New Cycloaddition and Annulation Strategies for Organic Synthesis

在化学系化学合成项目的支持下，Rick L.马萨诸塞州理工学院的丹海泽将研究环状有机分子化学合成新方法的发展。 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新的工具，用于合成重要的有机化合物，并应用于医学，农业，电子和其他领域。 碳环和杂环系统被并入许多生物学和医学上重要的化合物的化学结构中，并且开发用于其合成的高效方法在提供对在这些领域中具有重要应用的分子的改进的获取方面具有巨大价值。 该研究计划的目标是开发新的策略，以显着简化这些类别化合物的合成。 这些新方法的实用性将通过其应用于合成几种天然存在的化合物来证明，所述化合物具有已知的抗肿瘤剂活性，但其在自然界中不能从其来源大量获得。 研究生在此补助金下支持将作为麻省理工学院外展计划，每年访问CA的协调员。新英格兰地区的25所高中提供化学和科学职业介绍。 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中代表性不足的群体的成员所提出的研究的目的是提高化学家开发几种重要类别的有机化合物（包括多环芳族分子）的有效合成的能力，杂环体系如吲哚和咔唑，以及八元碳环化合物。将被调查的方法涉及机械新颖的转换，这些研究预计将推进我们的理解不寻常的反应物种，如应变碳环，乙烯基烯酮，和其他几类高度不饱和的共轭分子的化学。 从可持续性的角度来看，正在制定的方法有几个有吸引力的特点。 大多数方法是高度原子经济的，即，反应物的所有原子都结合在产物中，从而使化学废物的产生最小化。 此外，大多数待开发的新环加成反应仅通过热或光引发，避免了甚至催化量的试剂（特别是重金属催化剂）的需要。 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，并已被认为是值得支持的，通过评估使用基金会的智力价值和更广泛的影响审查标准。

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.