Decarboxylative Asymmetric Chlorination Using an Asymmetric Catalyst

Shibatomi et al. have reported first asymmetric organocatalyzed decarboxylative chlorination of β-keto acids. In the presence of the chiral binaphthyl-based primary amine catalyst (1), a β-ketocarboxylic acid (2) successfully reacts with N-chlorosuccinimide (NCS) to afford an α-chloroketone (3) in high yield and high enantioselectivity. The resulting β-chloroketone (3) can readily be converted and diversified into stereoinverted substituted products by the treatment with nucleophiles such as azide and thiol species. While there have been many reports of decarboxylative halogenation to date, this is the first report of asymmetric synthesis.