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

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教授正在开发催化方法，将丰富的化学原料转化为与制药和农用化学工业相关的附加值产品。这项研究的一个突出特点是，它将包括以对映体选择性的方式产生所谓的手性化合物，即高度控制分子的“左旋性”。虽然在制备结构复杂的化合物时往往会产生大量的废物，但建议的方法将副产品的产生降至最低，从而从源头上减少了化学废物。建议为从本科生到研究生的学生开展教育、培训和职业发展活动，这些活动预计将促进在STEM(科学、技术、工程和数学)中传统上代表人数较少的群体的个人参与。作为长期合作的一部分，参与资助项目的研究生实习生将参加基因泰克的暑期实习，从而受益于学术和工业环境中的职业发展经验。为了进一步扩大该奖项的更广泛影响，以及由于女性在制药和农化科学中的代表性仍然很低，Krische教授将继续组织两年一次的“催化和合成化学中的女性”研讨会，这是一个吸引了不同科学家队列的热门活动。根据德克萨斯大学奥斯汀分校的这一奖项，Krische实验室旨在进一步扩大以前在实验室开发的不同功能的手性pi-allyriu和pi-allylRu催化剂的化学空间。虽然几乎所有的对映选择性烯丙基取代都使用低pKA的亲核剂，但这里所关注的pi-烯丙基锂-C，O-苯甲酸酯催化剂在高温下是耐碱的，使得高pKA的亲核剂与廉价的无机碳酸盐碱结合使用。α-烯烃是丰富的原料(年产1亿吨)，但它们的原子效率高的转化为有用的手性产品通常需要质量密集型氧化剂(如苯二酚)或光化学促进。相比之下，新的碘结合的烯丙基Ru络合物催化的氢自动转移反应有望使α-烯烃的原子高效的烯丙基C-H官能化反应形成对映体富集物。此外，相关的Ru和Fe催化剂将用于丁二烯的无副产物加氢功能化(年产1200万吨)。所提出的催化剂是手性金属和配体，催化剂设计的一个特殊之处在于定义了以金属为中心的立体对称性，以实现最佳的不对称诱导。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，这些转化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智力优势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.