Highly Stereoselective Tandem Aza‐Michael Addition–Enolate Protonation to Form Partially Modified Retropeptide Mimetics Incorporating a Trifluoroalanine Surrogate

Fine-tuning of key reaction parameters, such as the solvent and the base used, led to a dramatic improvement in d.r. (from ≈1:1 to 38:1) in a tandem aza-Michael addition–enolate protonation sequence. Thus, the reaction of α-amino ester nucleophiles 1 with N-(α-trifluoromethyl)acryloyl-α-amino ester acceptors 2 produced an array of partially modified retropeptide mimetics 3 with good to excellent stereocontrol (R, R1, R2, X, X1=alkyl).