Amino acid homologation by the Blaise reaction: a new entry into nitrogen heterocycles.
A general strategy for the amino acid homologation via Blaise reaction and subsequent reduction is presented. This strategy involves the preparation of protected alpha-amino nitriles from the corresponding amino acids, followed by the zinc-mediated condensation of tert-butyl bromoacetate, to give the imidazolidones after iminozincate cyclization. Reduction gave the saturated imidazolidinones with cis or trans stereochemistry, depending on the reduction conditions. This strategy was applied to nonfunctionalized amino acids and to functionalized amino acids such as serine and aspartic acid. Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described.
Laboratoire de Chimie des Procédés et Substances Naturelles, Institut de Chimie Moléculaire et des Matériaux d'Orsay (UMR CNRS no. 8182), Université Paris-Sud, F-91405 Orsay, France.
Cam Thuy
CT
Hoang
Francelin
F
Bouillère
Sine
S
Johannesen
Anaïs
A
Zulauf
Cécilia
C
Panel
Annie
A
Pouilhès
Didier
D
Gori
Valérie
V
Alezra
Cyrille
C
Kouklovsky
D000596:Amino Acids / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D048289:Imidazolidines / Q000138:chemical synthesis*; D009570:Nitriles / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis
D000596:Amino Acids; D006571:Heterocyclic Compounds; D048289:Imidazolidines; D009570:Nitriles; D011760:Pyrrolidinones