Catalytic Cycloaddition Reactions and Their Applications

在化学系化学催化（CAT）和化学合成（SYN）项目的支持下，德克萨斯大学圣安东尼奥分校的Michael Doyle教授正在努力开发使用乙烯基重氮化合物构建分子的新方法，乙烯基重氮化合物是一种有机结构单元，在贫电子碳旁边有一个碳-碳双键，正式名称为类卡宾中心。目前正在研究催化剂，以调节和控制乙烯基重氮化合物与相容试剂的反应性，从而获得增值产品。这些研究正致力于建立新的方法来构建具有挑战性的键和杂芳族结构，这些结构是增值目标分子的常见组分，特别是对生物和药物化学有价值的杂环结构。这些活动将为不同程度的学生提供机会，扩阔他们在催化和合成化学方面的知识和经验。本科生正在融入研究计划，并为他们在STEM的职业生涯做好准备（科学、技术、工程和数学）学科，并为博士后研究人员提供机会，为他们在私营部门和学术界的化学科学职位做好准备。这是由于这些结构在药物、农业化学品和新材料靶中的普遍存在。Michael Doyle教授和他的研究团队正在鉴定催化剂，这些催化剂可以从乙烯基重氮化合物中挤出分子氮，形成高能双卡宾中间体，这些中间体与各种偶极环加成伙伴缩合，形成具有高度区域和立体控制的新型加成物。研究了硅烷基保护的烯醇重氮化合物的[3+1]-环加成反应的立体定向产物的随后的应变诱导开环反应性，并用于探索给体-受体环烯烃的环加成反应。正在开发使用三氟甲磺酰亚胺的酸催化条件以在随后的环加成反应中与乙烯基重氮[3+1]环加成产物接合，所述环加成反应导致能够环膨胀成中等尺寸产物的中间体结构。正在测试烯醇重氮化合物的高对映选择性催化环丙烷化反应，以制备能够参与环加成反应并保留对映富集的给体-受体环丙烷。这些活动将在德克萨斯大学圣安东尼奥举行，并增加在这个少数民族服务机构的包容性培训和研究机会。该奖项反映了NSF的法定使命，并已被认为是值得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的支持。

With the support of the Chemical Catalysis (CAT) and Chemical Synthesis (SYN) Programs in the Division of Chemistry, Professor Michael Doyle of the University of Texas, San Antonio is working to develop new ways to construct molecules using vinyl diazo compounds, organic building blocks that have a carbon-carbon double bond next to an electron-poor carbon, formally known as a carbenoid center. Catalysts are being studied to tune and control the reactivity of vinyl diazo compounds with compatible reagents to access value-added products. These investigations are working toward establishing new ways to construct challenging bonds and heteroaromatic structures that are common components of valued added target molecules, particularly heterocyclic structures of value to biological and medicinal chemistry. Synergistically, these activities will provide opportunities for students of different levels to broaden their knowledge and experience in catalytic and synthetic chemistry. Undergraduate students are being integrated into the research program with strong mentoring that prepares them for careers in STEM (science, technology, engineering and mathematics) disciplines, and opportunities are being provided to postdoctoral research associates to prepare them for positions in the chemical sciences in both the private sector and in academia.New modular methods for the synthesis of heterocycles and functionalized carbocycles are in high demand due to the prevalence of these structures in pharmaceutical, agrochemical, and new material targets. Professor Michael Doyle and his research team are identifying catalysts that extrude molecular nitrogen from vinyl diazo-compounds to form highly energetic metallocarbene intermediates that condense with a variety of dipolar cycloaddition partners to form novel adduce with a high degree of regio- and stereo control. The stereodefined products of [3+1]-cycloaddition reactions of silyl-protected enoldiazo compounds will be studied for subsequent strain-induced ring-opening reactivity and used to explore cycloaddition reactions of donor-acceptor cycloalkenes. Acid-catalyzed conditions with triflimide are being developed to engage vinyl diazo [3+1] cycloaddition products in subsequent cycloaddition reactions that lead to intermediate structures capable of ring expansion to medium-sized products. Highly enantioselective catalytic cyclopropanation reactions of enoldiazo compounds are being tested to prepare donor-acceptor cyclopropanes that are capable of engaging in cycloaddition reactions with retention of enantioenrichement. These activities will take place at the University of Texas, San Antonio, and augment the inclusive training and research opportunities at this minority-serving institution.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.