METHODOLOGY FOR THE SYNTHESIS OF OXYGEN CONTAINING HETEROCYCLES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。过氧物的极性重排是唯一可用于合成的合成有用的碳到氧的迁移。虽然这些转化是潜在的强大，但过氧化氢起始材料往往是危险的工作和不容易获得。在这里，我们建议开发一种新的碳氧重排反应，适用于叔醇和苄基或烯丙基仲醇。这将通过调节硫-氧键来实现，以提供具有良好的氧离开基团的亲电性氧物种。具体地说，我们提出精心设计的烷氧基硫离子将表现出与过氧物相同的重排反应性。这些转化预计将提供氧卡宾离子中间体，这使得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成为可能。这种方法可用于合成在非天然药物和天然产品中发现的各种含氧杂环。它还将解决目前缺乏构建中大型环醚和官能化吡喃和呋喃的通用方法的问题，并将特别有助于合成复杂的非天然单糖。这一方法将代表氧环合成方面的重大进步，总体上将填补极性重排方法的空白。它很可能与类似的碳-氮重排一样在合成上有用。

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.