Frozen Chirality of Tertiary Aromatic Amides: Access to Enantioenriched Tertiary α‐Amino Acid or Amino Alcohol without Chiral Reagent

Abstract

One of the fundamental and intriguing aspects of life is the homochirality of the essential molecules. In this field, the absolute asymmetric synthesis of α-amino acids is a major challenge. Herein, we report access, by chemical means, to tertiary α-amino acid derivatives in up to 96 % ee without using any chiral reagent. In our strategy, the dynamic axial chirality of tertiary aromatic amides is frozen in a crystal and is responsible for the stereoselectivity of the subsequent steps. Furthermore, we could control the configuration of the final product by manually sorting and selecting the initial crystals. Based on vibrational circular dichroism studies, we could rationalize the observed stereoselectivity.

Highly Stereoselective Aldol Reactions by Memory of Chirality: Synthesis of Quaternary β‐Hydroxy α‐Amino Acids

“…This type of cyclization has already been described in the past [32] . We could consider deprotecting the methionine derivatives using milder conditions, as we described in the case of frozen chirality (basic hydrolysis of oxazolidinone, esterification of the acid, then reduction of the amide to imine by Schwartz ’s reagent and mild hydrolysis), [33,34] in order to retain the methyl group. This is currently under investigation.…”