Synthesis of elaborate benzofuran‐2‐carboxamide derivatives through a combination of 8-aminoquinoline directed C–H arylation and transamidation chemistry

Abstract

Herein, we present a short and highly modular synthetic route that involves 8-aminoquinoline directed C–H arylation and transamidation chemistry, and which enables access to a wide range of elaborate benzofuran‐2‐carboxamides. For the directed C–H arylation reactions, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3‐arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a one‐pot, two‐step transamidation procedure, which proceeded via the intermediate N‐acyl‐Boc‐carbamates. Given the high efficiency and modularity of this synthetic strategy, it constitutes a very attractive method for generating structurally diverse collections of benzofuran derivatives for small molecule screening campaigns.