METHODOLOGY FOR THE SYNTHESIS OF OXYGEN CONTAINING HETEROCYCLES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。过氧化物的极性重排是合成中唯一有用的碳到氧迁移。虽然这些转化具有潜在的强大功能，但过氧化氢起始材料的使用往往是危险的，而且不易获得。在此，我们建议开发一种适用于叔醇和苯基或烯丙基仲醇的新型碳-氧重排方法。这将通过调整硫氧键来实现，以提供在氧上具有良好离去基的亲电氧。具体来说，我们提出精心设计的烷氧基磺酸离子将显示出与过氧化物相同的重排反应性。预计这些转化将提供一种氧羰基离子中间体，从而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。该方法可用于合成非天然药物制剂和天然产物中各种含氧杂环化合物。它还将解决目前缺乏用于构建大中型环醚和功能化吡喃和呋喃的通用方法的问题，并将对合成复杂的非天然单糖特别有用。这种方法在氧环合成方面取得了重大进展，总的来说填补了极性重排方法的空白。它很可能与类似的碳-氮重排一样具有综合用途。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polar rearrangements of peroxides are the only synthetically useful carbon-to-oxygen migrations available for synthesis. While these transformations are potentially powerful, the peroxide starting materials are often hazardous to work with and not readily available. Herein we propose to develop a novel carbon-to-oxygen rearrangement applicable to tertiary alcohols and benzylic or allylic secondary alcohols. This will be achieved by tuning sulfur-oxygen linkages to provide electrophilic oxygen species with a good leaving group on oxygen. Specifically, we propose that carefully designed alkoxysulfonium ions will display the same rearrangement reactivity profile as peroxides. These transformations are predicted to provide an oxocarbenium ion intermediate, which opens the possibility of performing tandem reactions to produce complex oxygen-containing polycyclic products from simple alcohol starting materials. This methodology would find utility in the synthesis of a wide variety of oxygen-containing heterocycles found in both non-natural medicinal agents and natural products. It would also provide a solution to the current lack of general methodology available for the construction of medium- and large-size cyclic ethers and functionalized pyrans and furans, and would be particularly useful for the synthesis of complex unnatural monosaccharides. This methodology would represent a significant advance in the synthesis of oxycycles and in general would fill a void in polar rearrangement methodology. It is likely to be as synthetically useful as the analogous carbon-to-nitrogen rearrangements.