1,3-Dipolar Cycloaddition of α-Amino Acid Schiff Base with Preserved Chirality via Reflexive Chirality Transfer (RCT) Process

Although optically pure α-amino acids are abundant, their chirality is easily lost, especially in the reaction via the formation of a carbanion or an enolate at the α-carbon. Therefore, precious chiral catalysis has been required to obtain optically active products even from optically pure α-amino acids as substrates. However, here we report a catalytic asymmetric 1,3-dipolar cycloaddition that preserves the α-carbon chirality of α-amino acid Schiff bases. In this process, readily available optically active α-amino acid Schiff bases are directly converted into optically active α-tetrasubstituted pyrrolidine derivatives without any external chiral additives, despite the loss of chirality at the α-carbon by the formation of planar 1,3-dipole intermediates. Mechanistic studies revealed that the α-carbon chirality of the α-amino acid Schiff base is transiently transferred to metal-centered chirality in 1,3-dipoles and is then restored as carbon-centered chirality in the products. This conceptually novel "Reflexive Chirality Transfer (RCT)" strategy offers a simple and cost-effective approach to optically active products from optically active resources and overcomes the current limitations of chiral pool synthesis.