Absolute Asymmetric Synthesis of Tertiary α‐Amino Acids

Abstract

Frozen: the spontaneous crystallization of an achiral compound in a chiral conformation is used as the unique source of chirality in an absolute asymmetric synthesis of tertiary amino acids. The dynamic axial chirality of tertiary aromatic amides is frozen in a crystal and is responsible for the stereoselectivity of the deprotonation/alkylation. α-Amino acid derivatives are synthesized in up to 96 % ee.

Supramolecular chirality induced by a weak thermal force

“…Some examples of external asymmetric forces able to induce enantioselection are irradiation with circularly polarized light causing asymmetric photosynthesis or photolysis, 2,7-9 heterogeneous catalysis, [10][11][12] stirring and vortex motions [13][14][15][16][17][18][19][20] and simultaneous acting of external elds. [21][22][23] Once the enantioselection is induced, the amplication of the mirror-asymmetry (chirality) can be realized by additional mechanisms.…”

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.…”

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

“…The next step was an extension of this latter methodology to the great challenge of absolute asymmetric synthesis of tertiary α‐amino acids; that is, to get rid of the initial chirality and to start from the simplest achiral α‐amino acid, glycine. We thus exploited the frozen chirality principle and described in a preliminary communication the absolute asymmetric synthesis of tertiary α‐amino acid derivatives with enantiomeric excesses up to 96 %. Herein, we describe the complete study, as well as the synthesis of amino alcohol and we propose an explanation for the observed stereoselectivity based on vibrational circular dichroism (VCD) and NMR studies.…”