TANDEM EPOXIDE-OLEFIN CYCLIZATION-PINACOL REARRANGEMENT

该建议概述了串联环氧化物-烯烃环合-频那醇重排反应的发展。该反应通过Lewis酸的作用，将含有三甲基硅氧基、烯基和环氧基的单环烷烃转化为顺式双环烷酮。各种环烷烃环尺寸、烯基取代基和环氧化物将被加入到反应底物中，并且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将被注意到。例如，在环氧化物的末端加入阳离子稳定官能团应该会导致环化模式从Exo切换到Endo。将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。总而言之，这些研究将提供一种有效的方法，可预测地产生各种高度取代的双环产品。由于这些产品中有几种可能具有生物活性，或者是导致生物重要化合物的中间体，这一过程无疑将在医学研究中得到广泛应用。环氧化物-烯烃环合-频那醇重排在一项改进的拉布丹二萜杂环烯D的全合成中得到了应用，该天然产物在实验室中从未合成过。

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.