Through the development of a one pot synthesis of fused substituted heteroaryl-lactones involving a Metal/Halogen Exchange reaction as key step, the reactivity of various mono- or bimetallic reagents (organolithiums, Grignard reagents and lithium organomagnesiate complexes) was explored to aim high chemoselectivity and efficiency starting from sensitive substrates.

Abstract

Herein we disclose an efficient one-pot route to a wide range of 3-substituted fused pyridinyl-lactones, so called aza-phthalides. The developed strategy involves a Metal/Halogen Exchange (MHE) reaction as key step, followed by an electrophile trapping using various carbonyl derivatives and a subsequent lactonization. To promote the MHE reaction with high chemoselectivity, our investigations have particularly focused on the nature of mono- or bimetallic derivatives as metalation reagents including organolithiums, Grignard reagents and lithium organomagnesiate complexes, and highlighted the positive salt effect on reactional sequence. An extension to fused heteroaryl-lactones (benzothienyl-, benzofuranyl- and naphthofuranyl scaffolds) was explored.