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of the CH2F cation for the oxygen atom in the alkylation of
enolates. This approach not only constitutes one of the scarce
examples of the selective O-alkylation of enolates, but also
provides a new synthetic entry to biologically relevant
monofluoromethyl ethers of interest to the pharmaceutical
and agrochemical industries.[9] This strategy might offer a
possible solution for the direct electrophilic trifluoro-
methylation of alcohols.[9] Our findings on the selective O-
alkylation of enolates by monofluoromethylsulfoxinium salts
3 also provides significant insight into the unusual reactivity
of fluorinated sulfoximines,[10c,12] as exemplified by the
important discovery by Hu and co-workers that monofluoro-
sulfoximines react with simple nitrones to give monofluoro-
alkenes with excellent E/Z stereoselectivity.[13] Although the
mechanisms of O-selective monofluoromethylation and C-
selective trifluoromethylation are unclear, these results
should shed more light on the mechanism of the electrophilic
trifluoromethylation reaction, including details regarding the
CF3 cation, the CF3 radical, and the mechanism of single-
electron transfer.[14,15] Molecular-mechanical and molecular-
orbital calculations, which should provide further insight into
the mechanisms of O-monofluoromethylation and C-
trifluoromethylation, are now under way.
[7] Although monofluoromethyl enol ethers of b-ketoesters were
not found by a SciFinder search, monofluoromethyl enol ethers
of b-ketoaldehydes are known, and their biological activity has
been reported: a) W. Hu, W. Zhu, D. Chen, J. Chen, Zhiwu
Baohu Xuebao 2009, 36, 189 – 190; b) D. Dong, J. Xing, Q. Fu, J.
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Obshch. Khim. 1969, 39, 206 – 210; e) Q.-Y. Chen, S.-W. Wu, J.
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M. Ogawa, J. Noguchi, T. Suhara, C. Halldin, K. Suzuki, Bioorg.
2335 – 2338; n) I. I. Gerus, A. A. Kolomeitsev, M. I. Kolycheva,
Pascali, A. Bogni, S. Furumoto, K. Terasaki, K. Yanai, Appl.
2219; t) K. G. Grozinger, R. W. Kriwacki, S. F. Leonard, T. P.
Miller, T. R. DeGrado, B. H. Mock, J. C. Lopshire, J. G. Rose-
nberger, C. Dusa, M. K. Das, W. J. Groh, D. P. Zipes, G. D.
Received: October 4, 2010
Published online: December 23, 2010
À
Keywords: C O bond formation · enolates · fluorine ·
O-alkylation · regioselectivity
.
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1888
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