Memory of chirality of tertiary aromatic amides: a simple and efficient method for the enantioselective synthesis of quaternary alpha-amino acids.
A new methodology for the asymmetric synthesis of quaternary alpha-substituted amino acids using memory of chirality has been developed. The strategy utilizes the dynamic axial chirality of tertiary aromatic amides to memorize the initial chirality of an alpha-amino acid during an enolization step. Starting from five different l-amino acids, the corresponding oxazolidin-5-ones containing a tertiary aromatic amide group have been synthesized in one step and then alkylated with various electrophiles, with good yields and enantioselectivities (up to 96% and up to >99% after recrystallization). One-step deprotection affords enantioenriched or enantiopure quaternary alpha-amino acids. We describe here the optimization process, the results obtained in each series and a plausible explanation, based on NMR studies, DFT calculations and crystallographic structures. The methodology presented herein constitutes an efficient synthesis of enantiopure quaternary alpha-amino acids (three steps only) starting from tertiary l-amino acids, without any external source of chirality.
Branca
Mathieu
M
Laboratoire de Chimie des Procédés et Substances Naturelles, ICMMO, CNRS UMR 8182, Université de Paris-Sud, F-91405 Orsay, France.
Pena
Sébastien
S
Guillot
Régis
R
Gori
Didier
D
Alezra
Valérie
V
Kouklovsky
Cyrille
C
D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
D000577:Amides; D000596:Amino Acids