ChemComm
Communication
3 For general reviews on transition-metal-catalyzed C–H activation of
arenes, see: (a) J. Q. Yu, R. Giri and X. Chen, Org. Biomol. Chem., 2006,
4, 4041; (b) D. Alberico, M. E. Scott and M. Lautens, Chem. Rev., 2007,
107, 174; (c) L.-M. Xu, B.-J. Li, Z. Yang and Z. J. Shi, Chem. Soc. Rev., 2010,
39, 712; (d) T. W. Lyons and M. S. Sanford, Chem. Rev., 2010, 110, 1147.
4 For examples on transition-metal-catalyzed C–H activation of arenes,
see: (a) A. R. Dick, K. L. Hull and M. S. Sanford, J. Am. Chem. Soc., 2004,
126, 2300; (b) R. Giri, J. Liang, J.-G. Lei, J.-J. Li, D.-H. Wang, X. Chen,
I. C. Naggar, C. Guo, B. M. Foxman and J.-Q. Yu, Angew. Chem., Int. Ed.,
2005, 44, 7420; (c) N. Chernyak, A. S. Dudnik, C. Huang and
V. Gevorgyan, J. Am. Chem. Soc., 2010, 132, 8270; (d) L. V. Desai,
H. A. Malik and M. S. Sanford, Org. Lett., 2006, 8, 1141.
Scheme 3 One-pot synthesis of 2-chloro/bromophenols.
5 For examples on palladium-catalyzed C–H halogenation of arenes, see: (a) D.
Kalyani, A. R. Dick, W. Q. Anani and M. S. Sanford, Tetrahedron, 2006,
62, 11483; (b) D. Kalyani, A. R. Dick, W. Q. Anani and M. S. Sanford, Org. Lett.,
2006, 8, 2523; (c) A. R. Dick, K. L. Hull and M. S. Sanford, J. Am. Chem. Soc.,
2004, 126, 2300; (d) R. Giri, X. Chen and J.-Q. Yu, Angew. Chem., Int. Ed., 2005,
44, 2122; (e) M. Sato, S. Nishiyama and T. Tanabe, J. Am. Chem. Soc., 2009,
´
131, 11310; ( f) X. Zhao, E. Dimitrijevic and V. M. Dong, J. Am. Chem. Soc.,
2009, 131, 3466; (g) X. Sun, G. Shan, Y. Sun and Y. Rao, Angew. Chem., Int.
Ed., 2013, 52, 4440; (h) A. John and K. M. Nicholas, J. Org. Chem., 2012,
77, 5600; (i) R. B. Bedford, C. J. Mitchell and R. L. Webster, Chem. Commun.,
2010, 46, 3095; ( j) L. Yang, Z. Lu and S. S. Stahl, Chem. Commun., 2009, 6460;
(k) K. Kikushima, T. Moriuchi and T. Hirao, Tetrahedron Lett., 2010, 51, 340.
6 K. Zhang, S. Cao, S. Zhang and Z. Shi, J. Am. Chem. Soc., 2006, 128, 7416.
7 R. B. Bedford, M. F. Haddow, C. J. Mitchell and R. L. Webster,
Angew. Chem., Int. Ed., 2011, 50, 5524.
8 For C–H activation through weak coordinations, see: (a) K. M. Engle,
T.-S. Mei, M. Wasa and J.-Q. Yu, Acc. Chem. Res., 2012, 45, 788;
(b) D.-H. Wang, D.-F. Wu and J.-Q. Yu, Org. Lett., 2006, 8, 3387;
(c) H.-X. Dai, A. F. Stepan, M. S. Plummer, Y.-H. Zhang and J.-Q. Yu, J. Am.
Chem. Soc., 2011, 133, 7222; (d) T.-S. Mei, D.-H. Wang and J.-Q. Yu, Org. Lett.,
2010, 12, 3140; (e) T.-S. Mei, R. Giri, N. Maugel and J.-Q. Yu, Angew. Chem.,
Int. Ed., 2008, 47, 5215; ( f) J.-J. Li, T.-S. Mei and J.-Q. Yu, Angew. Chem., Int.
Ed., 2008, 47, 6452; (g) G. Shan, X. Yang, L. Ma and Y. Rao, Angew. Chem., Int.
Ed., 2012, 51, 13070; (h) Y. Yang, Y. Lin and Y. Rao, Org. Lett., 2012, 14, 2874.
9 For a review on palladacycles, see: J. Dupont, C. S. Consorti and
J. Spencer, Chem. Rev., 2005, 105, 2527.
Scheme 4 KIE and separate rate constant studies.
results indicate that C–H activation was involved in the rate-limiting
step of this transformation. Although details about the mechanism
remain to be ascertained, on the basis of these observations, a plausible
mechanism for this reaction can be delineated as in the following. Step
(i) involves chelate-directed C–H activation of the substrate which will
afford a five-membered cyclopalladium (II) intermediate (TfOH might
be involved in the in situ generation of an electron-deficient Pd complex,
Pd(OTf)2,15 which can promote more challenging C–H activation
through weak coordination, even at room temperature). In the second
step (ii), Pd(II) was oxidized into a possible Pd(IV) intermediate16 by NCS.
The final step (iii) involved C–Cl bond-forming reductive elimination to
afford the chlorinated product and turned Pd(IV) back into Pd(II).
In summary, a practical, room-temperature Pd(II) catalyzed ortho-
chlorination/bromination reaction has been developed for the synth-
esis of 2-chloro/bromophenol derivatives from easily accessible phe-
nols. This reaction represents one of the rare examples of mild C–H
functionalization at ambient temperature. Moreover, it demonstrates
an excellent regioselectivity and reactivity in comparison with litera-
ture conditions for C–H halogenation. The practicality and efficiency
of this reaction was further exemplified by a gram-scale synthesis and
one-pot protocol for the preparation of 2-chloro/bromophenols.
Further studies on the application and mechanism of this new
reaction are in progress in our laboratory.
10 For some examples using different oxidants: (a) M. S. Chen,
N. Prabagaran, N. A. Labenz and M. C. White, J. Am. Chem. Soc., 2005,
127, 6970; (b) B. D. Dangel, J. A. Johnson and D. Sames, J. Am. Chem. Soc.,
2001, 123, 8149; (c) Y. Wie and N. Yoshikai, Org. Lett., 2011, 13, 5504;
´
(d) P. Novak, A. Correa, J. Gallardo-Donaire and R. Martin, Angew. Chem.,
Int. Ed., 2011, 50, 12236; (e) M. S. Chen and M. C. White, Science, 2007,
318, 783; ( f ) S. Ueda and H. Nagasawa, Angew. Chem., Int. Ed., 2008,
47, 6411; (g) L. M. Huffman, A. Casitas, M. Font, M. Canta, M. Costas,
X. Ribas and S. S. Stahl, Chem.–Eur. J., 2011, 17, 10643; (h) E. M. Simmons
and J. F. Hartwig, Nature, 2012, 483, 70; (i) Y. Zhao, W.-L. Yim, C. K. Tan
and Y.-Y. Yueng, Org. Lett., 2011, 13, 4308.
11 For a phenolic ester-directed C–H bond activation: B. Xiao, Y. Fu, J. Xu,
T.-J. Gong, J.-J. Dai, J. Yi and L. Liu, J. Am. Chem. Soc., 2010, 132, 468.
12 For a Boc-directed C–H bond activation, see: D.-H. Wang, X.-S. Hao,
D.-F. Wu and J.-Q. Yu, Org. Lett., 2006, 8, 3387.
13 For using carbamate as directing groups: (a) X. Zhao, C. S. Yeung
¨
and V. M. Dong, J. Am. Chem. Soc., 2010, 132, 5837; (b) N. Schroder,
J. Wencel-Delord and F. Glorius, J. Am. Chem. Soc., 2012, 134, 8298;
(c) Q. Zhang, H. Yu, Y. g. Li, L. Liu, Y. Huang and Y. Fu, Dalton
Trans., 2013, 42, 4175; (d) T. Gong, B. Xiao, Z. Liu, J. Wan, J. Xu,
D. Luo, Y. Fu and L. Liu, Org. Lett., 2011, 12, 3235; (e) R. Bedford,
R. Webster and C. Mitchell, Org. Biomol. Chem., 2009, 7, 4853;
( f ) D. Wang, X. Hao, D. Wu and J. Yu, Org. Lett., 2006, 8(15), 3387.
14 For an excellent example of bromination and iodination with Rh(III)
This work was supported by the national ‘973’ grant from the
Ministry of Science and Technology (grant # 2011CB965300),
National Natural Science Foundation of China (grant # 21142008)
and Tsinghua University Initiative Scientific Research Program. We
thank Mrs C. Wang for her help in our studies.
¨
catalyst: N. Schroder, J. Wencel-Delord and F. Glorius, J. Am. Chem.
Soc., 2012, 134, 8298.
15 It had been reported that the use of TfOH to tune the electrophilicity
of Pd(II) is a useful strategy to achieve difficult C–H activation. For
related references, please see: (a) T. Nishikata, A. R. Abela and
B. H. Lipshutz, Angew. Chem., Int. Ed., 2010, 49, 781; (b) X. Wang,
T.-S. Mei and J.-Q. Yu, J. Am. Chem. Soc., 2009, 131, 7520; (c) B. Xiao,
T. Gong, J. Xu, Z. Liu and L. Liu, J. Am. Chem. Soc., 2011, 133, 1466.
˜
Notes and references
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2 (a) K. Ohkubo, A. Fujimoto and S. Fukuzumi, J. Am. Chem. Soc., 16 For reviews about high-valent PdIV/III chemistry: (a) K. Muniz, Angew. Chem.,
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1264 | Chem. Commun., 2014, 50, 1262--1264
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