Selective Synthesis of (Z)- and (E)-β-Fluoro-α,β-Unsaturated Amides Using Palladium-Catalyzed Aminocarbonylation.

Abstract

The selective synthesis of (Z)- and (E)-β-fluoro-α,β-unsaturated amides via the palladium-catalyzed aminocarbonylation of 1-fluoro-2,2-diiodovinylarenes is described in the present study. Using {Pd(allyl)Cl}2 as a catalyst and DBU as a base in DMF, the primary product is (Z)-isomers. Conversely, the use of a Xantphos ligand along with {Pd(allyl)Cl}2 and Et3N as the bases in 1,4-dioxane leads to the selective formation of (E)-isomers. Notably, 1-fluoro-2,2-diiodovinylarenes with various substituents on the phenyl ring react with various secondary amines, producing the corresponding (Z)-isomeric amides with a high yield and selectivity. In contrast, (E)-isomeric amides exhibit lower yields and restricted applicability.