Developing An Intramolecular Cationic [2 + 2] Cycloaddition

分子内反应代表了有机合成中最重要的场所之一，因为它们能够以高度区域选择性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部化学合成计划的支持下，威斯康星大学麦迪逊分校的Richard Hsung教授的研究小组打算使用手性Fe（III）催化剂或手性布朗斯台德酸开发不对称分子内阳离子[2 + 2]环加成，并设计用于实现高度区域选择性和立体选择性的分子间环加成的等价物的临时栓系体系。最终目标是在具有抗癌和抗疟疾活性的天然产物（-）-bielschowskysin的全合成中表征阳离子[2 + 2]环加成。 实现阳离子[2 + 2]环加成将导致合成环丁烷的生物启发策略，并将使Hsung教授的计划显着影响环加成化学领域，该领域尚未得到充分探索，并有助于手性Fe（III）试剂领域的不对称催化领域以及布朗斯特酸。 设计和开发新的方法来快速组装复杂的结构和有效的策略来构建具有重要生物活性的天然物质仍然是现代有机化学的重要任务之一。 在这个NSF奖项的支持下，Hsung教授打算建立一个基于这一前提的研究计划，同时专注于环丁烷的[2 + 2]环加成歧管，环丁烷是一种四元全碳环，代表了药用实体中普遍存在的基序。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，他们提供了一个独特的机会，教本科生开发有用的合成方法的基础上的基本概念，结构设计，并提出了机械模型。通过实现这些目标，熊教授的研究工作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.