SGER: Investigation of Electron-Deficient Oxygen Sources and Application to Unprecedented Carbon-to-Oxygen Rearrangements

这项提议的目标是开发一种史无前例的碳氧重排，将醇转化为含氧杂环。目前，过氧化物经历了唯一已知的从碳到氧的迁移。这些已知的基于过氧化氢的重排用途有限，因为过氧化氢起始材料存在爆炸危险，而且不容易制备或处理。硫氧键将被调整，以提供与过氧物相同的重排反应性曲线。这些研究将集中于制备一系列具有不同电子和空间性质的烷氧基硫离子和磺酸酯，以评估诱导这种重排所需的标准。这些转化可能提供氧碳正离子中间体，从而打开了从简单的醇起始物质进行串联反应以生成复杂的含氧多环产物的可能性。在有机和高分子化学项目的这一小笔探索性研究拨款的支持下，佛蒙特州大学化学系的马蒂亚斯·布鲁尔教授正在研究制备含氧杂环的新方法。含氧杂环化合物存在于生物活性化合物中，用于治疗抗生素、心血管药物、神经调节剂、平喘剂、抗炎药、抗糖尿病药和疫苗。这些化合物往往在合成上具有挑战性，而且很难制备，限制了它们在生物医学研究中的使用。布鲁尔教授的方法将极大地促进这些化合物的制备，这反过来又将促进它们在生物医学研究中的使用，并可能导致新的和改进的药剂。

The goal of this proposal is to develop an unprecedented carbon-to-oxygen rearrangement that would convert alcohols into oxygen-containing heterocycles. Currently, peroxides undergo the only known carbon-to-oxygen migration. These known peroxide-based rearrangements are of limited utility because the peroxide starting materials pose explosion hazards and are not easily prepared or handled. Sulfur-oxygen linkages will be tuned to provide the same rearrangement reactivity profile as peroxides. These studies will focus on preparing a series of alkoxysulfonium ions and sulfenic esters with differing electronic and steric properties to evaluate the criteria necessary to induce such a rearrangement. These transformations may provide oxocarbenium ion intermediates, opening the possibility of performing tandem reactions to produce complex oxygen-containing polycyclic products from simple alcohol starting materials.With the support of this Small Grants for Exploratory Research award from the Organic and Macromolecular Chemistry Program, Professor Matthias Brewer, of the Department of Chemistry at the University of Vermont, is studying new methods to prepare oxygen-containing heterocycles. Oxygen-containing heterocycles are present in biologically active compounds used therapeutically as antibiotics, cardiovascular agents, neurological modulators, antiasthmatic agents, antiinflammatory agents, antidiabetic agents and vaccines. These compounds are often synthetically challenging and difficult to prepare, limiting their use in biomedical studies. Professor Brewer's methodology will greatly facilitate the preparation of these compounds, which in turn will facilitate their use in biomedical research and could lead to new and improved medicinal agents.