Synthesis of 2‐Chloro‐6‐(trifluoromethyl)pyridine‐3,5‐dicarbonitrile: A Versatile Building Block for the Synthesis of Substituted Trifluoro Methyl Pyridine Derivatives

A simple and highly efficient (concise 3‐step) synthesis of 2‐chloro–6‐(trifluoromethyl)pyridine‐3,5‐dicarbonitrile has been developed from readily available starting materials. Furthermore, the selective reactivity of this tetra‐ substituted pyridine with different carbon, sulfur, nitrogen and oxygen nucleophiles offers great scope for the synthesis of novel highly substituted pyridine derivatives in decent to good yields. A synthesis of 2‐chloro‐3,5‐dicyano‐6‐trifluoromethyl pyridine, a versatile building block for the synthesis of CF3‐containing N‐heterocycles is described. A wide range of highly substituted trifluoromethylated pyridines were synthesised through substitution by nucleophiles or by coupling with boronic acids. Reaction with 1,2 bis nucleophiles, such as hydrazines also allows differentiation of the two nitrile substituents, leading to trifluoromethyl aza bicyclic structures.