Understanding the axial chirality control of quinidine-derived ammonium cation-directed O-alkylation: a computational study

作者：Li, Han; Fan, Wu^*; Hong, Xin^*

来源：Organic and Biomolecular Chemistry, 2019, 17(7): 1916-1923.

DOI：10.1039/c8ob02173b

• DYNAMIC KINETIC RESOLUTION
• EFFECTIVE CORE POTENTIALS
• ENANTIOSELECTIVE SYNTHESIS
• MOLECULAR CALCULATIONS
• ATROPOSELECTIVE SYNTHESIS
• ASYMMETRIC-SYNTHESIS
• BIARYL ATROPISOMERS
• MICHAEL ADDITION
• ACID
• STEREOSELECTIVITY

As a privileged chiral scaffold, cinchona alkaloid and its derivatives have reached remarkable success in catalytic asymmetric organic synthesis. In addition to the wide applications of point chirality control, Smith and co-workers recently discovered a quinidine-derived ammonium cation-catalyzed O-alkylation of tetralones, providing an effective approach for the synthesis of axially chiral biaryls. Using density functional theory (DFT) calculations, we studied the reaction mechanism and origins of enantioselectivity of this novel transformation. A stepwise strategy is adopted to ensure efficient and thorough exploration of the massive conformational space of transition state. Our computations suggested that enolate oxygen forms two hydrogen bonds with the chiral ammonium catalyst, and the non-covalent interactions between the cationic benzylic fragment and the methoxy group of enolate plays a critical role in determining the enantioselectivity.

• 出版日期2019-2-21
• 单位中国烟草总公司郑州烟草研究院; 浙江大学