Green Chemistry for Valorization of Commodity Chemicals via pi-Allylmetal Intermediates

在化学系化学合成项目的支持下，德克萨斯大学奥斯汀分校的 Michael J. Krische 教授正在开发催化方法，将丰富的化学原料转化为与制药和农化行业相关的增值产品。该研究的一个突出特点是，它将包括以对映选择性方式生成所谓的“手性”化合物，即对分子的“手性”进行高度控制。尽管在制备结构复杂的化合物时经常会产生大量废物，但所提出的方法最大限度地减少了副产物的产生，从而从源头上减少了化学废物。为本科生到研究生阶段的学生提出了教育、培训和职业发展活动，这些活动预计将促进传统上在 STEM（科学、技术、工程和数学）领域代表性不足的群体的个人的参与。作为长期合作的一部分，参与资助项目的研究生学员将参加基因泰克的暑期实习，从而受益于学术和工业环境的职业发展经验。为了进一步扩大该奖项的更广泛影响，并且由于女性在制药和农业化学科学领域的代表性仍然严重不足，Krische 教授将继续组织两年一度的“催化和合成化学领域的女性”研讨会，这是一项吸引不同科学家群体的热门活动。在德克萨斯大学奥斯汀分校获得该奖项的情况下，Krische 实验室的目标是进一步扩展化学空间，以实现功能独特的手性 pi-allyridium 和先前在实验室开发的π-烯丙基钌催化剂。虽然几乎所有对映选择性烯丙基取代都利用低 pKa 亲核试剂，但这里感兴趣的 pi-烯丙基铱-C,O-苯甲酸酯催化剂在高温下具有碱耐受性，能够直接使用高 pKa 亲核试剂与廉价的无机碳酸酯碱组合。 α-烯烃是丰富的原料（每年生产 1 亿吨），但其原子效率转化为有用的手性产物通常需要质量密集型氧化剂（例如苯醌）或光化学促进。相比之下，新型碘化物结合的 pi-烯丙基钌配合物催化的氢自转移反应有望实现 α-烯烃的原子效率烯丙基 C-H 官能化，形成对映体富集的产物。此外，相关的钌和铁催化剂将用于丁二烯的无副产物加氢官能化（每年生产1200万吨）。所提出的催化剂是金属和配体的手性催化剂，催化剂设计的一个特点在于定义以金属为中心的立体异构性以实现最佳的不对称诱导。该项目有潜力在过渡金属催化转化的实践和理论方面取得根本性进展，可能有利于从简单的化学原料可持续生产与社会相关的材料。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Michael J. Krische of the University of Texas at Austin is developing catalytic methods for the conversion of abundant chemical feedstocks to value-added products that are relevant to the pharmaceutical and agrochemical industries. A prominent feature of the research is that it will include the generation of so-called 'chiral' compounds in an enantioselective manner, i.e. with high levels of control of the 'handedness' of the molecule. Whereas large volumes of waste often accompany the preparation of structurally complex compounds, the proposed methods minimize byproduct generation, thus reducing chemical waste at the source. Education, training, and career development activities for students from the undergraduate to graduate levels are proposed and these activities are anticipated to foster the participation of individuals belonging to groups traditionally underrepresented in STEM (science, technology, engineering and mathematics). As part of a longstanding collaboration, graduate student trainees involved in the funded project will participate in summer internships at Genentech, thus benefiting from career development experiences in both academic and industrial settings. To further extend the broader impacts of this award, and because women remain significantly underrepresented in pharmaceutical and agrochemical sciences, Professor Krische will continue to organize the biennial “Women in Catalysis and Synthetic Chemistry” symposium, a popular event that attracts a diverse cohort of scientists.Under this award at the University of Texas-Austin, the Krische lab aims to further extend the chemical space accessible to functionally distinct chiral pi-allyliridium and pi-allylruthenium catalysts previously developed in the laboratory. While nearly all enantioselective allylic substitutions exploit low-pKa pronucleophiles, the pi-allyliridium-C,O-benzoate catalysts of interest here are base-tolerant at high temperatures enabling direct use of high-pKa pronucleophiles in combination with inexpensive inorganic carbonate bases. alpha-Olefins are abundant feedstocks (100 M tons produced per year), yet their atom-efficient conversion to useful chiral products often requires mass-intensive oxidants (e.g., benzoquinone) or photochemical promotion. By contrast, hydrogen auto-transfer reactions catalyzed by novel iodide-bound pi-allylruthenium complexes holds promise for atom-efficient allylic C-H functionalizations of alpha-olefins to form enantiomerically enriched products. In addition, related ruthenium and iron catalysts will be used in byproduct-free hydrofunctionalizations of butadiene (12 M tons produced per year). The proposed catalysts are chiral-at-metal-and-ligand, and a special feature of the catalyst design resides in defining metal-centered stereogenicity for optimal asymmetric induction. The project has the potential to yield fundamental advances in the practice and theory of transition metal-catalyzed transformations that are likely to benefit the sustainable manufacture of societally-relevant materials from simple chemical feedstocks.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.