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.

在化学合成计划的支持下，杨百翰大学的史蒂文·L·城堡（Steven L. Castle of Brigham Young University）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）触发的，不需要添加外部催化剂。与其他针对类似实体的其他更常规的策略相比，这种方法的优点包括其简单性，缺乏昂贵或奢华的试剂或催化剂，可以从该化学作用和产生的分子范围，以及起始和产物形成所需的相对短的反应时间。结果，这些新方法为重要的化合物提供了有效的合成途径，其中包括有潜力作为药物。除了开发化学外，Castle及其学生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，从而帮助高中化学教师将有机化学融入他们的课程中。通过将学生暴露于有机和药物化学的时间比平时要早得多，希望高中生能够对化学产生更深入的欣赏，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的培训，对化学反应，沟通和批判性思维进行故障排除，这将为他们提供有价值的工具来从事STEM领域。该过程提供了高能亚氨基自由基，这些自由基能够进行多种化学转化，包括分子内过程。这些包括与载体和氢原子抽象反应的环化反应与距离胺基氮原子有规定距离的氢反应。自由基也能够间隔捕获以伪造新的C-C，C-N，C-O，C-S或C-X（X =卤素）键。除了研究胺基自由基的基本产生和反应性外，该方法的实用性还可以通过计划的fortuneycilclidin的计划收敛合成来证明，胺基自由基环化是关键步骤。 这款建筑新颖的生物碱天然产品尚未在实验室中合成，拟议的路线有可能证明拟议的基于米米尼基激进的串联串联环化化学的真正实用性。该奖项反映了NSF的法定任务，并通过使用该基金会的知识优点和广泛的影响来评估NSF的法定任务。