The Catalyst Controlled Regioselective C-H Functionalization of Arenes and Heterocycles

催化剂控制的芳烃和杂环的区域选择性 C-H 官能化

• 批准号: 1955086
• 负责人: Jeffrey Gustafson
• 金额: $ 45.5万
• 依托单位: San Diego State University Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955086&HistoricalAwards=false
• 关键词: Catalyst; Controlled; Regioselective; Functionalization; Arenes

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Jeffrey Gustafson of San Diego State University (SDSU) to develop reactions that can selectively modify biologically relevant molecules. Most biologically active molecules where occurring naturally or developed as unnatural therapeutic agents are structurally quite complex and have multiple positions that can be modified in a given reaction. A mixture of several different compounds is often obtained, resulting in the need for costly and time-consuming purification steps. The ability to develop a set of reactions that selectively modify different positions of a molecule is highly desirable. Such strategies have the potential to transform how complex molecules are made in a manner that is both more economical and environmentally friendly. Professor Gustafson and his team of students are addressing this need through the development of a set of small molecule catalysts that can direct a reaction to a specific location of a molecule. Educational impacts of this project include improving the SDSU student experience in organic chemistry through the incorporation of virtual reality experiences to aid students in the 3-dimensional visualization of organic molecules. Virtual reality is also to be used in outreach programs aimed at SDSU’s general population, as well as local high schools and community colleges. Additional societal benefits include the recruitment and participation of underrepresented students (high school, undergraduate, and graduate) in research projects and volunteer work as part of the aforementioned outreach projects. Professor Gustafson and his team of students develop ‘organocatalysts’ that effect the regioselective C-H functionalization of simple and complex aromatics. They design bifunctional catalysts that possess one moiety that interacts with the substrate and another moiety that interacts with a reactant, directing it to a specific C-H bond in the substrate. They study diverse transformations that traditionally yield poor regioselectivities including electrophilic aromatic substitution, vicarious nucleophilic substitution and the addition of radicals into aromatics. For the addition of electrophiles into aromatics they utilize bifunctional Lewis basic catalysts that intercept and direct the electrophile to a specific position. For the regioselective addition of nucleophiles into aromatics, they utilize a broad array of organocatalytic strategies such as cation-directed catalysis, hydrogen bonding catalysis and Lewis acid catalysis. Professor Gustafson and his lab focus on incorporating functionalities that add value to the molecular systems being targeted. The ability to site-selectively modify simple and complex aromatic systems can greatly simplify synthetic strategy and lessens the need for lengthy and costly purification steps. The site-selective modification of complex intermediates has the potential to transform how the late-stage structural optimization process, in natural product-inspired synthesis, the development of designed therapeutic agent and in the development of functional molecular scaffolds, in general.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.

有了这个奖项，NSF化学部的化学合成计划正在支持圣地亚哥州立大学（SDSU）的Jeffrey Gustafson教授的研究，以开发可以选择性地修饰生物相关分子的反应。天然存在或作为非天然治疗剂开发的大多数生物活性分子在结构上非常复杂，并且具有在给定反应中可以修饰的多个位置。通常得到几种不同化合物的混合物，导致需要昂贵且耗时的纯化步骤。非常需要开发一组选择性修饰分子不同位置的反应的能力。这种策略有可能改变复杂分子的制造方式，使其更加经济和环保。Gustafson教授和他的学生团队正在通过开发一系列小分子催化剂来解决这一需求，这些催化剂可以将反应引导到分子的特定位置。该项目的教育影响包括通过结合虚拟现实体验来改善SDSU学生在有机化学方面的体验，以帮助学生实现有机分子的三维可视化。虚拟现实也将用于针对SDSU普通人群以及当地高中和社区大学的推广计划。 其他社会福利包括招募和参与代表性不足的学生（高中，本科和研究生）参加研究项目和志愿工作，作为上述推广项目的一部分。Gustafson教授和他的学生团队开发了“有机催化剂”，可以影响简单和复杂芳烃的区域选择性C-H官能化。他们设计的双功能催化剂具有一个与底物相互作用的部分和另一个与反应物相互作用的部分，将其引导到底物中的特定C-H键。他们研究了传统上产生差的区域选择性的各种转化，包括亲电芳族取代，替代亲核取代和将自由基加成到芳族化合物中。为了将亲电试剂加成到芳族化合物中，它们利用双官能刘易斯碱性催化剂，该催化剂将亲电试剂拦截并引导到特定位置。对于亲核试剂与芳烃的区域选择性加成，它们利用了广泛的有机催化策略，如阳离子导向催化、氢键催化和刘易斯酸催化。Gustafson教授和他的实验室专注于整合功能，为目标分子系统增加价值。对简单和复杂的芳族体系进行位点选择性修饰的能力可以大大简化合成策略，并减少对冗长和昂贵的纯化步骤的需求。 复杂中间体的位点选择性修饰具有改变后期结构优化过程的潜力，在天然产物启发的合成中，设计的治疗剂的开发以及功能性分子支架的开发中，通常情况下。该奖项反映了NSF的法定使命，并通过使用基金会的知识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

Atropisomerism as inspiration for new chemistry

• DOI: 10.24820/ark.5550190.p011.382
• 发表时间: 2021-01-01
• 期刊: ARKIVOC
• 影响因子: 0.9
• 作者: Cardenas, Mariel M.;Nguyen, Ashley D.;Gustafson, Jeffrey L.
• 通讯作者: Gustafson, Jeffrey L.