Applications of Electron Transfer Initiated Cyclizations

本提案的目的是继续发展电子转移引发的环化反应，并使用这种方法合成生物学上重要的结构。 在该反应中，光引发的单电子氧化的烷基芳烃取代在homobenzylic位置与供电子取代基产生自由基阳离子含有基本上减弱和极化的苄基碳-碳键。 取代的亲核试剂，如羟基、醚和酰胺基团可以取代苄基自由基，导致环化反应。 温和的反应条件和单电子转移所表现出的独特的化学选择性使该反应成为一种潜在的非常强大的构建有机分子的新方法。 该项目的具体目标包括：彻底研究阳离子稳定取代基的类型，芳香族离去基团和亲核试剂。 这项研究包括新的异源级联反应的发展。化学引发的反应变体的发展。电子转移引发聚合物载体上的环化释放反应的研究进展。采用该反应作为关键步骤，简单地全合成来自pederin和mycalamide家族的有效的抗肿瘤剂和免疫抑制剂，以及这些序列在合成类似物中的用途。该计划为有机合成提供了新的方法，并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.