Stereodivergent synthesis of chiral succinimides via Rh-catalyzed asymmetric transfer hydrogenation

Chiral succinimide moieties are ubiquitous in biologically active natural products and pharmaceuticals. Until today, despite the great interest, little success has been made for stereodivergent synthesis of chiral succinimides. Here, we report a general and efficient method for accessing 3,4-disubstituted succinimides through a dynamic kinetic resolution strategy based on asymmetric transfer hydrogenation. The Rh catalyst system exhibit high activities, enantioselectivities, and diastereoselectivities (up to 2000 TON, up to >99% ee, and up to >99:1 dr). Products with syn- and anti-configuration are obtained separately by control of the reaction conditions. For the N-unprotected substrates, both the enol and the imide group can be reduced by control of reaction time and catalyst loading. In addition, the detailed reaction pathway and origin of stereoselectivity are elucidated by control experiments and theoretical calculations. This study offers a straightforward and stereodivergent approach to the valuable enantioenriched succinimides (all 4 stereoisomers) from cheap chemical feedstocks in a single reaction step.

Fangyuan Wang, Zongpeng Zhang, Yu Chen, Virginie Ratovelomanana-Vidal, Peiyuan Yu, Gen-Qiang Chen, Xumu Zhang