Synthesis of 2‐Phenyl‐4,6‐bis(trifluoromethyl)pyridine via NH ₄ I/Na ₂ S ₂ O ₄ ‐Mediated Cyclization of Ketoxime Acetates

Abstract

This chapter presents the procedure for synthesis of 2‐phenyl‐4,6‐ bis(trifluoromethyl) pyridine via NH 4 I/Na 2 S 2 O 4 ‐ mediated cyclization of ketoxime acetates. O‐Acyl oximes have been used as versatile building blocks to form N‐containing heterocycles through catalytic N–O bond reduction by transition metal‐mediated oxidative addition. In this work, the authors have developed a NH 4 I/Na 2 S 2 O 4 ‐based reductive system which enables the N–O bond cleavage of oximes and thereby promotes the assembly of pharmacologically significant fluorinated pyridines. Hence, this protocol provides a modular access to 4,6‐bis(trifluoromethyl)pyridines by the reductive cyclization of O‐acyl oximes and hexafluoroacetylacetone. Salient features of this method include easily available starting materials, broad functional group compatibility, good yields, and high regio‐ and chemo‐selectivity.