Organic Letters
Letter
Liu, Z.-J.; Wan, J.; Luo, D.-F.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 3235.
(c) Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132,
5837.
metalation. Then, an electrophilic attack at the meta-position of
the directing group occurred to give active species B through
the strong ortho/para-directing effect of the Ru−CAr σ-bond.
Meanwhile, an alkyl radical originated from a ruthenium-
mediated single-electron-transfer process. The deprotonation of
species B with the assistance of ruthenium(III) and a base
formed the more stable complex C. Finally, ligand exchange of
complex C with 2-phenoxypyridine released the final meta-
alkylated product, and the active species was recycled.
In conclusion, we achieved the synthesis of m-alkylphenols
via a ruthenium-catalyzed meta-selective C−H bonds alkylation
of 2-phenoxypyridines with alkyl bromide and the removal of
the directing groups. Mechanistic studies indicated that the m-
CAr−H bond alkylation might involve a radical process and that
a six-membered ruthenacycle complex was the active catalyst.
Furthermore, the application of the ruthenium-catalyzed m-
alkylphenol preparation in synthetic chemistry is underway.
(7) (a) Liu, B.; Jiang, H.-Z.; Shi, B.-F. J. Org. Chem. 2014, 79, 1521.
(b) Ma, W.; Ackermann, L. Chem. - Eur. J. 2013, 19, 13925. (c) Yao, J.;
Feng, R.; Wu, Z.; Liu, Z.; Zhang, Y. Adv. Synth. Catal. 2013, 355, 1517.
(d) Niu, L.; Yang, H.; Wang, R.; Fu, H. Org. Lett. 2012, 14, 2618.
(e) Ackermann, L.; Diers, E.; Manvar, A. Org. Lett. 2012, 14, 1154.
(f) Chu, J.-H.; Lin, P.-S.; Wu, M.-J. Organometallics 2010, 29, 4058.
(g) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009, 11,
3120. (h) Lou, S.-J.; Chen, Q.; Wang, Y.-F.; Xu, D.-Q.; Du, X.-H.; He,
J.-Q.; Mao, Y.-J.; Xu, Z.-Y. ACS Catal. 2015, 5, 2846.
(8) Cong, X.; You, J.; Gao, G.; Lan, J. Chem. Commun. 2013, 49, 662.
(9) Dai, H.-X.; Li, G.; Zhang, X.-G.; Stepan, A. F.; Yu, J.-Q. J. Am.
Chem. Soc. 2013, 135, 7567. (b) Leow, D.; Li, G.; Mei, T.; Yu, J.-Q.
Nature 2012, 486, 518. (c) Shen, P.-X.; Wang, X.-C.; Wang, P.; Zhu,
R.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 11574.
(10) Luo, J.; Preciado, S.; Larrosa, I. J. Am. Chem. Soc. 2014, 136,
4109.
(11) Yu, D.-G.; de Azambuja, F.; Glorius, F. Angew. Chem., Int. Ed.
2014, 53, 7710.
ASSOCIATED CONTENT
* Supporting Information
■
(12) (a) Zhu, L. Chin. Appl. Technol. 2016, 274, 109. (b) Nauen, R.;
Smagghe, G. Pest Manage. Sci. 2006, 62, 379. (c) Hamilton, A. J.;
Chen, L. J. Am. Chem. Soc. 1988, 110, 4379. (d) Elks, J. The Dictionary
of Drugs: Chemical Data, Structures and Bibliographies; Springer: New
York, 2014; pp 482−483. (e) Huffman, J. W.; Joyner, H. H.; Lee, M.
D.; Jordan, R. D.; Pennington, W. T. J. Org. Chem. 1991, 56, 2081.
(13) (a) Clark, A. M.; Rickard, C. E. F.; Roper, W. R.; Wright, L. J.
Organometallics 1999, 18, 2813. (b) Clark, A. M.; Rickard, C. E. F.;
Roper, W. R.; Wright, L. J. Organometallics 1998, 17, 4535.
(14) (a) Hofmann, N.; Ackermann, L. J. Am. Chem. Soc. 2013, 135,
5877. (b) Li, J.; Warratz, S.; Zell, D.; De Sarkar, S. D.; Ishikawa, E. E.;
Ackermann, L. J. Am. Chem. Soc. 2015, 137, 13894. (c) Paterson, A. J.;
St John-Campbell, S.; Mahon, M. F.; Press, N. J.; Frost, C. G. Chem.
Commun. 2015, 51, 12807. (d) Ruan, Z.; Zhang, S.-K.; Zhu, C.; Ruth,
P. N.; Stalke; Ackermann, L. Angew. Chem., Int. Ed. 2017, 56, 2045.
(e) Leitch, J. A.; McMullin, C. L.; Mahon, M. F.; Bhonoah, Y.; Frost,
C. G. ACS Catal. 2017, 7, 2616.
(15) (a) Li, G.; Ma, X. X.; Jia, C. Q.; Han, Q. Q.; Wang, Y.; Wang, J.
J.; Yu, L. Y.; Yang, S. L. Chem. Commun. 2017, 53, 1261. (b) Teskey,
C. J.; Lui, A. Y. W.; Greaney, M. F. Angew. Chem., Int. Ed. 2015, 54,
11677. (c) Yu, Q.; Hu, L. A.; Wang, Y.; Zheng, S. S.; Huang, J. H.
Angew. Chem., Int. Ed. 2015, 54, 15284. (d) Fan, Z. L.; Ni, J. B.; Zhang,
A. J. Am. Chem. Soc. 2016, 138, 8470. (e) Ackermann, L.; Hofmann,
N.; Vicente, R. Org. Lett. 2011, 13, 1875. (f) Li, J.; De Sarkar, S.;
Ackermann, L. Top. Organomet. Chem. 2015, 55, 217. (g) Saidi, O.;
Marafie, J.; Ledger, A. E.; Liu, P. M.; Mahon, M. F.; Kociok-Kohn, G.;
Whittlesey, M. K.; Frost, C. G. J. Am. Chem. Soc. 2011, 133, 19298.
(h) Warratz, S.; Burns, D. J.; Zhu, C.; Korvorapun, K.; Rogge, T.;
Scholz, J.; Jooss, C.; Gelman, D.; Ackermann, L. Angew. Chem., Int. Ed.
2017, 56, 1557.
S
The Supporting Information is available free of charge on the
1
Experimental details; H and 13C NMR spectra; X-ry
crystal structure data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Author Contributions
∥P.G. and X.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Natural Science
Foundation of China (NSFC, Nos. 21102005 and 21403006)
for financial support of this work.
REFERENCES
■
(1) Synthetic and Natural Phenols; Tyman, J. H. P., Ed.; Elsevier: New
York, 1996.
(2) Selected cross-coupling reactions involving phenols and their
derivatives: (a) Song, W.; Ackermann, L. Angew. Chem., Int. Ed. 2012,
51, 8251. (b) Hao, X.-Q.; Chen, L.-J.; Ren, B.; Li, L.-Y.; Yang, X.-Y.;
Gong, J.-F.; Niu, J.-L.; Song, M.-P. Org. Lett. 2014, 16, 1104. (c) Yu,
Z.; Ma, B.; Chen, M.; Wu, H.-H.; Liu, L.; Zhang, J. J. Am. Chem. Soc.
2014, 136, 6904. (d) Zhu, R.; Wei, J.; Shi, Z. Chem. Sci. 2013, 4, 3706.
(e) Sharma, U.; Naveen, T.; Maji, A.; Manna, S.; Maiti, D. Angew.
Chem., Int. Ed. 2013, 52, 12669. (f) Takise, R.; Muto, K.; Yamaguchi,
J.; Itami, K. Angew. Chem., Int. Ed. 2014, 53, 6791. (g) Correa, A.;
Martin, R. J. Am. Chem. Soc. 2014, 136, 7253.
(3) Wade, L. G., Jr. Organic Chemistry, 7th ed.; Pearson Education,
Inc.: Upper Saddle River, 2010; Chapter 17, pp 751−802.
(4) Bedford, R. B.; Coles, S. J.; Hursthouse, M. B.; Limmert, M. E.
Angew. Chem., Int. Ed. 2003, 42, 112.
(5) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L. J. Am.
Chem. Soc. 2010, 132, 468.
(6) (a) Xiao, B.; Gong, T.-J.; Liu, Z.-J.; Liu, J.-H.; Luo, D.-F.; Xu, J.;
Liu, L. J. Am. Chem. Soc. 2011, 133, 9250. (b) Gong, T.- J.; Xiao, B.;
D
Org. Lett. XXXX, XXX, XXX−XXX