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，过氧化物经历了唯一已知的碳到氧的迁移。这些已知的以过氧化物为基础的重排作用有限，因为过氧化物起始材料具有爆炸危险，不易制备或处理。硫氧键将被调整以提供与过氧化物相同的重排反应性。这些研究将集中在制备一系列具有不同电子和空间性质的烷氧基磺酸离子和亚砜酯，以评估诱导这种重排所需的标准。这些转化可能提供氧羰基离子中间体，开启了从简单醇起始材料进行串联反应以生产复杂含氧多环产物的可能性。在有机和大分子化学项目探索性研究小额资助的支持下，佛蒙特大学化学系的Matthias Brewer教授正在研究制备含氧杂环化合物的新方法。含氧杂环化合物存在于用于治疗的生物活性化合物中，如抗生素、心血管药物、神经调节剂、平喘剂、抗炎剂、抗糖尿病剂和疫苗。这些化合物通常具有合成挑战性且难以制备，限制了它们在生物医学研究中的应用。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应用，并可能导致新的和改进的药物。

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.