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

无需催化剂：用于合成复杂分子的亚氨基自由基的新热促进转化

• 批准号: 2247154
• 负责人: Steven Castle
• 金额: $ 55.48万
• 依托单位: Brigham Young University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247154&HistoricalAwards=false
• 关键词: No; Catalyst; Required; New; Thermally

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.

在化学系化学合成项目的支持下，Steven L.杨百翰大学的卡斯尔正在开发合成有机分子的新反应方法。这些反应由热能触发（即，微波辐射或常规加热），并且不需要添加外部催化剂。当与其他更常规的策略相比时，这种方法的优点包括其简单性，缺乏昂贵或奢侈的试剂或催化剂，可以经受这种化学并由其产生的分子的范围，以及引发和产物形成所需的相对短的反应时间。因此，这些新方法为重要类别的化合物提供了有效的合成途径，包括一些具有药物潜力的化合物。除了发展化学，教授城堡和他的学生计划通过创建课程计划，将帮助高中化学教师将有机化学纳入他们的课程，以推进干（科学，技术，工程和数学）教育。通过让学生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教育和专业上追求STEM途径。直接参与该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，这将为他们提供宝贵的工具，以追求STEM领域的职业生涯。根据该奖项，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-存在于容易获得的O-芳基肟醚中的O键。该过程提供了能够经历包括分子内过程的各种化学转化的高能亚胺基自由基。这些包括与侧链烯烃的环化反应和与距亚胺基氮原子规定距离的氢的氢原子夺取反应。自由基还能够被捕获在分子间以形成新的C-C、C-N、C-O、C-S或C-X（X =卤素）键。除了研究亚胺基自由基的基本生成和反应性之外，该方法的实用性将通过计划收敛合成fortuneicyclidin来证明，其中亚胺基环化是关键步骤。 这种结构新颖的生物碱天然产物还没有在实验室合成，拟议的路线有可能证明拟议的亚胺基基串联环化化学的真实的效用。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。