Silver-catalyzed asymmetric [3+2] cycloaddition via dynamic kinetic resolution: access to chiral oxazolines bearing C–N axial chirality

Abstract

A silver-catalyzed asymmetric [3+2] cycloaddition of N-aryl indole aldehydes/ketones with isocyanoacetates is reported. Facilitated by a cinchona alkaloid-derived ligand, this protocol enables the simultaneous construction of C–N axial chirality and two stereocenters in oxazolines under mild conditions. The reaction affords products in excellent yields (up to 99%) with high diastereo- and enantioselectivities (up to >20:1 dr, 99% ee). Furthermore, the resulting scaffolds can be readily transformed into axially chiral unnatural amino acids and peptide derivatives.