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

• Main Authors: Mei Kee Kam, Akira Sugiyama, Ryouta Kawanishi, Kazutaka Shibatomi
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Molecules
• Subjects: chlorination; S_N2 reaction; asymmetric synthesis; organocatalyst; tertiary alcohols; α-hydroxyketones
• Online Access: https://www.mdpi.com/1420-3049/25/17/3902
• ISSN: 1420-3049

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.