Categories: C-C Bond Formation > Heteroatom-containing Molecules, Alkanes > Trifluoromethylation
Synthesis of trifluoromethyl alkanes
| Related: |
 |
Recent Literature
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.
A mild, copper-catalyzed cross-coupling of Ruppert-Prakash type reagents
(TMSCF3, TMSC2F5, and TMSC3F7)
with aryl and alkyl bromides provides a diverse array of trifluoromethyl,
pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated
transformation enables also the late-stage functionalization of several drug
analogues.
X. Zhao, D. W. C. MacMillan, J. Am. Chem. Soc.,
2020, 142, 19480-19486.
In the presence of AgNO3 as the catalyst and K2S2O8
as the oxidant, reactions of aliphatic carboxylic acids with (bpy)Cu(CF3)3
and ZnMe2 in aqueous acetonitrile at 40°C provide the corresponding
decarboxylative trifluoromethylation products in good yield. The protocol is
applicable to various primary and secondary alkyl carboxylic acids and exhibits
wide functional group compatibility.
X. Tan, Z. Liu, H. Shen, P. Zhang, Z. Zhang, C. Li, J. Am. Chem. Soc., 2017,
139, 12430-12433.
In situ activation of alcohols by benzoxazolium salts enables a copper
metallaphotoredox-mediated direct deoxytrifluoromethylation.
N. E. Intermaggio, A. Millet, D. L. Davis, D. W. C. MacMillan, J. Am. Chem. Soc.,
2022, 144, 11961-11968.
Organocopper(III)
complexes with well-defined structures can undergo reductive elimination
for the formation of Csp3-Csp3 bonds. A general method for the synthesis of a series of [alkyl-CuIII-(CF3)3]− complexes
followed by reductive elimination provides alkyl-CF3 products with good yields.
M. Paeth, S. B. Tyndall, L.-Y. Chen, J.-C. Hong, W. P. Carson, X. Liu, X. Sun,
J. Liu, K. Yang, E. M. Hale, D. L. Tierney, B. Liu, Z. Cao, M.-J. Cheng, W. A.
Goddard III, W. Liu, J. Am. Chem. Soc.,
2019,
141, 3153-3159.
Trifluoromethyl thianthrenium triflate is a conveniently accessible
trifluoromethylating reagent, that can be used in electrophilic, radical, and
nucleophilic trifluoromethylation reactions.
H. Jia, A. P. Häring, F. Berger, L. Zhang, T. Ritter, J. Am. Chem. Soc.,
2021, 143, 7623-7628.
The use of TFSP, a readily available trifluoromethylation reagent prepared from DMAP and Tf2O, enables a general method for the hydrotrifluoromethylation
of styrenes under photoredox catalysis without polymerization. The substrate
scope was further extended to unactivated alkenes, acrylates, acrylamides, and
vinyl-heteroatom-substituted alkenes.
Y.-F. Yang, J.-H. Lin, J.-C. Xiao, Org. Lett., 2021, 23,
9277-9282.
A single electron oxidation of the commercially available CF3SO2Na
(Langlois' reagent) using Mn(OAc)3·2H2O as the oxidant
enables a simple and efficient method for hydrotrifluoromethylation of
unactivated alkenes. The reaction proceeds readily under mild conditions and
tolerates various functional groups.
B. Cui, H. Sun, Y. Xu, L. Li, L. Duan, Y.-M. Li, J. Org. Chem., 2018, 83,
6015-6024.
A light-driven, copper-mediated trifluoromethylation of O-alkyl
thiocarbonates offers broad functional group tolerance (e.g., alkyne, alkene,
phenol, free alcohol, electron-rich and -deficient arenes), orthogonality and
practicality. A radical organometallic mechanism is proposed.
Z.-Y. Liu, S. P. Cook, Org. Lett., 2021, 23,
739-744.
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.
A trifluoromethylation of alkenes or alkynes using trifluoromethanesulfonic
anhydride (Tf2O) as a trifluoromethylating reagent in the presence of CuX2
(X = Br, Cl), Zn powder, and 2,2'-bipyridine affords
bromo(chloro)trifluoromethylated products in good yields. CuX2 plays
a dual role as the catalyst and halide source, whereas 2,2′-bipyridine acts as
both the activation reagent and ligand.
Y. Ouyang, C.-L. Tong, X.-H. Xu, F.-L. Qing, Org. Lett., 2021, 23,
346-350.
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. 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.
N-(Diphenylmethylene)-1,1,1-trifluoromethanesulfonamide is a
bench-stable and readily accessible carboamination reagent, that enables a
facile and versatile trifluoromethylimination of alkenes under metal-free
photocatalytic conditions. The mild reaction conditions and good functional
group compatibility render this protocol highly valuable for the
difunctionalization of olefins.
Y. Zheng, Z. Liao, Z. Xie, H. Chen, K. Chen, H. Xiang, H. Yang, Org. Lett., 2023, 25,
2129-2133.
Trifluoromethylsulfonyl-pyridinium salt (TFSP) is an efficient, solid
trifluoromethylation reagent, which can be readily prepared from cheap and
easily available bulk industrial feedstocks. TFSP can generate a trifluoromethyl
radical under photocatalysis, that can be used for azido- or
cyano-trifluoromethylation reactions of alkenes.
M. Zhang, J.-H. Lin, J.-C. Xiao, Org. Lett., 2021, 23,
6079-6083.
A convenient Fe-catalyzed A-D-A-T-type radical-dual-difunctionalization and
cross-coupling of two different alkenes provides chain elongated and
trifluoromethylated aromatic alkenes.
J. Zhao, R.-X. Liu, C.-P. Luo, L. Yang,
Org. Lett., 2020, 22, 6776-6779.
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 selective C-C bond cleavage of cycloalkanols enables the synthesis of aryl
and alkyl ketones trifluoromethylated at the γ, δ, ε, position or more remote
terminal sites. This reaction was scalable to gram-scale, applicable to
structurally complex steroid trifluoromethylation, and extendable to
pentafluoroethylation.
S. Wu, J. Li, R. He, K. Jia, Y. Chen, Org. Lett., 2021, 23,
9204-9209.
A carbene-catalyzed radical trifluoromethylation of olefins with aldehydes in
the presence of Togni reagent provides β-trifluoromethyl-α-substituted ketones
with a broad scope and good yields.
B. Zhang, Q. Peng, D. Guo, J. Wang,
Org. Lett., 2020, 22, 443-447.
A constant current electrolysis synergizing with a Lewis-acid catalysis
protocol enables an external oxidant-free oxytrifluoromethylation and
aminotrifluoromethylation of styrene derivatives using sodium
trifluoromethanesulfinate as the trifluoromethyl source.
L. Zhang, G. Zhang, P. Wang, Y. Li, A. Lei, Org. Lett.,
2018, 20, 7396-7399.
An enantioselective copper-catalyzed trifluoromethylalkynylation of styrenes
affords structurally diverse CF3-containing propargylic compounds in
good yield with excellent enantioselectivities under very mild conditions via a
radical relay process. The reaction offers wide substrate scope and good
functional group tolerance. The trifluoromethylalkynylated products can be
converted into synthetically useful chiral terminal alkynes, allenes, and Z-alkenes.
L. Fu, S. Zhou, X. Wan, P. Chen, G. Liu, J. Am. Chem. Soc.,
2018,
140, 10965-10969.
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.
Related
CF3-cyclopropanes with aliphatic, aromatic, and even heteroaromatic
substituents were prepared on a multigram scale by deoxyfluorination of
cyclopropane carboxylic acids or their potassium salts (in case of labile
α-pyridine acetic acids) with sulfur tetrafluoride.
The reaction of redox-active esters as radical precursors and the
commercially available 2-bromo-3,3,3-trifluoropropene (BTP) as a radical
acceptor provides a wide range of secondary trifluoromethylated alkyl bromides
in good to excellent yields with broad functional group tolerance.
P. Guo, M. Tao, W.-W. Xu, A.-J. Wang, W. Li, Q. Yao, J. Tong, C.-Y. He, Org. Lett.,
2022, 24, 2145-2148.