Reaching New Horizons in Iminyl Radical Chemistry via Microwave Irradiation

美国国家科学基金会化学部的化学合成项目用这个奖项来支持杨百翰大学的Steven L. Castle教授的研究。卡斯尔教授正在开发一种新的方法来合成有机分子，这种方法是通过微波能量来促进的，而不是通过通常有毒、危险或昂贵的催化剂或试剂。与传统的有机合成技术相比，这些方法提供了更安全、更可持续、更有效的途径来合成具有潜在药物应用价值的化合物。一项关键的创新是使用微波触发级联过程，通过使一系列化学转化以受控的方式发生，将简单的前体转化为复杂而有用的化合物。Castle教授和他的学生正在通过制定课程计划来影响STEM教育，这些计划将帮助高中化学教师将有机化学纳入他们的课程。这些计划旨在通过让高中生接触令人兴奋的有机化学世界，并告诉他们化学对人类健康和生活质量的积极影响，激励他们追求STEM职业。Castle教授和他的同事使用o-芳基肟醚作为亚基自由基的前体。在微波照射下，这些物种经历O-N键的直接均裂。由此产生的亚胺基自由基然后通过环化或氢原子抽离（即碳氢活化）进行转化。在这两种情况下，自由基中间体都形成，随后被一种试剂捕获，形成新的C-C、C-N、C-O、C-S或C-X键。通过在没有金属催化剂或氧化还原循环的非还原条件下产生亚胺基自由基，这些反应允许广泛的功能化自由基陷阱被使用。此外，环化是立体选择性的，可以纳入级联过程。这些基于微波的方法的效用正在通过有效地构建生物碱家族的一个成员而得到证明。参与该项目的学生正在接受实验技术、故障排除、沟通和批判性思维方面的培训，这些培训将使他们能够从事化学或其他STEM领域的职业。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Steven L. Castle of Brigham Young University. Professor Castle is developing new methods for synthesizing organic molecules that are facilitated by microwave energy rather than by catalysts or reagents that are often toxic, hazardous, or expensive. In comparison to traditional organic synthesis techniques, these methods are providing safer, more sustainable, and more efficient routes to compounds that have potential application as pharmaceuticals. A key innovation is the use of microwaves to trigger cascade processes that convert simple precursors into complex and useful compounds by enabling a sequence of chemical transformations to occur in a controlled fashion. Professor Castle and his students are impacting STEM education by creating lesson plans that will assist high school chemistry teachers with incorporating organic chemistry into their courses. These plans are designed to inspire high school students to pursue STEM careers by exposing them to the exciting world of organic chemistry and teaching them about the positive impact that chemistry has on human health and quality of life.Professor Castle and his co-workers employ O-aryl oxime ethers as precursors of iminyl radicals. Upon irradiation with microwaves, these species undergo direct homolysis of the O-N bond. The resulting iminyl radicals are then transformed by either cyclization or hydrogen atom abstraction (i.e., C-H activation). In both cases, a radical intermediate is formed and subsequently trapped by a reagent that forges a new C-C, C-N, C-O, C-S, or C-X bond. By generating iminyl radicals under nonreducing conditions in the absence of metal catalysts or redox cycles, these reactions permit a wide range of functionalized radical traps to be used. Additionally, the cyclizations are stereoselective and can be incorporated into cascade processes. The utility of these microwave-based methods is being demonstrated through the efficient construction of a member of the securinega family of alkaloids. The student participants in this project are receiving training in experimental techniques, troubleshooting, communication, and critical thinking that will enable them to pursue careers in chemistry or other STEM fields.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.