Fe-Catalyzed Fluoroalkyl(hetero)arylation of Vinyl Azaarenes: Rapid and Modular Synthesis of Unsymmetrical 1,1-Bis(hetero)arylalkanes.

ABSTRACT: In contrast to transition-metal-catalyzed difunctionalization of activated alkenes, selective alkylarylation of vinyl azaarenes is underdeveloped. Consequently, the lack of modular and rapid syntheses of 1,1-bis(hetero)arylalkanes limits their exploration in medicinal chemistry. Herein we report a protocol using commercially available iron salts, bisphosphine ligands, fluoroalkyl halides, and Grignard reagents that enables the selective 1,2-fluoroalkyl(hetero)arylation of vinyl azaarenes. We demonstrate the versatility and robustness of the method through the selective synthesis of a range of unsymmetrical 1,1-bis(hetero)arylalkenes, including pyridine N-oxides, triazoles, pyrazines, carbazoles, indazoles, and 1,2-azaborines. Mechanistic insights from experimental and computational investigations support a radical pathway and provide insights into the role of non-covalent interactions in iron catalysis.

SUBMITTER: Guerrero M 

PROVIDER: S-EPMC11348425 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature