Trifluoromethylation of Organic Compounds and Related Reactions

This review concentrates on trifluoromethylation and related reactions from the authors' group. Mainly, our new rhodium complex catalyzed synthesis of trifluoromethyl and other fluorine compounds will be discussed. However, initially we would like to discuss the origins and development of this reaction. Thus, trifluoromethylation of aromatic and aliphatic halides with trifluoromethyl iodide in the presence copper powder will be discussed first, and then the application of this copper-mediated reaction to ethyl bromodifluoroacetate for the synthesis of difluoromethylene compounds will be presented. The investigation of the mechanism of this reaction led us to the Michael addition of the (ethoxycarbonyl) difluoromethyl group to alpha,beta-unsaturated carbonyl compounds. To improve this reaction, we examined the rhodium-catalyzed Michael reaction, and found that the fluorine substituent was introduced surprisingly not to the beta-position but to the alpha-position. This reaction could be used to introduce other fluoroalkyl groups, including the trifluoromethyl group, to the alpha-position of almost all Michael acceptors. Furthermore, this reaction was developed for the introduction of the trifluoromethyl or other fluoroalkyl groups into the alpha-position of ketones or carboxylic acid derivatives through silyl enol ethers or ketene silyl acetals.