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改进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结构单元，然而芳香族分子产生增值商品的化学反应通常受到阻碍，因为它导致产生多种产物，需要昂贵的纯化序列。Gustafson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芳香族支架的选择性修饰，最终为学术界和制药界感兴趣的分子提供更有效的合成策略。除了为研究生和本科生提供有机化学培训外，该项目还对教育产生了更广泛的影响，因为它建议将虚拟现实体验纳入其中，以帮助学生进行分子的三维可视化。虚拟现实还将用于针对SDSU普通人群以及当地高中和社区大学的推广计划。 Gustafson教授和他的合作者和学生团队设计了“有机催化剂”，通过亲电芳香取代和相关的芳香基团官能化反应影响简单和复杂芳香族化合物的区域选择性C-H官能化。这些转化传统上产生差的区域选择性，通常阻止它们被采用为可行的合成策略，特别是在更复杂的环境中。为了将亲电试剂加成到芳烃中，Gustafson小组设计了双功能刘易斯碱性催化剂，其将亲电试剂或亲电基团拦截并引导到特定位置。Gustafson小组也在探索类似的策略，用于在亲核芳族取代和替代亲核取代的背景下用亲核试剂官能化芳族化合物。 对于亲核试剂与芳烃的区域选择性加成，它们利用了广泛的经典有机催化策略，包括阳离子导向催化和氢键催化。位点选择性修饰简单和复杂芳族体系的能力大大简化了分子的合成，并为这些化学品在后期官能化策略的背景下使用打开了大门。为了设计更好、更有效的催化剂，Gustafson小组还与计算化学和电化学领域的合作者进行了机理研究。这项工作实现的复杂中间体的位点选择性修饰有可能改变药物、材料和其他功能分子的后期结构优化方式。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。

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.