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

Su Hyeon Park; Sunwoo Lee

doi:10.1021/acs.orglett.3c02809

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

Org Lett. 2023 Sep 22;25(37):6925-6930. doi: 10.1021/acs.orglett.3c02809. Epub 2023 Sep 10.

Authors

Su Hyeon Park¹, Sunwoo Lee¹

Affiliation

¹ Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea.

PMID: 37690119
DOI: 10.1021/acs.orglett.3c02809

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.