Organic Letters
Letter
Sons: Hoboken, 2013; pp 589−642. (f) Surry, D. S.; Buchwald, S. L.
Chem. Sci. 2011, 2, 27−50. (g) Surry, D. S.; Buchwald, S. L. Chem. Sci.
2010, 1, 13−31. (h) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.
2008, 108, 3054−3131. (i) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41,
1450−1460.
simple and functionalized cyclic secondary amines to afford the
tertiary amines 7a−m in good yields. Our primary goal was to
test our method by synthesizing some known building blocks
that have been employed for assembling bioactive molecules.
Toward this, the coupling products 7h (a key intermediate for
preparing protein kinase inhibitors),10 7j (used for synthesizing
KCNQ2/Q3 potassium channel opener11a and hedgehog
pathway inhibitor11b), and 7m (a building block for producing
potent epidermal growth factor (EGFR) receptor inhibitor)12
were successively obtained by using suitable coupling partners.
Notably, the present coupling reaction is very sensitive to steric
hindrance of both coupling partners because incomplete
conversion is observed during the preparation of 7n and 7o
even at a higher catalytic loading.
(2) Beletskaya, I. P.; Cheprakov, A. V. Organometallics 2012, 31,
7753−7808.
(3) (a) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J.
Am. Chem. Soc. 2008, 130, 13552−13554. (b) Bruno, N. C.; Tudge, M.
T.; Buchwald, S. L. Chem. Sci. 2013, 4, 916−920.
(4) Shen, Q.; Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130,
6586−6596.
(5) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.;
Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101−4111.
(6) For recent reports on Cu/ligand catalyzed aryl amination
reactions, see: (a) Deldaele, C.; Evano, G. ChemCatChem 2016, 8,
In summary, we have discovered that MNBO and related
amides are superior ligands for promoting Cu-catalyzed
coupling of aryl halides with amines. Over 10000 turnovers
were observed in the case of the Cu2O/MNBO-catalyzed
coupling reaction of some aryl iodides with primary amines.
Only 0.1−0.5 mol % Cu2O and ligand were necessary for
coupling reactions with a wide range of (hetero)aryl bromides
and amines. The mild, environmentally friendly reaction
conditions and high turnover numbers attributed the
potentiality of the present method toward the preparation of
aryl amines, particularly in large-scale production. Application
of this catalytic system to other coupling reactions is being
actively investigated in our laboratory and will be disclosed in
due course.
́
1319−1328. (b) Rovira, M.; Soler, M.; Guell, I.; Wang, M.-Z.; Gomez,
̈
L.; Ribas, X. J. Org. Chem. 2016, 81, 7315−7325. (c) Bethel, P. A.;
Roberts, B.; Bailey, A. Tetrahedron Lett. 2014, 55, 5186−5190.
(d) Fantasia, S.; Windisch, J.; Scalone, M. Adv. Synth. Catal. 2013, 355,
627−637.
(7) Altman, R. A.; Koval, E. D.; Buchwald, S. L. J. Org. Chem. 2007,
72, 6190−6199.
(8) Larsson, P.-F.; Correa, A.; Carril, M.; Norrby, P.-O.; Bolm, C.
Angew. Chem., Int. Ed. 2009, 48, 5691−5693.
(9) (a) Zhou, W.; Fan, M.; Yin, J.; Jiang, Y.; Ma, D. J. Am. Chem. Soc.
2015, 137, 11942−11946. (b) Fan, M.; Zhou, W.; Jiang, Y.; Ma, D.
Org. Lett. 2015, 17, 5934−5937. (c) Fan, M.; Zhou, W.; Jiang, Y.; Ma,
D. Angew. Chem., Int. Ed. 2016, 55, 6211−6215. (d) Xia, S.; Gan, L.;
Wang, K.; Li, Z.; Ma, D. J. Am. Chem. Soc. 2016, 138, 13493−13496.
(10) Qian, X.; Zhu, Y.-L. WO2015027222, 2015.
(11) (a) Amato, G.; Roeloffs, R.; Rigdon, G. C.; Antonio, B.; Mersch,
T.; McNaughton-Smith, G.; Wickenden, A. D.; Fritch, P.; Suto, M. J.
ACS Med. Chem. Lett. 2011, 2, 481−484. (b) Bhattarai, D.; Jung, J. H.;
Han, S.; Lee, H.; Oh, S. J.; Ko, H. W.; Lee, K. Eur. J. Med. Chem. 2017,
125, 1036−1050.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
(12) Zhou, W.; Ercan, D.; Janne, P. A.; Gray, N. S. Bioorg. Med.
̈
Chem. Lett. 2011, 21, 638−643.
Experimental procedures, spectral data, and copies of all
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the Chinese Academy of Sciences
(supported by the Strategic Priority Research Program, Grant
Nos. XDB20020200 and QYZDJ-SSW-SLH029) and the
National Natural Science Foundation of China (Grant No.
21621002) for financial support.
REFERENCES
■
(1) For reviews, see: (a) Shaughnessy, K. H.; Ciganek, E.; Devasher,
R. B. In Organic Reactions; Denmark, S. E., Ed.; John Wiley & Sons:
Hoboken, 2014; Vol. 85, pp 1−668. (b) Crawford, S. M.; Lavery, C.
B.; Stradiotto, M. Chem. - Eur. J. 2013, 19, 16760−16771.
(c) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C.
Chem. Soc. Rev. 2014, 43, 3525−3550. (d) Casitas, A.; Ribas, X. Chem.
Sci. 2013, 4, 2301−2318. (e) Jiang, Y.; Ma, D. In Copper-Mediated
Cross-Coupling Reactions; Evano, G., Blanchard, N., Eds.; John Wiley &
D
Org. Lett. XXXX, XXX, XXX−XXX