title: Tertiary aromatic amide for memory of chirality: access to enantioenriched alpha-substituted valine.
abstract: 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.
authors.affiliation: Laboratoire de Chimie des Procédés et Substances Naturelles, ICMMO, CNRS UMR 8182, Bât 410, Université Paris-Sud, F-91405 Orsay, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Branca
authors.forename: Didier
authors.initials: D
authors.lastname: Gori
authors.forename: Régis
authors.initials: R
authors.lastname: Guillot
authors.forename: Valérie
authors.initials: V
authors.lastname: Alezra
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kouklovsky
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D023303:Oxazolidinones / Q000737:chemistry; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000577:Amides; D000596:Amino Acids; D023303:Oxazolidinones; D001224:Aspartic Acid; D014633:Valine