CAREER: New methods to functionalize pyridines and diazines

美国国家科学基金会化学部的化学合成项目通过该职业奖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，可以将药物和农用化学品的常见组成部分转化为具有生物活性的衍生物。特别是，吡啶是目前药物化合物中最广泛遇到的结构之一。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活性，来制造复杂的药物。这个项目是有机合成、药物化学和催化的结合，为他的学生在化学科学的前沿做好准备。教育活动的重点是增加本科课程的入学率，通过新的药物化学课程为制药行业的研究生做好准备，并通过一系列新的“酒吧讲座”改变公众对社会化学的看法。吡啶广泛应用于化学科学领域，包括制药、农用化学品、材料和配体。尽管它们很重要，但目前的合成工具箱在制备有价值的吡啶衍生物方面存在不足。本项目开发了以磷化合物为试剂和催化剂的吡啶化学转化新工艺。在这个项目中解决了三个不同的问题：1)磷盐能否在具有“可切换”的位点选择性控制的复合多吡啶上形成？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3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背景系列讲座增加本科化学课程的入学人数。在研究生阶段，学生们正在学习一门新的药物化学课程，其中包括药物化学家的客座讲座。公众参与了一个新的“酒吧讲座”系列，处理当代和社会上有争议的化学方面。该奖项反映了美国国家科学基金会的法定使命，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 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.