Jump to main content
Jump to site search

Issue 5, 2014
Previous Article Next Article

Catalytic kinetic resolution of a dynamic racemate: highly stereoselective β-lactone formation by N-heterocyclic carbene catalysis

Author affiliations

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 constitutes an interesting class of DKRs in which the catalyst is responsible for the kinetic resolution to selectively and irreversibly capture an enantiomer of a substrate undergoing rapid racemization with the help of an exogenous base.

Graphical abstract: Catalytic kinetic resolution of a dynamic racemate: highly stereoselective β-lactone formation by N-heterocyclic carbene catalysis

Back to tab navigation

Supplementary files

Publication details

The article was received on 28 Jan 2014, accepted on 14 Feb 2014 and first published on 14 Feb 2014


Article type: Edge Article
DOI: 10.1039/C4SC00317A
Citation: Chem. Sci., 2014,5, 1974-1982
  •   Request permissions

    Catalytic kinetic resolution of a dynamic racemate: highly stereoselective β-lactone formation by N-heterocyclic carbene catalysis

    R. C. Johnston, D. T. Cohen, C. C. Eichman, K. A. Scheidt and P. Ha-Yeon Cheong, Chem. Sci., 2014, 5, 1974
    DOI: 10.1039/C4SC00317A

Search articles by author

Spotlight

Advertisements