Document Type

Article

Publication Date

5-2014

Publication Title

Chemical Science

Volume

5

Issue

5

Publisher Name

Royal Society of Chemistry

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.

Comments

Author Posting. © The Royal Society of Chemistry, 2014. This article is posted here by permission of the Royal Society of Chemistry for personal use, not for redistribution. The article was published in Chemical Science, Volume 5, Issue 5, May 2014. http://dx.doi.org/10.1039/C4SC00317A

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