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

作者：Tengbo Ding, Liang Long, Mei-Jie Yuan, Wei Xu, Sze‐Yung Wong, Hao Gao, Yongheng Wang, Ying‐Yeung Yeung, Xiaojian Jiang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c01224 · 被引用次数：5 · 研究领域：Vanadium and Halogenation Chemistry、Chemical Synthesis and Reactions、Oxidative Organic Chemistry Reactions

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.