MANGANESE (III) BASED OXIDATIVE FREE RADICAL CYCLIZATION

锰 (III) 基氧化自由基环化

• 批准号: 3305908
• 负责人: BARRY B. SNIDER
• 金额: $ 13.7万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3305908
• 关键词: alkenes; antifungal agents; chemical addition; chemical substitution; chemical synthesis; copper; cyclic compound; cyclization; cyclopropanes; diterpenes; free radical oxygen; haloalkene; manganese; oxidation; rare earth element; sesquiterpenes; solvents; sulfoxide; sweetening agents

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.

氧化自由基环化，其中初始 自由基是氧化产生的，/或环状自由基被氧化至 终止反应，具有相当大的合成潜力，因为更多 可以从更简单的前体制备高度功能化的产品 与标准锡氢化物还原自由基环化相比。 这 这项研究的目标是开发氧化自由基环化 成为一种可靠且通用的方法，用于合成高度 官能化的循环和多环化合物。 该提议包括 在开发新合成方法的几项相互关联的研究中 并检查氧化自由基环化的机制 将Mn（III），Cu（II）或CE（IV）作为氧化剂，几种天然 产品合成旨在利用和发展氧化自由基 环化。 在方法开发领域，我们计划检查：（1） 除炔烃，溶剂效应，（2）使用卤代烯烃来控制 环化的区域化学，（3）新的替代模式，（4） 通过添加氮气捕获，（5）诱捕醛，诱捕， （6）氧化，环化，氧化，环化，（7）氧化 环化，然后进行分子间捕获，（8）氧化， 环化，烯丙基化，氧化和环化，（9）使用共轭 β-酮酯，（10）使用亚硫氧化物对非对称自由基 环化，（11）探针，探针是自由基环化的可逆性， （12）不饱和甲硅烷基烯醇醚的氧化环化，（13） 不饱和甲己德氧甲丙烷的氧化环化和（14） 将其他自由基转化为铜羧酸盐。 在 总合成面积我们计划执行以下合成：（1） velloziolone，（2）键三环酸的钥匙中间体 合成，（3）Steviol，（4）Iresin，（5）Avenaciolide和（6）模型 阿克拉夫酮合成。 这项工作的重点是开发新合成 将广泛适用于宽广泛的方法 品种具有生物活性化合物。 迄今为止获得的结果建议 氧化自由基环化将是一种重要的新方法 适用于准备多种高度功能化的 循环和多环。 方法和合成项目具有 旨在提高对机械的理解 自由基化学和开发氧化的新应用 自由基环化。