Journal of the American Chemical Society
Communication
̈
̈
́
(3) (a) Laczay, P.; Voros, G.; Semjen, G. Comparative studies on the
efficacy of sulphachlorpyrazine and toltrazuril for the treatment of
caecal coccidiosis in chickens. Int. J. Parasitol. 1995, 25, 753−756.
(b) Silverstone, T.; Fincham, J.; Plumley, J. An evaluation of the
anorectic activity in man of a sustained release formulation of tiflorex.
Br. J. Clin. Pharmacol. 1979, 7, 353−356. (c) Counts, G. W.; Gregory,
D.; Zeleznik, D.; Turck, M. Cefazaflur, a new parenteral
cephalosporin: in vitro studies. Antimicrob. Agents Chemother. 1977,
11, 708−711. (d) Coombs, G. H.; Mottram, J. C. Trifluoromethio-
nine, a prodrug designed against methionine gamma-lyase-containing
pathogens, has efficacy in vitro and in vivo against Trichomonas
vaginalis. Antimicrob. Agents Chemother. 2001, 45, 1743−1745.
(e) Sato, D.; Kobayashi, S.; Yasui, H.; Shibata, N.; Toru, T.;
Yamamoto, M.; Tokoro, G.; Ali, V.; Soga, T.; Takeuchi, T.; Suematsu,
M.; Nozaki, T. Cytotoxic effect of amide derivatives of trifluor-
omethionine against the enteric protozoan parasite Entamoeba
histolytica. Int. J. Antimicrob. Agents 2010, 35, 56−61.
Scheme 8. Postulated Catalytic Cycle
(4) (a) Aufiero, M.; Sperger, T.; Tsang, A. S. K.; Schoenebeck, F.
Highly Efficient C−SeCF3 Coupling of Aryl Iodides Enabled by an
Air-Stable Dinuclear Pd(I) Catalyst. Angew. Chem., Int. Ed. 2015, 54,
10322−10326. (b) Glenadel, Q.; Ismalaj, E.; Billard, T. Electrophilic
Trifluoromethyl- and Fluoroalkylselenolation of Organometallic
tion (−SeCF3) with high selectivity. The method enables the
targeting of an impressive array of aliphatic C−H bonds (1°,
2°, and 3°) with broad functional group tolerance. This
protocol offers practicing synthetic organic chemists’ access to
the fluorine-containing alkyl chalcogeno (S, Se) moieties
directly in a step-economic manner. Preliminary mechanistic
investigations provided new insights into the reaction pathway
and enabled the formulation of a putative catalytic cycle.
Reagents. Eur. J. Org. Chem. 2017, 2017, 530−533. (c) Durr, A. B.;
̈
Fisher, H. C.; Kalvet, I.; Truong, K.-N.; Schoenebeck, F. Divergent
Reactivity of a Dinuclear (NHC)Nickel(I) Catalyst versus Nickel(0)
Enables Chemoselective Trifluoromethylselenolation. Angew. Chem.,
Int. Ed. 2017, 56, 13431−13435.
(5) Rayman, M. P. Selenium and human health. Lancet 2012, 379,
1256−1268.
(6) (a) Dennert, G.; Zwahlen, M.; Brinkman, M.; Vinceti, M.;
Zeegers, M. P. A.; Horneber, M. Selenium for preventing cancer.
Cochrane Database Syst. Rev. 2011, CD005195. (b) Flores-Mateo, G.;
Navas-Acien, A.; Pastor-Barriuso, R.; Guallar, E. Selenium and
coronary heart disease: a meta-analysis. Am. J. Clin. Nutr. 2006, 84,
762−773.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
Optimization details, experimental procedures, and
(7) Roughley, S. D.; Jordan, A. M. The Medicinal Chemist’s
Toolbox: An Analysis of Reactions Used in the Pursuit of Drug
Candidates. J. Med. Chem. 2011, 54, 3451−3479.
AUTHOR INFORMATION
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
(8) (a) Davies, H. M. L.; Morton, D. Recent Advances in C−H
Functionalization. J. Org. Chem. 2016, 81, 343−350. (b) Gandeepan,
■
P.; Muller, T.; Zell, D.; Cera, G.; Warratz, S.; Ackermann, L. 3d
̈
Transition Metals for C−H Activation. Chem. Rev. 2019, 119, 2192−
2452.
(9) Chen, C.; Xu, X.-H.; Yang, B.; Qing, F.-L. Copper-Catalyzed
Direct Trifluoromethylthiolation of Benzylic C−H Bonds via
Nondirected Oxidative C(sp3)−H Activation. Org. Lett. 2014, 16,
3372−3375.
(10) Wu, H.; Xiao, Z.; Wu, J.; Guo, Y.; Xiao, J.-C.; Liu, C.; Chen, Q.-
Y. Direct Trifluoromethylthiolation of Unactivated C(sp3) − H Using
Silver(I) Trifluoromethanethiolate and Potassium Persulfate. Angew.
Chem., Int. Ed. 2015, 54, 4070−4074.
ACKNOWLEDGMENTS
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We acknowledge Indiana University for partial support. We
also acknowledge the NIH (GM121668), Lilly Grantee Award,
and Amgen Young Investigator Award. Additional instrument
support was provided by NSF (CHE1726633) and IU OVPR.
(11) Guo, S.; Zhang, X.; Tang, P. Silver-Mediated Oxidative
Aliphatic C−H Trifluoromethylthiolation. Angew. Chem., Int. Ed.
2015, 54, 4065−4069.
REFERENCES
(12) Mukherjee, S.; Maji, B.; Tlahuext-Aca, A.; Glorius, F. Visible-
Light-Promoted Activation of Unactivated C(sp3)−H Bonds and
Their Selective Trifluoromethylthiolation. J. Am. Chem. Soc. 2016,
138, 16200−16203.
(13) Zhao, Y.; Lin, J.-H.; Hang, X.-C.; Xiao, J.-C. Ag-Mediated
Trifluoromethylthiolation of Inert Csp3−H Bond. J. Org. Chem. 2018,
83, 14120−14125.
(14) Xiong, H.-Y.; Besset, T.; Cahard, D.; Pannecoucke, X.
Palladium(II)-Catalyzed Directed Trifluoromethylthiolation of Un-
activated C(sp3)−H Bonds. J. Org. Chem. 2015, 80, 4204−4212.
(15) Xia, Y.; Wang, L.; Studer, A. Site-Selective Remote Radical C−
H Functionalization of Unactivated C−H Bonds in Amides Using
Sulfone Reagents. Angew. Chem., Int. Ed. 2018, 57, 12940−12944.
(16) (a) Wolff, M. E. Cyclization of N-Halogenated Amines (The
■
(1) (a) Xu, X.-H.; Matsuzaki, K.; Shibata, N. Synthetic Methods for
Compounds Having CF3−S Units on Carbon by Trifluoromethyla-
tion, Trifluoromethylthiolation, Triflylation, and Related Reactions.
Chem. Rev. 2015, 115, 731−764. (b) Gillis, E. P.; Eastman, K. J.; Hill,
M. D.; Donnelly, D. J.; Meanwell, N. A. Applications of Fluorine in
Medicinal Chemistry. J. Med. Chem. 2015, 58, 8315−8359.
(c) Yagupolskii, L. M.; Maletina, I. I.; Petko, K. I.; Fedyuk, D. V.;
Handrock, R.; Shavaran, S. S.; Klebanov, B. M.; Herzig, S. New
fluorine-containing hypotensive preparations. J. Fluorine Chem. 2001,
109, 87−94.
(2) (a) Hansch, C.; Leo, A.; Taft, R. W. A survey of Hammett
substituent constants and resonance and field parameters. Chem. Rev.
1991, 91, 165−195. (b) Leo, A.; Hansch, C.; Elkins, D. Partition
coefficients and their uses. Chem. Rev. 1971, 71, 525−616.
̈
̈
Hofmann-Loffler Reaction). Chem. Rev. 1963, 63, 55−64. (b) Loffler,
E
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX