Synthesis of all regioisomers of dihydroazapaullones

Abstract

We developed a unified synthetic route to dihydroazapaullones featuring a base‐mediated intramolecular Michael addition of N‐(2‐nitrobenzyl)‐2‐aminoazacinnamates as the key step for constructing the dihydroazaindole‐3‐acetate scaffold. N‐Benzylation of 2‐aminoazacinnamates with either 2‐nitrobenzaldehyde or 2‐nitrobenzyl bromide afforded the corresponding N‐(2‐nitrobenzyl) derivatives, which underwent base‐mediated cyclization to furnish dihydroazaindole‐3‐acetates bearing a 2‐nitrophenyl group at the C2 position. Subsequent nitro reduction followed by azepinone formation completed the synthesis of dihydroazapaullones. Notably, this strategy is applicable to the synthesis of all regioisomeric dihydroazapaullones.