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.