An easy stereoselective access to beta,gamma-aziridino alpha-amino ester derivatives via mannich reaction of benzophenone imines of glycine esters with N-sulfonyl alpha-chloroaldimines.
Mannich-type addition of benzophenone imine glycinates across newly synthesized N-(p-toluenesulfonyl) alpha-chloroaldimines afforded gamma-chloro-alpha,beta-diamino ester derivatives with moderate diastereoselectivity as separable mixtures of anti and syn diastereomers. The gamma-chloro-alpha,beta-diamino esters were efficiently cyclized under basic conditions to the corresponding beta,gamma-aziridino alpha-amino ester derivatives, representing a new class of conformationally constrained heterocyclic alpha,beta-diamino acid derivatives. The relative configuration of the aziridines was determined via X-ray diffraction analysis. Mechanisms and intermediate transition states to explain the stereochemical outcome of the Mannich reaction with different substrates or under different conditions are proposed. The synthetic importance of the beta,gamma-aziridino alpha-amino ester derivatives is demonstrated by their conversion into the corresponding Boc-protected derivatives and ring opening reactions to alpha,beta-diamino esters and a gamma-amino alpha,beta-unsaturated amino ester.
Kiss
Loránd
L
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Mangelinckx
Sven
S
Sillanpää
Reijo
R
Fülöp
Ferenc
F
De Kimpe
Norbert
N
D000596:Amino Acids / Q000138:chemical synthesis*; D001388:Aziridines / Q000737:chemistry; D001577:Benzophenones / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D000596:Amino Acids; D001388:Aziridines; D001577:Benzophenones; D004952:Esters; D007097:Imines; C033132:aziridine; D005998:Glycine