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舍夫林正在研究新的化学方法，用于大规模可持续和低成本的药物合成。催化是一个关键的经济驱动力，它是有价值的天然产物，药物，材料和分子器件合成的变革。这项合作的重点是用于在过程化学实验室中大规模构建药物支架的催化化学。 不幸的是，目前最成功和广泛使用的药物制造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。莱顿-默克团队试图通过确定新的可行的催化工艺来解决这个问题，而不是基于丰富和国内可用的金属，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工艺类型，以拓宽贱金属催化转化的新品种。该奖项的更广泛的影响进一步扩大了累积到社会的收益，因为教授Chirik和他的同事从事一系列的教育和推广活动。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，准备推广和翻译可持续化学的原则。外联工作是针对公众参与的目标，通过教育模块，强调催化和翻译的系统方法改变观念。职业发展和扩大属于代表性不足的群体的个人的参与是一系列拟议的研讨会，讲习班和社会媒体参与学术-工业界面的主要目标。在催化中使用地球丰富的过渡金属是可持续化学的关键组成部分。实现这些元素在药物合成中的全部潜力依赖于发现用于各种成键反应的稳健且可获得的前体。因此，资助的研究重点是将基础有机金属化学与新的键结构中的应用相结合，以促进发现多功能铁和钴前体，从而在整个合成化学和催化领域中得到更广泛的应用。合成方法，如氧化诱导的还原消除和芳烃取代从独特的金属三明治化合物正在探索，以扩大类型的铁和钴催化剂，可在一系列的氧化态。重点放在转换，可能会加速合成和发现的生物活性分子增加C（SP3）的内容。在这方面，积极感兴趣的方法包括不对称氢化、还原氢化和从底物类别的氢氨甲基化，所述底物类别包括具有远程氨基和羟基取代的烯烃，以及具有已知为贵金属催化剂毒物的杂环的那些。预计这项工作的结果将导致有机合成的理论和实践的根本性进展，使用地球丰富的过渡金属基催化剂，更可持续和经济的未来化学制造过程的承诺。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智力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 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.