Ring lithiation of pyridones

Abstract

Lithiation of 1-methyl-2-pyridone takes place mainly at the methyl group which then leads to a dimer (11) by addition to a second mol equivalent of pyridone at C-6. Lithiation of 1-methyl-4-pyridone takes place cleanly and efficiently at C-2; this lithio derivative gave a dimer (13) with a second mol equivalent of the pyridone and reacted with a variety of carbon electrophiles to produce 2-substituted 4-pyridones (14c–n). 1-Methoxymethyl-, 1-benzyloxymethyl-, and 1-(2-trimethylsilylethoxy)-methyl-4-pyridones also lithiate at C-2, though these lithio derivatives were much less reactive towards electrophiles.