Abstract
We describe herein the elaboration of a new type of a substrate based on the Ni(II) complex of a Schiff base of dehydroalanine, 1, and Michael addition of nucleophiles to it, leading to the synthesis of racemic α-amino acids. We have also developed a catalytic method for the asymmetric 1,4 conjugate addition of achiral CH-acids to 1 promoted by TADDOLs with enantioselective catalytic protonation of the intermediate enolate in the stereodetermining stage of the reaction. A sizable 80% ee of the product was observed.
Highlights
The asymmetric catalytic version of the reaction was used for amino acid synthesis with remarkable success, applying condensation of O’Donnel’s glycine imine derivatives and acrylic acid esters catalyzed by Cinchona alkaloid ammonium salts and synthetic quaternary ammonium salts as efficient chiral phase-transfer catalysts
It is generally assumed that the stereoselective formation of the C-C bonds and of the amino acid occur at the stage of the addition of the intermediate enolate of the glycine derivative to the activated C=C bond of acrylic derivatives
The substrate 1 proved to be very convenient for the synthesis of racemic α-amino acids by Michael addition of nucleophiles in analogy with an earlier described procedure for the synthesis of non-racemic amino acids, using chiral Ni(II) dehydroalanine Schiff base complexes with BPB.10e,f The reaction of 1 with nucleophiles was carried out according to Scheme 2, and the course of the reaction was monitored by TLC (SiO2, CHCl3/acetone)
Summary
Enantioselective conjugate addition is a fundamentally important transformation in asymmetric synthesis. The asymmetric catalytic version of the reaction was used for amino acid synthesis with remarkable success, applying condensation of O’Donnel’s glycine imine derivatives and acrylic acid esters catalyzed by Cinchona alkaloid ammonium salts and synthetic quaternary ammonium salts as efficient chiral phase-transfer catalysts. It is generally assumed that the stereoselective formation of the C-C bonds and of the amino acid occur at the stage of the addition of the intermediate enolate of the glycine derivative to the activated C=C bond of acrylic derivatives. The asymmetric catalytic version of the reaction was used for amino acid synthesis with remarkable success, applying condensation of O’Donnel’s glycine imine derivatives and acrylic acid esters catalyzed by Cinchona alkaloid ammonium salts and synthetic quaternary ammonium salts as efficient chiral phase-transfer catalysts.. It is generally assumed that the stereoselective formation of the C-C bonds and of the amino acid occur at the stage of the addition of the intermediate enolate of the glycine derivative to the activated C=C bond of acrylic derivatives. Within the ion pair formed by Cinchona alkaloid ammonium salt and the enolate.3 Another possibility of introducing asymmetry into the adduct by enantioselective catalytic protonation of the intermediate enolate was generally neglected. We have attempted to develop a catalytic variation for the asymmetric 1,4 conjugate addition of achiral CH-acids to 1 promoted by TADDOLs with asymmetric catalytic protonation of the intermediate enolate in the sterodetermining stage of the reaction
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