Regioselective homolytic substitution of benzo[c][2,7]naphthyridines

Benzo[c][2,7]naphthyridines bearing electron-withdrawing substituents (bromo, acetyl) at C-4 undergo regioselective homolytic substitutions at C-5 with nucleophilic 1,3,5-trioxanyl and ethoxycarbonyl radicals under Minisci conditions. Surprisingly, mainly 5,6-dihydro derivatives are formed in these reactions. Rearomatization with manganese dioxide leads to 4,5-disubstituted benzo[c][2,7]naphthyridines, which should be attractive building blocks for the synthesis of pyridoacridine alkaloids. Homolytic methylation at C-5 takes place with methyl radicals generated from acetic acid and acetaldehyde, respectively.