Study On Decarboxylation - Amino Reaction Of Aldehydes

As a class of highly valuable intermediates in organic synthesis, α-amino anions can react with various electrophiles to furnish significant amines. However, it is not easy to obtain α-amino anions directly from amines under mild conditions. Recently, we found that the lithium salt of diphenylglycinate imine, obtained by condensation of aldehyde and 2,2-diphenylglycine in methanol, could undergo decarboxylation in THF at room temperature to generate a delocalized 2-azaallyl anion. This chemistry has provided an opportunity to construct various amines from readily available, electrophilic aldehydes.The α-amino 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. Further studies indicate that the transformation can be developed into a one-pot procedure for the synthesis of α-methylidene-γ-amino acid esters directly from aldehydes. Aldehydes first were converted into Schiff base lithium salts by stirring with 2,2-diphenylglycine in methanol at room temperature, followed by reaction with MBH adduct in the presence of DABCO catalyst in CH3 CN at 0 ℃, to give the corresponding α-methylidene-γ-amino acid esters in high yields. The diastereoselectivity and isolated yield are similar to those obtained from the reaction of the preformed lithium salt with MBH adduct.α-Methylidene-γ-amino carbonyl compounds are versatile building blocks for many biologically active compounds. For example, α-methylidene-γ-amino acid esters can be readily converted to α-exo-methylidene-γ-lactams which are broadly present in many natural products and pharmaceuticals.In summary, we have developed a new and efficient method for the synthesis of substituted α-methylidene-γ-amino acid esters in high yields and good selectivity from readily available aldehydes by using an aminative Umpolung strategy.