O-Trifluoromethylation of ketones: an alternative straightforward route to alkenyl trifluoromethyl ethers

Abstract

Here we report an unprecedented O-trifluoromethylation of ketones using chloro(phenyl)trifluoromethyl-λ³-iodane (CPTFI). Our method provides a new strategy for the facile synthesis of various synthetically valuable alkenyl trifluoromethyl ethers, particularly those CF₃O-substituted terminal alkenes and cyclic alkenes that have been elusive until now, from simple aromatic, aliphatic, and cyclic ketones. The success of this reaction is attributed to the full utilization of the multifunctionality of CPTFI: (1) its strong Lewis acid activation ability, which enables weak nucleophiles such as Cl anions to attack the carbonyl group; (2) its bifunctionality, which allows for the introduction of CF₃ and Cl into the carbonyl group in one step, thus enabling the obtainment of alkenyl trifluoromethyl ethers by further removal of HCl. The further transformation in the synthesis of CF₃O-cyclopropanes, which were previously largely unexplored, reveals the significant potential of alkenyl trifluoromethyl ethers as valuable CF₃O-containing building blocks in the discovery of innovative materials, pharmaceuticals, and agrochemicals.