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. 2021 Jan 1;86(1):995-1001.
doi: 10.1021/acs.joc.0c02486. Epub 2020 Dec 15.

Stereoselective α-Chlorination of β-Keto Esters in the Presence of Hybrid Amide-Based Cinchona Alkaloids as Catalysts

Maciej Majdecki  1 , Piotr Grodek  1 , Janusz Jurczak  1
Affiliations

Stereoselective α-Chlorination of β-Keto Esters in the Presence of Hybrid Amide-Based Cinchona Alkaloids as Catalysts

Maciej Majdecki et al. J Org Chem. .

Abstract

We report an enantioselective phase transfer α-chlorination of β-keto esters catalyzed by hybrid amide-based Cinchona derivatives. The chlorination process proceeds with proper quantitative yields (up to <99%) and high asymmetric induction (up to 97% ee). We show that the use of only 0.5 mol % hybrid catalyst based on a Cinchona core allows the chlorination reaction to be conducted in a highly enantioselective manner with various indanone and tetralone carboxylate esters.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Previously reported Cinchona PTC catalysts in asymmetric chlorination.
Scheme 1
Scheme 1. Synthesis of Selected Amide-Based Cinchona Alkaloids
Scheme 2
Scheme 2. Study of the Ester Group
For example, compound 14a was obtained using 13a (1.0 mmol), NCS (1.05 mmol), KF (2 mmol), and catalyst 5 (0.5 mol%) in toluene (5 mL) for 30 min at −50 °C.
Figure 2
Figure 2
Proposed transition state model for catalyst 5 and substrate 13a.
Scheme 3
Scheme 3. Study of β-Keto Derivative Scope
(a)Molar ratio: NCS (1.05 equiv), catalyst 5 (0.005 equiv), and KF (2 equiv). (b) Isolated yields. (c) The ee values were determined by HPLC analysis using a chiral column Chiralcel OD-H.
See this image and copyright information in PMC

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