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

Synthesis of trifluoromethyl ketones


Recent Literature

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.

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.