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前所未有的碳氧重排，将醇转化为含氧杂环。目前，过氧化物经历唯一已知的碳-氧迁移。这些已知的基于过氧化物的重排具有有限的实用性，因为过氧化物起始材料造成爆炸危险并且不容易制备或处理。硫-氧键将被调整以提供与过氧化物相同的重排反应性特征。这些研究将集中在制备一系列的烷氧基锍离子和次磺酸酯具有不同的电子和空间性质，以评估必要的标准，以诱导这样的重排。这些转化可能提供氧碳正离子中间体，从而打开了进行串联反应以从简单的醇起始原料生产复杂的含氧多环产物的可能性。在有机和大分子化学项目的探索性研究小额赠款奖的支持下，佛蒙特大学化学系的Matthias Brewer教授，正在研究制备含氧杂环的新方法。含氧杂环存在于治疗上用作抗生素、心血管剂、神经调节剂、抗哮喘剂、抗炎剂、抗糖尿病剂和疫苗的生物活性化合物中。这些化合物通常在合成上具有挑战性，难以制备，限制了它们在生物医学研究中的应用。Brewer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.