Journal of the American Chemical Society
Communication
We next investigated the activation of difluoromethyl arenes
beyond PhCF2H. A wide variety of difluoromethyl (hetero)-
arenes react with KN(iPr)2/B3N3Me6/18-crown-6 in THF at
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Notes
The authors declare the following competing financial
interest(s): A patent application on this material has been
submitted.
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−80 °C to form stabilized ArCF2 synthons 3a−3k in high
yield (Figure 3a). When KCH2Ph was used in place of
KN(iPr)2, significantly lower yields were observed. Aryl
bromides are not tolerated by electrochemical and photoredox
benzylic fluorination methods,7,10,20 and are susceptible to o-
metalation/benzyne formation. However, we accessed these
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nucleophilic ArCF2 units through deprotonation/capture
reactions. 2- (3a, 67%), 3- (3b, 93%), and 4- (3c, 99%)
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bromobenzenes were all transformed into B3N3Me6/ArCF2
ACKNOWLEDGMENTS
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adducts in high yield. Difluoromethyl heteroarenes were also
deprotonated to reveal ArCF2 synthons. In addition
We are grateful to the Schindler lab for assistance with
purification, Jeff Kampf for crystallographic assistance, and
Devin Ferguson and the Sanford lab for helpful conversations.
This work was supported by the University of Michigan
Department of Chemistry, a Rackham Predoctoral Fellowship
(JBG), and an NSF CAREER (grant CHE-1350877). X-ray
diffractometers used were funded by the NSF (CHE
1625543).
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resonance-activated 2- and 4-difluoromethylpyridine (3d,
83%, 3f, 98% chemical yield), 3-difluoromethylpyridine and
7-difluoromethylquinoline were deprotonated in high yield
(3e, 3h, 91%, 94%). Difluoromethylated five-membered
heterocycles also undergo ArCF2H deprotonation, with 2-
difluoromethyl benzofuran (3i, 67%), N-benzyl-2-difluoro-
methyl-benzimidazole (3g, 94%), 1-difluoromethyl-4-(1-meth-
yl-4- pyrazolyl)benzene (3k, 95%), and 2-difluoromethyl-5-
(tert-butylacetylenyl)-thiophene (3j, 95%) providing access to
REFERENCES
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B3N3Me6 from the reaction to form 4b did not afford the
desired product. This result illustrates the synergistic require-
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ASSOCIATED CONTENT
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* Supporting Information
The Supporting Information is available free of charge on the
Crystallographic information for 1 (CIF)
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2004, 2004, 1759. (b) Clavel, P.; Leger-Lambert, M. P.; Biran, C.;
Serein-Spirau, F.; Bordeau, M.; Roques, N.; Marzouk, H. Synthesis
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Synthetic details, characterization (PDF)
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J. Am. Chem. Soc. XXXX, XXX, XXX−XXX