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. 2021 Aug 6;23(15):6143-6147.
doi: 10.1021/acs.orglett.1c02256. Epub 2021 Jul 28.

Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions

Lotte Stockhammer  1 , David Weinzierl  1 , Thomas Bögl  2 , Mario Waser  1
Affiliations

Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions

Lotte Stockhammer et al. Org Lett. .

Abstract

The asymmetric α-chlorination of activated aryl acetic acid esters can be carried out with high levels of enantioselectivities utilizing commercially available isothiourea catalysts under base-free conditions. The reaction, which proceeds via the in situ formation of chiral C1 ammonium enolates, is best carried out under cryogenic conditions combined with a direct trapping of the activated α-chlorinated ester derivative to prevent epimerization, thus allowing for enantioselectivities of up to e.r. 99:1.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Use of in Situ Generated C1 Ammonium Enolates, Pioneering α-Halogenation Approaches, and the Herein Investigated α-Chlorination
Scheme 2
Scheme 2. Application Scope
All reactions were carried out using 0.1 mmol 1 and showed >95% conversion unless otherwise stated. Repeated on a 1 mmol scale, providing 3dOMe in 71% yield and with e.r. 99:1.
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