Categories: C-C Bond Formation > Heteroatom-containing Molecules > Trihalomethyl Ketones, Trifluoromethylation
Synthesis of trifluoromethyl ketones
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Recent Literature
Fluoroarenes mediate a trifluoromethylation of carboxylic acids to provide
trifluoromethyl ketones. The fluoroarene activates the acid group and generates
the trifluoromethyl anion in situ. The protocol is safe and metal-free, operates
under mild reaction conditions in batch and continuous flow, and does not
require any external additives.
M. S. Said, N. S. Khonde, P. Kumar, J. M. Gajbhiye, Org. Lett., 2023, 25,
1094-1098.
The trifluoromethylation of aldehydes with (bpy)Cu(CF3)3, Et3SiH, and K2S2O8 in aqueous
acetone at room temperature provides the corresponding trifluoromethyl ketones
in satisfactory yields. The protocol is applicable to both aliphatic and
aromatic aldehydes and exhibits wide functional
group compatibility. A mechanism involving Cu(II)-mediated trifluoromethylation
of acyl radicals is proposed.
P. Zhang, H. Shen, L. Zhu, W. Cao, C. Li, Org. Lett.,
2018, 20, 7062-7065.
The use of anhydrides as in situ activating reagents enables an efficient and
convenient trifluoromethylation of a wide range of benzoic acids with TMSCF3
through addition-elimination to provide aryl trifluormethyl ketones in very
good yields.
X. Liu, L. Liu, T. Huang, J. Zhang, Z. Tang, C. Li, T. Chen, Org. Lett., 2021, 23,
4930-4934.
Related
A selective acylation of readily accessible organomagnesium reagents with
commercially available esters proceeds in short residence times in continuous
flow. Flow conditions prevent premature collapse of the hemiacetal intermediates
despite noncryogenic conditions, thus furnishing ketones in good yields.
B. Heinz, D. Djukanovic, M. A. Ganiek, B. Martin, B. Schenkel, P. Knochel,
Org. Lett., 2020, 22, 493-496.
Commercially available Selectfluor mediates a chemoselective synthesis of
α-halo-α,α-difluoromethyl ketones (-COCF3 and -COClCF2
motifs) from trimethyl(phenylethynyl)silane under catalyst-free and mild
conditions. In the presence of NaCl as halogen reagent, the reaction
provides α-chloro-α,α-difluoromethyl ketones.
X. Bai, Y. Bai, Y. Li, C. Zhao, H. Du, Y. Li, C. Shen, M. Zhang, L. Chen, Org. Lett., 2024,
26, 4508-4513.
A tandem process of a Claisen condensation and a retro-Claisen C-C bond cleavage
enables an efficient, operationally simple approach to trifluoromethyl ketones.
Enolizable alkyl phenyl ketones readily react with ethyl trifuoroacetate under
the promotion of NaH to afford trifluoromethyl ketones. This procedure can be
extended to the preparation of perfluoroalkyl ketones in excellent yield.
D. Yang, Y. Zhou, N. Xue, J. Qu, J. Org. Chem., 2013,
78, 4171-4176.
Enolizable carboxylic acids were converted in a single step to trifluoromethyl
ketones. Treatment of the acid with LDA generated an enediolate that was
trifluoroacetylated with EtO2CCF3. Quenching the reaction
mixture with aqueous HCl resulted in rapid decarboxylation and provided the
trifluoromethyl ketone product in good yield.
J. T. Reeves, J. J. Song, Z. Tan, H. Lee, N. K Yee, C. H. Senanayake, J. Org. Chem., 2008,
73, 9476-9478.
A chemoselective α-trifluoroacetylation of tertiary amides with
trifluoroacetic anhydride proceeds under mild conditions using 2,4,6-collidine
as a weak base. β-Ketoamides containing trifluoroacetyl or perfluoroacyl groups
were selectively obtained even in the presence of other functional groups such
as ketone, ester, etc.
T. Morita, K. Makino, M. Tsuda, H. Nakamura, Org. Lett., 2023, 25,
8901-8905.