A Green Chemistry Approach toward the Stereospecific Synthesis of Densely Functionalized Cyclopropanes via the Solid-State Photodenitrogenation of Crystalline 1-Pyrazolines
A Green Chemistry Approach toward the Stereospecific Synthesis of Densely Functionalized Cyclopropanes via the Solid-State Photodenitrogenation of Crystalline 1-Pyrazolines
复制标题
通过结晶 1-吡唑啉的固态光脱氮立体定向合成致密功能化环丙烷的绿色化学方法
DOI：
10.1021/acs.joc.1c01808
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Garcia-Garibay, Miguel A.
中科院分区：
文献类型：
--
作者：
Chang, Trevor Y.;Adrion, Daniel M.;Meyer, Alana Rose;Lopez, Steven A.;Garcia-Garibay, Miguel A.
环丙烷环在活性药物中具有突出的特征，这刺激了有效地将这种高度紧张的基序结合到此类分子中的合成方法的发展。因此，制备密集官能化的环丙烷，特别是嵌入复杂结构的核心内的环丙烷的优雅解决方案已经变得越来越受欢迎。在这里，我们报告的立体定向合成一组环丙烷与邻季立体中心通过无溶剂固态光脱氮结晶1-吡唑啉。在M062 X/6-31+G（d，p）水平上的密度泛函理论计算被用来确定合成1-吡唑啉的区域选择性的起源;有利的同相前沿分子轨道相互作用是观察到单个吡唑啉区域异构体的原因。研究还表明，N2的损失可能通过高度选择性的固态热反应发生。固态光反应的可扩展性是通过水性纳米晶悬浮液实现的，使得这种方法成为有效促进含环丙烷分子支架构建的“更绿色”替代方案。
The cyclopropane ring features prominently in active pharmaceuticals, and this has spurred the development of synthetic methodologies that effectively incorporate this highly strained motif into such molecules. As such, elegant solutions to prepare densely functionalized cyclopropanes, particularly ones embedded within the core of complex structures, have become increasingly sought-after. Here we report the stereospecific synthesis of a set of cyclopropanes with vicinal quaternary stereocenters via the solvent-free solid-state photodenitrogenation of crystalline 1-pyrazolines. Density functional theory calculations at the M062X/6-31+G(d,p) level of theory were used to determine the origin of regioselectivity for the synthesis of the 1-pyrazolines; favorable in-phase frontier molecular orbital interactions are responsible for the observation of a single pyrazoline regioisomer. It was also shown that the loss of N2may take place via a highly selective solid-state thermal reaction. Scalability of the solid-state photoreaction is enabled through aqueous nanocrystalline suspensions, making this method a “greener” alternative to effectively facilitate the construction of cyclopropane-containing molecular scaffolds.