Organic Process Research & Development
Technical Note
129.9, 126.4 (t, J = 247.0 Hz), 124.5, 112.8, 28.9, 25.6, 24.2. 19
NMR (375 MHz, C6D6, 23 °C, δ): −34.0.
F
2008, 130, 10060−10061. (e) Furuya, T.; Benitez, D.; Tkatchouk, E.;
Strom, A. E.; Tang, P.; Goddard, W. A., III; Ritter, T. J. Am. Chem. Soc.
2010, 132, 3793−3807. (f) Mazzotti, A. R.; Campbell, M. G.; Tang, P.;
Murphy, J. M.; Ritter, T. J. Am. Chem. Soc. 2013, 135, 14012−14015.
(g) Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 7520−
7521. (h) Chan, K. S. L.; Wasa, M.; Wang, X.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2011, 50, 9081−9084. (i) Watson, D. A.; Su, M.; Teverovskiy,
G.; Zhang, Y.; García-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science
General Procedure for Deoxyfluorination with Solid
PhenoFluor. PhenoFluor is moisture sensitive, and should be
appropriately stored in an inert gas atmosphere. CsF was finely
ground using a mortar in a glovebox, then was removed from
the glovebox, and dried at 200 °C under vacuum for 24 h, prior
to use. Reaction solvents and reagents must be dried for
optimal results. In a glovebox, a heteroaromatic compound
(0.500 mmol. 1.00 equiv), CsF (228 mg, 1.50 mmol, 3.00
equiv) and PhenoFluor (256−320 mg, 0.600−0.750 mmol,
1.20−1.50 equiv) were placed in a vial. Toluene or dioxane (5.0
mL) was added. The vial was sealed and removed from the
glovebox. The mixture was stirred at 23 °C for 30 min and
subsequently heated at 110 °C for 24 h. The mixture was
cooled to 23 °C and then filtered through a pad of Celite
eluting with CH2Cl2 (3 × 4 mL). The filtrate was concentrated
in vacuo, and the residue was purified by flash silica gel column
chromatography to afford the fluorinated compound.
2009, 325, 1661−1664. (j) Noel, T.; Maimone, T. J.; Buchwald, S. L.
̈
Angew. Chem., Int. Ed. 2011, 50, 8900−8903. (k) Maimone, T. J.;
Milner, P. J.; Kinzel, T.; Zhang, Y.; Takase, M. K.; Buchwald, S. L. J.
Am. Chem. Soc. 2011, 133, 18106−18109. (l) Lee, H. G.; Milner, P. J.;
Buchwald, S. L. Org. Lett. 2013, 15, 5602−5605. (m) Lee, H. G.;
Milner, P. J.; Buchwald, S. L. J. Am. Chem. Soc. 2014, 136, 3792−3795.
̈
(n) Wannberg, J.; Wallinder, C.; Unlusoy, M.; Skold, C.; Larhed, M. J.
̈
̈
Org. Chem. 2013, 78, 4184−4189.
(3) For other transition metal mediated aryl fluoride synthesis, see:
(a) Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem. Soc. 2009, 131,
1662−1663. (b) Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860−2863.
(c) Tang, P.; Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2010, 132,
12150−12154. (d) Tang, P.; Ritter, T. Tetrahedron 2011, 67, 4449−
4454. (e) Fier, P. S.; Hartwig, J. F. Science 2013, 342, 956−960.
General Procedure for Deoxyfluorination with Pheno-
Fluor Solution in Toluene (c = 0.100 M). Under air, a
phenol (1.00 equiv) and previously dried CsF (3.00 equiv)
were placed in a vial. The vial was evacuated and backfilled with
N2 gas (3 times). A solution of PhenoFluor in toluene (0.100
M, 1.20 equiv) was added via syringe. The mixture was stirred
at 23 °C for 30 min, then at 110 °C for 24 h. Once cooled to 23
°C, the mixture was filtered through a pad of Celite eluting with
CH2Cl2 (3 × 3 mL). The filtrate was concentrated in vacuo and
then purified by flash silica gel column chromatography.
̀
(f) Casitas, A.; Canta, M.; Sola, M.; Costas, M.; Ribas, X. J. Am. Chem.
Soc. 2011, 133, 19386−19392. (g) Fier, P. S.; Hartwig, J. F. J. Am.
Chem. Soc. 2012, 134, 10795−10798. (h) Fier, P. S.; Luo, J.; Hartwig,
J. F. J. Am. Chem. Soc. 2013, 135, 2552−2559. (i) Ye, Y.; Sanford, M. S.
J. Am. Chem. Soc. 2013, 135, 4648−4651. (j) Ye, Y.; Schimler, S. D.;
Hanley, P. S.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 16292−
16295. (k) Ichiishi, N.; Canty, A. J.; Yates, B. F.; Sanford, M. S. Org.
Lett. 2013, 15, 5134−5137. (l) Truong, T.; Klimovica, K.; Daugulis, O.
J. Am. Chem. Soc. 2013, 135, 9342−9345. (m) Mu, X.; Zhang, H.;
Chen, P.; Liu, G. Chem. Sci. 2014, 5, 275−280. (n) Lee, E.; Hooker, J.
M.; Ritter, T. J. Am. Chem. Soc. 2012, 134, 17456−17458.
(4) For other recent aryl fluoride synthesis, see: (a) Yamada, S.;
Gavryushin, A.; Knochel, P. Angew. Chem., Int. Ed. 2010, 49, 2215−
2218. (b) Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int.
Ed. 2010, 49, 2219−2222. (c) Wang, B.; Qin, L.; Neumann, K. D.;
Uppaluri, S.; Cerny, R. L.; DiMagno, S. G. Org. Lett. 2010, 12, 3352−
3355. (d) Vints, I.; Gatenyo, J.; Rozen, S. J. Org. Chem. 2013, 78,
11794−11797.
ASSOCIATED CONTENT
* Supporting Information
■
S
Detailed experimental procedures and spectroscopic character-
ization for all new compounds. This material is available free of
AUTHOR INFORMATION
Corresponding Author
(5) (a) Tang, P.; Wang, W.; Ritter, T. J. Am. Chem. Soc. 2011, 133,
11482−11484. (b) Sladojevich, F.; Arlow, S. I.; Tang, P.; Ritter, T. J.
Am. Chem. Soc. 2013, 135, 2470−2473.
■
(6) Available from Sigma-Aldrich and Strem Chemical Inc.
(7) Mendoza-Espinosa, D.; Donnadieu, B.; Bertrand, G. J. Am. Chem.
Soc. 2010, 132, 7264−7265.
Notes
The authors declare the following competing financial
interest(s): PhenoFluor is commercially available and licensed
to SciFluor Life Sciences. T.R. may financially benefit from
PhenoFluor sales.
(8) Solubility of alkali metal fluorides, see: Wynn, D. A.; Roth, M. M.;
Pollard, B. D. Talanta 1984, 31, 1036−1040.
(9) Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R. Tetrahedron
1999, 55, 14523−14534.
ACKNOWLEDGMENTS
■
We thank Filippo Sladojevich and Constanze N. Neumann for
helpful discussions, and the NIH (NIH-NIGMS GM088237) as
well as Daiichi-Sankyo Co., Ltd. for financial support.
REFERENCES
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(1) For recent reviews of fluorination reactions, see: (a) Liang, T.;
Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214−
8264. (b) Ruzziconi, R.; Buonerba, F. J. Fluor. Chem. 2013, 152, 12−
28. (c) Hollingworth, C.; Gouverneur, V. Chem. Commun. 2012, 48,
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2012, 45, 67−83. (e) Furuya, T.; Klein, J. E. M. N.; Ritter, T. Synthesis
2010, 1804−1821.
(2) For Pd-mediated aryl fluoride synthesis, see: (a) Hull, K. L.;
Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134−7135.
(b) Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 3796−
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dx.doi.org/10.1021/op500121w | Org. Process Res. Dev. 2014, 18, 1041−1044