Chemical Science
Edge Article
although the difference in energy of s*C–F orbitals is oen too
The optimized reaction conditions shown in Table 2, were
small to allow good selectivity.40,41 This mechanism would also used in mono-reduction of several triuoromethyl arenes. We
explain why intermediate X is resistant to further reduction. found that the reaction can be accomplished in the presence of
Furthermore, mixtures of silanes and alkoxides have previously amines, ethers, and acetals with several biphenyl and aryl
been implicated in single electron chemistry.42,43 However, it is substrates. Reducible groups, such as aryl halides, nitro arenes,
important to note that the presence of transition metal catalysts or nitriles are reduced under the reaction conditions. ortho-
is essential for C–F activation. In the absence of transition Substituted triuoromethyl arenes provided low yields of the
metals, we can fully recover the starting material, in agreement desired products.
with the observations made by Grubbs and Stoltz.43
Aer exploring the mechanism of the mono-deuorination
reaction, we turned our attention to further the reaction opti-
Conclusions
mization and the exploration of the substrate scope. In the We have discovered a combination of palladium and copper
process, we found that SIPrCuCl could be replaced by signi- catalysts that allows selective activation of a single C–F bond in
cantly less expensive and commercially available CuF2 or CuBr, triuoromethyl arenes under relatively mild conditions. This
with CuF2 generally providing superior selectivity. Other cop- discovery allowed the development of a method for selective
per(I) and copper(II) salts gave signicantly lower yields of the reduction of ArCF3 to ArCHF2. More importantly, the unique
desired product and/or signicantly lower selectivity. We also mechanism of the reaction and the unusual source of the
found that consistently better selectivity could be obtained selectivity provide new opportunities for the development of
using KOSiMe3 instead of NaOt-Bu.
useful transformations based on selective C–F activation.
Acknowledgements
Table 2 Optimized reaction conditions and substrate scope
Financial support by NSF (NSF CAREER award #1254636) is
gratefully acknowledged. We gratefully acknowledge Sarah E.
Flowers for assistance with X-ray crystallography.
Notes and references
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a
Ratio of ArCF2H and ArCH3. See ESI for a detailed description of
experimental procedure.
Chem. Sci.
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