CAS: Developing Nickel-Catalyzed Methods to Prepare High-Value Organofluorine Molecules

在化学系化学合成项目的支持下，利哈伊大学的大卫维克教授将研究如何使用地球上丰富的环境友好的镍金属作为催化剂，将含氟基团引入有机基质。 含氟药物在注册合成药物总数中的比例非常高（2019年为43%），1998-2020年，在所有分配了新ISO通用名称的农用化学品中，47%含有氟。 因此，开发更便宜和更有效的催化方法来引入氟化基团对健康和食品工业至关重要。 Vicic教授和团队将制备具有氟化基团的定义明确的镍络合物，以系统地确定允许镍将氟化基团释放到制药和农业化学领域感兴趣的有机支架上的实验条件。 实现清洁和高产率的氟化基团转移到有机基质是必要的，以将浪费的过程转化为更可持续的催化过程，这在学术界和工业界都具有重要价值。该项目还将创建一个基于网络的含氟化合物光谱数据库，以便不同背景的研究人员更容易进入这一领域，以促进更具包容性的劳动力。 培训研究生在周围学校进行科学推广也计划与利哈伊的学术推广办公室。 该项目将开发如何使用Vicic实验室开发的阴离子氟烷基镍络合物在温和条件下获得镍的高价态的方法。 接下来，Vicic小组将致力于确定释放氟烷基自由基所必需的状态。 然后，该团队将确定自由基添加到含有烯烃和芳烃官能团的底物的范围和选择性，研究光对均裂反应的影响，并研究将催化过程转化为电催化变体的方法。 该团队还将制备一系列带有有机和氟烷基配体的阴离子镍前体，并通过各种分析技术监测氟烷基化有机产物的消除。 以这种方式，氧化剂，金属氧化态，光和其他反应参数对高价镍还原消除的影响将被建立。 该团队还将确定制备含有化学和光化学可衍生的氟化基团的镍络合物的策略，然后开发直接制备含有此类基团的分子库的方法，用于发现化学。 这些活动协同为利哈伊大学的研究生和本科生提供了有机金属化学和催化方面的重要培训。该奖项反映了NSF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 Synthesis program in the Division of Chemistry, Professor David Vicic of Lehigh University will study ways to introduce fluorine-containing groups into organic substrates using the earth-abundant and environmentally friendly nickel metal as a catalyst. The percentage of fluorinated pharmaceuticals among the total number of registered synthetic drugs is extraordinary (43% in 2019), and 47% of all agrichemicals that were assigned new ISO common names contained fluorine from 1998-2020. As such, developing cheaper and more efficient catalytic methods to incorporate fluorinated groups is paramount to the health and food industries. Professor Vicic and team will prepare well-defined nickel complexes bearing fluorinated groups in order to systematically determine the experimental conditions that will allow nickel to release the fluorinated groups onto organic scaffolds that are of interest to the pharmaceutical and agrochemical fields. The realization of clean and high-yielding transfers of fluorinated groups to organic substrates is necessary to transform wasteful processes into more sustainable catalytic ones would be of significant value in n both academic and industrial circles. This project will also create a web-based spectral database for fluorinated compounds so that entry into this field can be more accessible to beginning researchers of diverse backgrounds in order to promote a more inclusive workforce. Training graduate students to perform science outreach at surrounding schools is also planned with Lehigh’s Academic Outreach Office. The project will develop methodology on how to access the higher-valent states of nickel under mild conditions using anionic fluoroalkyl nickel complexes that have been developed in the Vicic lab. Next, the Vicic group will work to determine which state is necessary for the release of fluoroalkyl radicals. The team will then identify the scope and selectivity of radical additions to substrates containing alkene and arene functionalities, study the effect of light on the homolysis reactions, and investigate methods to transform catalytic processes into electrocatalytic variants. The team will also prepare a family of anionic nickel precursors bearing organic and fluoroalkyl ligands and monitor the elimination of fluoroalkylated organic products by a variety of analytical techniques. In this way, the effect of oxidants, metal oxidation state, light, and other reaction parameters on reductive elimination at high-valent nickel will be established. The team will also identify strategies to prepare nickel complexes containing chemically and photochemically derivatizable fluorinated groups, and then develop methods for directly preparing libraries of molecules containing such groups for discovery chemistry. These activities are synergistically providing important training in organometallic chemistry and catalysis for a diverse group of graduate and undergraduate students at Lehigh University.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.