Physical Sciences and Mathematics Commons^™

Catalytic Kinetic Resolution Of A Dynamic Racemate: Highly Stereoselective Β-Lactone Formation By N-Heterocyclic Carbene Catalysis, Ryne C. Johnston, Daniel T. Cohen, Chad C. Eichman, Karl A. Scheidt, Paul Ha-Yeon Cheong

Chemistry: Faculty Publications and Other Works

This study describes the combined experimental and computational elucidation of the mechanism and origins of stereoselectivities in the NHC-catalyzed dynamic kinetic resolution (DKR) of α-substituted-β-ketoesters. Density functional theory computations reveal that the NHC-catalyzed DKR proceeds by two mechanisms, depending on the stereochemistry around the forming bond: 1) a concerted, asynchronous formal (2+2) aldol-lactonization process, or 2) a stepwise spiro-lactonization mechanism where the alkoxide is trapped by the NHC-catalyst. These mechanisms contrast significantly from mechanisms found and postulated in other related transformations. Conjugative stabilization of the electrophile and non-classical hydrogen bonds are key in controlling the stereoselectivity. This reaction constitutes an …