Catalytic Enantioselective Chlorofunctionalizations of N-Substituted Amides Using In Situ Generated HOCl as Hydrogen Bond Source

Asymmetric organocatalytic halocyclization represents a powerful method for the synthesis of valuable chiral haloheterocycles. However, its heavy dependence on substrates that contain hydrogen bond donors for enantiocontrol limits its broader application. Here we report a catalytic asymmetric chlorofunctionalization of olefinic amides that do not bear hydrogen bond donors, allowing for the efficient production of chlorooxazolidin-2-ones and chloroamino esters featuring quaternary stereocenters, achieved with high yields and excellent enantioselectivity. This catalytic protocol facilitates the synthesis of N-aryloxazolidin-2-ones and establishes a useful framework for synthesizing antibiotic analogues. Mechanistic studies indicate that trace amounts of water interact with the chlorinating agent to produce HOCl in situ, which acts as both a proton donor and a hypochlorite source, thereby promoting the asymmetric cyclization process. This strategy significantly broadens the potential of halocyclization for the development of a diverse array of functional molecules.