Molybdenum-Promoted Dearomatization Reactions

化学部的化学合成项目支持W. Dean Harman教授的项目。哈曼教授是弗吉尼亚大学化学系的教员和现任系主任。他正在开发新的方法来制备新的化合物，这些化合物有可能作为药物开发的先导化合物。他独特的方法利用了芳香环与金属络合时产生的不寻常的化学性质。这些不寻常的化学性质导致了新的化学反应，将原来扁平的芳环转化为更复杂的分子。金属的存在允许以可控的方式引入复杂性。新方法的发明为合成各种有趣的和潜在有用的分子提供了全新的途径。虽然不是这个提案的一部分。该项目处于有机、无机和药物化学的界面。学生在一个完全跨学科的研究环境中工作，研究范围广泛的问题，并通过参加专业会议和演讲，参与撰写同行评审的手稿，参与提案写作过程，以及与其他科学家会面，融入科学界。因此，它非常适合各级科学家的教育。哈曼教授的团队也处于有利地位，可以为科学领域代表性不足的学生提供最高水平的教育和培训。涉及K-12学生的外展活动也将是资助项目的一部分。最后，与来自本科院校的教授合作，可以让这些教授更多地接触到当前的研究方法，并让他们的学生接触到主要的研究项目。这项工作的目的是开发新的方法，以芳香族分子合成新的分子物质。这是通过利用芳香分子的独特化学性质来实现的，这种化学性质是由它与过渡金属的双偶配位产生的。这种作用改变了芳香族底物的化学反应性，使其能够被加工成新的有机化合物。值得注意的是，这些脱芳化反应导致了具有相当立体化学复杂性的新分子，非常适合于生物评价。以前，从锇、铼和钨中提取的重金属脱芳剂已经被研究过，利用它们强大的pi给体能力。在这项工作中，PI正在探索基于第二排金属的二hapto-coordinate脱芳化方法的可行性和实用性。研究了钼基芳香配合物的基本化学特征，并与类似的重金属体系进行了比较。键能、氧化态稳定性、pi相互作用、化学试剂耐受性、成本和可回收性等方面的差异最终导致了新的合成机会，以补充重金属基体系所提供的。通过这些研究形成的分子框架提供了新颖的结构，最终将在开发新的生物活性材料中具有价值。在许多情况下，根本没有其他容易获得这些化合物的方法。这项工作的其他更广泛的影响与研究生和本科生在有机、无机和有机金属化学领域的专业培训有关。此外，研究生通过与本科生的培训和合作来培养他们的指导技能。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。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor W. Dean Harman. Professor Harman is a faculty member and current chair in the Department of Chemistry at the University of Virginia. He is developing new methods for the preparation of novel chemical compounds that have the potential to serve as lead compounds for pharmaceutical development. His unique approach exploits the unusual chemical properties that arise when an aromatic ring is complexed to a metal. These unusual chemical properties lead to new chemical reactions that convert the originally flat aromatic ring into a significantly more complex molecule. The presence of the metal allows for introduction of the complexity in a controlled fashion. The invention of the new methods allows for completely new approaches to the synthesis of a variety of interesting and potentially useful molecules. While not part of this proposal. The project lies at the interface of organic, inorganic, and medicinal chemistry. Students work in a fully interdisciplinary research environment on a wide range of problems and become integrated into the scientific community through attendance and presentations at professional meetings, participation in writing peer-reviewed manuscripts, participating in the proposal-writing process, and meeting other scientists. Thus, it is well suited for the education of scientists at all levels. Professor Harman's group is also well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving K-12 students will also be part of the funded project. Finally, collaborations with professors from undergraduate institutions allow these professors greater exposure to current research methods, and expose their students to major research programs. The goal of this work is the development of new methods for the syntheses of novel molecular substances from aromatic molecules. This is being accomplished by leveraging the unique chemical properties of an aromatic molecule that result from its dihapto-coordination to a transition metal. Such action modifies the chemical reactivity of the aromatic substrate, allowing its elaboration into novel organic compounds. Significantly, these dearomatization reactions are leading to new molecules with considerable stereochemical complexity that are well suited for biological evaluation. Previously, heavy metal dearomatization agents derived from osmium, rhenium, and tungsten have been investigated, exploiting their powerful pi-donating abilities. In this work, the PI is exploring the feasibility and practicality of a dihapto-coordinate dearomatization methodology based on a second-row metal. Fundamental chemical features of molybdenum-based aromatic complexes are being investigated and compared to the analogous heavy metal systems. Differences in bond energies, oxidation state stabilities, pi-interactions, tolerance of chemical reagents, cost, and recyclability are ultimately leading to new synthetic opportunities that complement those provided by the heavy metal based systems. The molecular frameworks that are formed through these studies are providing novel architectures that ultimately will be valuable in the development of new biologically active materials. In many cases there are simply no other means for easily obtaining these compounds. Other broader impacts of this work are related to the professional training of graduate and undergraduate students in the areas of Organic, Inorganic, and Organometallic Chemistry. In addition, graduate students develop their mentoring skills by training and collaborating with undergraduate students.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.