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

美国国家科学基金会化学部的化学合成项目通过该奖项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学相关分子的反应。大多数天然存在的生物活性分子或作为非自然治疗剂开发的生物活性分子在结构上相当复杂，并且具有多个位置，可以在给定的反应中进行修改。通常会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。开发一系列有选择地修饰分子不同位置的反应的能力是非常可取的。这种策略有可能以一种更经济、更环保的方式改变复杂分子的制造方式。Gustafson教授和他的学生团队正在通过开发一套小分子催化剂来解决这一需求，这些催化剂可以将反应导向分子的特定位置。该项目的教育影响包括通过结合虚拟现实体验来帮助学生进行有机分子的三维可视化，从而改善SDSU学生在有机化学方面的体验。虚拟现实还将用于针对SDSU普通民众以及当地高中和社区大学的推广项目。额外的社会效益包括招募和参与代表性不足的学生（高中，本科生和研究生）的研究项目和志愿者工作，作为上述推广项目的一部分。古斯塔夫森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碳氢功能化。他们设计了双功能催化剂，其中一个片段与底物相互作用，另一个片段与反应物相互作用，将其导向底物中特定的C-H键。他们研究了不同的转化，传统上产生较差的区域选择性，包括亲电芳香取代，替代亲核取代和芳烃自由基的加成。为了将亲电试剂添加到芳烃中，他们使用双功能路易斯碱催化剂来拦截并引导亲电试剂到特定的位置。对于亲核试剂在芳烃中的区域选择性加成，他们利用了广泛的有机催化策略，如阳离子定向催化、氢键催化和路易斯酸催化。古斯塔夫森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。定位选择性修饰简单和复杂芳香体系的能力可以大大简化合成策略，减少对冗长和昂贵的纯化步骤的需要。一般来说，复杂中间体的位点选择性修饰有可能改变天然产物启发合成、设计治疗剂的开发和功能分子支架的开发等后期结构优化过程。该奖项反映了美国国家科学基金会的法定使命，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。

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.