Catalysis of Tin-Free Radical Reactions Under H2

H2 下锡自由基反应的催化

• 批准号: 9902464
• 负责人: JACK R NORTON
• 金额: $ 32.17万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902464
• 关键词: Address; Affect; Alkenes; Alkynes; Benchmarking; Biochemical; Biological; Carbon; Catalysis; Chemistry; Chicago; Complex; Cyclization; Development; Electron Transport; Evaluation; Free Radicals; Funding; Gases; Generations; Geometry; Hydrogen; Hydrogenation; Laboratories; Measures; Methods; Natural Products; Natural regeneration; Oxidation-Reduction; Oxygen; Pharmacologic Substance; Planet Earth; Procedures; Process; Reaction; Reagent; Source; Structure; System; Testing; Time; Tin; Transition Elements; United States National Institutes of Health; Universities; base; catalyst; chemical synthesis; design; functional group; novel; oxidation; pi bond; preservation; tool; wasting

PROJECT SUMMARY/ABSTRACT Organotin reagents are routinely used to carry out radical reactions that create C-C bonds or effect the reduction of certain functional groups. They are valuable tools for the small-scale, laboratory synthesis of molecules for biochemical evaluation. Unfortunately, these tin reagents are unsuitable for use in manufacturing, because they are difficult to remove and quite toxic. An alternative way of generating radical intermediates is by the transfer of hydrogen atoms to unsaturated substrates from the hydride complexes of first-row transition metals. Such hydrides are non-toxic and their use is sustainable: they can be regenerated by hydrogen gas, so the generation of radicals by this method is catalytic. One H2 molecule produces two hydrogen atoms — and two radicals — with almost no waste. This proposal seeks to determine which hydride complexes can best do this chemistry and to identify new uses for radical reactions. First, the relative rates at which various alkenes and alkynes give radicals by this method will be measured, and the uses of such radicals in cyclizations will be investigated. These radicals should be particularly useful for cyclizations onto C=O, C=S, and C=N double bonds, and for the construction of three- and four-membered all-carbon rings that are not readily available by other methods. Second, the formation of radicals that do not cyclize can be followed by the transfer of another hydrogen atom in a separate step, enabling the anti addition of H2 across a C=C bond. This reaction should permit the synthesis of natural products that have been unavailable by traditional hydrogenation methods. Third, these new methods of radical generation will be tested on natural product targets that have already been prepared via radicals generated by established methods. The present syntheses have often been non-optimal; late-stage, polyfunctional, substrates will be emphasized, in order to provide as effective a benchmark as possible for the methods that have been developed. Successful catalytic reactions will then be applied to the synthesis of pharmaceutically promising natural products that have not yet been prepared in the laboratory. Finally, hydride complexes — particularly anionic hydride complexes — may also be able to generate radicals by electron transfer to appropriate halides R–X. It should be possible to regenerate these hydrides under hydrogen with base, so these reactions can also be made catalytic. We will also test this new method of radical generation on a natural product target that has been made with established methods.

项目摘要/摘要 有机锡试剂通常用于进行自由基反应，这些反应产生C-C键或影响 某些官能团的减少。对于小规模的实验室合成来说，它们是宝贵的工具 用于生化评估的分子。不幸的是，这些锡试剂不适合用于 制造，因为它们很难去除，而且毒性很大。产生偏旁部首的另一种方法 中间体是通过氢原子从氢化物络合物转移到不饱和底物上。 第一排过渡金属。这种氢化物是无毒的，它们的使用是可持续的：它们可以再生 由氢气产生，所以这种方法产生的自由基是催化的。一个氢分子产生两个氢分子 氢原子和两个基团几乎没有废物。这项提案试图确定哪种氢化物 络合物可以最好地进行这种化学反应，并确定自由基反应的新用途。 首先，通过这种方法，各种烯烃和炔烃产生自由基的相对速率将是 测量，并将调查这些自由基在环化反应中的使用。这些激进分子应该是 特别适用于C=O，C=S和C=N双键上的环化反应，以及三个- 以及通过其他方法不易获得的四元全碳环。第二，形成了 没有环化的自由基之后可以在单独的步骤中转移另一个氢原子， 实现了氢在C=C键上的反加成。这个反应应该允许合成天然的 传统加氢方法无法获得的产品。第三，这些新的方法 自由基的生成将在已经通过自由基制备的天然产品目标上进行测试 由既定的方法产生。目前的合成往往是非最佳的；后期， 将重点强调多功能、基材，以便为 已经开发出的方法。成功的催化反应将被应用于合成 药用前景看好的天然产品，尚未在实验室中制备。 最后，氢化物络合物--特别是阴离子氢化物络合物--也可能产生 通过电子转移到适当的卤化物R-X的自由基。应该可以再生这些氢化物 在氢气和碱的作用下，这些反应也可以得到催化。我们还将测试这一新方法 用既定的方法在天然产品目标上产生激进的产物。