3
O
O
O
O
O
CF3
O
Pd(OAc)2 10 mol%
TDG 20 mol%
CF3
Pd(OAc)2 10 mol%
TDG 20 mol%
Br
Br
NH2
NH2
Br
+
+
N Br
N Br
R
R
Cl
DCE:TFA = 5:1
DCE:TFA = 5:1
60 °C, 24 h
Cl
O
O
2.5 eq.
2
R
R
TDG
1.0 eq.
1.2 eq.
60°C
24h
TDG
Br
1
2
3
4
5
O
O
O
O
O
Br
Br
O
O
O
O
Br
Br
Cl
Br
Br
Br
F
Br
O
Br
Cl
Br
Br
Br
b
3a
3b
3g
3c
3e
3j
86%
O
76%
O
63%
O
3d
88%
54%
5a
5b
5c
67%
73%
82%
O
O
Br
Br
Br Cl
Cl
Br
Br
a
Reagents and conditions: 4 (0.4 mmol), 2 (2.5 eq.), Pd(OAc)2
(10 mol%), TDG (20 mol%), DCE (2.5 mL), TFA (0.5 mL), 60
°C, 24 h. Isolated yield after column chromatography.
Br
O
O2N
3h
F
59%
b
b
3f
20%
O
34%
O
3i
80%
O
98%
O
O
Br
Br
Br
Br
Br
F
Acknowledgments
Cl
Cl
F
Cl
Cl
Br
We are grateful for financial support from the National
Natural Science Foundation of China (no. 21703162, 21971200)
and the Natural Science Foundation of Hubei Province
(2018CFB505).
b
b
3k
3l
3m
53%
54%
69%
3n
3s
3o
80%
O
57%
O
O
O
O
O
Br
Br
Br
Br
Br
O
F
References and notes
b
b
3p
36%
O
3q
3r
3t
50%
87%
O
37%
76%
O
1.
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Ind. Eng. Chem. Res. 2018, 57, 12314-12322.
O
O
Br
Br
Br
Br
Br
Br
S
Br
O
O
O
O
3u
3v
3w
3x
3y
30%
87%
53%
30%
90%
mono:di=1:1.1 mono:di=1:1.5
a
Reagents and conditions: 1 (0.4 mmol), 2 (1.2 eq.), Pd(OAc)2
(10 mol%), TDG (20 mol%), DCE (2.5 mL), TFA (0.5 mL), 60
°C, 24 h. Isolated yield after column chromatography. 1 (0.2
b
mmol), 2 (1.2 eq.), Pd(OAc)2 (10 mol%), TDG (20 mol%), DCE
(1 mL), TFA (0.2 mL), 60 °C, 24 h.
2.
3.
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Table 4. Optimization of the reaction conditions.a
O
O
O
CF3
Pd(OAc)2 10 mol%
TDG 20 mol%
4.
5.
Br
Br
NH2
+
N Br
DCE:TFA = 5:1
60 °C , 24 h
Cl
O
TDG
4a
2
5a
Entry
NBS
Yield 5a (%)
29%
1
2
3
4
1.5 eq.
2.0 eq.
2.3 eq.
2.5 eq.
42%
65%
73%
a
Reagents and conditions: 4a (0.1 mmol), 2, Pd(OAc)2 (10
mol%), TDG (20 mol%), DCE (1 mL), TFA (0.2 mL), 60 °C, 24
h. Isolated yield after column chromatography.
6. (a) Li, B.J.; Yang, S.D.; Shi, Z.J. Synlett 2008, 7, 949-957; (b)
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New J. Chem. 2019, 43, 3462-3468.
3. Conclusion
We have developed an efficient Pd-catalyzed ortho-C(sp2)‒H
bromination of benzaldehydes via a monodentate TDG strategy
which proceeds under mild conditions without the addition of
silver salts or an external ligand.
7.
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Table 5.
Scope of the ortho-C(sp2)−H dibromination of benzaldehydesa