Catalytic Kinetic Resolution of a Dynamic Racemate: Highly Stereoselective β-Lactone Formation by N-Heterocyclic Carbene Catalysis.

ABSTRACT: 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 constitu

SUBMITTER: Johnston RC 

PROVIDER: S-EPMC4096939 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature