Developing An Intramolecular Cationic [2 + 2] Cycloaddition

分子内反应是有机合成中最重要的场所之一，因为它们能够以高度区域和立体选择性的方式迅速产生大量的结构复杂性。在国家科学基金会化学系化学合成计划的支持下，威斯康星大学麦迪逊分校的Richard Hung教授的研究小组打算利用手性Fe(III)催化剂或手性Brnsted酸开发不对称分子内阳离子[2+2]环加成反应，并设计临时系留系统，以实现相当于高区域和立体选择性的分子间环加成反应。一个最终目标是将阳离子[2+2]环加成反应应用于具有抗癌和抗疟疾活性的天然产物(-)-Bielschowsky sin的全合成。实现阳离子[2+2]环加成反应将导致一种生物启发的环丁烷合成策略，并将使洪教授的计划能够显著影响一个未被探索的环加成化学领域，并有助于手性Fe(III)试剂和Brnsted酸领域的不对称催化领域。设计和开发能够快速组装复杂结构的新方法和构建具有重要生物活性的天然物质的有效策略仍然是现代有机化学的重要任务之一。在NSF这个奖项的支持下，洪教授打算在这一前提下建立一个研究计划，同时专注于[2+2]环加成流形，在通往环丁烷的途中，环丁烷是一种四元全碳环，代表了医学上有用的实体中的一个普遍主题。此外，这里提出的所有项目都涉及基础有机化学的各个方面。因此，它们为本科生提供了一个独特的机会，让他们根据基本概念、结构设计和提出的机械模型来开发有用的综合方法。通过实现这些目标，洪教授的研究努力将继续扩大合成有机化学对培训和教育的影响。

Intramolecular reactions represent one of the most important venues in organic synthesis, given their ability to expeditiously bring forth a great deal of structural complexity in a highly regio- and stereoselective manner. With support of this award from the Chemical Synthesis Program of the Division of Chemistry at the National Science Foundation, Professor Richard Hsung's research group at the University of Wisconsin-Madison intends to develop asymmetric intramolecular cationic [2 + 2] cycloadditions using chiral Fe(III) catalysts or chiral Brønsted acids, and to design temporary tethered systems for achieving an equivalent of highly regio- and stereoselective intermolecular cycloaddition. An ultimate goal is to feature the cationic [2 + 2] cycloaddition in a total synthesis of natural product, (-)-bielschowskysin, that possesses anti-cancer and anti-malarial activities. Achieving a cationic [2 + 2] cycloaddition will lead to a bio-inspired strategy for synthesizing cyclobutanes, and will allow Professor Hsung's program to significantly impact an area of cycloaddition chemistry that is under-explored and contribute to the field of asymmetric catalysis in areas of chiral Fe(III) reagents as well as Brønsted acids. Designing and developing new methods that can serve as approaches for rapid assembly of complex structures and efficient strategies for constructing natural occurring substances that possess important biological activities remain as one of important quests in modern organic chemistry. With support of this NSF award, Professor Hsung intends to build a research program based on this premise while focusing on a [2 + 2] cycloaddition manifold en route to cyclobutanes, a four-membered all-carbon containing ring that represents a prevalent motif among medicinally useful entities. In addition, all projects proposed here concern various aspects of basic organic chemistry. Thus, they provide a unique opportunity for teaching undergraduate students to develop useful synthetic methodologies based on fundamental concepts, structural designs, and proposed mechanistic models. By accomplishing these objectives, Professor Hsung's research efforts will continue to broaden the impact of synthetic organic chemistry on training and education.