Organocatalytic asymmetric synthesis of quaternary α-isoxazole-α-alkynyl amino acid derivatives

An enantioselective addition of 5-amino-isoxazoles with beta,gamma-alkynyl-alpha-ketimino esters catalyzed by a chiral phosphoric acid has been developed. This procedure allowed the formation of quaternary alpha-isoxazole-alpha-alkynyl amino acid derivatives with high yields (up to 99%) and good to excellent enantioselectivities (up to 97%), and the corresponding products enabled many further elaborations. The control experiment revealed that the hydrogen-bonding interaction of 5-amino-isoxazole with the chiral phosphoric acid played a vital role in the enantioselectivity, and the transition state of the reaction was proposed.

Automated summary

An enantioselective addition reaction catalyzed by a chiral phosphoric acid has been developed for the synthesis of quaternary alpha-isoxazole-alpha-alkynyl amino acid derivatives. The reaction showed high yields and good to excellent enantioselectivities, and the hydrogen-bonding interaction between the amino-isoxazole and chiral phosphoric acid played a vital role in the selectivity.