New Cycloaddition and Annulation Strategies for Organic Synthesis

在化学系化学合成计划的支持下，麻省理工学院的Rick L.Danheiser教授将研究开发化学合成环状有机分子的新方法。合成通常被描述为使化学成为可能的技术。所开发的合成方法将为学术界和工业界的研究人员提供新的工具，用于合成在医药、农业、电子等领域具有应用价值的重要有机化合物。碳环和杂环体系存在于许多具有重要生物和医药价值的化合物的化学结构中，开发高效的合成方法对于改善分子的获取途径具有重要的价值。这项研究计划的目标是开发新的策略，使这些类别的化合物的合成过程大大简化。这些新方法的实用性将通过它们在几种天然化合物的合成中的应用来证明，这些化合物具有已知的抗肿瘤药物活性，但在自然界中无法从其来源中大量获得。这笔助学金资助的研究生将担任麻省理工学院外展计划的协调员，该计划每年访问新英格兰地区约25所高中，提供关于化学和科学职业的演讲。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)领域中代表性较低的群体的成员。拟议的研究旨在提高化学家开发几类重要有机化合物的有效合成的能力，包括多环芳烃分子、杂环系统，如吲哚和咔唑，以及八元碳环化合物。将要研究的方法涉及到机械上新颖的转化，这些研究有望促进我们对不寻常的反应物种的化学理解，如应变碳环、乙烯基烯烃和其他几类高度不饱和的共轭分子。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。大多数方法是高度原子经济的，即反应物的所有原子都被结合到产品中，最大限度地减少了化学废物的产生。此外，将开发的大多数新的环加成反应都是简单地由热或光引发的，从而避免了甚至需要催化量的试剂(特别是重金属催化剂)。根据该计划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，还将接受科学道德培训和培训，以发展他们的口头和书面沟通技能。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 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.