CAREER: New methods to functionalize pyridines and diazines

通过这一职业奖项，美国国家科学基金会化学部化学合成计划支持科罗拉多州立大学化学系安德鲁·麦克纳利教授的研究。麦克纳利教授和他的学生开发了新的合成方法，使药物和农用化学品的常见组成部分可以转化为具有生物活性的衍生品。特别是，吡啶类化合物是当前药物化合物中最常见的结构之一。麦克纳利教授实验室的研究利用了吡啶上新的成键反应的独特反应性，以制造复杂的药物。这个项目是有机合成、药物化学和催化的结合，正在为他的学生在化学科学前沿的职业生涯做准备。教育活动的重点是增加本科生的入学人数，通过一个新的药物化学项目为制药业培养研究生，并通过一系列新的“酒吧讲座”改变公众对化学的看法。吡啶在化学科学中得到了广泛的应用，包括作为制药、农用化学品、材料和配体的应用。尽管它们很重要，但目前的合成工具包在制备有价值的吡啶衍生物方面存在不足。该项目利用含磷化合物作为试剂和催化剂，开发了吡啶的新化学转化。这个项目解决了三个不同的问题：1)在复杂的聚吡啶上是否可以通过“可切换”的位置选择性控制来形成膦盐？磷配体偶联反应能否在新的吡啶烷基化反应中实现sp2-sp3偶联？3)磷中间体和新的催化方法能否实现三位选择性卤化、三氟甲基化和胺化反应？教育计划的重点是通过化学上下文系列讲座增加本科生化学课程的招生人数。在研究生阶段，学生们正在注册一门新的药物化学课程，其中包括药物化学家的客座讲座。公众正通过一个新的“酒吧演讲”系列来讨论当代和社会中有争议的化学方面。这个奖项反映了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 this CAREER award, the Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Andrew McNally in the Department of Chemistry at Colorado State University. Professor McNally and his students develop new synthetic methods that allow common building blocks of pharmaceuticals and agrochemicals to be transformed into biologically active derivatives. In particular, pyridines are among the most widely encountered structures in current drug compounds. Research in Professor McNally's laboratory exploits the unique reactivity of new bond-forming reactions on pyridines, to make complex pharmaceuticals. This project is a combination of organic synthesis, medicinal chemistry and catalysis that is preparing his students for careers at the forefront of the chemical sciences. Educational activities focus on increasing enrollment into undergraduate programs, preparing graduate students for the pharmaceutical industry via a new medicinal chemistry program and changing the public's perception of chemistry in society through a new series of 'pub lectures'.Pyridines are used widely across the chemical sciences including applications as pharmaceuticals, agrochemicals, materials and ligands. Despite their importance, there are deficiencies in the current synthetic toolkit to prepare valuable pyridine derivatives. This project develops new chemical transformation of pyridines using phosphorus compounds as reagents and catalysts. Three distinct questions are addressed in this project: 1) Can phosphonium salts be formed on complex polypyridines with 'switchable' control of site-selectivity? Can phosphorus ligand-coupling reactions be used to enable sp2-sp3 coupling in new pyridine alkylation reactions? 3) Can phosphorus intermediates, and new catalytic approaches, enable 3-position selective halogenation, trifluoromethylation and amination reactions? The educational plan focuses on increasing the enrollment in the undergraduate chemistry program through a chemistry in context lecture series. At the graduate level, students are enrolling in a new medicinal chemistry course that includes guest lectures from medicinal chemists. The public is engaged through a new 'pub lecture' series that tackles contemporary and controversial aspects of chemistry in society.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.