Asymmetric Synthesis of Tertiary α -Hydroxyketones by Enantioselective Decarboxylative Chlorination and Subsequent Nucleophilic Substitution

Abstract

Chiral tertiary α-hydroxyketones were synthesized with high enantiopurity by asymmetric decarboxylative chlorination and subsequent nucleophilic substitution. We recently reported the asymmetric decarboxylative chlorination of β-ketocarboxylic acids in the presence of a chiral primary amine catalyst to obtain α-chloroketones with high enantiopurity. Here, we found that nucleophilic substitution of the resulting α-chloroketones with tetrabutylammonium hydroxide yielded the corresponding α-hydroxyketones without loss of enantiopurity. The reaction proceeded smoothly even at a tertiary carbon. The proposed method would be useful for the preparation of chiral tertiary alcohols.

Keywords

• chlorination
• S_N2 reaction
• asymmetric synthesis
• organocatalyst
• tertiary alcohols
• α-hydroxyketones