Categories: C-C Bond Formation > Heteroatom-containing Molecules, Chains > Trifluoromethylation
Synthesis of benzylic trifluoromethanes
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Recent Literature
A one-pot metal-free decarboxylative procedure for accessing
β,β,β-trifluoroethylarenes and -heteroarenes from readily available ketones and
aldehydes features several benefits, including ease of operation, readily
available reagents, mild reaction conditions, high functional-group
compatibility, and scalability.
Y. Qiao, T. Si, M.-H. Yang, R. A. Altman, J. Org. Chem., 2014,
79, 7122-7131.
A general, copper-mediated chemoselective trifluoromethylation at the benzylic
position of a wide variety of benzyl bromides facilitates the rapid creation of
structurally diverse medicinal candidates in drug discovery in good yields under
mild conditions by the use of a shelf-stable electrophilic trifluoromethylating
reagent.
H. Kawai, T. Furukawa, Y. Nomura, E. Tokunaga, N. Shibata, Org. Lett., 2011,
13, 3596-3599.
Trifluoroethylarenes can be directly accessed via nucleophilic
trifluoromethylation of benzylic electrophiles, but current catalytic methods
fail to transform electron-deficient substrates and heterocycles. A Cu-catalyzed
decarboxylative trifluoromethylation of benzylic bromodifluoroacetates
effectively provides a wide range of trifluoroethylarenes.
B. R. Ambler, L. Zhu, R. A. Altman, J. Org. Chem.,
2015,
80, 8449-8457.
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.
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.
The copper-catalyzed ring-opening of arylcyclopropanes in the presence of
N-fluorobis(arenesulfonyl)imides and (2,2′-bipyridine)Zn(CF3)2
affords γ-trifluoromethylated amines in good yields at room
temperature.
H. Zhang, H. Xiao, F. Jiang, Y. Fang, L. Zhu, C. Li, Org. Lett., 2021, 23,
2268-2272.
Related
A nickel-catalyzed reductive cross-coupling between industrial chemical CF3CH2Cl
and (hetero)aryl bromides and chlorides is synthetically simple, avoids the
preparation of arylmetals, and exhibits high functional group tolerance.
X. Li, X. Gao, C.-Y. He, X. Zhang, Org. Lett., 2021, 23,
1400-1405.
A readily available nickel/bis(oxazoline) catalyst effectively distinguishes
between a CF3 and an alkyl group and accomplishes a wide array of
enantioconvergent cross-couplings of arylzinc reagents with CF3-substituted
racemic secondary alkyl halides. This method can also be applied without
modification to the asymmetric synthesis of other families of fluorinated
organic compounds.
Y. Liang, G. C. Fu, J. Am. Chem. Soc., 2015,
137, 9523-9526.
A nickel-catalyzed enantioselective cross-coupling
reaction of aryl titanates with α-CF3-benzyl bromides enables the synthesis of chiral α-CF3-substituted benzhydryls in good yields and excellent enantioselectivities.
The use of commercially available anesthetic halothane as a cheap fluorinated
building block in a sequential one-pot reaction with two different aryl
titanates is also described.
A. Varenikov, E. Shapiro, M. Gandelman, Org. Lett., 2020, 22, 9386-9391.
Cobalt complexes generated from Co(acac)2 and bisphosphine
ligands catalyze asymmetric hydroboration reactions of
fluoroalkyl-substituted terminal alkenes with pinacolborane (HBpin) to afford the corresponding chiral
alkylboronates containing fluoroalkyl-substituted stereogenic carbon centers
with high enantioselectivity.
M. Hu, B. B. Tan, S. Ge, J. Am. Chem. Soc.,
2022, 144, 15333-15338.