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COMMUNICATION Singlet excited state of BODIPY promoted aerobic crossdehydrogenative-coupling reactions under visible light† Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x
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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*
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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 1 derivatives, are famous organic dyes, which are extensively used as labelling reagents, fluorescent switches, chemosensors 2 and laser dyes. 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 3 light catalysis. The use of BODIPY as photosensitizer (PS) to 4 promote tandem oxidation/[3+2] cycloaddition, cross5 dehydronative-coupling reaction and photo-oxidation have 6 been realized. However, all of these studies concluded that 3 * the triplet excited state ( PS ) of BODIPY is responsible for the visible light induced organic transformation, while its singlet 1 * excited state ( PS ) cannot drive the same reaction. It has been established that photoexcitation of PS results in singlet excited 1 * state PS , which is subsequently able to yield triplet excited 3 * 7 state PS via intersystem crossing (ISC) process. Because of the spin-orbital coupling limitation, the population of triplet 3 * 1 * excited PS is rather lower than that of singlet PS although 3 * triplet PS generally has a longer lifetime to associate with 8 organic substrates. For BODIPY, a series of heavy atoms, for example iodine shown in Scheme 1, have been specifically incorporated into simple BODIPY framework to enhance spin3 * 4-6 orbital coupling and hence the population of PS . It was commonly accepted that unmodified simple BODIPY is too short-lived to show any catalytic activity of visible light induced 4-6 organic transformation, albeit the higher population of 1 * singlet PS and excellent light-harvesting ability. 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: [email protected], [email protected] † Electronic Supplementary Information (ESI) available.
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-8phenyl-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 1 * PS 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 4-6,9 reported in the literature the active species of O2 is -• 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. 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 band (λ = 500 nm, Fig S3, ESI†). This result suggested that simple B-1 interacted with 1a intimately with quenching -1 constant K = 52.80 M in solution (Fig 1). The fluorescence 1 * lifetime derived from singlet excited state ( PS ) remained unchanged in the absence and presence of 1a (4.0 ns, Fig 1 * 1 * S2,ESI†), indicative that the quenching process of PS ( B-1 ) by 1a was too fast to be detected by the time-resolved instrument used. Because the energy of the singlet excited 1 * 1 * state PS ( B-1 ) is much lower than that of 1a, the energy
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*
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transfer process from B-1 to 1a could be ignored if it occurs. According to the determined oxidation potential Eox of 1a (0.82 V vs. SCE), reduction potential Ered of PS (B-1) (-1.20 V vs. SCE) and the excited state energy E00 (2.46 eV), which was read from cross-point of the absorption and fluorescence spectra of B-1 at 505 nm, the free energy change (ΔG) for electron1 * 1 * transfer from 1a to singlet excited state PS ( B-1 ) was calculated to be -0.44 eV. Therefore, the electron transfer 1 * from 1a to the singlet state PS of B-1 is thermodynamically feasible resulting in the fluorescence quenching.
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.
The most important observation is that the singlet excited 1 * state PS 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, 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 crosscoupling 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 * 1 * Because the fluorescent intensity and lifetime of PS ( B-1 ) was independent of the presence of molecular oxygen (O2), 3 * 3 * and no phosphorescence of PS ( B-1 ) could be detected in an atmosphere of either argon or O2, we could speculate that 1 * the unmodified BODIPY, B-1, features singlet excited state PS 3 * rather than triplet excited state PS . Due to the spin 8 1 * restriction, 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 10 species from BODIPY promoting organic transformation. 1 * As mentioned above, singlet excited state PS of B-1 gave 3 * no fluorescence response to O2, but triplet excited state PS 1 form singlet oxygen O2 via energy transfer process (Scheme 1, 10 previous work). To understand the role of O2 in this unique reaction, ESR experiments were carried out, where 2,2,6,6-
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tetramethyl-1-piperidine (TEMP) and 5,5-dimethyl-1-pyrrolineView Article Online 1 10.1039/C5CC03421C N-oxide (DMPO) were employed to trap DOI: the active species, O2 -• and O2 , respectively. When TEMP was added into the unmodified BODIPY (B-1) solution, no signal could be detected in the presence and absence of 1a. The result clearly 1 demonstrated no O2 formation in the solution. However, the -• signal of O2 from mixture of B-1 and 1a was observed when DMPO was used as the radical scavenger under the same -• condition. Without 1a, such a signal of O2 was absent from the solution.
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.
Scheme 2. Proposed mechanism
From these results, we could speculate the reaction mechanism shown in Scheme 2. Once irradiated by visible light, 1 * 1 * PS (B-1) is pumped to the singlet excited state PS ( B-1 ) which is immediately quenched by 1a via electron transfer
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+•
-•
process to generate radical cation 1a and radical anion PS . -• The generated radical anion PS delivered an electron to -• molecular O2 to form superoxide radical anion O2 and 12 simultaneously to regenerate PS to its ground state. The +• -• active species, O2 subsequently abstracts a proton form 1a • 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 3 * 9 1 * PS reported in the literatures, singlet excited state PS has been demonstrated to drive these reactions smoothly, which was obviously ignored before.
a,b
Table 2. B-1 Initiated Aerobic CDC Reactions between 1 and 2. View Article Online DOI: 10.1039/C5CC03421C N
1
+ CH3NO2
entry 1
B-1
B-1 (mol %) 4
2.5
O 2N
NO2
3c: 67 (52)d
N
N Br
NO2
Cl
NO2
NO2
3f: 61 (46)
3e: 70 (53)
O
covn. (%)
N
N NO2
3a (%)b
100
79
2
B-1
2
2.5
100
78
3
B-1
1
3
100
80
4
B-1
0.5
4
100
77
5
B-1
0.1
6
100
75
6
B-2
1
3
100
80
7
B-3
1
3
100
84
8
c
B-4
1
2
100
79
9
no B-1
-
3
10
9
d
N
3b: 72 (60)c
3d: 74 (58)
R3
NO2 3
NO2
3a: 80 (71)
3a
irradiation time (h)
R4
NO2
2a
condition
N
R2
N
N
visible light air, r.t. 1a
visble light air, r.t. 2
N
N
B-1
R4
N R2 + O 2
R3
F
N
R1
R1
Table 1. Screen the Reaction Conditions. a B-1
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10
no light
1
-
0
0
11
no O2
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 detected by 1H NMR spectroscopy using diphenylacetonitrile internal standard. c From reference 5. d In the air without irradiation for 4 h.
O
NO2
O
3h: 88 (73)
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
*
1
*
Furthermore, the singlet excited states PS ( B-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 (Table 4, 7a, 7b and 7c). Under the optimized conditions (Table S1, ESI†), methanol (MeOH) was found to be the best solvent for C-P bonds coupling. Gratifyingly, high yields of crosscoupling products were obtained regardless of electron-rich or electron-poor 1 (Table 4, 7e-7j). Table 3. B-1 Initiated Aerobic CDC Reactions between 1a and Dialkyl Malonates.a,b
N
With the understanding of the reaction, we examined the scope of this reaction using the simple B-1 (1 mol %) at room 11 temperature in air. 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 attached on the aromatic ring of 1 benefited for the coupling between 1,2,3,4-tetrahydroisoquinoline derivatives 1 and nitromethane 2. 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 crosscoupling with 1a.
NO2
O
3g: 85 (71)
N
O
+
O
N
B-1
OR
OR visible light MeOH, air, r.t.
RO
RO O
4
1a
5
N
N
OEt
O O OMe
OMe c
5a: 90 (75) a
O
EtO O
O
5b: 65 (51)c
N-phenyltetrahydroisoquinoline 1a (0.1 mmol), dialkyl malonates derivatives 4 (0.1 mmol) in 2 mL MeOH, 1 mol % B-1 (0.001 mmol), under air at room temperature, the conversions are 100%. b Yields detected by 1H NMR spectroscopy using diphenylacetonitrile as internal standard; the isolated product yields were given in parentheses. c Irradiation time: 6 h.
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Notes and references
Table 4. B-1 Initiated Aerobic CDC Reactions between 1 and Phosphite Ester.a,b
N
R2 + R4
O P R4 O H O
R3 1
N
7a: 96 (77)c
N
7c: 90 (77)d
N
O P O Ph O Ph
N
O P EtO OEt
F
7e: 98 (83)c
c
7d: 55 (42)
N Br
7h: 92 (83)
c
7g: 95 (78)
Cl
7f: 98 (85)c
EtO P O OEt
O P EtO OEt
c
O P EtO OEt
N
N
O P EtO OEt
R3
O P O Bn O Bn
7b: 94 (78)c
N
O P O R4 O R4 7
O P O iPr O iPr
EtO P OEt O
N
R2
6
N
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B-1 visible light MeOH, air, r.t.
O e
7i: 82 (69)
O O
N EtO P OEt O
O e
7j: 81 (65) 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 room temperature, the conversion was 100%. b 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 1 * singlet excited PS 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 3 * of triplet excited state PS in the literature. Mechanistic 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. 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.
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R1
R1
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This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
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COMMUNICATION Singlet excited state of BODIPY promoted aerobic crossdehydrogenative-coupling reactions under visible light† Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x
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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*
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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 1 derivatives, are famous organic dyes, which are extensively used as labelling reagents, fluorescent switches, chemosensors 2 and laser dyes. 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 3 light catalysis. The use of BODIPY as photosensitizer (PS) to 4 promote tandem oxidation/[3+2] cycloaddition, cross5 dehydronative-coupling reaction and photo-oxidation have 6 been realized. However, all of these studies concluded that 3 * the triplet excited state ( PS ) of BODIPY is responsible for the visible light induced organic transformation, while its singlet 1 * excited state ( PS ) cannot drive the same reaction. It has been established that photoexcitation of PS results in singlet excited 1 * state PS , which is subsequently able to yield triplet excited 3 * 7 state PS via intersystem crossing (ISC) process. Because of the spin-orbital coupling limitation, the population of triplet 3 * 1 * excited PS is rather lower than that of singlet PS although 3 * triplet PS generally has a longer lifetime to associate with 8 organic substrates. For BODIPY, a series of heavy atoms, for example iodine shown in Scheme 1, have been specifically incorporated into simple BODIPY framework to enhance spin3 * 4-6 orbital coupling and hence the population of PS . It was commonly accepted that unmodified simple BODIPY is too short-lived to show any catalytic activity of visible light induced 4-6 organic transformation, albeit the higher population of 1 * singlet PS and excellent light-harvesting ability. 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: [email protected], [email protected] † Electronic Supplementary Information (ESI) available.
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-8phenyl-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 1 * PS 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 4-6,9 reported in the literature the active species of O2 is -• 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. 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 band (λ = 500 nm, Fig S3, ESI†). This result suggested that simple B-1 interacted with 1a intimately with quenching -1 constant K = 52.80 M in solution (Fig 1). The fluorescence 1 * lifetime derived from singlet excited state ( PS ) remained unchanged in the absence and presence of 1a (4.0 ns, Fig 1 * 1 * S2,ESI†), indicative that the quenching process of PS ( B-1 ) by 1a was too fast to be detected by the time-resolved instrument used. Because the energy of the singlet excited 1 * 1 * state PS ( B-1 ) is much lower than that of 1a, the energy
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transfer process from B-1 to 1a could be ignored if it occurs. According to the determined oxidation potential Eox of 1a (0.82 V vs. SCE), reduction potential Ered of PS (B-1) (-1.20 V vs. SCE) and the excited state energy E00 (2.46 eV), which was read from cross-point of the absorption and fluorescence spectra of B-1 at 505 nm, the free energy change (ΔG) for electron1 * 1 * transfer from 1a to singlet excited state PS ( B-1 ) was calculated to be -0.44 eV. Therefore, the electron transfer 1 * from 1a to the singlet state PS of B-1 is thermodynamically feasible resulting in the fluorescence quenching.
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.
The most important observation is that the singlet excited 1 * state PS 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, 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 crosscoupling 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 * 1 * Because the fluorescent intensity and lifetime of PS ( B-1 ) was independent of the presence of molecular oxygen (O2), 3 * 3 * and no phosphorescence of PS ( B-1 ) could be detected in an atmosphere of either argon or O2, we could speculate that 1 * the unmodified BODIPY, B-1, features singlet excited state PS 3 * rather than triplet excited state PS . Due to the spin 8 1 * restriction, 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 10 species from BODIPY promoting organic transformation. 1 * As mentioned above, singlet excited state PS of B-1 gave 3 * no fluorescence response to O2, but triplet excited state PS 1 form singlet oxygen O2 via energy transfer process (Scheme 1, 10 previous work). To understand the role of O2 in this unique reaction, ESR experiments were carried out, where 2,2,6,6-
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tetramethyl-1-piperidine (TEMP) and 5,5-dimethyl-1-pyrrolineView Article Online 1 10.1039/C5CC03421C N-oxide (DMPO) were employed to trap DOI: the active species, O2 -• and O2 , respectively. When TEMP was added into the unmodified BODIPY (B-1) solution, no signal could be detected in the presence and absence of 1a. The result clearly 1 demonstrated no O2 formation in the solution. However, the -• signal of O2 from mixture of B-1 and 1a was observed when DMPO was used as the radical scavenger under the same -• condition. Without 1a, such a signal of O2 was absent from the solution.
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.
Scheme 2. Proposed mechanism
From these results, we could speculate the reaction mechanism shown in Scheme 2. Once irradiated by visible light, 1 * 1 * PS (B-1) is pumped to the singlet excited state PS ( B-1 ) which is immediately quenched by 1a via electron transfer
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+•
-•
process to generate radical cation 1a and radical anion PS . -• The generated radical anion PS delivered an electron to -• molecular O2 to form superoxide radical anion O2 and 12 simultaneously to regenerate PS to its ground state. The +• -• active species, O2 subsequently abstracts a proton form 1a • 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 3 * 9 1 * PS reported in the literatures, singlet excited state PS has been demonstrated to drive these reactions smoothly, which was obviously ignored before.
a,b
Table 2. B-1 Initiated Aerobic CDC Reactions between 1 and 2. View Article Online DOI: 10.1039/C5CC03421C N
1
+ CH3NO2
entry 1
B-1
B-1 (mol %) 4
2.5
O 2N
NO2
3c: 67 (52)d
N
N Br
NO2
Cl
NO2
NO2
3f: 61 (46)
3e: 70 (53)
O
covn. (%)
N
N NO2
3a (%)b
100
79
2
B-1
2
2.5
100
78
3
B-1
1
3
100
80
4
B-1
0.5
4
100
77
5
B-1
0.1
6
100
75
6
B-2
1
3
100
80
7
B-3
1
3
100
84
8
c
B-4
1
2
100
79
9
no B-1
-
3
10
9
d
N
3b: 72 (60)c
3d: 74 (58)
R3
NO2 3
NO2
3a: 80 (71)
3a
irradiation time (h)
R4
NO2
2a
condition
N
R2
N
N
visible light air, r.t. 1a
visble light air, r.t. 2
N
N
B-1
R4
N R2 + O 2
R3
F
N
R1
R1
Table 1. Screen the Reaction Conditions. a B-1
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10
no light
1
-
0
0
11
no O2
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 detected by 1H NMR spectroscopy using diphenylacetonitrile internal standard. c From reference 5. d In the air without irradiation for 4 h.
O
NO2
O
3h: 88 (73)
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
*
1
*
Furthermore, the singlet excited states PS ( B-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 (Table 4, 7a, 7b and 7c). Under the optimized conditions (Table S1, ESI†), methanol (MeOH) was found to be the best solvent for C-P bonds coupling. Gratifyingly, high yields of crosscoupling products were obtained regardless of electron-rich or electron-poor 1 (Table 4, 7e-7j). Table 3. B-1 Initiated Aerobic CDC Reactions between 1a and Dialkyl Malonates.a,b
N
With the understanding of the reaction, we examined the scope of this reaction using the simple B-1 (1 mol %) at room 11 temperature in air. 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 attached on the aromatic ring of 1 benefited for the coupling between 1,2,3,4-tetrahydroisoquinoline derivatives 1 and nitromethane 2. 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 crosscoupling with 1a.
NO2
O
3g: 85 (71)
N
O
+
O
N
B-1
OR
OR visible light MeOH, air, r.t.
RO
RO O
4
1a
5
N
N
OEt
O O OMe
OMe c
5a: 90 (75) a
O
EtO O
O
5b: 65 (51)c
N-phenyltetrahydroisoquinoline 1a (0.1 mmol), dialkyl malonates derivatives 4 (0.1 mmol) in 2 mL MeOH, 1 mol % B-1 (0.001 mmol), under air at room temperature, the conversions are 100%. b Yields detected by 1H NMR spectroscopy using diphenylacetonitrile as internal standard; the isolated product yields were given in parentheses. c Irradiation time: 6 h.
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Table 4. B-1 Initiated Aerobic CDC Reactions between 1 and Phosphite Ester.a,b
N
R2 + R4
O P R4 O H O
R3 1
N
7a: 96 (77)c
N
7c: 90 (77)d
N
O P O Ph O Ph
N
O P EtO OEt
F
7e: 98 (83)c
c
7d: 55 (42)
N Br
7h: 92 (83)
c
7g: 95 (78)
Cl
7f: 98 (85)c
EtO P O OEt
O P EtO OEt
c
O P EtO OEt
N
N
O P EtO OEt
R3
O P O Bn O Bn
7b: 94 (78)c
N
O P O R4 O R4 7
O P O iPr O iPr
EtO P OEt O
N
R2
6
N
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B-1 visible light MeOH, air, r.t.
O e
7i: 82 (69)
O O
N EtO P OEt O
O e
7j: 81 (65) 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 room temperature, the conversion was 100%. b 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 1 * singlet excited PS 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 3 * of triplet excited state PS in the literature. Mechanistic 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. 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.
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R1
R1
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