Pyridine C─N Transposition via Cycloaddition–Cycloreversion

Abstract

The selective incorporation of nitrogen atoms is fundamental to the design and synthesis of drugs and other functional molecules. Here, we describe a skeletal-editing approach to the transposition of pyridine nitrogen atoms, creating a route to 3-alkylated pyridines that are difficult to access using current methods. The reaction uses a cycloaddition/cycloreversion strategy (CACR) to transpose easily made 4-aryl and alkyl pyridines into the more challenging meta-functionalized isomers. The cycloaddition reaction introduces versatile sulfone functionality, that can be harnessed for further C─X and C─C bond formations for pyridine synthesis.