RESUMEN
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.
Asunto(s)
Amidas/química , Aminoácidos/química , Amino Alcoholes/química , Amidas/síntesis química , Dicroismo Circular , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Conformación Molecular , Oxazolidinonas/síntesis química , Oxazolidinonas/química , EstereoisomerismoRESUMEN
We describe an original asymmetric synthesis of (S)-α-methylDOPA proceeding by the concept of memory of chirality, the only source of chirality being the starting D-alanine. The initial chirality of the amino acid is temporarily transferred to a dynamic axial chirality of a tertiary aromatic amide. The (S)-α-methylDOPA hydrochloride is obtained after four steps with 98% ee.
Asunto(s)
Amidas/química , Aminoácidos/síntesis química , Metildopa/síntesis química , Aminoácidos/química , Metildopa/química , EstereoisomerismoRESUMEN
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.