Efficient Synthesis of β-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols

The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form C-sp3-CF3 and C-sp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of beta-CF3- and beta-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well.