Enantioselective Amination of 3‐Substituted‐2‐benzofuranones via Non‐covalent N‐Heterocyclic Carbene Catalysis

• Published in: Chemistry : a European journal 2024-01, Vol.30 (5), p.e202303115-n/a
• Main Authors: Mondal, Bhaskar Deb, Gorai, Sadhan, Nath, Rounak, Paul, Ankan, Guin, Joyram
• Format: Article
• Language: English
• Subjects: 2-benzofuranones; Amination; asymmetric amination; Carbenes; Catalysis; Chemistry; Covalence; Enantiomers; ion-pair; NHC; non-covalent catalysis; Substitutes; Substrates
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202303115

Herein, an efficient method for asymmetric α‐amination of 2‐benzofuranones with N‐heterocyclic carbene (NHC) catalysis is reported. The process is based on non‐covalent interaction of NHC with substrate, facilitating the formation of a chiral ion‐pair that encompasses enolate and azolium salt. The activated enolate adds to an electrophilic amine source with sufficient facial control to furnish an enantioenriched product having an amine substituted quaternary stereocenter. The process displays a broad substrate scope. A preparative scale synthesis has been achieved. Preliminary mechanistic investigations based on experimental and DFT studies suggest a reaction pathway that involves non‐covalent substrate/NHC interactions and essentially implicate the role of π‐π interaction in diastereomeric transition states for stereo‐chemical discrimination. Herein, we present an efficient enantioselective amination of 3‐substituted‐2‐benzofuranones utilizing non‐covalent N‐heterocyclic carbene (NHC) catalysis. The process is applicable to various functionalized substrates and it is found to be scalable. Mechanistic investigations based on control experimental and DFT studies suggest that the reaction operates via non‐covalent substrate/NHC interactions.