TANDEM EPOXIDE-OLEFIN CYCLIZATION-PINACOL REARRANGEMENT

该建议概述了串联环氧化物-烯烃环化-频哪醇重排的发展。 该反应通过刘易斯酸的作用将带有三甲基甲硅烷氧基、烯基和环氧基取代基的单环烷烃转化为顺式-双环烷酮。 各种环烷烃环的大小，烯基取代基，和环氧化物将被纳入反应底物，和这些变量中的每一个对设施，立体选择性，和区域选择性的反应的影响将被注意到。 例如，在环氧化物的末端引入阳离子稳定官能团应导致环化模式从外型转变为内型。 将探索的反应的另一变化是使用乙烯基硅烷作为烯基取代基。 这将导致在反应产物中存在碳-硅键，其可以被氧化成醇。 总的来说，这些研究将提供可预测地产生多种高度取代的双环产物的有效方法。 由于这些产物中的一些可能具有生物活性或成为产生生物学上重要的化合物的中间体，因此该方法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-频哪醇重排的效用在所提出的改性的拉布拉多二萜类cluytene D的全合成中得到证明，所述cluytene D是从未在实验室合成的天然产物。

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.