Development of and Mechanistic Studies on the Palladium and Iron-Cocatalyzed Nucleoboration of Olefins

在化学系化学催化项目的支持下，德克萨斯大学奥斯汀分校（UT-Austin）的Kami L. Hull正在研究一种钯和铁催化的工艺，该工艺可以将简单的化学原料（烯烃）转化为增值产品。这种所谓的“成核”方法以精细控制的方式将一个硼原子和另一个元素（通常是氮）原子加到烯烃中。存在选择性转化，随后将硼原子转化为各种各样的其他取代基，整个过程有望成为制造复杂化合物和对社会有价值的先进材料的通用方法。与方法开发相结合，资助的研究包括详细的机制研究，旨在阐明催化剂对如何发挥作用，以推进过渡金属基催化的基础知识，提高化学合成的效率和可持续性。赫尔博士和她的同事们参与了广泛的教育和推广活动，其中包括：ChemBridge计划，旨在提高在STEM（科学、技术、工程和数学）领域服务不足的年轻德克萨斯人的大学准备，以及持续努力在UT-Austin的师生中传播多样性、公平和包容性的共同价值观。资助的研究重点是对最近发现的Pd/ fe共催化烯烃氨基化反应的研究，它的特点是该过程的进一步发展（例如，扩大底物和亲核试剂的范围）和相关的机制研究，以获得对三酸铁（II）共催化剂潜在作用的见解。具体来说，在方法开发过程中（Aim 1），降冰片烯氨基合成成功的反应条件[关键试剂：PhthNH， B2Pin2, cat. 1]。Pd (MeCN) 2这有点难度,猫。Fe(OTf)2和O2]将进一步探索并扩展到更具挑战性的烯烃底物，在该过程的马尔可夫尼科夫加成阶段可能会遇到β -氢化物消除。除n基体系以外的亲核试剂，如基于基（如酚类）、基于基（如硫醇类）和基于c基（如吲哚类），也将被研究，还有替代的金属转化试剂（如硅基和锡基），以可能达到高度普遍的金属核化过程。为了进一步扩大平台的多功能性，在转化之前还在进行一种包含“pd行走”阶段（即区域异构化）的远程核核转化。在机制研究（Aim 2）中，铁在氨氧化转化步骤中的关键作用的起源正在被探索，它对aza-Wacker过程同样好奇的有益作用也在探索中。最后，为了开发一种更可持续的核成核过程（目标3），一种多相和可回收的Pd/Fe催化剂体系正在开发中。总而言之，正在进行的研究预计将扩展烯烃双官能化化学的多功能性，从而促进含氮（和其他杂原子）化合物的重要类别的合成，这些化合物在活性药物成分和其他类型的复杂分子中占有突出地位，在科学、工程和医学中具有实用价值。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, Kami L. Hull of the University of Texas at Austin (UT-Austin) is studying a palladium- and iron-catalyzed process that converts simple chemical feedstocks (olefins) into value-added products. This so-called "nucleoboration" method results in the addition of an atom of boron and one of another element, typically nitrogen, to the olefin in a finely controlled manner. Selective transformations exist to subsequently convert the boron atom into a wide variety of other substituents and the overall process promises to be a versatile approach for the manufacture of complex compounds and advanced materials of value to society. In combination with method development, the funded research encompasses detailed mechanistic studies designed to elucidate how the catalyst pair functions with the goals of advancing fundamental knowledge of transition metal-based catalysis and improving the efficiency and sustainability of chemical synthesis. The broader impacts of the funded project extend to the benefits accrued to society as Dr. Hull and her coworkers engage in an extensive range of educational and outreach activities, including: the ChemBridge program to improve the college readiness of young Texans who belong to groups underserved in STEM (science, technology, engineering and mathematics) fields, and ongoing efforts to propagate shared values of diversity, equity, and inclusivity among the faculty and students of UT-Austin.The funded research focuses on investigations of a recently discovered Pd/Fe-cocatalyzed aminoboration of alkenes and it features further development of the process (e.g., to expand both the substrate and nucleophile scope) and associated mechanistic studies to gain insights for the underlying role of the iron(II) triflate cocatalyst. Specifically, during the course of methodological development (Aim 1), reaction conditions for the successful aminoboration of norbornene [key reagents: PhthNH, B2Pin2, cat. Pd(MeCN)2Cl2, cat. Fe(OTf)2, and O2] will be further explored and extended to more challenging olefin substrates for which beta-hydride elimination following the Markovnikov addition stage of the process could be encountered. Nucleophiles other than N-based systems, such as O-based (e.g., phenols), S-based (e.g., thiols), and C-based (e.g., indoles), will also be investigated as will alternative transmetalation reagents (e.g., Si- and Sn-based) to potentially arrive upon a highly generalized nucleometallation process. In further efforts to broaden the versatility of the platform yet further, a remote nucleoboration transformation that incorporates a 'Pd-walking' stage (i.e., regioisomerization) prior to transmetalation is also being pursued. In mechanistic studies (Aim 2), the origin of the critical role for iron species in the transmetalation step of aminoboration is being explored as is its equally curious beneficial effect on the aza-Wacker process. Finally, in an effort to develop a more sustainable variant of the nucleoboration process (Aim 3), a heterogenous and recyclable Pd/Fe catalyst system is under development. All told, the studies being pursued are anticipated to extend the versatility of olefin difunctionalization chemistry and in so doing, facilitate the synthesis of important classes of nitrogen (and other heteroatom) containing compounds that are prominent among active pharmaceutical ingredients and other kinds of complex molecules of utility in science, engineering, and medicine.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.