Stereoselective Syntheses of Masked β-Amino Acid Containing Phthalides

We herein report a protocol for the asymmetric aldol-initiated cascade addition of isoxazolidin-5-ones to ortho-cyanobenzaldehydes by using Takemoto's bifunctional organocatalyst. This approach allows for the synthesis of various novel beta(2,2)-amino acid-phthalide conjugates with good enantio- and diastereoselectivities in reasonable yields and the further ring-opening of these compounds to acyclic carboxylic acid derivatives was demonstrated too.

Automated summary

We describe a protocol for the asymmetric aldol-initiated cascade addition of isoxazolidin-5-ones to ortho-cyanobenzaldehydes using Takemoto's bifunctional organocatalyst. This method allows for the synthesis of novel beta(2,2)-amino acid-phthalide conjugates with good enantio- and diastereoselectivities in reasonable yields, and the subsequent ring-opening of these compounds to acyclic carboxylic acid derivatives was demonstrated.