Synthesis of Fluorinated Pyridines and Their Conversion into Naphthyridines

Significance

In the reported study, fluorine containing pentasubstituted pyridine derivatives were prepared by an intermolecular cyclization of N-silyl-1-aza-allylic anion intermediates. Moreover, the resulting isoxazoyl pyridines were converted into 1,6-naphthyridin-4-one derivatives by a reductive ring-opening with PtO₂ [or Mo(CO)₆] and subsequent intramolecular cyclization, effectively and economically promoted by aqueous NaOH. The yields of the first cyclization are moderate to good, but the following cyclization to naphthyridin-4-ones proceeded with good to excellent yields. The reason for the low yield observed with propionitrile (R² = Et) are obviously due to the acidic α-protons. The substrate scope of this reaction was well studied with respect to aryl and heteroaryl nitriles.