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Updated: Oct 26, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Direct Enantioselective α-Alkoxylation of β-Keto Esters Enabled by Umpolung Strategy
Guo-Jia Kang1, Zhu-Lian Wu1, Lei Chen2
1School of Chemistry and Chemical Engineering, Southwest University, Chongqing400715, China.
Abstract:
Chiral ethers adjacent to a carbonyl group represent a valuable class of motifs; however, their catalytic asymmetric synthesis from readily available carbonyl compounds remains underexplored. Here, we present a catalytic asymmetric umpolung C-O bond-forming reaction of β-keto esters with alkyl hydroperoxides. This protocol employs in situ activation of alkyl hydroperoxides with trichloroacetonitrile, enabling the enantioselective alkoxy transfer to β-keto esters under catalysis by a chiral bifunctional organocatalyst, thereby allowing access to a broad range of highly functionalized, enantioenriched ethers bearing quaternary stereocenters.
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Factors Affecting α-Alkylation of Ketones: Choice of Base
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence, side reactions...

