Asymmetric synthesis of β-trifluoromethyl-β-amino acids, including highly sterically constrained α,α-dialkyl derivatives

Reported herein is asymmetric synthesis of β-trifluoromethyl-β-amino acids via Mannich addition reactions between (Ss)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine and lithium enolates of alkyl acetates. In particular, the scope of this approach allows for preparation of the previously illusive, highly sterically constrained α,α-dialkyl-β-trifluoromethyl-β-amino acids. The method affords the target products with good to excellent chemical yields and diastereoselectivities.

Graphical abstractβ-Trifluoromethyl-β-amino acids, including highly sterically constrained α,α-dialkyl-β-trifluoromethyl-β-amino acids, were synthesized via asymmetric Mannich addition reactions between (Ss)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine and lithium enolates of alkyl 2,2-(dialkyl)acetates.Figure optionsDownload full-size imageDownload as PowerPoint slide