MANGANESE (III) BASED OXIDATIVE FREE RADICAL CYCLIZATION

氧化自由基环化，其中初始 自由基被氧化生成和/或环状自由基被氧化成 终止反应，具有相当大的合成潜力，因为 高度官能化的产品可以由更简单的前体制备 与标准的氢化锡还原自由基环化相比。 的 本研究的目的是发展氧化自由基环化反应 成为一种可靠和通用的方法，用于合成高度 官能化的环状和多环化合物。 该提案包括 几个相互关联的研究开发新的合成方法， 研究氧化自由基环化的机制 以Mn（III）、Cu（II）或Ce（IV）为氧化剂， 旨在开发和发展氧化自由基的产品合成 环化反应 在方法开发领域，我们计划研究：（1） 添加到炔，溶剂效应，（2）使用卤代烯烃控制 环化反应的区域化学，（3）新的取代模式，（4） 通过添加腈来捕获，（5）通过添加醛来捕获， (6)氧化，环化，氧化，环化，（7）氧化 环化，然后分子间捕获，（8）氧化， 环化、烯丙基化、氧化和环化，（9）使用共轭 β-酮酯，（10）亚砜用于不对称自由基 环化，（11）自由基环化可逆性的探针， (12)不饱和甲硅烷基烯醇醚的氧化环化，（13） 不饱和甲硅烷基氧基环丙烷的氧化环化，和（14） 用羧酸铜将其它自由基转化为烯烃。 在 在全合成领域，我们计划进行以下合成：（1） velloziolone，（2）赤霉酸的关键三环中间体 合成，（3）甜菊醇，（4）Iresin，（5）燕麦素，和（6）模型 aklavinone合成 这项工作的重点是开发新的合成 将广泛适用于综合广泛的 多种生物活性化合物。 迄今取得的结果表明， 氧化自由基环化反应将是一种重要的新方法 适用于制备各种高度功能化的 环状和多环目标。 方法和综合项目有 目的是为了提高对 自由基化学和开发氧化的新应用 自由基环化。

Oxidative free-radical cyclization, in which the initial radical is generated oxidatively and/or the cyclic radical is oxidized to terminate the reaction, has considerable synthetic potential since more highly functionalized products can be prepared from simpler precursors than with the standard tin hydride reductive radical cyclizations. The goal of this research is to develop oxidative free-radical cyclization into a reliable and versatile method for the synthesis of highly functionalized cyclic and polycyclic compounds. This proposal consists of several interrelated studies developing new synthetic methods based on, and examining the mechanism of, oxidative free-radical cyclization using Mn(III), Cu(II) or Ce(IV) as the oxidant, and several natural product syntheses designed to exploit and develop oxidative free-radical cyclization. In the area of methods development we plan to examine: (1) addition to alkynes, solvent effects, (2) use of haloalkenes to control the regiochemistry of the cyclization, (3) new substitution patterns, (4) trapping by addition to nitriles, (5) trapping by addition to aldehydes, (6) oxidation, cyclization, oxidation, cyclization, (7) oxidative cyclization followed by intermolecular trapping, (8) oxidation, cyclization, allylation, oxidation and cyclization, (9) use of conjugated beta-keto esters, (10) use of sulfoxides for asymmetric free-radical cyclization, (11) probes for the reversibility of radical cyclization, (12) oxidative cyclization of unsaturated silyl enol ethers, (13) oxidative cyclization of unsaturated silyloxycyclopropanes, and (14) conversion of other radicals to alkenes with copper carboxylates. In the area of total synthesis we plan to carry out syntheses of: (1) velloziolone, (2) a key tricyclic intermediate for gibberellic acid synthesis, (3) steviol, (4) iresin, (5) avenaciolide, and (6) models for aklavinone synthesis. The focus of this work is the development of new synthetic methodology that will be broadly applicable in the synthesis of a wide variety biologically active compounds. Results obtained to date suggest that oxidative free-radical cyclization will be an important new method applicable to the preparation of a wide variety of highly functionalized cyclic and polycyclic targets. The methods and syntheses projects have been designed to lead to increased mechanistic understanding of free-radical chemistry and develop new applications of oxidative free-radical cyclizations.