The singlet excited state of BODIPY promoted aerobic cross-dehydrogenative-coupling reactions under visible light

Article abstract of DOI:10.1039/c5cc03421c

In contrast to previous studies, we disclose for the first time that the singlet excited state (¹PS?) of BODIPY rather than the triplet excited state (³PS?) can drive C-H bond activation to form C-C and C-P bonds smoothly, which offers new methods to promote organic transformation under visible light irradiation.

Full text of DOI:10.1039/c5cc03421c

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10.1039/C5CC03421C.
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DOI: 10.1039/C5CC03421C
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Singlet excited state of BODIPY promoted aerobic cross-
dehydrogenative-coupling reactions under visible light†
Received 00th January 20xx,
Accepted 00th January 20xx
Xu-Zhe Wang, Qing-Yuan Meng,* Jian-Ji Zhong, Xue-Wang Gao, Tao Lei, Lei-Min Zhao, Zhi-Jun Li,
Bin Chen, Chen-Ho Tung, and Li-Zhu Wu*
DOI: 10.1039/x0xx00000x
www.rsc.org/
In contrast to previous studies, we disclose for the first time that singlet
excited state (1PS*) of BODIPY rather than triplet excited state (3PS*) can
drive C-H bond activation to form C-C and C-P bonds smoothly, which
offers new ways to promote organic transformation under visible light
irradiation.
BODIPY,
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
derivatives, are famous organic dyes,1 which are extensively
used as labelling reagents, fluorescent switches, chemosensors
and laser dyes.2 Such organic dyes have recently aroused
growing interest from organic synthetic chemists because their
high efficiency of visible-light absorption, enhanced stability
and easy modification are promising characteristics for visible
light catalysis.3 The use of BODIPY as photosensitizer (PS) to
promote tandem oxidation/[3+2] cycloaddition,4 cross-
dehydronative-coupling reaction5 and photo-oxidation have
been realized.6 However, all of these studies concluded that
the triplet excited state (3PS*) of BODIPY is responsible for the
visible light induced organic transformation, while its singlet
excited state (1PS*) cannot drive the same reaction. It has been
established that photoexcitation of PS results in singlet excited
Scheme 1. The structure of B-1, B-2, B-3 and B-4
In this contribution, we report that this is not the case.
Irradiation of a simple BODIPY derivative, 4,4-difluoro-8-
phenyl-4-bora-3a,4a-diaza-s-indacene (B-1) in Scheme 1, by
visible light (white LEDs) in air can realize a typical aerobic
cross-dehydrogenative-coupling, leading to C-C and C-P bond
formation smoothly. Time-resolved spectroscopic and electron
spin resonance (ESR) studies reveals that singlet excited state
1PS* with high population interacts with the substrate, N-
phenyltetrahydroisoquinoline 1a, intimately to generate PS-•
radical anion, which delivers an electron to molecular oxygen
O2 to promote the transformation. In contrast to those
reported in the literature4-6,9 the active species of O2 is
1
state PS*, which is subsequently able to yield triplet excited
3
state PS* via intersystem crossing (ISC) process.7 Because of
-•
1
superoxide radical anion O2 rather than singlet oxygen O2.
This finding not only contributes to organic synthesis, but also
greatly expands the application of BODIPY.
the spin-orbital coupling limitation, the population of triplet
3
1
excited PS* is rather lower than that of singlet PS* although
triplet PS* generally has a longer lifetime to associate with
3
Initially, we found that simple unmodified B-1 is brightly
emissive to show strong fluorescence with a maximal peak at
509 nm in methanol at room temperature (Fig 1). Progressive
addition of N-phenyltetrahydroisoquinoline 1a quenched the
fluorescence upon excitation of B-1 at its typical absorption
organic substrates.8 For BODIPY, a series of heavy atoms, for
example iodine shown in Scheme 1, have been specifically
incorporated into simple BODIPY framework to enhance spin-
orbital coupling and hence the population of 3PS*.4-6 It was
commonly accepted that unmodified simple BODIPY is too
short-lived to show any catalytic activity of visible light induced
organic transformation,4-6 albeit the higher population of
singlet 1PS* and excellent light-harvesting ability.
band (λ = 500 nm, Fig S3, ESI†). This result suggested that
simple B-1 interacted with 1a intimately with quenching
constant K = 52.80 M-1 in solution (Fig 1). The fluorescence
lifetime derived from singlet excited state (1PS*) remained
unchanged in the absence and presence of 1a (4.0 ns, Fig
1
), indicative that the quenching process of PS* (1B-1*
)
a.Key Laboratory of Photochemical Conversion and Optoelectronic Materials,
Technical Institute of Physics and Chemistry & University of Chinese Academy of
Sciences, the Chinese Academy of Sciences, Beijing, 100190, P. R. China. E-mail:
mqy@mail.ipc.ac.cn, lzwu@mail.ipc.ac.cn
S2,ESI
†
by 1a was too fast to be detected by the time-resolved
instrument used. Because the energy of the singlet excited
1
state PS* (1B-1*) is much lower than that of 1a, the energy
† Electronic Supplementary Information (ESI) available.
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transfer process from 1B-1* to 1a could be ignored if it occurs. tetramethyl-1-piperidine (TEMP) and 5,5-dimethyVl-ie1w-pArytircrleoOlinnliene-
1
According to the determined oxidation potential Eox of 1a (0.82 N-oxide (DMPO) were employed to trap DthOeI: a10c.t1i0v3e9/sCp5eCcCie0s3,42O1C2
V vs. SCE), reduction potential Ered of PS (B-1) (-1.20 V vs. SCE) and O2-•, respectively. When TEMP was added into the
and the excited state energy E00 (2.46 eV), which was read unmodified BODIPY (B-1) solution, no signal could be detected
from cross-point of the absorption and fluorescence spectra of in the presence and absence of 1a. The result clearly
1
B-1 at 505 nm, the free energy change (ΔG) for electron- demonstrated no O2 formation in the solution. However, the
transfer from 1a to singlet excited state 1PS*
(
1B-1*) was signal of O2 from mixture of B-1 and 1a was observed when
-•
calculated to be -0.44 eV. Therefore, the electron transfer DMPO was used as the radical scavenger under the same
1
-•
from 1a to the singlet state PS* of B-1 is thermodynamically condition. Without 1a, such a signal of O2 was absent from
feasible resulting in the fluorescence quenching.
the solution.
Figure 1. Fluorescence spectra of B-1 (1.0 × 10-5 M) as a function of
concentration of 1a in MeOH, excitation at 480 nm. Inset was the Stern–
Volmer plot of B-1 vs. the concentration of 1a.
Figure 2. ESR experiments of (a) a solution in air-saturated MeOH of B-1 (1 ×
10-4 M) in the presence of DMPO (2.0 × 10-2 M) with irradiation for 30 s. (b)
A solution of B-1 in the presence of DMPO (2.0 × 10-2 M) and 1a with
irradiation for 30 s. (c) A solution in air-saturated MeOH of B-1 (1 × 10-4 M)
with TEMP (1 × 10-2 M), irradiation for 30 s. (d) A solution of B-1 with 1a in
the presence of TEMP (2.0 × 10-2 M), irradiation for 30 s.
The most important observation is that the singlet excited
state 1PS* of B-1 facilitated the conversion of 1a and
nitromethane 2a to their cross-coupling product smoothly at
ambient condition. With visible light irradiation by white LEDs,
0.1 mol % of B-1 was able to initiate the reaction to yield the
desired product in 100% conversion and 75% yield (Table 1).
Increasing the concentration of B-1 from 0.1 mol % to 4 mol %
greatly shortened the reaction time from 6 to 2.5 h (Table 1,
Scheme 2. Proposed mechanism
entries 1-5). For comparison, iodo-modified BODIPY (B-2, B-3
and B-4) were also synthesized to conduct the reaction under
the same condition and comparative yields for the cross-
coupling product were obtained (Table 1, entries 6-8). Control
experiments suggested the presence of O2 greatly improved
the yield of the reaction from 23% to 80% (Table 1, entries 3
and 11), but the absence of either light or PS (B-1) led to
negligible product formation (Table 1, entries 9 and 10).
1
Because the fluorescent intensity and lifetime of PS* (1B-1*
)
was independent of the presence of molecular oxygen (O2),
3
and no phosphorescence of PS* (3B-1*) could be detected in
an atmosphere of either argon or O2, we could speculate that
the unmodified BODIPY, B-1, features singlet excited state 1PS*
rather than triplet excited state 3PS*. Due to the spin
1
restriction, 8 the singlet excited state PS* is hard to sensitize
the triplet ground state of molecular O2 to generate singlet
1
oxygen O2, which was commonly recognized as active oxygen
species from BODIPY promoting organic transformation.10
1
As mentioned above, singlet excited state PS* of B-1 gave
no fluorescence response to O2, but triplet excited state PS*
3
From these results, we could speculate the reaction
mechanism shown in Scheme 2. Once irradiated by visible light,
form singlet oxygen 1O2 via energy transfer process (Scheme 1,
previous work).10 To understand the role of O2 in this unique
reaction, ESR experiments were carried out, where 2,2,6,6-
PS (B-1) is pumped to the singlet excited state 1PS* 1B-1*
( )
which is immediately quenched by 1a via electron transfer
2 | J. Name., 2012, 00, 1-3
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process to generate radical cation 1a+• and radical anion PS-•
.
Table 2. B-1 Initiated Aerobic CDC Reactions between 1 and 2.a,b
View Article Online
DOI: 10.1039/C5CC03421C
The generated radical anion PS-• delivered an electron to
R1
R2
R1
-•
molecular O2 to form superoxide radical anion O2 and
B-1
visble
simultaneously to regenerate PS to its ground state.12 The
R4
N
N
O N
R2
+
2
light
r.t.
active species, O2 subsequently abstracts a proton form 1a+•
-•
R3
R4 NO2
R3
air,
to produce hydroperoxide radical and 1a• intermediate. The
latter can be further oxidized by O2 to afford imine cation.
Then the nucleophiles would attack the imine cation to yield
the product. Different from the traditional triplet excited state
1
2
3
N
N
N
1
3PS* reported in the literatures,9 singlet excited state PS* has
NO2
NO2
O2
N
3b: 72 (60)c
3c: 67 (52)d
3a: 80 (71)
been demonstrated to drive these reactions smoothly, which
was obviously ignored before.
Table 1. Screen the Reaction Conditions. a
N
N
N
Br
NO2
Cl
NO2
F
NO2
B-1
3d: 74 (58)
3f: 61 (46)
N
3e: 70 (53)
N
+
CH3NO2
visible
air,
light
r.t.
NO2
O
O
1a
2a
3a
N
N
N
NO2
O
NO2
O
NO2
B-1
(mol %)
irradiation
time (h)
3a
entry
condition
covn. (%)
3g: 85 (71)
3h: 88 (73)
(%)b
3i: 95 (80)
a 1 (0.1 mmol), 2 mL 2, 1 mol % B-1 (0.001 mmol), under air at room temperature,
all the conversion was 100%, and irradiation time was 3 h. b Yields detected by 1H
NMR spectroscopy using an internal standard, diphenylacetonitrile; the isolated
product yields were given in parentheses. c Ratios of the two diastereoisomers
were 2:1. d Ratios of the two diastereoisomers were 1:1.
1
2
B-1
B-1
4
2
2.5
2.5
3
100
100
100
100
100
100
100
100
10
79
78
80
77
75
80
84
79
9
3
B-1
1
4
B-1
0.5
0.1
1
4
5
B-1
6
Furthermore, the singlet excited states 1PS* 1B-1*) could
(
directly accelerate formation of a C-P bond in addition to the
C-C bond. Good to excellent yields of cross-coupling products
were obtained for decreasing the steric effect of nucleophiles
6
B-2
3
7
B-3
B-4c
1
3
8
1
2
(Table 4, 7a
S1, ESI ), methanol (MeOH) was found to be the best solvent
, 7b and 7c). Under the optimized conditions (Table
9
no B-1
no lightd
no O2
-
3
†
10
11
1
-
0
0
for C-P bonds coupling. Gratifyingly, high yields of cross-
coupling products were obtained regardless of electron-rich or
electron-poor 1 (Table 4, 7e-7j).
1
3
25
23
a Reaction condition: 1a (0.05 mmol), 2a (1.0 mL). The reaction was in an air
atmosphere before visible light LEDs irradiation at room temperature. A small
amount of by-products, lactam and dimer of N-phenyltetrahydroisoquinoline
(10%) were detected by 1H NMR in the reaction. b Yields were based on 1a and
Table 3. B-1 Initiated Aerobic CDC Reactions between 1a and Dialkyl
Malonates.a,b
detected by 1H NMR spectroscopy using diphenylacetonitrile internal standard.
c
From reference 5. d In the air without irradiation for 4 h.
N
O
O
B-1
visible
N
+
OR
RO
OR
light
r.t.
With the understanding of the reaction, we examined the
scope of this reaction using the simple B-1 (1 mol %) at room
temperature in air.11 As tabulated in Table 2, the reactivity of
nitromethane over nitroethane or nitropropane was better in
the desired coupling products, which may be attributed to the
steric effect of the nucleophiles. Notably, functionalities of
chlorine and bromine were tolerated, providing an opportunity
for further modification. The electron-donating groups at-
RO
MeOH, air,
O
O
1a
4
5
N
N
OEt
O
O
EtO
OMe
O
OMe
O
5a: 90 (75)c
5b: 65 (51)c
tached on the aromatic ring of
between 1,2,3,4-tetrahydroisoquinoline derivatives
nitromethane . Similarly, N-phenyltetrahydroisoquinoline 1a
was treated with dialkyl malonates to yield the desired
product smoothly (Table 3). In contrast to diethyl malonate,
dimethyl malonate gave better performance for the cross-
1
benefited for the coupling
a N-phenyltetrahydroisoquinoline 1a (0.1 mmol), dialkyl malonates derivatives 4
1
and
(0.1 mmol) in 2 mL MeOH, 1 mol % B-1 (0.001 mmol), under air at room
b
Yields detected by 1H NMR
2
temperature, the conversions are 100%.
spectroscopy using diphenylacetonitrile as internal standard; the isolated product
yields were given in parentheses. c Irradiation time: 6 h.
coupling with 1a
.
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Table 4. B-1 Initiated Aerobic CDC Reactions between 1 and Phosphite
Notes and references
View Article Online
Ester.a,b
1
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R1
R2
R1
N
O
B-1
N
+
R2
R4
P
H
R4
visible
O
R4
P
O
R4
O
O
light
r.t.
air,
R3
2
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MeOH,
O
1
6
7
N
N
N
O
P
O
O
P
O
EtO
P
OEt
iPr
Bn
O
O
iPr
O
Bn
7a: 96 (77)c
7c: 90 (77)d
7b: 94 (78)c
3
N
N
N
O
P
O
O
EtO
P
O
P
EtO
7f: 98 (85)c
F
Cl
Ph
OEt
OEt
O
Ph
7e: 98 (83)c
7d: 55 (42)c
N
N
N
2010, 2, 527.
P
O
O
EtO
P
EtO
O
EtO
P
Br
O
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OEt
OEt
7i: 82 (69)e
7h: 92 (83)c
7g: 95 (78)c
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O
7j: 81 (65)e
a
N-phenyltetrahydroisoquinoline derivatives
1 (0.1 mmol), phosphonates
derivatives 6 (0.1 mmol) in 2 mL MeOH, 1 mol % B-1 (0.001 mmol), under air at
7
8
b
room temperature, the conversion was 100%. Yields detected by 1H NMR
spectroscopy using an internal standard, diphenylacetonitrile; the isolated
product yields were given in parentheses. c Irradiation time: 5 h. d Irradiation time:
4 h. e Irradiation time: 7 h.
Conclusions
In summary, we have demonstrated for the first time that
singlet excited 1PS* of BODIPY can promote organic
transformations smoothly to realize the C-C and C-P bond
formations through C-H bonds activation under visible light
irradiation. The activity is comparable or even better than that
of triplet excited state 3PS* in the literature. Mechanistic
9
1
studies reveal that singlet excited state PS* of B-1 interacts
with substrate
1 directly, and then the cascade electron
-
transfer to O2 producing active species O2 •, which plays a key
role in the reaction process. This exciting discovery is
anticipated to be a starting point using such a simple BODIPY
without tedious chemical modification to realize new organic
transformations in the future.
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and D. Ramaiah, Org. Lett., 2010, 12, 5720. (c) J. F. Lovell, T.
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(d) A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung
and K. Burgess, Chem. Soc. Rev., 2013, 42, 77.
We are grateful for financial support from the Ministry of
Science and Technology of China (2013CB834804,
2014CB239402 and 2013CB834505), the National Natural
Science Foundation of China (21390404, 91427303 and
21402217), the Key Research Programme of the Chinese
Academy of Sciences (KGZD-EW-T05) and the Chinese
Academy of Sciences.
11 The reduced isolated yields are due to product
decomposition during the process of isolation.
12 Donor-accepter complex was excluded by UV-Vis spectrum.
There was no new peaks formation, see from ESI S4.
4 | J. Name., 2012, 00, 1-3
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