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Categories: C-C Bond Formation > Heteroatom-containing Molecules, Alkanes > Trifluoromethylation

Synthesis of trifluoromethyl alkanes

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The combination of Et3SiH and K2S2O8 initiates radical reactions of primary and secondary alkyl bromides or iodides with BPyCu(CF3)3 (BPy = 2,2′-bipyridine) in aqueous acetone at room temperature to provide trifluoromethylated products in good yield. The protocol exhibits wide functional group compatibility.
H. Shen, Z. Liu, P. Zhang, X. Tan, Z. Zhang, C. Li, J. Am. Chem. Soc., 2017, 139, 9843-9846.


Sodium trifluoromethanesulfinate and iodine pentoxide as safe solid reagents enable a scalable, selective, and convenient iodotrifluoromethylation of a wide range of alkenes and alkynes in aqueous medium. Mechanistic studies confirm a free-radical processes, in which key radical intermediates such as CF3 and β-CF3 alkyl radicals have been detected by spin trapping and electron spin resonance.
Z. Hang, Z. Li, Z.-Q. Liu, Org. Lett., 2014, 16, 3648-3651.


In a photoredox vicinal chlorotrifluoromethylation in the presence of Ru(Phen)3Cl2 as catalyst, various terminal and internal alkenes can be transformed to their vicinal chlorotrifluoromethylated derivatives using CF3SO2Cl as a source for CF3 radicals and chloride ions.
S. H. Oh, Y. R. Malpani, N. Ha, Y.-S. Jung, S. B. Han, Org. Lett., 2014, 16, 1310-1313.


The use of NaSO2CF3 and NaBrO3 enables a free-radical bromotrifluoromethylation of olefins via a radical process. Sodium bromate acts not only as a single-electron oxidant but also as a bromine source.
Z.-Q. Liu, D. Liu, J. Org. Chem., 2017, 82, 1649-1656.


2,4,6-Trimethylpyridine catalyzes a trifluoromethylalkynylation of unactivated alkenes with alkynyl sulfones and Togni's reagent to provide various β-trifluoromethylated alkynes under metal-free conditions with a broad substrate scope and wide functional group compatibility. A mechanism involving catalytic nonchain radical processes is proposed.
S. Zhou, T. Song, H. Chen, Z. Liu, H. Shen, C. Li, Org. Lett., 2017, 19, 698-701.


A copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes provides various CF3-containing alkylnitriles with excellent enantiomeric excess. The reaction is initiated by a SET process between activated Togni’s CF3+ reagent and a Cu(I) catalyst. The released CF3 radical readily added to styrene to provide a benzylic radical, which is then trapped by a chiral Cu(II) cyanide species.
F. Wang, D. Wang, X. Wan, L. Wu, P. Chen, G. Liu, J. Am. Chem. Soc., 2016, 138, 15547-15550.


A highly practical copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes provides a general and straightforward way to synthesize various useful CF3-containing nitriles, which can be used for the preparation of pharmaceutically and agrochemically important compounds.
Y.-T. He, L.-H. Li, Y.-F. Yang, Z.-Z. Zhou, H.-L. Hua, X.-Y. Liu, Y.-M. Liang, Org. Lett., 2014, 16, 270-273.


A highly regioselective cyanotrifluoromethylation of electron-deficient styrenes with a trifluoromethylated hypervalent iodine reagent proceeds under mild conditions in the presence of a bulky phosphine and CuCN. The process involves the consecutive formation of two C-C bonds in a single addition reaction. In the presence of a p-methoxy substituent in the styrene, oxytrifluoromethylation occurs instead of the cyanotrifluoromethylation.
N. O. Ilchenko, P. G. Janson, K. J. Szabó, J. Org. Chem., 2013, 78, 11087-11091.


A photoredox-catalyzed azidotrifluoromethylation of substituted styrenes as well as various activated and nonactivated alkenes using [Ru(bpy)3(PF6)2] as the photocatalyst and Umemoto’s reagent as the CF3 source delivers a wide range β-trifluoromethylated azides or amines in good yields.
G. Dagousset, A. Carboni, E. Magnier, G. Masson, Org. Lett., 2014, 16, 4340-4343.


The use of a commercially available Umemoto’s reagent enables a metal-free trifluoromethylation of nitroalkanes. This method provides quaternary α-(trifluoromethyl)nitroalkanes, that can be elaborated to various complex nitrogen-containing molecules, including α-(trifluoromethyl)amines.
A. S. Gietter-Burch, V. Devannah, D. A. Watson, Org. Lett., 2017, 19, 2957-2960.