Facile synthesis of structurally diverse 5-oxopiperazine-2-carboxylates as dipeptide mimics and templates.
A sequence of Michael addition of a primary amine onto methyl 2-chloro-2-cyclopropylidene-acetate (1), acylation of the adduct with alpha-bromo acid chlorides under modified Schotten-Baumann conditions and ring-closing twofold nucleophilic substitution on the thus formed bishalides 3a-e with aliphatic or aromatic amines according to a very simple protocol with final acid/base extraction or filtration over silica gel for purification leads to the 3-spirocyclopropanated 5-oxopiperazine-2-carboxylates 2 or in two cases, after intermolecular transesterification of 2, to bicyclic oxopiperazines 6, with a remarkable variability of the substituents R1-R3 in 39-99% yields (20 examples). Starting with alpha-bromophenylacetic acid chloride, the trans-configured 6-phenyl-5-oxopiperazine-2-carboxylates are formed preferentially.
Limbach
Michael
M
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Lygin
Alexander V
AV
Korotkov
Vadim S
VS
Es-Sayed
Mazen
M
de Meijere
Armin
A
D000588:Amines / Q000737:chemistry; D032701:Biomimetics / Q000379:methods; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis*; D018716:Molecular Mimicry / Q000502:physiology*; D013237:Stereoisomerism
D000588:Amines; D002264:Carboxylic Acids; D004151:Dipeptides