Substrate‐Controlled Enantiodivergence in Ni‐Catalyzed Access to Phosphorylated Oxindoles With Quaternary Stereocenters
Abstract
A Ni-catalyzed enantioselective intermolecular Heck-phosphorylation of N-aryl acrylamides with phosphine oxides is developed. This redox-neutral cascade simultaneously forges C─C and C─P bonds, providing direct access to valuable 3,3-disubstituted phosphorylated oxindoles with quaternary stereocenters in good yields and high ee values. Notably, the reaction exhibits a unique substrate-controlled enantiodivergence: simply changing the leaving group (I vs. OTf) on the alkene partner switches the configuration of the product while employing the same enantiomer of the chiral catalyst. The synthetic utility is further demonstrated through product derivatizations. Density functional theory (DFT) calculations reveal that the leaving group dictates the order of migratory insertion versus anion exchange and, crucially, inverts the chiral environment at the enantioselectivity-determining oxidative addition transition state, providing a clear rationale for the observed stereodivergence.
Fields of Study & Subjects
Catalytic Cross-Coupling Reactions
Asymmetric Hydrogenation and Catalysis
Catalytic C–H Functionalization Methods
Publication details
- Journal / source
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Volume
- 65
- Issue
- 32
- Pages
- e4623924–e4623924
- Publication date
- 7 June 2026
- Language
- EN