Lewis Base Directed Intermolecular Hydrogen Atom Transfer

在化学系化学合成计划的支持下，约翰霍普金斯大学的托马斯·莱特卡教授正在研究有选择地修饰复杂分子中的一个碳氢键的新方法。这些类型的反应对于系统地改变生物活性分子以研究其反应性非常重要，而不必从头开始构建每个单独的分子。莱特卡教授和他的研究团队正在确定复杂分子中的基因座如何与碳氢键激活剂相互作用，并利用这些信息来预测和提高选择单个碳氢键进行激活的能力。这些研究中的碳氢键正在转化为碳-氟、碳-溴、碳-氧和碳-氮键，这些都是有机合成中有价值的C-H活化转化。Lectka教授还与JHU女性科学与工程(WISE)计划和JHU-NSF巴尔的摩小学STEM成就计划(SABES)合作，为当地高中生提供研究经验。在复杂分子环境中的现场选择性C-H官能化是当前的重大挑战，其动机是能够研究和修饰天然产品和药物靶标，而不必从基本的构建块单独制备每个类似物。莱特卡教授和他的研究小组正在研究一种解决这个问题的新方法，方法是开发氢原子转移试剂，这种试剂可以专门与底物配位，并选择性地激活单个碳-氢键，以形成C-X键。同时，该团队还在探索酮和烯酮以外的官能团类型，这些官能团可以影响氢原子转移试剂的选择性，并确定底物配位对金属添加剂的影响。这些活动为研究生的专业发展和本科生的研究经验提供了一个强大的培训平台。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 support from the Chemical Synthesis Program in the Division of Chemistry, Professor Thomas Lectka of Johns Hopkins University is studying new ways to selectively modify one carbon-hydrogen bond in a complex molecule that features many carbon-hydrogen bonds. These types of reactions are important for systematically altering biologically active molecules to study their reactivity without having to build each individual molecule from scratch. Professor Lectka and his research team are determining how loci in a complex molecule interact with a carbon-hydrogen bond-activating agent and using this information to predict and improve the ability to choose a single carbon-hydrogen bond for activation. The carbon-hydrogen bonds in these studies are being converted to carbon-fluorine, carbon-bromine, carbon-oxygen, and carbon-nitrogen bonds, valuable C-H activation transformations in organic synthesis. Professor Lectka is also partnering with the JHU Women in Science and Engineering (WISE) program and the JHU-NSF STEM Achievement in Baltimore Elementary Schools (SABES) program to provide research experiences for local high school students.Site-selective C-H functionalization in complex molecular settings is a current grand challenge motivated by the desire to be able to study and modify natural products and pharmaceutical targets without having to individually prepare each analogue from basic building blocks. Professor Lectka and his research group are investigating a new approach to this problem through the development of hydrogen-atom transfer reagents that can specifically coordinate to a substrate and selectively activate a single carbon-hydrogen bond for C-X bond formation. Simultaneously, this team is also exploring the types of functional groups beyond ketones and enones that can influence the selectivity of the hydrogen-atom transfer reagents and determining the effect of substrate coordination to metal additives. These activities are providing a strong training platform for the professional development of graduate students and research experiences for undergraduate students.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.