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carbocation M7. The further proton transfer between M7 (or
M7′) and the radical anion gives enamine M8. ESI-HRMS
analysis of the reaction mixture in toluene found a strong signal
at 310.2018, suggesting the presence of enamine M8 or its
corresponding imine (calcd [M + H]+ 310.2018). The
intramolecular cyclization of enamine M8 gives M9. Finally,
an amine-catalyzed umpolung coupling reaction generates N-
heterocyclic product 3. It should be noted that the reported
approach to this type of umpolung coupling reaction requires
the presence of a halogen-bonding activator.11
In conclusion, we have established an unprecedented
approach to N-heterocycles through site-selective β-malonyla-
tion of a diverse array of unprotected secondary aliphatic
amines with iodonium ylide. In this transformation, iodonium
ylide alone can manage all the distinct bond-formation events
through properly manipulating the highly unstable intermedi-
ates. As this approach provides a very concise way to
synthesize N-heterocycles, we expect this method will find
significant utility in medicinal and synthetic chemistry.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge at
(7) (a) McNally, A.; Haffemayer, B.; Collins, B. S. L.; Gaunt, M. J.
Nature 2014, 510, 129−133. (b) Smalley, A. P.; Gaunt, M. J. J. Am.
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Ozaki, K.; Gaunt, M. J. Angew. Chem., Int. Ed. 2017, 56, 11958−
11962.
Full experimental procedures and compound character-
Accession Codes
contain the supplementary crystallographic data for this paper.
cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336033.
(8) (a) Zhao, Z.; Luo, Y.; Liu, S.; Zhang, L.; Feng, L.; Wang, Y.
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AUTHOR INFORMATION
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(11) Saito, M.; Kobayashi, Y.; Tsuzuki, S.; Takemoto, Y. Angew.
Chem., Int. Ed. 2017, 56, 7653−7657.
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Natural Science
Foundation of China (21772113, 21971147) and the Natural
Science Foundation of Shandong Province for Distinguished
Young Scholars (ZR2019JQ08). We thank Prof. Di Sun of
Shandong University for assistance with the X-ray crystal
structure analysis.
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