Regioselective [2+2+2] Cyclotrimerizations

区域选择性 [2 2 2] 环三聚化

• 批准号: 2154773
• 负责人: Brian Popp
• 金额: $ 52.5万
• 依托单位: West Virginia University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154773&HistoricalAwards=false
• 关键词: Regioselective; 2+2+2; Cyclotrimerizations

With the support of the Chemical Synthesis Program in the Division of Chemistry, Gregory Dudley and Brian Popp of West Virginia University are studying selective new methods for preparing complex derivatives of benzene and other aromatic (benzenoid) compounds. Aromatic compounds offer many benefits to society with applications in the healthcare, agriculture, electronic, and energy sectors, but the elaboration of more complex examples is a challenge because it requires the correct placement of multiple substituents around the periphery of these cyclic molecules. The central hypothesis of the funded project is that derivatives of acetylene, a readily available two-carbon building block, and related compounds, can be stitched together with catalysts in a three-fold fashion to make derivatives of benzene with the orientation of their combination being precisely controlled by the nature of the three building blocks and the type of catalyst employed. The research, which will be integrated with university education and other synergistic activities, has the potential to advance fundamental knowledge in the field of chemical synthesis and create positive impact across and beyond the molecular sciences. The broader impacts of the funded project extend to supporting a wide range of outreach activities conducted by the research team members that will foster broadening participation in STEM (science, technology, engineering and mathematics) and including engagement of individuals from underserved Appalachian communities.Regioselective [2+2+2] cyclotrimerization as a route to aromatic compounds is a long-standing challenge with no general solution. Compared with functionalization of pre-existing arenes, direct benzannulation strategies are attractive but they have been notoriously difficult to reduce to practice, especially as a means to access highly substituted aromatic ring systems. The funded project is focused on overcoming these difficulties by combining a range of substrate control principles designed to enable the convergent assembly of alkynes and/or alkyne surrogates with precise regiocontrol. Two approaches to achieve high regioselectivity in Rh- or Ni-catalyzed benzannulation chemistries are being pursued: the first involves hydrogen bonding and other templating effects (including covalent tethering) between substrates, and the second utilizes vinyl sulfones as alkyne surrogates with a distinct stereoelectronic profile. Target-oriented synthesis (to illudalane-type sesquiterpenoids) and methodological development efforts in the Dudley laboratory will be focused on regioselective two-component couplings for the convergent synthesis of tetra-, penta-, and hexa-substituted benzene rings in which two of the three building blocks (alkynes and/or vinyl sulfones) are tethered together. Concurrent experimental and computational mechanistic and organometallic studies in the Popp laboratory will be focused on the development of three-component couplings involving vinyl sulfones as polarized alkyne surrogates. These complementary efforts involve graduate and undergraduate students working together in an immersive research training environment and it is anticipated that the experiences gained will help them to emerge as potential future leaders of the global innovation-based economy. The research is expected to lead to significant advances in the chemical synthesis of highly substituted benzene derivatives and to provide new design paradigms for regioselective [2+2+2] cyclotrimerization reactions based on theory, mechanism, and experiment.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.

在化学系化学合成项目的支持下，西弗吉尼亚大学的 Gregory Dudley 和 Brian Popp 正在研究选择性的新方法来制备苯和其他芳香族（苯环）化合物的复杂衍生物。芳香族化合物在医疗保健、农业、电子和能源领域的应用为社会带来了许多好处，但详细说明更复杂的例子是一个挑战，因为它需要在这些环状分子的外围正确放置多个取代基。该资助项目的中心假设是乙炔衍生物（一种容易获得的二碳结构单元）和相关化合物可以与催化剂以三重方式缝合在一起，以制造苯衍生物，其组合方向为由三种结构单元的性质和所用催化剂的类型精确控制。该研究将与大学教育和其他协同活动相结合，有潜力推进化学合成领域的基础知识，并在分子科学内外产生积极影响。该资助项目的更广泛影响延伸到支持研究团队成员开展的广泛外展活动，这些活动将促进更广泛地参与 STEM（科学、技术、工程和数学），并包括来自服务不足的阿巴拉契亚社区的个人的参与。 2+2+2]环三聚作为制备芳香族化合物的途径是一个长期存在的挑战，没有通用的解决方案。与现有芳烃的官能化相比，直接苯环化策略很有吸引力，但众所周知，它们很难付诸实践，特别是作为获得高度取代的芳环系统的一种手段。该资助项目的重点是通过结合一系列底物控制原理来克服这些困难，这些底物控制原理旨在使炔烃和/或炔烃替代物的聚合组装与精确的区域控制成为可能。目前正在寻求两种在 Rh 或 Ni 催化的苯并环化化学中实现高区域选择性的方法：第一种涉及底物之间的氢键和其他模板效应（包括共价束缚），第二种利用乙烯基砜作为具有独特立体电子特征的炔替代物。 Dudley 实验室的目标导向合成（伊鲁达烷型倍半萜类化合物）和方法开发工作将集中于区域选择性双组分偶联，用于四取代、五取代和六取代苯环的聚合合成，其中两个三个结构单元（炔烃和/或乙烯基砜）连接在一起。 Popp 实验室同时进行的实验和计算机理以及有机金属研究将重点开发涉及乙烯基砜作为极化炔替代物的三组分偶联。这些互补的努力涉及研究生和本科生在沉浸式研究培训环境中共同工作，预计所获得的经验将帮助他们成为全球创新型经济的未来潜在领导者。该研究有望在高取代苯衍生物的化学合成方面取得重大进展，并为基于理论、机理和实验的区域选择性[2+2+2]环三聚反应提供新的设计范式。该奖项体现了NSF的法定使命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，并被认为值得支持。