Synthesis of benzenes from pyridines via N to C switch

Abstract

The skeletal editing of heteroarenes introduces new disconnections to the chemistry lexicon, enabling the interconversion of ring systems via selective breaking/re-making of the carbon framework. We describe the one-pot transformation of pyridines into benzene derivatives, using a nucleophilic addition ring-opening/ring-closing (ANRORC) process with soft nucleophiles such as malonate. Triflic anhydride activates the pyridine to ANRORC synthesis via an isolable amine intermediate, which aromatizes on simple heating. The reaction has been exemplified with a room temperature protocol, along with direct syntheses of drug-like, tertiary-alkylated, and isotopically labeled benzoates.

Topics & Concepts