Accelerated and Concerted Aza‐Michael Addition and SuFEx Reaction in Microdroplets in Unitary and High‐Throughput Formats
Angewandte Chemie(2022)
摘要
The sulfur fluoride exchange (SuFEx) reaction is significant in drug discovery, materials science, and chemical biology. Conventionally, it involves installation of SO2 F followed by fluoride exchange by a catalyst. We report catalyst-free Aza-Michael addition to install SO2 F and then SuFEx reaction with amines, both occurring in concert, in microdroplets under ambient conditions. The microdroplet reaction is accelerated by a factor of ∼104 relative to the corresponding bulk reaction. We suggest that the superacidic microdroplet surface assists SuFEx reaction by protonating fluorine to create a good leaving group. The reaction scope was established by performing individual reactions in microdroplets of 18 amines in four solvents and confirmed using high-throughput desorption electrospray ionization experiments. The study demonstrates the value of microdroplet-assisted accelerated reactions in combination with high-throughput experimentation for characterization of reaction scope.
更多查看译文
关键词
Aza-Michael Addition,Click Chemistry,High-Throughput Experimentation,Microdroplet Acceleration,SuFEx Reaction
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要