Applications of Electron Transfer Initiated Cyclizations

这项建议的目的是继续发展电子转移引发的环化反应，并使用这种方法来合成具有生物重要性的结构。在该反应中，高苯基取代的烷基芳烃与给电子取代基光引发的单电子氧化反应生成含有大量弱化和极化的苄基碳-碳键的自由基阳离子。添加的亲核试剂，如羟基、乙醚和酰胺基团，可以取代苄基自由基，导致环化反应。反应条件温和，单电子转移显示出独特的化学选择性，使该反应成为一种潜在的非常有效的构建有机分子的新方法。该项目的具体目标包括：深入研究该反应所能容忍的阳离子稳定取代基、芳香族离开基团和亲核剂的类型。这项研究包括新的异源级联反应的开发。化学引发的反应的变种的发展。电子转移的发展引发了从聚合物载体上的环释放反应。将该反应作为从胡萝卜素和麦角酰胺家族合成高效抗肿瘤和免疫抑制剂的简要全合成的关键步骤，并将这些序列用于合成类似物。拟议的计划既为有机合成提供了新的方法，也为具有挑战性和医学重要性的结构提供了有效的途径。

The purpose of this proposal is to continue the development of the electron transfer initiated cyclization reaction and to use this methodology for the synthesis of biologically important structures. In this reaction the photoinitiated single electron oxidation of alkylarenes substituted at the homobenzylic position with an electron donating substituent produces radical cations containing substantially weakened and polarized benzylic carbon-carbon bonds. Appended nucleophiles, such as hydroxyl, ether, and amide groups can displace benzylic radicals, resulting in a cyclization reaction. The mild reaction conditions and unique chemoselectivity exhibited by single electron transfer make this reaction a potentially very powerful new method for constructing organic molecules. Specific goals for the project include: A thorough study of the types of cation stabilizing substituents, aromatic leaving groups, and nucleophiles tolerated by this reaction. This study includes the development of new heterogenerative cascade reactions. The development of a chemically initiated variant of the reaction. The development of an electron transfer initiated cyclorelease reaction from a polymer support. Employment of the reaction as the key step in brief total syntheses of potent antitumor and immunosuppressant agents from the pederin and mycalamide family, and the use of these sequences in the synthesis of analogs. The proposed program provides both new methodology for organic synthesis and efficient routes to challenging and medicinally important structures.