No Catalyst Required: New Thermally-Promoted Transformations of Iminyl Radicals for the Synthesis of Complex Molecules

在杨百翰大学化学系化学合成项目的支持下，杨百翰大学的Steven L. Castle教授正在开发合成有机分子的新反应方法。这些反应是由热能（即微波辐照或常规加热）触发的，不需要添加外部催化剂。与其他类似实体的更传统的策略相比，这种方法的优点包括它的简单性，缺乏昂贵或奢侈的试剂或催化剂，可以通过这种化学反应产生和产生的分子范围，以及引发和产物形成所需的相对较短的反应时间。因此，这些新方法为重要种类的化合物提供了有效的合成途径，包括一些有潜力成为药物的化合物。除了发展化学之外，Castle教授和他的学生们还计划通过制定课程计划来推进STEM（科学、技术、工程和数学）教育，帮助高中化学教师将有机化学纳入他们的课程。通过让学生比正常情况下更早地接触有机化学和药物化学，希望高中生能对化学有更深的了解，这有可能鼓励他们考虑在他们的教育和职业中追求STEM的道路。直接参与该项目的学生将接受实验技术、化学反应故障排除、沟通和批判性思维方面的培训，为他们在STEM领域的职业生涯提供宝贵的工具。在这个奖项下，Steven Castle教授和他的研究小组将在热条件下通过诱导相对弱的N-O键的均裂产生亚胺基自由基，这些键存在于现成的o -芳基肟醚中。这个过程提供了高能亚胺基自由基，这些亚胺基自由基能够经历包括分子内过程在内的各种化学转化。这些反应包括与垂链烯烃的环化反应和与距亚胺基氮原子一定距离的氢的氢原子提取反应。自由基也能在分子间形成新的C-C、C-N、C-O、C-S或C-X （X =卤素）键。除了研究亚胺基自由基的基本生成和反应性外，还将通过计划的聚合合成fortuneicylidin来证明该方法的实用性，其中亚胺基自由基环化是关键步骤。这种结构新颖的生物碱天然产物尚未在实验室中合成，所提出的路线有可能证明所提出的基于亚胺基自由基的串联环化化学的真正效用。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 the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Steven L. Castle of Brigham Young University is developing new reaction methodology for synthesizing organic molecules. These reactions are triggered by thermal energy (i.e., microwave irradiation or conventional heating) and do not require the addition of external catalysts. The advantages of this approach when compared to other, more conventional strategies to similar entities include its simplicity, the lack of expensive or extravagant reagents or catalysts, the scope of the molecules that can be subjected to and generated from this chemistry, and the relatively short reaction times that are required for initiation and product formation. As a result, these new methods provide efficient synthetic routes to important classes of compounds, including some with potential as pharmaceuticals. In addition to developing the chemistry, Professor Castle and his students plan to advance STEM (science, technology, engineering and mathematics) education by creating lesson plans that will help high school chemistry teachers to incorporate organic chemistry into their courses. By exposing students to organic and medicinal chemistry far sooner than they normally would be, it is hoped that high school students will develop a deeper appreciation for chemistry and this has the potential to encourage them to consider pursuing STEM pathways in their education and professionally. The students that are directly participating in this project are receiving training in experimental techniques, troubleshooting chemical reactoins, communication, and critical thinking that will provide them with valuable tools to pursue careers in STEM fields.Under this award, Professor Steven Castle and his research group will generate iminyl radicals under thermal conditions by inducing the homolytic cleavage of relatively weak N-O bonds that are present in readily available O-aryl oxime ethers. This process affords high energy iminyl radicals that are capable of undergoing a variety of chemical transformations including intramolecular processes. These include cyclization reactions with pendant alkenes and hydrogen atom abstraction reactions with hydrogens that are a prescribed distance from the iminyl nitrogen atom. The radicals are also capable of being trapped intermolecularly to forge new C-C, C-N, C-O, C-S, or C-X (X = halogen) bonds. In addition to studying the fundamental generation and reactivity of iminyl radicals, the utility of this methodology is to be demonstrated through the planned convergent synthesis of fortuneicyclidin, with iminyl radical cyclization being the key step. This architecturally novel alkaloid natural product has yet to be synthesized in the laboratory and the proposed route has the potential to demonstrate real utility of the proposed iminyl radical-based tandem cyclization chemistry.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.