A Simple Lewis Base Catalyst for the Asymmetric Steglich Rearrangement

Significance

The authors report an asymmetric Steglich rearrangement with Lewis base catalysts 1. Imidazole-based bicyclic catalysts 1 could be easily prepared via optical resolution or preparative HPLC separation and protection (three steps). The catalysts 1 are designed to avoid significant steric interaction at the nucleophilic nitrogen along with an efficient generation of a chiral environment for the following acyl transfer reaction. By optimization studies, C-acylated azlactones could be obtained with high enantiomeric ratio (up to 99:1 er) and moderate chemical yield. Catalyst 1 could be recovered by acid/base work-up and chromatographic purification, and recycled without any loss of enantioselectivity and reactivity.