Synthesis Of β-Branched α-Amino Acids Research Articles

Syn-Selective Synthesis of β-Branched α-Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates

A syn-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain.

Practical Stereoselective Synthesis of β-Branched α-Amino Acids through Efficient Kinetic Resolution in the Phase-Transfer-Catalyzed Asymmetric Alkylations

Phase-transfer-catalyzed alkylation of glycinate Schiff base with racemic secondary alkyl halides proceeded with excellent levels of syn- and enantioselectivities under the influence of chiral quaternary ammonium bromide 1d and 18-crown-6. The alkylation product can be selectively converted to the corresponding anti isomer, allowing the preparation of all the stereoisomers of beta-alkyl-alpha-amino acid derivatives, an extremely valuable chiral building block.