Lewis Base Directed Intermolecular Hydrogen Atom Transfer

路易斯碱定向分子间氢原子转移

• 批准号: 2102116
• 负责人: Thomas Lectka
• 金额: $ 50万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102116&HistoricalAwards=false
• 关键词: Lewis; Base; Directed; Intermolecular; Hydrogen

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.

在化学系化学合成项目的支持下，约翰霍普金斯大学的托马斯·莱克特卡教授正在研究选择性修饰复杂分子中一个碳氢键的新方法，该分子具有许多碳氢键。这些类型的反应对于系统地改变生物活性分子以研究它们的反应性而不必从头开始构建每个单独的分子是重要的。Lectka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-氢键被转化为碳-氟、碳-溴、碳-氧和碳-氮键，这些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 STEM成就巴尔的摩小学（SABES）计划合作，为当地高中生提供研究经验。在复杂分子环境中的H官能化是当前的巨大挑战，其动机是希望能够研究和修饰天然产物和药物靶标，而不必从基本结构单元单独制备每种类似物。Lectka教授和他的研究小组正在研究一种新的方法来解决这个问题，通过开发氢原子转移试剂，可以特异性地与底物配位，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价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Rational Computational Design of Systems Exhibiting Strong Halogen Bonding Involving Fluorine in Bicyclic Diamine Derivatives

• DOI: 10.1021/acs.joc.2c00497
• 发表时间: 2022-06-05
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Harry, Stefan Andrew;Vemulapalli, Srini;Lectka, Thomas
• 通讯作者: Lectka, Thomas

How Do Face-to-Face Stacked Aromatic Rings Activate Each Other to Electrophilic Aromatic Substitution?

面对面堆叠的芳香环如何相互激活以实现亲电芳香取代？

• DOI: 10.1021/acs.orglett.3c01401
• 发表时间: 2023
• 期刊: Organic Letters
• 影响因子: 5.2
• 作者: Kazim, Muhammad;Wang, Muyuan;Vemulapalli, Srini;Nguyen, Phuong Minh;Wang, Yuang;Siegler, Maxime A.;Dudding, Travis;Lectka, Thomas
• 通讯作者: Lectka, Thomas

An Electrochemical Approach to Directed Fluorination

定向氟化的电化学方法

• DOI: 10.1021/acs.joc.2c01886
• 发表时间: 2023
• 期刊: The Journal of Organic Chemistry
• 作者: Holt, Eric;Wang, Muyuan;Harry, Stefan Andrew;He, Chengkun;Wang, Yuang;Henriquez, Nicolas;Xiang, Michael Richard;Zhu, Andrea;Ghorbani, Fereshte;Lectka, Thomas
• 通讯作者: Lectka, Thomas

Through‐Space, Lone‐Pair Promoted Aromatic Substitution: A Relay Mechanism Can Beat Out Direct Activation

通过空间、孤独、配对促进芳香取代：中继机制可以击败直接激活

• DOI: 10.1002/chem.202301550
• 发表时间: 2023
• 期刊: Chemistry – A European Journal
• 作者: Kazim, Muhammad;Feng, Zhitao;Vemulapalli, Srini;Siegler, Maxime A.;Chopra, Anant;Minh Nguyen, Phuong;Gargiulo Holl, Maxwell;Guan, Liangyu;Dudding, Travis;Tantillo, Dean J.
• 通讯作者: Tantillo, Dean J.

C–C Bond Activation and Demethylenation of Epoxides by Amine Radical Dications

胺自由基双阳离子对环氧化物的 C–C 键激活和脱甲基化

• DOI: 10.1021/acs.joc.3c00605
• 发表时间: 2023
• 期刊: The Journal of Organic Chemistry
• 作者: Holt, Eric;Garrison, Nathaniel G.;Rowshanpour, Rozhin;Kim, Justin Jeeyoung;Henriquez, Nicolas;Lam, Winson;Kiame, Neil;Williams, Jack;Zhao, Sherrie;Dudding, Travis
• 通讯作者: Dudding, Travis