Journal of the American Chemical Society
Article
(5) (a) Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860−2863.
(b) Lee, E.; Kamlet, A. S.; Powers, D. C.; Neumann, C. N.; Boursalian,
G. B.; Furuya, T.; Choi, D. C.; Hooker, J. M.; Ritter, T. Science 2011,
334, 639−642. (c) Lee, E.; Hooker, J. M.; Ritter, T. J. Am. Chem. Soc.
2012, 134, 17456−17458. (d) Sladojevich, F.; Arlow, S. I.; Tang, P.;
Ritter, T. J. Am. Chem. Soc. 2013, 135, 2470−2473.
(6) (a) Kalow, J. A.; Doyle, A. G. J. Am. Chem. Soc. 2010, 132, 3268−
3269. (b) Katcher, M. H.; Doyle, A. G. J. Am. Chem. Soc. 2010, 132,
17402−17404. (c) Katcher, M. H.; Sha, A.; Doyle, A. G. J. Am. Chem.
Soc. 2011, 133, 15902−15905.
(7) (a) Rauniyar, V.; Lackner, A. D.; Hamilton, G. L.; Toste, F. D.
Science 2011, 334, 1681−1684. (b) Phipps, R. J.; Hiramatsu, K.; Toste,
F. D. J. Am. Chem. Soc. 2012, 134, 8376−8379. (c) Mankad, N. P.;
Toste, F. D. Chem. Sci. 2012, 3, 72−76. (d) Phipps, R. J.; Toste, F. D.
J. Am. Chem. Soc. 2013, 135, 1268−1271.
(8) (a) Hollingworth, C.; Hazari, A.; Hopkinson, M. N.; Tredwell,
M.; Benedetto, E.; Huiban, M.; Gee, A. D.; Brown, J. M.; Gouverneur,
V. Angew. Chem., Int. Ed. 2011, 50, 2613−2617. (b) Gao, Z.; Lim, Y.
H.; Tredwell, M.; Li, L.; Verhoog, S.; Hopkinson, M.; Kaluza, W.;
Collier, T. L.; Passchier, J.; Huiban, M.; Gouverneur, V. Angew. Chem.,
Int. Ed. 2012, 51, 6733−6737.
(9) (a) Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 10795−
10798. (b) Fier, P. S.; Luo, J.; Hartwig, J. F. J. Am. Chem. Soc. 2013,
135, 2552−2559.
(10) (a) Yin, F.; Wang, Z.; Li, Z.; Li, C. J. Am. Chem. Soc. 2012, 134,
10401−10404. (b) Li, Z.; Song, L.; Li, C. J. Am. Chem. Soc. 2013, 135,
4640−4643.
(11) (a) Rueda-Becerril, M.; Sazepin, C. C.; Leung, J. C. T.;
Okbinoglu, T.; Kennepohl, P.; Paquin, J.-F.; Sammis, G. M. J. Am.
Chem. Soc. 2012, 134, 4026−4029. (b) Leung, J. C. T.; Chatalova-
Sazepin, C.; West, J. G.; Rueda-Becerril, M.; Paquin, J.-F.; Sammis, G.
M. Angew. Chem., Int. Ed. 2012, 51, 10804−10807.
specialized photochemical equipment was used for any of the
experiments described herein.
SUMMARY
■
We have developed a photolytic method for direct benzylic
fluorination. Cheap and readily available diarylketones were
used as the catalysts. 9-Fluorenone catalyzed selective benzylic
C−H monofluorination and xanthone gem-difluorination.
Ketone-catalyzed photolytic C−H activation reactions were
traditionally carried out with UV irradiation and a large amount
of ketone. In contrast, we can use visible light to drive this C−
H fluorination reaction. Only a low loading of the diarylketone
catalysts is needed because of efficient catalyst turnover.
Methyl, methylene, and methine groups can all be fluorinated,
and a wide range of functional groups on the aromatic ring and
side-chain can be tolerated. We are currently developing new
catalyst systems for fluorinating the unactivated C−H groups.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization data. This
material is available free of charge via the Internet at http://
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
(12) (a) Topczewski, J. J.; Tewson, T. J.; Nguyen, H. M. J. Am. Chem.
Soc. 2011, 133, 19318−19321. (b) Barker, T. J.; Boger, D. L. J. Am.
Chem. Soc. 2012, 134, 13588−13591. (c) Suzuki, S.; Kitamura, Y.;
Lectard, S.; Hamashima, Y.; Sodeoka, M. Angew. Chem., Int. Ed. 2012,
51, 4581−4585. (d) Cochrane, N. A.; Nguyen, H.; Gagne, M. R. J. Am.
Chem. Soc. 2013, 135, 628−631. (e) Ye, Y.; Sanford, M. S. J. Am.
Chem. Soc. 2013, 135, 4648−4651. (f) Tian, T.; Zhong, W.-H.; Meng,
S.; Meng, X.-B.; Li, Z.-J. J. Org. Chem. 2013, 78, 728−732.
(13) For early examples of C−H fluorination, see: (a) Barton, D. H.
R.; Hesse, R. H.; Markwell, R. E.; Pechet, M. M.; Toh, H. T. J. Am.
Chem. Soc. 1976, 98, 3034−3035. (b) Feiring, A. E. J. Fluorine Chem.
1977, 10, 375−386. (c) Sket, B.; Zupan, M. J. Org. Chem. 1978, 43,
835−837. (d) Stavber, S.; Zupan, M. J. Org. Chem. 1983, 48, 2223−
2226. (e) Stavber, S.; Zupan, M. J. Org. Chem. 1991, 56, 7347−7350.
(f) Stavber, G.; Zupan, M.; Stavber, S. Tetrahedron Lett. 2007, 48,
2671−2673. (g) Feiring, A. E. J. Org. Chem. 1979, 44, 1252−1254.
(h) Misaki, S. J. Fluorine Chem. 1981, 17, 159−171. (i) Visser, G. W.
M.; Bakker, C. N. M.; Halteren, B. W. V.; Herscheid, J. D. M.;
Brinkman, G. A.; Hoekstra, A. J. Org. Chem. 1986, 51, 1886−1889.
(j) Meurs, J. H. H.; Sopher, D. W.; Eilenberg, W. Angew. Chem., Int.
Ed. 1989, 28, 927−928. (k) Wang, C. M.; Mallouk, T. E. J. Am. Chem.
Soc. 1990, 112, 2016−2018. (l) Banks, R. E.; Besheesh, M. K.;
Mohialdin-Khaffaf, S. N.; Sharif, I. J. Fluorine Chem. 1997, 81, 157−
161. (m) Chambers, R. D.; Kenwright, A. M.; Parsons, M.; Sandford,
G.; Moilliet, J. S. J. Chem. Soc. Perkin Trans. 1 2002, 2190−2197.
(14) (a) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc.
2006, 128, 7134−7135. (b) McMurtrey, K. B.; Racowski, J. M.;
Sanford, M. S. Org. Lett. 2012, 14, 4094−4097. (c) Racowski, J. M.;
Gary, J. B.; Sanford, M. S. Angew. Chem., Int. Ed. 2012, 51, 3414−3417.
(15) (a) Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131,
7520−7521. (b) Chan, K. S. L.; Wasa, M.; Wang, X.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2011, 50, 9081−9084.
ACKNOWLEDGMENTS
■
Financial support was provided by NIH/NIGMS (R01-
GM079554) and the Welch Foundation (I-1596). We thank
Prof. Joseph Ready for helpful discussions.
REFERENCES
■
(1) For reviews, see: (a) Bohm, H.-J.; Banner, D.; Bendels, S.; Kansy,
̈
M.; Kuhn, B.; Muller, K.; Obst-Sander, U.; Stahl, M. ChemBioChem
̈
2004, 5, 637−643. (b) Muller, K.; Faeh, C.; Diederich, F. Science 2007,
̈
317, 1881−1886. (c) Purser, S.; Moore, P. R.; Swallow, S.;
Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320−330. (d) Hagmann,
W. K. J. Med. Chem. 2008, 51, 4359−4369. (e) Phelps, M. E. Proc.
Natl. Acad. Sci. U.S.A. 2000, 97, 9226−9233. (f) Jeschke, P.
ChemBioChem 2004, 5, 570−589. (g) Ameduri, B.; Boutevin, B.
Well-Architectured Fluoropolymers: Synthesis, Properties and Applications;
Elsevier B.V.: Amsterdam, The Netherlands, 2004. (h) Okazoe, T.
Proc. Jpn. Acad., Ser. B 2009, 85, 276−289.
(2) For reviews, see: (a) Rozen, S. Eur. J. Org. Chem. 2005, 2433−
2447. (b) Sandford, G. J. Fluorine Chem. 2007, 128, 90−104. (c) Kirk,
K. L. Org. Process Res. Dev. 2008, 12, 305−321. (d) Furuya, T.;
Kuttruff, C. A.; Ritter, T. Curr. Opin. Drug Discov. Devel. 2008, 11,
803−819. (e) Furuya, T.; Klein, J. E. M. N.; Ritter, T. Synthesis 2010,
1804−1821. (f) Tredwell, M.; Gouverneur, V. Angew. Chem., Int. Ed.
2012, 51, 11426−11437. (g) Sibi, M. P.; Landais, Y. Angew. Chem., Int.
Ed. 2013, 52, 3570−3572.
(3) For synthesis of benzylic difluorides by C−H alkylation, see:
(a) Fujiwara, Y.; Dixon, J. A.; O’Hara, F.; Funder, E. D.; Dixon, D. D.;
́
Rodriguez, R. A.; Baxter, R. D.; Herle, B.; Sach, N.; Collins, M. R.;
Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95−99. (b) Zhou, Q.;
Ruffoni, A.; Gianatassio, R.; Fujiwara, Y.; Sella, E.; Shabat, D.; Baran, P.
S. Angew. Chem., Int. Ed. 2013, 52, 3949−3952.
(16) (a) Liu, W.; Huang, X.; Cheng, M.-J.; Nielsen, R. J.; Goddard,
W. A., III; Groves, J. T. Science 2012, 337, 1322−1325. (b) Liu, W.;
Groves, J. T. Angew. Chem., Int. Ed. 2013, 52, 6024−6027.
(4) (a) Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; García-
Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science 2009, 325, 1661−1664.
(b) Maimone, T, J.; Milner, P. J.; Kinzel, T.; Zhang, Y.; Takase, M. K.;
Buchwald, S. L. J. Am. Chem. Soc. 2011, 133, 18106−18109.
(17) (a) Bloom, S.; Pitts, C. R.; Miller, D. C.; Haselton, N.; Holl, M.
G.; Urheim, E.; Lectka, T. Angew. Chem., Int. Ed. 2012, 51, 10580−
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