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Enantioselective Dearomatization of Pyridinium Salts by Copper‐Catalyzed C4‐Selective Addition of Silicon Nucleophiles

Yao Xiao, Zhiyuan Zhao, Sebastian Kemper, Elisabeth Irran, Martin Oestreich

2024Angewandte Chemie International Edition11 citationsDOIOpen Access PDF

Abstract

Abstract A copper‐catalyzed C4‐selective addition of silicon nucleophiles released from an Si−B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH 3 CN) 4 PF 6 as the precatalyst and ( R , R )‐Ph‐BPE (1,2‐bis[(2 R ,5 R )‐2,5‐diphenylphospholan‐1‐yl]ethane) as the chiral ligand. A carbonyl group at C3 is required for this, likely acting a weak donor group to preorganize and direct the nucleophilic attack towards C4. The resulting 4‐silylated 1,4‐dihydropyridines can be further converted into functionalized piperidine derivatives.

Topics & Concepts

PyridiniumNucleophileChemistryEnantioselective synthesisPiperidineReagentCatalysisCopperOrganic chemistryLigand (biochemistry)Combinatorial chemistrySiliconChiral ligandMedicinal chemistryReceptorBiochemistryCatalytic C–H Functionalization MethodsCyclopropane Reaction MechanismsAsymmetric Synthesis and Catalysis
Enantioselective Dearomatization of Pyridinium Salts by Copper‐Catalyzed C4‐Selective Addition of Silicon Nucleophiles | Litcius