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

Reported herein is a Zn/Prophenol‐catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio‐ and diastereoselective construction of β‐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. Work of a Pro: A Zn/Prophenol‐catalyzed direct Mannich reaction using α‐fluoroketones allows efficient construction of β‐fluoroamine motifs with high enantio‐ and diastereoselectivities. A stereocomplementary aldol reaction is also described. Boc=tert‐butoxycarbonyl.