Symmetric Anion Mediated Dynamic Kinetic Asymmetric Knoevenagel Reaction for N−C and N−N Atropisomers Synthesis
Hongyu Qu, Chenyang Huo, Jimeng Ge, Xiaoping Xue, Zhenhua Gu, Ruixian Deng
Abstract
A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N-C and N-N atropisomers. The resulting highly enantio-pure pyridine-2,6(1H,3H)-diones exhibit diverse structures and functional groups. The key to excellent regio- and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst. This connected the enolate anion and iminium cation by a chiral backbone. The mechanism investigation via control experiments, correlation analysis, and density functional theory calculations further revealed how the stereochemical information was transferred from the catalyst into the axially chiral pyridine-2,6(1H,3H)-diones. The synthetic applications also demonstrated the reaction's potential.