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

通过π-烯丙基金属中间体实现商品化学品增值的绿色化学

• 批准号: 2246428
• 负责人: Michael Krische
• 金额: $ 54.84万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2246428&HistoricalAwards=false
• 关键词: Green; Chemistry; Valorization; Commodity; Chemicals

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.

在化学系化学合成计划的支持下，德克萨斯大学奥斯汀分校的Michael J. Krische教授正在开发将丰富的化学原料转化为与制药和农业化学工业相关的增值产品的催化方法。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。虽然大量的废物往往伴随着结构复杂的化合物的制备，但所提出的方法最大限度地减少了副产品的产生，从而从源头上减少了化学废物。建议为本科生到研究生阶段的学生开展教育、培训和职业发展活动，预计这些活动将促进属于传统上在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夏季实习，从而受益于学术和工业环境中的职业发展经验。为了进一步扩大这一奖项的广泛影响，而且由于妇女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妇女”专题讨论会，这是一项广受欢迎的活动，吸引了各种科学家。Krische实验室的目标是进一步扩展化学空间，使其可用于先前在实验室中开发的功能上不同的手性π-烯丙基铱和π-烯丙基钌催化剂。虽然几乎所有的对映选择性烯丙基取代都利用低pKa亲核试剂，但此处感兴趣的π-烯丙基铱-C，O-苯甲酸酯催化剂在高温下是耐碱的，使得能够直接使用高pKa亲核试剂与廉价的无机碳酸盐碱组合。α-烯烃是丰富的原料（每年生产1亿吨），但它们原子有效地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，由新型碘化物结合的π-烯丙基钌络合物催化的氢自转移反应有望使α-烯烃的原子有效的烯丙基C-H官能化以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）。所提出的催化剂是手性在金属和配体，和催化剂设计的一个特殊功能在于定义金属为中心的最佳不对称诱导的立体异构性。该项目有可能在过渡金属催化转化的实践和理论方面取得根本性进展，这可能有利于从简单的化学原料中可持续地制造与社会相关的材料。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。