Continuous-Flow Synthesis of Cyclobutenes Using LED Technology
Continuous-Flow Synthesis of Cyclobutenes Using LED Technology
复制标题
DOI：
10.1055/a-2086-0630
复制
发表时间：
2023-06-06
期刊：
影响因子：
2
通讯作者：
Baumann，Marcus
中科院分区：
文献类型：
--
作者：
Smyth，Megan;Moody，Thomas S. S.;Baumann，Marcus
环丁烯是具有相当大的合成兴趣的高度紧张的环系统，其可以通过烯烃和炔烃之间的环加成反应获得。然而，它们的传统制备依赖于光化学[2+2]环加成，该环加成利用低效中压汞灯发出的低波长UV辐射。本文报道了一种现代方法的发展，该方法使用大功率LED装置，结合连续流动反应器在UV-A和可见光的边界处发射。由此产生的流程使得一系列的环丁烯从马来酰亚胺和各种商业炔。这提供了一种更节能的方法，该方法易于扩展以获得高化学产率和短停留时间的多克量的环丁烯。这些产品的价值体现在基于流动的氢化反应，产生高度取代的环丁烷，这代表了现代药物化学计划中寻求的结构单元。
Cyclobutenes are highly strained ring systems of considerable synthetic interest that can be accessed via cycloaddition reactions between alkenes and alkynes. However, their traditional preparation relies on photochemical [2+2] cycloadditions that exploit low-wavelength UV radiation emitted from inefficient medium-pressure Hg lamps. This paper reports on the development of a modern approach using a high-power LED set-up emitting at the boundary of UV-A and visible light in conjunction with a continuous-flow reactor. The resulting flow process renders a series of cyclobutenes from maleimides and various commercial alkynes. This provides a more energy-efficient approach that is readily scalable to access multigram quantities of cyclobutenes in high chemical yields and short residence times. The value of these products is exemplified by flow-based hydrogenations yielding highly substituted cyclobutanes which represent sought after building blocks in modern medicinal chemistry programs.