Flow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy-Drug Sciences, University of Bari "A. Moro", Via E. Orabona 4, 70125, Bari, Italy.
Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6395-6399. doi: 10.1002/anie.202014881. Epub 2021 Feb 15.
Strained compounds are privileged moieties in modern synthesis. In this context, 1-azabicyclo[1.1.0]butanes are appealing structural motifs that can be employed as click reagents or precursors to azetidines. We herein report the first telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1-azabicyclo[1.1.0]butanes. The flow method allows for exquisite control of the reaction parameters, and the process operates at higher temperatures and safer conditions with respect to batch mode. The efficiency of this intramolecular cyclization/C3-lithiation/electrophilic quenching flow sequence is documented with more than 20 examples.
张力环化合物是现代合成中的优势基团。在这种情况下，1-氮杂双环[1.1.0]丁烷是一种吸引人的结构单元，可以作为点击试剂或氮杂环丁烷的前体。本文首次报道了 1-氮杂双环[1.1.0]丁烷的生成、锂化和亲电捕获的缩合连续流方案。该方法可以精确控制反应参数，并且相对于分批操作，该过程在更高的温度和更安全的条件下进行。该分子内环化/C3-锂化/亲电淬灭流序列的效率通过 20 多个实例得到了证明。
