New Cycloaddition and Annulation Strategies for Organic Synthesis

在化学系化学合成项目的支持下，麻省理工学院的Rick L. Danheiser教授将研究环状有机分子化学合成的新方法。合成通常被描述为化学的使能技术。在拟议的研究中开发的合成方法将为学术界和工业界的研究人员提供合成重要有机化合物的新工具，这些化合物可应用于医学、农业、电子和其他领域。碳环和杂环系统被纳入许多重要的生物和医学化合物的化学结构中，开发高效的合成方法对于提供在这些领域具有重要应用的分子的改进途径具有重要价值。这项研究计划的目标是开发新的策略，以极大地简化这类化合物的合成。这些新方法的实用性将通过它们在几种天然存在的化合物的合成上的应用得到证明，这些化合物已知具有抗肿瘤活性，但在自然界中无法从其来源获得大量的抗肿瘤药物。这项资助下的研究生将担任麻省理工学院外展项目的协调员，该项目每年访问新英格兰地区约25所高中，提供化学和科学职业方面的演讲。每年大约有1200-1500名高中生参加这些演讲，其中许多学生是STEM（科学、技术、工程和数学）领域代表性不足的群体的成员。本研究的目的是提高化学家高效合成几种重要有机化合物的能力，包括多环芳香族分子、杂环系统（如吲哚和咔唑）和八元碳环化合物。所研究的方法将涉及新的转化机制，这些研究有望促进我们对不寻常反应物质的化学理解，如应变碳环、乙烯烯和其他几种高度不饱和共轭分子。从可持续性的角度来看，正在开发的方法有几个吸引人的特点。大多数方法都是高度原子经济的，即所有反应物的原子都被纳入产品中，最大限度地减少了化学废物的产生。此外，大多数有待开发的新环加成物仅由热或光触发，避免了对催化量的试剂（特别是重金属催化剂）的需要。该项目资助的研究生将接受培训，以发展他们作为合成化学家的技能，还将接受科学伦理和口头和书面沟通技能的培训。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。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Rick L. Danheiser of the Massachusetts Institute of Technology will study the development of new methods for the chemical synthesis of cyclic organic molecules. Synthesis is often described as the enabling technology of chemistry. The synthetic methods developed in the proposed research will provide researchers in both academia and industry with new tools for the synthesis of important organic compounds with applications in medicine, agriculture, electronics, and other areas. Carbocyclic and heterocyclic ring systems are incorporated in the chemical structures of numerous biologically and medicinally important compounds, and the development of highly efficient methods for their synthesis has great value in providing improved access to molecules with important applications in these areas. The goal of this research program is the development of new strategies with the power to dramatically streamline the synthesis of these classes of compounds. The utility of these new methods will be demonstrated by their application to the synthesis of several naturally occurring compounds that have known activity as antitumor agents, but which are not available in quantity from their sources in nature. The graduate students supported under this grant will serve as coordinators for the MIT Outreach Program, which each year visits ca. 25 high schools in the New England region providing presentations on chemistry and careers in science. Approximately 1200-1500 high school students attend these presentations each year, with many of the students being members of underrepresented groups in STEM (science, technology, engineering and mathematics) fields.The aim of the proposed research is to advance the ability of chemists to develop efficient syntheses of several important classes of organic compounds including polycyclic aromatic molecules, heterocyclic systems such as indoles and carbazoles, and eight-membered carbocyclic compounds. The methods that will be investigated involve mechanistically novel transformations and these studies are expected to advance our understanding of the chemistry of unusual reactive species such as strained carbocyclic rings, vinylketenes, and several other classes of highly unsaturated conjugated molecules. From the perspective of sustainability, the methodology under development has several attractive features. Most of the methods are highly atom economical, i.e., all of the atoms of the reactants are incorporated in the products, minimizing the generation of chemical waste. In addition, most of the new cycloadditions to be developed are triggered simply by heat or light, avoiding the need for even catalytic amounts of reagents (especially heavy metal catalysts). The graduate students supported under this program will receive training to develop their skills as synthetic chemists, and will also receive training in scientific ethics and training to develop their oral and written communication skills.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.