Tertiary aromatic amide for memory of chirality: access to enantioenriched alpha-substituted valine.

A new methodology for the asymmetric synthesis of quaternary alpha-substituted amino acids using memory of chirality has been developed. This strategy employs dynamic axial chirality of tertiary aromatic amides to memorize the initial chirality of an alpha-amino acid during the enolization step. Starting from L-valine, an oxazolidin-5-one containing a tertiary aromatic amide was synthesized in one step and then alkylated with various electrophiles with good yield and enantioselectivity (up to 96%). Quaternary products can be obtained enantiomerically pure by recrystallization. One-step deprotection affords enantioenriched (S)-alpha-methyl valine (ee = 94%) or enantiopure (S)-alpha-isopropyl aspartic acid (ee >99%) in only three steps starting from L-valine.