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Scheme 2 Mechanistic working hypothesis for copper(II)-catalyzed imine
trifluoromethylation.
release the CF3 group from TMSCF3 through a hypervalent
silicon species.5 Through this anionic metathesis process, a
Cu(CF3)(OAc)(imine) intermediate 13 may be subsequently
generated. The coordination of imine 1 to the Lewis acid
copper(II) presumably polarizes the CvN bond and renders it
more labile to nucleophilic addition; concordantly, the Lewis
base imine ligand may further enhance the nucleophilicity of
the CF3 group. Cooperative CF3 group transfer will convert 13
to 14, and the in situ-generated TMSOAc presumably interacts
with 14 to furnish silylation product 15 and regenerate
Cu(OAc)2. The labile Si–N bond in 15 can then readily undergo
hydrolysis upon workup to afford 2.
In conclusion, we have discovered a new copper(II)-catalyzed
N-aryl imine trifluoromethylation without the use of fluoride
or HF-based activators. This method readily converts a variety
of N-aryl imines to corresponding amines with trifluoromethy-
lated stereogenic centers. Our current efforts are focused on
understanding the mechanistic details of these new reactions
and their application in medicinal agent synthesis.
Acknowledgements
This work was supported by Georgia State University and the
American Chemical Society Petroleum Research Fund (ACS
PRF 51571-DNI1). We thank Guan-Sai Liu for experiments
described in entries 13–14 of Table 2, and Cheng-Liang Zhu
for the assistance during the ESI† preparation.
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6244 | Org. Biomol. Chem., 2013, 11, 6242–6245
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