Synthesis of α-Methylidene-γ-amino Acid Esters from Aldehydes via an Aminative Umpolung Strategy.

This paper describes an efficient method for the synthesis of α-methylidene-γ-amino acid esters from readily available aldehydes by using aminative umpolung strategy. Electrophilic aromatic aldehydes were converted to α-imino anions via amination with 2,2-diphenylglycine in methanol and subsequent decarboxylation in acetonitrile. The in situ generated α-imino anions displayed high activity in the reaction with Morita-Baylis-Hillman adducts in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as catalyst, to give a variety of substituted α-methylidene-γ-amino acid esters in 54-96% yields with 3.2-7.1:1 diastereoselectivity. The resulting α-methylidene-γ-amino acid esters can be efficiently converted into biologically important α- exo-methylidene-γ-lactams under mild conditions. [ABSTRACT FROM AUTHOR]