Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral beta-Fluoroamines

摘要

Reported herein is a Zn/Prophenol-catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio-and diastereoselective construction of beta-fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover, a related aldol reaction was also developed. Together, these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C-F centers.