Journal of the American Chemical Society
Communication
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difluoromethylarene and the arene, and the rate of formation of
arene would be faster with electron-poor arenes than with
electron-rich arenes.
To assess the identity of the difluoromethylcopper species
that could react with the aryl iodide, we combined CuI, CsF,
and TMSCF2H and heated the mixture at 120 °C in the
absence of aryl iodide. Within 5 min, this reaction formed a
product with 19F NMR chemical shift and JH−F values (−116.6
ppm, J = 44 Hz) that match those reported previously for the
8,17,18
−
cuprate Cu(CF2H)2 .
This difluoromethylcuprate species
in this difluoromethylation reaction is clearly more stable than
the neutral CuCF2H.
Although speculative, we provide a rationalization of our
ability to develop copper-mediated difluoromethylation, despite
the instability of CuCF2H. We suggest that Cu(CF2H)2− acts as
a stable reservoir for the neutral CuCF2H. Because prior studies
have shown that two-coordinate cuprates react more slowly
with haloarenes than do neutral complexes,14a−c we suggest
that CuCF2H reacts with the haloarene. The low concen-
trations of CuCF2H should decrease the rate of bimolecular
decomposition, relative to reaction with the haloarene. Future
studies will assess these mechanistic hypotheses.
In summary, we have described a one-step procedure for the
difluoromethylation of aryl and vinyl iodides that occurs with
readily available and nonhazardous reagents. This reaction
tolerates amine, ether, amide, ester, aromatic bromide, and
protected alcohol functionalities and occurs in high yield with
sterically hindered aryl iodides. The simplicity and generality of
this method makes it attractive for the introduction of a CF2H
group into functionally diverse iodoarenes. Work is ongoing to
develop conditions for difluormethylation of electron-poor aryl
iodides, to develop reactions of heteroaryl iodides, and to
develop reactions of higher difluoroalkyl groups.
(16) Strieter, E. R.; Bhayana, B.; Buchwald, S. L. J. Am. Chem. Soc.
2009, 131, 78.
ASSOCIATED CONTENT
(17) For recent reviews of organocuprate chemistry, see: (a) Yoshikai,
N.; Nakamura, E. Chem. Rev. , dx.doi.org/10.1021/cr200241f
(b) Nakamura, E.; Mori, S. Angew. Chem., Int. Ed. 2000, 39, 3750.
(18) A different 19F NMR signal was observed when CsF and
TMSCF2H were allowed to react in the absence of CuI (−117.4 ppm,
doublet, J = 52 Hz). We have tentatively assigned the structure of this
difluoromethyl species to be the pentacoordinate silicate,
TMS(CF2H)2−, which is analogous to that of the silicate
TMS(CF3)2− formed from TMSCF3 and fluoride. (a) Maggiarosa,
N.; Tyrra, W.; Naumann, D.; Kirij, N. V.; Yagupolskii, Y. L. Angew.
Chem., Int. Ed. 1999, 38, 2252. (b) Kolomeitsev, A.; Bissky, G.; Lork,
E.; Movchun, V.; Rusanov, E.; Kirsch, P.; Roschenthaler, G. V. Chem.
Commun. 1999, 1107.
■
S
* Supporting Information
Experimental procedures and characterization of all new
compounds including H, 13C, and 19F NMR spectra. This
1
material is available free of charge via the Internet at http://
AUTHOR INFORMATION
■
Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NIH (GM-58108) for support of this work and
Ramesh Giri for checking the procedure.
REFERENCES
■
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