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Organic & Biomolecular Chemistry
Page 4 of 6
ARTICLE
Journal Name
the reaction is probably H-bond activation of the maleimide by
HFIP. Then, nucleophilic attack of aniline (1a) on 2a generates
intermediate 9, which subsequently undergoes hydrogen
transfer to afford the expected product 3a. Owing to HFIP–
maleimide association, aniline can only react in its para-
position, which is sterically less hindered than the ortho-
position.
Kuwahara, H. Ozaki and H. Sawai, J. Am. Chem. Soc., 2007,
DOI: 10.1039/C8OB03073A
1
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2
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F3C
CF3
H
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O
N
N
O
O
N
O
O
H
HFIP
1a
3a
N
N
O
O
N
2a
9
9
617.
3
4
(a) X. Elduque, A. Sanchez, K. Sharma, E. Pedroso and A.
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Scheme 5 Proposed reaction pathway.
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Conclusions
4
895. (b) C. A. Miller, H. I. Scholl and L. M. Long, J. Am. Chem.
In summary, we have developed the first HFIP-promoted
Michael addition reaction with both aromatic and
heteroaromatic C(sp2)−H as the nucleophiles and various
maleimides as electrophiles. The reaction proceeds for a wide
range of substrates with high para-selectivity, and the desired
diversified products are obtained in good to excellent isolated
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8, 9975. (b) N. Y. P. Kumar, T. Rogge, S. R. Yetra, A.
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1
yields
overall.
This
HFIP-promoted
transformation
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Gopula, S. H. Yang, T. S. Kuo, J. C. Hsieh, P. Y. Wu, J. P.
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complements the scope of Michael donors to a wide range of
C(sp2)−H nucleophiles.
6
7
(a) A. Mustafa, W. Asker, S. Khattab and S. M. A. D. Zayed, J.
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Conflicts of interest
There are no conflicts to declare.
4
861.
(a) F. Le Boucher d'Herouville, A. Millet, M. Scalone and V.
Michelet, J. Org. Chem., 2011, 76, 6925. (b) F. Berhal, O.
Esseiva, C. H. Martin, H. Tone, J. P. Genet, T. Ayad and V.
Ratovelomanana-Vidal, Org. Lett., 2011, 13, 2806. (c) R.
Shintani, K. Ueyama, I. Yamada and T. Hayashi, Org. Lett.,
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (81703330), the Natural Science
Foundation of Jiangsu Province (BK20170347), and Jiangsu Key
Laboratory of Neuropsychiatric Diseases (BM2013003). We
want to thank Dr. Zhenqing Zhang and Yang Ou in the
Department of Pharmaceutical Analysis at Soochow University
for HRMS spectroscopy assistance.
2
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