New chiral N-heterocyclic olefin bifunctional organocatalysis in α-functionalization of β-ketoesters

N-heterocyclic olefins (NHOs) possess an electron-rich and highly polarized C=C double bond due to the donating property of nitrogen atoms. This feature imparts exocyclic carbon atom of NHOs with strong basicity and high nucleophilicity. Although NHOs have been emerging as a new type of organocatalyst and ligand for metal complexes in organic synthesis, chiral NHO-mediated highly enantioselective organic transformations were still elusive. Herein, we developed a new type of chiral aminederived C-2-symmetric NHOs and employed them as efficient chiral bifunctional organocatalysts for asymmetric alpha-functionalization of beta-ketoesters. With as low as 0.1 mol% catalyst loading, the desired amination and trifluoromethylthiolation products were afforded in good yields with high enantioselectivities (up to 99% yield and 99% ee). Experimental studies and theoretical calculation disclosed that hydrogen-bonding interaction upon protonation and other weak interaction between substrate and catalyst were crucial for the enantiocontrol.

Automated summary

N-heterocyclic olefins (NHOs) with electron-rich and highly polarized C=C double bond possess strong basicity and high nucleophilicity due to the donating property of nitrogen atoms. In this study, a new type of chiral aminederived C-2-symmetric NHOs was developed and used as efficient chiral bifunctional organocatalysts for asymmetric alpha-functionalization of beta-ketoesters. With as low as 0.1 mol% catalyst loading, the desired amination and trifluoromethylthiolation products were obtained in good yields with high enantioselectivities (up to 99% yield and 99% ee). Experimental studies and theoretical calculation revealed the crucial role of hydrogen-bonding interaction upon protonation and other weak interactions between substrate and catalyst in enantiocontrol.