Organic Letters
Letter
KCNQ2 channel inhibitor.21 Furthermore, a three-component
coupling in neat condition provided an antimicrobial agent.22
In conclusion, we have developed a mild copper-catalyzed 2-
picolinamide directed electrophilic ortho-amination of anilines
and naphthylamines with O-benzoylhydroxylamines. The
reaction proceeds smoothly without any external oxidants or
additives. Notably, bicyclic anilines were also effective
substrates to a broad scope of dialkylamines under this
electrophilic amination strategy, which is a remarkable
discovery, compared to the existing methods. The amination
has also been demonstrated in water, providing an environ-
mentally benign methodology. Thus, we anticipate that this
practical electrophilic amination will be highly applicable in
academia and industrial research.
(b) Guram, A. S.; Buchwald, S. L. Palladium-Catalyzed Aromatic
Aminations with in situ Generated Aminostannanes. J. Am. Chem. Soc.
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and tin amides. J. Am. Chem. Soc. 1994, 116, 5969−5970.
(3) For Cu-catalysed cross-coupling reactions for C−N formation,
see: (a) Gao, J.; Bhunia, S.; Wang, K.; Gan, L.; Xia, S.; Ma, D.
Discovery of N-(Naphthalen-1-yl)-N′-alkyl Oxalamide Ligands
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(4) (a) Hardouin Duparc, V.; Bano, G. L.; Schaper, F. Chan−
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
Experimental procedures, spectroscopic data, X-ray
1
crystallography data, H and 13C NMR spectra for all
synthesized compounds (PDF)
(5) (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 6790−6791. (b) Uemura, T.; Imoto, S.; Chatani, N.
Chem. Lett. 2006, 35, 842−843.
Accession Codes
CCDC 1906594 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(6) (a) Roane, J.; Daugulis, O. A General Method for Aminoquino-
line-Directed, Copper-Catalyzed sp2 C−H Bond Amination. J. Am.
Chem. Soc. 2016, 138, 4601−4607. (b) Tran, L. D.; Roane, J.;
Daugulis, O. Directed Amination of Non-Acidic Arene C-H Bonds by
a Copper−Silver Catalytic System. Angew. Chem., Int. Ed. 2013, 52,
6043−6046.
(7) (a) Kim, H.; Heo, J.; Kim, J.; Baik, M.-H.; Chang, S. Copper-
Mediated Amination of Aryl C−H Bonds with the Direct Use of
Aqueous Ammonia via a Disproportionation Pathway. J. Am. Chem.
Soc. 2018, 140, 14350−14356. (b) Kim, H.; Chang, S. The Use of
Ammonia as an Ultimate Amino Source in the Transition Metal-
Catalyzed C−H Amination. Acc. Chem. Res. 2017, 50, 482−486.
(8) (a) Doran, T. M.; Gao, Y.; Simanski, S.; McEnaney, P.; Kodadek,
T. High affinity binding of conformationally constrained synthetic
oligomers to an antigen-specific antibody: Discovery of a diagnosti-
cally useful synthetic ligand for murine Type 1 diabetes autoanti-
bodies. Bioorg. Med. Chem. Lett. 2015, 25, 4910−4917. (b) Abdul-
Hay, S. O.; Bannister, T. D.; Wang, H.; Cameron, M. D.; Caulfield, T.
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AUTHOR INFORMATION
■
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by DST, SERB, Government of India
for the Ramanujan fellowship; Award No. SR/S2/RJN-97/
2012 and Extra Mural Research Grant No. EMR/2014/
000469 for financial support. H.M.B. and A.B. thank CSIR for
their fellowships.
Schurer, S. C.; Madoux, F.; Hodder, P.; Leissring, M. A. Selective
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Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-
Irreversible Thiol-Modifying Inhibitors. ACS Chem. Biol. 2015, 10,
2716−2724. (c) Gong, Y.; Somersan Karakaya, S.; Guo, X.; Zheng, P.;
Gold, B.; Ma, Y.; Little, D.; Roberts, J.; Warrier, T.; Jiang, X.; Pingle,
M.; Nathan, C. F.; Liu, G. Benzimidazole-based compounds kill
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(d) Gammons, M. V.; Fedorov, O.; Ivison, D.; Du, C.; Clark, T.;
Hopkins, C.; Hagiwara, M.; Dick, A. D.; Cox, R.; Harper, S. J.;
Hancox, J. C.; Knapp, S.; Bates, D. O. Topical Antiangiogenic SRPK1
Inhibitors Reduce Choroidal Neovascularization in Rodent Models of
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(e) Cheung, Y.-Y.; Yu, H.; Xu, K.; Zou, B.; Wu, M.; McManus, O.
B.; Li, M.; Lindsley, C. W.; Hopkins, C. R. Discovery of a Series of 2-
Phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as Novel Molecular
Switches that Modulate Modes of Kv7.2 (KCNQ2) Channel
Pharmacology: Identification of (S)-2-Phenyl-N-(2-(pyrrolidin-1-yl)-
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