Catalytic Cycloaddition Reactions and Their Applications

在化学系化学催化(CAT)和化学合成(SYN)计划的支持下，圣安东尼奥德克萨斯大学的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构建块，在缺乏电子的碳旁边具有碳-碳双键，正式名称为类卡宾中心。正在研究催化剂，以调整和控制乙烯基重氮化合物与相容试剂的反应性，以获得增值产品。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烃结构，这些结构是有价值的添加目标分子的常见成分，特别是对生物和药物化学有价值的杂环结构。协同作用，这些活动将为不同水平的学生提供机会，扩大他们在催化和合成化学方面的知识和经验。本科生正在被纳入研究计划，并得到强有力的指导，为他们在STEM(科学、技术、工程和数学)学科的职业生涯做准备，并向博士后研究助理提供机会，为他们在私营部门和学术界的化学科学职位做准备。由于杂环和官能化碳环合成的新模块化方法在制药、农用化学品和新材料目标中的普及，对这些结构的需求很高。Michael Doyle教授和他的研究团队正在寻找催化剂，这些催化剂从乙烯基重氮化合物中挤出分子氮，形成高能的金属卡宾中间体，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合物。硅基保护的重氮烯醇类化合物的[31]-环加成反应的立体定义产物将被用于后续应变诱导的开环反应，并用于探索给体-受体环烯的环加成反应。三氟化亚胺的酸催化条件正在被开发，以使乙烯基重氮[31]环加成产物参与随后的环加成反应，从而产生能够将环扩展到中等尺寸产品的中间结构。对偶氮烯醇类化合物的高对映选择性催化环丙烷化反应正在进行测试，以制备能够进行环加成反应并保留对映体富集性的给体-受体环丙烷。这些活动将在德克萨斯大学圣安东尼奥分校举行，并增加了这个为少数族裔服务的学院的包容性培训和研究机会。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 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.