The Catalyst-Controlled Regioselective Functionalization of Aromatics

在化学系化学合成和化学催化项目的支持下，圣地亚哥州立大学的杰弗里·古斯塔夫森教授正在研究修饰精细化学品和医药中间体的新方法。芳香族化合物是整个合成和药物化学中常见的构件，然而芳香族分子的化学反应往往会受到阻碍，因为它会导致多个产品的产生，从而需要昂贵的纯化步骤。古斯塔夫森博士和他的团队正在研究新的化学反应，旨在控制简单和复杂的芳香族支架的选择性修饰，最终产生更有效的合成策略，以获得学术界和制药界感兴趣的分子。除了为研究生和本科生提供有机化学方面的培训外，该项目还对教育产生了更广泛的影响，因为它建议结合虚拟现实体验来帮助学生进行分子的三维可视化。虚拟现实还将被用于针对SDSU普通人群以及当地高中和社区大学的外联项目。古斯塔夫森教授和他的合作者团队以及学生们设计了“有机催化剂”，通过亲电取代和相关的芳香族自由基官能化反应，影响简单和复杂芳烃的区域选择性C-H官能化。传统上，这些转变产生的区域选择性很差，往往使它们无法被采纳为可行的综合战略，特别是在更复杂的环境中。为了在芳烃中加成亲电体，古斯塔夫森团队设计了双功能Lewis碱性催化剂，这种催化剂可以截取亲电性或亲电基团并将其引导到特定位置。古斯塔夫森小组还在探索类似的策略，在亲核取代和替代亲核取代的背景下，将芳香族与亲核试剂功能化。对于亲核试剂与芳烃的区域选择性加成，他们利用了一系列经典的有机催化策略，包括阳离子导向催化和氢键催化。选择性地修饰简单和复杂芳香体系的能力极大地简化了分子的合成，并为这些化学物质在后期官能化策略中的应用打开了大门。为了设计出更好、更高效的催化剂，古斯塔夫森团队还与计算化学和电化学领域的合作者一起进行了机理研究。这项工作实现了对复杂中间体的现场选择性修饰，这可能会改变药物、材料和其他功能分子的后期结构优化的进行方式。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 the support of the Chemical Synthesis and Chemical Catalysis Programs in the Division of Chemistry, Professor Jeffrey Gustafson of San Diego State University is studying new approaches to modifying fine chemicals and pharmaceutical intermediates. Aromatic compounds are common building blocks throughout synthetic and pharmaceutical chemistry, however the chemical reactions of aromatic molecules to give value-added commodities is often hindered because it results in the generation of multiple products, necessitating costly purification sequences. Dr. Gustafson and his team are studying new chemical reactions aimed at controlling the selective modification of both simple and complex aromatic scaffolds, ultimately resulting in more efficient synthetic strategies towards molecules of interest to the academic and pharmaceutical communities. In addition to providing training in organic chemistry for graduate and undergraduate students, this project also impacts the education more broadly in that it proposes to incorporate Virtual Reality experiences to aid students in the 3-dimensional visualization of molecules. Virtual Reality will also be utilized in outreach programs aimed at SDSU’s general population, as well as local high schools and community colleges. Professor Gustafson and his team of collaborators and students design ‘organocatalysts’ that affect the regioselective C-H functionalization of simple and complex aromatics through electrophilic aromatic substitution and related aromatic radical functionalization reactions. These transformations traditionally yield poor regioselectivities, often preventing them from being adopted as viable synthetic strategies, particularly in more complex settings. For the addition of electrophiles into aromatics, the Gustafson group designs bifunctional Lewis basic catalysts that intercept and direct the electrophile, or electrophilic radical to a specific position. The Gustafson group is also exploring similar strategies for the functionalization of aromatics with nucleophiles in the context of nucleophilic aromatic substitution and vicarious nucleophilic substitution. For the regioselective addition of nucleophiles to aromatics, they utilize a broad array of classic organocatalytic strategies including cation directed catalysis and hydrogen-bonding catalysis. The ability to site-selectively modify simple and complex aromatic systems greatly simplifies the syntheses of molecules and opens the door for these chemistries to be used in the context of late-stage functionalization strategies. In order to allow for the design of better and more efficient catalysts, the Gustafson group is also performing mechanistic studies with collaborators in computational chemistry and electrochemistry. The site-selective modification of complex intermediates that this work enables has the potential to transform how the late-stage structural optimization of pharmaceuticals, materials and other functional molecules are carried out.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.