Categories: C-C Bond Formation > Heteroatom-containing Molecules > Trihalomethyl Ketones, Trifluoromethylation
Synthesis of α-trifluoromethyl carbonyl compounds
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Recent Literature
An organocatalytic α-trifluoromethylation and α-perfluoroalkylation of aldehydes
with commercially available perfluoroalkyl halides in the presence of a readily
available iridium photocatalyst and a chiral imidazolidinone catalyst delivers
products with high efficiency and enantioselectivity. α-Trifluoromethyl
aldehydes are versatile precursors for the construction of enantioenriched
trifluoromethylated building blocks.
D. A. Nagib, M. E. Scott, D. W. C. MacMillan, J. Am. Chem. Soc., 2009,
131, 10875-10877.
A Cu-catalyzed trifluoromethylation of silyl enol ethers with Togni's reagent as
electrophilic trifluoromethylating agent produces α-trifluoromethyl ketones in
good yields.
L. Li, Q.-Y. Chen, Y. Guo, J. Org. Chem., 2014,
79, 5145-5152.
In a continuous-flow, two-step procedure for the preparation of α-CF3-substituted
carbonyl compounds, carbonyl substrates were converted in situ into the
corresponding silyl enol ethers, mixed with a CF3 radical source, and
then irradiated with visible light using transparent tubing and a household
compact fluorescent lamp. The continuous protocol uses Eosin Y as an inexpensive
photoredox catalyst and requires only 20 min for both steps.
D. Cantillo, O. D. Frutos, J. A. Rincón, C. Mateos, C. O. Kappe, Org. Lett., 2014,
16, 876-879.
The use of 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-dihydropyrazine
achieves a salt-free stereoselective synthesis of silyl enol ethers from α-halo
carbonyl compounds. In this reaction, easily removable tetramethylpyrazine and
trimethylsilyl halides were generated as byproducts. The inertness of the
reaction byproducts enables one-pot transformations of the in situ generated
silyl enol ethers into various α-functionalized carbonyls.
S. Pramanik, S. Rej, S. Kando, H. Tsurugi, K. Mashima, J. Org. Chem., 2018, 83,
2395-2401.
Pyridinium-masked enols serve as substrates to produce ketones bearing tri-,
di-, and monofluoromethyl in the presence of [Ir(dF(Me)ppy)]2(dtbbpy)]PF6
under blue light (455 nm) irradiation. By simply changing the F-source,
α-trifluoromethyl ketones, α-difluoromethyl ketones, and α-monofluoromethyl
ketones could be easily prepared in good yields in one step.
J. Xu, Y. Li, X. Zhu, S. Lv, Y. Xu, T. Cheng, G. Liu, R. Liu, Org. Lett., 2023, 25,
6211-6216.
An electrochemical synthesis of fluorinated ketones from enol acetates and RfSO2Na
in an undivided cell under constant current conditions proceeds via
perfluoroalkyl radical generation from sodium perfluoroalkyl sulfinate followed
by addition to the enol acetate and transformation of the resulting C radical to
a fluorinated ketone.
V. A. Vil', V. M. Merkulova, A. I. Ilovaisky, S. A. Paveliev, G. I. Nikishin,
A. O. Terent'ev, Org. Lett., 2021, 23,
5107-5112.
An anthraquinone-catalyzed photooxidative keto-trifluoromethylation of
styrenes with the readily available Langlois reagent (CF3SO2Na)
under an oxygen atmosphere proceeds smoothly to give α-trifluoromethyl ketones
in good yield with good selectivity.
E. Yamaguchi, Y. Kamito, K. Matsuo, J. Ishihara, A. Itoh, Synthesis, 2018, 50,
3161-3168.
Photoredox catalysis enables a direct oxidative addition of CF3 and H2O
to alkynes to provide α-trifluoromethyl ketones via rapid enol-keto
tautomerization. The reaction exhibits high functional group tolerance and
regioselectivity. In addition, trifluoromethylated heterocycles of various sizes
were synthesized from α-CF3-substituted diketones.
Y. R. Malpani, B. K. Biswas, H. S. Han, Y.-S. Jung, S. B. Han, Org. Lett.,
2018, 20, 1693-1697.
Related
A regioselective gold-catalyzed hydration of CF3- and SF5-alkynes
provides the corresponding trifluoromethylated and pentasulfanylated ketones in
good yield as single regioisomers. CF3 and SF5 serve as
highly efficient directing groups.
M. Cloutier, M. Roudias, J.-F. Paquin,
Org. Lett., 2019, 21, 3866-3870.
A nickel-catalyzed asymmetric reductive cross-coupling trifluoroalkylation of
acyl chlorides enables an enantioselective synthesis of α-trifluoromethylated
ketones. A one-pot reduction furnished alcohols bearing β-CF3-substituted
stereogenic carbons with excellent diastereoselectivity. The reactions offer
high yields/enantioselectivity, mild conditions, and good functional group
compatibility.
B.-B. Wu, J. Xu, K.-J. Bian, Q. Gao, X.-S. Wang, J. Am. Chem. Soc.,
2022, 144, 6543-6550.
A nickel-catalyzed reductive cross-coupling reaction of acyl chlorides with
racemic secondary α-trifluoromethyl bromides provides structurally interesting
chiral α-CF3 carbonyl compounds with great enantioselectivity and
good functional group tolerance.
J. Wu, H. Wu, X. Liu, Y. Zhang, G. Huang, C. Zhang, Org. Lett.,
2022, 24, 4322-4327.
N-Heterocyclic Carbene Catalyzed Highly Chemoselective Intermolecular
Crossed Acyloin Condensation of Aromatic Aldehydes with Trifluoroacetaldehyde
Ethyl Hemiacetal
B. T. Ramanjaneyulu, S. Mahesh, R. V. Anand, Org. Lett.,
2015,
17, 6-9.