GOALI: An Industrial-Academic Collaboration for Sustainable Catalysis with Earth Abundant Metals

在化学系化学催化项目的支持下，普林斯顿大学的Paul Chirik教授和默克催化实验室的Marion Emmert和Michael Shevlin正在研究新的化学方法，以实现可持续和低成本的大规模药物合成。催化是一个关键的经济驱动力，它对有价值的天然产物、药物、材料和分子装置的合成具有变革性。此次合作的重点是催化化学，用于在过程化学实验室中大规模构建药物支架。不幸的是，目前，最成功和广泛使用的制药催化剂依赖于地球上最不丰富的金属，从而损害了环境的可持续性。普林斯顿-默克团队试图通过寻找新的可行的催化过程来解决这个问题，而不是基于丰富的和国内可用的金属，如铁、钴和镍。除了预期的经济和环境效益外，新的催化剂技术还将用于扩大可以实现的化学过程的类型，以扩大新兴的贱金属催化转化。由于Chirik教授和他的同事参与了一系列教育和外展活动，该奖项的广泛影响进一步扩大，为社会带来了收益。参与资助研究的学生将受益于这种工业-学术合作所带来的独特培训环境，他们很可能成为未来的科学和技术领导者，随时准备促进和转化可持续化学的原则。外联工作的目标是通过强调催化和翻译的系统方法的教育模块来改变公众的看法。职业发展和扩大代表性不足群体的个人参与是一系列拟议的学术-工业界面研讨会、讲习班和社会媒体参与的主要目标。富土过渡金属在催化中的应用是可持续化学的重要组成部分。实现这些元素在药物合成中的全部潜力依赖于发现强大的和可获得的前体，用于各种成键反应。因此，该基金的研究重点是将基本有机金属化学与新键结构的应用相结合，以激发在整个合成化学和催化界更广泛使用的多功能铁和钴前体的发现。人们正在探索氧化诱导还原消除和芳烃置换等独特金属夹层化合物的合成方法，以扩大铁和钴催化剂的种类，使其能够跨越一系列氧化态。重点放在转化，可能加快合成和发现生物活性分子增加C（sp3）的含量。在这方面的积极兴趣的过程包括不对称氢化，还原性氢甲酰化和氢胺甲基化从底物类包括烯烃与远端氨基和羟基取代，以及那些杂环是已知的贵金属催化剂的有毒物质。预计这项工作的发现将导致利用富土过渡金属基催化剂进行有机合成的理论和实践的根本性进展，并有望在未来实现更可持续和更经济的化学制造工艺。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 the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Paul Chirik of Princeton University and Marion Emmert and Michael Shevlin at the Merck Catalysis Laboratory are studying new chemical methods for the sustainable and low-cost synthesis of pharmaceuticals at scale. Catalysis is a key economic driver and it is transformative for the synthesis of valuable natural products, pharmaceuticals, materials and molecular devices. This collaboration focuses on the catalytic chemistry used to build the scaffolds of pharmaceutical drugs on scale in process chemistry laboratories. Unfortunately, at the present time, the most successful and widely used catalysts for pharmaceutical manufacture rely on the least abundant metals on earth, thus compromising environmental sustainability. The Princeton-Merck team seeks to combat this problem by identifying new viable catalytic processes based instead on metals that are both abundant and domestically available, such as iron, cobalt, and nickel. In addition to the anticipated economic and environmental benefits that it will provide, the new catalyst technology will be applied to expanding the types of chemical processes that can be achieved to broaden the emerging repertoire of base metal-catalyzed transformations. The broader impacts of the award are further extended by the gains accrued to society as Professor Chirik and his co-workers engage in a range of educational and outreach activities. Students participating in the funded research will benefit from the unique training environment enabled by this industrial-academic collaboration and they are likely to emerge as future science and technology leaders who are ready to promote and translate the principles of sustainable chemistry. Outreach efforts are directed toward public engagement with the goal of changing perceptions through educational modules that emphasize a systems approach to catalysis and translation. Career development and broadening participation from individuals belonging to underrepresented groups are the primary goals of a range of proposed seminars, workshops, and social media engagements at the academic-industrial interface.The use of earth abundant transition metals in catalysis is a critical component of sustainable chemistry. Realizing the full potential of these elements in drug synthesis is reliant on the discovery of robust and accessible precursors for a diverse array of bond-forming reactions. Accordingly, the funded research is focused on interfacing fundamental organometallic chemistry with applications in new bond constructions to motivate the discovery of versatile iron and cobalt precursors for broader use throughout the synthetic chemistry and catalysis community. Synthetic methods such as oxidatively-induced reductive elimination and arene displacement from unique metal sandwich compounds are being explored to expand the types of iron and cobalt catalysts that are available across a range of oxidation states. Emphasis is placed on transformations that may accelerate the synthesis and discovery of bioactive molecules with increased C(sp3) content. Processes of active interest in this regard include asymmetric hydrogenation, reductive hydroformylation, and hydroaminomethylation from substrate classes encompassing alkenes with remote amino- and hydroxyl-substitution, as well as those with heterocycles that are known poisons for precious metal catalysts. It is anticipated that the findings of this work will lead to fundamental advances in the theory and practice of organic synthesis using earth abundant transition metal-based catalysts with the promise of more sustainable and economical future chemical manufacturing processes.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.