Study On Copper-Catalyzed Ring-opening Trifluoromethylation Of Cyclopropanols

Trifluoromethyl group （CF₃） is an important structural motif in many pharmaceutical compounds. Drug molecules containing trifluoromethyl can significantly improve their lipophilic, absorbability and metabolic stability. Meanwhile,β-substituted ketone in the field of organic chemical synthesis is an important starting materials and synthetic intermediates. For example,β-substituted ketones are extremely useful intermediates in organic synthesis and act as precursors to enones, annulated compounds, heterocyclic derivatives, and dicarbonyl products.β-trifluoromethyl ketones are important and difficult to synthesis. The reaction conditions are mostly relatively harsh. In the conventional synthetic methods such as nucleophilic addition "CF₃^-" reagent with unsaturated carbonyl compounds. However, this method has a poor regioselectivity. In order to solve this problem, recently attention has shifted to the using of "CF₃⁺" binding agent to synthesize β-trifluoromethyl ketones by a radical process with the transition metal. As we all know, cyclopropanols are easily prepared with the development of Kulinkovich reaction. Importantly, cyclopropanols can undergo synthetically useful ring-opening transformations for the formation of β-substituent （e.g., halogen, aryl, alkyl etc.） ketones. In this context, we are interested in the construction of β-trifluoromethyl ketones from cyclopropanols. The ring-opening trifluoromethylation of cyclopropanols not only expands the concept and utility of C-C bond cleavage trifluoromethylation, but also enable the development of a facile and new route to the synthesis of P-trifluoromethyl ketones. Moreover, our study also adds a new research area of cyclopropanols transformation chemistry.