Design, Synthesis, and Application of a Family of Chiral Non‐C2‐Symmetric NHCs with a Fused Sidechain

• Published in: Angewandte Chemie International Edition Vol. 64; no. 27; pp. e202508572 - n/a
• Main Authors: Cai, Zhen‐Xi, Zhang, Qi, Wei, Tian‐Yu, Tian, Hu, Jiang, Jia‐Wei, Wei, Zhang‐Yi, Yin, Liang
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.07.2025
• Edition: International ed. in English
• Subjects: Amides; Amination; Asymmetric catalysis; Asymmetry; Bromination; Catalysis; Chemical synthesis; Chiral NHC; Conjugate silylation; Copper; Copper catalyst; Cross coupling; Enantiomers; Ligands; Organic compounds; Oxidation; Palladium; Phosphoric acid; Quinolines; SN2′ silylation; Steric hindrance; Transition metals
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202508572

Although a considerable number of chiral nitrogen heterocyclic carbenes (NHCs) have been developed yet it is highly necessary to develop new NHCs bearing multiple sites for facile modifications of both electronic nature and steric hindrance. Herein, we uncover a new family of chiral non‐C2‐Symmetric NHCs with a fused sidechain, whose precursors are synthesized by a simple five‐step route. The synthesis includes Pd‐catalyzed cross‐coupling or nucleophilic addition/oxidation, chiral phosphoric acid‐catalyzed asymmetric reduction of 2‐aryl‐quinolines, bromination at C8, Buchwald–Hartwig amination, and cyclization with methyl orthoformate. Among nine prepared NHCs, YC‐NHC8 is the optimal ligand for Cu(I)‐catalyzed asymmetric SN2′ silylation, YC‐NHC3 works as the best ligand for Cu(I)‐catalyzed enantioselective conjugate silylation of simple α,β‐unsaturated amides, and YC‐NHC9 serves as the most suitable ligand for copper(I)‐catalyzed asymmetric silylation of azadienes. Remarkably, these three reactions are successfully run under a catalyst loading of 0.1 mol%, indicating that YC‐NHCs may have the potential to be broadly used in efficient asymmetric transition metal catalysis. A new family of chiral non‐C2‐Symmetric NHCs with a fused sidechain was synthesized and used as efficient ligands in three copper(I)‐catalyzed enantioselective reactions at the catalyst loading of 1 mol%, including SN2′ silylation, conjugate silylation of α,β‐unsaturated amides, and silylation of azadienes.