Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

Abstract

Readily available 4-bromobenzo[c][2,7]naphthyridine undergoes regioselective direct ring metalation at C-5 with TMPMgCl∙LiCl at −40 °C. Quenching with various electrophiles gives a broad range of 5-substituted products, which are building blocks for the synthesis of heterocyclic natural products and analogues thereof. In combination with a Parham-type cyclization a novel approach to pyrido[4,3,2-mn]acridones has been worked out.

Keywords

• alkaloids
• cyclization
• metalation
• naphthyridine
• pyridoacridine