10.1002/ejoc.202100868
European Journal of Organic Chemistry
COMMUNICATION
a) Radical trapping experiments
TEMPO (1.5 equiv)
Acknowledgements
N
CF2CO2Et
Me
standard conditions
TEMPOCF2CO2Et
N
Financial support from the National Natural Science Foundation
of China (No. 21871049) is gratefully acknowledged.
+
N
51%
O
N
3a 0%
O
Keywords: Cascade/cyclization • Difluoroalkylation • Photoca-
1a
Me
standard conditions
talysis • Polycyclic imidazoles • Radicals
Ph
+
3a 8%
CF2CO2Et
60%
1,1-diphenyl ethene (1.5 equiv)
Ph
[1]
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26, 2684-2712; For Selected examples: d) V. O. Iaroshenko, D. Ostrov-
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b) Interalmolecular cyclization reaction
N
fac-Ir(ppy)3 (0.01 equiv)
no reaction
Ph
+
+
BrCF2CO2Et
1.5 equiv
Cs2CO3 (1.2 equiv)
3 W blue LEDs
DCM (0.1 M), r.t.
1.5 equiv
N
Ac
Scheme 3. Mechanism studies
[2]
of a free radical pathway and the formation of ▪CF2CO2Et during
the procedure. To preliminarily explore the role of photo-
irradiation, the light on/off experiment was performed (details in
SI). The result showed that continuous exposure to visible light
is indispensable to the high reaction efficiency, indicating that a
radical chain propagation process is unlikely to be
a
predominant pathway. Additionally, we calculated the apparent
quantum yield of this protocol (details in SI), and a value of (0.60)
unambiguously indicates that this reaction proceeds via
photocatalytic pathway rather than radical chain propagation.
Finally, we tried internalmolecular version of this transformation
with N-acetyl benzoimidazole and styrene as the substrates
under the standard conditions; however, no reaction happened
with the conservation of all the starting materials (Scheme 3b).
On the basis of the above experiments and related refer-
[3]
a) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110,
624-655; b) C. G. Newton, S.-G. Wang, C. C. Oliveira, N. Cramer,
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ences[13]
, we proposed a reaction mechanism as follows
(Scheme 4, take the formation of 3a for example). Under irradia-
tion of visible light, the photocatalyst [Ir3+] transfers to an excited-
state [Ir3+]* which is subsequently oxidized by Rf-Br to form
difluoroalkyl radical (▪Rf) and the [Ir4+] complex. The addition of
Rf radical to 1a generates intermediate I, and I could be con-
verted into the radical intermediate II via intramolecular radical
cyclization to the C2 of benzimidazole ring. Subsequent oxidiza-
tion of II by [Ir4+] complex forms the cation intermediate III which
is deprotonated under a base to yield terminal product 3a.
In conclusion, we have described an efficient approach to
difluoroalkylated polycyclic benzimidazole derivatives from direct
radical cycloaddition of imidazoles and olefins. Mechanism
studies indicated a photocatalytic radical cascade cyclization
strategy. This methodology is featured with green reaction
conditions and commendable functional group compatibility.
[4]
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Ye, J. Am. Chem. Soc. 2018, 140, 5360-5364; b) J. Loup, V. Müller, D.
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[6]
[7]
a) S.-J. Lou, Z. Mo, M. Nishiura, Z. Hou, J. Am. Chem. Soc. 2020, 142,
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Huang, J. Wang, A. K. Singh, A. Lei, Chem. Rev. 2017, 117, 9016-9085;
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Ouyang, Y. Lai, J. Huang, R. Luo, Org. Chem. Front. 2021, 8, 1345-
1363.
[Ir3+
]
hv
Rf
N
N
Rf
H
[Ir3+]*
Me
Me
N
N
-H
3a
Br Rf
Rf
III
O
O
[Ir4+
]
N
[8]
a) S. Mai, Y. Luo, X. Huang, Z. Shu, B. Li, Y. Lan, Q. Song, Chem.
Commun. 2018, 54, 10240-10243; b) K. Sun, S.-J. Li, X.-L. Chen, Y.
Liu, X.-Q. Huang, D.-H. Wei, L.-B. Qu, Y.-F. Zhao, B. Yu, Chem. Com-
mun. 2019, 55, 2861-2864; c) F.-L. Zeng, K. Sun, X.-L. Chen, X.-Y. Yu-
an, S.-Q. He, Y. Liu, Y.-Y. Peng, L.-B. Qu, Q.-Y. Lv, B. Yu, Adv. Synth.
Catal. 2019, 361, 5176-5181; d) R. Boora, G. Ravi kumar, B. V. Subba
Reddy, Org. Biomol. Chem. 2019, 17, 9627-9630; e) Y. Yuan, Y. Zheng,
N
N
Rf
H
N
Rf
Me
N
N
I
II
O
O
Me
1a
2
O
Me
Scheme 4. Proposed mechanism
4
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