Issue 7, 2019

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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
04 sep. 2018
Accepted
27 sep. 2018
First published
03 oct. 2018

Org. Biomol. Chem., 2019,17, 1916-1923

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

H. Li, W. Fan and X. Hong, Org. Biomol. Chem., 2019, 17, 1916 DOI: 10.1039/C8OB02173B

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