Polarizability Matters in Enantio-selection

Abstract

AbstractThe origin of enantio-selection in chiral induction events is usually thought to be consequences of steric, electronic, or conformational effects. Polarizability, as a fundamental electronic property, has been well recognized for controlling molecules’ stability and chemical reactivity in the classic hard and soft acids and bases (HSAB) theory as well as modern density functional theory (DFT) frameworks. However, the underlying connection between polarizability and enantio-selection has long been largely overlooked. Uncovered herein is a new type of electronic effect based on polarizability that was shown to be well capable of rationalizing an extensive range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in the ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates’ local polarizabilities and observed enantio-selections were also demonstrated in three widely known asymmetric catalytic systems. This broadly applicable polarizability-based scenario helps shed new light on the nature of chiral induction, and it appears to be more effective factor governing both of the sense and magnitude of enantio-selection. A balanced consideration on such new polarizability effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.