Directed Zincation or Magnesiation of the 2-Pyridone and 2,7-Naphthyridone Scaffold Using TMP Bases

A regioselective zincation of the 2-pyridone and 2,7-naphthyridone scaffolds has been developed. Zincations of the methoxyethoxymethyl (MEM)-protected compounds using TMP2Zn.2MgCl(2).2LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping with electrophiles provided functionalized 2-pyridones and 2,7-naphthyridones. I/Mg exchange of iodinated 2-pyridone and 2,7-naphthyridone using iPrMgCl.LiCl afforded magnesiated intermediates that reacted with electrophiles. A second magnesiation of the 2-pyridone scaffold was achieved by using TMPMgCl.LiCl. Additionally, we report CoCl2-catalyzed cross-couplings of the 1-chloro-2,7-naphthyridines with arylzinc halides.