Asymmetric α-Chlorination of β-Keto Esters Using Hypervalent Iodine-Based Cl-Transfer Reagents in Combination with Cinchona Alkaloid Catalysts

We herein report an unprecedented strategy for the asymmetric alpha-chlorination of beta-keto esters with hypervalent iodine-based Cl-transfer reagents using simple Cinchona alkaloid catalysts. Our investigations support an alpha-chlorination mechanism where the Cinchona species serves as a nucleophilic catalyst by reacting with the chlorinating agent to generate a chiral electrophilic Cl-transfer reagent in situ. Using at least 20 mol-% of the alkaloid catalyst allows for good yields and enantioselectivities for a variety of different beta-keto esters under operationally simple conditions.

Automated summary

This study introduces an unprecedented strategy for the asymmetric alpha-chlorination of beta-keto esters using simple Cinchona alkaloid catalysts and hypervalent iodine-based Cl-transfer reagents. The Cinchona species was found to act as a nucleophilic catalyst, generating a chiral electrophilic Cl-transfer reagent in situ, leading to good yields and enantioselectivities under operationally simple conditions.