Rhodium-Catalyzed Allylic Amination for the Enantioselective Synthesis of Tertiary β-Fluoroamines.

The utilization of β-fluoroamines as pharmaceutical components for drug development has attracted a considerable amount of interest. However, direct access to tertiary β-fluoroamines is challenging. We herein report the rhodium-catalyzed asymmetric amination of tertiary allylic trichloroacetimidates with anilines and cyclic aliphatic amines to access tertiary β-fluoroamines, where the α-carbon atom is bonded to four different substituents, in good yield with high levels of enantioselectivity.

Scope and Mechanistic Probe into Asymmetric Synthesis of α-Trisubstituted-α-Tertiary Amines by Rhodium Catalysis.

Asymmetric reactions that convert racemic mixtures into enantioenriched amines are of significant importance due to the prevalence of amines in pharmaceuticals, with about 60% of drug candidates containing tertiary amines. Although transition-metal catalyzed allylic substitution processes have been developed to provide access to enantioenriched α-disubstituted allylic amines, enantioselective synthesis of sterically demanding α-tertiary amines with a tetrasubstituted carbon stereocenter remains a major challenge. Herein, we report a chiral diene-ligated rhodium-catalyzed asymmetric substitution of racemic tertiary allylic trichloroacetimidates with aliphatic secondary amines to afford α-trisubstituted-α-tertiary amines.