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.
Keywords: 2-benzofuranones; NHC; asymmetric amination; ion-pair; non-covalent catalysis.
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