Expeditious Synthesis of Highly Functional 4-Trifluoromethyl-Substituted Oxazoles Enabled by Cobalt(II) Metalloradical Catalysis

A synthetic strategy for the catalytic cycloaddition of α-trifluoromethyl-α-diazoketones with nitriles has been achieved based on cobalt(II) metalloradical catalysis. The easily accessible starting materials, cost-effective catalyst, and experimental simplicity rendered this protocol a robust and practical approach to construct diverse functionalized 4-CF3-substituted oxazoles with high efficiency. A wide substrate scope of both α-trifluoromethylated diazoketones and nitriles is amenable to this catalytic system. The high level of functional group tolerance of this protocol provides several opportunities for precise late-stage modifications of bioactive and drug-like molecules. Mechanistic experiments and spectroscopic investigations confirm the radical nature of the reaction and reveal the involvement of both monocarbene and biscarbene radical intermediates during the catalytic process.