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，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。这些反应由热能（即微波辐射或常规加热）引发，不需要添加外部催化剂。与其他更传统的类似实体策略相比，这种方法的优点包括其简单性、无需昂贵或奢侈的试剂或催化剂、可以经历这种化学反应并由这种化学反应产生的分子范围，以及相对较短的时间。引发和产物形成所需的反应时间。因此，这些新方法为重要的化合物类别提供了有效的合成路线，包括一些具有药物潜力的化合物。除了发展化学之外，Castle 教授和他的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，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化学和药物化学，我们希望高中生能够对化学有更深的认识，这有可能鼓励他们考虑在教育和职业生涯中追求 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，这将为他们在 STEM 领域追求职业生涯提供宝贵的工具。在该奖项下，Steven Castle 教授和他的研究小组将在热条件下通过诱导存在于容易获得的O-芳基肟醚中的相对较弱的N-O键的均裂而产生亚氨基自由基。该过程提供高能亚氨基自由基，能够进行各种化学转化，包括分子内过程。这些包括与侧链烯烃的环化反应以及与距亚氨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形成新的 C-C、C-N、C-O、C-S 或 C-X（X = 卤素）键。除了研究亚氨基自由基的基本生成和反应性外，该方法的实用性还将通过计划的财富环素的聚合合成来证明，其中亚氨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氨基自由基的串联环化化学的真正实用性。该奖项反映了 NSF 的法定使命，并被认为值得通过以下方式获得支持：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。