Enantioselectivity in Transition Metal Catalyzed Propargylic Substitution Reactions: A Theoretical Perspective

In recent years, asymmetric catalytic propargylic substitution reactions have undergone remarkable development, enabling the construction of chiral carbon centers adjacent to intact carbon-carbon triple bonds. For the rational design and further advancement of new asymmetric transformations, a detailed understanding of the origins of enantioselectivity in previously reported reactions, obtained through quantum chemical calculations, is indispensable. In this context, recent density functional theory (DFT) calculations on transition-metal-catalyzed asymmetric propargylic substitution reactions have increasingly revealed that not only conventional steric effects and exchange repulsion but also weak attractive interactions, such as π-π and CH/π interactions, play critical roles in determining stereoselectivity. This review summarizes recent theoretical efforts to clarify the origins of enantioselectivity in transition-metal-catalyzed propargylic substitution reactions.