1,5-Dimethyl-4-phenylimidazolidin-2-one-derived iminic glycinimides: useful new reagents for practical asymmetric synthesis of alpha-amino acids.
New 1,5-dimethyl-4-phenylimidazolidin-2-one-derived acyclic chiral iminic glycine reagents have been prepared and diastereoselectively alkylated with activated alkyl halides and electrophilic olefins in the presence of lithium chloride under (a) strong bases (LHMDS, KOBu(t)) and low temperature (-78 degrees C) conditions, (b) solid-liquid phase-transfer catalysis reaction (LiOH, TBAB, -20 degrees C) conditions, and (c) in the presence of organic bases (DBU, BEMP, TMG, -20 degrees C). In the case of dielectrophiles C- and N-alkylation takes place to afford heterocyclic derivatives. Hydrolysis of alkylated products has been carried out (a) in two-step procedures with LiOOH or LiOH followed by acidic hydrolysis or Dowex purification, (b) in one single-step under refluxing water to give the corresponding alpha-amino acid, (c) in the presence of DBU in methanol to provide N-protected alpha-amino acids methyl esters, or (d) by a protection-hydrolysis procedure to afford N-Boc-protected alpha-amino acids. The chiral imidazolidinone has generally been recovered in good yield. This methodology has been shown to be useful for the synthesis of acyclic and heterocyclic (S)- and (R)-alpha-amino acids.
Guillena
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Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Alicante, Apartado 99, 03080 Alicante, Spain.
Nájera
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D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D006868:Hydrolysis; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D000596:Amino Acids; D007093:Imidazoles; D007097:Imines; D007202:Indicators and Reagents