Stereodivergent Synthesis of All Stereoisomers of 2,3-Disubstituted δ‑Lactam Derivatives via Organocatalytic Cascade Reactions and Base-Induced Epimerization

Dong-Sheng Ji,† Rui Zhang,† Xu-Yan Han, Xiu-Qin Hu,* and Peng-Fei Xu*

https://doi.org/10.1021/acs.orglett.3c03861

Abstract

A protocol was developed to achieve stereodivergent synthesis of stereoisomers of δ-lactam bearing vicinal chiral centers. Organocatalytic cascade reactions were employed to produce the target products as the kinetic products, which exhibited remarkable enantioselectivities. In the presence of DBU, the kinetic product underwent epimerization to form a thermodynamically more stable diastereomer without loss in enantioselectivity. By simply switching the chiral organocatalyst and its enantiomer, we can efficiently obtain four stereoisomers with high enantioselectivities.