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

在化学系化学合成计划的支持下，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(即微波辐射或常规加热)引发的，不需要添加外部催化剂。与其他更传统的类似实体的方法相比，这种方法的优势包括它的简单性，不需要昂贵或昂贵的试剂或催化剂，这种化学可以产生的分子的范围，以及引发和产物形成所需的相对较短的反应时间。因此，这些新方法为重要类别的化合物提供了有效的合成路线，包括一些具有潜在药用价值的化合物。除了开发化学，Castle教授和他的学生还计划通过创建教案来推进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。通过让学生比平时更早地接触有机和药物化学，希望高中生对化学有更深的欣赏，这有可能鼓励他们考虑在教育和专业上走STEM道路。直接参与这个项目的学生正在接受实验技术、化学反应故障排除、沟通和批判性思维方面的培训，这些培训将为他们在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较弱的N-O键的均质裂解来产生亚胺基自由基，这些N-O键存在于现成的O-芳基肟醚中。这个过程提供了高能的亚胺基自由基，能够经历包括分子内过程在内的各种化学转化。这些反应包括与侧链烯烃的环化反应和与亚胺基氮原子相距规定距离的氢原子的抽提反应。自由基还能够被分子间捕获以形成新的C-C、C-N、C-O、C-S或C-X(X=卤素)键。除了研究亚胺自由基的基本生成和反应活性外，该方法的实用性还将通过计划中的收敛合成三叶草环素来展示，其中亚胺自由基的环化是关键步骤。这种结构新颖的生物碱天然产物尚未在实验室中合成，建议的路线有可能展示建议的基于亚胺基团的串联环化化学的真正效用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.