Alkynyl Triazenes as Fluoroalkyne Surrogates: Regioselective Access to 4‑Fluoro-2-pyridones by a Rh(III)-Catalyzed C–H Activation–Lossen Rearrangement–Wallach Reaction

Fluorinated pyridones
are an important scaffold displaying relevant
biological activities. Efficient assembly strategies of pyridones
are transition metal-catalyzed C–H annulations with alkynes.
The inaccessibility and extreme lability of fluoro alkynes render
any direct utilization in catalysis futile. We report a highly regioselective
synthesis of 4-fluoro-2-pyridones using 1-alkynyl triazenes as a convenient
fluoroalkyne surrogates. The protocol comprises an alkenyl C–H
annulation with 1-alkynyl triazenes followed by a treatment with HF·pyridine
smoothly delivering a broad range of 4-fluoro-2-pyridones in a one-pot
fashion in 90 min at 23–60 °C. Notably, a rare Lossen
rearrangement occurs during the C–H functionalization part
of the transformation, allowing selective access to the less-available
4-fluoro-2-pyridone framework. Furthermore, the triazenyl intermediate
was elaborated into additional fluorine-containing substituents like
fluorinated alkoxy and trifluoromethyl groups.