Enantioselective synthesis of chiral acyclic nitriles containing α-all-carbon quaternary stereocenters via synergistic palladium and phase-transfer catalysis

• Main Authors: Guo, Cheng, Dong, Yufei, Wang, Yiyang, Du, Xuan, Ma, Runxia, Tan, Choon-Hong, Luan, Xinjun, Ren, Jingyun
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2025
• Subjects: Chemistry; Phase-transfer catalysis; Decarboxylative asymmetric allylic alkylation
• Online Access: https://hdl.handle.net/10356/182256
• Institution: Nanyang Technological University

Herein, we present a practical strategy for the asymmetric synthesis of chiral acyclic nitriles featuring α-all-carbon quaternary stereocenters, utilizing synergistic palladium and phase-transfer catalysis from allyl 2-cyanoacetates under mild conditions. This approach offers an efficient and reliable method for the in situ generation of tertiary α-cyano carbanions through intramolecular palladium-catalyzed decarboxylative allylic alkylation. Additionally, it enables highly enantioselective control of simple nitriles via ion-pairing interactions with chiral phase-transfer catalysts. The synthetic utility of this method is further demonstrated by its scalability to gram-scale synthesis and its subsequent transformation into a variety of chiral functionalized compounds containing acyclic all-carbon quaternary stereocenters.