TANDEM EPOXIDE-OLEFIN CYCLIZATION-PINACOL REARRANGEMENT

串联环氧化物-烯烃环化-频哪醇重排

• 批准号: 6209541
• 负责人: STEVEN L CASTLE
• 金额: $ 3.09万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-23 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6209541
• 关键词: alkenes; bicyclic compound; cyclization; epoxides; molecular rearrangement

This proposal outlines the development of a tandem epoxide-olefin cyclization-pinacol rearrangement. This reaction will convert monocyclic alkanes bearing trimethylsilyloxy, alkenyl, and epoxy substituents into cis-bicyclic alkanones by the action of a Lewis acid. A variety of cycloalkane ring sizes, alkenyl substituents, and epoxides will be incorporated into the reaction substrates, and the effects that each of these variables has on the facility, stereoselectivity, and regioselectivity of the reaction will be noted. For example, incorporating cation-stabilizing functionality at the terminus of the epoxide should cause the mode of cyclization to switch from exo to endo. Another variation of the reaction that will be explored is the use of a vinylsilane as the alkenyl substituent. This would result in the presence of a carbon-silicon bond in the reaction product, which can be oxidized to an alcohol. Collectively, these studies will provide an effective method of predictably generating a wide variety of highly substituted bicyclic products. As several of these products are likely to either have biological activity or be intermediates leading to biologically significant compounds, this process will doubtless find wide application in medicinal research. The utility of the tandem epoxide-olefin cyclization- pinacol rearrangement is demonstrated in a proposed total synthesis of the modified labdane diterpenoid cluytene D, a natural product which has never been synthesized in the laboratory.

该提案概述了串联环氧化物-烯烃环化-频哪醇重排的发展。 该反应将通过路易斯酸的作用将带有三甲基甲硅烷氧基、烯基和环氧取代基的单环烷烃转化为顺式双环烷酮。 各种环烷烃环大小、烯基取代基和环氧化物将被纳入反应底物中，并且将注意到这些变量中的每一个对反应的便利性、立体选择性和区域选择性的影响。 例如，在环氧化物末端引入阳离子稳定功能应导致环化模式从外型转变为内型。 将要探索的反应的另一种变化是使用乙烯基硅烷作为烯基取代基。 这将导致反应产物中存在碳-硅键，该键可以被氧化成醇。 总的来说，这些研究将提供一种有效的方法来可预测地生成各种高度取代的双环产物。 由于其中一些产品可能具有生物活性或者是产生具有生物学意义的化合物的中间体，因此该过程无疑将在医学研究中得到广泛应用。 串联环氧化物-烯烃环化-频哪醇重排的实用性在改性拉丹烷二萜 cluytene D 的全合成中得到了证明，这是一种从未在实验室合成过的天然产物。