METHODOLOGY FOR THE SYNTHESIS OF OXYGEN CONTAINING HETEROCYCLES

含氧杂环的合成方法

• 批准号: 7381409
• 负责人: MATTHIAS BREWER
• 金额: $ 1.69万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381409
• 关键词: METHODOLOGY; SYNTHESIS; OXYGEN; CONTAINING; HETEROCYCLES

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。过氧化物的极性重排是可用于合成的唯一合成有用的碳-氧迁移。虽然这些转化可能是强大的，但过氧化物起始材料通常是危险的，并且不容易获得。在此，我们提出了一种新的碳氧重排适用于叔醇和苄基或烯丙基仲醇。这将通过调节硫-氧键以提供在氧上具有良好离去基团的亲电氧物质来实现。具体而言，我们建议，精心设计的烷氧基锍离子将显示相同的重排反应性的过氧化物。这些转换预计提供一个oxocarbenium离子中间体，这打开了可能性，进行串联反应，以产生复杂的含氧多环产品从简单的醇原料。该方法可用于合成在非天然药物和天然产物中发现的多种含氧杂环。它还将为目前缺乏可用于构建中型和大型环醚和官能化吡喃和呋喃的通用方法提供解决方案，并且将特别适用于合成复杂的非天然单糖。这种方法将代表在氧环化合物的合成中的显著进步，并且通常将填补极性重排方法中的空白。它可能与类似的碳-氮重排一样在合成上有用。