9, 15.3, 14.5, 13.2. HRMS (ESI): m/z [M + H]+ calcd for 76.8, 29.7, 21.3, 17.2, 15.5, 13.3. HRMS (ESI): m/z [M + H]+ calcd
+
+
C
22H2411BF2N2O2 : 397.1893; found: 397.1882, D ¼ 2.91 ppm.
for C28H3011BF2N2 : 443.2465; found: 443.2461, D ¼ 0.86 ppm.
5,5-Diuoro-2-(4-uorophenyl)-1,3,7,9,10-pentamethyl-5H-
5,5-Diuoro-1,3,7,9,10-pentamethyl-2,8-di-m-tolyl-5H-4l,5l-
5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinine (3h). An dipyrrolo[1,2-c:20,10-f][1,3,2]diazaborinine (4c). An orange
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1
solid, (yield: 20.5 mg, 23%) 1H NMR (400 MHz, CDCl3) d 7.33 (t, orange solid, (yield: 22.3 mg, 20%) H NMR (400 MHz, CDCl3)
J ¼ 7.5 Hz, 2H), 7.17 (d, J ¼ 7.5 Hz, 2H), 7.05–7.00 (m, 4H), 2.71 d 7.54–7.50 (m, J ¼ 7.8 Hz, 2H), 7.41 (t, 2H), 7.34 (t, J ¼ 7.8 Hz,
(s, 3H), 2.49 (s, 6H), 2.41 (s, 6H), 2.35 (s, 6H). 13C NMR (126 2H), 7.19 (d, J ¼ 7.8 Hz, 2H), 2.74 (s, 3H), 2.51 (s, 6H), 2.37 (s,
MHz, CDCl3) d 152.3, 141.5, 137.9, 137.0, 133.7, 132.2, 131.0, 6H). 13C NMR (126 MHz, CDCl3) d 152.4, 142.3, 137.4, 136.0,
128.2, 127.8, 127.4, 21.5, 17.2, 15.5, 13.3. HRMS (ESI): m/z [M ꢂ 133.2, 132.3, 130.3, 130.0, 129.1, 122.5, 17.3, 15.5, 13.2. HRMS
F]+ calcd for C28H2911BFN2+: 423.2402; found: 423.2409, D ¼ (ESI): m/z [M ꢂ F]+ calcd for C26H2311B79Br2FN2+: 551.0300;
ꢂ1.64 ppm.
found: 551.0293, D ¼ ꢂ1.20 ppm.
5,5-Diuoro-2,8-bis(4-methoxyphenyl)-1,3,7,9,10-pentamethyl-
Methyl4-(5,5-diuoro-8-(4-methoxyphenyl)-1,3,7,9,10-pen-
5H-4l,5l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinine (4e). An tamethyl-5H-5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinin-
1
orange solid, (yield: 17.7 mg, 19%) H NMR (400 MHz, CDCl3) 2-yl)benzoate (5). An orange solid (second step's yield: 52%).
d 7.14 (d, J ¼ 8.7 Hz, 4H), 6.98 (d, J ¼ 8.7 Hz, 4H), 3.86 (s, 6H), 2.70 1H NMR (400 MHz, CDCl3) d 8.11 (d, J ¼ 7.3 Hz, 2H), 7.32 (d, J
(s, 3H), 2.48 (s, 6H), 2.33 (s, 6H). 13C NMR (126 MHz, CDCl3) ¼ 7.4 Hz, 2H), 7.14 (d, J ¼ 7.6 Hz, 2H), 6.99 (d, J ¼ 7.7 Hz, 2H),
d 158.7, 152.4, 141.4, 137.0, 133.2, 132.1, 131.5, 126.0, 113.9, 55.3, 3.95 (s, 3H), 3.86 (s, 3H), 2.72 (s, 3H), 2.50 (s, 6H), 2.35 (s, 6H).
17.2, 15.5, 13.3. HRMS (ESI): m/z [M
+
H]+ calcd for 13C NMR (126 MHz, CDCl3) d 166.6, 158.4, 153.6, 150.5, 141.4,
C28H2911BF2N2O2 : 455.2301; found: 455.2307, D ¼ ꢂ1.46 ppm.
138.6, 137.5, 135.9, 133.5, 132.2, 131.7, 131.6, 131.0, 130.0,
+
5,5-Diuoro-1,3,7,9,10-pentamethyl-2,8-bis(4-(triuoromethyl)- 129.2, 128.3, 125.3, 113.5, 54.9, 51.8, 16.9, 15.2, 15.0, 13.0,
phenyl)-5H-4l,5l-dipyrrolo[1,2-c:20,10-f] [1,3,2]diazaborinine (4f). 12.8. HRMS (ESI): m/z [M ꢂ F]+ calcd for C29H2911BFN2O3
:
+
An orange solid, (yield: 21.1 mg, 19%) 1H NMR (400 MHz, CDCl3) 483.2250; found: 483.2258, D ¼ 1.66 ppm.
d 7.71 (d, J ¼ 7.9 Hz, 4H), 7.36 (d, J ¼ 7.9 Hz, 4H), 2.74 (s, 3H), 2.50
5,5-Diuoro-1,3,7,9-tetramethyl-2,10-diphenyl-5H-5l,6l-dipyr-
(s, 6H), 2.36 (s, 6H). 13C NMR (126 MHz, CDCl3) d 152.4, 142.6, rolo[1,2-c:20,10-f][1,3,2]diazaborinine (7). An orange solid (yield:
137.6, 137.5, 132.4, 130.7, 129.5, 129.3, 125.4, 123.1, 17.4, 15.5, 37.0 mg, 46%), 1H NMR (400 MHz, CDCl3) d 7.55–7.48 (m, 3H),
13.3. HRMS (ESI): m/z [M ꢂ F]+ calcd for C28H2311BF7N2 : 7.40 (t, J ¼ 7.4 Hz, 2H), 7.37–7.29 (m, 3H), 7.19–7.15 (m, 2H), 6.03
+
531.1837; found: 531.1832, D ¼ 0.98 ppm.
(s, 1H), 2.61 (s, 3H), 2.55 (s, 3H), 1.41 (s, 3H), 1.32 (s, 3H). 13C
Dimethyl 4,40-(5,5-diuoro-1,3,7,9,10-pentamethyl-5H-4l, 5l- NMR (126 MHz, CDCl3) d 155.6, 154.0, 143.2, 142.0, 139.2, 135.2,
dipyrrolo[1,2-c:20,10-f][1,3,2] diazaborinine-2,8-diyl) dibenzoate 133.7, 133.7, 131.7, 131.0, 130.2, 129.2, 129.0, 128.3, 128.0, 127.0,
(4g). An orange solid, (yield: 29.8 mg, 28%) 1H NMR (400 MHz, 121.4, 14.6, 14.4, 13.3, 12.7. HRMS (ESI): m/z [M + H]+ calcd for
CDCl3) d 8.12 (d, J ¼ 7.9 Hz, 4H), 7.32 (d, J ¼ 7.9 Hz, 4H), 3.96 (s, C25H2411BF2N2 : 401.2001; found: 401.2008, D ¼ 1.20 ppm.
+
6H), 2.74 (s, 3H), 2.51 (s, 6H), 2.37 (s, 6H). 13C NMR (126 MHz,
(E)-5,5-Diuoro-1,3,7,9,10-pentamethyl-2-styryl-5H-5l,6l-dipyr-
CDCl3) d 166.9, 152.4, 142.4, 138.7, 137.4, 132.8, 132.5, 130.4, rolo[1,2-c:20,10-f][1,3,2]diazaborinine (9a). A brownish red solid
129.7, 128.9, 52.2, 17.4, 15.6, 13.3. HRMS (ESI): m/z [M ꢂ F]+ (yield: 27.7 mg, 38%, single substitute: double substitute ¼
calcd for C30H2911BFN2O4 : 511.2199; found: 511.2196, D ¼ 98 : 2). 1H NMR (400 MHz, CDCl3) d 7.48 (d, J ¼ 7.3 Hz, 2H), 7.36
+
0.55 ppm.
(t, J ¼ 7.3 Hz, 2H), 7.26 (t, 1H), 6.95 (d, J ¼ 16.5 Hz, 1H), 6.68 (d, J ¼
5,5-Diuoro-2,8-bis(4-uorophenyl)-1,3,7,9,10-pentamethyl- 16.5 Hz, 1H), 6.08 (s, 1H), 2.67 (s, 3H), 2.64 (s, 3H), 2.53 (s, 3H),
5H-4l, 5l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine (4h). An 2.50 (s, 3H), 2.43 (s, 3H). 13C NMR (126 MHz, CDCl3) d 154.0,
1
orange solid, (yield: 18.2 mg, 20%) H NMR (400 MHz, CDCl3) 152.9, 141.3, 141.2, 137.8, 136.6, 132.5, 132.0, 131.9, 128.7, 128.5,
d 7.16 (m, 8H), 2.71 (s, 3H), 2.47 (s, 6H), 2.32 (s, 6H). 13C NMR (126 127.5, 126.1, 121.5, 119.9, 77.3, 77.0, 76.8, 17.5, 17.0, 15.3, 14.5,
MHz, CDCl3) d 163.1, 161.1, 152.4, 142.0, 137.3, 132.7, 132.1, 13.8. HRMS (ESI): m/z [M ꢂ F]+ calcd for C22H2311BFN2 : 345.1933;
+
129.7, 115.5, 115.4, 17.3, 15.5, 13.2. HRMS (ESI): m/z [M ꢂ F]+ calcd found: 345.1935,D ¼ ꢂ0.73 ppm.
for C26H2411BF3N2 : 431.2972; found: 431.2970, D ¼ 0.46 ppm.
(E)-5,5-Diuoro-1,3,7,9,10-pentamethyl-2-(4-methylstyryl)-5H-
+
2,8-Bis(4-chlorophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl- 5l,6l-dipyrrolo[1,2-c:20,10-f][1,3,2]diazaborinine (9b). A brownish
5H-4l, 5l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine (4i). An red solid (yield: 18.6 mg, 25%, single substitute: double substi-
1
1
orange solid, (yield: 49.3 mg, 51%) H NMR (400 MHz, CDCl3) tute ¼ 95 : 5). H NMR (400 MHz, CDCl3) d 7.38 (d, J ¼ 8.0 Hz,
d 7.42 (d, J ¼ 8.4 Hz, 4H), 7.16 (d, J ¼ 8.4 Hz, 4H), 2.71 (s, 3H), 2H), 7.17 (d, J ¼ 8.0 Hz, 2H), 6.90 (d, J ¼ 16.5 Hz, 1H), 6.65 (d, J ¼
2.48 (s, 6H), 2.33 (s, 6H). 13C NMR (126 MHz, CDCl3) d 152.3, 16.5 Hz, 1H), 6.07 (s, 1H), 2.66 (s, 3H), 2.64 (s, 3H), 2.53 (s, 3H),
142.1, 137.3, 133.3, 132.5, 132.2, 131.7, 128.7, 17.3, 15.5, 13.2. 2.49 (s, 3H), 2.43 (s, 3H), 2.36 (s, 3H). 13C NMR (126 MHz, CDCl3)
HRMS (ESI): m/z [M ꢂ F]+ calcd for C26H2311BCl2FN2+: 463.1310; d 153.8, 153.1, 141.2, 141.0, 137.4, 136.5, 135.0, 132.5, 132.1,
found: 463.1300, D ¼ ꢂ2.09 ppm.
129.4, 128.8, 126.1, 121.4, 118.9, 110.0, 21.2, 17.5, 16.9, 15.3,
+
2,8-Bis(4-bromophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl- 14.5, 13.8. HRMS (ESI): m/z [M ꢂ F]+ calcd for C23H2511BFN2 :
5H-4l, 5l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine (4j). An 359.2089; found: 359.2098, D ¼ ꢂ2.39 ppm.
1
orange solid, (yield: 27.2 mg, 24%) H NMR (400 MHz, CDCl3)
(E)-5,5-Diuoro-2-(4-uorostyryl)-1,3,7,9,10-pentamethyl-5H-
d 7.57 (d, J ¼ 8.4 Hz, 4H), 7.10 (d, J ¼ 8.4 Hz, 4H), 2.71 (s, 3H), 5l,6l-dipyrrolo[1,2-c:20,10-f][1,3,2]diazaborinine (9c). A brownish
2.48 (s, 6H), 2.33 (s, 6H). 13C NMR (126 MHz, CDCl3) d 152.3, red solid (yield: 16.6 mg, 22%, single substitute: double substi-
142.1, 137.2, 132.7, 132.5, 132.3, 132.0, 131.7, 121.4, 17.3, 15.5, tute ¼ 96 : 4). 1H NMR (400 MHz, CDCl3) d 7.47 (dd, J ¼ 8.6 Hz,
13.2. HRMS (ESI): m/z [M + H]+ calcd for C26H2311B79Br2F2N2
570.0284; found: 570.0285, D ¼ 0.26 ppm.
:
2H), 7.07 (t, J ¼ 8.6 Hz, 2H), 6.89 (d, J ¼ 16.5 Hz, 1H), 6.66 (d, J ¼
+
16.5 Hz, 1H), 6.11 (s, 1H), 2.68 (s, 3H), 2.67 (s, 3H), 2.56 (s, 3H),
2,8-Bis(3-bromophenyl)-5,5-diuoro-1,3,7,9,10-pentamethyl- 2.52 (s, 3H), 2.46 (s, 3H). 13C NMR (126 MHz, CDCl3) d 163.3,
5H-4l, 5l-dipyrrolo [1,2-c:20,10-f] [1,3,2] diazaborinine (4k). An 161.3, 154.2, 152.7, 141.3, 136.5, 133.9, 132.6, 133.0, 130.6,
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128.3, 127.6, 121.6, 119.7, 115.7, 115.5, 17.5, 17.0, 15.3, 14.5,
2 (a) A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung
and K. Burgess, Chem. Soc. Rev., 2013, 42, 77–88; (b)
S. G. Awuah and Y. You, RSC Adv., 2012, 2, 11169–11183;
(c) T. Kowada, H. Maeda and K. Kikuchi, Chem. Soc. Rev.,
2015, 44, 4953–4972; (d) S. H. Lim, C. Thivierge, P. Nowak-
13.8. HRMS (ESI): m/z [M ꢂ F]+ calcd for C22H2211BF2N2 :
+
363.1839; found: 363.1834, D ¼ 1.15 ppm.
(E)-2-(4-Chlorostyryl)-5,5-diuoro-1,3,7,9,10-pentamethyl-5H-
5l,6l-dipyrrolo[1,2-c:20,10-f]
[1,3,2]diazaborinine
(9d).
A
`
brownish red solid (yield: 53.4 mg, 67%, single substitute:
double substitute ¼ 96 : 4). 1H NMR (400 MHz, CDCl3) d 7.39 (d,
J ¼ 8.5 Hz, 2H), 7.31 (d, J ¼ 8.5 Hz, 2H), 6.92 (d, J ¼ 16.5 Hz, 1H),
6.62 (d, J ¼ 16.5 Hz, 1H), 6.08 (s, 1H), 2.66 (s, 3H), 2.63 (s, 3H),
2.53 (s, 3H), 2.48 (s, 3H), 2.42 (s, 3H). 13C NMR (126 MHz, CDCl3)
d 154.4, 152.6, 141.5, 141.4, 136.5, 136.3, 133.0, 132.7, 131.9,
130.3, 128.8, 128.1, 127.3, 121.7, 120.6, 17.5, 17.0, 15.2, 14.5,
Sliwinska, J. Han, H. van den Bergh, G. Wagnieres,
K. Burgess and H. B. Lee, J. Med. Chem., 2010, 53, 2865–2874.
´
´
´
3 C. F. A. Gomez-Duran, I. Esnal, I. Valois-Escamilla, A. Urıas-
˜
´
´
Benavides, J. Banuelos, I. Lopez Arbeloa, I. Garcıa-Moreno
and E. Pena-Cabrera, Chem.–Eur. J., 2016, 22, 1048–1061.
˜
4 (a) X. Li, S. Huang and Y. Hu, Org. Biomol. Chem., 2012, 10,
2369–2372; (b) L. Jiao, C. Yu, J. Li, Z. Wang, M. Wu and
E. Hao, J. Org. Chem., 2009, 74, 7525–7528; (c) N. Boens,
B. Verbelen and W. Dehaen, Eur. J. Org. Chem., 2015, 2015,
6577–6595.
13.8. HRMS (ESI): m/z [M + H]+ calcd for C22H2211BCl2F2N2 :
+
398.1527; found: 398.1522, D ¼ ꢂ1.42 ppm.
(E)-2-(4-Bromostyryl)-5,5-diuoro-1,3,7,9,10-pentamethyl-5H-
5l,6l-dipyrrolo [1,2-c:20,10-f] [1,3,2]diazaborinine (9e).
A
5 H. M. L. Davies, J. Du Bois and J.-Q. Yu, Chem. Soc. Rev., 2011,
40, 1855–1856.
brownish red solid (yield: 24.7 mg, 28%, single substitute:
double substitute ¼ 94 : 6). 1H NMR (400 MHz, CDCl3) d 7.49 (d,
J ¼ 8.4 Hz, 2H), 7.36 (d, J ¼ 8.5 Hz, 2H), 6.97 (d, J ¼ 16.5 Hz, 1H),
6.62 (d, J ¼ 16.5 Hz, 1H), 6.11 (s, 1H), 2.68 (s, 3H), 2.66 (s, 3H),
2.56 (s, 3H), 2.51 (s, 3H), 2.45 (s, 3H). 13C NMR (126 MHz, CDCl3)
d 154.4, 152.5, 141.5, 141.4, 136.7, 136.5, 132.7, 131.9, 131.8,
130.3, 128.0, 127.6, 121.7, 121.1, 120.7, 17.5, 17.0, 15.3, 14.5,
6 (a) B. Verbelen, S. Boodts, J. Hoens, N. Boens and
W. Dehaen, Angew. Chem., Int. Ed., 2015, 54, 4612–4616;
Angew. Chem., 2015, 127, 4695–4699; (b) B. Verbelen, V. Leen,
L. Wang, N. Boens and W. Dehaen, Chem. Commun., 2012,
48, 9129–9131; (c) X. Zhou, Q. Wu, Y. Yu, C. Yu, E. Hao,
Y. Wei, X. Mu and L. Jiao, Org. Lett., 2016, 18, 736–739; (d)
J. L. Belmonte-Vazquez, R. Sola-Llano, J. Banuelos,
´ ´
L. Betancourt-Mendiola, M. A. Vazquez-Guevara, I. Lopez-
Arbeloa and E. Pena-Cabrera, Dyes Pigm., 2017, 147, 246–259.
7 C. Thivierge, R. Bandichhor and K. Burgess, Org. Lett., 2007,
9, 2135–2138.
+
13.8. HRMS (ESI): m/z [M ꢂ F]+ calcd for C22H2211BBrFN2 :
´
˜
423.1038; found: 423.1035, D ¼ ꢂ0.63 ppm.
˜
(E)-5,5-Diuoro-1,3,7,9,10-pentamethyl-2-(pent-1-en-1-yl)-5H-
5l,6l-dipyrrolo[1,2-c:20,10-f] [1,3,2] diazaborinine (9f).
A
brownish red solid (yield: 33.6 mg, 51%, single substitute:
1
double substitute ¼ 89 : 11). H NMR (400 MHz, CDCl3) d 6.16
8 L. Luo, D. Wu, W. Li, S. Zhang, Y. Ma, S. Yan and J. You, Org.
Lett., 2014, 16, 6080–6083.
(d, J ¼ 16.1 Hz, 1H), 6.03 (s, 1H), 5.75 (dt, J ¼ 16.1, 6.9 Hz, 1H),
2.59 (s, 3H), 2.56 (s, 3H), 2.51 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H),
2.21 (qd, J ¼ 6.9, 2H), 1.50 (m, J ¼ 7.4 Hz, 2H), 0.97 (t, J ¼ 7.4 Hz,
3H). 13C NMR (126 MHz, CDCl3) d 153.2, 152.9, 141.0, 140.3,
136.5, 135.3, 132.1, 132.0, 129.5, 121.0, 120.6, 35.9, 22.7, 17.4,
16.8, 15.1, 14.4, 13.7, 13.6. HRMS (ESI): m/z [M + H]+ calcd for
9 (a) R. Beaud, R. J. Phipps and M. J. Gaunt, J. Am. Chem. Soc.,
2016, 138, 13183–13186; (b) L. Chan, A. McNally, Q. Y. Toh,
A. Mendoza and M. J. Gaunt, Chem. Sci., 2015, 6, 1277–1281;
(c) E. A. Merritt and B. Olofsson, Angew. Chem., Int. Ed.,
2009, 48, 9052–9070; (d) V. V. Zhdankin and P. J. Stang,
Chem. Rev., 2008, 108, 5299–5358; (e) Q. Y. Toh, A. McNally,
S. Vera, N. Erdmann and M. J. Gaunt, J. Am. Chem. Soc.,
2013, 135, 3772–3775; (f) X. Qian, J. Han and L. Wang,
Tetrahedron Lett., 2016, 57, 607–610; (g) X. Wang, D. Huang,
X. Wang, X. Zeng, X. Wang and Y. Hu, Tetrahedron Lett.,
2016, 57, 4235–4238; (h) N. Gigant, L. Chausset-Boissarie,
M.-C. Belhomme, T. Poisson, X. Pannecoucke and
I. Gillaizeau, Org. Lett., 2013, 15, 278–281.
+
C19H2611BF2N2 : 331.2152; found: 331.2159, D ¼ ꢂ0.73 ppm.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This study was nancially supported by the fund from the State
Key Laboratory of Drug Research (grant no. SIMM1705KF06);
Institutes for Drug Discovery and Development, Chinese
Academy of Sciences (CASIMM0120163010), and One Hundred
Talent Program of Chinese Academy of Sciences and the
National Natural Science Foundation of China (81225022).
10 N. Boens, B. Verbelen and W. Dehaen, Eur. J. Org. Chem.,
2015, 2015, 6577–6595.
11 R. J. Phipps, L. McMurray, S. Ritter, H. A. Duong and
M. J. Gaunt, J. Am. Chem. Soc., 2012, 134, 10773–10776.
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Soc., 2011, 133, 13778–13781; (b) M. G. Suero, E. D. Bayle,
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RSC Adv., 2018, 8, 5542–5549 | 5549