Organic Letters
Letter
ne/tBuOH 22/1) was vital to achieve high yields, which could
be ascribed to the formation of a possible conjugated acid−
base pair (tBuO···H···OtBu), consistent with our recent
publication.19
Daheng Wen − Shanghai Key Laboratory of Molecular
Catalysis and Innovative Materials, Department of
Chemistry, Fudan University, Shanghai 200438, China
Qingshu Zheng − Shanghai Key Laboratory of Molecular
Catalysis and Innovative Materials, Department of
Chemistry, Fudan University, Shanghai 200438, China
On the basis of these control experiments and combined
with previous reports,18 a plausible mechanism is proposed in
Scheme 4d. Initially, after the coordination of the NHC ligand
derived from APr·HCl with Ni(0), the generated active
catalytic species A was readily reacted with aryl chlorides to
form intermediate B via oxidative addition. The intermediate B
could be immediately trapped by amines generated from the
corresponding amides under strong basic conditions, leading to
the formation of intermediate C. After reductive elimination,
product amines were produced along with the regeneration of
active species A to complete the catalytic cycle.
In summary, an unprecedented Ni-catalyzed amination of
aryl chlorides with inactive amides as amino sources under
mild reaction conditions has been developed. Moderate to
excellent yields were obtained for both coupling partners with
electron-rich, electron-poor, and sterically hindered substitu-
ents with low catalyst loading. The selectivity for the amination
was relatively good, and no possible carbonyl products were
generated. The plausible mechanism was proposed based on
several control experiments in which a strong base was
responsible for the cleavage of the amide’s C−N bond under
ambient reaction conditions. This protocol complements the
routine nickel-catalyzed cross-coupling transformations of
amides, potentially providing a new approach to achieve
aromatic amines from amides and aryl chlorides with earth-
abundant metal catalysts.
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Key R&D Program of
China (no. 2016YFA0202902), the National Natural Science
Foundation of China (nos. 21572036, 21871059, and
21861132002), and the Department of Chemistry at Fudan
University is gratefully acknowledged.
REFERENCES
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(1) (a) Bednarek, C.; Wehl, I.; Jung, N.; Schepers, U.; Brase, S. The
berg, A.; Breneman, C. M.; Liebman, J. F. The Amide Linkage:
Structural Significance in Chemistry, Biochemistry and Materials Science;
Wiley−VCH: New York, 2003.
(2) Dunetz, J. R.; Magano, J.; Weisenburger, G. A. Large-Scale
ASSOCIATED CONTENT
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sı
* Supporting Information
(4) (a) Meng, G.; Shi, S.; Lalancette, R.; Szostak, R.; Szostak, M.
J. Am. Chem. Soc. 2018, 140, 727−734. (b) Ruider, S. A.; Maulide, N.
(5) For reviews on amide activation, see: (a) Li, G.; Szostak, M.
Chem. Rec. 2020, 20, 649−659. (b) Dander, J. E.; Garg, N. K.
The Supporting Information is available free of charge at
1
Experimental procedures and H, 13C, and 19F NMR
spectra of compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Bo Tu − Shanghai Key Laboratory of Molecular Catalysis and
Innovative Materials, Department of Chemistry, Fudan
University, Shanghai 200438, China; Email: botu@
́
therein.
Tao Tu − Shanghai Key Laboratory of Molecular Catalysis
and Innovative Materials, Department of Chemistry, Fudan
University, Shanghai 200438, China; State Key Laboratory
of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032,
China; Green Catalysis Center and College of Chemistry,
Zhengzhou University, Zhengzhou 450001, China;
(7) Sabatini, M. T.; Boulton, L. T.; Sneddon, H. F.; Sheppard, T. D.
Nat. Catal. 2019, 2, 10−17.
Rev. 2020, 120, 2613−2692.
(9) Select examples: (a) Murugesan, K.; Chandrashekhar, V. G.;
Protoc. 2020, 15, 1313−1337. (b) Zhang, L.; Liardet, L.; Luo, J. S.;
̈
Authors
Amination. Nat. Catal 2019, 2, 366−373. (c) Tang, S.; Wang, S.; Liu,
2018, 57, 4737−4741. (d) Li, G. C.; Ji, C. L.; Hong, X.; Szostak, M.
Jinpeng Li − Shanghai Key Laboratory of Molecular Catalysis
and Innovative Materials, Department of Chemistry, Fudan
University, Shanghai 200438, China
Changyu Huang − Shanghai Key Laboratory of Molecular
Catalysis and Innovative Materials, Department of
Chemistry, Fudan University, Shanghai 200438, China
D
Org. Lett. XXXX, XXX, XXX−XXX