Tertiary aromatic amide for memory of chirality: access to enantioenriched alpha-substituted valine.
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.
Branca
Mathieu
M
Laboratoire de Chimie des Procédés et Substances Naturelles, ICMMO, CNRS UMR 8182, Bât 410, Université Paris-Sud, F-91405 Orsay, France.
Gori
Didier
D
Guillot
Régis
R
Alezra
Valérie
V
Kouklovsky
Cyrille
C
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
D000577:Amides; D000596:Amino Acids; D023303:Oxazolidinones; D001224:Aspartic Acid; D014633:Valine